Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting--a report from the American Society of Echocardiography Dyssynchrony Writing Group endorsed by the Heart Rhythm Society.

PubMed

Gorcsan, John; Abraham, Theodore; Agler, Deborah A; Bax, Jeroen J; Derumeaux, Genevieve; Grimm, Richard A; Martin, Randy; Steinberg, Jonathan S; Sutton, Martin St John; Yu, Cheuk-Man

2008-03-01

Echocardiography plays an evolving and important role in the care of heart failure patients treated with biventricular pacing, or cardiac resynchronization therapy (CRT). Numerous recent published reports have utilized echocardiographic techniques to potentially aide in patient selection for CRT prior to implantation and to optimized device settings afterwards. However, no ideal approach has yet been found. This consensus report evaluates the contemporary applications of echocardiography for CRT including relative strengths and technical limitations of several techniques and proposes guidelines regarding current and possible future clinical applications. Principal methods advised to qualify abnormalities in regional ventricular activation, known as dyssynchrony, include longitudinal velocities by color-coded tissue Doppler and the difference in left ventricular to right ventricular ejection using routine pulsed Doppler, or interventricular mechanical delay. Supplemental measures of radial dynamics which may be of additive value include septal-to-posterior wall delay using M-mode in patients with non-ischemic disease with technically high quality data, or using speckle tracking radial strain. A simplified post-CRT screening for atrioventricular optimization using Doppler mitral inflow velocities is also proposed. Since this is rapidly changing field with new information being added frequently, future modification and refinements in approach are anticipated to continue.

Biomarkers in electrophysiology: role in arrhythmias and resynchronization therapy

PubMed Central

Bose, Abhishek; Truong, Quynh A.

2015-01-01

Circulating biomarkers related to inflammation, neurohormones, myocardial stress, and necrosis have been associated with commonly encountered arrhythmic disorders such as atrial fibrillation (AF) and more malignant processes including ventricular arrhythmias (VA) and sudden cardiac death (SCD). Both direct and indirect biomarkers implicated in the heart failure cascade have potential prognostic value in patients undergoing cardiac resynchronization therapy (CRT). This review will focus on the role of biomarkers in AF, history of SCD, and CRT with an emphasis to improve clinical risk assessment for arrhythmias and patient selection for device therapy. Notably, information obtained from biomarkers may supplement traditional diagnostic and imaging techniques, thus providing an additional benefit in the management of patients. PMID:25715916

Usefulness of cardiac resynchronization therapy in the management of Doxorubicin-induced cardiomyopathy.

PubMed

Ajijola, Olujimi A; Nandigam, K Veena; Chabner, Bruce A; Orencole, Mary; Dec, G William; Ruskin, Jeremy N; Singh, Jagmeet P

2008-05-01

Doxorubicin is a widely used antineoplastic agent that may cause irreversible dilated cardiomyopathy. Doxorubicin-induced cardiomyopathy (DIC) can occur several years after exposure and carries a poor prognosis. Although cardiac resynchronization therapy (CRT) is a useful intervention in end-stage heart failure unresponsive to optimal medical therapies, its efficacy in DIC remains unknown. Four consecutive patients receiving CRT for DIC were evaluated before and after CRT. CRT resulted in improvements in the mean left ventricular ejection fraction at 1 month from 21+/-4.7% to 34+/-5% (p=0.03) and at 6 months (to 46+/-7.5%, p=0.01). CRT-induced reverse remodeling was observed, with a mean reduction in left ventricular internal diameter at end-diastole from 54.75+/-3.7 to 52.5+/-1.9 mm at 1 month (p=0.06) and further to 47+/-2.3 mm at 6 months (p=0.03). All patients experienced reductions in heart failure symptoms and improvements in New York Heart Association functional class (p<0.05). The impact of CRT was sustained over a follow-up of 18.5+/-3.5 months. In conclusion, this study suggests that patients with DIC, refractory to optimal pharmacologic therapy and meeting criteria for resynchronization device implantation, may achieve sustained benefit from CRT.

Coronary Sinus Lead Positioning.

PubMed

Roka, Attila; Borgquist, Rasmus; Singh, Jagmeet

2015-12-01

Although cardiac resynchronization therapy improves morbidity and mortality in patients with cardiomyopathy, heart failure, and electrical dyssynchrony, the rate of nonresponders using standard indications and implant techniques is still high. Optimal coronary sinus lead positioning is important to increase the chance of successful resynchronization. Patient factors such as cause of heart failure, type of dyssynchrony, scar burden, coronary sinus anatomy, and phrenic nerve capture may affect the efficacy of the therapy. Several modalities are under investigation. Alternative left ventricular lead implantation strategies are occasionally required when the transvenous route is not feasible or would result in a suboptimal lead position. Copyright © 2015 Elsevier Inc. All rights reserved.

Coronary Sinus Lead Positioning.

PubMed

Roka, Attila; Borgquist, Rasmus; Singh, Jagmeet

2017-01-01

Although cardiac resynchronization therapy improves morbidity and mortality in patients with cardiomyopathy, heart failure, and electrical dyssynchrony, the rate of nonresponders using standard indications and implant techniques is still high. Optimal coronary sinus lead positioning is important to increase the chance of successful resynchronization. Patient factors such as cause of heart failure, type of dyssynchrony, scar burden, coronary sinus anatomy, and phrenic nerve capture may affect the efficacy of the therapy. Several modalities are under investigation. Alternative left ventricular lead implantation strategies are occasionally required when the transvenous route is not feasible or would result in a suboptimal lead position. Copyright © 2016 Elsevier Inc. All rights reserved.

Inverse Relationship of Blood Pressure to Long-Term Outcomes and Benefit of Cardiac Resynchronization Therapy in Patients With Mild Heart Failure: A Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Long-Term Follow-Up Substudy.

PubMed

Biton, Yitschak; Moss, Arthur J; Kutyifa, Valentina; Mathias, Andrew; Sherazi, Saadia; Zareba, Wojciech; McNitt, Scott; Polonsky, Bronislava; Barsheshet, Alon; Brown, Mary W; Goldenberg, Ilan

2015-09-01

Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with left ventricular dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase systolic blood pressure (SBP). Therefore, we hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values. The independent contribution of SBP to outcome was analyzed in 1267 patients with left bundle brunch block enrolled in Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). SBP was assessed as continuous measures and further categorized into approximate quintiles. The risk of long-term HF or death and CRT with defibrillator versus implantable cardioverter defibrillator benefit was assessed in multivariate Cox proportional hazards regression models. Multivariate analysis showed that in the implantable cardioverter defibrillator arm, each 10-mm Hg decrement of SBP was independently associated with a significant 21% (P<0.001) increased risk for HF or death, and patients with lower quintile SBP (<110 mm Hg) experienced a corresponding >2-fold risk-increase. CRT with defibrillator provided the greatest HF or mortality risk reduction in patients with SBP<110 mm Hg hazard ratio of 0.34, P<0.001, when compared with hazard ratio of 0.52, P<0.001, in those with 110>SBP≥136 mm Hg and hazard ratio of 0.94, P=0.808, with SBP>136 mm Hg (P for trend=0.001). In patients with mild HF, prolonged QRS, and left bundle brunch block, low SBP is related to higher risk of mortality or HF with implantable cardioverter defibrillator therapy alone. Treatment with CRT is associated with incremental clinical benefits in patients with lower baseline SBP values. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271. © 2015 American Heart Association, Inc.

Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT.

PubMed

Capitanio, Selene; Nanni, Cristina; Marini, Cecilia; Bonfiglioli, Rachele; Martignani, Cristian; Dib, Bassam; Fuccio, Chiara; Boriani, Giuseppe; Picori, Lorena; Boschi, Stefano; Morbelli, Silvia; Fanti, Stefano; Sambuceti, Gianmario

2015-11-01

Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III-IV) after CRT using (11)C-hydroxyephedrine (HED) PET/CT. Ten IHF patients (mean age = 68; range = 55-81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with "impaired innervation" (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation. This work might contribute to identify imaging parameters that could predict the response to CRT therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Non-invasive electromechanical activation imaging as a tool to study left ventricular dyssynchronous patients: Implication for CRT therapy.

PubMed

Dawoud, Fady; Spragg, David D; Berger, Ronald D; Cheng, Alan; Horáček, B Milan; Halperin, Henry R; Lardo, Albert C

2016-01-01

Electromechanical de-coupling is hypothesized to explain non-response of dyssynchrony patient to cardiac resynchronization therapy (CRT). In this pilot study, we investigated regional electromechanical uncoupling in 10 patients referred for CRT using two non-invasive electrical and mechanical imaging techniques (CMR tissue tracking and ECGI). Reconstructed regional electrical and mechanical activation captured delayed LBBB propagation direction from septal to anterior/inferior and finally to lateral walls as well as from LV apical to basal. All 5 responders demonstrated significantly delayed mechanical and electrical activation on the lateral LV wall at baseline compared to the non-responders (P<.05). On follow-up ECGI, baseline electrical activation patterns were preserved in native rhythm and global LV activation time was reduced with biventricular pacing. The combination of novel imaging techniques of ECGI and CMR tissue tracking can be used to assess spatial concordance of LV electrical and mechanical activation to gain insight into electromechanical coupling. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiac resynchronization therapy with special focus on patency of coronary sinus and its branches: conceptual viewpoint and semi-theoretical considerations on lead-induced obstruction.

PubMed

Stirbys, Petras

2006-01-01

Cardiac resynchronization therapy appears to be useful for patients with severe chronic congestive heart failure. However, many questions still arise concerning the effectiveness of this kind of therapy since hemodynamic improvement is not observed in all patients. Heterogeneity of conclusions reported by several multicenter clinical trials and prominent experts demonstrates that many uncertainties related to cardiac resynchronization therapy still exist. We tried to reveal some inadequacies in clinical results by focusing on cardiac venous blood return which is likely complicated by the presence of lead inside the coronary sinus and its branches. Downstream traversing lead may occlude (partially or completely) the ostia of minor tributaries and target vein of lead final positioning. Thrombosis may also be incited within the coronary sinus itself. Remaining lumen predetermined by the lead body and subsequent thrombosis may be insufficient to provide adequate blood flow. Resulting detrimental venous return presumably may slightly depress myocardial contractility which may be significant in very sensitive group of patients assigned to the New York Heart Association class III or IV. Cardiac venous blood pumping conditions (or venous drainage) are likely also complicated by abnormal activation of left ventricle. The contributory role of these two subtle causes unfavorably influencing venous drainage is still unknown. It may be treated as a hypothetical attempt to find the clue and needs future studies for verification.

ALternate Site Cardiac ResYNChronization (ALSYNC): a prospective and multicentre study of left ventricular endocardial pacing for cardiac resynchronization therapy.

PubMed

Morgan, John M; Biffi, Mauro; Gellér, László; Leclercq, Christophe; Ruffa, Franco; Tung, Stanley; Defaye, Pascal; Yang, Zhongping; Gerritse, Bart; van Ginneken, Mireille; Yee, Raymond; Jais, Pierre

2016-07-14

The ALternate Site Cardiac ResYNChronization (ALSYNC) study evaluated the feasibility and safety of left ventricular endocardial pacing (LVEP) using a market-released pacing lead implanted via a single pectoral access by a novel atrial transseptal lead delivery system. ALSYNC was a prospective clinical investigation with a minimum of 12-month follow-up in 18 centres of cardiac resynchronization therapy (CRT)-indicated patients, who had failed or were unsuitable for conventional CRT. The ALSYNC system comprises the investigational lead delivery system and LVEP lead. Patients required warfarin therapy post-implant. The primary study objective was safety at 6-month follow-up, which was defined as freedom from complications related to the lead delivery system, implant procedure, or the lead ≥70%. The ALSYNC study enrolled 138 patients. The LVEP lead implant success rate was 89.4%. Freedom from complications meeting the definition of primary endpoint was 82.2% at 6 months (95% CI 75.6-88.8%). In the study, 14 transient ischaemic attacks (9 patients, 6.8%), 5 non-disabling strokes (5 patients, 3.8%), and 23 deaths (17.4%) were observed. No death was from a primary endpoint complication. At 6 months, the New York Heart Association class improved in 59% of patients, and 55% had LV end-systolic volume reduction of 15% or greater. Those patients enrolled after CRT non-response showed similar improvement with LVEP. The ALSYNC study demonstrates clinical feasibility, and provides an early indication of possible benefit and risk of LVEP. NCT01277783. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Rare case of left-dominant arrhythmogenic right ventricular cardiomyopathy with dramatic reverse remodeling after cardiac resynchronization as an adjunct to pharmacological therapy.

PubMed

Hsiao, Chih-Chung; Kuo, Jen-Yuan; Yun, Chun-Ho; Hung, Chung-Lieh; Tsai, Cheng-Ho; Yeh, Hung-I

2012-01-01

A 57-year-old man presented with near syncope and hemodynamic compromise after exercise. A sustained ventricular tachycardia (VT) of right bundle-branch block morphology was evident upon examination at our emergency department. Baseline 12-lead electrocardiography revealed a sinus rhythm with a complete left bundle-branch block after successful cardioversion of the VT. Coronary angiography revealed patent coronary arteries, whereas left ventriculography demonstrated impaired systolic function, accompanied by a peculiar basal lateral aneurysm. Both echocardiography and magnetic resonance imaging were consistent with a diagnosis of left-dominant arrhythmogenic right ventricular cardiomyopathy. Four months later, substantial ventricular reverse remodeling and clinical improvements were observed after cardiac resynchronization therapy with a defibrillator, as an adjunct to conventional pharmacological therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Prognostic benefit of optimum left ventricular lead position in cardiac resynchronization therapy: follow-up of the TARGET Study Cohort (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy).

PubMed

Kydd, Anna C; Khan, Fakhar Z; Watson, William D; Pugh, Peter J; Virdee, Munmohan S; Dutka, David P

2014-06-01

This study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT). An optimal LV lead position in CRT is associated with improved clinical outcome. A strategy of speckle-tracking echocardiography can be used to guide the implanter to the site of latest activation and away from segments of low strain amplitude (scar). Long-term, prospective survival data according to LV lead position in CRT are limited. Data from a follow-up registry of 250 consecutive patients receiving CRT between June 2008 and July 2010 were studied. The study population comprised patients recruited to the derivation group and the subsequent TARGET (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy) randomized, controlled trial. Final LV lead position was described, in relation to the pacing site determined by pre-procedure speckle-tracking echocardiography, as optimal (concordant/adjacent) or suboptimal (remote). All-cause mortality was recorded at follow-up. An optimal LV lead position (n = 202) conferred LV remodeling response superior to that of a suboptimal lead position (change in LV end-systolic volume: -24 ± 15% vs. -12 ± 17% [p < 0.001]; change in ejection fraction: +7 ± 8% vs. +4 ± 7% [p = 0.02]). During long-term follow-up (median: 39 months; range: <1 to 61 months), an optimal LV lead position was associated with improved survival (log-rank p = 0.003). A suboptimal LV lead placement independently predicted all-cause mortality (hazard ratio: 1.8; p = 0.024). An optimal LV lead position at the site of latest mechanical activation, avoiding low strain amplitude (scar), was associated with superior CRT response and improved survival that persisted during follow-up. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

PubMed

Duncker, D; Veltmann, C

2018-05-09

In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

The Role of CMR in Cardiomyopathies

PubMed Central

Kramer, Christopher M.

2015-01-01

Cardiac magnetic resonance imaging (CMR) has made major inroads in the new millenium in the diagnosis and assessment of prognosis for patients with cardiomyopathies. Imaging of left and right ventricular structure and function and tissue characterization with late gadolinium enhancement (LGE) as well as T1 and T2 mapping enable accurate diagnosis of the underlying etiology. In the setting of coronary artery disease, either transmurality of LGE or contractile reserve in response to dobutamine can assess the likelihood of recovery of function after revascularization. The presence of scar reduces the likelihood of response to medical therapy and to cardiac resynchronization therapy in heart failure. The presence and extent of LGE relate to overall cardiovascular outcome in cardiomyopathies. An emerging major role for CMR in cardiomyopathies is to identify myocardial scar for diagnostic and prognostic purposes. PMID:26033902

Noninvasive, automatic optimization strategy in cardiac resynchronization therapy.

PubMed

Reumann, Matthias; Osswald, Brigitte; Doessel, Olaf

2007-07-01

Optimization of cardiac resynchronization therapy (CRT) is still unsolved. It has been shown that optimal electrode position,atrioventricular (AV) and interventricular (VV) delays improve the success of CRT and reduce the number of non-responders. However, no automatic, noninvasive optimization strategy exists to date. Cardiac resynchronization therapy was simulated on the Visible Man and a patient data-set including fiber orientation and ventricular heterogeneity. A cellular automaton was used for fast computation of ventricular excitation. An AV block and a left bundle branch block were simulated with 100%, 80% and 60% interventricular conduction velocity. A right apical and 12 left ventricular lead positions were set. Sequential optimization and optimization with the downhill simplex algorithm (DSA) were carried out. The minimal error between isochrones of the physiologic excitation and the therapy was computed automatically and leads to an optimal lead position and timing. Up to 1512 simulations were carried out per pathology per patient. One simulation took 4 minutes on an Apple Macintosh 2 GHz PowerPC G5. For each electrode pair an optimal pacemaker delay was found. The DSA reduced the number of simulations by an order of magnitude and the AV-delay and VV - delay were determined with a much higher resolution. The findings are well comparable with clinical studies. The presented computer model of CRT automatically evaluates an optimal lead position and AV-delay and VV-delay, which can be used to noninvasively plan an optimal therapy for an individual patient. The application of the DSA reduces the simulation time so that the strategy is suitable for pre-operative planning in clinical routine. Future work will focus on clinical evaluation of the computer models and integration of patient data for individualized therapy planning and optimization.

Implantable cardiac resynchronization therapy devices to monitor heart failure clinical status.

PubMed

Fung, Jeffrey Wing-Hong; Yu, Cheuk-Man

2007-03-01

Cardiac resynchronization therapy is a standard therapy for selected patients with heart failure. With advances in technology and storage capacity, the device acts as a convenient platform to provide valuable information about heart failure status in these high-risk patients. Unlike other modalities of investigation which may only allow one-off evaluation, heart failure status can be monitored by device diagnostics including heart rate variability, activity status, and intrathoracic impedance in a continuous basis. These parameters do not just provide long-term prognostic information but also may be useful to predict upcoming heart failure exacerbation. Prompt and early intervention may abort decompensation, prevent hospitalization, improve quality of life, and reduce health care cost. Moreover, this information may be applied to titrate the dosage of medication and monitor response to heart failure treatment. This review will focus on the prognostic and predictive values of heart failure status monitoring provided by these devices.

Understanding nonresponders of cardiac resynchronization therapy--current and future perspectives.

PubMed

Yu, Cheuk-Man; Wing-Hong Fung, Jeffrey; Zhang, Qing; Sanderson, John E

2005-10-01

Cardiac resynchronization therapy (CRT) is now an established nonpharmacologic therapy for advanced heart failure with electromechanical delay. Despite compelling evidence of the benefits of CRT, one troubling issue is the lack of a favorable response in about one-third of patients. Currently, there is no unifying definition of responders, and published data were based on acute hemodynamic changes, chronic left ventricular reverse remodeling, as well as the intermediate or long-term clinical response. The lack of improvement with CRT can be due to many factors including the placement of the left ventricular pacing lead in an inappropriate location, the absence of electrical conduction delay or mechanical dyssynchrony despite wide QRS complexes, and possibly failure to optimize the CRT settings after device implantation. In acute hemodynamic studies, placing the left ventricular leads at the free wall region has been suggested to generate the best pulse pressure and positive dp/dt. The degree of mechanical dyssynchrony has recently been assessed noninvasively in CRT patients by echocardiography and in particular by tissue Doppler imaging. These studies suggested that responders of left ventricular reverse remodeling or systolic function had more severe systolic dyssynchrony. However, further studies are needed to examine the clinical utility of these parameters when applied to the standardized anatomic or functional endpoints. Optimization of atrioventricular and interventricular pacing intervals may also reduce the number of nonresponders, though newer methods, especially interventricular pacing intervals, are still under clinical investigation. With the adjunctive use of imaging technology, physicians are able to characterize the response to CRT objectively, and cardiac imaging is an important clinical tool for determining more precisely the presence and degree of mechanical dyssynchrony.

Unexpected and rapid recovery of left ventricular function in patients with peripartum cardiomyopathy: impact of cardiac resynchronization therapy.

PubMed

Mouquet, Frederic; Mostefa Kara, Meriem; Lamblin, Nicolas; Coulon, Capucine; Langlois, Stephane; Marquie, Christelle; de Groote, Pascal

2012-05-01

Aim Peripartum cardiomyopathy (PPCM) is a rare cause of dilated cardiomyopathy responsible for heart failure toward the end of pregnancy, which can lead to chronic heart failure in 50% of cases. In this short report, we assessed the benefit of cardiac resynchronization in patients with PPCM and chronic systolic dysfunction despite optimal medical treatment. For the last 10 years, we managed eight patients diagnosed with PPCM. Two of them presented severe systolic dysfunction, and medical treatment resulted in limited improvement from 10% to 25% and from 25% to 28% despite optimal treatment for 9 and 6 years, respectively. These two patients were porposed to receive an implantatable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT). Six months after ICD-CRT treatment, we observed a significant improvement in systolic function from 25% to 45% and 28% to 50%, respectively, and positive remodelling with reduction of left ventricular end-diastolic volume from 216 to 144 mL and from 354 to 105 mL, which represent a 34% and a 70% reduction, respectively. Physicians in charge of patients with PPCM should offer the opportunity of CRT for patients whose cardiac function has not significantly improved under standard medical treatment.

Ventricular antitachycardia pacing therapy in patients with heart failure implanted with a cardiac resynchronization therapy defibrillator device: Efficacy, safety, and impact on mortality.

PubMed

Landolina, Maurizio; Lunati, Maurizio; Boriani, Giuseppe; Pietro Ricci, Renato; Proclemer, Alessandro; Facchin, Domenico; Rordorf, Roberto; Morani, Giovanni; Maines, Massimiliano; Gasparini, Gianni; Molon, Giulio; Turrini, Pietro; Gasparini, Maurizio

2016-02-01

Cardiac resynchronization therapy defibrillator can terminate ventricular tachycardia (VT) and fast VT (FVT) via antitachycardia pacing (ATP). We evaluated efficacy and safety of ATP, whether ATP induces ventricular arrhythmias after inappropriate ATP or atrial fibrillation (AF) after appropriate ATP, and whether ATP is associated with mortality. A total of 1404 patients with a cardiac resynchronization therapy defibrillator were followed in a prospective multicenter observational research. All-cause mortality rates were estimated in patient subgroups in order to uncouple the trigger (VT/FVT or other rhythms causing inappropriate detections) from ATP therapy. Over a median follow-up of 31 months, 2938 VT/FVT episodes were treated with ATP in 360 patients. The adjusted ATP success rate was 63% (95% confidence interval [CI] 57%-69%) on FVTs and 68% (95% CI 62%-74%) on VTs. Acceleration occurred in 55 (1.87%) and syncope in 4 (0.14%) of all ATP-treated episodes. In 14 true VT/FVT episodes in 5 patients, AF followed ATP therapy. In 4 episodes in 2 patients, VT followed ATP inappropriately applied during AF. Death rate per 100 patient-years was 5.6 (95% CI 4.3-7.5) in patients with appropriate ATP and 1.5 (95% CI 0.4-6.1) in patients with inappropriate ATP (P = .045). ATP was effective in terminating VT/FVT episodes and displayed a good safety profile. ATP therapies by themselves did not increase death risk; prognosis was indeed better in patients without arrhythmic episodes, even if they received inappropriate ATP, than in patients with ATP on VT/FVT episodes. Adverse outcomes observed in patients receiving implantable cardioverter-defibrillator therapies are probably related to the arrhythmia itself, a marker of disease progression, rather than to adverse effects of ATP. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Association between frequent cardiac resynchronization therapy optimization and long-term clinical response: a post hoc analysis of the Clinical Evaluation on Advanced Resynchronization (CLEAR) pilot study.

PubMed

Delnoy, Peter Paul; Ritter, Philippe; Naegele, Herbert; Orazi, Serafino; Szwed, Hanna; Zupan, Igor; Goscinska-Bis, Kinga; Anselme, Frederic; Martino, Maria; Padeletti, Luigi

2013-08-01

The long-term clinical value of the optimization of atrioventricular (AVD) and interventricular (VVD) delays in cardiac resynchronization therapy (CRT) remains controversial. We studied retrospectively the association between the frequency of AVD and VVD optimization and 1-year clinical outcomes in the 199 CRT patients who completed the Clinical Evaluation on Advanced Resynchronization study. From the 199 patients assigned to CRT-pacemaker (CRT-P) (New York Heart Association, NYHA, class III/IV, left ventricular ejection fraction <35%), two groups were retrospectively composed a posteriori on the basis of the frequency of their AVD and VVD optimization: Group 1 (n = 66) was composed of patients 'systematically' optimized at implant, at 3 and 6 months; Group 2 (n = 133) was composed of all other patients optimized 'non-systematically' (less than three times) during the 1 year study. The primary endpoint was a composite of all-cause mortality, heart failure-related hospitalization, NYHA functional class, and Quality of Life score, at 1 year. Systematic CRT optimization was associated with a higher percentage of improved patients based on the composite endpoint (85% in Group 1 vs. 61% in Group 2, P < 0.001), with fewer deaths (3% in Group 1 vs. 14% in Group 2, P = 0.014) and fewer hospitalizations (8% in Group 1 vs. 23% in Group 2, P = 0.007), at 1 year. These results further suggest that AVD and VVD frequent optimization (at implant, at 3 and 6 months) is associated with improved long-term clinical response in CRT-P patients.

Efficient preloading of the ventricles by a properly timed atrial contraction underlies stroke work improvement in the acute response to cardiac resynchronization therapy

PubMed Central

Hu, Yuxuan; Gurev, Viatcheslav; Constantino, Jason; Trayanova, Natalia

2013-01-01

Background The acute response to cardiac resynchronization therapy (CRT) has been shown to be due to three mechanisms: resynchronization of ventricular contraction, efficient preloading of the ventricles by a properly timed atrial contraction, and mitral regurgitation reduction. However, the contribution of each of the three mechanisms to the acute response of CRT, specifically stroke work improvement, has not been quantified. Objective The goal of this study was to use an MRI-based anatomically accurate 3D model of failing canine ventricular electromechanics to quantify the contribution of each of the three mechanisms to stroke work improvement and identify the predominant mechanisms. Methods An MRI-based electromechanical model of the failing canine ventricles assembled previously by our group was further developed and modified. Three different protocols were used to dissect the contribution of each of the three mechanisms to stroke work improvement. Results Resynchronization of ventricular contraction did not lead to significant stroke work improvement. Efficient preloading of the ventricles by a properly timed atrial contraction was the predominant mechanism underlying stroke work improvement. Stroke work improvement peaked at an intermediate AV delay, as it allowed ventricular filling by atrial contraction to occur at a low diastolic LV pressure but also provided adequate time for ventricular filling before ventricular contraction. Diminution of mitral regurgitation by CRT led to stroke work worsening instead of improvement. Conclusion Efficient preloading of the ventricles by a properly timed atrial contraction is responsible for significant stroke work improvement in the acute CRT response. PMID:23928177

Prognostic Role of Right Ventricular Function in Patients With Heart Failure Undergoing Cardiac Resynchronization Therapy.

PubMed

Rapacciuolo, Antonio; Maffè, Stefano; Palmisano, Pietro; Ferraro, Anna; Cecchetto, Antonella; D'Onofrio, Antonio; Solimene, Francesco; Musatti, Paola; Paffoni, Paola; Esposito, Francesca; Parravicini, Umberto; Agresta, Alessia; Botto, Giovanni Luca; Malacrida, Maurizio; Stabile, Giuseppe

2016-11-01

Because 20% to 40% of patients undergoing cardiac resynchronization therapy (CRT) do not respond to it, identification of potential factors predicting response is a relevant research topic. There is a possible association between right ventricular function and response to CRT. We analyzed 227 patients from the Cardiac Resynchronization Therapy Modular Registry (CRT-MORE) who received CRT according to current guidelines from March to December 2013. Response to therapy was defined as a decrease of ≥15% in left ventricular end-systolic volume (LVESV) at 6 months. The tricuspid annular plane systolic excursion (TAPSE) value that best predicted improvement in LVESV (sensitivity 68%, specificity 54%) was 17 mm. Stratifying patients according to TAPSE, LVESV decreased ≥15% in 78% of patients with TAPSE >17 mm (vs 59% in patients with TAPSE ≤17 mm; P = 0.006). At multivariate analysis, TAPSE >17 mm was independently associated with LVESV improvement (odds ratio: 1.97, 95% confidence interval: 1.03-3.80, P < 0.05), together with ischemic etiology (odds ratio: 0.39, 95% confidence interval: 0.20-0.75, P < 0.01). These results were confirmed for New York Heart Association class III to IV patients (79% echocardiographic response rate in patients with TAPSE >17 mm vs 55% in patients with TAPSE <17 mm; P = 0.012). Baseline signs of right ventricular dysfunction suggest possible remodeling after CRT. A TAPSE value of 17 mm was identified as a good cutoff for predicting a better response to CRT in patients with both mildly symptomatic and severe heart failure. © 2016 Wiley Periodicals, Inc.

[Cardiac resynchronization therapy for heart failure - from experimental pacing to evidence-based therapy].

PubMed

Götze, S; Butter, C; Fleck, E

2006-01-01

Within the last decade, cardiac resynchronization therapy (CRT) has become an evidence-based cornerstone for a subset of patients with chronic heart failure. For those, who suffer from ischemic or non-ischemic cardiomyopathies at NYHA III or IV, have sinus rhythm, a left bundle branch block and a left ventricular ejection fraction below 35%, CRT has evolved as an important treatment option with promising results. Numerous studies have shown that in these patients pacemaker-mediated correction of intra- and interventicular conduction disturbances can improve not only clinical symptoms, exercise tolerance and the frequency of hospitalizations, but even more important the overall mortality. These clinical results are due to several functional aspects. In the failing heart characteristic intra- and interventricular alterations in electrical conduction result in mechanical asynchrony that leads to an abnormal contraction of the left ventricle with delayed activation of the lateral wall, a paradoxical septal movement, a reduced diastolic filling and a mitral regurgitation due to dyssynchrony of papillary muscle activation. It is conceivable that these functional changes have fatal consequences for the failing heart. AV-optimized left- or biventricular stimulation by modern pacemakers can correct the pathological dyssynchrony, thereby improving cardiac function and clinical outcome in these patients. Although tremendous progress in cardiac resynchronization therapy has been made during the last decade, a couple of questions still need to be resolved. Critical issues are the identification of patients, who will predictably benefit from CRT, the value of CRT-pacemakers versus CRT-ICDs, and the usefullness of CRT in patients with atrial fibrillation.

Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial.

PubMed

Khan, Fakhar Z; Virdee, Mumohan S; Palmer, Christopher R; Pugh, Peter J; O'Halloran, Denis; Elsik, Maros; Read, Philip A; Begley, David; Fynn, Simon P; Dutka, David P

2012-04-24

This study sought to assess the impact of targeted left ventricular (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT). Placement of the LV lead to the latest sites of contraction and away from the scar confers the best response to CRT. We conducted a randomized, controlled trial to compare a targeted approach to LV lead placement with usual care. A total of 220 patients scheduled for CRT underwent baseline echocardiographic speckle-tracking 2-dimensional radial strain imaging and were then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy]), the LV lead was positioned at the latest site of peak contraction with an amplitude of >10% to signify freedom from scar. In group 2 (control) patients underwent standard unguided CRT. Patients were classified by the relationship of the LV lead to the optimal site as concordant (at optimal site), adjacent (within 1 segment), or remote (≥2 segments away). The primary endpoint was a ≥15% reduction in LV end-systolic volume at 6 months. Secondary endpoints were clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and combined all-cause mortality and heart failure-related hospitalization. The groups were balanced at randomization. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031), giving an absolute difference in the primary endpoint of 15% (95% confidence interval: 2% to 28%). Compared with controls, TARGET patients had a higher clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined endpoint (log-rank test, p = 0.031). Compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure-related hospitalization. (Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy [TARGET] study); ISRCTN19717943). Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Implantation of a cardiac resynchronization therapy-defibrillator device in a patient with persistent left superior vena cava.

PubMed

Atar, İlyas; Karaçağlar, Emir; Özçalık, Emre; Özin, Bülent; Müderrisoğlu, Haldun

2015-06-01

Presence of a persistent left superior vena cava (PLSVC) is generally clinically asymptomatic and discovered incidentally during central venous catheterization. However, PLSVC may cause technical difficulties during cardiac device implantation. An 82-year-old man with heart failure symptoms and an ejection fraction (EF) of 20% was scheduled for resynchronization therapy-defibrillator device (CRT-D) implantation. A PLSVC draining via a dilated coronary sinus into an enlarged right atrium was diagnosed. First, an active-fixation right ventricular lead was inserted into the right atrium through the PLSVC. The stylet was preshaped to facilitate its passage to the right ventricular apex. An atrial lead was positioned on the right atrium free wall, and an over-the-wire coronary sinus lead deployed to a stable position. CRT-D implantation procedure was successfully completed.

Cardiac Resynchronization Therapy (CRT)

MedlinePlus

... with other treatments to achieve the best results. Heart Failure Questions to Ask Your Doctor Use these questions ... and procedures related to heart disease and stroke. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

Clinical benefit of cardiac resynchronization therapy with a defibrillator in patients with an ejection fraction > 35% estimated by cardiac magnetic resonance.

PubMed

Fabregat-Andrés, Oscar; García-González, Pilar; Valle-Muñoz, Alfonso; Estornell-Erill, Jordi; Pérez-Boscá, Leandro; Palanca-Gil, Victor; Payá-Serrano, Rafael; Quesada-Dorador, Aurelio; Morell, Salvador; Ridocci-Soriano, Francisco

2014-02-01

Cardiac resynchronization therapy with a defibrillator prolongs survival and improves quality of life in advanced heart failure. Traditionally, patients with ejection fraction > 35 estimated by echocardiography have been excluded. We assessed the prognostic impact of this therapy in a group of patients with severely depressed systolic function as assessed by echocardiography but with an ejection fraction > 35% as assessed by cardiac magnetic resonance. We analyzed consecutive patients admitted for decompensated heart failure between 2004 and 2011. The patients were in functional class II-IV, with a QRS ≥ to 120 ms, ejection fraction ≤ 35% estimated by echocardiography, and a cardiac magnetic resonance study. We included all patients (n=103) who underwent device implantation for primary prevention. Ventricular arrhythmia, all-cause mortality and readmission for heart failure were considered major cardiac events. The patients were divided into 2 groups according to systolic function assessed by magnetic resonance. The 2 groups showed similar improvements in functional class and ejection fraction at 6 months. We found a nonsignificant trend toward a higher risk of all-cause mortality in patients with systolic function ≤ 35% at long-term follow-up. The presence of a pattern of necrosis identified patients with a worse prognosis for ventricular arrhythmias and mortality in both groups. We conclude that cardiac resynchronization therapy with a defibrillator leads to a similar clinical benefit in patients with an ejection fraction ≤ 35% or > 35% estimated by cardiac magnetic resonance. Analysis of the pattern of late gadolinium enhancement provides additional information on arrhythmic risk and long-term prognosis. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Evaluation of synergistic effects of resynchronization therapy and a β-blocker up-titration strategy based on a predefined patient-management program: the RESTORE study.

PubMed

Palmisano, Pietro; Ammendola, Ernesto; D'Onofrio, Antonio; Accogli, Michele; Calò, Leonardo; Ruocco, Antonio; Rapacciuolo, Antonio; Del Giorno, Giuseppe; Bianchi, Valter; Malacrida, Maurizio; Valsecchi, Sergio; Gronda, Edoardo

2015-01-01

Prior studies have suggested that a substantial number of eligible heart failure (HF) patients fail to receive β-blocker therapy, or receive it at a suboptimal dose. The aim of this study is to assess the benefit of a predefined management program designed for β-blocker up-titration, evaluating the synergistic effect of cardiac resynchronization therapy (CRT) and β-blockers in a HF population. The Resynchronization Therapy and β-Blocker Titration (RESTORE) study is a prospective, case-control, multicenter cohort study designed to test the hypothesis that a β-blocker up-titration strategy based on a predefined management program maximizes the beneficial effect of CRT, increasing the number of patients reaching the target dose of β-blockers and improving their clinical outcome. All study patients receive an implantable defibrillator for CRT delivery in accordance with current guidelines. Enrollments started in December 2011 and are scheduled to end in December 2014. Approximately 250 consecutive patients will be prospectively enrolled in 6 Italian centers and followed up for 24 months after implantation. The primary endpoint is to demonstrate that CRT may allow titration of β-blockers until the optimal dose, or at least to the effective dose, in patients with HF. This study might provide important information about the benefit of a predefined management program for β-blocker up-titration in patients receiving CRT. Moreover, assessment of health-care utilization and the consumption of resources will allow estimating the potential utility of remote monitoring by means of an automated telemedicine system in facilitating the titration of β-blockers in comparison with a standard in-hospital approach. © 2015 Wiley Periodicals, Inc.

Prognostic value of heart rate variability footprint and standard deviation of average 5-minute intrinsic R-R intervals for mortality in cardiac resynchronization therapy patients.

PubMed

Gilliam, F Roosevelt; Singh, Jagmeet P; Mullin, Christopher M; McGuire, Maureen; Chase, Kellie J

2007-10-01

Cardiac resynchronization therapy devices provide effective therapy for heart failure. Heart rate variability (HRV) parameters in the device such as HRV footprint and SD of average 5-minute intrinsic R-R intervals (SDANN) are related to autonomic function and may be used to identify patients with a higher risk of mortality. We examined the relationship between HRV and mortality in a prospective cohort study. The 842 patients (mean age, 67.7 +/- 11.2; 23.5 % female; New York Heart Association class III, 88.6%; class IV, 11.4%) included in the analysis were implanted with a cardiac resynchronization therapy with defibrillation device and had baseline HRV measurements available. During a median of 11.6 months of follow-up, 7.8% (66/842) of patients died. Heart rate variability footprint and SDANN were significant predictors of mortality (all P < .05); patients with lower HRV values were at greater risk for death, compared with patients with higher HRV values. Heart rate variability changes over time tended to predict the risk of mortality in follow-up (P = nonsignificant); patients with low baseline HRV and small changes in HRV during the follow-up period were at the highest risk for death (7% mortality for SDANN and 8.9% for HRV footprint), and patients with high baseline HRV and large changes in HRV were at the lowest risk (1.5% mortality for SDANN and 2.4% for HRV footprint). Results were consistent when adjusted for age, sex, body mass index, and diastolic blood pressure. Continuously measured device HRV parameters provide prognostic information about patient mortality that may be helpful for risk stratification.

Incidence, predictors, and procedural results of upgrade to resynchronization therapy: the RAFT upgrade substudy.

PubMed

Essebag, Vidal; Joza, Jacqueline; Birnie, David H; Sapp, John L; Sterns, Laurence D; Philippon, Francois; Yee, Raymond; Crystal, Eugene; Kus, Teresa; Rinne, Claus; Healey, Jeffrey S; Sami, Magdi; Thibault, Bernard; Exner, Derek V; Coutu, Benoit; Simpson, Chris S; Wulffhart, Zaev; Yetisir, Elizabeth; Wells, George; Tang, Anthony S L

2015-02-01

The resynchronization-defibrillation for ambulatory heart failure trial (RAFT) study demonstrated that adding cardiac resynchronization therapy (CRT) in selected patients requiring de novo implantable cardiac defibrillators (ICD) reduced mortality as compared with ICD therapy alone, despite an increase in procedure-related adverse events. Data are lacking regarding the management of patients with ICD therapy who develop an indication for CRT upgrade. Participating RAFT centers provided data regarding de novo CRT-D (CRT with ICD) implant, upgrade to CRT-D during RAFT (study upgrade), and upgrade within 6 months after presentation of study results (substudy). Substudy centers enrolled 1346 (74.9%) patients in RAFT, including 644 de novo, 80 study upgrade, and 60 substudy CRT attempts. The success rate (initial plus repeat attempts) was 95.2% for de novo versus 96.3% for study upgrade and 90.0% for substudy CRT attempts (P=0.402). Acute complications occurred among 26.2% of de novo versus 18.8% of study upgrade and 3.4% of substudy CRT implantation attempts (P<0.001). The most common complication was left ventricular lead dislodgement. The principal reasons for not yet attempting upgrade in the substudy were patient preference (31.9%), New York Heart Association Class I (17.0%), and a QRS<150 ms (13.1%). Among a broad group of implant physicians, CRT upgrades were performed in patients with an ICD in situ with no difference in implant success rate and a reduced acute complication rate as compared with a de novo CRT implant. Decisions to upgrade were influenced by predictors of benefit in subgroup analyses of the RAFT study and other trials. © 2014 American Heart Association, Inc.

Pectoral nerves (PECS) and intercostal nerve block for cardiac resynchronization therapy device implantation.

PubMed

Fujiwara, Atsushi; Komasawa, Nobuyasu; Minami, Toshiaki

2014-01-01

A 71-year-old man was scheduled to undergo cardiac resynchronization therapy device (CRTD) implantation. He was combined with severe chronic heart failure due to ischemic heart disease. NYHA class was 3 to 4 and electrocardiogram showed non-sustained ventricular. Ejection fraction was about 20% revealed by transthoracic echocardiogram. He was also on several anticoagulation medications. We planned to implant the device under the greater pectoral muscle. As general anesthesia was considered risky, monitored anesthesia care utilizing peripheral nerve block and slight sedation was scheduled. Pectoral nerves (PECS) block and intercostal block was performed under ultrasonography with ropivacaine. For sedation during the procedure, continuous infusion of dexmedetomidine without a loading dose was performed. The procedure lasted about 3 hours, but the patient showed no pain or restlessness. Combination of PECS block and intercostal block may provide effective analgesia for CRTD implantation.

Towards an atrio-ventricular delay optimization assessed by a computer model for cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Ojeda, David; Le Rolle, Virginie; Tse Ve Koon, Kevin; Thebault, Christophe; Donal, Erwan; Hernández, Alfredo I.

2013-11-01

In this paper, lumped-parameter models of the cardiovascular system, the cardiac electrical conduction system and a pacemaker are coupled to generate mitral ow pro les for di erent atrio-ventricular delay (AVD) con gurations, in the context of cardiac resynchronization therapy (CRT). First, we perform a local sensitivity analysis of left ventricular and left atrial parameters on mitral ow characteristics, namely E and A wave amplitude, mitral ow duration, and mitral ow time integral. Additionally, a global sensitivity analysis over all model parameters is presented to screen for the most relevant parameters that a ect the same mitral ow characteristics. Results provide insight on the in uence of left ventricle and atrium in uence on mitral ow pro les. This information will be useful for future parameter estimation of the model that could reproduce the mitral ow pro les and cardiovascular hemodynamics of patients undergoing AVD optimization during CRT.

The Use of Epicardial Electrogram as a Simple Guide to Select the Optimal Site of Left Ventricular Pacing in Cardiac Resynchronization Therapy

PubMed Central

Fatemi, Marjaneh; Le Gal, Grégoire; Blanc, Jean-Jacques; Mansourati, Jacques; Etienne, Yves

2011-01-01

Cardiac resynchronization therapy (CRT) has been demonstrated to improve symptoms and survival in patients with left ventricular (LV) systolic dysfunction and dyssynchrony. To achieve this goal, the LV lead should be positioned in a region of delayed contraction. We hypothesized that pacing at the site of late electrical activation was also associated with long-term response to CRT. We conducted a retrospective study on 72 CRT patients. For each patient, we determined the electrical delay (ED) from the onset of QRS to the epicardial EGM and the ratio of ED to QRS duration (ED/QRS duration). After a followup of 30 ± 20 months, 47 patients responded to CRT. Responders had a significantly longer ED and greater ratio of ED/QRS duration than nonresponders. An ED/QRS duration ≥0.38 predicted a response to CRT with 89% specificity and 53% sensitivity. PMID:21403903

Cardiac implantable electronic device infection due to Mycobacterium species: a case report and review of the literature.

PubMed

Al-Ghamdi, Bandar; Widaa, Hassan El; Shahid, Maie Al; Aladmawi, Mohammed; Alotaibi, Jawaher; Sanei, Aly Al; Halim, Magid

2016-08-24

Infection of cardiac implantable electronic devices is a serious cardiovascular disease and it is associated with a high mortality. Mycobacterium species may rarely cause cardiac implantable electronic devices infection. We are reporting a case of miliary tuberculosis in an Arab patient with dilated cardiomyopathy and a cardiac resynchronization therapy-defibrillator device that was complicated with infection of his cardiac resynchronization therapy-defibrillator device. To our knowledge, this is the third case in the literature with such a presentation and all patients died during the course of treatment. This underscores the importance of early diagnosis and management. We also performed a literature review of reported cases of cardiac implantable electronic devices infection related to Mycobacterium species. Cardiac implantable electronic devices infection due to Mycobacterium species is an uncommon but a well-known entity. Early diagnosis and prompt management may result in a better outcome.

The Role of Echocardiography in the Optimization of Cardiac Resynchronization Therapy: Current Evidence and Future Perspectives.

PubMed

Spartalis, Michael; Tzatzaki, Eleni; Spartalis, Eleftherios; Damaskos, Christos; Athanasiou, Antonios; Livanis, Efthimios; Voudris, Vassilis

2017-01-01

Cardiac resynchronization therapy (CRT) has become a mainstay in the management of heart failure. Up to one-third of patients who received resynchronization devices do not experience the full benefits of CRT. The clinical factors influencing the likelihood to respond to the therapy are wide QRS complex, left bundle branch block, female gender, non-ischaemic cardiomyopathy (highest responders), male gender, ischaemic cardiomyopathy (moderate responders) and narrow QRS complex, non-left bundle branch block (lowest, non-responders). This review provides a conceptual description of the role of echocardiography in the optimization of CRT. A literature survey was performed using PubMed database search to gather information regarding CRT and echocardiography. A total of 70 studies met selection criteria for inclusion in the review. Echocardiography helps in the initial selection of the patients with dyssynchrony, which will benefit the most from optimal biventricular pacing and provides a guide to left ventricular (LV) lead placement during implantation. Different echocardiographic parameters have shown promise and can offer the possibility of patient selection, response prediction, lead placement optimization strategies and optimization of device configurations. LV ejection fraction along with specific electrocardiographic criteria remains the cornerstone of CRT patient selection. Echocardiography is a non-invasive, cost-effective, highly reproducible method with certain limitations and accuracy that is affected by measurement errors. Echocardiography can assist with the identification of the appropriate electromechanical substrate of CRT response and LV lead placement. The targeted approach can improve the haemodynamic response, as also the patient-specific parameters estimation.

The Role of Echocardiography in the Optimization of Cardiac Resynchronization Therapy: Current Evidence and Future Perspectives

PubMed Central

Spartalis, Michael; Tzatzaki, Eleni; Spartalis, Eleftherios; Damaskos, Christos; Athanasiou, Antonios; Livanis, Efthimios; Voudris, Vassilis

2017-01-01

Background: Cardiac resynchronization therapy (CRT) has become a mainstay in the management of heart failure. Up to one-third of patients who received resynchronization devices do not experience the full benefits of CRT. The clinical factors influencing the likelihood to respond to the therapy are wide QRS complex, left bundle branch block, female gender, non-ischaemic cardiomyopathy (highest responders), male gender, ischaemic cardiomyopathy (moderate responders) and narrow QRS complex, non-left bundle branch block (lowest, non-responders). Objective: This review provides a conceptual description of the role of echocardiography in the optimization of CRT. Method: A literature survey was performed using PubMed database search to gather information regarding CRT and echocardiography. Results: A total of 70 studies met selection criteria for inclusion in the review. Echocardiography helps in the initial selection of the patients with dyssynchrony, which will benefit the most from optimal biventricular pacing and provides a guide to left ventricular (LV) lead placement during implantation. Different echocardiographic parameters have shown promise and can offer the possibility of patient selection, response prediction, lead placement optimization strategies and optimization of device configurations. Conclusion: LV ejection fraction along with specific electrocardiographic criteria remains the cornerstone of CRT patient selection. Echocardiography is a non-invasive, cost-effective, highly reproducible method with certain limitations and accuracy that is affected by measurement errors. Echocardiography can assist with the identification of the appropriate electromechanical substrate of CRT response and LV lead placement. The targeted approach can improve the haemodynamic response, as also the patient-specific parameters estimation. PMID:29387277

Scar Characterization to Predict Life-Threatening Arrhythmic Events and Sudden Cardiac Death in Patients With Cardiac Resynchronization Therapy: The GAUDI-CRT Study.

PubMed

Acosta, Juan; Fernández-Armenta, Juan; Borràs, Roger; Anguera, Ignasi; Bisbal, Felipe; Martí-Almor, Julio; Tolosana, Jose M; Penela, Diego; Andreu, David; Soto-Iglesias, David; Evertz, Reinder; Matiello, María; Alonso, Concepción; Villuendas, Roger; de Caralt, Teresa M; Perea, Rosario J; Ortiz, Jose T; Bosch, Xavier; Serra, Luis; Planes, Xavier; Greiser, Andreas; Ekinci, Okan; Lasalvia, Luis; Mont, Lluis; Berruezo, Antonio

2018-04-01

The aim of this study was to analyze whether scar characterization could improve the risk stratification for life-threatening ventricular arrhythmias and sudden cardiac death (SCD). Among patients with a cardiac resynchronization therapy (CRT) indication, appropriate defibrillator (CRT-D) therapy rates are low. Primary prevention patients with a class I indication for CRT were prospectively enrolled and assigned to CRT-D or CRT pacemaker according to physician's criteria. Pre-procedure contrast-enhanced cardiac magnetic resonance was obtained and analyzed to identify scar presence or absence, quantify the amount of core and border zone (BZ), and depict BZ distribution. The presence, mass, and characteristics of BZ channels in the scar were recorded. The primary endpoint was appropriate defibrillator therapy or SCD. 217 patients (39.6% ischemic) were included. During a median follow-up of 35.5 months (12 to 62 months), the primary endpoint occurred in 25 patients (11.5%) and did not occur in patients without myocardial scar. Among patients with scar (n = 125, 57.6%), those with implantable cardioverter-defibrillator (ICD) therapies or SCD exhibited greater scar mass (38.7 ± 34.2 g vs. 17.9 ± 17.2 g; p < 0.001), scar heterogeneity (BZ mass/scar mass ratio) (49.5 ± 13.0 vs. 40.1 ± 21.7; p = 0.044), and BZ channel mass (3.6 ± 3.0 g vs. 1.8 ± 3.4 g; p = 0.018). BZ mass (hazard ratio: 1.06 [95% confidence interval: 1.04 to 1.08]; p < 0.001) and BZ channel mass (hazard ratio: 1.21 [95% confidence interval: 1.10 to 1.32]; p < 0.001) were the strongest predictors of the primary endpoint. An algorithm based on scar mass and the absence of BZ channels identified 148 patients (68.2%) without ICD therapy/SCD during follow-up with a 100% negative predictive value. The presence, extension, heterogeneity, and qualitative distribution of BZ tissue of myocardial scar independently predict appropriate ICD therapies and SCD in CRT patients. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Canadian Cardiovascular Society guidelines on the use of cardiac resynchronization therapy: implementation.

PubMed

Parkash, Ratika; Philippon, François; Shanks, Miriam; Thibault, Bernard; Cox, Jafna; Low, Aaron; Essebag, Vidal; Bashir, Jamil; Moe, Gordon; Birnie, David H; Larose, Eric; Yee, Raymond; Swiggum, Elizabeth; Kaul, Padma; Redfearn, Damian; Tang, Anthony S; Exner, Derek V

2013-11-01

Recent studies have provided the impetus to update the recommendations for cardiac resynchronization therapy (CRT). This article provides guidance on the implementation of CRT and is intended to serve as a framework for the implementation of CRT within the Canadian health care system and beyond. These guidelines were developed through a critical evaluation of the existing literature, and expert consensus. The panel unanimously adopted each recommendation. The 9 recommendations relate to patient selection in the presence of comorbidities, delivery and optimization of CRT, and resources required to deliver this therapy. The strength of evidence was weighed, taking full consideration of any risk of bias, and any imprecision, inconsistency, and indirectness of the available data. The strength of each recommendation and the quality of evidence were adjudicated. Trade-offs between desirable and undesirable consequences of alternative management strategies were considered, as were values, preferences, and resource availability. These guidelines were externally reviewed by experts, modified based on those reviews, and will be updated as new knowledge is acquired. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

A randomized pilot study of optimization of cardiac resynchronization therapy in sinus rhythm patients using a peak endocardial acceleration sensor vs. standard methods.

PubMed

Ritter, Philippe; Delnoy, Peter Paul H M; Padeletti, Luigi; Lunati, Maurizio; Naegele, Herbert; Borri-Brunetto, Alberto; Silvestre, Jorge

2012-09-01

Non-response rate to cardiac resynchronization therapy (CRT) might be decreased by optimizing device programming. The Clinical Evaluation on Advanced Resynchronization (CLEAR) study aimed to assess the effects of CRT with automatically optimized atrioventricular (AV) and interventricular (VV) delays, based on a Peak Endocardial Acceleration (PEA) signal system. This multicentre, single-blind study randomized patients in a 1 : 1 ratio to CRT optimized either automatically by the PEA-based system, or according to centres' usual practices, mostly by echocardiography. Patients had heart failure (HF) New York Heart Association (NYHA) functional class III/IV, left ventricular ejection fraction (LVEF) <35%, QRS duration >150 or >120 ms with mechanical dyssynchrony. Follow-up was 1 year. The primary endpoint was the proportion of patients who improved their condition at 1 year, based on a composite of all-cause death, HF hospitalizations, NYHA class, and quality of life. In all, 268 patients in sinus rhythm (63% men; mean age: 73.1 ± 9.9 years; mean NYHA: 3.0 ± 0.3; mean LVEF: 27.1 ± 8.1%; and mean QRS duration: 160.1 ± 22.0 ms) were included and 238 patients were randomized, 123 to PEA and 115 to the control group. At 1 year, 76% of patients assigned to PEA were classified as improved, vs. 62% in the control group (P= 0.0285). The percentage of patients with improved NYHA class was significantly (P= 0.0020) higher in the PEA group than in controls. Fatal and non-fatal adverse events were evenly distributed between the groups. PEA-based optimization of CRT in HF patients significantly increased the proportion of patients who improved with therapy, mainly through improved NYHA class, after 1 year of follow-up.

Adherence to 2016 European Society of Cardiology guidelines predicts outcome in a large real-world population of heart failure patients requiring cardiac resynchronization therapy.

PubMed

Stabile, Giuseppe; Pepi, Patrizia; Palmisano, Pietro; D'Onofrio, Antonio; De Simone, Antonio; Caico, Salvatore Ivan; Pecora, Domenico; Rapacciuolo, Antonio; Arena, Giuseppe; Marini, Massimiliano; Pieragnoli, Paolo; Badolati, Sandra; Savarese, Gianluca; Maglia, Gianpiero; Iuliano, Assunta; Botto, Giovanni Luca; Malacrida, Maurizio; Bertaglia, Emanuele

2018-04-14

Professional guidelines are based on the best available evidence. However, patients treated in clinical practice may differ from those included in reference trials. The aim of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in a large population of patients implanted with a CRT device stratified in accordance with the 2016 European heart failure (HF) guidelines. We collected data on 930 consecutive patients from the Cardiac Resynchronization Therapy MOdular REgistry. The primary end point was a composite of death and HF hospitalization. Five hundred sixty-three (60.5%) patients met class I indications, 145 (15.6%) class IIa, 108 (11.6%) class IIb, and 114 (12.3%) class III. After a median follow-up of 1001 days, 120 patients who had an indication for CRT implantation had died and 71 had been hospitalized for HF. The time to the end point was longer in patients with a class I indication (hazard ratio 0.55; 95% confidence interval 0.39-0.76; P = .0001). After 12 months, left ventricular (LV) end-systolic volume had decreased by ≥15% in 61.5% of patients whereas in 57.5% of patients the absolute LV ejection fraction improvement was ≥5%. Adherence to class I was also associated with an absolute LV ejection fraction increase of >5% (P = .0142) and an LV end-systolic volume decrease of ≥15% (P = .0055). In our population, ∼60% of patients underwent implantation according to the 2016 European HF guidelines class I indication. Adherence to class I was associated with a lower death and HF hospitalization rate and better LV reverse remodeling. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Economic Value and Cost-Effectiveness of Cardiac Resynchronization Therapy Among Patients With Mild Heart Failure: Projections From the REVERSE Long-Term Follow-Up.

PubMed

Gold, Michael R; Padhiar, Amie; Mealing, Stuart; Sidhu, Manpreet K; Tsintzos, Stelios I; Abraham, William T

2017-03-01

This study investigated the cost effectiveness of early cardiac resynchronization therapy (CRT) implantation among patients with mild heart failure (HF). The differential cost effectiveness between CRT using a defibrillator (CRT-Ds) and CRT using a pacemaker (CRT-P) was also assessed. Cardiac resynchronization has been shown to be cost effective in New York Heart Association (NYHA) functional classes III/IV but is less studied in class II HF. The incremental costs of early CRT implementation in mild HF compared with the costs potentially avoided because of delaying disease progression to advanced HF are also unknown. Finally, combined biventricular pacing and defibrillator (CRT-D) devices are more expensive than biventricular pacemakers (CRT-P), but the relative cost effectiveness is controversial. Data from the 5-year follow-up phase of REVERSE (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction) were used. The economics were evaluated from the U.S. Medicare perspective based on published clinical projections. Probabilistic estimates yielded $8,840/quality-adjusted life year (QALY) gained (95% confidence interval [CI]: $6,705 to $10,804/QALY gained) for CRT-ON versus CRT-OFF (i.e., programmed "ON" or "OFF" at pre-specified post-implantation timings) and $43,678/QALY gained for CRT-D versus CRT-P (95% CI: $35,164 to $53,589/QALY gained) over the patient's lifetime. Results were robust to choice of patient subgroup and alterations of ±10% to key model parameters. An "early" CRT-D class II strategy totaled $95,292 compared with $91,511 for a "late" implantation. An "early" implant offered on average 1.00 year of additional survival for $3,781, resulting in an ICER of $3,795/LY gained. This study demonstrates CRT cost effectiveness in mild HF. The incremental CRT-D costs are justified by the anticipated benefits, despite increased procurement costs and shorter generator longevities. "Early" CRT-D implants have essential cost parity with "late" implants while increasing the patient's survival. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

QRS analysis using wavelet transformation for the prediction of response to cardiac resynchronization therapy: a prospective pilot study.

PubMed

Vassilikos, Vassilios P; Mantziari, Lilian; Dakos, Georgios; Kamperidis, Vasileios; Chouvarda, Ioanna; Chatzizisis, Yiannis S; Kalpidis, Panagiotis; Theofilogiannakos, Efstratios; Paraskevaidis, Stelios; Karvounis, Haralambos; Mochlas, Sotirios; Maglaveras, Nikolaos; Styliadis, Ioannis H

2014-01-01

Wider QRS and left bundle branch block morphology are related to response to cardiac resynchronization therapy (CRT). A novel time-frequency analysis of the QRS complex may provide additional information in predicting response to CRT. Signal-averaged electrocardiograms were prospectively recorded, before CRT, in orthogonal leads and QRS decomposition in three frequency bands was performed using the Morlet wavelet transformation. Thirty eight patients (age 65±10years, 31 males) were studied. CRT responders (n=28) had wider baseline QRS compared to non-responders and lower QRS energies in all frequency bands. The combination of QRS duration and mean energy in the high frequency band had the best predicting ability (AUC 0.833, 95%CI 0.705-0.962, p=0.002) followed by the maximum energy in the high frequency band (AUC 0.811, 95%CI 0.663-0.960, p=0.004). Wavelet transformation of the QRS complex is useful in predicting response to CRT. © 2013.

Phase shifting two coupled circadian pacemakers - Implications for jet lag

NASA Technical Reports Server (NTRS)

Gander, P. H.; Kronauer, R. E.; Graeber, R. C.

1985-01-01

Two Van der Pol oscillators with reciprocal linear velocity coupling are utilized to model the response of the human circadian timing system to abrupt displacements of the environmental time cues (zeitgebers). The core temperature rhythm and sleep-wake cycle simulated by the model are examined. The relationship between the masking of circadian rhythms by environmental variables and behavioral and physiological events and the rates of resynchronization is studied. The effects of zeitgeber phase shifts and zeitgeber strength on the resynchronization rates are analyzed. The influence of intrinsic pacemakers periods and coupling strength on resynchronization are investigated. The simulated data reveal that: resynchronization after a time zone shift depends on the magnitude of the shift; the time of day of the shift has little influence on resynchronization; the strength of zeitgebers affects the rate and direction of the resynchronization; the intrinsic pacemaker periods have a significant effect on resynchronization; and increasing the coupling between the oscillators results in an increase in the rate of resynchronization. The model data are compared to transmeridian flight studies data and similar resynchronization patterns are observed.

Reliability and accuracy of sleep apnea scans in novel cardiac resynchronization therapy devices: an independent report of two cases.

PubMed

Fox, Henrik; Nölker, Georg; Gutleben, Klaus-Jürgen; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf

2014-03-01

Pacemaker apnea scan algorithms are able to screen for sleep apnea. We investigated whether these systems were able to accurately detect sleep-disordered breathing (SDB) in two patients from an outpatient clinic. The first patient suffered from ischemic heart failure and severe central sleep apnea (CSA) and underwent adaptive servoventilation therapy (ASV). The second patient suffered from dilated cardiomyopathy and moderate obstructive sleep apnea (OSA). Pacemaker read-outs did not match polysomnography (PSG) recordings well and overestimated the apnea-hypopnea index. However, ASV therapy-induced SDB improvements were adequately recognized by the apnea scan of the Boston Scientific INVIVE® cardiac resynchronization therapy pacemaker. Detection of obstructive respiratory events using impedance-based technology may underestimate the number of events, as frustrane breathing efforts induce impedance changes without significant airflow. By contrast, in the second case, apnea scan overestimated the number of total events and of obstructive events, perhaps owing to a very sensitive but less specific hypopnea definition and detection within the diagnostic algorithm of the device. These two cases show that a pacemaker apnea scan is able to reflect SDB, but PSG precision is not met by far. The device scan revealed the decline of SDB through ASV therapy for CSA in one patient, but not for OSA in the second case. To achieve reliable monitoring of SDB, further technical developments and clinical studies are necessary.

Early prediction of cardiac resynchronization therapy response by non-invasive electrocardiogram markers.

PubMed

Ortigosa, Nuria; Pérez-Roselló, Víctor; Donoso, Víctor; Osca, Joaquín; Martínez-Dolz, Luis; Fernández, Carmen; Galbis, Antonio

2018-04-01

Cardiac resynchronization therapy (CRT) is an effective treatment for those patients with severe heart failure. Regrettably, there are about one third of CRT "non-responders", i.e. patients who have undergone this form of device therapy but do not respond to it, which adversely affects the utility and cost-effectiveness of CRT. In this paper, we assess the ability of a novel surface ECG marker to predict CRT response. We performed a retrospective exploratory study of the ECG previous to CRT implantation in 43 consecutive patients with ischemic (17) or non-ischemic (26) cardiomyopathy. We extracted the QRST complexes (consisting of the QRS complex, the S-T segment, and the T wave) and obtained a measure of their energy by means of spectral analysis. This ECG marker showed statistically significant lower values for non-responder patients and, joint with the duration of QRS complexes (the current gold-standard to predict CRT response), the following performances: 86% accuracy, 88% sensitivity, and 80% specificity. In this manner, the proposed ECG marker may help clinicians to predict positive response to CRT in a non-invasive way, in order to minimize unsuccessful procedures.

Focused report : implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT), implications for driving a commercial motor vehicle (CMV).

DOT National Transportation Integrated Search

2011-05-27

This report was prepared by MANILA Consulting Group, Inc. under Contract No. GS-10F-0177N; Order No. DTMC75-10-F-00013, entitled Medical Programs Research and Analysis Panels Project, with the Department of Transportations Federal Motor Carrier...

Predictors of Total Mortality and Echocardiographic Response for Cardiac Resynchronization Therapy: A Cohort Study

PubMed Central

Gazzoni, Guilherme Ferreira; Fraga, Matheus Bom; Ferrari, Andres Di Leoni; Soliz, Pablo da Costa; Borges, Anibal Pires; Bartholomay, Eduardo; Kalil, Carlos Antonio Abunader; Giaretta, Vanessa; Rohde, Luis Eduardo Paim

2017-01-01

Background Clinical studies demonstrate that up to 40% of patients do not respond to cardiac resynchronization therapy (CRT), thus, appropriate patient selection is critical to the success of CRT in heart failure. Objective Evaluation of mortality predictors and response to CRT in the Brazilian scenario. Methods Retrospective cohort study including patients submitted to CRT in a tertiary hospital in southern Brazil from 2008 to 2014. Survival was assessed through a database of the State Department of Health (RS). Predictors of echocardiographic response were evaluated using Poisson regression. Survival analysis was performed by Cox regression and Kaplan Meyer curves. A two-tailed p value less than 0.05 was considered statistically significant. Results A total of 170 patients with an average follow-up of 1011 ± 632 days were included. The total mortality was 30%. The independent predictors of mortality were age (hazard ratio [HR] of 1.05, p = 0.027), previous acute myocardial infarction (AMI) (HR of 2.17, p = 0.049) and chronic obstructive pulmonary disease (COPD) (HR of 3.13, p = 0.015). The percentage of biventricular stimulation at 6 months was identified as protective factor of mortality ([HR] 0.97, p = 0.048). The independent predictors associated with the echocardiographic response were absence of mitral insufficiency, presence of left bundle branch block and percentage of biventricular stimulation. Conclusion Mortality in patients submitted to CRT in a tertiary hospital was independently associated with age, presence of COPD and previous AMI. The percentage of biventricular pacing evaluated 6 months after resynchronizer implantation was independently associated with improved survival and echocardiographic response. PMID:29185615

Non-responders to cardiac resynchronization therapy: Insights from multimodality imaging and electrocardiography. A brief review.

PubMed

Carità, Patrizia; Corrado, Egle; Pontone, Gianluca; Curnis, Antonio; Bontempi, Luca; Novo, Giuseppina; Guglielmo, Marco; Ciaramitaro, Gianfranco; Assennato, Pasquale; Novo, Salvatore; Coppola, Giuseppe

2016-12-15

Cardiac resynchronization therapy (CRT) is a successful strategy for heart failure (HF) patients. The pre-requisite for the response is the evidence of electrical dyssynchrony on the surface electrocardiogram usually as left bundle branch block (LBBB). Non-response to CRT is a significant problem in clinical practice. Patient selection, inadequate delivery and sub-optimal left ventricle lead position may be important causes. In an effort to improve CRT response multimodality imaging (especially echocardiography, computed tomography and cardiac magnetic resonance) could play a decisive role and extensive literature has been published on the matter. However, we are so far from routinary use in clinical practice. Electrocardiography (with respect to left ventricle capture and QRS narrowing) may represent a simple and low cost approach for early prediction of potential non-responder, with immediate practical implications. This brief review covers the current recommendations for CRT in HF patients with particular attention to the potential benefits of multimodality imaging and electrocardiography in improving response rate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Resynchronization of circadian sleep-wake and temperature cycles in the squirrel monkey following phase shifts of the environmental light-dark cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wexler, D.B.; Moore-ede, M.C.

1986-12-01

Circadian rhythms in physiological and behavioral functions gradually resynchronize after phase shifts in environmental time cues. In order to characterize the rate of circadian resynchronization in a diurnal primate model, the temperature, locomotor activity, and polygraphically determined sleep-wake states were monitored in squirrel monkeys before and after 8-h phase shifts of an environmental light-dark cycle of 12 h light and 12 h dark (LD 12:12). For the temperature rhythm, resynchronization took 4 d after phase delay shift and 5 d after phase advance shift; for the rest-activity cycle, resynchronization times were 3 d and 6 d, respectively. The activity acrophasemore » shifted more rapidly than the temperature acrophase early in the post-delay shift interval, but this internal desynchronization between rhythms disappeared during the course of resynchronization. Further study of the early resynchronization process requires emphasis on identifying evoked effects and measuring circadian pacemaker function. 13 references.« less

Resynchronization of circadian sleep-wake and temperature cycles in the squirrel monkey following phase shifts of the environmental light-dark cycle

NASA Technical Reports Server (NTRS)

Wexler, D. B.; Moore-Ede, M. C.

1986-01-01

Circadian rhythms in physiological and behavioral functions gradually resynchronize after phase shifts in environmental time cues. In order to characterize the rate of circadian resynchronization in a diurnal primate model, the temperature, locomotor activity, and polygraphically determined sleep-wake states were monitored in squirrel monkeys before and after 8-h phase shifts of an environmental light-dark cycle of 12 h light and 12 h dark (LD 12:12). For the temperature rhythm, resynchronization took 4 d after phase delay shift and 5 d after phase advance shift; for the rest-activity cycle, resynchronization times were 3 d and 6 d, respectively. The activity acrophase shifted more rapidly than the temperature acrophase early in the post-delay shift interval, but this internal desynchronization between rhythms disappeared during the course of resynchronization. Further study of the early resynchronization process requires emphasis on identifying evoked effects and measuring circadian pacemaker function.

Frequent Activation Delay-Induced Mechanical Dyssynchrony and Dysfunction in the Systemic Right Ventricle.

PubMed

Forsha, Daniel; Risum, Niels; Smith, P Brian; Kanter, Ronald J; Samad, Zainab; Barker, Piers; Kisslo, Joseph

2016-11-01

Patients with systemic right ventricles frequently experience progressive heart failure and conduction abnormalities leading to abnormal ventricular activation. Activation delay-induced mechanical dyssynchrony can contribute to ventricular failure and is identified by a classic strain pattern of paradoxical opposing wall motion that is an excellent predictor of response to cardiac resynchronization therapy in adults with left bundle branch block. The specific aims of this study were to compare right ventricular (RV) mechanics in an adult systemic right ventricle population versus control subjects, evaluate the feasibility of this RV strain pattern analysis, and determine the frequency of the classic pattern. Young adults (n = 25) with d-transposition of the great arteries, status post Mustard or Senning palliation (TGA-MS), were ambispectively enrolled and compared with healthy young adults (n = 30) who were prospectively enrolled. All subjects were imaged using novel three-apical view (18-segment) RV longitudinal speckle-tracking strain analysis (EchoPAC) and electrocardiographic data. Patients with TGA-MS had diminished RV global peak systolic strain compared with control subjects (-12.0 ± 4.0% vs -23.3 ± 2.3%, P < .001). Most patients with TGA-MS had intrinsic or left ventricular paced right bundle branch block. A classic pattern was present in 11 of 25 subjects (44%), but this pattern would have been missed in four of 11 based only on the RV four-chamber (six-segment) model. Only three subjects underwent cardiac resynchronization therapy. Both subjects who had the classic pattern responded to cardiac resynchronization therapy, whereas the one nonresponder did not have the classic pattern. Systemic right ventricles demonstrated decreased function and increased mechanical dyssynchrony. The classic pattern of activation delay-induced mechanical dyssynchrony was frequently seen in this TGA-MS population and associated with activation delays. This comprehensive RV approach demonstrated incremental value. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Association between patient activity and long-term cardiac death in patients with implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators.

PubMed

Zhao, Shuang; Chen, Keping; Su, Yangang; Hua, Wei; Chen, Silin; Liang, Zhaoguang; Xu, Wei; Dai, Yan; Liu, Zhimin; Fan, Xiaohan; Hou, Cuihong; Zhang, Shu

2017-05-01

Background Patient activity (PA) has been demonstrated to predict all-cause mortality. However, the association between PA and cardiac death is unclear. Aims The aims of this study were to determine whether PA can predict cardiac death and what is the cut-off of PA to discriminate cardiac death, as well as the mechanism underlying the relationship between PA and survival in patients with home monitoring. Methods This study retrospectively analysed clinical and implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator device data in 845 patients. Data regarding PA and PP variability during the first 30-60 days of home monitoring were collected, and mean values were calculated. The primary endpoint was cardiac death, and the secondary endpoint was all-cause mortality. Results The mean PA percentage was 11 ± 5.8%. Based on receiver operating characteristic curve analysis, we determined that a PA cut-off value of 7.84% (113 min) can predict cardiac death. During a mean follow-up period of 31.1 ± 12.9 months (ranging from three to 60 months), PA ≤ 7.84% was associated with increased risks of cardiac death in an unadjusted analysis; after adjusting in a multivariate Cox model, the relationship remained significant between PA≤7.84% and cardiac death (hazard ratio = 3.644, 95% confidence interval = 2.424-5.477, p < 0.001). Moreover, a significant correlation was observed between PA and PP variability ( r = 0.601, p < 0.001). Conclusions A baseline PA ≤ 7.84% was associated with a higher risk of cardiac death in patients who have survived more than three months after implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator implantation. PA had a sizable effect on heart rate variability, reflecting autonomic function.

Programming Cardiac Resynchronization Therapy for Electrical Synchrony: Reaching Beyond Left Bundle Branch Block and Left Ventricular Activation Delay.

PubMed

Varma, Niraj; O'Donnell, David; Bassiouny, Mohammed; Ritter, Philippe; Pappone, Carlo; Mangual, Jan; Cantillon, Daniel; Badie, Nima; Thibault, Bernard; Wisnoskey, Brian

2018-02-06

QRS narrowing following cardiac resynchronization therapy with biventricular (BiV) or left ventricular (LV) pacing is likely affected by patient-specific conduction characteristics (PR, qLV, LV-paced propagation interval), making a universal programming strategy likely ineffective. We tested these factors using a novel, device-based algorithm (SyncAV) that automatically adjusts paced atrioventricular delay (default or programmable offset) according to intrinsic atrioventricular conduction. Seventy-five patients undergoing cardiac resynchronization therapy (age 66±11 years; 65% male; 32% with ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 162±16 ms) with intact atrioventricular conduction (PR interval 194±34, range 128-300 ms), left bundle branch block, and optimized LV lead position were studied at implant. QRS duration (QRSd) reduction was compared for the following pacing configurations: nominal simultaneous BiV (Mode I: paced/sensed atrioventricular delay=140/110 ms), BiV+SyncAV with 50 ms offset (Mode II), BiV+SyncAV with offset that minimized QRSd (Mode III), or LV-only pacing+SyncAV with 50 ms offset (Mode IV). The intrinsic QRSd (162±16 ms) was reduced to 142±17 ms (-11.8%) by Mode I, 136±14 ms (-15.6%) by Mode IV, and 132±13 ms (-17.8%) by Mode II. Mode III yielded the shortest overall QRSd (123±12 ms, -23.9% [ P <0.001 versus all modes]) and was the only configuration without QRSd prolongation in any patient. QRS narrowing occurred regardless of QRSd, PR, or LV-paced intervals, or underlying ischemic disease. Post-implant electrical optimization in already well-selected patients with left bundle branch block and optimized LV lead position is facilitated by patient-tailored BiV pacing adjusted to intrinsic atrioventricular timing using an automatic device-based algorithm. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The economic impact of battery longevity in implantable cardioverter-defibrillators for cardiac resynchronization therapy: the hospital and healthcare system perspectives.

PubMed

Landolina, Maurizio; Morani, Giovanni; Curnis, Antonio; Vado, Antonello; D'Onofrio, Antonio; Bianchi, Valter; Stabile, Giuseppe; Crosato, Martino; Petracci, Barbara; Ceriotti, Carlo; Bontempi, Luca; Morosato, Martina; Ballari, Gian Paolo; Gasparini, Maurizio

2017-08-01

Patients receiving cardiac resynchronization therapy defibrillators (CRT-Ds) are likely to undergo one or more device replacements, mainly for battery depletion. We assessed the economic impact of battery depletion on the overall cost of CRT-D treatment from the perspectives of the healthcare system and the hospital. We also compared devices of different generations and from different manufacturers in terms of therapy cost. We analysed data on 1792 CRT-Ds implanted in 1399 patients in 9 Italian centres. We calculated the replacement probability and the total therapy cost over 6 years, stratified by device generation and manufacturer. Public tariffs from diagnosis-related groups were used together with device prices and hospitalization costs. Generators were from 3 manufacturers: Boston Scientific (667, 37%), Medtronic (973, 54%), and St Jude Medical (152, 9%). The replacement probability at 6 years was 83 and 68% for earlier- and recent-generation devices, respectively. The need for replacement increased total therapy costs by more than 50% over the initial implantation cost for hospitals and by more than 30% for healthcare system. The improved longevity of recent-generation CRT-Ds reduced the therapy cost by ∼6% in both perspectives. Among recent-generation CRT-Ds, the replacement probability of devices from different manufacturers ranged from 12 to 70%. Consequently, the maximum difference in therapy cost between manufacturers was 40% for hospitals and 19% for the healthcare system. Differences in CRT-D longevity strongly affect the overall therapy cost. While the use of recent-generation devices has reduced the cost, significant differences exist among currently available systems. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Worsening of left ventricular end-systolic volume and mitral regurgitation without increase in left ventricular dyssynchrony on acute interruption of cardiac resynchronization therapy.

PubMed

Kuppahally, Suman S; Fowler, Michael B; Vagelos, Randall; Wang, Paul; Al-Ahmad, Amin; Paloma, Allan; Liang, David

2009-08-01

Responders to cardiac resynchronization therapy (CRT) have greater left ventricular (LV) dyssynchrony than nonresponders prior to CRT. We conducted this study to see whether the long term responders have more worsening of LV dyssynchrony and LV function on acute interruption of CRT. We identified 22 responders and 13 nonresponders who received CRT as per standard criteria for 23.73 +/- 7.9 months (median 24.5 months). We assessed the acute change in LV function, mitral regurgitation (MR) and compared LV dyssynchrony in CRT on and off modes. On turning off CRT, there was no significant worsening of LV dyssynchrony in both responders and nonresponders. The dyssynchrony measurements by SPWMD, TDI and 3D echocardiography did not correlate significantly. LVESV increased (p = 0.02) and MR (p = 0.01) worsened in CRT-off mode in responders only without significant change in LVEF or LV dimensions. In long-term responders to CRT, there is alteration in the function of remodeled LV with acute interruption of CRT, without significant worsening of LV dyssynchrony. The role of different echocardiographic parameters in the assessment of LV dyssynchrony remains controversial. Even after long-term CRT reversely remodels the LV, the therapy needs to be continued uninterrupted for sustained benefits.

Reduced appropriate implantable cardioverter-defibrillator therapy after cardiac resynchronization therapy-induced left ventricular function recovery: a meta-analysis and systematic review.

PubMed

Chatterjee, Neal A; Roka, Attila; Lubitz, Steven A; Gold, Michael R; Daubert, Claude; Linde, Cecilia; Steffel, Jan; Singh, Jagmeet P; Mela, Theofanie

2015-11-01

For patients undergoing cardiac resynchronization therapy (CRT) with implantable cardioverter-defibrillator (ICD; CRT-D), the effect of an improvement in left ventricular ejection fraction (LVEF) on appropriate ICD therapy may have significant implications regarding management at the time of ICD generator replacement. We conducted a meta-analysis to determine the effect of LVEF recovery following CRT on the incidence of appropriate ICD therapy. A search of multiple electronic databases identified 709 reports, of which 6 retrospective cohort studies were included (n = 1740). In patients with post-CRT LVEF ≥35% (study n = 4), the pooled estimated rate of ICD therapy (5.5/100 person-years) was significantly lower than patients with post-CRT LVEF <35% [incidence rate difference (IRD): -6.5/100 person-years, 95% confidence interval (95% CI): -8.8 to -4.2, P < 0.001]. Similarly, patients with post-CRT LVEF ≥45% (study n = 4) demonstrated lower estimated rates of ICD therapy (2.3/100 person-years) compared with patients without such recovery (IRD: -5.8/100 person-years, 95% CI: -7.6 to -4.0, P < 0.001). Restricting analysis to studies discounting ICD therapies during LVEF recovery (study n = 3), patients with LVEF recovery (≥35 or ≥45%) had significantly lower rates of ICD therapy compared with patients without such recovery (P for both <0.001). Patients with primary prevention indication for ICD, regardless of LVEF recovery definition, had very low rates of ICD therapy (0.4 to 0.8/100-person years). Recovery of LVEF post-CRT is associated with significantly reduced appropriate ICD therapy. Patients with improvement of LVEF ≥45% and those with primary prevention indication for ICD appear to be at lowest risk. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

A review of economic evaluation models for cardiac resynchronization therapy with implantable cardioverter defibrillators in patients with heart failure.

PubMed

Tomini, F; Prinzen, F; van Asselt, A D I

2016-12-01

Cardiac resynchronization therapy with a biventricular pacemaker (CRT-P) is an effective treatment for dyssynchronous heart failure (DHF). Adding an implantable cardioverter defibrillator (CRT-D) may further reduce the risk of sudden cardiac death (SCD). However, if the majority of patients do not require shock therapy, the cost-effectiveness ratio of CRT-D compared to CRT-P may be high. The objective of this study was to systematically review decision models evaluating the cost-effectiveness of CRT-D for patients with DHF, compare the structure and inputs of these models and identify the main factors influencing the ICERs for CRT-D. A comprehensive search strategy of Medline (Ovid), Embase (Ovid) and EconLit identified eight cost-effectiveness models evaluating CRT-D against optimal pharmacological therapy (OPT) and/or CRT-P. The selected economic studies differed in terms of model structure, treatment path, time horizons, and sources of efficacy data. CRT-D was found cost-effective when compared to OPT but its cost-effectiveness became questionable when compared to CRT-P. Cost-effectiveness of CRT-D may increase depending on improvement of all-cause mortality rates and HF mortality rates in patients who receive CRT-D, costs of the device, and battery life. In particular, future studies need to investigate longer-term mortality rates and identify CRT-P patients that will gain the most, in terms of life expectancy, from being treated with a CRT-D.

Clinical Assessment of Intraventricular Blood Transport in Patients Undergoing Cardiac Resynchronization Therapy

NASA Astrophysics Data System (ADS)

Rossini, Lorenzo; Martinez-Legazpi, P.; Benito, Y.; Perez Del Villar, C.; Gonzalez-Mansilla, A.; Barrio, A.; Yotti, R.; Kahn, A. M.; Shadden, S. C.; Fernandez-Aviles, F.; Bermejo, J.; Del Alamo, J. C.

2015-11-01

In the healthy heart, left ventricular (LV) filling generates flow patterns which have been proposed to optimize blood transport by coupling diastole and systole phases. We present a novel image-based method to assess how flow patterns influence LV blood transport in patients undergoing cardiac resynchronization therapy (CRT). Solving the advection equation with time-varying inflow boundary conditions allows to track the transport of blood entering the LV in the different filling waves, as well as the transport barriers which couple filling and ejection. The velocity fields were obtained using echocardiographic color Doppler velocimetry, which provides two-dimensional time-resolved flow maps in the apical long axis three-chamber view of the LV. We analyze flow transport in a group of patients with CRT devices as well as in healthy volunteers. In the patients under CRT, the device programming was varied to analyze flow transport under different values of the atrioventricular (AV) conduction delay and to model tachycardia. This analysis illustrates how CRT influences the transit of blood inside the LV, contributes to conserving kinetic energy and favors the generation of hemodynamic forces that accelerate blood in the direction of the LV outflow tract.

Interactive visualization for scar transmurality in cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Reiml, Sabrina; Toth, Daniel; Panayiotou, Maria; Fahn, Bernhard; Karim, Rashed; Behar, Jonathan M.; Rinaldi, Christopher A.; Razavi, Reza; Rhode, Kawal S.; Brost, Alexander; Mountney, Peter

2016-03-01

Heart failure is a serious disease affecting about 23 million people worldwide. Cardiac resynchronization therapy is used to treat patients suffering from symptomatic heart failure. However, 30% to 50% of patients have limited clinical benefit. One of the main causes is suboptimal placement of the left ventricular lead. Pacing in areas of myocardial scar correlates with poor clinical outcomes. Therefore precise knowledge of the individual patient's scar characteristics is critical for delivering tailored treatments capable of improving response rates. Current research methods for scar assessment either map information to an alternative non-anatomical coordinate system or they use the image coordinate system but lose critical information about scar extent and scar distribution. This paper proposes two interactive methods for visualizing relevant scar information. A 2-D slice based approach with a scar mask overlaid on a 16 segment heart model and a 3-D layered mesh visualization which allows physicians to scroll through layers of scar from endocardium to epicardium. These complementary methods enable physicians to evaluate scar location and transmurality during planning and guidance. Six physicians evaluated the proposed system by identifying target regions for lead placement. With the proposed method more target regions could be identified.

Is speckle tracking actually helpful for cardiac resynchronization therapy?

PubMed

Tanaka, Hidekazu; Hirata, Ken-Ichi

2016-06-01

What is the specific role of echocardiography in cardiac resynchronization therapy (CRT)? CRT has proven to be highly effective for improving symptoms and survival of patients with advanced heart failure (HF) and wide QRS. However, a significant minority of patients do not respond favorably to CRT on the basis of standard clinical selection criteria, including the electrocardiographic QRS width. Subsequently, echocardiographic assessment of left ventricular (LV) dyssynchrony has been considered useful for CRT for selected responders, but findings by multicenter studies suggest that its predictive value was not sufficiently robust to replace routine selection criteria for CRT. A more recent approach, however, using speckle-tracking echocardiography yields more accurate quantification of regional wall contraction. Speckle-tracking approaches have therefore generated a great deal of interest about their clinical applications for CRT. Although reports on speckle tracking have not been included in any recommendations as to whether patients should undergo CRT based on the current guidelines, speckle tracking can play an important supplementary part in CRT on the basis of a case-by-case clinical decision for challenging cases. Here, we review the strengths of speckle-tracking methods, and their current potential for clinical use in CRT.

Implementation study of an analog spiking neural network for assisting cardiac delay prediction in a cardiac resynchronization therapy device.

PubMed

Sun, Qing; Schwartz, François; Michel, Jacques; Herve, Yannick; Dalmolin, Renzo

2011-06-01

In this paper, we aim at developing an analog spiking neural network (SNN) for reinforcing the performance of conventional cardiac resynchronization therapy (CRT) devices (also called biventricular pacemakers). Targeting an alternative analog solution in 0.13- μm CMOS technology, this paper proposes an approach to improve cardiac delay predictions in every cardiac period in order to assist the CRT device to provide real-time optimal heartbeats. The primary analog SNN architecture is proposed and its implementation is studied to fulfill the requirement of very low energy consumption. By using the Hebbian learning and reinforcement learning algorithms, the intended adaptive CRT device works with different functional modes. The simulations of both learning algorithms have been carried out, and they were shown to demonstrate the global functionalities. To improve the realism of the system, we introduce various heart behavior models (with constant/variable heart rates) that allow pathologic simulations with/without noise on the signals of the input sensors. The simulations of the global system (pacemaker models coupled with heart models) have been investigated and used to validate the analog spiking neural network implementation.

Effectiveness of prophylactic implantation of cardioverter-defibrillators without cardiac resynchronization therapy in patients with ischaemic or non-ischaemic heart disease: a systematic review and meta-analysis

PubMed Central

Theuns, Dominic A.M.J.; Smith, Tim; Hunink, Myriam G.M.; Bardy, Gust H.; Jordaens, Luc

2010-01-01

Aims Much controversy exists concerning the efficacy of primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with low ejection fraction due to coronary artery disease (CAD) or dilated cardiomyopathy (DCM). This is also related to the bias created by function improving interventions added to ICD therapy, e.g. resynchronization therapy. The aim was to investigate the efficacy of ICD-only therapy in primary prevention in patients with CAD or DCM. Methods and results Public domain databases, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials, were searched from 1980 to 2009 for randomized clinical trials of ICD vs. conventional therapy. Two investigators independently abstracted the data. Pooled estimates were calculated using both fixed-effects and random-effects models. Eight trials were included in the final analysis (5343 patients). Implantable cardioverter-defibrillators significantly reduced the arrhythmic mortality [relative risk (RR): 0.40; 95% confidence interval (CI): 0.27–0.67] and all-cause mortality (RR: 0.73; 95% CI: 0.64–0.82). Regardless of aetiology of heart disease, ICD benefit was similar for CAD (RR: 0.67; 95% CI: 0.51–0.88) vs. DCM (RR: 0.74; 95% CI: 0.59–0.93). Conclusions The results of this meta-analysis provide strong evidence for the beneficial effect of ICD-only therapy on the survival of patients with ischaemic or non-ischaemic heart disease, with a left ventricular ejection fraction ≤35%, if they are 40 days from myocardial infarction and ≥3 months from a coronary revascularization procedure. PMID:20974768

Usefulness of Sodium Bicarbonate for the Prevention of Contrast-Induced Nephropathy in Patients Undergoing Cardiac Resynchronization Therapy.

PubMed

Alonso, Pau; Sanz, Jorge; García-Orts, Ana; Reina, Samuel; Jiménez, Sonia; Osca, Joaquín; Cano, Oscar; Andrés, Ana; Sancho-Tello, María José; Martínez, Luis

2017-11-01

The use of contrast media during cardiac resynchronization therapy (CRT) devices implantation is associated with the risk of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the possible beneficial role of periprocedural intravenous volume expansion with isotonic saline and sodium bicarbonate solution in patients who undergo CRT implantation. Eligible patients were randomly assigned in a 1:1 ratio to receive hydration plus one-sixth molar sodium bicarbonate (study group) or not (control group). Primary end point was CIN incidence. Secondary end points were (1) a combined end point of death, heart transplantation, or hospitalization for heart failure at 12 months, (2) incidence of death, and (3) the need for renal replacement therapy at 12 months. Final analysis was performed with 93 patients. In the hydration group CIN incidence was significantly reduced related to control group (0% vs 11%, p = 0.02). There was a trend to reduce the combined end point in hydration group (12.5% vs 22%, p = 0.14). Finally, CIN incidence was related to a higher 12 months mortality (25% vs 7%, p = 0.03). In conclusion, CIN incidence was 11% in a nonselected population of patients receiving a CRT device. CIN appearance could be reduced by using a hydration protocol based on sodium bicarbonate and isotonic saline. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of intravenous amiodarone on QT and T peak-T end dispersions in patients with nonischemic heart failure treated with cardiac resynchronization-defibrillator therapy and electrical storm.

PubMed

Ogiso, Masataka; Suzuki, Atsushi; Shiga, Tsuyoshi; Nakai, Kenji; Shoda, Morio; Hagiwara, Nobuhisa

2015-02-01

The effect of intravenous amiodarone on spatial and transmural dispersion of ventricular repolarization in patients receiving cardiac resynchronization therapy (CRT) remains unclear. We studied 14 patients with nonischemic heart failure who received CRT with a defibrillator, experienced electrical storm and were treated with intravenous amiodarone. Each patient underwent 12-lead electrocardiography (ECG) and 187-channel repolarization interval-difference mapping electrocardiography (187-ch RIDM-ECG) before and during the intravenous administration of amiodarone infusion. A recurrence of ventricular tachyarrhythmia was observed in 2 patients during the early period of intravenous amiodarone therapy. Intravenous amiodarone increased the corrected QT interval (from 470±52 ms to 508±55 ms, P=0.003), but it significantly decreased the QT dispersion (from 107±35 ms to 49±27 ms, P=0.001), T peak-T end (Tp-e) dispersion (from 86±17 ms to 28±28 ms, P=0.001), and maximum inter-lead difference between corrected Tp-e intervals as measured by using the 187-ch RIDM-ECG (from 83±13 ms to 50±19 ms, P=0.001). Intravenous amiodarone suppressed the electrical storm and decreased the QT and Tp-e dispersions in patients treated by using CRT with a defibrillator.

A Pilot Study Assessing ECG versus ECHO Ventriculoventricular Optimization in Pediatric Resynchronization Patients.

PubMed

Punn, Rajesh; Hanisch, Debra; Motonaga, Kara S; Rosenthal, David N; Ceresnak, Scott R; Dubin, Anne M

2016-02-01

Cardiac resynchronization therapy indications and management are well described in adults. Echocardiography (ECHO) has been used to optimize mechanical synchrony in these patients; however, there are issues with reproducibility and time intensity. Pediatric patients add challenges, with diverse substrates and limited capacity for cooperation. Electrocardiographic (ECG) methods to assess electrical synchrony are expeditious but have not been extensively studied in children. We sought to compare ECHO and ECG CRT optimization in children. Prospective, pediatric, single-center cross-over trial comparing ECHO and ECG optimization with CRT. Patients were assigned to undergo either ECHO or ECG optimization, followed for 6 months, and crossed-over to the other assignment for another 6 months. ECHO pulsed-wave tissue Doppler and 12-lead ECG were obtained for 5 VV delays. ECG optimization was defined as the shortest QRSD and ECHO optimization as the lowest dyssynchrony index. ECHOs/ECGs were interpreted by readers blinded to optimization technique. After each 6 month period, these data were collected: ejection fraction, velocimetry-derived cardiac index, quality of life, ECHO-derived stroke distance, M-mode dyssynchrony, study cost, and time. Outcomes for each optimization method were compared. From June 2012 to December 2013, 19 patients enrolled. Mean age was 9.1 ± 4.3 years; 14 (74%) had structural heart disease. The mean time for optimization was shorter using ECG than ECHO (9 ± 1 min vs. 68 ± 13 min, P < 0.01). Mean cost for charges was $4,400 ± 700 less for ECG. No other outcome differed between groups. ECHO optimization of synchrony was not superior to ECG optimization in this pilot study. ECG optimization required less time and cost than ECHO optimization. © 2015 Wiley Periodicals, Inc.

Relationship between improvement in left ventricular dyssynchrony and contractile function and clinical outcome with cardiac resynchronization therapy: the MADIT-CRT trial.

PubMed

Pouleur, Anne-Catherine; Knappe, Dorit; Shah, Amil M; Uno, Hajime; Bourgoun, Mikhail; Foster, Elyse; McNitt, Scott; Hall, W Jackson; Zareba, Wojciech; Goldenberg, Ilan; Moss, Arthur J; Pfeffer, Marc A; Solomon, Scott D

2011-07-01

To assess long-term effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) dyssynchrony and contractile function, by two-dimensional speckle-tracking echocardiography, compared with implantable cardioverter defibrillator (ICD) only in MADIT-CRT. We studied 761 patients in New York Heart Association I/II, ejection fraction ≤30%, and QRS ≥130 ms [n = 434, CRT-defibrillator (CRT-D), n = 327, ICD] with echocardiographic studies available at baseline and 12 months. Dyssynchrony was determined as the standard deviation of time to peak transverse strain between 12 segments of apical four- and two-chamber views, and contractile function as global longitudinal strain (GLS) by averaging longitudinal strain over these 12 segments. We compared changes in LV dyssynchrony and contractile function between treatment groups and assessed relationships between these changes over the first year and subsequent outcomes (median post 1-year follow-up = 14.9 months). Mean changes in LV dyssynchrony and contractile function measured by GLS in the overall population were, respectively, -29 ± 83 ms and -1 ± 2.9%. However, both LV dyssynchrony (CRT-D: -47 ± 83 ms vs. ICD: -6 ± 76 ms, P < 0.001) and contractile function (CRT-D: -1.4 ± 3.1% vs. ICD: -0.4 ± 2.5%, P < 0.001) improved to a greater extent in the CRT-D group compared with the ICD-only group. A greater improvement in dyssynchrony and contractile function at 1 year was associated with lower rates of the subsequent primary outcome of death or heart failure, adjusting for baseline dyssynchrony and contractile function, treatment arm, ischaemic status, and change in LV end-systolic volume. Each 20 ms decrease in LV dyssynchrony was associated with a 7% reduction in the primary outcome (P = 0.047); each 1% improvement in GLS over the 12-month period was associated with a 24% reduction in the primary outcome (P < 0.001). Cardiac resynchronization therapy resulted in a significant improvement in both LV dyssynchrony and contractile function measured by GLS compared with ICD only and these improvements were associated with better subsequent outcomes.

Inductionless or limited shock testing is possible in most patients with implantable cardioverter- defibrillators/cardiac resynchronization therapy defibrillators: results of the multicenter ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing Versus Upper Limit of Vulnerability: Risk Reduction Evaluation With Implantable Cardioverter-Defibrillator Implantations).

PubMed

Day, John D; Doshi, Rahul N; Belott, Peter; Birgersdotter-Green, Ulrika; Behboodikhah, Mahnaz; Ott, Peter; Glatter, Kathryn A; Tobias, Serge; Frumin, Howard; Lee, Byron K; Merillat, John; Wiener, Isaac; Wang, Samuel; Grogin, Harlan; Chun, Sung; Patrawalla, Rob; Crandall, Brian; Osborn, Jeffrey S; Weiss, J Peter; Lappe, Donald L; Neuman, Stacey

2007-05-08

Implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators have relied on multiple ventricular fibrillation (VF) induction/defibrillation tests at implantation to ensure that the device can reliably sense, detect, and convert VF. The ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing Versus Upper Limit of Vulnerability: Risk Reduction Evaluation With Implantable Cardioverter-Defibrillator Implantations) is the first large, multicenter, prospective trial comparing vulnerability safety margin testing versus defibrillation safety margin testing with a single VF induction/defibrillation. A total of 426 patients receiving an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator underwent vulnerability safety margin or defibrillation safety margin screening at 14 J in a randomized order. After this, patients underwent confirmatory testing, which required 2 VF conversions without failure at < or = 21 J. Patients who passed their first 14-J and confirmatory tests, irrespective of the results of their second 14-J test, had their devices programmed to a 21-J shock for ventricular tachycardia (VT) or VF > or = 200 bpm and were followed up for 1 year. Of 420 patients who underwent 14-J vulnerability safety margin screening, 322 (76.7%) passed. Of these, 317 (98.4%) also passed 21-J confirmatory tests. Of 416 patients who underwent 14-J defibrillation safety margin screening, 343 (82.5%) passed, and 338 (98.5%) also passed 21-J confirmatory tests. Most clinical VT/VF episodes (32 of 37, or 86%) were terminated by the first shock, with no difference in first shock success. In all observed cases in which the first shock was unsuccessful, subsequent shocks terminated VT/VF without complication. Although spontaneous episodes of fast VT/VF were limited, there was no difference in the odds of first shock efficacy between groups. Screening with vulnerability safety margin or defibrillation safety margin may allow for inductionless or limited shock testing in most patients.

Impact of the right ventricular lead position on clinical outcome and on the incidence of ventricular tachyarrhythmias in patients with CRT-D.

PubMed

Kutyifa, Valentina; Bloch Thomsen, Poul Erik; Huang, David T; Rosero, Spencer; Tompkins, Christine; Jons, Christian; McNitt, Scott; Polonsky, Bronislava; Shah, Amil; Merkely, Bela; Solomon, Scott D; Moss, Arthur J; Zareba, Wojciech; Klein, Helmut U

2013-12-01

Data on the impact of right ventricular (RV) lead location on clinical outcome and ventricular tachyarrhythmias in cardiac resynchronization therapy with defibrillator (CRT-D) patients are limited. To evaluate the impact of different RV lead locations on clinical outcome in CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial. We investigated 742 of 1089 CRT-D patients (68%) with adjudicated RV lead location enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial to evaluate the impact of RV lead location on cardiac events. The primary end point was heart failure or death; secondary end points included ventricular tachycardia (VT), ventricular fibrillation (VF), or death and VT or VF alone. Eighty-six patients had the RV lead positioned at the RV septal or right ventricular outflow tract region, combined as nonapical RV group, and 656 patients had apical RV lead location. There was no difference in the primary end point in patients with nonapical RV lead location versus those with apical RV lead location (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.54-1.80; P = .983). Echocardiographic response to CRT-D was comparable across RV lead location groups (P > .05 for left ventricular end-diastolic volume, left ventricular end-systolic volume, and left atrial volume percent change). However, nonapical RV lead location was associated with significantly higher risk of VT/VF/death (HR 2.45; 95% CI 1.36-4.41; P = .003) and VT/VF alone (HR 2.52; 95% CI 1.36-4.65; P = .002), predominantly in the first year after device implantation. Results were consistent in patients with left bundle branch block. In CRT-D patients, there is no benefit of nonapical RV lead location in clinical outcome or echocardiographic response. Moreover, nonapical RV lead location is associated with an increased risk of ventricular tachyarrhythmias, particularly in the first year after device implantation. Published by Elsevier Inc.

Socio-economic analysis of cardiac resynchronization therapy.

PubMed

Field, Michael E; Sweeney, Michael O

2006-12-01

The field of electrical device therapy has benefited from two basically independent lines of investigation demonstrating mortal benefit from either cardiac resynchronization therapy (CRT) or implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure. Current clinical evidence data is insufficient to conclude that CRT-defibrillation (CRTD) offers an advantage over CRT-pacing (CRTP) alone. The cost of adding a defibrillator to the CRTP device is substantial and will act as a barrier to wide scale penetration. Annualized sudden death rates are very low in certain primary prevention populations. Consequently, the potential for overtreatment is very large and the negative costs of ICD therapy are distributed equally among those patients who will have a life saving benefit and those who were "destined" never to require the therapy. The perception that these costs are acceptable if lives are saved is commonly cited as justification for expensive therapy on a population scale, but there is an important and practical difference between costs per unit life saved and costs among patients who really never needed the device. Until the a priori predictors of volumetric response to CRT are better understood, the use of CRTD in class IV patients should be discouraged since ICD therapy is unlikely to extend life in volumetric non-responders. Similarly, the use of CRTD in patients who are "destined" for significant volumetric response is probably unwise since their risk of sudden death is minimized due to favorable substrate modification. Clinical trials comparing conventional ICDs, CRTP and CRTD are necessary to rationalize use of expensive hardware resources among different patient populations. Additionally, the importance of patient preference regarding end of life care should receive greater emphasis. While CRTP may be considered palliative in terminal heart failure, the decision to offer CRTD must include a discussion with the patient regarding mode of death and the potential for the defibrillator to replace a sudden and peaceful death with a prolonged death from progressive pump failure.

Defibrillation threshold testing fails to show clinical benefit during long-term follow-up of patients undergoing cardiac resynchronization therapy defibrillator implantation.

PubMed

Michowitz, Yoav; Lellouche, Nicolas; Contractor, Tahmeed; Bourke, Tara; Wiener, Isaac; Buch, Eric; Boyle, Noel; Bersohn, Malcolm; Shivkumar, Kalyanam

2011-05-01

The utility of defibrillation threshold testing in patients undergoing implantable cardioverter-defibrillator (ICD) implantation is controversial. Higher defibrillation thresholds have been noted in patients undergoing implantation of cardiac resynchronization therapy defibrillators (CRT-D). Since the risks and potential benefits of testing may be higher in this population, we sought to assess the impact of defibrillation safety margin or vulnerability safety margin testing in CRT-D recipients. A total of 256 consecutive subjects who underwent CRT-D implantation between January 2003 and December 2007 were retrospectively reviewed. Subjects were divided into two groups based on whether (n= 204) or not (n= 52) safety margin testing was performed. Patient characteristics, tachyarrhythmia therapies, procedural results, and clinical outcomes were recorded. Baseline characteristics, including heart failure (HF) severity, were comparable between the groups. Four cases of HF exacerbation (2%), including one leading to one death, were recorded in the tested group immediately post-implantation. No complications were observed in the untested group. After a mean follow-up of 32 ± 20 months, the proportion of appropriate shocks in the two groups was similar (31 vs. 25%, P = 0.49). There were three cases of failed appropriate shocks in the tested group, despite adequate safety margins at implantation, whereas no failed shocks were noted in the untested group. Survival was similar in the two groups. Defibrillation efficacy testing during implant of CRT-D was associated with increased morbidity and did not predict the success of future device therapy or improve survival during long-term follow-up.

Improving pacemaker therapy in congenital heart disease: contractility and resynchronization.

PubMed

Karpawich, Peter P

2015-01-01

Designed as effective therapy for patients with symptomatic bradycardia, implantable cardiac pacemakers initially served to improve symptoms and survival. With initial applications to the elderly and those with severe myocardial disease, extended longevity was not a major concern. However, with design technology advances in leads and generators since the 1980s, pacemaker therapy is now readily applicable to all age patients, including children with congenital heart defects. As a result, emphasis and clinical interests have advanced beyond simply quantity to quality of life. Adverse cardiac effects of pacing from right ventricular apical or epicardial sites with resultant left bundle branch QRS configurations have been recognized. As a result, and with the introduction of newer catheter-delivered pacing leads, more recent studies have focused on alternative or select pacing sites such as septal, outflow tract, and para-bundle of His. This is especially important in dealing with pacemaker therapy among younger patients and those with congenital heart disease, with expected decades of artificial cardiac stimulation, in which adverse myocellular changes secondary to pacing itself have been reported. As a correlate to these alternate or select pacing sites, applications of left ventricular pacing, either via the coronary sinus, intraseptal or epicardial, alone or in combination with right ventricular pacing, have gained interest for patients with heart failure. Although cardiac resynchronization pacing has, to date, had limited clinical applications among patients with congenital heart disease, the few published reports do indicate potential benefits as a bridge to cardiac transplant. Copyright © 2015 Elsevier Inc. All rights reserved.

Echocardiographic phase imaging to predict reverse remodeling after cardiac resynchronization therapy.

PubMed

Buss, Sebastian J; Humpert, Per M; Bekeredjian, Raffi; Hardt, Stefan E; Zugck, Christian; Schellberg, Dieter; Bauer, Alexander; Filusch, Arthur; Kuecherer, Helmut; Katus, Hugo A; Korosoglou, Grigorios

2009-05-01

The aim of our study was to investigate whether echocardiographic phase imaging (EPI) can predict response in patients who are considered for cardiac resynchronization therapy (CRT). CRT improves quality of life, exercise capacity, and outcome in patients with bundle-branch block and advanced heart failure. Previous studies used QRS duration to select patients for CRT; the accuracy of this parameter to predict functional recovery, however, is controversial. We examined 42 patients with advanced heart failure (New York Heart Association [NYHA] functional class III to IV, QRS duration >130 ms, and ejection fraction <35%) before and 6 to 8 months after CRT. Left ventricular (LV) dyssynchrony was estimated by calculating the SD of time to peak velocities (Ts-SD) by conventional tissue Doppler imaging (TDI), and the mean phase index (mean EPI-Index) was calculated by EPI in 12 mid-ventricular and basal segments. Patients who were alive and had significant relative decrease in end-systolic LV volume of Delta ESV >or=15% at 6 to 8 months of follow-up were defined as responders. All others were classified as nonresponders. The Ts-SD and the mean EPI-Index were related to Delta ESV (r = 0.43 for Ts-SD and r = 0.67 for mean EPI-Index, p < 0.01 for both), and both parameters yielded similar accuracy for the prediction of LV remodeling (area under the curve of 0.87 for TDI vs. 0.90 for EPI, difference between areas = 0.03, p = NS) and ejection fraction (EF) improvement (area under the curve of 0.87 for TDI vs. 0.93 for EPI, difference between areas = 0.06, p = NS). Furthermore, patients classified as responders by EPI (mean EPI-Index

The disconnect between the guidelines, the appropriate use criteria, and reimbursement coverage decisions: the ultimate dilemma.

PubMed

Fogel, Richard I; Epstein, Andrew E; Mark Estes, N A; Lindsay, Bruce D; DiMarco, John P; Kremers, Mark S; Kapa, Suraj; Brindis, Ralph G; Russo, Andrea M

Recently, the American College of Cardiology Foundation in collaboration with the Heart Rhythm Society published appropriate use criteria (AUC) for implantable cardioverter-defibrillators and cardiac resynchronization therapy. These criteria were developed to critically review clinical situations that may warrant implantation of an implantable cardioverter-defibrillator or cardiac resynchronization therapy device, and were based on a synthesis of practice guidelines and practical experience from a diverse group of clinicians. When the AUC was drafted, the writing committee recognized that some of the scenarios that were deemed "appropriate" or "may be appropriate" were discordant with the clinical requirements of many payers, including the Medicare National Coverage Determination (NCD). To charge Medicare for a procedure that is not covered by the NCD may be construed as fraud. Discordance between the guidelines, the AUC, and the NCD places clinicians in the difficult dilemma of trying to do the "right thing" for their patients, while recognizing that the "right thing" may not be covered by the payer or insurer. This commentary addresses these issues. Options for reconciling this disconnect are discussed, and recommendations to help clinicians provide the best care for their patients are offered. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Battery longevity in cardiac resynchronization therapy implantable cardioverter defibrillators.

PubMed

Alam, Mian Bilal; Munir, Muhammad Bilal; Rattan, Rohit; Flanigan, Susan; Adelstein, Evan; Jain, Sandeep; Saba, Samir

2014-02-01

Cardiac resynchronization therapy (CRT) implantable cardioverter defibrillators (ICDs) deliver high burden ventricular pacing to heart failure patients, which has a significant effect on battery longevity. The aim of this study was to investigate whether battery longevity is comparable for CRT-ICDs from different manufacturers in a contemporary cohort of patients. All the CRT-ICDs implanted at our institution from 1 January 2008 to 31 December 2010 were included in this analysis. Baseline demographic and clinical data were collected on all patients using the electronic medical record. Detailed device information was collected on all patients from scanned device printouts obtained during routine follow-up. The primary endpoint was device replacement for battery reaching the elective replacement indicator (ERI). A total of 646 patients (age 69 ± 13 years), implanted with CRT-ICDs (Boston Scientific 173, Medtronic 416, and St Jude Medical 57) were included in this analysis. During 2.7 ± 1.5 years follow-up, 113 (17%) devices had reached ERI (Boston scientific 4%, Medtronic 25%, and St Jude Medical 7%, P < 0.001). The 4-year survival rate of device battery was significantly worse for Medtronic devices compared with devices from other manufacturers (94% for Boston scientific, 67% for Medtronic, and 92% for St Jude Medical, P < 0.001). The difference in battery longevity by manufacturer was independent of pacing burden, lead parameters, and burden of ICD therapy. There are significant discrepancies in CRT-ICD battery longevity by manufacturer. These data have important implications on clinical practice and patient outcomes.

Disease management: remote monitoring in heart failure patients with implantable defibrillators, resynchronization devices, and haemodynamic monitors.

PubMed

Abraham, William T

2013-06-01

Heart failure represents a major public health concern, associated with high rates of morbidity and mortality. A particular focus of contemporary heart failure management is reduction of hospital admission and readmission rates. While optimal medical therapy favourably impacts the natural history of the disease, devices such as cardiac resynchronization therapy devices and implantable cardioverter defibrillators have added incremental value in improving heart failure outcomes. These devices also enable remote patient monitoring via device-based diagnostics. Device-based measurement of physiological parameters, such as intrathoracic impedance and heart rate variability, provide a means to assess risk of worsening heart failure and the possibility of future hospitalization. Beyond this capability, implantable haemodynamic monitors have the potential to direct day-to-day management of heart failure patients to significantly reduce hospitalization rates. The use of a pulmonary artery pressure measurement system has been shown to significantly reduce the risk of heart failure hospitalization in a large randomized controlled study, the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients (CHAMPION) trial. Observations from a pilot study also support the potential use of a left atrial pressure monitoring system and physician-directed patient self-management paradigm; these observations are under further investigation in the ongoing LAPTOP-HF trial. All these devices depend upon high-intensity remote monitoring for successful detection of parameter deviations and for directing and following therapy.

Occurrence of simultaneous cathodal-anodal capture with left ventricular quadripolar leads for cardiac resynchronization therapy: an electrocardiogram evaluation.

PubMed

Occhetta, Eraldo; Dell'Era, Gabriele; Giubertoni, Ailia; Magnani, Andrea; Rametta, Francesco; Blandino, Alessandro; Magnano, Vincenzo; Malacrida, Maurizio; Marino, Paolo

2017-04-01

The occurrence of left ventricular (LV) anodal activation during pacing with modern multipolar cardiac resynchronization therapy (CRT) systems has never been reported. The aim of our study was to demonstrate, by means of electrocardiogram (ECG) analysis, the occurrence of simultaneous cathodal-anodal LV capture with quadripolar LV leads. We studied 10 first-time recipients of a CRT device equipped with a quadripolar LV lead. During follow-up, standard supine 12-lead ECGs were obtained in available cathode-to-anode LV pacing configurations with a pulse amplitude equal to twice the pacing threshold. The occurrence of simultaneous cathodal-anodal LV capture was defined as the presence of variations in electrocardiographic ventricular activation (EVA) when the distal tip (cathode)-to-device can (anode) pacing configuration was compared with the distal tip (cathode)-to-proximal ring (anode) configuration. In eight patients, we found differences in EVA when different LV sites were paced through the unipolar LV tip and unipolar LV ring configurations. In these patients, a difference in EVA was detected in 61.5% (59 of 96) of the ECG leads (marked difference in 31.3%, slight difference in 30.2%). Changes in EVA between unipolar tip-to-can and bipolar tip-to-ring pacing that were suggestive of cathodal-anodal LV capture were found in six patients. In these patients, a total of 30 (41.7%) ECG leads showed a difference in EVA (marked difference in 20.8%, slight difference in 20.8%). In our experience, additional anodal capture by the proximal LV ring during LV pacing is provable in most recipients of a resynchronization device equipped with a multipolar LV lead. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

DDD pacemaker for severe heart failure-alternate to CRT.

PubMed

Krishnamani, N C

Patients with severe systolic Heart Failure continue to have poor quality of life and increased mortality in spite of optimal medical management. Cardiac Resynchronization Therapy [CRT] is promising modality in patients with systolic heart failure and electrocardiographic [ECG] evidence of left bundle branch block [LBBB]. Cost issues continue to elude many deserving cases of this therapy in our society. Relatively cost effective Dual chamber pacing [DDD] with right atrial and isolated left ventricular pacing [RA-LV] can be a good alternative. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Pediatric Electrocardiographic Imaging (ECGI) Applications

PubMed Central

Silva, Jennifer N. A.

2014-01-01

Summary Noninvasive electrocardiographic imaging (ECGI) has been used in pediatric and congenital heart patients to better understand their electrophysiologic substrates. In this article we focus on the 4 subjects related to pediatric ECGI: 1) ECGI in patients with congenital heart disease and Wolff-Parkinson-White syndrome, 2) ECGI in patients with hypertrophic cardiomyopathy and pre-excitation, 3) ECGI in pediatric patients with Wolff-Parkinson-White syndrome, and 4) ECGI for pediatric cardiac resynchronization therapy. PMID:25722754

Effect of PR Interval on Outcomes Following Cardiac Resynchronization Therapy: A Secondary Analysis of the COMPANION Trial.

PubMed

Lin, Jeffrey; Buhr, Kevin A; Kipp, Ryan

2017-02-01

Prolonged PR intervals may impair atrioventricular mechanical coupling and adversely affect cardiac performance. We hypothesize that patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals will have improved survival from CRT-D regardless of whether left bundle branch block (LBBB) or non-LBBB is present. A total of 308 patients enrolled in the optimal pharmacologic therapy (OPT) and 595 patients in the cardiac resynchronization therapy with defibrillation (CRT-D) arms of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure trial were stratified according to normal (≤230 ms) or prolonged PR interval (>230 ms). The incidence of all-cause mortality (ACM) or hospitalization (primary endpoint) and ACM (secondary endpoint) was compared using Kaplan-Meier curves. Cox proportional hazards models for the primary and secondary endpoints were fit with LBBB status and baseline PR interval. CRT-D treatment reduced both hospitalization/ACM (P = 0.002) and ACM (P = 0.003) compared to OPT. However, CRT-D was increasingly more effective in reducing ACM hazard in patients with longer baseline PR intervals (P = 0.002) regardless of LBBB status. In particular, in the prolonged baseline PR interval subgroup, ACM was reduced with CRT-D compared to OPT (P = 0.001) with little evidence of ACM reduction in the normal PR subgroup (P = 0.07). In patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals, restoration of atrioventricular mechanical coupling with CRT-D may improve survival regardless of LBBB status. In patients with non-LBBB, a benefit from CRT-D may occur with prolonged PR intervals. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Tailor-made heart simulation predicts the effect of cardiac resynchronization therapy in a canine model of heart failure.

PubMed

Panthee, Nirmal; Okada, Jun-ichi; Washio, Takumi; Mochizuki, Youhei; Suzuki, Ryohei; Koyama, Hidekazu; Ono, Minoru; Hisada, Toshiaki; Sugiura, Seiryo

2016-07-01

Despite extensive studies on clinical indices for the selection of patient candidates for cardiac resynchronization therapy (CRT), approximately 30% of selected patients do not respond to this therapy. Herein, we examined whether CRT simulations based on individualized realistic three-dimensional heart models can predict the therapeutic effect of CRT in a canine model of heart failure with left bundle branch block. In four canine models of failing heart with dyssynchrony, individualized three-dimensional heart models reproducing the electromechanical activity of each animal were created based on the computer tomographic images. CRT simulations were performed for 25 patterns of three ventricular pacing lead positions. Lead positions producing the best and the worst therapeutic effects were selected in each model. The validity of predictions was tested in acute experiments in which hearts were paced from the sites identified by simulations. We found significant correlations between the experimentally observed improvement in ejection fraction (EF) and the predicted improvements in ejection fraction (P<0.01) or the maximum value of the derivative of left ventricular pressure (P<0.01). The optimal lead positions produced better outcomes compared with the worst positioning in all dogs studied, although there were significant variations in responses. Variations in ventricular wall thickness among the dogs may have contributed to these responses. Thus CRT simulations using the individualized three-dimensional heart models can predict acute hemodynamic improvement, and help determine the optimal positions of the pacing lead. Copyright © 2016 Elsevier B.V. All rights reserved.

Importance of heart rate during exercise for response to cardiac resynchronization therapy.

PubMed

Maass, Alexander H; Buck, Sandra; Nieuwland, Wybe; Brügemann, Johan; van Veldhuisen, Dirk J; Van Gelder, Isabelle C

2009-07-01

Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60-70% of patients. To study exercise-related factors predicting response to CRT. We retrospectively examined consecutive patients in whom a CRT device was implanted. All underwent cardiopulmonary exercise testing prior to implantation and after 6 months. The occurrence of chronotropic incompetence and heart rates exceeding the upper rate of the device, thereby compromising biventricular stimulation, was studied. Response was defined as a decrease in LVESV of 10% or more after 6 months. We included 144 patients. After 6 months 86 (60%) patients were responders. Peak VO2 significantly increased in responders. Chronotropic incompetence was more frequently seen in nonresponders (21 [36%] vs 9 [10%], P = 0.03), mostly in patients in SR. At moderate exercise, defined as 25% of the maximal exercise tolerance, that is, comparable to daily life exercise, nonresponders more frequently went above the upper rate of the device (13 [22%] vs 2 [3%], P < 0.0001), most of whom were patients in permanent AF. Multivariate analysis revealed heart rates not exceeding the upper rate of the device during moderate exercise (OR 15.8 [3.3-76.5], P = 0.001) and nonischemic cardiomyopathy (OR 2.4 [1.0-5.7], P = 0.04) as predictive for response. Heart rate exceeding the upper rate during moderate exercise is an independent predictor for nonresponse to CRT in patients with AF, whereas chronotropic incompetence is a predictor for patients in SR.

Battery longevity of implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators: technical, clinical and economic aspects. An expert review paper from EHRA.

PubMed

Boriani, Giuseppe; Merino, Josè; Wright, David J; Gadler, Fredrik; Schaer, Beat; Landolina, Maurizio

2018-05-10

In recent years an extension of devices longevity has been obtained for implantable cardioverter-defibrillators (ICDs), including ICDs for cardiac resynchronization therapy (CRT-D) through improved battery chemistry and device technology and this implies important clinical benefits (reduced need for device replacements and associated complications, particularly infections), as well as economic benefits, in line with patient preferences and needs. From a clinical point of view, the availability of this improvement in technology allows to better tune the choice of the device to be implanted, taking into account that the reasons supporting the value of an extended device longevity as a clinical priority may differ according to the clinical setting (purely electrical diseases or left ventricular dysfunction/heart failure, respectively). From an economic point of view, extension of device longevity may have an important impact in reducing long-term costs of device therapy, with substantial daily savings in favour of devices with extended longevity, up to 30%, depending on clinical scenarios. In studies based on projections, an extension of device longevity allowed to calculate that the cost per day of ICDs may be substantially reduced, and this allows to overcome the frequent perception of ICD and CRT-D devices as treatments with unaffordable costs and to overturn the misconception that up-front costs are the only metric with which to value device treatments. In view of its clinical and economic value, device longevity should be a determining factor in device choice by physicians and healthcare commissioners and should be appropriately considered and valued in comparative tenders.

Accuracy of manual QRS duration assessment: its importance in patient selection for cardiac resynchronization and implantable cardioverter defibrillator therapy.

PubMed

Tomlinson, David R; Bashir, Yaver; Betts, Timothy R; Rajappan, Kim

2009-05-01

Patients with left ventricular systolic dysfunction and electrocardiographic QRS duration (QRSd) >or=120 ms may obtain symptomatic and prognostic benefits from cardiac resynchronization therapy (CRT). However, clinical trials do not describe the methods used to measure QRSd. We investigated the effect of electrocardiogram (ECG) display format and paper speed on the accuracy of manual QRSd assessment and concordance of manual QRSd with computer-calculated mean and maximal QRSd. Six cardiologists undertook QRSd measurements on ECGs, with computer-calculated mean QRSd close to 120 ms. Display formats were 12-lead, 6-limb, and 6-precordial leads, each at 25 and 50 mm/s. When the computer-calculated mean was used to define QRSd, manual assessment demonstrated 97 and 83% concordance at categorizing QRSd as < and >or=120 ms, respectively. Using the computer-calculated maximal QRSd, manual assessment demonstrated 83% concordance when QRSd was <120 ms and 19% concordance when QRSd was >or=120 ms. The six-precordial lead format demonstrated significantly less intra and inter-observer variabilities than the 12-lead, but this did not improve concordance rates. Manual QRSd assessments demonstrate significant variability, and concordance with computer-calculated measurement depends on whether QRSd is defined as the mean or maximal value. Consensus is required both on the most appropriate definition of QRSd and its measurement.

Malfunction of subpectorally implanted cardiac resynchronization therapy defibrillators due to weakened header bond.

PubMed

Hayat, Sajad A; Kojodjojo, Pipin; Mason, Anthony; Benfield, Ann; Wright, Ian; Whinnett, Zachary; Lim, Phang Boon; Davies, D Wyn; Lefroy, David; Peters, Nicholas S; Kanagaratnam, Prapa

2013-03-01

Implantable cardioverter defibrillator (ICD) implantation has increased significantly over the last 10 years. Concerns about the safety and reliability of ICD systems have been raised, with premature lead failure and battery malfunctions accounting for the majority of reported adverse events. We describe the unique mode of presentation, diagnosis, and management of cardiac resynchronization therapy defibrillators (CRT-D) malfunctions that were caused by weakened bonding between the generator and header. Between June 2008 and December 2009, 22 Teligen™ ICDs and 24 Cognis™ CRT-Ds were implanted subpectorally at our institution, until a product advisory was issued. Of 24 Cognis™ CRT-D implants, 3 patients presented with CRT-D malfunctions. All our cases presented with initially intermittent and then persisting increases in shock lead impedance, associated with nonphysiological noise in the shock electrogram channels. These issues were rectified by generator change. Postexplant laboratory analysis confirmed inadequate bonding between device header and titanium casing in all cases, resulting in loosening and rocking of the header followed by fatigue-induced fracture of the shock circuitry. Weakened bonding between the header and generator casing of subpectorally implanted CRT-Ds can result in fractures and malfunction of the HV circuit. Physicians monitoring patients with devices affected by the product advisory should remain vigilant in order to diagnose and manage similar device malfunction expediently. © 2012 Wiley Periodicals, Inc.

Role of echocardiography before cardiac resynchronization therapy: new advances and current developments.

PubMed

Marechaux, Sylvestre; Menet, Aymeric; Guyomar, Yves; Ennezat, Pierre-Vladimir; Guerbaai, Raphaëlle Ashley; Graux, Pierre; Tribouilloy, Christophe

2016-11-01

The role of echocardiography in improving the selection of patients who will benefit from cardiac resynchronization therapy (CRT) remains a source of debate. Although previous landmark reports have demonstrated a link between mechanical dyssynchrony, assessed by delays between left ventricle (LV) walls and response to CRT, the predictive value of these findings has not yet been confirmed in multicenter trials. Indeed, recent studies demonstrated that the classical assessment of LV mechanical dyssynchrony using delay between walls by echocardiography depends not only on LV electrical activation delay (electrical dyssynchrony), but also on abnormalities in regional contractility of the LV and/or loading conditions, which do not represent an appropriate target for CRT. Recent reports highlighted the value of new indices of electromechanical dyssynchrony obtained by echocardiography, to predict LV response and outcome after CRT including septal flash, left bundle branch block-typical pattern by longitudinal strain, apical rocking, septal strain patterns, and systolic stretch index. This was achieved using a mechanistic approach, based on the contractile consequences of electrical dyssynchrony. These indices are rarely found in patients with narrow QRS (<120 ms), whereas their frequency rises in patients with an increase in QRS duration (>120 ms). Theses indices should improve candidate selection for CRT in clinical practice, especially for patients in whom the benefit of CRT remains uncertain, for example, patients with intermediate QRS width (120-150 ms). © 2016, Wiley Periodicals, Inc.

Technology Advances to Improve Response to Cardiac Resynchronization Therapy: What Clinicians Should Know.

PubMed

Auricchio, Angelo; Heggermont, Ward A

2018-06-01

Cardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure patients with reduced left ventricular ejection fraction, prolonged QRS duration, and abnormal QRS morphology. The ultimate goals of modern CRT are to improve the proportion of patients responding to CRT and to maximize the response to CRT in patients who do respond. While the rate of CRT nonresponders has moderately but progressively decreased over the last 20 years, mostly in patients with left bundle branch block, in patients without left bundle branch block the response rate is almost unchanged. A number of technological advances have already contributed to achieve some of the objectives of modern CRT. They include novel lead design (the left ventricular quadripolar lead, and multipoint pacing), or the possibility to go beyond conventional delivery of CRT (left ventricular endocardial pacing, His bundle pacing). Furthermore, to improve CRT response, a triad of actions is paramount: reducing the burden of atrial fibrillation, reducing the number of appropriate and inappropriate interventions, and adequately predicting heart failure episodes. As in other fields of cardiology, technology and innovations for CRT delivery have been at the forefront in transforming-improving-patient care; therefore, these innovations are discussed in this review. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Percutaneous Epicardial Pacing using a Novel Insulated Multi-electrode Lead.

PubMed

Syed, Faisal F; DeSimone, Christopher V; Ebrille, Elisa; Gaba, Prakriti; Ladewig, Dorothy J; Mikell, Susan B; Suddendorf, Scott H; Gilles, Emily J; Danielsen, Andrew J; Lukášová, Markéta; Wolf, Jiří; Leinveber, Pavel; Novák, Miroslav; Stárek, Zdeněk; Kara, Tomas; Bruce, Charles J; Friedman, Paul A; Asirvatham, Samuel J

2015-08-01

Epicardial cardiac resynchronization therapy (CRT) permits unrestricted electrode positioning. However, this requires surgical placement of device leads and the risk of unwanted phrenic nerve stimulation. We hypothesized that shielded electrodes can capture myocardium without extracardiac stimulation. In 6 dog and 5 swine experiments, we used a percutaneous approach to access the epicardial surface of the heart, and deploy novel leads housing multiple electrodes with selective insulation. Bipolar pacing thresholds at prespecified sites were tested compare electrode threshold data both facing towards and away from the epicardial surface. In 151 paired electrode recordings (70 in 6 dogs; 81 in 5 swine), thresholds facing myocardium were lower than facing away (median [IQR] mA: dogs 0.9 [0.4-1.6] vs 4.6 [2.1 to >10], p<0.0001; swine 0.5 [0.2-1] vs 2.5 [0.5-6.8], p<0.0001). Myocardial capture was feasible without extracardiac stimulation at all tested sites, with mean ± SE threshold margin 3.6±0.7 mA at sites of high output extracardiac stimulation (p=0.004). Selective electrode insulation confers directional pacing to a multielectrode epicardial pacing lead. This device has the potential for a novel percutaneous epicardial resynchronization therapy that permits placement at an optimal pacing site, irrespective of the anatomy of the coronary veins or phrenic nerves.

Manual vs. automatic capture management in implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators.

PubMed

Murgatroyd, Francis D; Helmling, Erhard; Lemke, Bernd; Eber, Bernd; Mewis, Christian; van der Meer-Hensgens, Judith; Chang, Yanping; Khalameizer, Vladimir; Katz, Amos

2010-06-01

The Secura ICD and Consulta CRT-D are the first defibrillators to have automatic right atrial (RA), right ventricular (RV), and left ventricular (LV) capture management (CM). Complete CM was evaluated in an implantable cardioverter defibrillator (ICD) population. Two prospective clinical studies were conducted in 28 centres in Europe and Israel. Automatic CM data were compared with manual threshold measurements, the CM applicability was determined, and adjustments to pacing outputs were analysed. In total, 160 patients [age 64.6 +/- 10.4 years, 77% male, 80 ICD and 80 cardiac resynchronization therapy defibrillator (CRT-D)] were included. The differences between automatic and manual measurements were 2.5 V) due to raised RA threshold in seven (4.4%), high RV threshold in nine (5.6%), and high LV threshold in three patients (3.8%). All high threshold detections and all automatic modulations of pacing output were adjudicated appropriate. Complete CM adjusts pacing output appropriately, permitting a reduction in office visits while it may maximize device longevity. The study was registered at ClinicalTrials.gov identifiers: NCT00526227 and NCT00526162.

Manual Intracardiac Electrogram Method Is Accurate Alternative to Echocardiography for Atrioventricular and Interventricular Optimization in Cardiac Resynchronization Therapy.

PubMed

Pezo Nikolić, Borka; Lovrić, Daniel; Ljubas Maček, Jana; Rešković Lukšić, Vlatka; Matasić, Richard; Šeparović Hanževački, Jadranka

2017-12-01

Some manufacturers do not provide automated intracardiac electrogram method (IEGM) systems for atrioventricular (AV) and interventricular (VV) delay optimization in cardiac resynchronization therapy (CRT). We aimed to evaluate the accuracy of manual IEGM method in 48 patients previously implanted with Medtronic Syncra CRT. All patients underwent standard device interrogation followed by CRT optimization by IEGM method and by echocardiography one month after implantation. The patient mean age was 60.7±11.8 years and there were 33 (68.8%) males. After CRT implantation, the left ventricular ejection fraction increased from 28.0±7.9% to 39.1±11.0% (p<0.001). Optimal aortic flow Velocity Time Integral (aVTI) was obtained when VV was set to 20-50 ms left ventricular pre-activation. There was a strong correlation between VV values determined by echocardiography and IEGM (R=0.823, p<0.001). We found no significant difference in AV, VV and aVTI values between echocardiography and IEGM method. However, IEGM was significantly less time-consuming than echocardiography [20 (10-28) vs. 40 (35-60) minutes, p<0.001]. Manual IEGM method may be good alternative to echocardiography and automated IEGM method. It also emphasizes the need for implementation of automated IEGM systems in as many CRT devices as possible.

A Case of a Cardiac Resynchronization Therapy-Defibrillator Exhibiting a Lower and Alternately Variable Basic Rate.

PubMed

Iwazaki, Keigo; Kojima, Toshiya; Murasawa, Takahide; Yokota, Jun; Tanimoto, Hikaru; Matsuda, Jun; Fukuma, Nobuaki; Matsubara, Takumi; Shimizu, Yu; Oguri, Gaku; Hasumi, Eriko; Kubo, Hitoshi; Chang, Kyungho; Fujiu, Katsuhito; Komuro, Issei

2018-05-30

A cardiac resynchronization therapy defibrillator (CRT-D) (Medtronic Inc. Protecta XT) was implanted in a 67-year-old man who had cardiac sarcoidosis with extremely low cardiac function. He had ventricular tachycardia which was controlled by catheter ablation, medication and pacing. The programmed mode was DDI, lower rate was 90 beats/minute, paced AV delay was 150 ms, and the noncompetitive atrial pacing (NCAP) function was programmed as 300 ms.After his admission for pneumonia and heart failure, we changed his DDI mode to a DDD mode because he had atrial tachycardia, which led to inadequate bi-ventricular pacing. After a while, there were cycle lengths which were longer than his device setting and alternately varied. We were able to avoid this phenomenon with AV delay of 120 ms and NCAP of 200 ms.NCAP is an algorithm which creates a gap above a certain period after the detection of an atrial signal during the postventricular atrial refractory period of the pacemaker. This is to prevent atrial tachycardia and repetitive non-reentrant ventriculoatrial (VA) synchrony in the presence of retrograde VA conduction. But in this case, NCAP algorithm induced much lower rate than the programmed basic lower rate. This situation produced some arrhythmias and exacerbated symptoms of heart failure. This had to be paid attention to, especially when the device was programmed at high basic heart rate.

Adaptive servo ventilation improves Cheyne-Stokes respiration, cardiac function, and prognosis in chronic heart failure patients with cardiac resynchronization therapy.

PubMed

Miyata, Makiko; Yoshihisa, Akiomi; Suzuki, Satoshi; Yamada, Shinya; Kamioka, Masashi; Kamiyama, Yoshiyuki; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

2012-09-01

Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT. Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group. ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Quantification of the rates of resynchronization of heart rate with body temperature rhythms in man following a photoperiod shift

NASA Technical Reports Server (NTRS)

Hetherington, N. W.; Rosenblatt, L. S.; Higgins, E. A.; Winget, C. M.

1973-01-01

A mathematical model previously presented by Rosenblatt et al. (1973) for estimating the rates of resynchronization of individual biorhythms following transmeridian flights or photoperiod shifts is extended to estimation of rates at which two biorythms resynchronize with respect to each other. Such quantification of the rate of restoration of the initial phase relationship of the two biorhythms is pointed out as a valuable tool in the study of internal desynchronosis.

Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy.

PubMed

Zile, Michael R; Abraham, William T; Weaver, Fred A; Butter, Christian; Ducharme, Anique; Halbach, Marcel; Klug, Didier; Lovett, Eric G; Müller-Ehmsen, Jochen; Schafer, Jill E; Senni, Michele; Swarup, Vijay; Wachter, Rolf; Little, William C

2015-10-01

Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Carotid baroreceptor stimulation (baroreflex activation therapy, BAT) results in centrally mediated reduction of sympathetic and increase in parasympathetic activity. Because patients treated with cardiac resynchronization therapy (CRT) may have less sympathetic/parasympathetic imbalance, we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT. New York Heart Association (NYHA) Class III patients with an ejection fraction (EF) ≤35% were randomized (1 : 1) to ongoing guideline-directed medical and device therapy (GDMT, control) or ongoing GDMT plus BAT. Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events (MANCE). Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life (QoL), 6-min hall walk distance (6MHWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and HF hospitalization rate. In this sample, 146 patients were randomized (70 control; 76 BAT) and were 140 activated (45 with CRT and 95 without CRT). MANCE-free rate at 6 months was 100% in CRT and 96% in no-CRT group. At 6 months, in the no-CRT group, QoL score, 6MHWD, LVEF, NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls. Changes in efficacy endpoints in the CRT group favoured BAT; however, the improvements were less than in the no-CRT group and were not statistically different from control. BAT is safe and significantly improved QoL, exercise capacity, NTpro-BNP, EF, and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients. These effects were most pronounced in patients not treated with CRT. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Computational cardiology: the bidomain based modified Hill model incorporating viscous effects for cardiac defibrillation

NASA Astrophysics Data System (ADS)

Cansız, Barış; Dal, Hüsnü; Kaliske, Michael

2017-10-01

Working mechanisms of the cardiac defibrillation are still in debate due to the limited experimental facilities and one-third of patients even do not respond to cardiac resynchronization therapy. With an aim to develop a milestone towards reaching the unrevealed mechanisms of the defibrillation phenomenon, we propose a bidomain based finite element formulation of cardiac electromechanics by taking into account the viscous effects that are disregarded by many researchers. To do so, the material is deemed as an electro-visco-active material and described by the modified Hill model (Cansız et al. in Comput Methods Appl Mech Eng 315:434-466, 2017). On the numerical side, we utilize a staggered solution method, where the elliptic and parabolic part of the bidomain equations and the mechanical field are solved sequentially. The comparative simulations designate that the viscoelastic and elastic formulations lead to remarkably different outcomes upon an externally applied electric field to the myocardial tissue. Besides, the achieved framework requires significantly less computational time and memory compared to monolithic schemes without loss of stability for the presented examples.

[Acute and chronic heart failure].

PubMed

Kresoja, K-P; Schmidt, G; Kherad, B; Krackhardt, F; Spillmann, F; Tschöpe, C

2017-11-01

The initial therapy of chronic heart failure is still based on diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and in specific cases mineralocorticoid receptor antagonists. The new European Society of Cardiology (ESC) guidelines published in 2016 introduced angiotensin-receptor-neprilysin inhibitors, such as sacubitril/valsartan (LCZ 696) as new therapeutic agents in patients with chronic and progressive heart failure. New subgroup analyses for LCZ 696 have been published showing a beneficial effect in the context of various comorbidities, such as renal insufficiency, diabetes and hypotension. Furthermore, new data are available on intravenous iron substitution in chronic heart failure and on the indications for implantable converter defibrillators, cardiac resynchronization therapy and other cardiac devices. Medicinal therapy of acute heart failure is still limited. For patients who cannot be treated with medicinal therapy, mechanical circulatory support, such as extracorporeal membrane oxygenation (ECMO) should be recommended.

Hypercalcemic crisis and primary hyperparathyroidism: Cause of an unusual electrical storm.

PubMed

Guimarães, Tatiana; Nobre Menezes, Miguel; Cruz, Diogo; do Vale, Sónia; Bordalo, Armando; Veiga, Arminda; Pinto, Fausto J; Brito, Dulce

2017-12-01

Hypercalcemia is a known cause of heart rhythm disorders, however its association with ventricular arrhythmias is rare. The authors present a case of a fifty-three years old male patient with a ischemic and ethanolic dilated cardiomyopathy, and severely reduced ejection fraction, carrier of cardiac resynchronization therapy (CRT) with cardioverter defibrillator (ICD), admitted in the emergency department with an electrical storm, with multiple appropriated ICD shocks, refractory to antiarrhythmic therapy. In the etiological investigation was documented severe hypercalcemia secondary to primary hyperparathyroidism undiagnosed until then. Only after the serum calcium level reduction ventricular tachycardia was stopped. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Dynamic left ventricular dyssynchrony and severe mitral regurgitation caused by exercise: should we go beyond the guidelines?

PubMed

Laflamme, Emilie; Philippon, François; O'Connor, Kim; Sarrazin, Jean-François; Auffret, Vincent; Chauvette, Vincent; Dubois, Michelle; Voisine, Pierre; Bergeron, Sébastien; Sénéchal, Mario

2018-01-01

Guidelines for cardiac resynchronization therapy (CRT) have been established, but there may be a subgroup of patients not identified in these guidelines who may benefit from this therapy. We report a patient with a dynamic left ventricular dyssynchrony and severe mitral regurgitation caused by exercise successfully treated with CRT. Exercise testing should be considered in patients with left ventricular ejection fraction <35% and QRS <130 ms with severe heart failure symptoms that are unexplained by rest echocardiography evaluation in order to rule out ischemia and/or dynamic left ventricular dyssynchrony. In the presence of exercise-induced left ventricular bundle branch block, the implantation of CRT should be contemplated.

Transvenous versus open chest lead placement for resynchronization therapy in patients with heart failure: comparison of ventricular electromechanical synchronicity.

PubMed

Zhang, Hai-Bo; Meng, Xu; Han, Jie; Li, Yan; Zhang, Ye; Jiang, Teng-Yong; Zhao, Ying-Xin; Zhou, Yu-Jie

2017-04-01

Transvenous lead placement is the standard approach for left ventricular (LV) pacing in cardiac resynchronization therapy (CRT), while the open chest access epicardial lead placement is currently the most frequently used second choice. Our study aimed to compare the ventricular electromechanical synchronicity in patients with heart failure after CRT with these two different LV pacing techniques. We enrolled 33 consecutive patients with refractory heart failure secondly to dilated cardiomyopathy who were eligible for CRT in this study. Nineteen patients received transvenous (TV group) while 14 received open chest (OP group) LV lead pacing. Intra- and inter-ventricular electromechanical synchronicity was assessed by tissue Doppler imaging (TDI) before and one year after CRT procedure. Before CRT procedure, the mean QRS-duration, maximum time difference to systolic peak velocity among 12 left ventricle segments (LV Ts-12), standard deviation of time difference to systolic peak velocity of 12 left ventricle segments (LV Ts-SD), and inter-ventricular mechanical delay (IVMD) in OP and TV group were 166 ± 17 ms and 170 ± 21 ms, 391 ± 42 ms and 397 ± 36 ms, 144 ± 30 ms and 148 ± 22 ms, 58 ± 25 ms and 60 ± 36 ms, respectively (all P > 0.05). At one year after the CRT, the mean QRS-duration, LV Ts-12, LV Ts-SD, and IVMD in TV and OP group were 128 ± 14 ms and 141 ± 22 ms ( P = 0.031), 136 ± 37 ms and 294 ± 119 ms ( P = 0.023), 50 ± 22 ms and 96 ± 34 ms ( P = 0.015), 27 ± 11 ms and 27 ± 26 ms ( P = 0.86), respectively. The LV lead implantation procedure time was 53.4 ± 16.3 min for OP group and 136 ± 35.1 min for TV group ( P = 0.016). The mean LV pacing threshold increased significantly from 1.7 ± 0.6 V/0.5 ms to 2.3 ± 1.6 V/0.5 ms ( P < 0.05) in TV group while it remained stable in the OP group. Compared to conventional endovascular approach, open chest access of LV pacing for CRT leads to better improvement of the intraventricular synchronization.

The role of repeating optimization of atrioventricular interval during interim and long-term follow-up after cardiac resynchronization therapy.

PubMed

Zhang, Qing; Fung, Jeffrey Wing-Hong; Chan, Yat-Sun; Chan, Hamish Chi-Kin; Lin, Hong; Chan, Skiva; Yu, Cheuk-Man

2008-02-29

Cardiac resynchronization therapy (CRT) is an effective therapy for heart failure patients with electromechanical delay. Optimization of atrioventricular interval (AVI) is a cardinal component for the benefits. However, it is unknown if the AVI needs to be re-optimized during long-term follow-up. Thirty-one patients (66+/-11 years, 20 males) with sinus rhythm who received CRT underwent serial optimization of AVI at day 1, 3-month and during long-term follow-up by pulse Doppler echocardiography (PDE). At long-term follow-up, the optimal AVI and cardiac output (CO) estimated by non-invasive impedance cardiography (ICG) were compared with those by PDE. The follow-up was 16+/-11 months. There was no significant difference in the mean optimal AVI when compared between any 2 time points among day 1 (99+/-30 ms), 3-month (97+/-28 ms) and long-term follow-up (94+/-28 ms). However, in individual patient, the optimal AVI remained unchanged only in 14 patients (44%), and was shortened in 12 (38%) and lengthened in 6 patients (18%). During long-term follow-up, although the mean optimal AVIs obtained by PDE or ICG (94+/-28 vs. 92+/-29 ms) were not different, a discrepancy was found in 14 patients (45%). For the same AVI, the CO measured by ICG was systematically higher than that by PDE (3.5+/-0.8 Vs. 2.7+/-0.6 L/min, p<0.001). Optimization of AVI after CRT appears necessary during follow-up as it was readjusted in 55% of patients. Although AVI optimization by ICG was feasible, further studies are needed to confirm its role in optimizing AVI after CRT.

Cardiac Resynchronization Therapy Online: What Patients Find when Searching the World Wide Web.

PubMed

Modi, Minal; Laskar, Nabila; Modi, Bhavik N

2016-06-01

To objectively assess the quality of information available on the World Wide Web on cardiac resynchronization therapy (CRT). Patients frequently search the internet regarding their healthcare issues. It has been shown that patients seeking information can help or hinder their healthcare outcomes depending on the quality of information consulted. On the internet, this information can be produced and published by anyone, resulting in the risk of patients accessing inaccurate and misleading information. The search term "Cardiac Resynchronisation Therapy" was entered into the three most popular search engines and the first 50 pages on each were pooled and analyzed, after excluding websites inappropriate for objective review. The "LIDA" instrument (a validated tool for assessing quality of healthcare information websites) was to generate scores on Accessibility, Reliability, and Usability. Readability was assessed using the Flesch Reading Ease Score (FRES). Of the 150 web-links, 41 sites met the eligibility criteria. The sites were assessed using the LIDA instrument and the FRES. A mean total LIDA score for all the websites assessed was 123.5 of a possible 165 (74.8%). The average Accessibility of the sites assessed was 50.1 of 60 (84.3%), on Usability 41.4 of 54 (76.6%), on Reliability 31.5 of 51 (61.7%), and 41.8 on FRES. There was a significant variability among sites and interestingly, there was no correlation between the sites' search engine ranking and their scores. This study has illustrated the variable quality of online material on the topic of CRT. Furthermore, there was also no apparent correlation between highly ranked, popular websites and their quality. Healthcare professionals should be encouraged to guide their patients toward the online material that contains reliable information. © 2016 Wiley Periodicals, Inc.

Feasibility and Association of Neurohumoral Blocker Up-titration After Cardiac Resynchronization Therapy.

PubMed

Martens, Pieter; Verbrugge, Frederik H; Nijst, Petra; Bertrand, Philippe B; Dupont, Matthias; Tang, Wilson H; Mullens, Wilfried

2017-08-01

Cardiac resynchronization therapy (CRT) improves mortality and morbidity on top of optimal medical therapy in heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the association between neurohumoral blocker up-titration after CRT implantation and clinical outcomes. Doses of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta-blockers were retrospectively evaluated in 650 consecutive CRT patients implanted from October 2008 to August 2015 and followed in a tertiary multidisciplinary CRT clinic. All 650 CRT patients were on a maximal tolerable dose of ACE-I/ARB and beta-blocker at the time of CRT implantation. However, further up-titration was successful in 45.4% for ACE-I/ARB and in 56.8% for beta-blocker after CRT-implantation. During a mean follow-up of 37 ± 22 months, a total of 139 events occurred for the combined end point of heart failure admission and all-cause mortality. Successful, versus unsuccessful, up-titration was associated with adjusted hazard ratios of 0.537 (95% confidence interval 0.316-0.913; P = .022) for ACE-I/ARB and 0.633 (0.406-0.988; P = .044) for beta-blocker on the combined end point heart failure admission and all-cause mortality. Patients in the up-titration group exhibited a similar risk for death or heart failure admission as patients treated with the maximal dose (ACE-I/ARB: P = .133; beta-blockers: P = .709). After CRT, a majority of patients are capable of tolerating higher dosages of neurohumoral blockers. Up-titration of neurohumoral blockers after CRT implantation is associated with improved clinical outcomes, similarly to patients treated with the guideline-recommended target dose at the time of CRT implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of genetic markers for treatment success in heart failure patients: insight from cardiac resynchronization therapy.

PubMed

Schmitz, Boris; De Maria, Renata; Gatsios, Dimitris; Chrysanthakopoulou, Theodora; Landolina, Maurizio; Gasparini, Maurizio; Campolo, Jonica; Parolini, Marina; Sanzo, Antonio; Galimberti, Paola; Bianchi, Michele; Lenders, Malte; Brand, Eva; Parodi, Oberdan; Lunati, Maurizio; Brand, Stefan-Martin

2014-12-01

Cardiac resynchronization therapy (CRT) can improve ventricular size, shape, and mass and reduce mitral regurgitation by reverse remodeling of the failing ventricle. About 30% of patients do not respond to this therapy for unknown reasons. In this study, we aimed at the identification and classification of CRT responder by the use of genetic variants and clinical parameters. Of 1421 CRT patients, 207 subjects were consecutively selected, and CRT responder and nonresponder were matched for their baseline parameters before CRT. Treatment success of CRT was defined as a decrease in left ventricular end-systolic volume >15% at follow-up echocardiography compared with left ventricular end-systolic volume at baseline. All other changes classified the patient as CRT nonresponder. A genetic association study was performed, which identified 4 genetic variants to be associated with the CRT responder phenotype at the allelic (P<0.035) and genotypic (P<0.031) level: rs3766031 (ATPIB1), rs5443 (GNB3), rs5522 (NR3C2), and rs7325635 (TNFSF11). Machine learning algorithms were used for the classification of CRT patients into responder and nonresponder status, including combinations of the identified genetic variants and clinical parameters. We demonstrated that rule induction algorithms can successfully be applied for the classification of heart failure patients in CRT responder and nonresponder status using clinical and genetic parameters. Our analysis included information on alleles and genotypes of 4 genetic loci, rs3766031 (ATPIB1), rs5443 (GNB3), rs5522 (NR3C2), and rs7325635 (TNFSF11), pathophysiologically associated with remodeling of the failing ventricle. © 2014 American Heart Association, Inc.

Machine Learning Algorithm Predicts Cardiac Resynchronization Therapy Outcomes: Lessons From the COMPANION Trial.

PubMed

Kalscheur, Matthew M; Kipp, Ryan T; Tattersall, Matthew C; Mei, Chaoqun; Buhr, Kevin A; DeMets, David L; Field, Michael E; Eckhardt, Lee L; Page, C David

2018-01-01

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in heart failure patients with reduced left ventricular function and intraventricular conduction delay. However, individual outcomes vary significantly. This study sought to use a machine learning algorithm to develop a model to predict outcomes after CRT. Models were developed with machine learning algorithms to predict all-cause mortality or heart failure hospitalization at 12 months post-CRT in the COMPANION trial (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure). The best performing model was developed with the random forest algorithm. The ability of this model to predict all-cause mortality or heart failure hospitalization and all-cause mortality alone was compared with discrimination obtained using a combination of bundle branch block morphology and QRS duration. In the 595 patients with CRT-defibrillator in the COMPANION trial, 105 deaths occurred (median follow-up, 15.7 months). The survival difference across subgroups differentiated by bundle branch block morphology and QRS duration did not reach significance ( P =0.08). The random forest model produced quartiles of patients with an 8-fold difference in survival between those with the highest and lowest predicted probability for events (hazard ratio, 7.96; P <0.0001). The model also discriminated the risk of the composite end point of all-cause mortality or heart failure hospitalization better than subgroups based on bundle branch block morphology and QRS duration. In the COMPANION trial, a machine learning algorithm produced a model that predicted clinical outcomes after CRT. Applied before device implant, this model may better differentiate outcomes over current clinical discriminators and improve shared decision-making with patients. © 2018 American Heart Association, Inc.

Tpeak - Tend and Tpeak - Tend /QT ratio as markers of ventricular arrhythmia risk in cardiac resynchronization therapy patients.

PubMed

Barbhaiya, Chirag; Po, Jose Ricardo F; Hanon, Sam; Schweitzer, Paul

2013-01-01

Cardiac resynchronization therapy (CRT) increases transmural dispersion of repolarization (TDR) and can be pro-arrhythmic. However, overall arrhythmia risk was not increased in large-scale CRT clinical trials. Increased TDR as measured by T(peak ) -T(end) (TpTe) was associated with arrhythmia risk in CRT in a single-center study. This study investigates whether QT interval, TpTe, and TpTe/QT ratio are associated with ventricular arrhythmias in patients with CRT-defibrillator (CRT-D). Post-CRT-D implant electrocardiograms of 128 patients (age 71.3 years ± 10.3) with at least 2 months of follow-up at our institution's device clinic (mean follow-up of 28.5 months ± 17) were analyzed for QT interval, TpTe, and TpTe/QT ratio. Incidence of ventricular arrhythmias was determined based on routine and directed device interrogations. Appropriate implantable cardioverter-defibrillator therapy for sustained ventricular tachycardia or ventricular fibrillation was delivered in 18 patients (14%), and nonsustained ventricular tachycardia (NSVT) was detected but did not require therapy in 58 patients (45%). Patients who received appropriate defibrillator therapy had increased TpTe/QT ratio (0.24 ± 0.03 ms vs 0.20 ± 0.04, P = 0.0002) and increased TpTe (105.56 ± 20.36 vs 87.82 ± 22.32 ms, P = 0.002), and patients with NSVT had increased TpTe/QT ratio (0.22 ± 0.04 vs 0.20 ± 0.04, P = 0.016). Increased QT interval was not associated with risk of ventricular arrhythmia. The relative risk for appropriate defibrillator therapy of T(p) T(e) /QT ratio ≥ 0.25 was 3.24 (P = 0.016). Increased TpTe and increased TpTe/QT ratio are associated with increased incidence of ventricular arrhythmias in CRT-D. The utility of TpTe interval and TpTe/QT ratio as potentially modifiable risk factors for ventricular arrhythmias in CRT requires further study. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Respiratory motion compensated overlay of surface models from cardiac MR on interventional x-ray fluoroscopy for guidance of cardiac resynchronization therapy procedures

NASA Astrophysics Data System (ADS)

Manzke, R.; Bornstedt, A.; Lutz, A.; Schenderlein, M.; Hombach, V.; Binner, L.; Rasche, V.

2010-02-01

Various multi-center trials have shown that cardiac resynchronization therapy (CRT) is an effective procedure for patients with end-stage drug invariable heart failure (HF). Despite the encouraging results of CRT, at least 30% of patients do not respond to the treatment. Detailed knowledge of the cardiac anatomy (coronary venous tree, left ventricle), functional parameters (i.e. ventricular synchronicity) is supposed to improve CRT patient selection and interventional lead placement for reduction of the number of non-responders. As a pre-interventional imaging modality, cardiac magnetic resonance (CMR) imaging has the potential to provide all relevant information. With functional information from CMR optimal implantation target sites may be better identified. Pre-operative CMR could also help to determine whether useful vein target segments are available for lead placement. Fused with X-ray, the mainstay interventional modality, improved interventional guidance for lead-placement could further help to increase procedure outcome. In this contribution, we present novel and practicable methods for a) pre-operative functional and anatomical imaging of relevant cardiac structures to CRT using CMR, b) 2D-3D registration of CMR anatomy and functional meshes with X-ray vein angiograms and c) real-time capable breathing motion compensation for improved fluoroscopy mesh overlay during the intervention based on right ventricular pacer lead tracking. With these methods, enhanced interventional guidance for left ventricular lead placement is provided.

Depression, psychological distress, and quality of life in patients with cardioverter defibrillator with or without cardiac resynchronization therapy.

PubMed

Knackstedt, Christian; Arndt, Marlies; Mischke, Karl; Marx, Nikolaus; Nieman, Fred; Kunert, Hanns Jürgen; Schauerte, Patrick; Norra, Christine

2014-05-01

Congestive heart failure is frequent and leads to reduced exercise capacity, reduced quality of life (QoL), and depression in many patients. Cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICD) offer therapeutic options and may have an impact on QoL and depression. This study was performed to evaluate physical and mental health in patients undergoing ICD or combined CRT/ICD-implantation (CRT-D). Echocardiography, spiroergometry, and psychometric questionnaires [Beck Depression Inventory, General World Health Organization Five Well-being Index (WHO-5), Brief Symptom Inventory and 36-item Short Form (SF-36)] were obtained in 39 patients (ICD: 17, CRT-D: 22) at baseline and 6-month follow-up (FU) after device implantation. CRT-D patients had a higher NYHA class and broader left bundle branch block than ICD patients at baseline. At FU, ejection fraction (EF), peak oxygen uptake, and NYHA class improved significantly in CRT-D patients but remained unchanged in ICD patients. Patients with CRT-D implantation showed higher levels of depressive symptoms, psychological distress, and impairment in QoL at baseline and FU compared to ICD patients. These impairments remained mostly unchanged in all patients after 6 months. Overall, these findings imply that there is a need for careful assessment and treatment of psychological distress and depression in ICD and CRT-D patients in the course of device implantation as psychological burden seems to persist irrespective of physical improvement.

Sudden visual loss after cardiac resynchronization therapy device implantation.

PubMed

De Vitis, Luigi A; Marchese, Alessandro; Giuffrè, Chiara; Carnevali, Adriano; Querques, Lea; Tomasso, Livia; Baldin, Giovanni; Maestranzi, Gisella; Lattanzio, Rosangela; Querques, Giuseppe; Bandello, Francesco

2017-03-10

To report a case of sudden decrease in visual acuity possibly due to a cardiogenic embolism in a patient who underwent cardiac resynchronization therapy (CRT) device implantation. A 62-year-old man with severe left ventricular systolic dysfunction and a left bundle branch block was referred to our department because of a sudden decrease in visual acuity. Nine days earlier, he had undergone cardiac transapical implantation of a CRT device, which was followed, 2 days later, by an inflammatory reaction. The patient underwent several general and ophthalmologic examinations, including multimodal imaging. At presentation, right eye (RE) best-corrected visual acuity (BCVA) was counting fingers and RE pupil was hyporeactive. Fundus examination revealed white-centered hemorrhagic dots suggestive of Roth spots. Fluorescein angiography showed delay in vascular perfusion during early stage, late hyperfluorescence of the macula and optic disk, and peripheral perivascular leakage. The first visual field test showed complete loss of vision RE and a normal left eye. Due to suspected giant cell arteritis, temporal artery biopsy was performed. Thirty minutes after the procedure, an ischemic stroke with right hemisyndrome and aphasia occurred. The RE BCVA worsened to hands motion. Four months later, RE BCVA did not improve, despite improvement in fluorescein angiography inflammatory sign. We report a possible cardiogenic embolism secondary to undiagnosed infective endocarditis causing monocular visual loss after CRT device implantation. It remains unclear how the embolus caused severe functional damage without altering the retinal anatomical structure.

An intelligent classifier for prognosis of cardiac resynchronization therapy based on speckle-tracking echocardiograms.

PubMed

Chao, Pei-Kuang; Wang, Chun-Li; Chan, Hsiao-Lung

2012-03-01

Predicting response after cardiac resynchronization therapy (CRT) has been a challenge of cardiologists. About 30% of selected patients based on the standard selection criteria for CRT do not show response after receiving the treatment. This study is aimed to build an intelligent classifier to assist in identifying potential CRT responders by speckle-tracking radial strain based on echocardiograms. The echocardiograms analyzed were acquired before CRT from 26 patients who have received CRT. Sequential forward selection was performed on the parameters obtained by peak-strain timing and phase space reconstruction on speckle-tracking radial strain to find an optimal set of features for creating intelligent classifiers. Support vector machine (SVM) with a linear, quadratic, and polynominal kernel were tested to build classifiers to identify potential responders and non-responders for CRT by selected features. Based on random sub-sampling validation, the best classification performance is correct rate about 95% with 96-97% sensitivity and 93-94% specificity achieved by applying SVM with a quadratic kernel on a set of 3 parameters. The selected 3 parameters contain both indexes extracted by peak-strain timing and phase space reconstruction. An intelligent classifier with an averaged correct rate, sensitivity and specificity above 90% for assisting in identifying CRT responders is built by speckle-tracking radial strain. The classifier can be applied to provide objective suggestion for patient selection of CRT. Copyright © 2011 Elsevier B.V. All rights reserved.

Value of mechanical dyssynchrony as assessed by radionuclide ventriculography to predict the cardiac resynchronization therapy response.

PubMed

Tournoux, Francois; Chequer, Renata; Sroussi, Marjorie; Hyafil, Fabien; Algalarrondo, Vincent; Cohen-Solal, Alain; Bodson-Clermont, Paule; Le Guludec, Dominique; Rouzet, Francois

2016-11-01

To assess the value of mechanical dyssynchrony measured by equilibrium radionuclide angiography (ERNA) in predicting long-term outcome in cardiac resynchronization therapy (CRT) patients. We reviewed 146 ERNA studies performed in heart failure patients between 2001 and 2011 at our institution. Long-term follow-up focused on death from any cause or heart transplantation. Phase images were computed using the first harmonic Fourier transform. Intra-ventricular dyssynchrony was calculated as the delay between the earliest and most delayed 20% of the left ventricular (LV) (IntraV-20/80) and inter-ventricular dyssynchrony as the difference between LV- and right ventricular (RV)-mode phase angles (InterV). Eighty-three patients (57%) were implanted with a CRT device after ERNA. Median follow-up was 35 [21-50] months. Twenty-four events were observed during the first 41 months. Median baseline ERNA dyssynchrony values were 28 [3 to 46] degrees for intraV-20/80 and 9 [-6 to 24] degrees for interV. Comparing survival between CRT and non-CRT patients according to dyssynchrony status, log-rank tests showed no difference in survival in patients with no ERNA dyssynchrony (P = 0.34) while a significant difference was observed in ERNA patients with high level of mechanical dyssynchrony (P = 0.004). ERNA mechanical dyssynchrony could be of value in CRT patient selection. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Electrocardiographic parameters predict super-response in cardiac resynchronization therapy.

PubMed

Cvijić, Marta; Žižek, David; Antolič, Bor; Zupan, Igor

2015-01-01

Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients. However, determinants of response to CRT remain elusive. The aim of the study was to assess the value of ECG parameters to predict super-response in CRT patients. A 12-lead surface ECG was recorded at baseline and immediately after CRT-device implantation. Baseline ECG parameters (QRS duration, bundle branch morphology, axis, PR interval, QTc, intrinsicoid deflection) and post-implant paced QRS duration were analyzed; relative change in QRS duration was calculated. Decrease of left ventricular end-systolic volume ≥30% after 12 months was classified as super-response. In group of 101 patients, 32 (31.7%) were super-responders. There were no significant differences in baseline ECG parameters between super-responders and other patients. Post-implant QRS duration was shorter in super-responders (148 ± 22 ms vs. 162 ± 28 ms; P=0.010). Only in super-responders was significant QRS reduction observed after implantation. Relative QRS shortening was higher in super-responders (12.1% (6.8 to 22.2) vs. 1.7% (-11.9 to 11.8); P=0.005). In a multivariable analysis post-implant QRS duration and relative QRS shortening remained independent predictor of super-response. Absolute post-implant QRS duration and relative QRS shortening are the only ECG parameters associated with super-response in CRT. Further prospective studies on larger population are warranted to determine our findings. Copyright © 2015 Elsevier Inc. All rights reserved.

Interlead distance and left ventricular lead electrical delay predict reverse remodeling during cardiac resynchronization therapy.

PubMed

Merchant, Faisal M; Heist, E Kevin; Nandigam, K Veena; Mulligan, Lawrence J; Blendea, Dan; Riedl, Lindsay; McCarty, David; Orencole, Mary; Picard, Michael H; Ruskin, Jeremy N; Singh, Jagmeet P

2010-05-01

Both anatomic interlead separation and left ventricle lead electrical delay (LVLED) have been associated with outcomes following cardiac resynchronization therapy (CRT). However, the relationship between interlead distance and electrical delay in predicting CRT outcomes has not been defined. We studied 61 consecutive patients undergoing CRT for standard clinical indications. All patients underwent intraprocedural measurement of LVLED. Interlead distances in the horizontal (HD), vertical (VD), and direct (DD) dimensions were measured from postprocedure chest radiographs (CXR). Remodeling indices [percent change in left ventricle (LV) ejection fraction, end-diastolic, end-systolic dimensions] were assessed by transthoracic echocardiogram. There was a positive correlation between corrected LVLED and HD on lateral CXR (r = 0.361, P = 0.004) and a negative correlation between LVLED and VD on posteroanterior (PA) CXR (r =-0.281, P = 0.028). To account for this inverse relationship, we developed a composite anatomic distance (defined as: lateral HD-PA VD), which correlated most closely with LVLED (r = 0.404, P = 0.001). Follow-up was available for 48 patients. At a mean of 4.1 +/- 3.2 months, patients with optimal values for both corrected LVLED (>or=75%) and composite anatomic distance (>or=15 cm) demonstrated greater reverse LV remodeling than patients with either one or neither of these optimized values. We identified a significant correlation between LV-right ventricular interlead distance and LVLED; additionally, both parameters act synergistically in predicting LV anatomic reverse remodeling. Efforts to optimize both interlead distance and electrical delay may improve CRT outcomes.

Usefulness and limitation of dobutamine stress echocardiography to predict acute response to cardiac resynchronization therapy.

PubMed

Sénéchal, Mario; Lancellotti, Patrizio; Garceau, Patrick; Champagne, Jean; Dubois, Michelle; Magne, Julien; Blier, Louis; Molin, Frank; Philippon, François; Dumesnil, Jean G; Pierard, Luc; O'Hara, Gilles

2010-01-01

It has been hypothesized that a long-term response to cardiac resynchronization therapy (CRT) could correlate with myocardial viability in patients with left ventricular (LV) dysfunction. Contractile reserve and viability in the region of the pacing lead have not been investigated in regard to acute response after CRT. Fifty-one consecutive patients with advanced heart failure, LV ejection fraction 120 ms, and intraventricular asynchronism >or= 50 ms were prospectively included. The week before CRT implantation, the presence of viability was evaluated using dobutamine stress echocardiography. Acute responders were defined as a >or=15% increase in LV stroke volume. The average of viable segments was 5.8 +/- 1.9 in responders and 3.9 +/- 3 in nonresponders (P = 0.03). Viability in the region of the pacing lead had an excellent sensitivity (96%), but a low specificity (56%) to predict acute response to CRT. Mitral regurgitation (MR) was reduced in 21 patients (84%) with acute response. The presence of MR was a poor predictor of response (sensibility 93% and specificity 17%). However, combining the presence of MR and viability in the region of the pacing lead yields a sensibility (89%) and a specificity (70%) to predict acute response to CRT. Myocardial viability is an important factor influencing acute hemodynamic response to CRT. In acute responders, significant MR reduction is frequent. The combined presence of MR and viability in the region of the pacing lead predicts acute response to CRT with the best accuracy.

Clinical presentation at first heart failure hospitalization does not predict recurrent heart failure admission.

PubMed

Kosztin, Annamaria; Costa, Jason; Moss, Arthur J; Biton, Yitschak; Nagy, Vivien Klaudia; Solomon, Scott D; Geller, Laszlo; McNitt, Scott; Polonsky, Bronislava; Merkely, Bela; Kutyifa, Valentina

2017-11-01

There are limited data on whether clinical presentation at first heart failure (HF) hospitalization predicts recurrent HF events. We aimed to assess predictors of recurrent HF hospitalizations in mild HF patients with an implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Data on HF hospitalizations were prospectively collected for patients enrolled in MADIT-CRT. Predictors of recurrent HF hospitalization (HF2) after the first HF hospitalization were assessed using Cox proportional hazards regression models including baseline covariates and clinical presentation or management at first HF hospitalization. There were 193 patients with first HF hospitalization, and 156 patients with recurrent HF events. Recurrent HF rate after the first HF hospitalization was 43% at 1 year, 52% at 2 years, and 55% at 2.5 years. Clinical signs and symptoms, medical treatment, or clinical management of HF at first HF admission was not predictive for HF2. Baseline covariates predicting recurrent HF hospitalization included prior HF hospitalization (HR = 1.59, 95% CI: 1.15-2.20, P = 0.005), digitalis therapy (HR = 1.58, 95% CI: 1.13-2.20, P = 0.008), and left ventricular end-diastolic volume >240 mL (HR = 1.62, 95% CI: 1.17-2.25, P = 0.004). Recurrent HF events are frequent following the first HF hospitalization in patients with implanted implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Neither clinical presentation nor clinical management during first HF admission was predictive of recurrent HF. Prior HF hospitalization, digitalis therapy, and left ventricular end-diastolic volume at enrolment predicted recurrent HF hospitalization, and these covariates could be used as surrogate markers for identifying a high-risk cohort. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Cardiac resynchronization therapy with His bundle pacing as a method of treatment of chronic heart failure in patients with permanent atrial fibrillation and left bundle branch block.

PubMed

Boczar, Krzysztof; Sławuta, Agnieszka; Ząbek, Andrzej; Dębski, Maciej; Gajek, Jacek; Lelakowski, Jacek; Małecka, Barbara

CRT is a therapeutic option for patients with heart failure, sinus rhythm, prolonged QRS complex duration and reduced ejection fraction. We present a case of 71-year-old woman with dilated cardiomyopathy, NYHA functional class III and AF. We implanted CRT combined with direct His-bundle pacing. The indication for such a therapy was a left bundle branch block with a QRS complex of 178ms and a left ventricular EF of 15%, left ventricular end-diastolic diameter (LVEDD) of 75mm. After 8months of follow-up the LVEDD was 60mm with EF 35-40%. Copyright © 2017. Published by Elsevier Inc.

Imaging the Propagation of the Electromechanical Wave in Heart Failure Patients with Cardiac Resynchronization Therapy.

PubMed

Bunting, Ethan; Lambrakos, Litsa; Kemper, Paul; Whang, William; Garan, Hasan; Konofagou, Elisa

2017-01-01

Current electrocardiographic and echocardiographic measurements in heart failure (HF) do not take into account the complex interplay between electrical activation and local wall motion. The utilization of novel technologies to better characterize cardiac electromechanical behavior may lead to improved response rates with cardiac resynchronization therapy (CRT). Electromechanical wave imaging (EWI) is a noninvasive ultrasound-based technique that uses the transient deformations of the myocardium to track the intrinsic EW that precedes myocardial contraction. In this paper, we investigate the performance and reproducibility of EWI in the assessment of HF patients and CRT. EWI acquisitions were obtained in five healthy controls and 16 HF patients with and without CRT pacing. Responders (n = 8) and nonresponders (n = 8) to CRT were identified retrospectively on the basis of left ventricular (LV) reverse remodeling. Electromechanical activation maps were obtained in all patients and used to compute a quantitative parameter describing the mean LV lateral wall activation time (LWAT). Mean LWAT was increased by 52.1 ms in HF patients in native rhythm compared to controls (P < 0.01). For all HF patients, CRT pacing initiated a different electromechanical activation sequence. Responders exhibited a 56.4-ms ± 28.9-ms reduction in LWAT with CRT pacing (P < 0.01), while nonresponders showed no significant change. In this initial feasibility study, EWI was capable of characterizing local cardiac electromechanical behavior as it pertains to HF and CRT response. Activation sequences obtained with EWI allow for quantification of LV lateral wall electromechanical activation, thus providing a novel method for CRT assessment. © 2016 Wiley Periodicals, Inc.

Metabolomic does not predict response to cardiac resynchronization therapy in patients with heart failure.

PubMed

Padeletti, Luigi; Modesti, Pietro A; Cartei, Stella; Checchi, Luca; Ricciardi, Giuseppe; Pieragnolia, Paolo; Sacchi, Stefania; Padeletti, Margherita; Alterini, Brunetto; Pantaleo, Pietro; Hu, Xiaoyu; Tenori, Leonardo; Luchinat, Claudio

2014-04-01

Metabolomic, a systematic study of metabolites, may be a useful tool in understanding the pathological processes that underlie the occurrence and progression of a disease. We hypothesized that metabolomic would be helpful in assessing a specific pattern in heart failure patients, also according to the underlining causes and in defining, prior to device implantation, the responder and nonresponder patient to cardiac resynchronization therapy (CRT). In this prospective study, blood and urine samples were collected from 32 heart failure patients who underwent CRT. Clinical, electrocardiography and echocardiographic evaluation was performed in each patient before CRT and after 6 months of follow-up. Thirty-nine age and sex-matched healthy individuals were chosen as control group. For each sample, 1H-NMR spectra, Nuclear Overhauser Enhancement Spectroscopy, Carr-Purcell-Meiboom-Gill and diffusion edited spectra were measured. A different metabolomic fingerprint was demonstrated in heart failure patients compared to healthy controls with high accuracy level. Metabolomics fingerprint was similar between patients with ischemic and nonischemic dilated cardiomyopathy. At 6-month follow-up, metabolomic fingerprint was different from baseline. At follow-up, heart failure patients’ metabolomic fingerprint remained significantly different from that of healthy controls, and accuracy of cause discrimination remained low. Responders and nonresponders had a similar metabolic fingerprint at baseline and after 6 months of CRT. It is possible to identify a metabolomic fingerprint characterizing heart failure patients candidate to CRT, it is independent of the different causes of the disease and it is not predictive of the response to CRT.

Empiric versus imaging guided left ventricular lead placement in cardiac resynchronization therapy (ImagingCRT): study protocol for a randomized controlled trial.

PubMed

Sommer, Anders; Kronborg, Mads Brix; Poulsen, Steen Hvitfeldt; Böttcher, Morten; Nørgaard, Bjarne Linde; Bouchelouche, Kirsten; Mortensen, Peter Thomas; Gerdes, Christian; Nielsen, Jens Cosedis

2013-04-26

Cardiac resynchronization therapy (CRT) is an established treatment in heart failure patients. However, a large proportion of patients remain nonresponsive to this pacing strategy. Left ventricular (LV) lead position is one of the main determinants of response to CRT. This study aims to clarify whether multimodality imaging guided LV lead placement improves clinical outcome after CRT. The ImagingCRT study is a prospective, randomized, patient- and assessor-blinded, two-armed trial. The study is designed to investigate the effect of imaging guided left ventricular lead positioning on a clinical composite primary endpoint comprising all-cause mortality, hospitalization for heart failure, or unchanged or worsened functional capacity (no improvement in New York Heart Association class and <10% improvement in six-minute-walk test). Imaging guided LV lead positioning is targeted to the latest activated non-scarred myocardial region by speckle tracking echocardiography, single-photon emission computed tomography, and cardiac computed tomography. Secondary endpoints include changes in LV dimensions, ejection fraction and dyssynchrony. A total of 192 patients are included in the study. Despite tremendous advances in knowledge with CRT, the proportion of patients not responding to this treatment has remained stable since the introduction of CRT. ImagingCRT is a prospective, randomized study assessing the clinical and echocardiographic effect of multimodality imaging guided LV lead placement in CRT. The results are expected to make an important contribution in the pursuit of increasing response rate to CRT. Clinicaltrials.gov identifier NCT01323686. The trial was registered March 25, 2011 and the first study subject was randomized April 11, 2011.

Influence of pacing site characteristics on response to cardiac resynchronization therapy.

PubMed

Wong, Jorge A; Yee, Raymond; Stirrat, John; Scholl, David; Krahn, Andrew D; Gula, Lorne J; Skanes, Allan C; Leong-Sit, Peter; Klein, George J; McCarty, David; Fine, Nowell; Goela, Aashish; Islam, Ali; Thompson, Terry; Drangova, Maria; White, James A

2013-07-01

Transmural scar occupying left ventricular (LV) pacing regions has been associated with reduced response to cardiac resynchronization therapy (CRT). However, spatial influences of lead tip delivery relative to scar at both pacing sites remain poorly explored. This study evaluated scar distribution relative to LV and right ventricular (RV) lead tip placement through coregistration of late gadolinium enhancement MRI and cardiac computed tomographic (CT) findings. Influences on CRT response were assessed by serial echocardiography. Sixty patients receiving CRT underwent preimplant late gadolinium enhancement MRI, postimplant cardiac CT, and serial echocardiography. Blinded segmental evaluations of mechanical delay, percentage scar burden, and lead tip location were performed. Response to CRT was defined as a reduction in LV end-systolic volume ≥15% at 6 months. The mean age and LV ejection fraction were 64±9 years and 25±7%, respectively. Mean scar volume was higher among CRT nonresponders for both the LV (23±23% versus 8±14% [P=0.01]) and RV pacing regions (40±32% versus 24±30% [P=0.04]). Significant pacing region scar was identified in 13% of LV pacing regions and 37% of RV pacing regions. Absence of scar in both regions was associated with an 81% response rate compared with 55%, 25%, and 0%, respectively, when the RV, LV, or both pacing regions contained scar. LV pacing region dyssynchrony was not predictive of response. Myocardial scar occupying the LV pacing region is associated with nonresponse to CRT. Scar occupying the RV pacing region is encountered at higher frequency and seems to provide a more intermediate influence on CRT response.

Characteristics of Responders to Cardiac Resynchronization Therapy: The Impact of Echocardiographic Left Ventricular Volume

PubMed Central

Park, Mi Young; Altman, Robert K.; Orencole, Mary; Kumar, Prabhat; Parks, Kimberly A.; Heist, Kevin E.; Singh, Jagmeet P.; Picard, Michael H.

2012-01-01

Summary Background One third of patients who receive cardiac resynchronization therapy (CRT) are classified as nonresponders. Characteristics of responders to CRT have been studied in multiple clinical trials. Hypothesis We aimed to examine characteristics of CRT responders in a routine clinical practice. Method One hundred and twenty five patients were examined retrospectively from a multidisciplinary CRT clinic program. Echocardiographic CRT response was defined as a decrease in left ventricular (LV) end systolic volume (ESV) of ≥ 15% and/or absolute increase of 5% in LV ejection fraction (EF) at 6 month visit. Results There were 81 responders and 44 nonresponders. By univariate analyses, female gender, nonischemic cardiomyopathy etiology, baseline QRS duration, the presence of left bundle branch block (LBBB) and left ventricular end-diastolic volume (LVEDV) index predicted CRT response. However, multivariate analysis demonstrated only QRS duration, LBBB and LVEDV index were independent predictors (QRS width: Odd ratio [OR] 1.027, 95% CI 1.004 – 1.050, p = 0.023; LBBB: OR 3.568, 95% CI 1.284 – 9.910, p=0.015; LV EDV index: OR 0.970, 95% CI 0.953 – 0.987, p= 0.001). While female gender and nonischemic etiology were associated with an improved CRT response on univariate analyses, after adjusting for LV volumes, they were not independent predictors. Conclusion QRS width, LBBB and LVEDV index are independent predictors for echocardiographic CRT response. Previously reported differences in CRT response for gender and cardiomyopathy etiology are associated with differences in baseline LV volumes in our clinical practice. PMID:22886700

Universal algorithm for diagnosis of biventricular capture in patients with cardiac resynchronization therapy.

PubMed

Jastrzebski, Marek; Kukla, Piotr; Fijorek, Kamil; Czarnecka, Danuta

2014-08-01

An accurate and universal method for diagnosis of biventricular (BiV) capture using a standard 12-lead electrocardiogram (ECG) would be useful for assessment of cardiac resynchronization therapy (CRT) patients. Our objective was to develop and validate such an ECG method for BiV capture diagnosis that would be independent of pacing lead positions-a major confounder that significantly influences the morphologies of paced QRS complexes. On the basis of an evaluation of 789 ECGs of 443 patients with heart failure and various right ventricular (RV) and left ventricular (LV) lead positions, the following algorithm was constructed and validated. BiV capture was diagnosed if the QRS in lead I was predominantly negative and either V1 QRS was predominantly positive or V6 QRS was of negative onset and predominantly negative (step 1), or if QRS complex duration was <160 ms (step 2). All other ECGs were classified as loss of LV capture. The algorithm showed good accuracy (93%), sensitivity (97%), and specificity (90%) for detection of loss of LV capture. The performance of the algorithm did not differ among apical, midseptal, and outflow tract RV lead positions and various LV lead positions. LV capture leaves diagnostic hallmarks in the fused BiV QRS related to different vectors of depolarization and more rapid depolarization of the ventricles. An accurate two-step ECG algorithm for BiV capture diagnosis was developed and validated. This algorithm is universally applicable to all CRT patients, regardless of the positions of the pacing leads. ©2014 Wiley Periodicals, Inc.

Time Course of Electrical Remodeling of Native Conduction After Cardiac Resynchronization Therapy and Its Impact on Clinical Outcome.

PubMed

Cvijić, Marta; Žižek, David; Antolič, Bor; Zupan, Igor

2017-03-01

Cardiac resynchronization therapy (CRT) induces structural and electrical remodeling (ER) in heart failure (HF) patients. Our aim was to assess time course of ER of native conduction and mechanical remodeling after CRT and impact of CRT-induced ER on clinical outcome. We prospectively included 62 patients (aged 66 ± 10 years). Echocardiographic and ECG parameters were measured at baseline and 1, 3, 6, 9, and 12 months after implantation. Biventricular pacing was temporary inhibited during each follow-up to record intrinsic ECG. ER was defined as a decrease in native pre-implantation QRS duration ≥10 ms. During follow-up HF hospitalizations, cardiovascular death and transplantation (combined end point) were recorded. There were significant changes in intrinsic ECG parameters during follow-up; the narrowing of QRS duration was already observed after 1 month (median 185 ms [interquartile range (IQR) 175-194] vs 180 ms [170-194]; P < .001). Left ventricular (LV) volumes decreased only after 3 months of CRT (median end-systolic volume 167 mL [137-206] vs 140 mL [112-196]; P < .001). Only patients with ER (n = 24) exhibited significant mechanical remodeling and showed superior survival free from the combined end point compared with patients without ER (log-rank P = .028). Electrical remodeling of native conduction precedes detectable left ventricular structural changes after CRT. ER of native conduction is associated with better clinical outcome following CRT. Copyright © 2016 Elsevier Inc. All rights reserved.

Left Ventricular Lead Placement Targeted at the Latest Activated Site Guided by Electrophysiological Mapping in Coronary Sinus Branches Improves Response to Cardiac Resynchronization Therapy.

PubMed

Liang, Yanchun; Yu, Haibo; Zhou, Weiwei; Xu, Guoqing; Sun, Y I; Liu, Rong; Wang, Zulu; Han, Yaling

2015-12-01

Electrophysiological mapping (EPM) in coronary sinus (CS) branches is feasible for guiding LV lead placement to the optimal, latest activated site at cardiac resynchronization therapy (CRT) procedures. However, whether this procedure optimizes the response to CRT has not been demonstrated. This study was to evaluate effects of targeting LV lead at the latest activated site guided by EPM during CRT. Seventy-six consecutive patients with advanced heart failure who were referred for CRT were divided into mapping (MG) and control groups (CG). In MG, the LV lead, also used as a mapping bipolar electrode, was placed at the latest activated site determined by EPM in CS branches. In CG, conventional CRT procedure was performed. Patients were followed for 6 months after CRT. Baseline characteristics were comparable between the 2 groups. In MG (n = 29), EPM was successfully performed in 85 of 91 CS branches during CRT. A LV lead was successfully placed at the latest activated site guided by EPM in 27 (93.1%) patients. Compared with CG (n = 47), MG had a significantly higher rate (86.2% vs. 63.8%, P = 0.039) of response (>15% reduction in LV end-systolic volume) to CRT, a higher percentage of patients with clinical improvement of ≥2 NYHA functional classes (72.4% vs. 44.7%, P = 0.032), and a shorter QRS duration (P = 0.004). LV lead placed at the latest activated site guided by EPM resulted in a significantly greater CRT response, and a shorter QRS duration. © 2015 Wiley Periodicals, Inc.

Bridging the gap between heart failure and the device clinic.

PubMed

Rickard, John; Wilkoff, Bruce L

2017-08-01

While cardiac resynchronization therapy (CRT) is a mainstay in the management of selected patients with chronic systolic dysfunction, many patients are noted to experience less than expected or no benefit at all from the therapy. Multidisciplinary care has been shown to provide benefit in follow up for patients receiving CRT devices. Areas covered: This review will focus on the apparent reasons behind less than optimal outcomes following CRT as well as multidisciplinary approaches to treating patients with CRT devices. The literature review focused mainly on the data behind multidisciplinary care of CRT patients. Expert commentary: A multidisciplinary approach incorporating input from various cardiology backgrounds is an important strategy in ensuring optimal outcomes in patients receiving CRT devices. Breaking down the 'silo' effect amongst cardiac subspecialties is vital in achieving high level multidisciplinary care.

Towards an interactive electromechanical model of the heart

PubMed Central

Talbot, Hugo; Marchesseau, Stéphanie; Duriez, Christian; Sermesant, Maxime; Cotin, Stéphane; Delingette, Hervé

2013-01-01

In this work, we develop an interactive framework for rehearsal of and training in cardiac catheter ablation, and for planning cardiac resynchronization therapy. To this end, an interactive and real-time electrophysiology model of the heart is developed to fit patient-specific data. The proposed interactive framework relies on two main contributions. First, an efficient implementation of cardiac electrophysiology is proposed, using the latest graphics processing unit computing techniques. Second, a mechanical simulation is then coupled to the electrophysiological signals to produce realistic motion of the heart. We demonstrate that pathological mechanical and electrophysiological behaviour can be simulated. PMID:24427533

Novel Biomarkers in Cardiac Resynchronization Therapy: Hepatocyte Growth Factor Is an Independent Predictor of Clinical Outcome.

PubMed

Perge, Péter; Boros, András Mihály; Szilágyi, Szabolcs; Zima, Endre; Molnár, Levente; Gellér, László; Prohászka, Zoltán; Merkely, Béla; Széplaki, Gábor

2018-03-23

Cardiac resynchronization therapy (CRT) is beneficial for selected heart failure (HF) patients, although nonresponse to therapy is still prevalent. We investigated a set of novel biomarkers associated with various pathophysiological pathways of HF. Our purpose was to assess their ability to predict clinical outcomes after CRT. We studied 136 chronic HF patients undergoing CRT. We measured the plasma levels of fractalkine, pentraxin-3, hepatocyte growth factor (HGF), carbohydrate antigen-125, and matrix metalloproteinase-9 before and 6 months after CRT. The primary endpoint of the study was 5-year all-cause mortality, and we considered the absence of 6-month reverse remodelling (defined as at least a 15% decrease in end-systolic volume) as a secondary endpoint. Fifty-eight patients died during the 5-year follow-up period and 66 patients were categorized as nonresponders. In multivariable models, only an increased HGF was an independent predictor of both mortality (HR, 1.35; 95%CI, 1.11-1.64; P=.003; per 1 standard deviation increase) and the absence of reverse remodelling (OR, 1.83; 95%CI, 1.10-3.04; P=.01; per 1 standard deviation increase). Applying HGF to the basic multivariable model of both mortality (net reclassification improvement=0.69; 95%CI, 0.39-0.99; P<.0001; integrated discrimination improvement=0.06; 95%CI, 0.02-0.11) and reverse remodelling (net reclassification improvement=0.39; 95%CI, 0.07-0.71; P=.01; integrated discrimination improvement=0.03; 95%CI, 0.00-0.06) resulted in a statistically significant reclassification and discrimination improvement. Of the investigated biomarkers, only HGF predicted clinical outcomes following CRT independently of other parameters. Reclassification analyses showed that HGF measurements could be useful in refining patient selection. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Prediction of clinical outcome in patients treated with cardiac resynchronization therapy - the role of NT-ProBNP and a combined response score.

PubMed

Bakos, Z; Chatterjee, N C; Reitan, C; Singh, J P; Borgquist, R

2018-04-24

Cardiac resynchronization therapy (CRT) is an established therapy for appropriately selected patients with heart failure. Response to CRT has been heterogeneously defined using both clinical and echocardiographic measures, with poor correlation between the two. The study cohort was comprised of 202 CRT-treated patients and CRT response was defined at 6 months post-implant. Echocardiographic response (E+) was defined as a reduction in LVESV ≥ 15%, clinical response as an improvement of ≥ 1 NYHA class (C+), and biomarker response as a ≥ 25% reduction in NT-proBNP(B+). The association of response measures (E+, B+, C+; response score range 0-3) and clinical endpoints at 3 years was assessed in landmarked Cox models. Echo and clinical responders demonstrated greater declines in NT-proBNP than non-responders (median [E+/B+]: -52%, [E+]: -27%, [C+]: -39% and [E-/C-]: -13%; p = 0.01 for trend). Biomarker (HR 0.43 [95% CI: 0.22-0.86], p = 0.02) and clinical (HR 0.40 [0.23-0.70] p = 0.001) response were associated with a significantly reduced risk of the primary endpoint. When integrating each response measure into a composite score, each 1 point increase was associated with a 31% decreased risk for a composite endpoint of mortality, LVAD, transplant and HF hospitalization (HR 0.69 [95% CI: 0.50-0.96], p = 0.03), and a 52% decreased risk of all-cause mortality (HR 0.48 [95% CI: 0.26-0.89], p = 0.02). Serial changes in NT-proBNP are associated with clinical outcomes following CRT implant. Integration of biomarker, clinical, and echocardiographic response may discriminate CRT responders versus non-responders in a clinically meaningful way, and with higher accuracy. The cohort was combined from study NCT01949246 and the study based on local review board approval 2011/550 in Lund, Sweden.

A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

PubMed

Chen, Yu-Yang; Shu, Xiao-Rong; Su, Zi-Zhuo; Lin, Rong-Jie; Zhang, Hai-Feng; Yuan, Wo-Liang; Wang, Jing-Feng; Xie, Shuang-Lun

2017-12-12

Thyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 ≥ 3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.

Cardiac-resynchronization therapy for mild-to-moderate heart failure.

PubMed

Tang, Anthony S L; Wells, George A; Talajic, Mario; Arnold, Malcolm O; Sheldon, Robert; Connolly, Stuart; Hohnloser, Stefan H; Nichol, Graham; Birnie, David H; Sapp, John L; Yee, Raymond; Healey, Jeffrey S; Rouleau, Jean L

2010-12-16

Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter-defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD-CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD-CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD-CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. (Funded by the Canadian Institutes of Health Research and Medtronic of Canada; ClinicalTrials.gov number, NCT00251251.).

Impact of Current Versus Previous Cardiac Resynchronization Therapy Guidelines on the Proportion of Patients With Heart Failure Eligible for Therapy.

PubMed

Lyons, Kristin J; Ezekowitz, Justin A; Liang, Li; Heidenreich, Paul A; Yancy, Clyde W; DeVore, Adam D; Hernandez, Adrian F; Fonarow, Gregg C

2017-05-01

This study sought to ascertain the impact of heart failure (HF) guideline change on the number of patients eligible to undergo cardiac resynchronization therapy (CRT). The 2013 HF guideline of the American College of Cardiology Foundation and American Heart Association (ACCF/AHA) narrowed the recommendations for CRT. The impact of this guideline change on the number of eligible patients for CRT has not been described. Using data from Get With The Guidelines-Heart Failure between 2012 and 2015, this study evaluated the proportion of hospitalized patients with HF who were eligible for CRT on the basis of historical and current guideline recommendations. The authors identified 25,102 hospitalizations for HF that included patients with a left ventricular ejection fraction (LVEF) ≤35% from 283 hospitals. Patients with a medical, system-related, or patient-related reason for not undergoing CRT were excluded. Overall, 49.1% (n = 12,336) of patients with HF, an LVEF ≤35%, and no documented contraindication were eligible for CRT on the basis of historical guidelines, and 33.1% (n = 8,299) of patients were eligible for CRT on the basis of current guidelines, a 16.1% absolute reduction in eligibility (p < 0.0001). Patients eligible for CRT on the basis of current guidelines were more likely to have CRT with an implantable cardioverter-defibrillator or CRT with pacing only placed or prescribed at discharge (57.8% vs. 54.9%; p < 0.0001) compared with patients eligible for CRT on the basis of historical guidelines. In this population of patients with HF, an LVEF ≤35%, and no documented contraindication for CRT, the current ACCF/AHA HF guidelines reduce the proportion of patients eligible for CRT by approximately 15%. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cardiac resynchronization therapy (CRT) in heart failure--a model to assess the economic value of this new medical technology.

PubMed

Banz, Kurt

2005-01-01

This article describes the framework of a comprehensive European model developed to assess clinical and economic outcomes of cardiac resynchronization therapy (CRT) versus optimal pharmacological therapy (OPT) alone in patients with heart failure. The model structure is based on information obtained from the literature, expert opinion, and a European CRT Steering Committee. The decision-analysis tool allows a consideration of direct medical and indirect costs, and computes outcomes for distinctive periods of time up to 5 years. Qualitative data can also be entered for cost-utility analysis. Model input data for a preliminary economic appraisal of the economic value of CRT in Germany were obtained from clinical trials, experts, health statistics, and medical tariff lists. The model offers comprehensive analysis capabilities and high flexibility so that it can easily be adapted to any European country or special setting. The illustrative analysis for Germany indicates that CRT is a cost-effective intervention. Although CRT is associated with average direct medical net costs of Euro 5880 per patient, this finding means that 22% of its upfront implantation cost is recouped already within 1 year because of significantly decreased hospitalizations. With 36,600 Euros the incremental cost per quality-adjusted life-year (QALY) gained is below the euro equivalent (41,300 Euros, 1 Euro = US1.21 dollars) of the commonly used threshold level of US50,000 dollars considered to represent cost-effectiveness. The sensitivity analysis showed these preliminary results to be fairly robust towards changes in key assumptions. The European CRT model is an important tool to assess the economic value of CRT in patients with moderate to severe heart failure. In the light of the planned introduction of Diagnosis Related Group (DRG) based reimbursement in various European countries, the economic data generated by the model can play an important role in the decision-making process.

Quantification of ventricular resynchronization reserve by radionuclide phase analysis in heart failure patients: a prospective long-term study.

PubMed

Dauphin, Raphael; Nonin, Emilie; Bontemps, Laurence; Vincent, Madeleine; Pinel, Alain; Bonijoly, Serge; Barborier, Denis; Ribier, Arnaud; Fernandes, Christine Mestre; Bert-Marcaz, Patrick; Itti, Roland; Chevalier, Philippe

2011-03-01

Phase analysis, developed to assess dyssynchrony from ECG-gated radionuclide ventriculography, has shown promising results. We hypothesized that quantifying the cardiac resynchronization reserve, that is, the extent of response to cardiac resynchronization therapy (CRT), by radionuclide imaging could potentially identify patients who are best suited for CRT. Seventy-four patients ages 64.8±10.1 years were prospectively studied from July 2004 to July 2006, of whom 62.2% and 37.8%, respectively, were in New York Heart Association class 3 and 4. Mean QRS width was 173±25 ms. ECG-gated radionuclide ventriculography to quantify interventricular and intraventricular dyssynchrony was performed at baseline with and without CRT and at the 3-month follow-up visit. Amino-terminal-pro-brain natriuretic peptide (NT-pro-BNP) levels were also determined at baseline and at 3 months. During a mean follow-up of 10.1±7.6 months, there were 37 (50%) clinical events that defined the nonresponder group, including cardiac death or readmission for worsening heart failure. In multivariate Cox model analysis, higher NT-pro-BNP blood levels were associated with a significant increase in the risk for event (hazard ratio=1.085 for a 100 pg/L increase in NT-pro-BNP; 95% confidence interval, 1.014 to 1.161). Each 10° elevation in intraventricular dyssynchrony was associated with a decrease in the risk of events (hazard ratio=0.456, 95% confidence interval, 0.304 to 0.683). Receiver operating characteristic curve analysis demonstrated that an interventricular dyssynchrony cutoff value of 25.5° for intraventricular synchrony yielded 91.4% sensitivity and 84.4% specificity for predicting a good response to CRT. The quantification of interventricular dyssynchrony with radionuclide phase analysis suggests that early postimplantation interventricular dyssynchrony may provide identification of CRT responders.

Quantitative Analysis of Electro-Anatomical Maps: Application to an Experimental Model of Left Bundle Branch Block/Cardiac Resynchronization Therapy

PubMed Central

Duchateau, Nicolas; Kostantyn Butakov, Constantine Butakoff; Andreu, David; Fernández-Armenta, Juan; Bijnens, Bart; Berruezo, Antonio; Sitges, Marta; Camara, Oscar

2017-01-01

Electro-anatomical maps (EAMs) are commonly acquired in clinical routine for guiding ablation therapies. They provide voltage and activation time information on a 3-D anatomical mesh representation, making them useful for analyzing the electrical activation patterns in specific pathologies. However, the variability between the different acquisitions and anatomies hampers the comparison between different maps. This paper presents two contributions for the analysis of electrical patterns in EAM data from biventricular surfaces of cardiac chambers. The first contribution is an integrated automatic 2-D disk representation (2-D bull’s eye plot) of the left ventricle (LV) and right ventricle (RV) obtained with a quasi-conformal mapping from the 3-D EAM meshes, that allows an analysis of cardiac resynchronization therapy (CRT) lead positioning, interpretation of global (total activation time), and local indices (local activation time (LAT), surrogates of conduction velocity, inter-ventricular, and transmural delays) that characterize changes in the electrical activation pattern. The second contribution is a set of indices derived from the electrical activation: speed maps, computed from LAT values, to study the electrical wave propagation, and histograms of isochrones to analyze regional electrical heterogeneities in the ventricles. We have applied the proposed methods to look for the underlying physiological mechanisms of left bundle branch block (LBBB) and CRT, with the goal of optimizing the therapy by improving CRT response. To better illustrate the benefits of the proposed tools, we created a set of synthetically generated and fully controlled activation patterns, where the proposed representation and indices were validated. Then, the proposed analysis tools are used to analyze EAM data from an experimental swine model of induced LBBB with an implanted CRT device. We have analyzed and compared the electrical activation patterns at baseline, LBBB, and CRT stages in four animals: two without any structural disease and two with an induced infarction. By relating the CRT lead location with electrical dyssynchrony, we evaluated current hypotheses about lead placement in CRT and showed that optimal pacing sites should target the RV lead close to the apex and the LV one distant from it. PMID:29164019

Effect of PR interval prolongation on long-term outcomes in patients with left bundle branch block vs non-left bundle branch block morphologies undergoing cardiac resynchronization therapy.

PubMed

Rickard, John; Karim, Mohammad; Baranowski, Bryan; Cantillon, Daniel; Spragg, David; Tang, W H Wilson; Niebauer, Mark; Grimm, Richard; Trulock, Kevin; Wilkoff, Bruce; Varma, Niraj

2017-10-01

Although the influence of QRS duration (QRSd) and/or bundle branch block morphology on outcomes of cardiac resynchronization therapy (CRT) have been well studied, the effect of PR interval remains uncertain. The purpose of this study was to evaluate the impact of PR prolongation (PRp) before CRT on long-term outcomes, specifically taking into account bundle branch block morphology and QRSd. We extracted clinical data on consecutive patients undergoing CRT. Multivariate models were constructed to analyze the effect of PRp (≥200 ms) on the combined endpoint of death, heart transplant, or left ventricular assist device. Kaplan-Meier curves were constructed stratifying patients based on bundle branch block and QRSd (dichotomized by 150 ms). Of the 472 patients who met inclusion criteria, 197 (41.7%) had PR interval ≥200 ms. During follow-up (mean 5.1 ± 2.6 years) there were 214 endpoints, of which 109 (23.1%) occurred in patients with PRp. In multivariate analysis, PRp was independently associated with worsened outcomes (hazard ratio 1.34, 95% confidence interval 1.01-1.77, P = .04). When stratified by bundle branch block morphology, PRp was significantly associated with worsened outcomes (log-rank P <.001) in patients with LBBB but not in those with non-LBBB (log-rank P = .55). Among patients with LBBB, stratified by QRSd, patients without PRp had improved outcomes compared to those with PRp independent of QRSd (log-rank P <.001). PRp is an independent predictor of impaired long-term outcome after CRT among patients with LBBB but not in non-LBBB patients. Notably, among LBBB patients, PRp is a more important predictor than QRSd in assessing long-term outcomes. Copyright © 2017. Published by Elsevier Inc.

Imaging the propagation of the electromechanical wave in heart failure patients with cardiac resynchronization therapy

PubMed Central

Bunting, Ethan; Lambrakos, Litsa; Kemper, Paul; Whang, William; Garan, Hasan; Konofagou, Elisa

2016-01-01

Background Current electrocardiographic and echocardiographic measurements in heart failure (HF) do not take into account the complex interplay between electrical activation and local wall motion. The utilization of novel technologies to better characterize cardiac electromechanical behavior may lead to improved response rates with cardiac resynchronization therapy (CRT). Electromechanical Wave Imaging (EWI) is a non-invasive ultrasound-based technique that uses the transient deformations of the myocardium to track the intrinsic electromechanical wave that precedes myocardial contraction. In this paper, we investigate the performance and reproducibility of EWI in the assessment of HF patients and CRT. Methods EWI acquisitions were obtained in 5 healthy controls and 16 HF patients with and without CRT pacing. Responders (n=8) and non-responders (n=8) to CRT were identified retrospectively on the basis of left ventricular (LV) reverse remodeling. Electromechanical activation maps were obtained in all patients and used to compute a quantitative parameter describing the mean activation time of the LV lateral wall (LWAT). Results Mean LWAT was increased by 52.1 ms in HF patients in native rhythm compared to controls (p<0.01). For all HF patients, CRT pacing initiated a different electromechanical activation sequence. Responders exhibited a 56.4±28.9 ms reduction in LWAT with CRT pacing (p<0.01), while non-responders showed no significant change. Conclusion In this initial feasibility study, EWI was capable of characterizing local cardiac electromechanical behavior as it pertains to HF and CRT response. Activation sequences obtained with EWI allow for quantification of LV lateral wall electromechanical activation, thus providing a novel method for CRT assessment. PMID:27790723

Real-world geographic variations in the use of cardiac implantable electronic devices - The PANORAMA 2 observational cohort study.

PubMed

Bastian, Dirk; Ebrahim, Iftikhar O; Chen, Ju-Yi; Chen, Mien-Cheng; Huang, Dejia; Huang, Jin-Long; Kuznetsov, Vadim A; Maus, Bärbel; Naik, Ajay M; Verhees, Koen J P; Fagih, Ahmed R Al

2018-06-13

Currently, several geographies around the world remain underrepresented in medical device trials. The PANORAMA 2 study was designed to assess contemporary region-specific differences in clinical practice patterns of patients with cardiac implantable electronic devices (CIEDs). In this prospective, multicenter, observational, multi-national study, baseline and implant data of 4,706 patients receiving Medtronic CIEDs (either de novo device implants, replacements, or upgrades) were analyzed, consisting of: 54% implantable pulse generators (IPGs), 20.3% implantable cardiac defibrillators (ICDs), 15% cardiac resynchronization therapy defibrillators (CRT-Ds), 5.1% cardiac resynchronization therapy pacemakers (CRT-Ps), from 117 hospitals in 23 countries across 4 geographical regions between 2012 and 2016. For all device types, in all regions, there were less females than males enrolled, and women were less likely to have ischemic cardiomyopathy. Implant procedure duration differed significantly across the geographies for all device types. Subjects from emerging countries, women and older patients were less likely to receive a magnetic resonance imaging (MRI)-compatible device. Defibrillation testing differed significantly between the regions. European patients had the highest rates of atrial fibrillation (AF), and the lowest number of implanted single-chamber IPGs. Evaluation of stroke history suggested that the general embolic risk is more strongly associated with stroke than AF. We provide comprehensive descriptive data on patients receiving Medtronic CIEDs from several geographies, some of which are understudied in randomized controlled trials (RCTs). We found significant variations in patient characteristics. Several medical decisions appear to be affected by socioeconomic factors. Long-term follow-up data will help evaluate if these variations require adjustments to outcome expectations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Does Age Influence Cardiac Resynchronization Therapy Use and Outcome?

PubMed

Heidenreich, Paul A; Tsai, Vivian; Bao, Haikun; Curtis, Jeptha; Goldstein, Mary; Curtis, Lesley; Hernandez, Adrian; Peterson, Pamela; Turakhia, Mintu P; Masoudi, Frederick A

2015-06-01

This study sought to describe the use of CRT-D and its association with survival for older patients. Many patients who receive cardiac resynchronization therapy with defibrillator (CRT-D) in practice are older than those included in clinical trials. We identified patients undergoing ICD implantation in the National Cardiovascular Disease Registry (NCDR) ICD registry from 2006 to 2009, who also met clinical trial criteria for CRT, including left ventricular ejection fraction (LVEF) ≤35%, QRS ≥120 ms, and New York Heart Association (NYHA) functional class III or IV. NCDR registry data were linked to the social security death index to determine the primary outcome of time to death from any cause. We identified 70,854 patients from 1,187 facilities who met prior trial criteria for CRT-D. The mean age of the 58,147 patients receiving CRT-D was 69.4 years with 6.4% of patients age 85 or older. CRT use was 80% or higher among candidates in all age groups. Follow-up was available for 42,285 patients age ≥65 years at 12 months. Receipt of CRT-D was associated with better survival at 1 year (82.1% vs. 77.1%, respectively) and 4 years (54.0% vs. 46.2% , respectively) than in those receiving only an ICD (p < 0.001). The CRT association with improved survival was not different for different age groups (p = 0.86 for interaction). More than 80% of older patients undergoing ICD implantation who were candidates for a CRT-D received the combined device. Mortality in older patients undergoing ICD implantation was high but was lower for those receiving CRT-D. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Comparison of right ventricular septal pacing and right ventricular apical pacing in patients receiving cardiac resynchronization therapy defibrillators: the SEPTAL CRT Study

PubMed Central

Leclercq, Christophe; Sadoul, Nicolas; Mont, Lluis; Defaye, Pascal; Osca, Joaquim; Mouton, Elisabeth; Isnard, Richard; Habib, Gilbert; Zamorano, Jose; Derumeaux, Genevieve; Fernandez-Lozano, Ignacio; Dupuis, Jean-Marc; Rouleau, Frédéric; Tassin, Aude; Bordachar, Pierre; Clémenty, Jacques; Lafitte, Stephane; Ploux, Sylvan; Reant, Patricia; Ritter, Philippe; Defaye, Pascal; Jacon, Peggy; Mondesert, Blandine; Saunier, Carole; Vautrin, Estelle; Kacet, Salem; Guedon-Moreau, Laurence; Klug, Didier; Kouakam, Claude; Marechaux, Sylvestre; Marquie, Christelle; Polge, Anne Sophie; Richardson, Marjorie; Chevallier, Philippe; De Breyne, Brigitte; Lotek, Marcin M.; Nonin, Emilie; Pineau, Julien; Deharo, Jean-Claude; Bastard, Emilie; Franceschi, Frédéric; Habib, Gilbert; Jego, Christophe; Peyrouse, Eric; Prevot, Sebastien; Saint-Joseph, Hôpital; Bremondy, Michel; Faure, Jacques; Ferracci, Ange; Lefevre, Jean; Pisapia, Andre; Davy, Jean-Marc; Cransac, Frederic; Cung, Tien Tri; Georger, Frederic; Pasquie, Jean-Luc; Raczka, Franck; Sportouch-Dukhan, Catherine; Sadoul, Nicolas; Blangy, Hugues; Bruntz, Jean-François; Freysz, Luc; Groben, Laurent; Huttin, Olivier; Bammert, Antoine; Burban, Marc; Cebron, Jean-Pierre; Gras, Daniel; Frank, Robert; Duthoit, Guillaume; Hidden-Lucet, Françoise; Himbert, Caroline; Isnard, Richard; Lacotte, Jérôme; Pousset, Françoise; Zerah, Thierry; Leclercq, Christophe; Bellouin, Annaïk; Crocq, Christophe; Deplace, Christian; Donal, Erwan; Hamon, Cécile; Mabo, Philippe; Romain, Olivier; Solnon, Aude; Frederic, Anselme; Bauer, Fabrice; Bernard, Mathieu; Godin, Benedicte; Kurtz, Baptiste; Savoure, Arnaud; Copie, Xavier; Lascault, Gilles; Paziaud, Olivier; Piot, Olivier; Touche, Thierry; Delay, Toulouse Marc; Chilon, Talia; Detis, Nicolas; Duparc, Alexandre; Hebrard, Aurélien; Massabuau, Pierre; Maury, Philippe; Mondoly, Pierre; Rumeau, Philippe; Pasteur, Clinique; Boveda, Serge; Adrover, Laurence; Combes, Nicolas; Deplagne, Antoine; Marco-Baertich, Isabelle; Fondard, Olivier; Martínez, Juan Gabriel; Ibañez Criado, José Luis; Ortuño, Diego; Mont, Lluis; Berruezo, Antonio; Eduard, Belu; Martín, Ana; Merschon, Franco M.; Sitges, Marta; Tolosana, José María; Vidal, Bárbara; Hebron, H. Valle; i Mitjans, Angel Moya; Rodriguez, Oscar Alcalde; Rodriguez Palomares, José Fernando; Rivas, Nuria; Teixidó, Gisela; de Hierro, H. Puerta; Lozano, Ignacio Fernández; Ruiz Bautista, Maria Lorena; Castro, Victor; Cavero, Miguel Angel; Gutierrez, Carlos; Ros, Natalia; de la Victoria, H. Virgen; Alzueta Rodriguez, Francisco Javier; Cabrera, Fernando; Cordero, Alberto Barrera; Peña, José Luis; de Valme Sevilla, H.; Gonzáles, Juan Lealdel Ojo; Garcia Medina, Mª Dolores; Jiménez, Ricardo Pavón; Villagomez, David; de la Salud Toledo, H. Virgen; Castellanos Martinez, Eduardo; Alcalá, Juan; Maicas, Carolina; Arias Palomares, Miguel Angel; Puchol, Alberto; Valencia, H. La Fé; OscaAsensi, Joaquim; Carmona, Anastasio Quesada; De Carranza, Mª José Sancho-Tello; De Ros, José Olagüe; Pareja, Enrique Castro; Pérez, Oscar Cano; Saez, Ana Osa; Hortega, H. Rio; Guilarte, Benito Herreros; Muñoz San Jose, Juan Francisco; Pérez Sanz, Teresa Myriam; Logeart, Damien; Gil, Maria Lopez; Leclercq, Christophe; Lozano, Ignacio Fernandez; de Hierro, H. Puerta; Derumeaux, Genevieve

2016-01-01

Abstract Aims Cardiac resynchronization therapy (CRT) is a recommended treatment of heart failure (HF) patients with depressed left ventricular ejection fraction and wide QRS. The optimal right ventricular (RV) lead position being a matter of debate, we sought to examine whether RV septal (RVS) pacing was not inferior to RV apical (RVA) pacing on left ventricular reverse remodelling in patients receiving a CRT-defibrillator. Methods and results Patients (n = 263, age = 63.4 ± 9.5 years) were randomly assigned in a 1:1 ratio to RVS (n = 131) vs. RVA (n = 132) pacing. Left ventricular end-systolic volume (LVESV) reduction between baseline and 6 months was not different between the two groups (−25.3 ± 39.4 mL in RVS group vs. −29.3 ± 44.5 mL in RVA group, P = 0.79). Right ventricular septal pacing was not non-inferior (primary endpoint) to RVA pacing with regard to LVESV reduction (average difference = −4.06 mL; P = 0.006 with a −20 mL non-inferiority margin). The percentage of ‘echo-responders’ defined by LVESV reduction >15% between baseline and 6 months was similar in both groups (50%) with no difference in the time to first HF hospitalization or death (P = 0.532). Procedural or device-related serious adverse events occurred in 68 patients (RVS = 37) with no difference between the two groups (P = 0.401). Conclusion This study demonstrates that septal RV pacing in CRT is non-inferior to apical RV pacing for LV reverse remodelling at 6 months with no difference in the clinical outcome. No recommendation for optimal RV lead position can hence be drawn from this study. ClinicalTrials. gov number NCT 00833352. PMID:26374852

Distinctive Left Ventricular Activations Associated With ECG Pattern in Heart Failure Patients.

PubMed

Derval, Nicolas; Duchateau, Josselin; Mahida, Saagar; Eschalier, Romain; Sacher, Frederic; Lumens, Joost; Cochet, Hubert; Denis, Arnaud; Pillois, Xavier; Yamashita, Seigo; Komatsu, Yuki; Ploux, Sylvain; Amraoui, Sana; Zemmoura, Adlane; Ritter, Philippe; Hocini, Mélèze; Haissaguerre, Michel; Jaïs, Pierre; Bordachar, Pierre

2017-06-01

In contrast to patients with left bundle branch block (LBBB), heart failure patients with narrow QRS and nonspecific intraventricular conduction delay (NICD) display a relatively limited response to cardiac resynchronization therapy. We sought to compare left ventricular (LV) activation patterns in heart failure patients with narrow QRS and NICD to patients with LBBB using high-density electroanatomic activation maps. Fifty-two heart failure patients (narrow QRS [n=18], LBBB [n=11], NICD [n=23]) underwent 3-dimensional electroanatomic mapping with a high density of mapping points (387±349 LV). Adjunctive scar imaging was available in 37 (71%) patients and was analyzed in relation to activation maps. LBBB patients typically demonstrated (1) a single LV breakthrough at the septum (38±15 ms post-QRS onset); (2) prolonged right-to-left transseptal activation with absence of direct LV Purkinje activity; (3) homogeneous propagation within the LV cavity; and (4) latest activation at the basal lateral LV. In comparison, both NICD and narrow QRS patients demonstrated (1) multiple LV breakthroughs along the posterior or anterior fascicles: narrow QRS versus LBBB, 5±2 versus 1±1; P =0.0004; NICD versus LBBB, 4±2 versus 1±1; P =0.001); (2) evidence of early/pre-QRS LV electrograms with Purkinje potentials; (3) rapid propagation in narrow QRS patients and more heterogeneous propagation in NICD patients; and (4) presence of limited areas of late activation associated with LV scar with high interindividual heterogeneity. In contrast to LBBB patients, narrow QRS and NICD patients are characterized by distinct mechanisms of LV activation, which may predict poor response to cardiac resynchronization therapy. © 2017 American Heart Association, Inc.

Applicability of the iterative technique for cardiac resynchronization therapy optimization: full-disclosure, 50-sequential-patient dataset of transmitral Doppler traces, with implications for future research design and guidelines.

PubMed

Jones, Siana; Shun-Shin, Matthew J; Cole, Graham D; Sau, Arunashis; March, Katherine; Williams, Suzanne; Kyriacou, Andreas; Hughes, Alun D; Mayet, Jamil; Frenneaux, Michael; Manisty, Charlotte H; Whinnett, Zachary I; Francis, Darrel P

2014-04-01

Full-disclosure study describing Doppler patterns during iterative atrioventricular delay (AVD) optimization of biventricular pacemakers (cardiac resynchronization therapy, CRT). Doppler traces of the first 50 eligible patients undergoing iterative Doppler AVD optimization in the BRAVO trial were examined. Three experienced observers classified conformity to guideline-described patterns. Each observer then selected the optimum AVD on two separate occasions: blinded and unblinded to AVD. Four Doppler E-A patterns occurred: A (always merged, 18% of patients), B (incrementally less fusion at short AVDs, 12%), C (full separation at short AVDs, as described by the guidelines, 28%), and D (always separated, 42%). In Groups A and D (60%), the iterative guidelines therefore cannot specify one single AVD. On the kappa scale (0 = chance alone; 1 = perfect agreement), observer agreement for the ideal AVD in Classes B and C was poor (0.32) and appeared worse in Groups A and D (0.22). Blinding caused the scattering of the AVD selected as optimal to widen (standard deviation rising from 37 to 49 ms, P < 0.001). By blinding 28% of the selected optimum AVDs were ≤60 or ≥200 ms. All 50 Doppler datasets are presented, to support future methodological testing. In most patients, the iterative method does not clearly specify one AVD. In all the patients, agreement on the ideal AVD between skilled observers viewing identical images is poor. The iterative protocol may successfully exclude some extremely unsuitable AVDs, but so might simply accepting factory default. Irreproducibility of the gold standard also prevents alternative physiological optimization methods from being validated honestly.

Association of hypothyroidism with adverse events in patients with heart failure receiving cardiac resynchronization therapy.

PubMed

Sharma, Ajay K; Vegh, Eszter; Orencole, Mary; Miller, Alexandra; Blendea, Dan; Moore, Stephanie; Lewis, Gregory D; Singh, Jagmeet P; Parks, Kimberly A; Heist, E Kevin

2015-05-01

Hypothyroidism is associated with an adverse prognosis in cardiac patients in general and in particular in patients with heart failure (HF). The aim of this study was to evaluate the impact of hypothyroidism on patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of level of control of hypothyroidism on risk of adverse events after CRT implantation was also evaluated. We included consecutive patients in whom a CRT device was implanted from April 2004 to April 2010 at our institution with sufficient follow-up data available for analysis; 511 patients were included (age 68.5±12.4 years, women 20.4%); 84 patients with a clinical history of hypothyroidism, on treatment with thyroid hormone repletion or serum thyroid-stimulating hormone level≥5.00 μU/ml, were included in the hypothyroid group. The patients were followed for up to 3 years after implant for a composite end point of hospitalization for HF, left ventricular assist device placement, or heart transplant and cardiac death; 215 composite end point events were noted in this period. In a multivariate model, hypothyroidism (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.027 to 2.085, p=0.035), female gender (HR 0.64, 95% CI 0.428 to 0.963, p=0.032), and creatinine (HR 1.26, 95% CI 1.145 to 1.382, p<0.001) were significantly associated with occurrence of the composite end point; 53.6% of patients with hypothyroidism at baseline developed the composite end point compared with 39.8% of those with euthyroidism (p=0.02). In conclusion, hypothyroidism is associated with a worse prognosis after CRT implantation. Copyright © 2015 Elsevier Inc. All rights reserved.

Reducing operator radiation exposure during cardiac resynchronization therapy.

PubMed

Brambilla, Marco; Occhetta, Eraldo; Ronconi, Martina; Plebani, Laura; Carriero, Alessandro; Marino, Paolo

2010-12-01

To quantify the reduction in equivalent dose at operator's hand that can be achieved by placement of a radiation-absorbing drape (RADPAD) during long-lasting cardiac resynchronization therapy (CRT) procedures. This is a prospective observational study that included 22 consecutive patients with drug-refractory heart failure who underwent implantation of a CRT device. The cases were randomly assigned to Group A (11 cases), performed without RADPAD, and to Group B (11 cases), performed using RADPAD. Dose equivalent at the examiner's hand was measured as H(p)(0.07) and as a time-adjusted H(p)(0.07) rate (mGy/min) with a direct reading dosimeter. The mean fluoroscopy time was 20.8 ± 7.7 min and the mean dose area product (DAP) was 118.6 ± 45.3 Gy cm(2). No significant differences were found between body mass index, fluoroscopy time, and DAP between patients examined with or without RADPAD. The correlation between the fluoroscopy time and the DAP was high (R(2) = 0.94, P < 0.001). Mean dose and dose rate measurement without the RADPAD at the finger and hand were H(p)(0.07) = 1.27 ± 0.47 mGy per procedure and H(p)(0.07) rate = 0.057 ± 0.011 mGy/min, respectively. The dosage was reduced with the RADPAD to H(p)(0.07) = 0.48 ± 0.20 (P < 0.05) and to H(p)(0.07) rate = 0.026 ± 0.008 (P < 0.001), respectively. A mean reduction of 54% in the equivalent dose rate to the operator's hand can be achieved with the use of RADPAD. The use of the RADPAD in CRT devices implantation will make unlikely the necessity of limiting the yearly number of implants for high volume operators.

Multipolar pacing by cardiac resynchronization therapy with a defibrillators treatment in type 2 diabetes mellitus failing heart patients: impact on responders rate, and clinical outcomes.

PubMed

Sardu, Celestino; Barbieri, Michelangela; Santamaria, Matteo; Giordano, Valerio; Sacra, Cosimo; Paolisso, Pasquale; Spirito, Alessandro; Marfella, Raffaele; Paolisso, Giuseppe; Rizzo, Maria Rosaria

2017-06-09

Type 2 diabetes mellitus (T2DM) is a multi factorial disease, affecting clinical outcomes in failing heart patients treated by cardiac resynchronization therapy with a defibrillator (CRT-d). One hundred and ninety-five T2DM patients received a CRT-d treatment. Randomly the study population received a CRT-d via multipolar left ventricle (LV) lead pacing (n 99, multipolar group), vs a CRT-d via bipolar LV pacing (n 96, bipolar group). These patients were followed by clinical, and instrumental assessment, and telemetric device control at follow up. In this study we evaluated, in a population of failing heart T2DM patients, cardiac deaths, all cause deaths, arrhythmic events, CRT-d responders rate, hospitalizations for HF worsening, phrenic nerve stimulation (PNS), and LV catheter dislodgment events (and re-intervention for LV catheter re-positioning), comparing multipolar CRT-d vs bipolar CRT-d group of patients at follow up. At follow up there was a statistical significant difference about atrial arrhythmic events [7 (7%) vs 16 (16.7%), p value 0.019], hospitalizations for HF worsening [15 (15.2% vs 24 (25%), p value 0.046], LV catheter dislodgments [1 (1%) vs 9 (9.4%), p value 0018], PNS [5 (5%) vs 18 (18.7%), p value 0.007], and LV re-positioning [1 (1%) vs 9 (9.4%), p value 0.018], comparing multipolar CRT-d vs bipolar CRT-d group of patients. Multipolar pacing was an independent predictor of all these events. CRT-d pacing via multipolar LV lead vs bipolar LV lead may reduce arrhythmic burden, hospitalization rate, PNS, LV catheters dislodgments, and re-interventions in T2DM failing heart patients. Clinical trial number NCT03095196.

Atrial fibrillation in cardiac resynchronization therapy with a defibrillator: a risk factor for mortality, appropriate and inappropriate shocks.

PubMed

van Boven, Nick; Theuns, Dominic; Bogaard, Kjell; Ruiter, Jaap; Kimman, Geert; Berman, Lily; VAN DER Ploeg, Tjeerd; Kardys, Isabella; Umans, Victor

2013-10-01

Knowledge about predictive factors for mortality and (in)appropriate shocks in cardiac resynchronization therapy with a defibrillator (CRT-D) should be available and updated to predict clinical outcome. We retrospectively analyzed 543 consecutive patients assigned to CRT-D in 2 tertiary medical centers. The aim of this study was to assess risk factors for all-cause mortality, appropriate and inappropriate shocks. Mean follow-up time was 3.2 (±1.8) years. A total of 110 (20%) patients died, 71 (13%) received ≥1 appropriate shocks, and 33 (6.1%) received ≥1 inappropriate shocks. No patients received a His bundle ablation and biventricular pacing percentage was not analyzed. Multivariable Cox regression analysis showed that a history of atrial fibrillation (AF) (HR 1.74 CI 1.06-2.86), higher creatinine (HR 1.12; CI 1.08-1.16), and a poorer left ventricular ejection fraction (LVEF) (HR 0.97; CI 0.94-1.01) independently predict all-cause mortality. In the entire cohort, history of AF and secondary prevention were independent predictors of appropriate shocks and variables associated with inappropriate shocks were history of AF and QRS ≥150 milliseconds. In primary prevention patients, history of AF also predicted appropriate shocks as did ischemic cardiomyopathy and poorer LVEF. History of AF, QRS ≥150 milliseconds, and lower creatinine were associated with inappropriate shocks in this subgroup. Appropriate shocks increased mortality risk, but inappropriate shocks did not. In symptomatic CHF patients treated with CRT-D, history of AF is an independent risk factor not only for mortality, but also for appropriate and inappropriate shocks. Further efforts in AF management may optimize the care in CRT-D patients. © 2013 Wiley Periodicals, Inc.

Ventilatory gas exchange and early response to cardiac resynchronization therapy.

PubMed

Kim, Chul-Ho; Olson, Lyle J; Shen, Win K; Cha, Yong-Mei; Johnson, Bruce D

2015-11-01

Cardiac resynchronization therapy (CRT) is an accepted intervention for chronic heart failure (HF), although approximately 30% of patients are non-responders. The purpose of this study was to determine whether exercise respiratory gas exchange obtained before CRT implantation predicts early response to CRT. Before CRT implantation, patients were assigned to either a mild-moderate group (Mod G, n = 33, age 67 ± 10 years) or a moderate-severe group (Sev G, n = 31, age 67 ± 10 years), based on abnormalities in exercise gas exchange. Severity of impaired gas exchange was based on a score from the measures of VE/VCO(2) slope, resting PETCO(2) and change of PETCO(2) from resting to peak. All measurements were performed before and 3 to 4 months after CRT implantation. Although Mod G did not have improved gas exchange (p > 0.05), Sev G improved significantly (p < 0.05) post-CRT. In addition, Mod G did not show improved right ventricular systolic pressure (RSVP; pre vs post: 37 ± 14 vs 36 ± 11 mm Hg, p > 0.05), yet Sev G showed significantly improved RVSP, by 23% (50 ± 14 vs 42 ± 12 mm Hg, p < 0.05). Both groups had improved left ventricular ejection fraction (p < 0.05), New York Heart Association class (p < 0.05) and quality of life (p < 0.05), but no significant differences were observed between groups (p > 0.05). No significant changes were observed in brain natriuretic peptide in either group post-CRT. Based on pre-CRT implantation ventilatory gas exchange, subjects with the most impaired values appeared to have more improvement post-CRT, possibly associated with a decrease in RVSP. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Evaluation of in-hospital NT-proBNP changes in heart failure patients to identify the six-month clinical response following cardiac resynchronization therapy.

PubMed

Davoodi, Gholamreza; Bagheri, Ahmadreza; Yamini-Sharif, Ahmad; Boroumand, Mohammadali; Saroukhani, Sepideh; Sahebjam, Mohammad

2014-01-01

N-terminal pro β-type natriuretic peptide (NT-proBNP) is a valuable marker for monitoring the response to treatment in patients with heart failure. Based on the clinically observed improvement of heart failure symptoms early after cardiac resynchronization therapy (CRT), we sought to investigate whether CRT induce any significant reduction in the plasma level of NT-proBNP in three days after implantation and whether it is correlated with patients' response at six months. In this prospective study, 21 consecutive patients with severe heart failure (New York Heart Association class 3.19±0.40) who underwent CRT were enrolled. Being alive, no hospitalization due to decompensated heart failure, and improvement of at least one NYHA functional class at six months were classified as clinical responsiveness. The plasma level of NT-proBNP was measured before, three days, and six months after CRT. Clinical evaluation, echocardiographic study, and six-minute walking test were performed before and six months after the procedure. At six months' follow-up, 16 (76.2%) patients were responders. The plasma level of NT-proBNP at three days after CRT increased almost equally in both responder and non-responder groups of patients (∆NT-proBNP was 40.94±135.74 vs. 54.80±88.98); however, at six months' follow-up, the NT-proBNP changes statistically differed across the two groups of patients (P=0.005). According to our findings, NT-proBNP percent deviation from baseline to three days after CRT appears to be not correlated with the patients' clinical response after six months, which was incongruent to the patients' clinical improvement after CRT.

Risk Factors and Temporal Trends of Complications Associated With Transvenous Implantable Cardiac Defibrillator Leads.

PubMed

Koneru, Jayanthi N; Jones, Paul W; Hammill, Eric F; Wold, Nicholas; Ellenbogen, Kenneth A

2018-05-10

The transvenous implantable cardioverter-defibrillator (ICD) lead is the most common source of complications in a traditional ICD system. This investigation aims to determine the incidence, predictors, and costs associated with these complications using a large insurance database. Data from the OptumLabs™ Data Warehouse, which include diagnosis, physician and procedure codes, and claims from patient hospitalizations, were analyzed. Patients with a de novo ICD or cardiac resynchronization therapy defibrillator implanted from January 1, 2003, through June 30, 2015, were included; those who did not have continuous coverage beginning 1 year before implantation were excluded, resulting in 40 837 patients followed up over an average of 2.3±2.1 years. Patients were followed up until they had the procedure or their last active date in the database. Of 20 580 device procedures, 2165 (5.3%) and 771 (1.9%) had mechanical and infectious complications, respectively. The 5-year rate of freedom from mechanical complication was 92.0% and 89.3% for ICDs and cardiac resynchronization therapy defibrillators, respectively. Infectious complications were more likely in patients with a history of atrial fibrillation, diabetes mellitus, and renal disease, and the risk increased with subsequent device procedures. Younger age, female sex, lack of comorbidities, and implantations between 2003 and 2008 were associated with more mechanical complications. Incidence of mechanical and infectious complications of transvenous ICD leads over long-term follow-up is much higher in the real world than in clinical studies. In our study cohort, 1 of 4 transvenous ICD leads had mechanical complications when followed up to 10 years. The high rate of reintervention leads to additional complications. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Impact of Cardiac Resynchronization Therapy on Left Ventricular Mechanics: Understanding the Response through a New Quantitative Approach Based on Longitudinal Strain Integrals.

PubMed

Bernard, Anne; Donal, Erwan; Leclercq, Christophe; Schnell, Frédéric; Fournet, Maxime; Reynaud, Amélie; Thebault, Christophe; Mabo, Philippe; Daubert, J-Claude; Hernandez, Alfredo

2015-06-01

The mechanisms of improvement of left ventricular (LV) function with cardiac resynchronization therapy (CRT) are not yet elucidated. The aim of this study was to describe a new tool based on automatic quantification of the integrals of regional longitudinal strain signals and evaluate changes in LV strain distribution after CRT. This was a retrospective observational study of 130 patients with heart failure before CRT device implantation and after 3 to 6 months of follow-up. Integrals of regional longitudinal strain signals (from the beginning of the cardiac cycle to strain peak [IL,peak] and to the instant of aortic valve closure [IL,avc]) were analyzed retrospectively with custom-made algorithms. Response to CRT was defined as a decrease in LV end-systolic volume of ≥15%. Responders (61%) and nonresponders (39%) showed similar baseline values of regional IL,peak and IL,avc. At follow-up, significant improvements of midlateral IL,peak and of midlateral IL,avc were noted only in responders. Midlateral IL,avc showed a relative increase of 151 ± 276% in responders, whereas a decrease of 33 ± 69% was observed in nonresponders. The difference between IL,avc and IL,peak (representing wasted energy of the LV myocardium) of the lateral wall showed a relative change of -59 ± 103% in responders between baseline and CRT, whereas in nonresponders, the relative change was 21 ± 113% (P = .009). Strain integrals revealed changes between baseline and CRT in the lateral wall, demonstrating the beneficial effects of CRT on LV mechanics with favorable myocardial reverse remodeling. Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure.

PubMed

Cleland, John G; Abraham, William T; Linde, Cecilia; Gold, Michael R; Young, James B; Claude Daubert, J; Sherfesee, Lou; Wells, George A; Tang, Anthony S L

2013-12-01

Cardiac resynchronization therapy (CRT) with or without a defibrillator reduces morbidity and mortality in selected patients with heart failure (HF) but response can be variable. We sought to identify pre-implantation variables that predict the response to CRT in a meta-analysis using individual patient-data. An individual patient meta-analysis of five randomized trials, funded by Medtronic, comparing CRT either with no active device or with a defibrillator was conducted, including the following baseline variables: age, sex, New York Heart Association class, aetiology, QRS morphology, QRS duration, left ventricular ejection fraction (LVEF), and systolic blood pressure. Outcomes were all-cause mortality and first hospitalization for HF or death. Of 3782 patients in sinus rhythm, median (inter-quartile range) age was 66 (58-73) years, QRS duration was 160 (146-176) ms, LVEF was 24 (20-28)%, and 78% had left bundle branch block. A multivariable model suggested that only QRS duration predicted the magnitude of the effect of CRT on outcomes. Further analysis produced estimated hazard ratios for the effect of CRT on all-cause mortality and on the composite of first hospitalization for HF or death that suggested increasing benefit with increasing QRS duration, the 95% confidence bounds excluding 1.0 at ∼140 ms for each endpoint, suggesting a high probability of substantial benefit from CRT when QRS duration exceeds this value. QRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm. QRS morphology did not provide additional information about clinical response. NCT00170300, NCT00271154, NCT00251251.

Atrial electrogram quality in single-pass defibrillator leads with floating atrial bipole in patients with permanent atrial fibrillation and cardiac resynchronization therapy.

PubMed

Sticherling, Christian; Müller, Dirk; Schaer, Beat A; Krüger, Silke; Kolb, Christof

2018-03-27

Many patients receiving cardiac resynchronization therapy (CRT) suffer from permanent atrial fibrillation (AF). Knowledge of the atrial rhythm is important to direct pharmacological or interventional treatment as well as maintaining AV-synchronous biventricular pacing if sinus rhythm can be restored. A single pass single-coil defibrillator lead with a floating atrial bipole has been shown to obtain reliable information about the atrial rhythm but has never been employed in a CRT-system. The purpose of this study was to assess the feasibility of implanting a single coil right ventricular ICD lead with a floating atrial bipole and the signal quality of atrial electrograms (AEGM) in CRT-defibrillator recipients with permanent AF. Seventeen patients (16 males, mean age 73 ± 6 years, mean EF 25 ± 5%) with permanent AF and an indication for CRT-defibrillator placement were implanted with a designated CRT-D system comprising a single pass defibrillator lead with a atrial floating bipole. They were followed-up for 103 ± 22 days using remote monitoring for AEGM transmission. All patients had at last one AEGM suitable for atrial rhythm diagnosis and of 100 AEGM 99% were suitable for visual atrial rhythm assessment. Four patients were discharged in sinus rhythm and one reverted to AF during follow-up. Atrial electrograms retrieved from a single-pass defibrillator lead with a floating atrial bipole can be reliably used for atrial rhythm diagnosis in CRT recipients with permanent AF. Hence, a single pass ventricular defibrillator lead with a floating bipole can be considered in this population. Copyright © 2018 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

Predictors of response to cardiac resynchronization therapy: A prospective cohort study.

PubMed

Abreu, Ana; Oliveira, Mário; Silva Cunha, Pedro; Santa Clara, Helena; Santos, Vanessa; Portugal, Guilherme; Rio, Pedro; Soares, Rui; Moura Branco, Luísa; Alves, Marta; Papoila, Ana Luísa; Ferreira, Rui; Mota Carmo, Miguel

2017-06-01

Cardiac resynchronization therapy (CRT) has modified the prognosis of chronic heart failure (HF) with left ventricular systolic dysfunction. However, 30% of patients do not have a favorable response. The big question is how to determine predictors of response. To identify baseline characteristics that might influence echocardiographic response to CRT. We performed a prospective single-center hospital-based cohort study of consecutive HF patients selected to CRT (NYHA class II-IV, left ventricular ejection fraction (LVEF) <35% and QRS complex ≥120 ms). Responders were defined as those with a ≥5% absolute increase in LVEF at six months. Clinical, electrocardiographic, laboratory, echocardiographic, autonomic, endothelial and cardiopulmonary function parameters were assessed before CRT device implantation. Logistic regression models were used. Seventy-nine patients were included, 54 male (68.4%), age 68.1 years (standard deviation 10.2), 19 with ischemic etiology (24%). At six months, 51 patients (64.6%) were considered responders. Although by univariate analysis baseline tricuspid annular plane systolic excursion (TAPSE) and serum creatinine were significantly different in responders, on multivariate analysis only TAPSE was independently associated with response, with higher values predicting a positive response to CRT (OR=1.13; 95% CI: 1.02-1.26; p=0.020). TAPSE ≥15 mm was strongly associated with response, and TAPSE <15 mm with non-response (p=0.005). Responders had no TAPSE values below 10 mm. From a range of clinical and technical baseline characteristics, multivariate analysis only identified TAPSE as an independent predictor of CRT response, with TAPSE <15 mm associated with non-response. This study highlights the importance of right ventricular dysfunction in CRT response. ClinicalTrials.gov identifier: NCT02413151. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

What happens to non-responders in cardiac resynchronization therapy?

PubMed

Rio, Pedro; Oliveira, Mário Martins; Cunha, Pedro Silva; da Silva, Manuel Nogueira; Branco, Luísa Moura; Galrinho, Ana; Soares, Rui; Feliciano, Joana; Pimenta, Ricardo; Ferreira, Rui Cruz

2017-12-01

Left ventricular reverse remodeling (LVRR) is strongly related to the long-term prognosis of patients undergoing cardiac resynchronization therapy (CRT). The aim of this study was to assess the long-term clinical outcome of patients without LVRR at six months after CRT implantation and to determine the prognostic impact of clinical response in this population. We analyzed 178 consecutive patients who underwent successful CRT device implantation (age 64±11 years; 69% male; 89% in New York Heart Association [NYHA] functional class III; 35% with ischemic cardiomyopathy). Clinical status and echocardiographic parameters were determined before and six months after CRT implantation. We identified those without criteria for LVRR (≥10% increase in left ventricular ejection fraction with ≥15% reduction in left ventricular end-systolic diameter compared to baseline). Clinical responders were defined by a sustained improvement of at least one NYHA functional class. At six-month assessment after CRT, 109 (61%) patients showed LVRR. During a mean follow-up of 56±21 months, 47 (26%) patients died, with higher mortality in the group without LVRR (36% vs. 20%, p=0.023). Clinical response was greater in patients with LVRR (88% vs. 55%, p<0.001). In patients without LVRR, clinical response to CRT was the strongest independent predictor of survival (hazard ratio: 0.120; 95% confidence interval: 0.039-0.366; p<0.001). Although patients without LVRR six months after CRT implantation had a worse prognosis, with higher all-cause mortality, clinical response can be an independent predictor of survival in this population. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Impact of basal inferolateral scar burden determined by automatic analysis of 99mTc-MIBI myocardial perfusion SPECT on the long-term prognosis of cardiac resynchronization therapy.

PubMed

Morishima, Itsuro; Okumura, Kenji; Tsuboi, Hideyuki; Morita, Yasuhiro; Takagi, Kensuke; Yoshida, Ruka; Nagai, Hiroaki; Tomomatsu, Toshiro; Ikai, Yoshihiro; Terada, Kazushi; Sone, Takahito; Murohara, Toyoaki

2017-04-01

Left-ventricular (LV) scarring may be associated with a poor response to cardiac resynchronization therapy (CRT). The automatic analysis of myocardial perfusion single-photon emission computed tomography (MP-SPECT) may provide objective quantification of LV scarring. We investigated the impact of LV scarring determined by an automatic analysis of MP-SPECT on short-term LV volume response as well as long-term outcome. We studied consecutive 51 patients who were eligible to undergo 99mTc-MIBI MP-SPECT both at baseline and 6 months after CRT (ischaemic cardiomyopathies 31%). Quantitative perfusion SPECT was used to evaluate the defect extent (an index of global scarring) and the LV 17-segment regional uptake ratio (an inverse index of regional scar burden). The primary outcome was the composite of overall mortality or first hospitalization for worsening heart failure. A high global scar burden and a low mid/basal inferolateral regional uptake ratio were associated with volume non-responders to CRT at 6 months. The basal inferolateral regional uptake ratio remained as a predictor of volume non-response after adjusting for the type of cardiomyopathy. During a median follow-up of 36.1 months, the outcome occurred in 28 patients. The patients with a low basal inferolateral regional uptake ratio with a cutoff value of 57% showed poor prognosis (log-rank P= 0.006). The scarring determined by automatic analysis of MP-SPECT images may predict a poor response to CRT regardless of the pathogenesis of cardiomyopathy. The basal inferolateral scar burden in particular may have an adverse impact on long-term prognosis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Sensor-based electromagnetic navigation to facilitate implantation of left ventricular leads in cardiac resynchronization therapy.

PubMed

Döring, Michael; Sommer, Philipp; Rolf, Sascha; Lucas, Johannes; Breithardt, Ole A; Hindricks, Gerhard; Richter, Sergio

2015-02-01

Implantation of cardiac resynchronization therapy (CRT) devices can be challenging, time consuming, and fluoroscopy intense. To facilitate placement of left ventricular (LV) leads, a novel electromagnetic navigation system (MediGuide™, St. Jude Medical, St. Paul, MN, USA) has been developed, displaying real-time 3-D location of sensor-embedded delivery tools superimposed on prerecorded X-ray cine-loops of coronary sinus venograms. We report our experience and advanced progress in the use of this new electromagnetic tracking system to guide LV lead implantation. Between January 2012 and December 2013, 71 consecutive patients (69 ± 9 years, 76% male) were implanted with a CRT device using the new electromagnetic tracking system. Demographics, procedural data, and periprocedural adverse events were gathered. The impact of the operator's experience, optimized workflow, and improved software technology on procedural data were analyzed. LV lead implantation was successfully achieved in all patients without severe adverse events. Total procedure time measured 87 ± 37 minutes and the median total fluoroscopy time (skin-to-skin) was 4.9 (2.5-7.8) minutes with a median dose-area-product of 476 (260-1056) cGy*cm(2) . An additional comparison with conventional CRT device implantations showed a significant reduction in fluoroscopy time from 8.0 (5.8; 11.5) to 4.5 (2.8; 7.3) minutes (P = 0.016) and radiation dose from 603 (330; 969) to 338 (176; 680) cGy*cm(2) , respectively (P = 0.044 ). Use of the new navigation system enables safe and successful LV lead placement with improved orientation and significantly reduced radiation exposure during CRT implantation. © 2014 Wiley Periodicals, Inc.

Effect of Smaller Left Ventricular Capture Threshold Safety Margins to Improve Device Longevity in Recipients of Cardiac Resynchronization-Defibrillation Therapy.

PubMed

Steinhaus, Daniel A; Waks, Jonathan W; Collins, Robert; Kleckner, Karen; Kramer, Daniel B; Zimetbaum, Peter J

2015-07-01

Device longevity in cardiac resynchronization therapy (CRT) is affected by the pacing capture threshold (PCT) and programmed pacing amplitude of the left ventricular (LV) pacing lead. The aims of this study were to evaluate the stability of LV pacing thresholds in a nationwide sample of CRT defibrillator recipients and to determine potential longevity improvements associated with a decrease in the LV safety margin while maintaining effective delivery of CRT. CRT defibrillator patients in the Medtronic CareLink database were eligible for inclusion. LV PCT stability was evaluated using ≥2 measurements over a 14-day period. Separately, a random sample of 7,250 patients with programmed right atrial and right ventricular amplitudes ≤2.5 V, LV thresholds ≤ 2.5 V, and LV pacing ≥90% were evaluated to estimate theoretical battery longevity improvement using LV safety margins of 0.5 and 1.5 V. Threshold stability analysis in 43,256 patients demonstrated LV PCT stability of <0.5 V in 77% of patients and <1 V in 95%. Device longevity analysis showed that the use of a 0.5-V safety margin increased average battery longevity by 0.62 years (95% confidence interval 0.61 to 0.63) compared with a safety margin of 1.5 V. Patients with LV PCTs >1 V had the greatest increases in battery life (mean increase 0.86 years, 95% confidence interval 0.85 to 0.87). In conclusion, nearly all CRT defibrillator patients had LV PCT stability <1.0 V. Decreasing the LV safety margin from 1.5 to 0.5 V provided consistent delivery of CRT for most patients and significantly improved battery longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

Elevated serum creatinine at baseline predicts poor outcome in patients receiving cardiac resynchronization therapy.

PubMed

Shalaby, Alaa; El-Saed, Aiman; Voigt, Andrew; Albany, Constantine; Saba, Samir

2008-05-01

Renal insufficiency is recognized as a predictor of mortality and poor outcome in heart failure patients. We sought to study the impact of baseline serum creatinine on subsequent outcome in cardiac resynchronization therapy (CRT) recipients. We retrospectively reviewed hospital records of all CRT recipients at Pittsburgh Veterans Affairs (VA) Healthcare System (2003-2005) and University of Pittsburgh Medical Center (2004). We recorded clinical characteristics at the time of implantation including demographics, New York Heart Association (NYHA) functional class, ejection fraction, QRS duration, cardiomyopathy etiology, medical history, medication use, and serum creatinine. Mortality alone and mortality combined with heart failure hospitalization were the study endpoints. Out of the 330 patients studied, a total of 66 (20.0%) patients died over a mean follow-up duration of 19.7 +/- 9.0 months (range 1-44). The cohort was studied by three creatinine tertiles (0.6-1.0, 1.1-1.3, 1.4-3.0 mg/dL). Both study endpoints were observed more frequently in patients in the highest creatinine tertile compared to others (28.7% vs 14.0%, P = 0.008 for death and 41.6% vs 21.5%, P = 0.001 for the combined endpoint). High creatinine remained an independent predictor of mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.06-3.39, P = 0.032) and the combined endpoint (HR 1.94, 95% CI 1.20-3.13, P = 0.007) in multivariate adjusted models. Studied as a continuous variable, increase in creatinine level by 0.1 mg/dL was associated with an 11% increase in mortality risk and a 7% increase in the combined endpoint. In an unselected cohort of CRT recipients, the baseline creatinine was found to predict worse survival and poor outcome over a modest follow-up duration.

Comparative Effectiveness of Cardiac Resynchronization Therapy Defibrillators Versus Standard Implantable Defibrillators in Medicare Patients.

PubMed

Zusterzeel, Robbert; Caños, Daniel A; Sanders, William E; Silverman, Henry; MaCurdy, Thomas E; Worrall, Christopher M; Kelman, Jeffrey; Marinac-Dabic, Danica; Strauss, David G

2015-07-01

Previous analyses have shown that there is lower mortality with cardiac resynchronization therapy defibrillators (CRT-D) in patients with left bundle branch block (LBBB) but demonstrated mixed results in patients without LBBB. We evaluated the comparative effectiveness of CRT-D versus standard implantable defibrillators (ICDs) separately in patients with LBBB and right bundle branch block (RBBB) using Medicare claims data. Medicare records from CRT-D and ICD recipients from 2002 to 2009 that were followed up for up to 48 months were analyzed. We used propensity scores to match patients with ICD to those with CRT-D. In LBBB, 1:1 matching with replacement resulted in 54,218 patients with CRT-D and 20,763 with ICD, and in RBBB, 1:1 matching resulted in 7,298 patients with CRT-D and 7,298 with ICD. In LBBB, CRT-D had a 12% lower risk of heart failure hospitalization or death (hazard ratio [HR] 0.88, 95% confidence interval 0.86 to 0.90) and 5% lower death risk (HR 0.95, 0.92 to 0.97) compared with ICD. In RBBB, CRT-D had a 15% higher risk of heart failure hospitalization or death (HR 1.15, 1.10 to 1.20) and 13% higher death risk (HR 1.13, 1.07 to 1.18). Sensitivity analysis revealed that accounting for covariates not captured in the Medicare database may lead to increased benefit with CRT-D in LBBB and no difference in RBBB. In conclusion, in a large Medicare population, CRT-D was associated with lower mortality in LBBB but higher mortality in RBBB. The absence of certain covariates, in particular those that determine treatment selection, may affect the results of comparative effectiveness studies using claims data. Published by Elsevier Inc.

T-wave area as biomarker of clinical response to cardiac resynchronization therapy.

PubMed

Végh, Eszter M; Engels, Elien B; van Deursen, Caroline J M; Merkely, Béla; Vernooy, Kevin; Singh, Jagmeet P; Prinzen, Frits W

2016-07-01

There is increasing evidence that left bundle branch block (LBBB) morphology on the electrocardiogram is a positive predictor for response to cardiac resynchronization therapy (CRT). We previously demonstrated that the vectorcardiography (VCG)-derived T-wave area predicts echocardiographic CRT response in LBBB patients. In the present study, we investigate whether the T-wave area also predicts long-term clinical outcome to CRT. This is a retrospective study consisting of 335 CRT recipients. Primary endpoint were the composite of heart failure (HF) hospitalization, heart transplantation, left ventricular assist device implantation or death during a 3-year follow-up period. HF hospitalization and death alone were secondary endpoints. The patient subgroup with a large T-wave area and LBBB 36% reached the primary endpoint, which was considerably less (P < 0.01) than for patients with LBBB and a small T-wave area or non-LBBB patients with a small or large T-wave area (48, 57, and 51%, respectively). Similar differences were observed for the secondary endpoints, HF hospitalization (31 vs. 51, 51, and 38%, respectively, P < 0.01) and death (19 vs. 42, 34, and 42%, respectively, P < 0.01). In multivariate analysis, a large T-wave area and LBBB were the only independent predictors of the combined endpoint besides high creatinine levels and use of diuretics. T-wave area may be useful as an additional biomarker to stratify CRT candidates and improve selection of those most likely to benefit from CRT. A large T-wave area may derive its predictive value from reflecting good intrinsic myocardial properties and a substrate for CRT. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The roles of the Q (q) wave in lead I and QRS frontal axis for diagnosing loss of left ventricular capture during cardiac resynchronization therapy.

PubMed

Cao, Yuan-Yuan; Su, Yan-Gang; Bai, Jin; Wang, Wei; Wang, Jing-Feng; Qin, Sheng-Mei; Ge, Jun-Bo

2015-01-01

Loss of left ventricular (LV) capture may lead to deterioration of heart failure in patients with cardiac resynchronization therapy (CRT). Recognition of loss of LV capture in time is important in clinical practice. A total of 422 electrocardiograms were acquired and analyzed from 53 CRT patients at 8 different pacing settings (LV only, right ventricle [RV] only, biventricular [BV] pacing with LV preactivation of 60, 40, 20, and 0 milliseconds and RV preactivation of 20 and 40 milliseconds). A modified Ammann algorithm by adding a third step-presence of Q (q, or QS) wave-to the original 2-step Ammann algorithm and a QRS axis shift method were devised to identify the loss of LV capture. The accuracy of modified Ammann algorithm was significantly higher than that of Ammann algorithm (78.9% vs. 69.1%, P < 0.001). The accuracy of the axis shift method was 66.4%, which was significantly lower than the modified Ammann algorithm (P < 0.001) and similar to the original one (P = 0.412). However, in the ECGs with QRS axis shift, 96.8% were correctly classified. LV preactivation or simultaneous BV activation and LV lead positioned in nonposterior or noninferior wall could elevate the accuracies of the modified Ammann algorithm and the QRS axis shift method. The accuracy of the modified Ammann algorithm is greatly improved. The QRS axis shift method can help diagnose LV capture. The LV preactivation, or simultaneous BV activation and LV lead positioned in nonposterior or noninferior wall can increase the diagnostic power of the modified Ammann algorithm and QRS axis shift method. © 2014 Wiley Periodicals, Inc.

Meta-Analysis of the Relation of Baseline Right Ventricular Function to Response to Cardiac Resynchronization Therapy.

PubMed

Sharma, Abhishek; Bax, Jerome J; Vallakati, Ajay; Goel, Sunny; Lavie, Carl J; Kassotis, John; Mukherjee, Debabrata; Einstein, Andrew; Warrier, Nikhil; Lazar, Jason M

2016-04-15

Right ventricular (RV) dysfunction has been associated with adverse clinical outcomes in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves left ventricular (LV) size and function in patients with markedly abnormal electrocardiogram QRS duration. However, relation of baseline RV function with response to CRT has not been well described. In this study, we aim to investigate the relation of baseline RV function with response to CRT as assessed by change in LV ejection fraction (EF). A systematic search of studies published from 1966 to May 31, 2015 was conducted using PubMed, CINAHL, Cochrane CENTRAL, and the Web of Science databases. Studies were included if they have reported (1) parameters of baseline RV function (tricuspid annular plane systolic excursion [TAPSE] or RVEF or RV basal strain or RV fractional area change [FAC]) and (2) LVEF before and after CRT. Random-effects metaregression was used to evaluate the effect of baseline RV function parameters and change in LVEF. Sixteen studies (n = 1,764) were selected for final analysis. Random-effects metaregression analysis showed no significant association between the magnitude of the difference in EF before and after CRT with baseline TAPSE (β = 0.005, p = 0.989); baseline RVEF (β = 0.270, p = 0.493); baseline RVFAC (β = -0.367, p = 0.06); baseline basal strain (β = -0.342, p = 0.462) after a mean follow-up period of 10.5 months. In conclusion, baseline RV function as assessed by TAPSE, FAC, basal strain, or RVEF does not determine response to CRT as assessed by change in LVEF. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of right ventricular septal pacing and right ventricular apical pacing in patients receiving cardiac resynchronization therapy defibrillators: the SEPTAL CRT Study.

PubMed

Leclercq, Christophe; Sadoul, Nicolas; Mont, Lluis; Defaye, Pascal; Osca, Joaquim; Mouton, Elisabeth; Isnard, Richard; Habib, Gilbert; Zamorano, Jose; Derumeaux, Genevieve; Fernandez-Lozano, Ignacio

2016-02-01

Cardiac resynchronization therapy (CRT) is a recommended treatment of heart failure (HF) patients with depressed left ventricular ejection fraction and wide QRS. The optimal right ventricular (RV) lead position being a matter of debate, we sought to examine whether RV septal (RVS) pacing was not inferior to RV apical (RVA) pacing on left ventricular reverse remodelling in patients receiving a CRT-defibrillator. Patients (n = 263, age = 63.4 ± 9.5 years) were randomly assigned in a 1:1 ratio to RVS (n = 131) vs. RVA (n = 132) pacing. Left ventricular end-systolic volume (LVESV) reduction between baseline and 6 months was not different between the two groups (-25.3 ± 39.4 mL in RVS group vs. -29.3 ± 44.5 mL in RVA group, P = 0.79). Right ventricular septal pacing was not non-inferior (primary endpoint) to RVA pacing with regard to LVESV reduction (average difference = -4.06 mL; P = 0.006 with a -20 mL non-inferiority margin). The percentage of 'echo-responders' defined by LVESV reduction >15% between baseline and 6 months was similar in both groups (50%) with no difference in the time to first HF hospitalization or death (P = 0.532). Procedural or device-related serious adverse events occurred in 68 patients (RVS = 37) with no difference between the two groups (P = 0.401). This study demonstrates that septal RV pacing in CRT is non-inferior to apical RV pacing for LV reverse remodelling at 6 months with no difference in the clinical outcome. No recommendation for optimal RV lead position can hence be drawn from this study. NCT 00833352. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiac resynchronization therapy for patients with cardiac sarcoidosis.

PubMed

Sairaku, Akinori; Yoshida, Yukihiko; Nakano, Yukiko; Hirayama, Haruo; Maeda, Mayuho; Hashimoto, Haruki; Kihara, Yasuki

2017-05-01

Sarcoidosis with cardiac involvement is a rare pathological condition, and therefore cardiac resynchronization therapy (CRT) for patients with cardiac sarcoidosis is even further rare. We aimed to clarify the clinical features of patients with cardiac sarcoidosis who received CRT. We retrospectively reviewed the clinical data on CRT at three cardiovascular centres to detect cardiac sarcoidosis patients. We identified 18 (8.9%) patients with cardiac sarcoidosis who met the inclusion criteria out of 202 with systolic heart failure who received CRT based on the guidelines. The majority of the patients were female [15 (83.3%)] and underwent an upgrade from a pacemaker or implantable cardioverter defibrillator [13 (72.2%)]. We found 1 (5.6%) cardiovascular death during the follow-up period (mean ± SD, 4.7 ± 3.0 years). Seven (38.9%) patients had a composite outcome of cardiovascular death or hospitalization from worsening heart failure within 5 years after the CRT. Twelve (66.7%) patients had a history of sustained ventricular arrhythmias or those occurring after the CRT. Among the overall patients, no significant improvement was found in either the end-systolic volume or left ventricular ejection fraction (LVEF) 6 months after the CRT. A worsening LVEF was, however, more likely to be seen in 5 (27.8%) patients with ventricular arrhythmias after the CRT than in those without (P = 0.04). An improved clinical composite score was seen in 10 (55.6%) patients. Cardiac sarcoidosis patients receiving CRT may have poor LV reverse remodelling and a high incidence of ventricular arrhythmias. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Atrioventricular and ventricular-to-ventricular programming in patients with cardiac resynchronization therapy: results from ALTITUDE.

PubMed

Steinberg, Benjamin A; Wehrenberg, Scott; Jackson, Kevin P; Hayes, David L; Varma, Niraj; Powell, Brian D; Day, John D; Frazier-Mills, Camille G; Stein, Kenneth M; Jones, Paul W; Piccini, Jonathan P

2015-12-01

Cardiac resynchronization therapy (CRT) improves outcomes in patients with heart failure, yet response rates are variable. We sought to determine whether physician-specified CRT programming was associated with improved outcomes. Using data from the ALTITUDE remote follow-up cohort, we examined sensed atrioventricular (AV) and ventricular-to-ventricular (VV) programming and their associated outcomes in patients with de novo CRT from 2009-2010. Outcomes included arrhythmia burden, left ventricular (LV) pacing, and all-cause mortality at 4 years. We identified 5709 patients with de novo CRT devices; at the time of implant, 34% (n = 1959) had entirely nominal settings programmed, 40% (n = 2294) had only AV timing adjusted, 11% (n = 604) had only VV timing adjusted, and 15% (n = 852) had both AV and VV adjusted from nominal programming. Suboptimal LV pacing (<95%) during follow-up was similar across groups; however, the proportion with atrial fibrillation (AF) burden >5% was lowest in the AV-only adjusted group (17.9%) and highest in the nominal (27.7%) and VV-only adjusted (28.3%) groups. Adjusted all-cause mortality was significantly higher among patients with non-nominal AV delay >120 vs. <120 ms (adjusted heart rate (HR) 1.28, p = 0.008) but similar when using the 180-ms cutoff (adjusted HR 1.13 for >180 vs. ≤180 ms, p = 0.4). Nominal settings for de novo CRT implants are frequently altered, most commonly the AV delay. There is wide variability in reprogramming. Patients with nominal or AV-only adjustments appear to have favorable pacing and arrhythmia outcomes. Sensed AV delays less than 120 ms are associated with improved survival.

Posterior shift of the anterior papillary muscle in patients with heart failure: a potential role in the effect of cardiac resynchronization therapy.

PubMed

Hara, Tetsuya; Yamashiro, Kohei; Okajima, Katsunori; Hayashi, Takatoshi; Kajiya, Teishi

2009-11-01

The anatomical relationship between left ventricular pacing site and the anterior papillary muscle (A-PM) may have a major influence on the improvement of mitral regurgitation (MR) in cardiac resynchronization therapy (CRT). The aims of the present study were to assess the anatomical relationship between coronary veins and papillary muscles in patients with and without heart failure (HF), and to examine its contribution to the response to CRT. Sixty-one patients (36 patients with HF, 25 patients without HF) who underwent multi-detector computed tomography were studied. We measured the angle between the anterior papillary muscle and coronary veins (Ang. 1) and the angle between the anterior edge of the left ventricular free wall and A-PM (Ang. 2). Angle 1 of the posterolateral vein in the patients with HF was significantly smaller than those without HF (54.9 +/- 11.1, 68.7 +/- 15.8 degrees, respectively, P = 0.02). Supportively, Angle 2 of patients with HF was larger than that of patients without HF (100 +/- 13.0, 87.3 +/- 10.7 degrees, respectively, P < 0.01). Significant decreases in left ventricular end-diastolic diameter, the grade of MR, and brain natriuretic peptide level after 6 months of CRT were observed (P < 0.01, P = 0.04, P < 0.01, respectively) in patients with severe A-PM displacement (Ang. 2 > 100 degrees), but not in patients with Ang. 2 < 100 degrees. A-PM tends to be located in a more posterior wall in patients with HF. Displacement of A-PM may have a potential role as a predictor of the response to CRT.

Gender-Related Differences in Outcomes of Patients with Cardiac Resynchronization Therapy.

PubMed

Nevzorov, Roman; Porter, Avital; Mostov, Shanie; Kazum, Shirit; Eisen, Alon; Goldenberg, Gustavo; Iakobishvili, Zaza; Kusniec, Jairo; Golovchiner, Gregory; Strasberg, Boris; Haim, Moti

2018-05-01

Gender-related differences (GRD) exist in the outcome of patients with cardiac resynchronization therapy (CRT). To assess GRD in patients who underwent CRT. A retrospective cohort of 178 patients who were implanted with a CRT in a tertiary center 2005-2009 was analyzed. Primary outcome was 1 year mortality. Secondary endpoints were readmission and complication rates. No statistically significant difference was found in 1 year mortality rates (14.6% males vs. 11.8% females, P = 0.7) or in readmission rate (50.7% vs. 41.2%, P = 0.3). The complication rate was only numerically higher in women (14.7% vs. 5.6%, P = 0.09). Men more often had CRT-defibrillator (CRT-D) implants (63.2% vs. 35.3%, P = 0.003) and had a higher rate of ischemic cardiomyopathy (79.2% vs. 38.2%, P < 0.001). There was a trend to higher incidence of ventricular fibrillation/ventricular tachycardia in men before CRT implantation (29.9% vs. 14.7%, P = 0.07%). A higher proportion of men upgraded from implantable cardioverter defibrillator (ICD) to CRT-D, 20.8% vs. 8.8%, P = 0.047. On multivariate model, chronic renal failure was an independent predictor of 1 year mortality (hazard ratio [HR] 3.6; 95% confidence interval [95%CI] 1.4-9.5), CRT-D had a protective effect compared to CRT-pacemaker (HR 0.3, 95%CI 0.12-0.81). No GRD was found in 1 year mortality or readmission rates in patients treated with CRT. There was a trend toward a higher complication rate in females. Men were implanted more often with CRT-D and more frequently underwent upgrading of ICD to CRT-D.

The Shortest QRS Duration of an Electrocardiogram Might Be an Optimal Electrocardiographic Predictor for Response to Cardiac Resynchronization Therapy.

PubMed

Chen, Jan-Yow; Lin, Kuo-Hung; Chang, Kuan-Cheng; Chou, Che-Yi

2017-08-03

QRS duration has been associated with the response to cardiac resynchronization therapy (CRT). However, the methods for defining QRS duration to predict the outcome of CRT have discrepancies in previous reports. The aim of this study was to determine an optimal measurement of QRS duration to predict the response to CRT.Sixty-one patients who received CRT were analyzed. All patients had class III-IV heart failure, left ventricular ejection fraction not more than 35%, and complete left bundle branch block. The shortest, longest, and average QRS durations from the 12 leads of each electrocardiogram (ECG) were measured. The responses to CRT were determined using the changes in echocardiography after 6 months. Thirty-five (57.4%) patients were responders and 26 (42.6%) patients were non-responders. The pre-procedure shortest, average, and longest QRS durations and the QRS shortening (ΔQRS) of the shortest QRS duration were significantly associated with the response to CRT in a univariate logistic regression analysis (P = 0.002, P = 0.03, P = 0.04 and P = 0.04, respectively). Based on the measurement of the area under curve of the receiver operating characteristic curve, only the pre-procedure shortest QRS duration and the ΔQRS of the shortest QRS duration showed significant discrimination for the response to CRT (P = 0.002 and P = 0.038, respectively). Multivariable logistic regression showed the pre-procedure shortest QRS duration is an independent predictor for the response to CRT.The shortest QRS duration from the 12 leads of the electrocardiogram might be an optimal measurement to predict the response to CRT.

Effect of cardiac resynchronization therapy on beat-to-beat T-wave amplitude variability.

PubMed

Žižek, David; Cvijić, Marta; Tasič, Jerneja; Jan, Matevž; Frljak, Sabina; Zupan, Igor

2012-11-01

T-wave amplitude variability (TAV) is a promising non-invasive predictor of arrhythmic events in patients with dilated cardiomyopathy. We aimed to evaluate the effect of cardiac resynchronization therapy (CRT) on native TAV, its relation with left ventricular (LV) reverse remodelling and the occurrence of ventricular tachyarrhythmias (VTs). In this prospective study, we included 40 heart failure patients with left bundle branch block in sinus rhythm (25 male; 16 with ischaemic aetiology; aged 62.7 ± 9.5 years; New York Heart Association class II-IV). Echocardiographic parameters and TAV were evaluated at baseline and 6 months after implantation of CRT device combined with an implantable cardioverter-defibrillator. T-wave amplitude variability was determined by a 20-min high-resolution electrocardiogram Holter recording during native conduction. After TAV assessment, patients were monitored for 15.7 ± 5.2 months for the occurrence of VTs. Decrease in median TAV [from 40.45 μV (24.75-56.00) to 28.15 μV (20.93-37.95), P = 0.004] was observed after 6 months of CRT. However, decrease of median TAV was only noticed in patients with LV reverse remodelling [46.9 μV (27.5-70.0) to 25.8 μV (20.2-32.4), P < 0.001] and in patients without VTs [40.5 μV (27.5-55.9) to 24.4 μV (17.1-31.5), P < 0.001]. Native median TAV > 35.4 µV after 6 months of CRT had an 83% sensitivity and 93% specificity for predicting the occurrence of VTs. Decrease of TAV after CRT is associated with LV reverse remodelling and indicates a reduction of the intrinsic arrhythmogenic substrate. Median TAV after CRT had a good predicting value for VT occurrence in long-term follow-up.

Impact of myocardial viability assessed by myocardial perfusion imaging on ventricular tachyarrhythmias in cardiac resynchronization therapy.

PubMed

Žižek, David; Cvijić, Marta; Ležaić, Luka; Salobir, Barbara Gužič; Zupan, Igor

2013-12-01

The presence of myocardial fibrosis is associated with ventricular tachyarrhythmia (VT) occurrence irrespective of cardiomyopathy etiology. The aim of our study was to evaluate the impact of global and regional viability on VTs in patients undergoing cardiac resynchronization therapy (CRT). Fifty-seven patients with advanced heart failure (age 62.3 ± 10.2; 38 men; 24 ischemic etiology) were evaluated using single-photon emission computed tomography myocardial perfusion imaging before CRT defibrillator device implantation. Global myocardial viability was determined by the number of viable segments in a 20-segment model. Regional viability was calculated as the mean tracer activity in the corresponding segments at left ventricular (LV) lead position. LV lead segments were determined at implant venography using 2 projections (left anterior oblique 30 and right anterior oblique 30) of coronary sinus tributaries. Patients were followed 30 (24-34) months for the occurrence of VTs. VTs were registered in 18 patients (31.6%). Patients without VTs had significantly more viable segments (17.6 ± 2.35 vs 14.2 ± 4.0; P = .002) and higher regional myocardial viability at LV lead position (66.1% ± 10.3% vs 54.8% ± 11.4% of tracer activity; P = .001) than those with VTs. In multivariate logistic regression models, the number of viable segments (OR = 0.66; 95% confidence interval (CI) 0.53-0.85; P = .001) and regional viability (OR = 0.90; 95% CI 0.85-0.97; P = .003) were the only independent predictors of VT occurrence. Global and regional myocardial viability are independently related to the occurrence of VTs in patients after CRT.

Cardiac-resynchronization therapy in heart failure with a narrow QRS complex.

PubMed

Ruschitzka, Frank; Abraham, William T; Singh, Jagmeet P; Bax, Jeroen J; Borer, Jeffrey S; Brugada, Josep; Dickstein, Kenneth; Ford, Ian; Gorcsan, John; Gras, Daniel; Krum, Henry; Sogaard, Peter; Holzmeister, Johannes

2013-10-10

Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure with a wide QRS complex. Mechanical dyssynchrony also occurs in patients with a narrow QRS complex, which suggests the potential usefulness of CRT in such patients. We conducted a randomized trial involving 115 centers to evaluate the effect of CRT in patients with New York Heart Association class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a QRS duration of less than 130 msec, and echocardiographic evidence of left ventricular dyssynchrony. All patients underwent device implantation and were randomly assigned to have CRT capability turned on or off. The primary efficacy outcome was the composite of death from any cause or first hospitalization for worsening heart failure. On March 13, 2013, the study was stopped for futility on the recommendation of the data and safety monitoring board. At study closure, the 809 patients who had undergone randomization had been followed for a mean of 19.4 months. The primary outcome occurred in 116 of 404 patients in the CRT group, as compared with 102 of 405 in the control group (28.7% vs. 25.2%; hazard ratio, 1.20; 95% confidence interval [CI], 0.92 to 1.57; P=0.15). There were 45 deaths in the CRT group and 26 in the control group (11.1% vs. 6.4%; hazard ratio, 1.81; 95% CI, 1.11 to 2.93; P=0.02). In patients with systolic heart failure and a QRS duration of less than 130 msec, CRT does not reduce the rate of death or hospitalization for heart failure and may increase mortality. (Funded by Biotronik and GE Healthcare; EchoCRT ClinicalTrials.gov number, NCT00683696.).

Different regions of latest electrical activation during left bundle-branch block and right ventricular pacing in cardiac resynchronization therapy patients determined by coronary venous electro-anatomic mapping.

PubMed

Mafi Rad, Masih; Blaauw, Yuri; Dinh, Trang; Pison, Laurent; Crijns, Harry J; Prinzen, Frits W; Vernooy, Kevin

2014-11-01

Current targeted left ventricular (LV) lead placement strategy is directed at the latest activated region during intrinsic activation. However, cardiac resynchronization therapy (CRT) is most commonly applied by simultaneous LV and right ventricular (RV) pacing without contribution from intrinsic conduction. Therefore, targeting the LV lead to the latest activated region during RV pacing might be more appropriate. We investigated the difference in LV electrical activation sequence between left bundle-branch block (LBBB) and RV apex (RVA) pacing using coronary venous electro-anatomic mapping (EAM). Twenty consecutive CRT candidates with LBBB underwent intra-procedural coronary venous EAM during intrinsic activation and RVA pacing using EnSite NavX. Left ventricular lead placement was aimed at the latest activated region during LBBB according to current recommendations. In all patients, LBBB was associated with a circumferential LV activation pattern, whereas RVA pacing resulted in activation from the apex of the heart to the base. In 10 of 20 patients, RVA pacing shifted the latest activated region relative to LBBB. In 18 of 20 patients, the LV lead was successfully positioned in the latest activated region during LBBB. For the whole study population, LV lead electrical delay, expressed as percentage of QRS duration, was significantly shorter during RVA pacing than during LBBB (72 ± 13 vs. 82 ± 5%, P = 0.035). Right ventricular apex pacing alters LV electrical activation pattern in CRT patients with LBBB, and shifts the latest activated region in a significant proportion of these patients. These findings warrant reconsideration of the current practice of LV lead targeting for CRT. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Battery longevity from cardiac resynchronization therapy defibrillators: differences between manufacturers and discrepancies with published product performance reports.

PubMed

Alam, Mian Bilal; Munir, Muhammad Bilal; Rattan, Rohit; Adelstein, Evan; Jain, Sandeep; Saba, Samir

2017-03-01

Cardiac resynchronization therapy (CRT) is an important treatment for heart failure that requires constant ventricular pacing, placing a high energy burden on CRT defibrillators (CRT-D). Longer battery life reduces the need for device changes and associated complications, thereby affecting patient outcomes and cost of care. We therefore investigated the time to battery depletion of CRT-D from different manufacturers and compared these results with manufacturers' published product performance reports (PPRs). All CRT-D recipients at our institution between January 2008 and December 2010 were included in this study cohort. The patients were followed up to the endpoint of battery depletion and were otherwise censored at the time of death, last follow-up, or device removal for any reason other than battery depletion. A total of 621 patients [173 Boston Scientific (BSC), 391 Medtronic (MDT), and 57 St. Jude Medical (SJM)] were followed up for a median of 3.7 (IQR 1.6-5.0) years, during which time 253 (41%) devices were replaced for battery depletion. Compared with MDT devices, battery depletion was 85 and 54% less likely to happen with BSC and SJM devices, respectively (P < 0.001 for pairwise comparisons). Product performance reports from all manufacturers significantly overestimated battery longevity by more than 20% 6 years after device implantation. Large differences in CRT-D battery longevity exist between manufacturers. Industry-published PPRs significantly overestimate device longevity. These data have important implications to patients, healthcare professionals, hospitals, and third-party payers. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Prognostic role of coronary flow reserve for left ventricular functional improvement after cardiac resynchronization therapy in patients with dilated cardiomyopathy.

PubMed

Djordjevic Dikic, Ana; Nikcevic, Gabrijela; Raspopovic, Srdjan; Jovanovic, Velibor; Tesic, Milorad; Beleslin, Branko; Stepanovic, Jelena; Giga, Vojislav; Milasinovic, Goran

2014-12-01

The aim of the study was to assess the value of coronary flow reserve (CFR) for predicting improvement of left ventricular function after cardiac resynchronization therapy (CRT). Study population included 40 patients (mean age 58 ± 9 years) with heart failure (ejection fraction 25, 7 ± 5, 4%) and QRS duration of 158 ± 22 ms, planned for CRT. Before and after CRT implantation, CFR was measured non-invasively during hyperaemia induced with adenosine. Responders were defined by decrease in end-systolic volume ≥15%. Follow-up echocardiography and CFR measurements were obtained after 6 months. At baseline there was no significant difference in left ventricular ejection fraction (LVEF), QRS duration, 6 min walk test distance and coronary flow velocity at rest between responder (n = 26) vs. non-responder group (n = 14, P = ns). Before CRT implantation, responders compared with non-responders, showed a greater increase in coronary flow velocity during hyperaemia, and consequently higher CFR: 2.41 ± 0.60 vs. 1.61 ± 0.45 (P = 0.001). There was significant correlation between CFR before CRT implantation and LVEF after 6 months (r = 0.545, P = 0.001). End-diastolic, end-systolic left ventricular diameter, and CFR before CRT were predictors of LV functional improvement. By multivariate analysis, only CFR before CRT was independent predictor of left ventricular recovery in the follow-up period (P = 0.001). Our results demonstrate that preserved CFR in patients with dilated cardiomyopathy is predictive of left ventricular improvement after CRT implantation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

The impact of age and gender on cardiac resynchronization therapy outcome.

PubMed

Zardkoohi, Omeed; Nandigam, Veena; Murray, Lorne; Heist, E Kevin; Mela, Theofanie; Orencole, Mary; Ruskin, Jeremy N; Singh, Jagmeet P

2007-11-01

Cardiac resynchronization therapy (CRT) outcome varies significantly among patients. We aimed to determine the impact of age, gender, and heart failure etiology on the long-term outcome of patients receiving CRT. A total of 117 patients with drug-refractory heart failure, New York Heart Association (NYHA) Class III or IV, and a wide QRS complex, who received CRT, were followed for one year. Long-term outcome was measured as a combined end point of hospitalization for heart failure and/or all cause mortality. Efficacy of CRT was compared between men and women, between older and younger patients, and between patients with ischemic and nonischemic heart disease. Time to the primary end point was estimated by the Kaplan-Meier method and comparisons were made using the Breslow-Wilcoxon test. Baseline clinical characteristics were comparable between gender, age, and heart failure etiology subgroups. There was no significant difference in the combined end point between older versus younger (age >70, (n = 71), versus age < 70, (n = 46), P = 0.52); both genders (men, n = 91 vs women, n = 26, P = 0.46) and etiology of the cardiomyopathy (ischemic (n = 79) vs nonischemic (n = 38), P = 0.12). Substratification of the genders by the etiology of the cardiomyopathy, showed that women with ischemic cardiomyopathy (IW, n = 10) had a trend to a worse outcome compared to the other groups i.e., nonischemic women (NIW, n = 16), ischemic men (IM, n = 69), and nonischemic men (NIM, n = 22), P = 0.04. After adjusting for potential covariates, a Cox regression analysis showed no significant difference between the groups (P = 0.61). CRT outcome appears independent of age, gender, and heart failure etiology in this single institution study.

Variability of coronary venous anatomy in patients undergoing cardiac resynchronization therapy: a high-speed rotational venography study.

PubMed

Blendea, Dan; Shah, Ravi V; Auricchio, Angelo; Nandigam, Veena; Orencole, Mary; Heist, E Kevin; Reddy, Vivek Y; McPherson, Craig A; Ruskin, Jeremy N; Singh, Jagmeet P

2007-09-01

Imaging the coronary venous (CV) tree to delineate the coronary sinus and its tributaries can facilitate electrophysiological procedures, such as cardiac resynchronization therapy (CRT) and catheter ablation. Venography also allows visualization of the left atrial (LA) veins, which may be a potential conduit for ablative or pacing strategies given their proximity to foci that can trigger atrial fibrillation. The aim of this study was to provide a detailed description of CV anatomy using rotational venography in patients undergoing CRT. Coronary sinus (CS) size and the presence, size, and angulation of its tributaries were determined from the analysis of rotational CV angiograms from 51 patients (age 68 +/- 11 years; n = 12 women) undergoing CRT. The CS, posterior veins, and lateral veins were identified in 100%, 76%, and 91% of patients. Lateral veins were less prevalent in patients with a history of lateral myocardial infarction than in patients without such a history (33% vs. 96%; P = .014). The diameters of the CS and its tributaries were fairly variable (7.3-18.9 mm for CS, 1.3-10.5 mm for CS tributaries). The CS was larger in men than in women and in cases of ischemic than in cases of nonischemic cardiomyopathy (all P <.05). The vein of Marshall, the most constant LA vein, was identified in 37 patients; its diameter is 1.7 +/- 0.5 mm, and its takeoff angle is 154 degrees +/- 15 degrees , making the vein potentially accessible for cannulation. Differences in CV anatomy that are related to either gender or coronary artery disease could have important practical implications during the left ventricular lead implantation. The anatomical features of the vein of Marshall make it a feasible potential conduit for epicardial LA pacing.

Acute hemodynamic effects of right and left ventricular lead positions during the implantation of cardiac resynchronization therapy defibrillators.

PubMed

Stockinger, Jochem; Staier, Klaus; Schiebeling-Römer, Jochen; Keyl, Cornelius

2011-11-01

To evaluate the acute hemodynamic effects of different right (RV) and left ventricular (LV) pacing sites in patients undergoing the implantation of a cardiac resynchronization therapy defibrillator (CRT-D). Stroke volume index (SVI), assessed via pulse contour analysis, and dp/dt max, obtained in the abdominal aorta, were analyzed in 21 patients with New York Heart Association class III heart failure and left bundle branch block (mean ejection fraction of 24 ± 6%), scheduled for CRT-D implantation under general anesthesia. We compared the hemodynamic effects of RV apical (A), RV septal (B), and biventricular pacing using the worst (lowest SVI; C) and best (highest SVI; D) coronary sinus lead positions. Mean arterial pressure, SVI, and dp/dt max did not differ significantly between RV apical and septal pacing. Dp/dt max and SVI increased significantly during biventricular pacing (dp/dt max: B, 588 ± 160 mmHg/s; C, 651 ± 218 mmHg/s, P = 0.03 vs B; D, 690 ± 220 mmHg/s, P = 0.02 vs C; SVI: B, 33.6 ± 5.5 mL/m², C, 34.8 ± 6.1 mL/m², P = 0.08 vs B, D 36.0 ± 6.0 mL/m², P < 0.001 vs C). The best hemodynamic response was associated with lateral or inferior lead positions in 15 patients. Other LV lead positions were most effective in six patients. The optimal LV lead position varies significantly among patients and should be individually determined during CRT-D implantation. The impact of the RV stimulation site in patients with intraventricular conduction delay, undergoing CRT-D implantation, has to be investigated in further studies.

Impact of Iron Deficiency on Response to and Remodeling After Cardiac Resynchronization Therapy.

PubMed

Martens, Pieter; Verbrugge, Frederik; Nijst, Petra; Dupont, Matthias; Tang, W H Wilson; Mullens, Wilfried

2017-01-01

Iron deficiency is prevalent in heart failure with reduced ejection fraction and relates to symptomatic status, readmission, and all-cause mortality. The relation between iron status and response to cardiac resynchronization therapy (CRT) remains insufficiently elucidated. This study assesses the impact of iron deficiency on clinical response and reverse cardiac remodeling and outcome after CRT. Baseline characteristics, change in New York Heart Association functional class, reverse cardiac remodeling on echocardiography, and clinical outcome (i.e., all-cause mortality and heart failure readmissions) were retrospectively evaluated in consecutive CRT patients who had full iron status and complete blood count available at implantation, implanted at a single tertiary care center with identical dedicated multidisciplinary CRT follow-up from October 2008 to August 2015. A total of 541 patients were included with mean follow-up of 38 ± 22 months. Prevalence of iron deficiency was 56% at implantation. Patients with iron deficiency exhibited less symptomatic improvement 6 months after implantation (p value <0.001). In addition, both the decrease in left ventricular end-diastolic diameter (-3.1 vs -6.2 mm; p value = 0.011) and improvement in ejection fraction (+11% vs +15%, p value = 0.001) were significantly lower in patients with iron deficiency. Iron deficiency was significantly associated with an increased risk for heart failure admission or all-cause mortality (adjusted hazard ratio 1.718, 95% confidence interval 1.178 to 2.506), irrespectively of the presence of anemia (Hemoglobin <12 g/dl in women and <13 g/dl in men). In conclusion, iron deficiency is prevalent and affects both clinical response and reverse cardiac remodeling after CRT implantation. Moreover, it is a powerful predictor of adverse clinical outcomes in CRT. Copyright © 2016 Elsevier Inc. All rights reserved.

A cohort study of cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy.

PubMed

Martinelli Filho, Martino; de Lima Peixoto, Giselle; de Siqueira, Sérgio Freitas; Martins, Sérgio Augusto Mezzalira; Nishioka, Silvana Angelina D'ório; Pedrosa, Anísio Alexandre Andrade; Teixeira, Ricardo Alkmim; Dos Santos, Johnny Xavier; Costa, Roberto; Kalil Filho, Roberto; Ramires, José Antônio Franchini

2018-03-02

Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure. However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC). We aimed to assess the role of CRT in a cohort of patients with CCC. This retrospective study compared the outcomes of CCC patients who underwent CRT with those of dilated (DCM) and ischaemic cardiomyopathies (ICM). The primary endpoint was all-cause mortality and the secondary endpoints were the rate of non-advanced New York Heart Association (NYHA) class 12 months after CRT and echocardiographic changes evaluated at least 6 months after CRT. There were 115 patients in the CCC group, 177 with DCM, and 134 with ICM. The annual mortality rates were 25.4%, 10.4%, and 11.3%, respectively (P < 0.001). Multivariate analysis adjusted for potential confounders showed that the CCC group had a two-fold [hazard ratio 2.34 (1.47-3.71), P < 0.001] higher risk of death compared to the DCM group. The rate of non-advanced NYHA class 12 months after CRT was significantly higher in non-CCC groups than in the CCC group (DCM 74.0% vs. ICM 73.9% vs. 56.5%, P < 0.001). Chronic Chagas cardiomyopathy and ICM patients had no improvement in the echocardiographic evaluation, but patients in the DCM group had an increase in left ventricular ejection fraction and a decrease in left ventricular end-diastolic diameter. This study showed that CCC patients submitted to CRT have worse prognosis compared to patients with DCM and ICM who undergo CRT. Studies comparing CCC patients with and without CRT are warranted.

The pathophysiology of heart failure.

PubMed

Kemp, Clinton D; Conte, John V

2012-01-01

Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

F 16915 prevents heart failure-induced atrial fibrillation: a promising new drug as upstream therapy.

PubMed

Le Grand, Bruno; Letienne, Robert; Dupont-Passelaigue, Elisabeth; Lantoine-Adam, Frédérique; Longo, Frédéric; David-Dufilho, Monique; Michael, Georghia; Nishida, Kunihiro; Catheline, Daniel; Legrand, Philippe; Hatem, Stéphane; Nattel, Stanley

2014-07-01

Atrial fibrillation (AF) is a common complication of heart failure. The aim of the present study was to investigate the effects of a new pure docosahexaenoic acid derivative called F 16915 in experimental models of heart failure-induced atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a dog model of tachypacing-induced congestive heart failure and (2) in a rat model of heart failure induced by occlusion of left descending coronary artery and 2 months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean duration of AF induced by burst pacing in the dog model (989 ± 111 s in the vehicle group to 79 ± 59 s with F 16915, P < 0.01). This dose of F 16915 also significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle group versus 1/5 with F 16915, P < 0.05). In the rat model, the percentage of shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly restored after 2 months (32.6 ± 7.4 %, n = 9 vs 17.6 ± 3.4 %, n = 9 in the vehicle group, P < 0.01). F 16915 also reduced the de-phosphorylation of connexin43 from atria tissue. The present results show that treatment with F 16915 reduced the heart dilation, resynchronized the gap junction activity, and reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a promising new drug as upstream therapy for the treatment of AF in patients with heart failure.

Chronic Heart Failure: Contemporary Diagnosis and Management

PubMed Central

Ramani, Gautam V.; Uber, Patricia A.; Mehra, Mandeep R.

2010-01-01

Chronic heart failure (CHF) remains the only cardiovascular disease with an increasing hospitalization burden and an ongoing drain on health care expenditures. The prevalence of CHF increases with advancing life span, with diastolic heart failure predominating in the elderly population. Primary prevention of coronary artery disease and risk factor management via aggressive blood pressure control are central in preventing new occurrences of left ventricular dysfunction. Optimal therapy for CHF involves identification and correction of potentially reversible precipitants, target-dose titration of medical therapy, and management of hospitalizations for decompensation. The etiological phenotype, absolute decrease in left ventricular ejection fraction and a widening of QRS duration on electrocardiography, is commonly used to identify patients at increased risk of progression of heart failure and sudden death who may benefit from prophylactic implantable cardioverter-defibrillator placement with or without cardiac resynchronization therapy. Patients who transition to advanced stages of disease despite optimal traditional medical and device therapy may be candidates for hemodynamically directed approaches such as a left ventricular assist device; in selected cases, listing for cardiac transplant may be warranted. PMID:20118395

Hemodynamic Improvement in Cardiac Resynchronization Does Not Require Improvement in Left Ventricular Rotation Mechanics

PubMed Central

Ashikaga, Hiroshi; Leclercq, Christophe; Wang, Jiangxia; Kass, David A.; McVeigh, Elliot R.

2010-01-01

Background Earlier studies have yielded conflicting evidence on whether or not cardiac resynchronization therapy (CRT) improves left ventricular (LV) rotation mechanics. Methods and Results In dogs with left bundle branch block and pacing-induced heart failure (n=7), we studied the effects of CRT on LV rotation mechanics in vivo by 3-dimensional tagged magnetic resonance imaging with a temporal resolution of 14 ms. CRT significantly improved hemodynamic parameters but did not significantly change the LV rotation or rotation rate. LV torsion, defined as LV rotation of each slice with respect to that of the most basal slice, was not significantly changed by CRT. CRT did not significantly change the LV torsion rate. There was no significant circumferential regional heterogeneity (anterior, lateral, inferior, and septal) in LV rotation mechanics in either left bundle branch block with pacing-induced heart failure or CRT, but there was significant apex-to-base regional heterogeneity. Conclusions CRT acutely improves hemodynamic parameters without improving LV rotation mechanics. There is no significant circumferential regional heterogeneity of LV rotation mechanics in the mechanically dyssynchronous heart. These results suggest that LV rotation mechanics is an index of global LV function, which requires coordination of all regions of the left ventricle, and improvement in LV rotation mechanics appears to be a specific but insensitive index of acute hemodynamic response to CRT. PMID:20478988

An ontology-based annotation of cardiac implantable electronic devices to detect therapy changes in a national registry.

PubMed

Rosier, Arnaud; Mabo, Philippe; Chauvin, Michel; Burgun, Anita

2015-05-01

The patient population benefitting from cardiac implantable electronic devices (CIEDs) is increasing. This study introduces a device annotation method that supports the consistent description of the functional attributes of cardiac devices and evaluates how this method can detect device changes from a CIED registry. We designed the Cardiac Device Ontology, an ontology of CIEDs and device functions. We annotated 146 cardiac devices with this ontology and used it to detect therapy changes with respect to atrioventricular pacing, cardiac resynchronization therapy, and defibrillation capability in a French national registry of patients with implants (STIDEFIX). We then analyzed a set of 6905 device replacements from the STIDEFIX registry. Ontology-based identification of therapy changes (upgraded, downgraded, or similar) was accurate (6905 cases) and performed better than straightforward analysis of the registry codes (F-measure 1.00 versus 0.75 to 0.97). This study demonstrates the feasibility and effectiveness of ontology-based functional annotation of devices in the cardiac domain. Such annotation allowed a better description and in-depth analysis of STIDEFIX. This method was useful for the automatic detection of therapy changes and may be reused for analyzing data from other device registries.

Estrus resynchronization in ewes with unknown pregnancy status.

PubMed

Miranda, Vladinis O; Oliveira, Fernando C; Dias, Jenniffer H; Vargas Júnior, Sergio F; Goularte, Karina L; Sá Filho, Manoel F; Sá Filho, Ocilon G de; Baldassarre, Hernan; Vieira, Arnaldo D; Lucia, Thomaz; Gasperin, Bernardo G

2018-01-15

Although fixed-time artificial insemination (FTAI) protocols are available for sheep, estrus resynchronization has not been previously reported. The objectives of this study were to evaluate the effect of estrus resynchronization with exogenous progestogen on endogenous progesterone levels and to compare pregnancy rates after two consecutive estrus synchronizations in ewes. In Experiment 1, ewes (n = 20) received an intravaginal device (IVD) containing 60 mg medroxyprogesterone acetate (MPA) for 10 days. At the IVD withdrawal (D0), ewes received 250 IU eCG and were allocated into two treatments: either no further treatment (Control; n = 10) or estrus resynchronization (Resynch; n = 10) from D12 to D19. Serum progesterone (P4) levels did not differ at D12 and D19 (P > 0.05), but were greater at D15 for the Control compared with the Resynch group (P < 0.05). In experiment 2, ewes (n = 250) were submitted to a first synchronization protocol followed by estrus detection and either artificial insemination (AI) or natural mating (NM). Subsequently, ewes were divided into two groups: Control (n = 104): which received no further treatment and were bred by NM; and Resynch (n = 146): which were submitted to a second synchronization starting on D14 (first IVD withdrawal = D0) and to NM after second IVD withdrawal (D20). Cumulative pregnancy rates did not differ between the Control (67.3%, 70/104) and Resynch (62.3%, 91/146) groups. In a third experiment, ewes (n = 83) were bred by two consecutive FTAI within a 20-day interval. Pregnancy rates after the first (30.1%, 25/83) and the second FTAI (36.2%, 21/58) did not differ (P > 0.05). In conclusion, although exogenous progestogen supplementation reduced circulating levels of P4, pregnancy maintenance was unaffected. Estrus resynchronization in ewes is feasible, resulting in similar fertility after the first and the second services. The use of resynchronization coupled with artificial insemination using semen from genetically superior rams may potentially accelerate genetic improvement in sheep herds by allowing a higher differential selection compared with natural breeding. Copyright © 2017 Elsevier Inc. All rights reserved.

Cryptographic synchronization recovery by measuring randomness of decrypted data

DOEpatents

Maestas, Joseph H.; Pierson, Lyndon G.

1990-01-01

The invention relates to synchronization of encrypted data communication systems and a method which looks for any lack of pattern or intelligent information in the received data and triggers a resynchronization signal based thereon. If the encrypter/decrypter pairs are out of cryptographic synchronization, the received (decrypted) data resembles pseudorandom data. A method and system are provided for detecting such pseudorandom binary data by, for example, ones density. If the data is sufficiently random the system is resynchronized.

Changes in parameters of right ventricular function with cardiac resynchronization therapy.

PubMed

Sharma, Abhishek; Lavie, Carl J; Vallakati, Ajay; Garg, Akash; Goel, Sunny; Lazar, Jason; Fonarow, Gregg C

2017-11-01

Studies have shown that cardiac resynchronization therapy (CRT) significantly improves right ventricle (RV) size and function in patients with heart failure (HF). CRT does not lead to improvement in RV function independent of baseline clinical variables. A systematic search of studies published between 1966 to August 31, 2015 was conducted using Pub Med, CINAHL, Cochrane CENTRAL and the Web of Science databases. Studies reporting tricuspid annular plane systolic excursion (TAPSE) or RV basal strain or RV long axis diameter or RV short axis diameter or RV fractional area change (FAC), before and after CRT, were identified. A meta-analysis was performed using random effects with inverse variance method to determine the pooled mean difference in various parameters of RV function after CRT. Meta-regression analysis was performed to test the relationship between change in various parameters of RV functions after CRT and covariates- age, QRS duration, and left ventricular ejection fraction (LVEF). Thirteen studies (N=1541) were selected for final analysis. CRT therapy led to statistically significant increases in TAPSE [1.21 (95% CI 0.55-1.86; p<0.001)], RV FAC [2.26 (95% CI 0.50-4.01; p<0.001)] and basal strain [2.82 (95% CI 0.59-5.05; p<0.001)] and statistically significant decreases in mean RV long axis diameter [-2.94 (95% CI -5.07- -0.82; p=0.005)] and short axis diameter [-1.39 (95% CI -2.10- -0.67; p=0.876)] after a mean follow up period of 9 months. However, after meta-regression analysis for age, QRS duration, and baseline LVEF as covariates, there was no significant improvement in any of the parameters of RV function after CRT. There was a statistically significant improvement in TAPSE, RV basal strain, RV fractional area, RV long axis and short axis with CRT. However, improvement in these echocardiographic parameters of RV function after CRT was not independent of baseline clinical variables but statistically dependent on age, QRS duration and baseline LVEF. © 2017 Wiley Periodicals, Inc.

Association of apical rocking with long-term major adverse cardiac events in patients undergoing cardiac resynchronization therapy.

PubMed

Ghani, Abdul; Delnoy, Peter Paul H M; Ottervanger, Jan Paul; Ramdat Misier, Anand R; Smit, Jaap Jan J; Adiyaman, Ahmet; Elvan, Arif

2016-02-01

Correctly identifying patients who will benefit from cardiac resynchronization therapy (CRT) is still challenging. 'Apical rocking' is observed in asynchronously contracting ventricles and is associated with echocardiographic response to CRT. The association of apical rocking and long-term clinical outcome is however unknown at present. We assessed the predictive value of left ventricular (LV) apical rocking on a long-term clinical outcome in patients treated with CRT. Consecutive heart failure patients treated with primary indication for CRT-D between 2005 and 2009 were included in a prospective registry. Echocardiography was performed prior to CRT to assess apical rocking, defined as motion of the LV apical myocardium perpendicular to the LV long axis. Major adverse cardiac event (MACE) was defined as combined end point of cardiac death and/or heart failure hospitalization and/or appropriate therapy (ATP and/or ICD shocks). All echocardiograms were assessed by independent cardiologists, blinded for clinical data. Multivariable analyses were performed to adjust for potential confounders. Two hundred and ninety-five patients with echocardiography prior to implantation were included in the final analyses. Apical rocking was present in 45% of the study patients. Apical rocking was significantly more common in younger patients, females, patients with sinus rhythm, non-ischaemic cardiomyopathy, and in patients with LBBB and wider QRS duration. During a mean clinical follow-up of 5.2 ± 1.6 years, 92 (31%) patients reached the end point of the study (MACE). Patients with MACE had shorter QRS duration, had more ischaemic cardiomyopathy, and were more often on Amiodarone. In univariate analyses, MACE was associated with shorter QRS duration, ischaemic aetiology, and the absence of apical rocking. After multivariable analyses, apical rocking was associated with less MACE (hazards ratio, HR 0.44, 95% confidence interval, CI 0.25-0.77). Apical rocking is an independent predictor of a favourable long-term outcome in CRT-D patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Survival after shock therapy in implantable cardioverter-defibrillator and cardiac resynchronization therapy-defibrillator recipients according to rhythm shocked. The ALTITUDE survival by rhythm study.

PubMed

Powell, Brian D; Saxon, Leslie A; Boehmer, John P; Day, John D; Gilliam, F Roosevelt; Heidenreich, Paul A; Jones, Paul W; Rousseau, Matthew J; Hayes, David L

2013-10-29

This study sought to determine if the risk of mortality associated with inappropriate implantable cardioverter-defibrillator (ICD) shocks is due to the underlying arrhythmia or the shock itself. Shocks delivered from ICDs are associated with an increased risk of mortality. It is unknown if all patients who experience inappropriate ICD shocks have an increased risk of death. We evaluated survival outcomes in patients with an ICD and a cardiac resynchronization therapy defibrillator enrolled in the LATITUDE remote monitoring system (Boston Scientific Corp., Natick, Massachusetts) through January 1, 2010. First shock episode rhythms from 3,809 patients who acutely survived the initial shock were adjudicated by 7 electrophysiologists. Patients with a shock were matched to patients without a shock (n = 3,630) by age at implant, implant year, sex, and device type. The mean age of the study group was 64 ± 13 years, and 78% were male. Compared with no shock, there was an increased rate of mortality in those who received their first shock for monomorphic ventricular tachycardia (hazard ratio [HR]: 1.65, p < 0.0001), ventricular fibrillation/polymorphic ventricular tachycardia (HR: 2.10, p < 0.0001), and atrial fibrillation/flutter (HR: 1.61, p = 0.003). In contrast, mortality after first shocks due to sinus tachycardia and supraventricular tachycardia (HR: 0.97, p = 0.86) and noise/artifact/oversensing (HR: 0.91, p = 0.76) was comparable to that in patients without a shock. Compared with no shock, those who received their first shock for ventricular rhythms and atrial fibrillation had an increased risk of death. There was no significant difference in survival after inappropriate shocks for sinus tachycardia or noise/artifact/oversensing. In this study, the adverse prognosis after first shock appears to be more related to the underlying arrhythmia than to an adverse effect from the shock itself. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Left Ventricular Architecture, Long-Term Reverse Remodeling, and Clinical Outcome in Mild Heart Failure With Cardiac Resynchronization: Results From the REVERSE Trial.

PubMed

St John Sutton, Martin; Linde, Cecilia; Gold, Michael R; Abraham, William T; Ghio, Stefano; Cerkvenik, Jeffrey; Daubert, Jean-Claude

2017-03-01

This study sought to determine the effects of abnormal left ventricular (LV) architecture on cardiac remodeling and clinical outcomes in mild heart failure (HF). Cardiac resynchronization therapy (CRT) is an established treatment for HF that improves survival in part by favorably remodeling LV architecture. LV shape is a dynamic component of LV architecture on which contractile function depends. Transthoracic 2-dimensional echocardiography was used to quantify changes in LV architecture over 5 years of follow-up of patients with mild HF from the REVERSE study. REVERSE was a prospective study of patients with large hearts (LV end-diastolic dimension ≥55 mm), LV ejection fraction <40%, and QRS duration >120 ms randomly assigned to CRT-ON (n = 419) and CRT-OFF (n = 191). CRT-OFF patients were excluded from this analysis. LV dimensions, volumes, mass index, and LV ejection fraction were calculated. LV architecture was assessed using the sphericity index, as follows: (LV end-diastolic volume)/(4/3 × π × r 3 ) × 100%. LV architecture improved over time and demonstrated significant associations between LV shape, age, sex, and echocardiography metrics. Changes in LV architecture were strongly correlated with changes in LV end-systolic volume index and LV end-diastolic volume index (both p < 0.0001). Sphericity index emerged as a predictor of death and HF hospitalization in spite of the low adverse event rate. A decrease in LV end-systolic volume index >15% occurred in more than two-thirds of patients, which indicates considerable reverse remodeling. We demonstrated that change in LV architecture in patients with mild HF with CRT is associated with structural and functional remodeling. Mean LV filling pressure was elevated, and the inability to lower it was an additional predictor of HF hospitalization or death. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

LV mechanical dispersion as a predictor of ventricular arrhythmia in patients with advanced systolic heart failure : A pilot study.

PubMed

Banasik, G; Segiet, O; Elwart, M; Szulik, M; Lenarczyk, R; Kalarus, Z; Kukulski, T

2016-11-01

Myocardial mechanical dyssynchrony induced by the presence of postinfarction scar and/or conduction abnormalities in patients with a left ventricular ejection fraction (LVEF) of < 35 % may be associated with a greater propensity toward inducing serious ventricular arrhythmia [(ventricular tachycardia (VT), ventricular fibrillation (VF)] and sudden cardiac death. The assessment of regional myocardial function using tissue Doppler echocardiography (TDE) allows for noninvasive analysis of regional mechanical dysfunction (LV mechanical dispersion). The aim of this study was to evaluate the TDE-based mechanical dispersion as a potential echocardiographic predictor of VT/VF. The study group consisted of 47 consecutive ambulatory patients with implanted cardiac resynchronization therapy-defibrillator (CRT-D) devices who were divided into two groups: Group 1 (n = 29) comprised patients with recorded episodes of VT/VF, in whom baseline TDE data were available, and group 2 (n = 18) comprised patients without registered VT/VF in the device memory within 4 years after implantation. LV mechanical dispersion was defined as the standard deviation of the time measured from the beginning of the QRS complex to the peak longitudinal strain in apical four-chamber and two-chamber views. A retrospective quantitative assessment of LV regional deformation was based on the color tissue velocity recordings. The average time to event after implantation was 345 days. Patients with electrical events demonstrated greater mechanical dispersion: 99.14 ± 33.60 vs. 72.98 ± 19.70, p=0.002. During the 4-year follow-up, patients with documented VT/VF were characterized by significantly higher LV mechanical dispersion as compared with patients without electrical events. Measurement of LV mechanical dispersion might be helpful in determining the risk of sudden cardiac death.

Causes and prevention of sudden cardiac death in the elderly.

PubMed

Tung, Patricia; Albert, Christine M

2013-03-01

Sudden cardiac death (SCD) is a major cause of mortality in elderly individuals owing to a high prevalence of coronary heart disease, systolic dysfunction, and congestive heart failure (CHF). Although the incidence of SCD increases with age, the proportion of cardiac deaths that are sudden decreases owing to high numbers of other cardiac causes of death in elderly individuals. Implantable cardioverter-defibrillator (ICD) therapy has been demonstrated to improve survival and prevent SCD in selected patients with systolic dysfunction and CHF. However, ICD therapy in elderly patients might not be effective because of a greater rate of pulseless electrical activity underlying SCD and other competing nonarrhythmic causes of death in this population. Although under-represented in randomized trials of ICD use, elderly patients comprise a substantial proportion of the population that qualifies for and receives an ICD for primary prevention under current guidelines. Cardiac resynchronization therapy (CRT), which has been demonstrated to reduce mortality in selected populations with heart failure, is also more commonly used in this group of patients than in younger individuals. In this Review, we examine the causes of SCD in elderly individuals, and discuss the existing evidence for effectiveness of ICD therapy and CRT in this growing population.

Dual- versus single-coil implantable defibrillator leads: review of the literature.

PubMed

Neuzner, Jörg; Carlsson, Jörg

2012-04-01

The preferred use of dual-coil implantable defibrillator lead systems in current implantable defibrillator therapy is likely based on data showing statistically lower defibrillation thresholds with dual-coil defibrillator lead systems. The following review will summarize the clinical data for dual- versus single-coil defibrillator leads in the left and right pectoral implant locations, and will then discuss the clinical implications of single- versus dual-coil usage for atrial defibrillation, venous complications, and the risks associated with lead extraction. It will be noted that there are no comparative clinical studies on the use and outcomes of single- versus dual-coil lead systems in implantable defibrillator therapy over a long-term follow-up. The limited long-term reliability of defibrillator leads is a major concern in implantable defibrillator and cardiac resynchronization therapy. A simpler single-coil defibrillator lead system may improve the long-term performance of implanted leads. Furthermore, the superior vena cava coil is suspected to increase interventional risk in transvenous lead extraction. Therefore, the need for objective data on extractions and complications will be emphasized.

Cardiac Resynchronization Therapy and phase resetting of the sinoatrial node: A conjecture

NASA Astrophysics Data System (ADS)

Cantini, Federico; Varanini, Maurizio; Macerata, Alberto; Piacenti, Marcello; Morales, Maria-Aurora; Balocchi, Rita

2007-03-01

Congestive heart failure is a severe chronic disease often associated with disorders that alter the mechanisms of excitation-contraction coupling that may result in an asynchronous left ventricular motion which may further impair the ability of the failing heart to eject blood. In recent years a therapeutic approach to resynchronize the ventricles (cardiac resynchronization therapy, CRT) has been performed through the use of a pacemaker device able to provide atrial-based biventricular stimulation. Atrial lead senses the spontaneous occurrence of cells depolarization and sends the information to the generator which, in turn, after a settled delay [atrioventricular (AV) delay], sends electrical impulses to both ventricles to stimulate their synchronous contraction. Recent studies performed on heart rate behavior of chronically implanted patients at different epochs after implantation have shown that CRT can lead to sustained overall improvement of heart function with a reduction in morbidity and mortality. At this moment, however, there are no studies about CRT effects on spontaneous heart activity of chronically implanted patients. We performed an experimental study in which the electrocardiographic signal of five subjects under chronic CRT was recorded during the activity of the pacemaker programmed at different AV delays and under spontaneous cardiac activity after pacemaker deactivation. The different behavior of heart rate variability during pacemaker activity and after pacemaker deactivation suggested the hypothesis of a phase resetting mechanism induced by the pacemaker stimulus on the sinoatrial (SA) node, a phenomenon already known in literature for aggregate of cardiac cells, but still unexplored in vivo. The constraints imposed by the nature of our study (in vivo tests) made it impossible to plan an experiment to prove our hypothesis directly. We therefore considered the best attainable result would be to prove the accordance of our data to the conjecture through the use of models and physical considerations. We first used the data of literature on far-field effects of cardiac defibrillators to prove that the pacemaker impulses delivered to the two ventricles were able to induce modifications in membrane voltage at the level of the SA node. To simulate a phase resetting mechanism of the SA node, we used a Van der Pol modified model to allow the possibility of changing the refractory period and the firing frequency of the cells separately. With appropriate parameters of the model we reproduced phase response curves that can account for our experimental data. Furthermore, the simulated curves closely resemble the functional form proposed in literature for perturbed aggregate of cardiac cells. Despite the small sample of subjects investigated and the limited number of ECG recordings at different AV delays, we think we have proved the plausibility of the proposed conjecture.

Differentiating Electromechanical From Non-Electrical Substrates of Mechanical Discoordination to Identify Responders to Cardiac Resynchronization Therapy.

PubMed

Lumens, Joost; Tayal, Bhupendar; Walmsley, John; Delgado-Montero, Antonia; Huntjens, Peter R; Schwartzman, David; Althouse, Andrew D; Delhaas, Tammo; Prinzen, Frits W; Gorcsan, John

2015-09-01

Left ventricular (LV) mechanical discoordination, often referred to as dyssynchrony, is often observed in patients with heart failure regardless of QRS duration. We hypothesized that different myocardial substrates for LV mechanical discoordination exist from (1) electromechanical activation delay, (2) regional differences in contractility, or (3) regional scar and that we could differentiate electromechanical substrates responsive to cardiac resynchronization therapy (CRT) from unresponsive non-electrical substrates. First, we used computer simulations to characterize mechanical discoordination patterns arising from electromechanical and non-electrical substrates and accordingly devise the novel systolic stretch index (SSI), as the sum of posterolateral systolic prestretch and septal systolic rebound stretch. Second, 191 patients with heart failure (QRS duration ≥120 ms; LV ejection fraction ≤35%) had baseline SSI quantified by automated echocardiographic radial strain analysis. Patients with SSI≥9.7% had significantly less heart failure hospitalizations or deaths 2 years after CRT (hazard ratio, 0.32; 95% confidence interval, 0.19-0.53; P<0.001) and less deaths, transplants, or LV assist devices (hazard ratio, 0.28; 95% confidence interval, 0.15-0.55; P<0.001). Furthermore, in a subgroup of 113 patients with intermediate electrocardiographic criteria (QRS duration of 120-149 ms or non-left bundle branch block), SSI≥9.7% was independently associated with significantly less heart failure hospitalizations or deaths (hazard ratio, 0.41; 95% confidence interval, 0.23-0.79; P=0.004) and less deaths, transplants, or LV assist devices (hazard ratio, 0.27; 95% confidence interval, 0.12-0.60; P=0.001). Computer simulations differentiated patterns of LV mechanical discoordination caused by electromechanical substrates responsive to CRT from those related to regional hypocontractility or scar unresponsive to CRT. The novel SSI identified patients who benefited more favorably from CRT, including those with intermediate electrocardiographic criteria, where CRT response is less certain by ECG alone. © 2015 American Heart Association, Inc.

Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy.

PubMed

Foley, Paul W X; Stegemann, Berthold; Ng, Kelvin; Ramachandran, Sud; Proudler, Anthony; Frenneaux, Michael P; Ng, Leong L; Leyva, Francisco

2009-11-01

The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) predicts mortality and morbidity after cardiac resynchronization therapy (CRT). Growth differentiation factor-15, a transforming growth factor-beta-related cytokine which is up-regulated in cardiomyocytes via multiple stress pathways, predicts mortality in patients with heart failure treated pharmacologically. Growth differentiation factor-15 was measured before and 360 days (median) after implantation in 158 patients with heart failure [age 68 +/- 11 years (mean +/- SD), left ventricular ejection fraction (LVEF) 23.1 +/- 9.8%, New York Class Association (NYHA) class III (n = 117) or IV (n = 41), and QRS 153.9 +/- 28.2 ms] undergoing CRT and followed up for a maximum of 5.4 years for events. In a stepwise Cox proportional hazards model with bootstrapping, adopting log GDF-15, log NT pro-BNP, LVEF, and NYHA class as independent variables, only log GDF-15 [hazard ratio (HR), 3.76; P = 0.0049] and log NT pro-BNP (HR, 2.12; P = 0.0171) remained in the final model. In the latter, the bias-corrected slope was 0.85, the optimism (O) was -0.06, and the c-statistic was 0.74, indicating excellent internal validity. In univariate analyses, log GDF-15 [HR, 5.31; 95% confidence interval (CI), 2.31-11.9; likelihood ratio (LR) chi(2) = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55-5.26; LR chi(2) = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91-17.5; LR chi(2) = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR chi(2) for all endpoints. Pre-implant GDF-15 is a strong predictor of mortality and morbidity after CRT, independent of NT pro-BNP. The predictive value of these analytes is enhanced by combined measurement.

Longevity of implantable cardioverter-defibrillators for cardiac resynchronization therapy in current clinical practice: an analysis according to influencing factors, device generation, and manufacturer.

PubMed

Landolina, Maurizio; Curnis, Antonio; Morani, Giovanni; Vado, Antonello; Ammendola, Ernesto; D'onofrio, Antonio; Stabile, Giuseppe; Crosato, Martino; Petracci, Barbara; Ceriotti, Carlo; Bontempi, Luca; Morosato, Martina; Ballari, Gian Paolo; Gasparini, Maurizio

2015-08-01

Device replacement at the time of battery depletion of implantable cardioverter-defibrillators (ICDs) may carry a considerable risk of complications and engenders costs for healthcare systems. Therefore, ICD device longevity is extremely important both from a clinical and economic standpoint. Cardiac resynchronization therapy defibrillators (CRT-D) battery longevity is shorter than ICDs. We determined the rate of replacements for battery depletion and we identified possible determinants of early depletion in a series of patients who had undergone implantation of CRT-D devices. We retrieved data on 1726 consecutive CRT-D systems implanted from January 2008 to March 2010 in nine centres. Five years after a successful CRT-D implantation procedure, 46% of devices were replaced due to battery depletion. The time to device replacement for battery depletion differed considerably among currently available CRT-D systems from different manufacturers, with rates of batteries still in service at 5 years ranging from 52 to 88% (log-rank test, P < 0.001). Left ventricular lead output and unipolar pacing configuration were independent determinants of early depletion [hazard ratio (HR): 1.96; 95% 95% confidence interval (CI): 1.57-2.46; P < 0.001 and HR: 1.58, 95% CI: 1.25-2.01; P < 0.001, respectively]. The implantation of a recent-generation device (HR: 0.57; 95% CI: 0.45-0.72; P < 0.001), the battery chemistry and the CRT-D manufacturer (HR: 0.64; 95% CI: 0.47-0.89; P = 0.008) were additional factors associated with replacement for battery depletion. The device longevity at 5 years was 54%. High left ventricular lead output and unipolar pacing configuration were associated with early battery depletion, while recent-generation CRT-Ds displayed better longevity. Significant differences emerged among currently available CRT-D systems from different manufacturers. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Significance of change in serum bilirubin in predicting left ventricular reverse remodeling and outcomes in heart failure patients with cardiac resynchronization therapy.

PubMed

Hosoda, Junya; Ishikawa, Toshiyuki; Matsumoto, Katsumi; Iguchi, Kohei; Matsushita, Hirooki; Ogino, Yutaka; Taguchi, Yuka; Sugano, Teruyasu; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi

2017-11-01

Research on the correlation of serum bilirubin level with cardiac function as well as outcomes in heart failure patients with cardiac resynchronization therapy (CRT) has not yet been reported. The aim of this study was to analyze the relationship between change in serum bilirubin level and left ventricular reverse remodeling, and also to clarify the impact of bilirubin change on clinical outcomes in CRT patients. We evaluated 105 consecutive patients who underwent CRT. Patients who had no serum total-bilirubin data at both baseline and 3-9 months' follow-up or had died less than 3 months after CRT implantation were excluded. Accordingly, a total of 69 patients were included in the present analysis. The patients were divided into two groups: decreased bilirubin group (serum total-bilirubin level at follow-up≤that at baseline; n=48) and increased bilirubin group (serum total-bilirubin level at follow-up>that at baseline; n=21). Mean follow-up period was 39.3 months. In the decreased bilirubin group, mean left ventricular end-systolic diameter decreased from 54.5mm to 50.2mm (p=0.001) and mean left ventricular ejection fraction increased significantly from 29.8% to 37.0% (p=0.001). In the increased bilirubin group, there was no significant change in echocardiographic parameters from baseline to follow-up. In Kaplan-Meyer analysis, cardiac mortality combined with heart failure hospitalization in the increased bilirubin group was significantly higher than that in the decreased bilirubin group (log-rank p=0.018). Multivariate Cox regression analysis revealed that increased bilirubin was an independent predictor of cardiac mortality combined with heart failure hospitalization (OR=2.66, p=0.023). The change in serum bilirubin is useful for assessment of left ventricular reverse remodeling and prediction of outcomes in heart failure patients with CRT. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Super-response to cardiac resynchronization therapy may predict late phrenic nerve stimulation.

PubMed

Juliá, Justo; López-Gil, María; Fontenla, Adolfo; Lozano, Álvaro; Villagraz, Lola; Salguero, Rafael; Arribas, Fernando

2017-11-22

Changes in the anatomical relationship between left phrenic nerve and coronary veins may occur due to the reverse remodelling observed in super-responders to cardiac resynchronization therapy (CRT) and might be the underlying mechanism in patients developing late-onset phrenic nerve stimulation (PNS) without evidence of lead dislodgement (LD). In this study, we sought to evaluate the role of super-response (SR) to CRT as a potential predictor of late-onset PNS. Consecutive patients implanted with a left ventricular (LV) lead in a single centre were retrospectively analysed. Phrenic nerve stimulation was classified as 'early' when it occurred within 3 months of implantation and 'late' for occurrences thereafter. 'Late' PNS was considered related to LD (LD-PNS) when LV threshold differed by > 1 V or impedance >250 Ω from baseline values or in case of radiological displacement. Cases not meeting the former criteria were classified as 'non-LD-PNS'. Super-response was defined as a decrease ≥30% of the left ventricluar end-systolic volume at 1-year echocardiography. At 32 ± 7 months follow-up, PNS occurred in 20 of 139 patients. Late non-LD-PNS incidence was significantly higher in the SR group (8/61; 13.1%) when compared with the non-SR (1/78; 1.3%) (P = 0.010). Super-response remained the only predictor of non-LD-PNS at multivariate analysis (odds ratio: 11.62, 95% confidence interval 1.41-95.68, P = 0.023). Incidence of late non-LD-PNS is higher among SR to CRT, suggesting a potential role of the changes in the anatomical relationship between left phrenic nerve and coronary veins. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Impact of cardiac resynchronization therapy on inflammatory biomarkers and cardiac remodeling: The paradox of functional and echocardiographic response.

PubMed

Almeida-Morais, Luís; Abreu, Ana; Oliveira, Mário; Silva Cunha, Pedro; Rodrigues, Inês; Portugal, Guilherme; Rio, Pedro; Soares, Rui; Mota Carmo, Miguel; Cruz Ferreira, Rui

2018-02-01

Response to cardiac resynchronization therapy (CRT) can currently be assessed by clinical or echocardiographic criteria, and there is no strong evidence supporting the use of one rather than the other. Reductions in B-type natriuretic peptide (BNP) and C-reactive protein (CRP) have been shown to be associated with CRT response. This study aims to assess variation in BNP and CRP six months after CRT and to correlate this variation with criteria of functional and echocardiographic response. Patients undergoing CRT were prospectively enrolled between 2011 and 2014. CRT response was defined by echocardiography (15% reduction in left ventricular end-systolic volume) and by cardiopulmonary exercise testing (10% increase in peak oxygen consumption) from baseline to six months after device implantation. A total of 115 patients were enrolled (68.7% male, mean age 68.6±10.5 years). Echocardiographic response was seen in 51.4% and 59.2% were functional responders. There was no statistical correlation between the two. Functional response was associated with a significantly greater reduction in BNP (-167.6±264.1 vs. -24.9±269.4 pg/ml; p=0.044) and CRP levels (-1.6±4.4 vs. 2.4±9.9 mg/l; p=0.04). Nonetheless, a non-significant reduction in BNP and CRP was observed in echocardiographic responders (BNP -144.7±260.2 vs. -66.1±538.2 pg/ml and CRP -7.1±24.3 vs. 0.8±10.3 mg/l; p>0.05). An increase in exercise capacity after CRT implantation is associated with improvement in myocardial remodeling and inflammatory biomarkers. This finding highlights the importance of improvement in functional capacity after CRT implantation, not commonly considered a criterion of CRT response. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

The arterial baroreflex effectiveness index in risk stratification of chronic heart failure patients who are candidates for cardiac resynchronization therapy.

PubMed

Fernandes Serôdio, João; Martins Oliveira, Mário; Matoso Laranjo, Sérgio; Tavares, Cristiano; Silva Cunha, Pedro; Abreu, Ana; Branco, Luísa; Alves, Sandra; Rocha, Isabel; Cruz Ferreira, Rui

2016-06-01

Baroreflex function is an independent marker of prognosis in heart failure (HF). However, little is known about its relation to response to cardiac resynchronization therapy (CRT). The aim of this study is to assess arterial baroreflex function in HF patients who are candidates for CRT. The study population consisted of 25 patients with indication for CRT, aged 65±10 years, NYHA functional class ≥III in 52%, QRS width 159±15 ms, left ventricular ejection fraction (LVEF) 29±5%, left ventricular end-systolic volume (LVESV) 150±48 ml, B-type natriuretic peptide (BNP) 357±270 pg/ml, and peak oxygen consumption (peak VO2) 18.4±5.0 ml/kg/min. An orthostatic tilt test was performed to assess the baroreflex effectiveness index (BEI) by the sequence method. This group was compared with 15 age-matched healthy individuals. HF patients showed a significantly depressed BEI during tilt (31±12% vs. 49±18%, p=0.001). A lower BEI was associated with higher BNP (p=0.038), lower peak VO2 (p=0.048), and higher LVESV (p=0.031). By applying a cut-off value of 25% for BEI, two clusters of patients were identified: lower risk cluster (BEI >25%) QRS 153 ms, LVESV 129 ml, BNP 146 pg/ml, peak VO2 19.0 ml/kg/min; and higher risk cluster (IEB ≤25%) QRS 167 ms, LVESV 189 ml, BNP 590 pg/ml, peak VO2 16.2 ml/kg/min. Candidates for CRT show depressed arterial baroreflex function. Lower BEI was observed in high-risk HF patients. Baroreflex function correlated closely with other clinical HF parameters. Therefore, BEI may improve risk stratification in HF patients undergoing CRT. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Does permanent atrial fibrillation modify response to cardiac resynchronization therapy in heart failure patients?

PubMed

Abreu, Ana; Oliveira, Mário; Silva Cunha, Pedro; Santa Clara, Helena; Portugal, Guilherme; Gonçalves Rodrigues, Inês; Santos, Vanessa; Morais, Luís; Selas, Mafalda; Soares, Rui; Branco, Luísa; Ferreira, Rui; Mota Carmo, Miguel

2017-10-01

The benefits of cardiac resynchronization therapy (CRT) documented in heart failure (HF) may be influenced by atrial fibrillation (AF). We aimed to compare CRT response in patients in AF and in sinus rhythm (SR). We prospectively studied 101 HF patients treated by CRT. Rates of clinical, echocardiographic and functional response, baseline NYHA class and variation, left ventricular ejection fraction, volumes and mass, atrial volumes, cardiopulmonary exercise test (CPET) duration (CPET dur), peak oxygen consumption (VO 2 max) and ventilatory efficiency (VE/VCO 2 slope) were compared between AF and SR patients, before and at three and six months after implantation of a CRT device. All patients achieved ≥95% biventricular pacing, and 5.7% underwent atrioventricular junction ablation. Patients were divided into AF (n=35) and SR (n=66) groups; AF patients were older, with larger atrial volumes and lower CPET dur and VO 2 max before CRT. The percentages of clinical and echocardiographic responders were similar in the two groups, but there were more functional responders in the AF group (71% vs. 39% in SR patients; p=0.012). In SR patients, left atrial volume and left ventricular mass were significantly reduced (p=0.015 and p=0.021, respectively), whereas in AF patients, CPET dur (p=0.003) and VO 2 max (p=0.001; 0.083 age-adjusted) showed larger increases. Clinical and echocardiographic response rates were similar in SR and AF patients, with a better functional response in AF. Improvement in left ventricular function and volumes occurred in both groups, but left ventricular mass reduction and left atrial reverse remodeling were seen exclusively in SR patients (ClinicalTrials.gov identifier: NCT02413151; FCT code: PTDC/DES/120249/2010). Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Influence of automatic frequent pace-timing adjustments on effective left ventricular pacing during cardiac resynchronization therapy.

PubMed

Varma, Niraj; Stadler, Robert W; Ghosh, Subham; Kloppe, Axel

2017-05-01

Cardiac resynchronization therapy (CRT) requires effective left ventricular (LV) pacing (i.e. sufficient energy and appropriate timing to capture). The AdaptivCRT™ (aCRT) algorithm serves to maintain ventricular fusion during LV or biventricular pacing. This function was tested by comparing the morphological consistency of ventricular depolarizations and percentage effective LV pacing in CRT patients randomized to aCRT vs. echo-optimization. Continuous recordings (≥20 h) of unipolar LV electrograms from aCRT (n = 38) and echo-optimized patients (n = 22) were analysed. Morphological consistency was determined by the correlation coefficient between each beat and a template beat. Effective LV pacing of paced beats was assessed by algorithmic analysis of negative initial EGM deflection in each evoked response. The %CRT pacing delivered, %effective LV pacing (i.e. % of paced beats with effective LV pacing), and overall %effective CRT (i.e. product of %CRT pacing and %effective LV pacing) were compared between aCRT and echo-optimized patients. Demographics were similar between groups. The mean correlation coefficient between individual beats and template was greater for aCRT (0.96 ± 0.03 vs. 0.91 ± 0.13, P = 0.07). Although %CRT pacing was similar for aCRT and echo-optimized (median 97.4 vs. 98.6%, P = 0.14), %effective LV pacing was larger for aCRT [99.6%, (99.1%, 99.9%) vs. 94.3%, (24.3%, 99.8%), P=0.03]. For aCRT vs. echo-optimized groups, the proportions of patients with ≥90% effective LV pacing was 92 vs. 55% (P = 0.002), and with ≥90% effective CRT was 79 vs. 45%, respectively (P = 0.018). AdaptivCRT™ significantly increased effective LV pacing over echo-optimized CRT. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Electrical remodeling reflected by QRS and T vector changes following cardiac resynchronization therapy is related to survival in heart failure patients with left bundle branch block.

PubMed

Floré, V; Bartunek, J; Goethals, M; Verstreken, S; Timmermans, W; De Pauw, F; Van Bockstal, K; Vanderheyden, M

2015-01-01

We investigated changes in electrocardiographic spatial QRS and T vectors as markers of electrical remodeling before and after cardiac resynchronization therapy (CRT) and their association with altered outcome. In 41 patients with LBBB, ECGpost was recorded during intrinsic rhythm after interrupting CRT pacing and compared to the pre-implant ECGpre and the ECG during CRT (ECGCRT). Mean spatial angles between QRS and T vectors were determined with the Kors matrix conversion. Left ventricular ejection fraction (LVEF) was determined with nuclear isotope ventriculography before CRT implantation (LVEFpre) and at inclusion (LVEFpost). Following CRT, LVEF improved significantly from 26 ± 10 to 36 ± 14% (p=0.01). Duration of QRSpre (168 ± 15 ms) was not different from QRSpost (166 ± 15 ms). A smaller angle between QRSCRT and Tpost was related to a greater angle between Tpre and Tpost (Pearson's R -0.61 - p<0.001). During follow-up (30 ± 2 months) 9 patients (22%) died. Univariate Cox regression revealed higher mortality in the patients with lower LVEFpost (HR 1.10, p=0.01), a larger angle QRSCRTTpost (HR 1.03, p=0.03), a smaller angle QRSpreQRSpost (HR 0.97, p=0.03) and smaller angle TpreTpost (HR 0.95, p<0.01). After adjusting for LVEFpost, only smaller angle TpreTpost was associated with mortality (HR 0.96, p=0.03). Electrical remodeling can be quantified by measuring the angles between spatial QRS and T vectors before, during and after CRT. In absence of QRS duration changes, more extensive electrical remodeling is associated with a significantly better survival. QRS and T vector changes deserve further investigation to better understand the individual response to CRT. Copyright © 2015 Elsevier Inc. All rights reserved.

Accuracy of computer-calculated and manual QRS duration assessments: Clinical implications to select candidates for cardiac resynchronization therapy.

PubMed

De Pooter, Jan; El Haddad, Milad; Stroobandt, Roland; De Buyzere, Marc; Timmermans, Frank

2017-06-01

QRS duration (QRSD) plays a key role in the field of cardiac resynchronization therapy (CRT). Computer-calculated QRSD assessments are widely used, however inter-manufacturer differences have not been investigated in CRT candidates. QRSD was assessed in 377 digitally stored ECGs: 139 narrow QRS, 140 LBBB and 98 ventricular paced ECGs. Manual QRSD was measured as global QRSD, using digital calipers, by two independent observers. Computer-calculated QRSD was assessed by Marquette 12SL (GE Healthcare, Waukesha, WI, USA) and SEMA3 (Schiller, Baar, Switzerland). Inter-manufacturer differences of computer-calculated QRSD assessments vary among different QRS morphologies: narrow QRSD: 4 [2-9] ms (median [IQR]), p=0.010; LBBB QRSD: 7 [2-10] ms, p=0.003 and paced QRSD: 13 [6-18] ms, p=0.007. Interobserver differences of manual QRSD assessments measured: narrow QRSD: 4 [2-6] ms, p=non-significant; LBBB QRSD: 6 [3-12] ms, p=0.006; paced QRSD: 8 [4-18] ms, p=0.001. In LBBB ECGs, intraclass correlation coefficients (ICCs) were comparable for inter-manufacturer and interobserver agreement (ICC 0.830 versus 0.837). When assessing paced QRSD, manual measurements showed higher ICC compared to inter-manufacturer agreement (ICC 0.902 versus 0.776). Using guideline cutoffs of 130ms, up to 15% of the LBBB ECGs would be misclassified as <130ms or ≥130ms by at least one method. Using a cutoff of 150ms, this number increases to 33% of ECGs being misclassified. However, by combining LBBB-morphology and QRSD, the number of misclassified ECGs can be decreased by half. Inter-manufacturer differences in computer-calculated QRSD assessments are significant and may compromise adequate selection of individual CRT candidates when using QRSD as sole parameter. Paced QRSD should preferentially be assessed by manual QRSD measurements. Copyright © 2017 Elsevier B.V. All rights reserved.

Economic impact of longer battery life of cardiac resynchronization therapy defibrillators in Sweden.

PubMed

Gadler, Fredrik; Ding, Yao; Verin, Nathalie; Bergius, Martin; Miller, Jeffrey D; Lenhart, Gregory M; Russell, Mason W

2016-01-01

The objective of this study was to quantify the impact that longer battery life of cardiac resynchronization therapy defibrillator (CRT-D) devices has on reducing the number of device replacements and associated costs of these replacements from a Swedish health care system perspective. An economic model based on real-world published data was developed to estimate cost savings and avoided device replacements for CRT-Ds with longer battery life compared with devices with industry-standard battery life expectancy. Base-case comparisons were performed among CRT-Ds of three manufacturers - Boston Scientific Corporation, St. Jude Medical, and Medtronic - over a 6-year time horizon, as per the available clinical data. As a sensitivity analysis, we evaluated CRT-Ds as well as single-chamber implantable cardioverter defibrillator (ICD-VR) and dual-chamber implantable cardioverter defibrillator (ICD-DR) devices over a longer 10-year period. All costs were in 2015 Swedish Krona (SEK) discounted at 3% per annum. Base-case analysis results show that up to 603 replacements and up to SEK 60.4 million cumulative-associated costs could be avoided over 6 years by using devices with extended battery life. The pattern of savings over time suggests that savings are modest initially but increase rapidly beginning in the third year of follow-up with each year's cumulative savings two to three times the previous year. Evaluating CRT-D, ICD-VR, and ICD-DR devices together over a longer 10-year period, the sensitivity analysis showed 2,820 fewer replacement procedures and associated cost savings of SEK 249.3 million for all defibrillators with extended battery life. Extended battery life is likely to reduce device replacements and associated complications and costs, which may result in important cost savings and a more efficient use of health care resources as well as a better quality of life for heart failure patients in Sweden.

Survival After Rate-Responsive Programming in Patients With Cardiac Resynchronization Therapy-Defibrillator Implants Is Associated With a Novel Parameter: The Heart Rate Score.

PubMed

Olshansky, Brian; Richards, Mark; Sharma, Arjun; Wold, Nicholas; Jones, Paul; Perschbacher, David; Wilkoff, Bruce L

2016-08-01

Rate-responsive pacing (DDDR) versus nonrate-responsive pacing (DDD) has shown no survival benefit for patients undergoing cardiac resynchronization therapy defibrillator (CRT-D) implants. The heart rate score (HRSc), an indicator of heart rate variation, may predict survival. We hypothesized that high-risk HRSc CRT-D patients will have improved survival with DDDR versus DDD alone. All CRT-D patients in LATITUDE remote monitoring (2006-2011), programmed DDD, had HRSc calculated at first data upload after implant (median 1.4 months). Patients subsequently reprogrammed to DDDR 7.6 median months later were compared with a propensity-matched DDD group and followed for 21.4 median months by remote monitoring. Data were adjusted for age, sex, lower rate limit, percent atrial pacing, percent biventricular pacing, and implant year. The social security death index was used to identify deaths. Remote monitoring provided programming and histogram data. DDDR programming in CRT-D patients was associated with improved survival (adjusted hazard ratio =0.77; P<0.001). However, only those with baseline HRSc ≥70% (2308/6164) had improved HRSc with DDDR (from 88±9% to 78±15%; P<0.001) and improved survival (hazard ratio =0.74; P<0.001). Patients with a high baseline HRSc and significant improvement over time were more likely to survive (hazard ratio =0.63; P=0.006). For patients with HRSc <70%, DDDR reprogramming increased the HRSc from 46±11% to 50±15% (P<0.001); survival did not change. The HRSc did not change with DDD pacing over time. In CRT-D patients with HRSc ≥70%, DDDR reprogramming improved the HRSc and was associated with survival. Patients with lower HRSc had no change in survival with DDDR programming. © 2016 American Heart Association, Inc.

Association of intraventricular mechanical dyssynchrony with response to cardiac resynchronization therapy in heart failure patients with a narrow QRS complex

PubMed Central

van Bommel, Rutger J.; Tanaka, Hidekazu; Delgado, Victoria; Bertini, Matteo; Borleffs, Carel Jan Willem; Ajmone Marsan, Nina; Holzmeister, Johannes; Ruschitzka, Frank; Schalij, Martin J.; Bax, Jeroen J.; Gorcsan, John

2010-01-01

Aims Current criteria for cardiac resynchronization therapy (CRT) are restricted to patients with a wide QRS complex (>120 ms). Overall, only 30% of heart failure patients demonstrate a wide QRS complex, leaving the majority of heart failure patients without this treatment option. However, patients with a narrow QRS complex exhibit left ventricular (LV) mechanical dyssynchrony, as assessed with echocardiography. To further elucidate the possible beneficial effect of CRT in heart failure patients with a narrow QRS complex, this two-centre, non-randomized observational study focused on different echocardiographic parameters of LV mechanical dyssynchrony reflecting atrioventricular, interventricular and intraventricular dyssynchrony, and the response to CRT in these patients. Methods and results A total of 123 consecutive heart failure patients with a narrow QRS complex (<120 ms) undergoing CRT was included at two centres. Several widely accepted measures of mechanical dyssynchrony were evaluated: LV filling ratio (LVFT/RR), LV pre-ejection time (LPEI), interventricular mechanical dyssynchrony (IVMD), opposing wall delay (OWD), and anteroseptal posterior wall delay with speckle tracking (ASPWD). Response to CRT was defined as a reduction ≥15% in left ventricular end-systolic volume at 6 months follow-up. Measures of dyssynchrony can frequently be observed in patients with a narrow QRS complex. Nonetheless, for LVFT/RR, LPEI, and IVMD, presence of predefined significant dyssynchrony is <20%. Significant intraventricular dyssynchrony is more widely observed in these patients. With receiver operator characteristic curve analyses, both OWD and ASPWD demonstrated usefulness in predicting response to CRT in narrow QRS patients with a cut-off value of 75 and 107 ms, respectively. Conclusion Mechanical dyssynchrony can be widely observed in heart failure patients with a narrow QRS complex. In particular, intraventricular measures of mechanical dyssynchrony may be useful in predicting LV reverse remodelling at 6 months follow-up in heart failure patients with a narrow QRS complex, but with more stringent cut-off values than currently used in ‘wide’ QRS patients. PMID:20864484

Usefulness of high-speed rotational coronary venous angiography during cardiac resynchronization therapy.

PubMed

Blendea, Dan; Mansour, Moussa; Shah, Ravi V; Chung, Jeffrey; Nandigam, Veena; Heist, E Kevin; Mela, Theofanie; Reddy, Vivek Y; Manzke, Robert; McPherson, Craig A; Ruskin, Jeremy N; Singh, Jagmeet P

2007-11-15

Standard coronary venous angiography (SCVA) provides a static, fixed projection of the coronary venous (CV) tree. High-speed rotational coronary venous angiography (RCVA) is a novel method of mapping CV anatomy using dynamic, multiangle visualization. The purpose of this study was to assess the value of RCVA during cardiac resynchronization therapy. Digitally acquired rotational CV angiograms from 49 patients (mean age 69 +/- 11 years) who underwent left ventricular lead implantation were analyzed. RCVA, which uses rapid isocentric rotation over a 110 degrees arc, acquiring 120 frames/angiogram, was compared with SCVA, defined as 2 static orthogonal views: right anterior oblique 45 degrees and left anterior oblique 45 degrees . RCVA demonstrated that the posterior vein-to-coronary sinus (CS) angle and the left marginal vein-to-CS angle were misclassified in 5 and 11 patients, respectively, using SCVA. RCVA identified a greater number of second-order tributaries with diameters >1.5 mm than SCVA. The CV branch selected for lead placement was initially identified in 100% of patients using RCVA but in only 74% of patients using SCVA. RCVA showed that the best angiographic view for visualizing the CS and its tributaries differed significantly among different areas of the CV tree and among patients. The area of the CV tree that showed less variability was the CS ostium, which had a fairly constant relation with the spine in shallow right anterior oblique and left anterior oblique projections. In conclusion, RCVA provided a more precise map of CV anatomy and the spatial relation of venous branches. It allowed the identification of fluoroscopic views that could facilitate cannulation of the CS. The final x-ray view displaying the appropriate CV branch for left ventricular lead implantation was often different from the conventional left anterior oblique and right anterior oblique views. RCVA identified the target branch for lead implantation more often than SCVA.

Remote monitoring reduces healthcare use and improves quality of care in heart failure patients with implantable defibrillators: the evolution of management strategies of heart failure patients with implantable defibrillators (EVOLVO) study.

PubMed

Landolina, Maurizio; Perego, Giovanni B; Lunati, Maurizio; Curnis, Antonio; Guenzati, Giuseppe; Vicentini, Alessandro; Parati, Gianfranco; Borghi, Gabriella; Zanaboni, Paolo; Valsecchi, Sergio; Marzegalli, Maurizio

2012-06-19

Heart failure patients with implantable cardioverter-defibrillators (ICDs) or an ICD for resynchronization therapy often visit the hospital for unscheduled examinations, placing a great burden on healthcare providers. We hypothesized that Internet-based remote interrogation systems could reduce emergency healthcare visits. This multicenter randomized trial involving 200 patients compared remote monitoring with standard patient management consisting of scheduled visits and patient response to audible ICD alerts. The primary end point was the rate of emergency department or urgent in-office visits for heart failure, arrhythmias, or ICD-related events. Over 16 months, such visits were 35% less frequent in the remote arm (75 versus 117; incidence density, 0.59 versus 0.93 events per year; P=0.005). A 21% difference was observed in the rates of total healthcare visits for heart failure, arrhythmias, or ICD-related events (4.40 versus 5.74 events per year; P<0.001). The time from an ICD alert condition to review of the data was reduced from 24.8 days in the standard arm to 1.4 days in the remote arm (P<0.001). The patients' clinical status, as measured by the Clinical Composite Score, was similar in the 2 groups, whereas a more favorable change in quality of life (Minnesota Living With Heart Failure Questionnaire) was observed from the baseline to the 16th month in the remote arm (P=0.026). Remote monitoring reduces emergency department/urgent in-office visits and, in general, total healthcare use in patients with ICD or defibrillators for resynchronization therapy. Compared with standard follow-up through in-office visits and audible ICD alerts, remote monitoring results in increased efficiency for healthcare providers and improved quality of care for patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00873899.

Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation

PubMed Central

Gasparini, Maurizio; Auricchio, Angelo; Metra, Marco; Regoli, François; Fantoni, Cecilia; Lamp, Barbara; Curnis, Antonio; Vogt, Juergen; Klersy, Catherine

2008-01-01

Aims To investigate the effects of cardiac resynchronization therapy (CRT) on survival in heart failure (HF) patients with permanent atrial fibrillation (AF) and the role of atrio-ventricular junction (AVJ) ablation in these patients. Methods and results Data from 1285 consecutive patients implanted with CRT devices are presented: 1042 patients were in sinus rhythm (SR) and 243 (19%) in AF. Rate control in AF was achieved by either ablating the AVJ in 118 patients (AVJ-abl) or prescribing negative chronotropic drugs (AF-Drugs). Compared with SR, patients with AF were significantly older, more likely to be non-ischaemic, with higher ejection fraction, shorter QRS duration, and less often received ICD back-up. During a median follow-up of 34 months, 170/1042 patients in SR and 39/243 in AF died (mortality: 8.4 and 8.9 per 100 person-year, respectively). Adjusted hazard ratios were similar for all-cause and cardiac mortality [0.9 (0.57–1.42), P = 0.64 and 1.00 (0.60–1.66) P = 0.99, respectively]. Among AF patients, only 11/118 AVJ-abl patients died vs. 28/125 AF-Drugs patients (mortality: 4.3 and 15.2 per 100 person-year, respectively, P < 0.001). Adjusted hazard ratios of AVJ-abl vs. AF-Drugs was 0.26 [95% confidence interval (CI) 0.09–0.73, P = 0.010] for all-cause mortality, 0.31 (95% CI 0.10–0.99, P = 0.048) for cardiac mortality, and 0.15 (95% CI 0.03–0.70, P = 0.016) for HF mortality. Conclusion Patients with HF and AF treated with CRT have similar mortality compared with patients in SR. In AF, AVJ ablation in addition to CRT significantly improves overall survival compared with CRT alone, primarily by reducing HF death. PMID:18390869

Investigation of a novel algorithm for synchronized left-ventricular pacing and ambulatory optimization of cardiac resynchronization therapy: results of the adaptive CRT trial.

PubMed

Martin, David O; Lemke, Bernd; Birnie, David; Krum, Henry; Lee, Kathy Lai-Fun; Aonuma, Kazutaka; Gasparini, Maurizio; Starling, Randall C; Milasinovic, Goran; Rogers, Tyson; Sambelashvili, Alex; Gorcsan, John; Houmsse, Mahmoud

2012-11-01

In patients with sinus rhythm and normal atrioventricular conduction, pacing only the left ventricle with appropriate atrioventricular delays can result in superior left ventricular and right ventricular function compared with standard biventricular (BiV) pacing. To evaluate a novel adaptive cardiac resynchronization therapy ((aCRT) algorithm for CRT pacing that provides automatic ambulatory selection between synchronized left ventricular or BiV pacing with dynamic optimization of atrioventricular and interventricular delays. Patients (n = 522) indicated for a CRT-defibrillator were randomized to aCRT vs echo-optimized BiV pacing (Echo) in a 2:1 ratio and followed at 1-, 3-, and 6-month postrandomization. The study met all 3 noninferiority primary objectives: (1) the percentage of aCRT patients who improved in their clinical composite score at 6 months was at least as high in the aCRT arm as in the Echo arm (73.6% vs 72.5%, with a noninferiority margin of 12%; P = .0007); (2) aCRT and echo-optimized settings resulted in similar cardiac performance, as demonstrated by a high concordance correlation coefficient between aortic velocity time integrals at aCRT and Echo settings at randomization (concordance correlation coefficient = 0.93; 95% confidence interval 0.91-0.94) and at 6-month postrandomization (concordance correlation coefficient = 0.90; 95% confidence interval 0.87-0.92); and (3) aCRT did not result in inappropriate device settings. There were no significant differences between the arms with respect to heart failure events or ventricular arrhythmia episodes. Secondary end points showed similar benefit, and right-ventricular pacing was reduced by 44% in the aCRT arm. The aCRT algorithm is safe and at least as effective as BiV pacing with comprehensive echocardiographic optimization. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Refining success of cardiac resynchronization therapy using a simple score predicting the amount of reverse ventricular remodelling: results from the Markers and Response to CRT (MARC) study.

PubMed

Maass, Alexander H; Vernooy, Kevin; Wijers, Sofieke C; van 't Sant, Jetske; Cramer, Maarten J; Meine, Mathias; Allaart, Cornelis P; De Lange, Frederik J; Prinzen, Frits W; Gerritse, Bart; Erdtsieck, Erna; Scheerder, Coert O S; Hill, Michael R S; Scholten, Marcoen; Kloosterman, Mariëlle; Ter Horst, Iris A H; Voors, Adriaan A; Vos, Marc A; Rienstra, Michiel; Van Gelder, Isabelle C

2018-02-01

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in systolic heart failure patients with ventricular conduction delay. Variability of individual response to CRT warrants improved patient selection. The Markers and Response to CRT (MARC) study was designed to investigate markers related to response to CRT. We prospectively studied the ability of 11 clinical, 11 electrocardiographic, 4 echocardiographic, and 16 blood biomarkers to predict CRT response in 240 patients. Response was measured by the reduction of indexed left ventricular end-systolic volume (LVESVi) at 6 months follow-up. Biomarkers were related to LVESVi change using log-linear regression on continuous scale. Covariates that were significant univariately were included in a multivariable model. The final model was utilized to compose a response score. Age was 67 ± 10 years, 63% were male, 46% had ischaemic aetiology, LV ejection fraction was 26 ± 8%, LVESVi was 75 ± 31 mL/m2, and QRS was 178 ± 23 ms. At 6 months LVESVi was reduced to 58 ± 31 mL/m2 (relative reduction of 22 ± 24%), 130 patients (61%) showed ≥ 15% LVESVi reduction. In univariate analysis 17 parameters were significantly associated with LVESVi change. In the final model age, QRSAREA (using vectorcardiography) and two echocardiographic markers (interventricular mechanical delay and apical rocking) remained significantly associated with the amount of reverse ventricular remodelling. This CAVIAR (CRT-Age-Vectorcardiographic QRSAREA -Interventricular Mechanical delay-Apical Rocking) response score also predicted clinical outcome assessed by heart failure hospitalizations and all-cause mortality. The CAVIAR response score predicts the amount of reverse remodelling after CRT and may be used to improve patient selection. Clinical Trials: NCT01519908. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Clinical feasibility of exercise-based A-V interval optimization for cardiac resynchronization: a pilot study.

PubMed

Choudhuri, Indrajit; MacCarter, Dean; Shaw, Rachael; Anderson, Steve; St Cyr, John; Niazi, Imran

2014-11-01

One-third of eligible patients fail to respond to cardiac resynchronization therapy (CRT). Current methods to "optimize" the atrio-ventricular (A-V) interval are performed at rest, which may limit its efficacy during daily activities. We hypothesized that low-intensity cardiopulmonary exercise testing (CPX) could identify the most favorable physiologic combination of specific gas exchange parameters reflecting pulmonary blood flow or cardiac output, stroke volume, and left atrial pressure to guide determination of the optimal A-V interval. We assessed relative feasibility of determining the optimal A-V interval by three methods in 17 patients who underwent optimization of CRT: (1) resting echocardiographic optimization (the Ritter method), (2) resting electrical optimization (intrinsic A-V interval and QRS duration), and (3) during low-intensity, steady-state CPX. Five sequential, incremental A-V intervals were programmed in each method. Assessment of cardiopulmonary stability and potential influence on the CPX-based method were assessed. CPX and determination of a physiological optimal A-V interval was successfully completed in 94.1% of patients, slightly higher than the resting echo-based approach (88.2%). There was a wide variation in the optimal A-V delay determined by each method. There was no observed cardiopulmonary instability or impact of the implant procedure that affected determination of the CPX-based optimized A-V interval. Determining optimized A-V intervals by CPX is feasible. Proposed mechanisms explaining this finding and long-term impact require further study. ©2014 Wiley Periodicals, Inc.

British randomised controlled trial of AV and VV optimization ("BRAVO") study: rationale, design, and endpoints.

PubMed

Whinnett, Zachary I; Sohaib, S M Afzal; Jones, Siana; Kyriacou, Andreas; March, Katherine; Coady, Emma; Mayet, Jamil; Hughes, Alun D; Frenneaux, Michael; Francis, Darrel P

2014-04-03

Echocardiographic optimization of pacemaker settings is the current standard of care for patients treated with cardiac resynchronization therapy. However, the process requires considerable time of expert staff. The BRAVO study is a non-inferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay with an alternative method using non-invasive blood pressure monitoring that can be automated to consume less staff resources. BRAVO is a multi-centre, randomized, cross-over, non-inferiority trial of 400 patients with a previously implanted cardiac resynchronization device. Patients are randomly allocated to six months in each arm. In the echocardiographic arm, AV delay is optimized using the iterative method and VV delay by maximizing LVOT VTI. In the haemodynamic arm AV and VV delay are optimized using non-invasive blood pressure measured using finger photoplethysmography. At the end of each six month arm, patients undergo the primary outcome measure of objective exercise capacity, quantified as peak oxygen uptake (VO2) on a cardiopulmonary exercise test. Secondary outcome measures are echocardiographic measurement of left ventricular remodelling, quality of life score and N-terminal pro B-type Natriuretic Peptide (NT-pro BNP). The study is scheduled to complete recruitment in December 2013 and to complete follow up in December 2014. If exercise capacity is non-inferior with haemodynamic optimization compared with echocardiographic optimization, it would be proof of concept that haemodynamic optimization is an acceptable alternative which has the potential to be more easily implemented. Clinicaltrials.gov NCT01258829.

Complications leading to surgical revision in implantable cardioverter defibrillator patients: comparison of patients with single-chamber, dual-chamber, and biventricular devices.

PubMed

Duray, Gabor Z; Schmitt, Joern; Cicek-Hartvig, Sule; Hohnloser, Stefan H; Israel, Carsten W

2009-03-01

Implantable cardioverter defibrillator (ICD) technology has become more complex, particularly with respect to biventricular resynchronization devices. The incidence of hardware-related complications in single (SC)-, dual (DC)-, and triple (BiV)-chamber devices requiring surgical revision has not been investigated systematically. We analysed data from consecutive ICD recipients implanted between January 2000 and December 2007 with respect to the need of surgical re-intervention for device- or lead-related complications. Generator exchanges due to normal battery depletion were not considered. From 816 patients (81% male, 69% ischaemic cardiomyopathy, 48% secondary prevention ICDs) followed for 31 +/- 24 months (2118 cumulative patient-years), 98 patients underwent 110 revisions (5.2% per patient-year). Complications included lead-related revision procedures in 81 cases and generator-related problems in 29 cases. The annual incidence of surgical revision due to complications was 11.8% in BiV compared with 4.9% in SC and 4.1% in DC patients (P = 0.002). This higher revision rate was mainly caused by lead-related complications. Implantation of a BiV system was an independent risk factor of the need for surgical revision (relative risk 2.37, 95% confidence interval 1.38-4.04). Even with long-lasting operator experience, complications requiring surgical revision remain a clinically important problem of ICD therapy. The incidence of complications is significantly higher in BiV resynchronization devices than in SC and DC systems.

Minimal invasive epicardial lead implantation: optimizing cardiac resynchronization with a new mapping device for epicardial lead placement.

PubMed

Maessen, J G; Phelps, B; Dekker, A L A J; Dijkman, B

2004-05-01

To optimize resynchronization in biventricular pacing with epicardial leads, mapping to determine the best pacing site, is a prerequisite. A port access surgical mapping technique was developed that allowed multiple pace site selection and reproducible lead evaluation and implantation. Pressure-volume loops analysis was used for real time guidance in targeting epicardial lead placement. Even the smallest changes in lead position revealed significantly different functional results. Optimizing the pacing site with this technique allowed functional improvement up to 40% versus random pace site selection.

Effect of early or late resynchronization based on different methods of pregnancy diagnosis on reproductive performance of dairy cows.

PubMed

Sinedino, L D P; Lima, F S; Bisinotto, R S; Cerri, R L A; Santos, J E P

2014-01-01

The aim of this study was to compare the reproductive performance of dairy cows subjected to early (ER) or late (LR) resynchronization programs after nonpregnancy diagnoses based on either pregnancy-associated glycoproteins (PAG) ELISA or transrectal palpation, respectively. In addition, the accuracy of the PAG ELISA for early pregnancy diagnosis was assessed. Lactating Holstein cows were subjected to a Presynch-Ovsynch protocol with timed artificial insemination (AI) performed between 61 and 74 DIM. On the day of the first postpartum AI, 1,093 cows were blocked by parity and assigned randomly to treatments; however, because of attrition, 452 ER and 520 LR cows were considered for the statistical analyses. After the first postpartum AI, cows were observed daily for signs of estrus and inseminated on the same day of detected estrus. Cows from ER that were not reinseminated in estrus received the first GnRH injection of the Ovsynch protocol for resynchronization 2d before pregnancy diagnosis. On d 28 after the previous AI (d 27 to 34), pregnancy status was determined by PAG ELISA, and nonpregnant cows continued on the Ovsynch protocol for reinsemination. Pregnant cows had pregnancy status reconfirmed on d 46 after AI (d 35 to 52) by transrectal palpation, and those that lost the pregnancies were resynchronized. Cows assigned to LR had pregnancy diagnosed by transrectal palpation on d 46 after AI (d 35 to 52) and nonpregnant cows were resynchronized with the Ovsynch protocol. Blood was sampled on d 28 after AI (d 27 to 34) from cows in both treatments that had not been reinseminated on estrus and again on d 46 after AI (d 35 to 52) for assessment of PAG ELISA to determine the accuracy of the test. Cows were subjected to treatments for 72d after the first insemination. Pregnancy per AI (P/AI) at first postpartum timed AI did not differ between treatments and averaged 28.9%. The proportion of nonpregnant cows that were resynchronized and received timed AI was greater for ER than for LR (30.0 vs. 7.6%). Cows in ER had a shorter interval between inseminations when inseminated following spontaneous estrus (21.7±1.1 vs. 27.8±0.8d) or after timed AI (35.3±1.2 vs. 55.2±1.4d). Nevertheless, the ER did not affect the rate of pregnancy (adjusted hazard ratio=1.23; 95% confidence interval=0.94 to 1.61) or the median days postpartum to pregnancy (ER=132 vs. LR=140). A total of 2,129 PAG ELISA were evaluated. Overall, sensitivity, specificity, and positive and negative predictive values averaged 95.1, 89.0, 90.1, and 94.5%, respectively, and the accuracy was 92.1%. In conclusion, PAG ELISA for early diagnosis of pregnancy had acceptable accuracy, but early resynchronization after nonpregnancy diagnosis with PAG ELISA did not improve the rate of pregnancy or reduce days open in dairy cows continuously observed for estrus. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Characterization and predictors of first and subsequent inappropriate ICD therapy by heart rate ranges: Result of the MADIT-RIT efficacy analysis.

PubMed

Kutyifa, Valentina; Daubert, James P; Olshansky, Brian; Huang, David T; Zhang, Claire; Ruwald, Anne-Christine H; McNitt, Scott; Zareba, Wojciech; Moss, Arthur J; Schuger, Claudio

2015-09-01

Data on inappropriate implantable cardioverter-defibrillator (ICD) therapy and effects of programming by heart rate are lacking. We aimed to characterize inappropriate ICD therapy and assess the effects of novel programming by heart rate. Incidence and causes of inappropriate therapy by heart rate range (below or above 200 bpm) were assessed. Predictors of inappropriate therapy and effects of programming by heart rate were evaluated with multivariate Cox regression models. Crossovers were excluded. Inappropriate therapy occurred in 9.2% of the total patient population, with 19% of patients randomized to study arm A, 3.6% in arm B, and 4.7% in arm C. Inappropriate therapies <200 bpm were attributable to supraventricular tachycardia (SVT)/sinus tachycardia (78%) or atrial fibrillation/flutter (20%). Inappropriate therapy ≥200 bpm occurred because of SVT (47%), atrial fibrillation/flutter (41%), or electromagnetic interference (13%). Conventional ICD programming was associated with more inappropriate therapy <200 bpm than high-rate or delayed therapy, as were younger age, history of atrial arrhythmia, advanced New York Heart Association functional class, ICD versus cardiac resynchronization therapy with defibrillator, and absence of diabetes. High-rate and long-delay therapy significantly reduced the risk of inappropriate therapy in the <200 bpm range. Long delay was associated with further reduction of fast (≥200 bpm) inappropriate therapy (P = .032) and a reduction in subsequent inappropriate episodes (P = .006). In MADIT-RIT, inappropriate ICD therapy is most frequent at rates below 200 bpm and can be predicted, and effectively prevented, with high-rate cutoff programming. Long-delay therapy effectively reduces fast inappropriate therapy ≥200 bpm and subsequent events. [ http://clinicaltrials.gov/ct2/show/NCT00947310]. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Relationship between age and inappropriate implantable cardioverter-defibrillator therapy in MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy).

PubMed

Biton, Yitschak; Huang, David T; Goldenberg, Ilan; Rosero, Spencer; Moss, Arthur J; Kutyifa, Valentina; McNitt, Scott; Strasberg, Boris; Zareba, Wojciech; Barsheshet, Alon

2016-04-01

There is limited data regarding the relationship between age and inappropriate therapy among patients with an implantable cardioverter-defibrillator (ICD) and resynchronization therapy. We aimed to investigate this relationship and the effect of ICD programming on inappropriate therapy by age. In the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) 1500 patients were randomized to 3 ICD programming arms: (A) conventional with ventricular tachycardia (VT) therapy ≥170; (B) high-rate cutoff with VT therapy ≥200, and (C) prolonged 60-second delay for VT therapy ≥170. We investigated the relationship between age, the risk of inappropriate ICD therapy (including antitachycardia pacing [ATP] or shock), and ICD programming. Cumulative incidence function Kaplan-Meier graphs showed an inverse relationship between increasing quartiles of age (Q1: ≤55, Q2: 56-64, Q3: 65-71, and Q4: ≥72 years) and the risk for inappropriate therapy. Multivariate analyses showed that each increasing decade of life was associated with 34% (P < .001), 27% (P < .001), and 26% (P < .001) reduction in the risk of inappropriate shock, inappropriate ATP, and any inappropriate therapy, respectively. Treatment arms B and C as compared with arm A were associated with a significant reduction in the risk of inappropriate therapies across all age quartiles (P < .001 for all). Among patients with a primary prevention indication for an ICD, there is an inverse relationship between age and inappropriate ICD therapy. Innovative ICD programming of high-rate cutoff or prolonged delay for VT therapy is associated with significant reductions in inappropriate therapy among all age groups. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Reduction of inappropriate anti-tachycardia pacing therapies and shocks by a novel suite of detection algorithms in heart failure patients with cardiac resynchronization therapy defibrillators: a historical comparison of a prospective database.

PubMed

Lunati, Maurizio; Proclemer, Alessandro; Boriani, Giuseppe; Landolina, Maurizio; Locati, Emanuela; Rordorf, Roberto; Daleffe, Elisabetta; Ricci, Renato Pietro; Catanzariti, Domenico; Tomasi, Luca; Gulizia, Michele; Baccillieri, Maria Stella; Molon, Giulio; Gasparini, Maurizio

2016-09-01

Implantable cardioverter defibrillators improve survival of patients at risk for ventricular arrhythmias, but inappropriate shocks occur in up to 30% of patients and have been associated with worse quality of life and prognosis. In heart failure patients with cardiac resynchronization therapy defibrillators (CRT-Ds), we evaluated whether a new generation of detection and discrimination algorithms reduces inappropriate shocks. We analysed 1983 Medtronic CRT-D patients (80% male, 67 ± 10 years), 1368 with standard devices (Control CRT-D) and 615 with new generation devices (New CRT-D). Expert electrophysiologists reviewed and classified the electrograms of all device-detected ventricular tachycardia/fibrillation episodes. Total follow-up was 3751 patients-years. Incidence of inappropriate shocks at 1 year was 2.8% [95% confidence interval (CI) = 2.0-3.5] in Control CRT-D and 0.9% (CI = 0.4-2.2) in New CRT-D (hazard ratio = 0.37, CI = 0.21-0.66, P < 0.001). In New CRT-D, inappropriate shocks were reduced by 77% [incidence rate ratio (IRR) = 0.23, CI = 0.16-0.35, P < 0.001] and inappropriate anti-tachycardia pacing by 81% (IRR = 0.19, CI = 0.11-0.335, P < 0.001). Annual rate per 100 patient-years for appropriate VF detections was 3.0 (CI = 2.1-4.2) in New CRT-D and 3.2 (CI = 2.1-5.0) in Control CRT-D (P = 0.68), for syncope was 0.4 (CI = 0.2-0.9) in New CRT-D and 0.7 (CI = 0.5-1.0) in Control CRT-D (P = 0.266), and for death was 1.0 (CI = 0.6-1.6) in New CRT-D and 3.5 (CI = 3.0-4.1) in Control CRT-D (P < 0.001). Detection and discrimination algorithms used in new generation CRT-D significantly reduced inappropriate shocks when compared with standard CRT-D. This result, with no compromise on VF sensitivity or risk of syncope, has important implications for patients' quality of life and prognosis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Recent advances in heart failure.

PubMed

Kassi, Mahwash; Hannawi, Bashar; Trachtenberg, Barry

2018-03-01

Acute heart failure continues to be a challenge as there is limited benefit of numerous agents that have been tested. Cardiac resynchronization therapy remains standard of care, yet timing and need for implantable cardiac defibrillator has been brought into question with the recent randomized trials. Several recent advances have been made towards management of heart failure both in drug and device therapy. The purpose of this review is to provide an update on the most important recent studies on heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Two new drugs have been added to the armamentarium for HFrEF; ivabradine and angiotensin receptor-neprilysin inhibitors (ARNIs). Initial data from a new left ventricular assist device (LVAD) pump, the HeartMate 3 (HM III), have demonstrated no reports of pump thrombosis at 6 months, but stroke and right ventricle failure continue to be a challenge with comparable rates compared with the HeartMate II. Several large studies in HFpEF failed to show improvement in outcomes and management continues to be geared towards lifestyle modification and symptom relief. Newer therapies and devices have met with great success, yet there are several therapies that provide no benefit and even harm. A careful review of the recent literature remains instrumental to the effective management of patients with heart failure.

Anodal right ventricular capture during left ventricular stimulation in CRT-implantable cardioverter defibrillators.

PubMed

Thibault, Bernard; Roy, Denis; Guerra, Peter G; Macle, Laurent; Dubuc, Marc; Gagné, Pierre; Greiss, Isabelle; Novak, Paul; Furlani, Aldo; Talajic, Mario

2005-07-01

Cardiac resynchronization therapy (CRT) has been shown to improve symptoms of patients with moderate to severe heart failure. Optimal CRT involves biventricular or left ventricular (LV) stimulation alone, atrio-ventricular (AV) delay optimization, and possibly interventricular timing adjustment. Recently, anodal capture of the right ventricle (RV) has been described for patients with CRT-pacemakers. It is unknown whether the same phenomenon exists in CRT systems associated with defibrillators (CRT-ICD). The RV leads used in these systems are different from pacemaker leads: they have a larger diameter and shocking coils, which may affect the occurrence of anodal capture. We looked for anodal RV capture during LV stimulation in 11 consecutive patients who received a CRT-ICD system with RV leads with a true bipolar design. Fifteen patients who had RV leads with an integrated design were used as controls. Anodal RV and LV thresholds were determined at pulse width (pw) durations of 0.2, 0.5, and 1.0 ms. RV anodal capture during LV pacing was found in 11/11 patients at some output with true bipolar RV leads versus 0/15 patients with RV leads with an integrated bipolar design. Anodal RV capture threshold was more affected by changes in pw duration than LV capture threshold. In CRT-ICD systems, RV leads with a true bipolar design with the proximal ring also used as the anode for LV pacing are associated with a high incidence of anodal RV capture during LV pacing. This may affect the clinical response to alternative resynchronization methods using single LV stimulation or interventricular delay programming.

Insights from Novel Noninvasive CT and ECG Imaging Modalities on Electromechanical Myocardial Activation in a Canine Model of Ischemic Dyssynchronous Heart Failure.

PubMed

Dawoud, Fady; Schuleri, Karl H; Spragg, David D; Horáček, B Milan; Berger, Ronald D; Halperin, Henry R; Lardo, Albert C

2016-12-01

The interplay between electrical activation and mechanical contraction patterns is hypothesized to be central to reduced effectiveness of cardiac resynchronization therapy (CRT). Furthermore, complex scar substrates render CRT less effective. We used novel cardiac computed tomography (CT) and noninvasive electrocardiographic imaging (ECGI) techniques in an ischemic dyssynchronous heart failure (DHF) animal model to evaluate electrical and mechanical coupling of cardiac function, tissue viability, and venous accessibility of target pacing regions. Ischemic DHF was induced in 6 dogs using coronary occlusion, left bundle ablation and tachy RV pacing. Full body ECG was recorded during native rhythm followed by volumetric first-pass and delayed enhancement CT. Regional electrical activation were computed and overlaid with segmented venous anatomy and scar regions. Reconstructed electrical activation maps show consistency with LBBB starting on the RV and spreading in a "U-shaped" pattern to the LV. Previously reported lines of slow conduction are seen parallel to anterior or inferior interventricular grooves. Mechanical contraction showed large septal to lateral wall delay (80 ± 38 milliseconds vs. 123 ± 31 milliseconds, P = 0.0001). All animals showed electromechanical correlation except dog 5 with largest scar burden. Electromechanical decoupling was largest in basal lateral LV segments. We demonstrated a promising application of CT in combination with ECGI to gain insight into electromechanical function in ischemic dyssynchronous heart failure that can provide useful information to study regional substrate of CRT candidates. © 2016 Wiley Periodicals, Inc.

Effect of resynchronization with GnRH or progesterone (P4) intravaginal device (CIDR) on Day 23 after timed artificial insemination on cumulative pregnancy and embryonic losses in CIDR-GnRH synchronized Nili-Ravi buffaloes.

PubMed

Arshad, Usman; Qayyum, Arslan; Hassan, Mubbashar; Husnain, Ali; Sattar, Abdul; Ahmad, Nasim

2017-11-01

The objective of the present study was to determine the effect of resynchronization on Day 23 with either GnRH or P4 (controlled internal drug release device containing progesterone; CIDR) on pregnancy rate, cumulative pregnancy, and embryonic and fetal losses in CIDR-GnRH synchronized Nili-Ravi buffaloes. Buffaloes (n = 181) of mixed parity, lactating, 181 ± 73 days postpartum, a body condition score (BCS) of 3.2 ± 0.5 (scale of 1-5), and 450-600 kg weight were subjected to synchronization and resynchronization. All buffaloes received CIDR on Day -9.5. In addition, GnRH was injected 36 h after CIDR removal, and timed artificial insemination (TAI) was performed 18 h later (Day 0). On Day 23, buffaloes were randomly assigned to receive one of the following treatments: 1) CON (n = 63), 2) P4 (n = 55), and 3) GnRH (n = 63) for resynchronization (2nd AI). Pregnancy rate, and embryonic and fetal losses were monitored by serial ultrasonography on Days 30, 45, 60, and 90 after synchronization (1st TAI), respectively. The pregnancy rate in GnRH-treated buffaloes remained significantly and consistently higher (P < 0.05) than in the CON group at Days 30, 45, 60, and 90 after 1st TAI. Based on the pregnancy diagnosis, on Day 30 post 1st TAI, buffaloes that remained non-pregnant in the CON, P4, and GnRH groups received: 1) Artificial insemination on detected estrus (AIDE; n = 37), 2) CIDR-GnRH protocol (CIDR; n = 27), and 3) Ovsynch protocol (OVS; n = 23), respectively. The pregnancy rate in resynchronized buffaloes did not differ (P > 0.05) between the OVS and CIDR groups; whereas the, cumulative pregnancy rate in GnRH + OVS buffaloes (81%) after 1st and 2 nd AI when determined on Day 64 was higher (P < 0.05) than that in CON + AIDE (59%) buffaloes. The embryonic losses were significantly lower (P < 0.05) in GnRH-treated (18%) buffaloes, than in CON (42%) buffaloes on Day 45 post 1st TAI. Fetal losses were fewer and did not differ (P > 0.05) due to treatments on Day 60 or 90 post 1st AI. In conclusion, 1) the pregnancy rate and cumulative pregnancy rate in GnRH-treated buffaloes were higher than in CON buffaloes on Day 64 after synchronization and resynchronization, and 2) embryonic and fetal losses were lower in GnRH-treated buffaloes than in CON buffaloes when determined from Day 31-90 post 1st TAI. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiac resynchronization therapy by multipoint pacing improves response of left ventricular mechanics and fluid dynamics: a three-dimensional and particle image velocimetry echo study.

PubMed

Siciliano, Mariachiara; Migliore, Federico; Badano, Luigi; Bertaglia, Emanuele; Pedrizzetti, Gianni; Cavedon, Stefano; Zorzi, Alessandro; Corrado, Domenico; Iliceto, Sabino; Muraru, Denisa

2017-11-01

To characterize the effect of multipoint pacing (MPP) compared to biventricular pacing (BiV) on left ventricle (LV) mechanics and intraventricular fluid dynamics by three-dimensional echocardiography (3DE) and echocardiographic particle imaging velocimetry (Echo-PIV). In 11 consecutive patients [8 men; median age 65 years (57-75)] receiving cardiac resynchronization therapy (CRT) with a quadripolar LV lead (Quartet,St.Jude Medical,Inc.), 3DE and Echo-PIV data were collected for each pacing configuration (CRT-OFF, BiV, and MPP) at follow-up after 6 months. 3DE data included LV volumes, LV ejection fraction (LVEF), strain, and systolic dyssynchrony index (SDI). Echo-PIV was used to evaluate the directional distribution of global blood flow momentum, ranging from zero, when flow force is predominantly along the base-apex direction, up to 90° when it becomes transversal. MPP resulted in significant reduction in end-diastolic and end-systolic volumes compared with both CRT-OFF (P = 0.02; P = 0.008, respectively) and BiV (P = 0.04; P = 0.03, respectively). LVEF and cardiac output were significant superior in MPP compared with CRT-OFF, but similar between MPP and BiV. Statistical significant differences when comparing global longitudinal and circumferential strain and SDI with MPP vs. CRT-OFF were observed (P = 0.008; P = 0.008; P = 0.01, respectively). There was also a trend towards improvement in strain between BiV and MPP that did not reach statistical significance. MPP reflected into a significant reduction of the deviation of global blood flow momentum compared with both CRT-OFF and BiV (P = 0.002) indicating a systematic increase of longitudinal alignment from the base-apex orientation of the haemodynamic forces. These preliminary results suggest that MPP resulted in significant improvement of LV mechanics and fluid dynamics compared with BiV. However, larger studies are needed to confirm this hypothesis. © Crown copyright 2016.

The Myocardial Ischemia Evaluated by Real-Time Contrast Echocardiography May Predict the Response to Cardiac Resynchronization Therapy: A Large Animal Study

PubMed Central

Chen, Yongle; Cheng, Leilei; Yao, Haohua; Chen, Haiyan; Wang, Yongshi; Zhao, Weipeng; Pan, Cuizhen; Shu, Xianhong

2014-01-01

Evidence-based criteria for applying cardiac resynchronization therapy (CRT) in patients with ischemic cardiomyopathy are still scarce. The aim of the present study was to evaluate the predictive value of real-time myocardial contrast echocardiography (RT-MCE) in a preclinical canine model of ischemic cardiomyopathy who received CRT. Ischemic cardiomyopathy was produced by ligating the first diagonal branch in 20 beagles. Dogs were subsequently divided into two groups that were either treated with bi-ventricular pacing (CRT group) or left untreated (control group). RT-MCE was performed at baseline, before CRT, and 4 weeks after CRT. Two-dimensional speckle tracking imaging was used to evaluate the standard deviation of circumferential (Cir12SD), radial (R12SD), and longitudinal (L12SD) strains of left ventricular segments at basal as well as middle levels. Four weeks later, the Cir12SD, R12SD, and myocardial blood flow (MBF) of the treated group were significantly improved compared to their non-CRT counterparts. Furthermore, MBF values measured before CRT were significantly higher in responders than in non-responders to bi-ventricular pacing. Meanwhile, no significant differences were observed between the responder and non-responder groups in terms of Cir12SD, R12SD, and L12SD. A high degree of correlation was found between MBF values before CRT and LVEF after CRT. When MBF value>24.9 dB/s was defined as a cut-off point before CRT, the sensitivity and specificity of RT-MCE in predicting the response to CRT were 83.3% and 100%, respectively. Besides, MBF values increased significantly in the CRT group compared with the control group after 4 weeks of pacing (49.8±15.5 dB/s vs. 28.5±4.6 dB/s, p<0.05). Therefore, we considered that myocardial perfusion may be superior to standard metrics of LV synchrony in selecting appropriate candidates for CRT. In addition, CRT can improve myocardial perfusion in addition to cardiac synchrony, especially in the setting of ischemic cardiomyopathy. PMID:25469632

Antibacterial Envelope Is Associated With Low Infection Rates After Implantable Cardioverter-Defibrillator and Cardiac Resynchronization Therapy Device Replacement: Results of the Citadel and Centurion Studies.

PubMed

Henrikson, Charles A; Sohail, M Rizwan; Acosta, Helbert; Johnson, Eric E; Rosenthal, Lawrence; Pachulski, Roman; Dan, Dan; Paladino, Walter; Khairallah, Farhat S; Gleed, Kent; Hanna, Ibrahim; Cheng, Alan; Lexcen, Daniel R; Simons, Grant R

2017-10-01

This study sought to determine whether the nonabsorbable TYRX Antibacterial Envelope (TYRX) reduces major cardiovascular implantable electronic device (CIED) infections 12 months after implant. TYRX is a monofilament polypropylene mesh impregnated with minocycline and rifampin specifically designed to hold a CIED in place and elute antimicrobials over time. There are limited data on its ability to reduce CIED infections. We prospectively enrolled patients who underwent generator replacement with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT), treated with TYRX. The primary endpoints were major CIED infection and CIED mechanical complications. Given the differences in infection rates among ICD and CRT patients, 3 different control populations were used: a published benchmark rate for ICD patients, and both site-matched and comorbidity-matched controls groups for CRT patients. Overall, a major CIED infection occurred in 5 of 1,129 patients treated with TYRX (0.4%; 95% confidence interval: 0.0% to 0.9%), significantly lower than the 12-month benchmark rate of 2.2% (p = 0.0023). Among the TYRX-treated CRT cohort, the major CIED infection rate was 0.7% compared with an infection rate of 1.0% and 1.3% (p = 0.38 and p = 0.02) in site-matched and comorbidity-matched control groups, respectively. Among the ICD group, the 12-month infection rate was 0.2% compared with the published benchmark of 2.2% (p = 0.0052). The most common CIED mechanical complication in study patients was pocket hematoma, which occurred in 18 of the 1,129 patients (1.6%; 95% confidence interval: 0.8 to 2.5), which is comparable with a published rate of 1.6%. Use of TYRX was associated with a lower major CIED infection rate. (TYRX™ Envelope for Prevention of Infection Following Replacement With a CRT or ICD; [Centurion]; NCT01043861/NCT01043705). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The potential of multi-slice computed tomography based volumetry for demonstrating reverse remodeling induced by cardiac resynchronization therapy.

PubMed

Langer, Christoph; Schroeder, Janina; Peterschroeder, Andreas; Vaske, Bernhard; Faber, Lothar; Welge, Dirk; Niethammer, Matthias; Lamp, Barbara; Butz, Thomas; Bitter, Thomas; Oldenburg, Olaf; Horstkotte, Dieter

2010-07-01

Multi-slice computed tomography (MSCT) was proved to provide precise cardiac volumetric assessment. Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with heart failure and reduced ejection fraction (HFREF). In HFREF patients we investigated the potential of MSCT based wall motion analysis in order to demonstrate CRT-induced reversed remodeling. Besides six patients with normal cardiac pump function serving as control group seven HFREF patients underwent contrast enhanced MSCT before and after CRT. Short cardiac axis views of the left ventricle (LV) in end-diastole (ED) and end-systole (ES) served for planimetry. Pre- and post-CRT MSCT based volumetry was compared with 2D echo. To demonstrate CRT-induced reverse remodeling, MSCT based multi-segment color-coded polar maps were introduced. With regard to the HFREF patients pre-CRT MSCT based volumetry correlated with 2D echo data for LV-EDV (MSCT 278.3+/-75.0mL vs. echo 274.4+/-85.6mL) r=0.380, p=0.401, LV-ESV (MSCT 226.7+/-75.4mL vs. echo 220.1+/-74.0mL) r=0.323, p=0.479 and LV-EF (MSCT 20.2+/-8.8% vs. echo 20.0+/-11.9%) r=0.617, p=0.143. Post-CRT MSCT correlated well with 2D echo: LV-EDV (MSCT 218.9+/-106.4mL vs. echo 188.7+/-93.1mL) r=0.87, p=0.011, LV-ESV (MSCT 145+/-71.5mL vs. echo 125.6+/-78mL) r=0.84, p=0.018 and LV-EF (MSCT 29.6+/-11.3mL vs. echo 38.6+/-14.6mL) r=0.89, p=0.007. There was a significant increase of the mid-ventricular septum in terms of absolute LV wall thickening of the responders (pre 0.9+/-2.1mm vs. post 3.3+/-2.2mm; p<0.0005). MSCT based volumetry involving multi-segment color-coded polar maps offers wall motion analysis to demonstrate CRT-induced reverse remodeling which needs to be further validated. 2010 Elsevier Ltd. All rights reserved.

Initial clinical experience with cardiac resynchronization therapy utilizing a magnetic navigation system.

PubMed

Gallagher, Peter; Martin, Laura; Angel, Lori; Tomassoni, Gery

2007-02-01

The placement of left ventricular (LV) leads during cardiac resynchronization therapy (CRT) involves many technical difficulties. These difficulties increase procedural times and decrease procedural success rates. A total of 50 patients with severe cardiomyopathy (mean LV ejection fraction was 21 +/- 6%) and a wide QRS underwent CRT implantation. Magnetic navigation (Stereotaxis, Inc.) was used to position a magnet-tipped 0.014'' guidewire (Cronus guidewire) within the coronary sinus (CS) vasculature. LV leads were placed in a lateral CS branch, either using a standard CS delivery sheath or using a "bare-wire" approach without a CS delivery sheath. The mean total procedure time was 98.1 +/- 29.1 minutes with a mean fluoroscopy time of 22.7 +/- 15.1 minutes. The mean LV lead positioning time was 10.4 +/- 7.6 minutes. The use of a delivery sheath was associated with longer procedure times 98 +/- 32 minutes vs 80 +/- 18 minutes (P = 0.029), fluoroscopy times 23 +/- 15 minutes vs 13 +/- 4 minutes (P = 0.0007) and LV lead positioning times 10 +/- 6 minutes vs 4 +/- 2 minutes (P = 0.015) when compared to a "bare-wire" approach. When compared with 52 nonmagnetic-assisted control CRT cases, magnetic navigation reduced total LV lead positioning times (10.4 +/- 7.6 minutes vs 18.6 +/- 18.9 minutes; P = 0.005). If more than one CS branch vessel was tested, magnetic navigation was associated with significantly shorter times for LV lead placement (16.2 +/- 7.7 minutes vs 36.4 +/- 23.4 minutes; P = 0.004). Magnetic navigation is a safe, feasible, and efficient tool for lateral LV lead placement during CRT. Magnetic navigation during CRT allows for control of the tip direction of the Cronus 0.014'' guidewire using either a standard CS delivery sheath or "bare-wire" approach. Although there are some important limitations to the 0.014'' Cronus magnetic navigation can decrease LV lead placement times compared with nonmagnetic-assisted control CRT cases, particularly if multiple CS branches are to be tested.

Troponin T elevation after permanent pacemaker implantation.

PubMed

Chen, Xueying; Yu, Ziqing; Bai, Jin; Hu, Shulan; Wang, Wei; Qin, Shengmei; Wang, Jingfeng; Sun, Zhe; Su, Yangang; Ge, Junbo

2017-08-01

The objective of the study is to study the incidence, significance, and factors associated with cardiac troponin T (CTNT) elevation after pacemaker implantation. Three hundred seventy-four patients (104 single-chamber pacemakers or ICD, 243 dual-chamber pacemakers, and 27 cardiac resynchronization therapy/cardiac resynchronization therapy defibrillator) who had normal levels of CTNT at baseline and underwent implantation of a permanent pacemaker system were included in this study. Serum levels of CTNT were measured at baseline, 6 and 24 h after the implantation procedure. The median of CTNT levels increased from 0.012 ng/mL at baseline to 0.032 and 0.019 ng/mL at 6 and 24 h after the procedure, respectively (all p < 0.0001). Elevated CTNT levels were noted in 208 patients (55.6%) at 6 h after the implantation, among which 29 patients (7.8%) had CTNT levels exceeding the range of minimal myocardial damage (>0.09 ng/mL). After 1-year follow-up, the incidence of complications including dislodgement of the lead, pocket infection, pneumothorax, hemothorax, and vein thrombus and cardiac outcomes including hospitalization of heart failure, coronary artery disease, arrhythmia, and cardiovascular mortality was not significantly different between the normal and elevated CTNT groups at 6 h after the procedure. By logistic regression analysis, gender, N-terminal pro-B type natriuretic peptide (NT-pro-BNP) at baseline, left ventricular ejection fractions (LVEF), estimated glomerular filtration rate (eGFR), and fluoroscopy time were independently associated with CTNT elevation after adjusted for age, pacemaker types, right ventricle lead location (RVA or RVOT), heart function, and left ventricular end systolic dimension. Pacemaker implantation was found to be accompanied with CTNT elevation in 55.6% of the patients at 6 h after the procedure, and its kinetics were fast, which might not be related to the complications and adverse cardiac outcomes within 1 year of follow-up. Moreover, gender, NT-pro-BNP at baseline, LVEF, eGFR, and fluoroscopy time were found to be independent predictors of CTNT elevation.

Survival in Women Versus Men Following Implantation of Pacemakers, Defibrillators, and Cardiac Resynchronization Therapy Devices in a Large, Nationwide Cohort.

PubMed

Varma, Niraj; Mittal, Suneet; Prillinger, Julie B; Snell, Jeff; Dalal, Nirav; Piccini, Jonathan P

2017-05-10

Whether outcomes differ between sexes following treatment with pacemakers (PM), implantable cardioverter defibrillators, and cardiac resynchronization therapy (CRT) devices is unclear. Consecutive US patients with newly implanted PM, implantable cardioverter defibrillators, and CRT devices from a large remote monitoring database between 2008 and 2011 were included in this observational cohort study. Sex-specific all-cause survival postimplant was compared within each device type using a multivariable Cox proportional hazards model, stratified on age and adjusted for remote monitoring utilization and ZIP-based socioeconomic variables. A total of 269 471 patients were assessed over a median 2.9 [interquartile range, 2.2, 3.6] years. Unadjusted mortality rates (MR; deaths/100 000 patient-years) were similar between women versus men receiving PMs (n=115 076, 55% male; MR 4193 versus MR 4256, respectively; adjusted hazard ratio, 0.87; 95% CI, 0.84-0.90; P <0.001) and implantable cardioverter defibrillators (n=85 014, 74% male; MR 4417 versus MR 4479, respectively; adjusted hazard ratio, 0.98; 95% CI, 0.93-1.02; P =0.244). In contrast, survival was superior in women receiving CRT defibrillators (n=61 475, 72% male; MR 5270 versus male MR 7175; adjusted hazard ratio, 0.73; 95% CI, 0.70-0.76; P <0.001) and also CRT pacemakers (n=7906, 57% male; MR 5383 versus male MR 7625, adjusted hazard ratio, 0.69; 95% CI, 0.61-0.78; P <0.001). This relative difference increased with time. These results were unaffected by age or remote monitoring utilization. Women accounted for less than 30% of high-voltage implants and fewer than half of low-voltage implants in a large, nation-wide cohort. Survival for women and men receiving implantable cardioverter defibrillators and PMs was similar, but dramatically greater for women receiving both defibrillator- and PM-based CRT. © 2017 The Authors and St. Jude Medical. Published on behalf of the American Heart Association, Inc., by Wiley.

An integrated platform for image-guided cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Ma, Ying Liang; Shetty, Anoop K.; Duckett, Simon; Etyngier, Patrick; Gijsbers, Geert; Bullens, Roland; Schaeffter, Tobias; Razavi, Reza; Rinaldi, Christopher A.; Rhode, Kawal S.

2012-05-01

Cardiac resynchronization therapy (CRT) is an effective procedure for patients with heart failure but 30% of patients do not respond. This may be due to sub-optimal placement of the left ventricular (LV) lead. It is hypothesized that the use of cardiac anatomy, myocardial scar distribution and dyssynchrony information, derived from cardiac magnetic resonance imaging (MRI), may improve outcome by guiding the physician for optimal LV lead positioning. Whole heart MR data can be processed to yield detailed anatomical models including the coronary veins. Cine MR data can be used to measure the motion of the LV to determine which regions are late-activating. Finally, delayed Gadolinium enhancement imaging can be used to detect regions of scarring. This paper presents a complete platform for the guidance of CRT using pre-procedural MR data combined with live x-ray fluoroscopy. The platform was used for 21 patients undergoing CRT in a standard catheterization laboratory. The patients underwent cardiac MRI prior to their procedure. For each patient, a MRI-derived cardiac model, showing the LV lead targets, was registered to x-ray fluoroscopy using multiple views of a catheter looped in the right atrium. Registration was maintained throughout the procedure by a combination of C-arm/x-ray table tracking and respiratory motion compensation. Validation of the registration between the three-dimensional (3D) roadmap and the 2D x-ray images was performed using balloon occlusion coronary venograms. A 2D registration error of 1.2 ± 0.7 mm was achieved. In addition, a novel navigation technique was developed, called Cardiac Unfold, where an entire cardiac chamber is unfolded from 3D to 2D along with all relevant anatomical and functional information and coupled to real-time device detection. This allowed more intuitive navigation as the entire 3D scene was displayed simultaneously on a 2D plot. The accuracy of the unfold navigation was assessed off-line using 13 patient data sets by computing the registration error of the LV pacing lead electrodes which was found to be 2.2 ± 0.9 mm. Furthermore, the use of Unfold Navigation was demonstrated in real-time for four clinical cases.

Effects of simultaneous and optimized sequential cardiac resynchronization therapy on myocardial oxidative metabolism and efficiency.

PubMed

Christenson, Stuart D; Chareonthaitawee, Panithaya; Burnes, John E; Hill, Michael R S; Kemp, Brad J; Khandheria, Bijoy K; Hayes, David L; Gibbons, Raymond J

2008-02-01

Cardiac resynchronization therapy (CRT) can improve left ventricular (LV) hemodynamics and function. Recent data suggest the energy cost of such improvement is favorable. The effects of sequential CRT on myocardial oxidative metabolism (MVO(2)) and efficiency have not been previously assessed. Eight patients with NYHA class III heart failure were studied 196 +/- 180 days after CRT implant. Dynamic [(11)C]acetate positron emission tomography (PET) and echocardiography were performed after 1 hour of: 1) AAI pacing, 2) simultaneous CRT, and 3) sequential CRT. MVO(2) was calculated using the monoexponential clearance rate of [(11)C]acetate (k(mono)). Myocardial efficiency was expressed in terms of the work metabolic index (WMI). P values represent overall significance from repeated measures analysis. Global LV and right ventricular (RV) MVO(2) were not significantly different between pacing modes, but the septal/lateral MVO(2) ratio differed significantly with the change in pacing mode (AAI pacing = 0.696 +/- 0.094 min(-1), simultaneous CRT = 0.975 +/- 0.143 min(-1), and sequential CRT = 0.938 +/- 0.189 min(-1); overall P = 0.001). Stroke volume index (SVI) (AAI pacing = 26.7 +/- 10.4 mL/m(2), simultaneous CRT = 30.6 +/- 11.2 mL/m(2), sequential CRT = 33.5 +/- 12.2 mL/m(2); overall P < 0.001) and WMI (AAI pacing = 3.29 +/- 1.34 mmHg*mL/m(2)*10(6), simultaneous CRT = 4.29 +/- 1.72 mmHg*mL/m(2)*10(6), sequential CRT = 4.79 +/- 1.92 mmHg*mL/m(2)*10(6); overall P = 0.002) also differed between pacing modes. Compared with simultaneous CRT, additional changes in septal/lateral MVO(2), SVI, and WMI with sequential CRT were not statistically significant on post hoc analysis. In this small selected population, CRT increases LV SVI without increasing MVO(2), resulting in improved myocardial efficiency. Additional improvements in LV work, oxidative metabolism, and efficiency from simultaneous to sequential CRT were not significant.

Increasing sex differences in the use of cardiac resynchronization therapy with or without implantable cardioverter-defibrillator

PubMed Central

Chatterjee, Neal A.; Borgquist, Rasmus; Chang, Yuchiao; Lewey, Jennifer; Jackson, Vicki A.; Singh, Jagmeet P.; Metlay, Joshua P.; Lindvall, Charlotta

2017-01-01

Aims Previous studies have identified sex disparities in the use of cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICD), although the basis of underutilization in women remains poorly understood. The aim of this study was to assess sex differences in patterns of CRT use with our without ICD. Methods and results In this cross-sectional study using the National Inpatient Sample database we identified 311 009 patients undergoing CRT implantation in the United States between 2006 and 2012. Demographic and clinical characteristics were compared between men and women undergoing CRT implantation, with special attention to clinical predictors of left ventricular reverse remodelling (CRT response, score range: 0–4) and reduced ICD efficacy (score range: 0–7). When compared to men, women undergoing CRT implantation were significantly more likely to have ≥ 3 predictors of CRT response (47.3 vs. 33.2%, P < 0.001) and less likely to have ≥3 predictors of reduced ICD efficacy (27.0 vs. 37.3%, P < 0.001). Despite this, men were significantly more likely to undergo CRT with ICD (CRT-D) as the type of CRT (88.6 vs. 80.1% of all CRT implants). Compared to those with the greatest likelihood of CRT response (score ≥ 3), those with the least likelihood of CRT response had a significant decreased odds of CRT-D implant (adj odds ratio 0.27 [0.24–0.31], P < 0.001), with a greater decreased odds in women compared to men (P, for sex interaction <0.001). The difference in the % of CRT-D implant in men vs. women increased over the study period (P, sex Δ time trend = 0.012). Conclusion In this large, contemporary cohort, sex differences in CRT-D implantation were inversely related to predicted CRT efficacy and have increased over time. Future efforts to narrow the gap in CRT-D implantation in men and women may help better align device selection with those most likely to benefit. PMID:28065904

Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy

PubMed Central

Ptaszynska-Kopczynska, Katarzyna; Szpakowicz, Anna; Marcinkiewicz-Siemion, Marta; Lisowska, Anna; Waszkiewicz, Ewa; Witkowski, Marcin; Jakim, Piotr; Galar, Bogdan; Musial, Wlodzimierz J.

2016-01-01

Introduction Increased expression of interleukin-6 (IL-6) has been described in left ventricular dysfunction in the course of chronic heart failure. Cardiac resynchronization therapy (CRT) is a unique treatment method that may reverse the course of chronic heart failure (CHF) with reduced ejection fraction (HF-REF). We aimed to evaluate the IL-6 system, including soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130), in HF-REF patients, with particular emphasis on CRT effects. Material and methods The study enrolled 88 stable HF-REF patients (63.6 ±11.1 years, 12 females, EF < 35%) and 35 comorbidity-matched controls (63.5 ±9.8 years, 7 females). Forty-five HF-REF patients underwent CRT device implantation and were followed up after 6 months. Serum concentrations of IL-6, sIL-6R and sgp130 were determined using ELISA kits. Results The HF-REF patients had higher IL-6 (median: 2.6, IQR: 1.6–3.8 vs. 2.1, IQR: 1.4–3.1 pg/ml, p = 0.03) and lower sIL-6R concentrations compared to controls (median: 51, IQR: 36–64 vs. 53. IQR 44–76 ng/ml, p = 0.008). There was no significant difference between sgp130 concentrations. In the HF-REF group IL-6 correlated negatively with EF (r = –0.5, p = 0.001) and positively with BNP (r = 0.5, p = 0.008) and CRP concentrations (r = 0.4, p = 0.02). Patients who presented a positive response after CRT showed a smaller change of sIL-6R concentration compared to nonresponders (ΔsIL-6R: –0.2 ±7.1 vs. 7 ±14 ng/ml; p = 0.04). Conclusions HF-REF patients present higher IL-6 and lower sIL-6R levels. IL-6 concentration reflects their clinical status. CRT-related improvement of patients’ functional status is associated with a smaller change of sIL-6R concentration in time. PMID:28883848

Complications and 1-year benefit of cardiac resynchronization therapy in patients over 75 years of age - Insights from the German Device Registry.

PubMed

Köbe, Julia; Andresen, Dietrich; Maier, Sebastian; Stellbrink, Christoph; Kleemann, Thomas; Gonska, Bernd-Dieter; Reif, Sebastian; Hochadel, Matthias; Senges, Jochen; Eckardt, Lars

2017-02-01

Evidence on cardiac resynchronization therapy (CRT) in older patients is scarce and conflicting. Nevertheless, CRT in the elderly is of major practical relevance as heart failure prevalence increases with age. The German Device Registry (DEVICE) is a nationwide, prospective registry with a longitudinal follow-up design investigating device implantations in 60 German centres. The present analysis of DEVICE focussed on perioperative complication rates and 1-year outcome of patients ≥75years (n=320) compared to younger patients (n=879) receiving a CRT device. Comorbidities were more common in older patients (chronic kidney disease (CKD): 27.5% vs. 21.5%, p=0.029; atrial fibrillation (AF): 26.9% vs. 15.6%, p<0.001). Despite higher NYHA classes in the older age group, ejection fractions were comparable (27.2±7.1% ≥75years, 26.2±7.1% <75years, p=0.06). Perioperative complications and mortality rates did not show significant difference between groups. After new device implantation, absolute 1-year mortality was higher in older patients (11.0% ≥75years, 6.4% <75years, p=0.014), with a significantly lower proportion of cardiac deaths in the older group (p=0.05). Patients ≥75years being alive after 1year had lower response rates, with chronic kidney disease (OR 0.46, p<0.05) and smaller QRS complexes (OR 0.31, p<0.01) being particular risk factors for missing improvement of heart failure symptoms. As expected severe heart failure (NYHA IV) was a strong independent predictor of death (HR 1.95, p=0.01), whereas AF as underlying rhythm could be worked out as predictor for mortality especially in the younger patients (HR 2.31, p=0.002). Patients ≥75years of age receiving a CRT device do not have a higher perioperative mortality and complication rate although comorbidities (CKD and AF) occur more frequently. The absolute 1-year mortality is higher; nevertheless, the proportion of cardiac deaths is even lower in the older patients reflecting a benefit of CRT in this group. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A systematic approach to designing reliable VV optimization methodology: assessment of internal validity of echocardiographic, electrocardiographic and haemodynamic optimization of cardiac resynchronization therapy.

PubMed

Kyriacou, Andreas; Li Kam Wa, Matthew E; Pabari, Punam A; Unsworth, Beth; Baruah, Resham; Willson, Keith; Peters, Nicholas S; Kanagaratnam, Prapa; Hughes, Alun D; Mayet, Jamil; Whinnett, Zachary I; Francis, Darrel P

2013-08-10

In atrial fibrillation (AF), VV optimization of biventricular pacemakers can be examined in isolation. We used this approach to evaluate internal validity of three VV optimization methods by three criteria. Twenty patients (16 men, age 75 ± 7) in AF were optimized, at two paced heart rates, by LVOT VTI (flow), non-invasive arterial pressure, and ECG (minimizing QRS duration). Each optimization method was evaluated for: singularity (unique peak of function), reproducibility of optimum, and biological plausibility of the distribution of optima. The reproducibility (standard deviation of the difference, SDD) of the optimal VV delay was 10 ms for pressure, versus 8 ms (p=ns) for QRS and 34 ms (p<0.01) for flow. Singularity of optimum was 85% for pressure, 63% for ECG and 45% for flow (Chi(2)=10.9, p<0.005). The distribution of pressure optima was biologically plausible, with 80% LV pre-excited (p=0.007). The distributions of ECG (55% LV pre-excitation) and flow (45% LV pre-excitation) optima were no different to random (p=ns). The pressure-derived optimal VV delay is unaffected by the paced rate: SDD between slow and fast heart rate is 9 ms, no different from the reproducibility SDD at both heart rates. Using non-invasive arterial pressure, VV delay optimization by parabolic fitting is achievable with good precision, satisfying all 3 criteria of internal validity. VV optimum is unaffected by heart rate. Neither QRS minimization nor LVOT VTI satisfy all validity criteria, and therefore seem weaker candidate modalities for VV optimization. AF, unlinking interventricular from atrioventricular delay, uniquely exposes resynchronization concepts to experimental scrutiny. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Early Changes in QRS Frequency Following Cardiac Resynchronization Predict Hemodynamic Response in Left Bundle Branch Block Patients.

PubMed

Niebauer, Mark J; Rickard, John; Tchou, Patrick J; Varma, Niraj

2016-05-01

QRS characteristics are the cornerstone of patient selection in cardiac resynchronization therapy (CRT) and the presence of left bundle branch block (LBBB) and baseline QRS ≥150 milliseconds portends a good outcome. We previously showed that baseline QRS frequency analysis adds predictive value to LBBB alone and have hypothesized that a change in frequency characteristics following CRT may produce additional predictive value. We examined the QRS frequency characteristics of 182 LBBB patients before and soon after CRT. Patients were assigned to responder and nonresponder groups. Responders were defined by a decrease in left ventricular end-systolic volume (LVESV) ≥15% following CRT. We analyzed the QRS in ECG leads I, AVF, and V3 before and soon after CRT using the discrete Fourier transform algorithm. The percentage of total QRS power within discrete frequency intervals before and after CRT was calculated. The reduction in lead V3 power <10 Hz was the best indicator of response. Baseline QRS width was similar between the responders and nonresponders (162.2 ± 17.2 milliseconds vs. 158 ± 22.1 milliseconds, respectively; P = 0.180). Responders exhibited a greater reduction in QRS power <10 Hz (-17.0 ± 11.9% vs. -6.6 ± 12.5%; P < 0.001) and a significant AUC (0.743; P < 0.001). A ≥8% decline in QRS power <10 Hz produced the best predictive values (PPV = 84%, NPV = 59%). Importantly, when patients with baseline QRS <150 milliseconds were compared, the AUC improved (0.892, P < 0.001). Successful CRT produces a significant reduction in QRS power below 10 Hz, particularly when baseline QRS <150 milliseconds. These results indicate that QRS frequency changes after CRT provide additional predictive value to QRS alone. © 2016 Wiley Periodicals, Inc.

Echocardiography Practice: Insights into Appropriate Clinical Use, Technical Competence and Quality Improvement Program

PubMed Central

Kossaify, Antoine; Grollier, Gilles

2014-01-01

Echocardiography accounts for nearly half of all cardiac imaging techniques. It is a widely available and adaptable tool, as well as being a cost-effective and mainly a non-invasive test. In addition, echocardiography provides extensive clinical data, which is related to the presence or advent of different modalities (tissue Doppler imaging, speckle tracking imaging, three-dimensional mode, contrast echo, etc.), different approaches (transesophageal, intravascular, etc.), and different applications (ie, heart failure/resynchronization studies, ischemia/stress echo, etc.). In view of this, it is essential to conform to criteria of appropriate use and to keep standards of competence. In this study, we sought to review and discuss clinical practice of echocardiography in light of the criteria of appropriate clinical use, also we present an insight into echocardiographic technical competence and quality improvement project. PMID:24516342

Distribution of guidance models for cardiac resynchronization therapy in the setting of multi-center clinical trials

NASA Astrophysics Data System (ADS)

Rajchl, Martin; Abhari, Kamyar; Stirrat, John; Ukwatta, Eranga; Cantor, Diego; Li, Feng P.; Peters, Terry M.; White, James A.

2014-03-01

Multi-center trials provide the unique ability to investigate novel techniques across a range of geographical sites with sufficient statistical power, the inclusion of multiple operators determining feasibility under a wider array of clinical environments and work-flows. For this purpose, we introduce a new means of distributing pre-procedural cardiac models for image-guided interventions across a large scale multi-center trial. In this method, a single core facility is responsible for image processing, employing a novel web-based interface for model visualization and distribution. The requirements for such an interface, being WebGL-based, are minimal and well within the realms of accessibility for participating centers. We then demonstrate the accuracy of our approach using a single-center pacemaker lead implantation trial with generic planning models.

Use of an Active-Fixation Coronary Sinus Lead to Implant a Biventricular Pacemaker via the Femoral Vein

PubMed Central

Shandling, Adrian; Donohue, Daniel; Tobias, Serge; Wu, Iris; Brar, Ramandeep

2010-01-01

Cardiac resynchronization therapy, which involves the placement of a pacing lead in the right atrium and in each ventricle, is effective in treating heart failure that is caused by left bundle branch block and cardiomyopathy. The left ventricular lead is usually placed into a lateral branch of the coronary sinus via the subclavian route. When the subclavian route is unavailable, insertion of a standard, passive-fixation coronary sinus lead via the femoral approach is feasible; however, the likelihood of subsequent dislodgment is high. Herein, we describe the placement of a novel, self-retaining, active-fixation coronary sinus lead—the Attain StarFix® Model 4195 OTW Lead—in an elderly heart-failure patient, via the femoral approach. We believe that this is the 1st report of this procedure. PMID:20200636

Perioperative management of patients with cardiac implantable electronic devices.

PubMed

Poveda-Jaramillo, R; Castro-Arias, H D; Vallejo-Zarate, C; Ramos-Hurtado, L F

2017-05-01

The use of implantable cardiac devices in people of all ages is increasing, especially in the elderly population: patients with pacemakers, cardioverter-defibrillators or cardiac resynchronization therapy devices regularly present for surgery for non-cardiac causes. This review was made in order to collect and analyze the latest evidence for the proper management of implantable cardiac devices in the perioperative period. Through a detailed exploration of PubMed, Academic Search Complete (EBSCO), ClinicalKey, Cochrane (Ovid), the search software UpToDate, textbooks and patents freely available to the public on Google, we selected 33 monographs, which matched the objectives of this publication. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Association between Latest Activated Sites in the Left Ventricle and Akinetic Segments in Patients with Ischemic Cardiomyopathy.

PubMed

Sadeghian, Hakimeh; Kousari, Aliasghar; Majidi, Shahla; Rezvanfard, Mehrnaz; Kazemisaeid, Ali; Moezzi, Seyed Ali; Vasheghani Farahani, Ali; Abdar Esfahani, Morteza; Sahebjam, Mohammad; Zoroufian, Arezoo; Sadeghian, Afsaneh

2016-07-06

Background: It is not clear whether the latest activation sites in the left ventricle (LV) are matched with infracted regions in patients with ischemic cardiomyopathy (ICM). We aimed to investigate whether the latest activation sites in the LV are in agreement with the region of akinesia in patients with ICM. Methods: Data were analyzed in 106 patients (age = 60.5 ± 12.1 y, male = 88.7%) with ICM (ejection fraction ≤ 35%) who were refractory to pharmacological therapy and were referred to the echocardiography department for an evaluation of the feasibility of cardiac resynchronization therapy. Wall motion abnormalities, time to peak systolic myocardial velocity (Ts) of 6 basal and 6 mid-portion segments of the LV, and 4 frequently used dyssynchrony indices were measured using 2-dimensional echocardiography and tissue Doppler imaging (TDI). To evaluate the influence of the electrocardiographic pattern, we categorized the patients into 2 groups: patients with QRS ≤ 120 ms and those with QRS >120 ms. Results: A total of 1 272 segments were studied. The latest activation sites (with longest Ts) were most frequently located in the mid-anterior (n = 32, 30.2%) and basal-anterior segments (n = 29, 27.4%), while the most common sites of akinesia were the mid-anteroseptal (n = 65, 61.3%) and mid-septal (n = 51, 48.1%) segments. Generally, no significant concordance was found between the latest activated segments and akinesia either in all the patients or in the QRS groups. Detailed analysis within the segments indicated a good agreement between akinesia and delayed activation in the basal-lateral segment solely in the patients with QRS duration ≤ 120 ms (Φ = 0.707; p value ≤ 0.001). Conclusion: The akinetic segment on 2-dimensional echocardiogram was not matched with the latest activation sites in the LV determined by TDI in patients with ICM.

Association between Latest Activated Sites in the Left Ventricle and Akinetic Segments in Patients with Ischemic Cardiomyopathy

PubMed Central

Sadeghian, Hakimeh; Kousari, Aliasghar; Majidi, Shahla; Rezvanfard, Mehrnaz; Kazemisaeid, Ali; Moezzi, Seyed Ali; Vasheghani Farahani, Ali; Abdar Esfahani, Morteza; Sahebjam, Mohammad; Zoroufian, Arezoo; Sadeghian, Afsaneh

2016-01-01

Background: It is not clear whether the latest activation sites in the left ventricle (LV) are matched with infracted regions in patients with ischemic cardiomyopathy (ICM). We aimed to investigate whether the latest activation sites in the LV are in agreement with the region of akinesia in patients with ICM. Methods: Data were analyzed in 106 patients (age = 60.5 ± 12.1 y, male = 88.7%) with ICM (ejection fraction ≤ 35%) who were refractory to pharmacological therapy and were referred to the echocardiography department for an evaluation of the feasibility of cardiac resynchronization therapy. Wall motion abnormalities, time to peak systolic myocardial velocity (Ts) of 6 basal and 6 mid-portion segments of the LV, and 4 frequently used dyssynchrony indices were measured using 2-dimensional echocardiography and tissue Doppler imaging (TDI). To evaluate the influence of the electrocardiographic pattern, we categorized the patients into 2 groups: patients with QRS ≤ 120 ms and those with QRS >120 ms. Results: A total of 1 272 segments were studied. The latest activation sites (with longest Ts) were most frequently located in the mid-anterior (n = 32, 30.2%) and basal-anterior segments (n = 29, 27.4%), while the most common sites of akinesia were the mid-anteroseptal (n = 65, 61.3%) and mid-septal (n = 51, 48.1%) segments. Generally, no significant concordance was found between the latest activated segments and akinesia either in all the patients or in the QRS groups. Detailed analysis within the segments indicated a good agreement between akinesia and delayed activation in the basal-lateral segment solely in the patients with QRS duration ≤ 120 ms (Φ = 0.707; p value ≤ 0.001). Conclusion: The akinetic segment on 2-dimensional echocardiogram was not matched with the latest activation sites in the LV determined by TDI in patients with ICM. PMID:27956911

Novel ICD Programming and Inappropriate ICD Therapy in CRT-D Versus ICD Patients: A MADIT-RIT Sub-Study.

PubMed

Kutyifa, Valentina; Daubert, James P; Schuger, Claudio; Goldenberg, Ilan; Klein, Helmut; Aktas, Mehmet K; McNitt, Scott; Stockburger, Martin; Merkely, Bela; Zareba, Wojciech; Moss, Arthur J

2016-01-01

The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate therapy (MADIT-RIT) trial showed a significant reduction in inappropriate implantable cardioverter defibrillator (ICD) therapy in patients programmed to high-rate cut-off (Arm B) or delayed ventricular tachycardia therapy (Arm C), compared with conventional programming (Arm A). There is limited data on the effect of cardiac resynchronization therapy with a cardioverter defibrillator (CRT-D) on the effect of ICD programming. We aimed to elucidate the effect of CRT-D on ICD programming to reduce inappropriate ICD therapy in patients implanted with CRT-D or an ICD, enrolled in MADIT-RIT. The primary end point of this study was the first inappropriate ICD therapy. Secondary end points were inappropriate anti-tachycardia pacing and inappropriate ICD shock. The study enrolled 742 (49%) patients with an ICD and 757 (51%) patients with a CRT-D. Patients implanted with a CRT-D had 62% lower risk of inappropriate ICD therapy than those with an ICD only (hazard ratio [HR] =0.38, 95% confidence interval: 0.25-0.57; P<0.001). High-rate cut-off or delayed ventricular tachycardia therapy programming significantly reduced the risk of inappropriate ICD therapy compared with conventional ICD programming in ICD (HR=0.14 [B versus A]; HR=0.21 [C versus A]) and CRT-D patients (HR=0.15 [B versus A]; HR=0.23 [C versus A]; P<0.001 for all). There was a significant reduction in inappropriate anti-tachycardia pacings in both group and a significant reduction in inappropriate ICD shock in CRT-D patients. Patients implanted with a CRT-D have lower risk of inappropriate ICD therapy than those with an ICD. Innovative ICD programming significantly reduces the risk of inappropriate ICD therapy in both ICD and CRT-D patients. http://clinicaltrials.gov; Unique identifier: NCT00947310. © 2016 American Heart Association, Inc.

Changes in Implantation Patterns and Therapy Rates of Implantable Cardioverter Defibrillators over Time in Ischemic and Dilated Cardiomyopathy Patients.

PubMed

Vandenberk, Bert; Garweg, Christophe; Voros, Gabor; Floré, Vincent; Marynissen, Thomas; Sticherling, Christian; Zabel, Markus; Ector, Joris; Willems, Rik

2016-08-01

Clinical guidelines on implantable cardioverter defibrillator (ICD) therapy changed significantly in the last decades with potential inherent effects on therapy efficacy. We aimed to study therapy rates in time and the association between therapies and mortality. All patients receiving an ICD, primary and secondary prevention, were included in a single-center retrospective registry. Information on first appropriate and inappropriate therapies was documented. Dates of implant were divided in P1: 1996-2001, P2: 2002-2008, and P3: 2009-2014. A total of 727 patients, 84.9% male-66.4% ischemic cardiomyopathy (ICM)-56% primary prevention-mean follow-up 5.2 ± 4.1 years, were included. There was a shift from secondary to primary prevention indications, from ischemic to non-ICM, and from single chamber to cardiac resynchronization therapy defibrillator devices. The annual 1- and 3-year appropriate shock (AS) rate declined from 29.4% and 15.1% in P1, over 13.3% and 9.2% in P2 to 7.8% and 5.7% in P3 (log-rank P < 0.001), while inappropriate shock (IAS) rates remained unchanged (log-rank P = 0.635). After multivariate regression analysis a higher age at implant, lower left ventricular ejection fraction, history of stroke, diabetes mellitus, intake of loop diuretics or digitalis, higher creatinine, and longer QTc were independent predictors of mortality. These changes in clinical practice with a shift to primary prevention and rise in non-ICM implants caused a significant decrease in AS incidence, while IAS remained stable. Receiving AS or IAS was not an independent predictor of mortality in our real-life cohort. © 2016 Wiley Periodicals, Inc.

Minimally invasive surgical implantation of left ventricular epicardial leads for ventricular resynchronization using video-assisted thoracoscopy.

PubMed

Fernández, Angel L; García-Bengochea, José B; Ledo, Ramiro; Vega, Marino; Amaro, Antonio; Alvarez, Julián; Rubio, José; Sierra, Juan; Sánchez, Daniel

2004-04-01

Cardiac resynchronization via left ventricular or biventricular pacing is an option for selected patients with ventricular systolic dysfunction and widened QRS complex. Stimulation through a coronary vein is the technique of choice for left ventricular pacing, but this approach results in a failure rate of approximately 8%. We describe our initial experience with minimally invasive surgical implantation of left ventricular epicardial leads using video-assisted thoracoscopy. A total of 14 patients with congestive heart failure, NYHA functional class 3.2 (0.6) and mean ejection fraction 22.9 (6.8)% were included in this study. Left bundle branch block, QRS complex >140 ms and abnormal septal motion were observed in all cases. Epicardial leads were implanted on the left ventricular free wall under general anesthesia using video-assisted thoracoscopic surgery. Lead implantation was successful in 13 patients. Conversion to a small thoracotomy was necessary in one patient. All patients were extubated in the operating room. None of the patients died during their hospital stay. Follow-up showed reversal of ventricular asynchrony and significant improvement in ejection fraction and functional class. Minimally invasive surgery for ventricular resynchronization using video-assisted thoracoscopy in selected patients is a safe procedure that makes it possible to choose the best site for lead implantation and provides adequate short- and medium-term stimulation.

Pinealectomy shortens resynchronisation times of house sparrow ( Passer domesticus) circadian rhythms

NASA Astrophysics Data System (ADS)

Kumar, Vinod; Gwinner, Eberhard

2005-09-01

In many birds periodic melatonin secretion by the pineal organ is essential for the high-amplitude self-sustained output of the circadian pacemaker, and thus for the persistence of rhythmicity in 24 h oscillations controlled by it. The elimination of the pineal melatonin rhythm, or a reduction of its amplitude, renders the circadian pacemaker a less self-sustained, often highly damped, oscillatory system. A reduction in the degree of self-sustainment of a rhythm should not only increase its range of entrainment but also shorten the resynchronization times following phase-shifts of the zeitgeber. This hypothesis has not yet been directly tested. We therefore carried out the present study in which house sparrows (Passer domesticus) were subjected to both 6-h advance and 6-h delay phase-shifts of the light-dark cycle before and after the pinealectomy, and the rhythms in locomotion and feeding were recorded. The results indicate that following the delay, but not the advance, phase shift, resynchronization times were significantly shorter after pinealectomy. The dependence of resynchronization times on the presence or absence of the pineal organ is not only of theoretical interest but might also be of functional significance in the natural life of birds. A reduction or elimination of the amplitude of the melatonin secretion rhythm by the pineal organ might be responsible for faster adjustment to changes in zeitgeber conditions in nature.

The subcutaneous implantable cardioverter-defibrillator.

PubMed

Grace, Andrew

2014-01-01

To consider the case of need that underpinned the development of the subcutaneous implantable cardioverter-defibrillator (SICD), the preclinical and clinical data obtained so far, its current role and likely future. The data from prospective clinical evaluation of the device demonstrated safety and efficacy leading to Food and Drug Administration approval. This superseded earlier reports from Europe that raised some clinical concerns, previously anticipated through the introduction of new technology. Recent estimates indicate maybe 55% of patients in routine clinical practice needing an ICD are potentially suitable for a subcutaneous device. The SICD provides a useful alternative for high-energy (ICD) therapy in those deemed at risk and who need defibrillation and in whom there are no indications for cardiac resynchronization, bradycardia support or antitachycardia pacing. There is the possibility of both higher specificity and the avoidance of myo-cellular damage with shock delivery, and if these two aspects play out subcutaneous defibrillation could become an option of choice in many settings.

A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy.

PubMed

Nakamura, Makiko; Sunagawa, Osahiko; Hokama, Ryo; Tsuchiya, Hiroyuki; Miyara, Takafumi; Taba, Yoji; Touma, Takashi

2016-09-28

The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.

A COMPUTATIONAL APPROACH TO UNDERSTANDING THE CARDIAC ELECTROMECHANICAL ACTIVATION SEQUENCE IN THE NORMAL AND FAILING HEART, WITH TRANSLATION TO THE CLINICAL PRACTICE OF CRT

PubMed Central

Constantino, Jason; Hu, Yuxuan; Trayanova, Natalia A.

2012-01-01

Cardiac resynchronization therapy (CRT) is an established clinical treatment modality that aims to recoordinate contraction of the heart in dyssynchrous heart failure (DHF) patients. Although CRT reduces morbidity and mortality, a significant percentage of CRT patients fail to respond to the therapy, reflecting an insufficient understanding of the electromechanical activity of the DHF heart. Computational models of ventricular electromechanics, are now poised to fill this knowledge gap and provide a comprehensive characterization of the spatiotemporal electromechanical interactions in the normal and DHF heart. The objective of this paper is to demonstrate the powerful utility of computational models of ventricular electromechanics in characterizing the relationship between the electrical and mechanical activation in the DHF heart, and how this understanding can be utilized to devise better CRT strategies. The computational research presented here exploits knowledge regarding the three dimensional distribution of the electromechanical delay, defined as the time interval between myocyte depolarization and onset of myofiber shortening, in determining the optimal location of the LV pacing electrode for CRT. The simulation results shown here also suggest utilizing myocardial efficiency and regional energy consumption as a guide to optimize CRT. PMID:22884712

Potential role of biventricular pacing beyond advanced systolic heart failure.

PubMed

Fang, Fang; Sanderson, John E; Yu, Cheuk-Man

2013-01-01

Cardiac resynchronization therapy (CRT) is an effective therapy for advanced heart failure (HF) patients. The indications are well defined in recent guidelines and broadly indicate that CRT is suitable for chronic HF patients with left ventricular ejection fraction (EF) ≤35% and in NYHA class III or IV (Class I), and those with prolonged QRS duration ≥120 ms with left bundle branch block (LBBB) QRS morphology, or QRS duration ≥150 ms irrespective of QRS morphology (Class IIa). For patients with NYHA class II symptoms, CRT is recommended for patients with EF ≤30% and QRS duration ≥130 ms with LBBB QRS morphology (Class I, level of evidence: A), or QRS duration ≥150 ms irrespective of QRS morphology (Class IIa, level of evidence: A). However, CRT may benefit additional patients outside these criteria. In this review, we summarize the role of CRT in some subgroups, including patients with mild and moderate HF, upgrading to CRT from right ventricular (RV) pacing, bradycardia patients with routine pacing indications, congenital heart disease and specific cardiomyopathies. It is possible that CRT can give symptomatic and mortality benefits in some of these subgroups in the future and further clinical trials are warranted.  

The effects of gender on electrical therapies for the heart: procedural considerations, results and complications: A report from the XII Congress of the Italian Association on Arrhythmology and Cardiostimulation (AIAC).

PubMed

Diemberger, Igor; Marazzi, Raffaella; Casella, Michela; Vassanelli, Francesca; Galimberti, Paola; Luzi, Mario; Borrelli, Alessio; Soldati, Ezio; Golzio, Pier Giorgio; Fumagalli, Stefano; Francia, Pietro; Padeletti, Luigi; Botto, Gianluca; Boriani, Giuseppe

2017-12-01

Use of cardiac implantable devices and catheter ablation is steadily increasing in Western countries following the positive results of clinical trials. Despite the advances in scientific knowledge, tools development, and techniques improvement we still have some grey area in the field of electrical therapies for the heart. In particular, several reports highlighted differences both in medical behaviour and procedural outcomes between female and male candidates. Women are referred later for catheter ablation of supraventricular arrhythmias, especially atrial fibrillation, leading to suboptimal results. On the opposite females present greater response to cardiac resynchronization, while the benefit of implantable defibrillator in primary prevention seems to be less pronounced. Differences on aetiology, clinical profile, and development of myocardial scarring are the more plausible causes. This review will discuss all these aspects together with gender-related differences in terms of acute/late complications. We will also provide useful hints on plausible mechanisms and practical procedural aspects. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Chronic Heart Failure: We Are Fighting the Battle, but Are We Winning the War?

PubMed Central

Atherton, John J.

2012-01-01

Heart failure represents an end-stage phenotype of a number of cardiovascular diseases and is generally associated with a poor prognosis. A number of organized battles fought over the last two to three decades have resulted in considerable advances in treatment including the use of drugs that interfere with neurohormonal activation and device-based therapies such as implantable cardioverter defibrillators and cardiac resynchronization therapy. Despite this, the prevalence of heart failure continues to rise related to both the aging population and better survival in patients with cardiovascular disease. Registries have identified treatment gaps and variation in the application of evidenced-based practice, including the use of echocardiography and prescribing of disease-modifying drugs. Quality initiatives often coupled with multidisciplinary, heart failure disease management promote self-care and minimize variation in the application of evidenced-based practice leading to better long-term clinical outcomes. However, to address the rising prevalence of heart failure and win the war, we must also turn our attention to disease prevention. A combined approach is required that includes public health measures applied at a population level and screening strategies to identify individuals at high risk of developing heart failure in the future. PMID:24278681

Baseline asynchrony, assessed circumferentially using temporal uniformity of strain, besides coincidence between site of latest mechanical activation and presumed left ventricular lead position, predicts favourable prognosis after resynchronization therapy.

PubMed

Cavallino, Chiara; Rondano, Elisa; Magnani, Andrea; Leva, Lucia; Inglese, Eugenio; Dell'era, Gabriele; Occhetta, Eraldo; Bortnik, Miriam; Marino, Paolo N

2012-06-01

Traditional indexes of LV dyssynchrony (DYS) in pts to be resynchronized are sensitive to noise, while the concordance between LV lead position and site of latest mechanical activation is suggested to be, in these patients, clinically relevant. Both aspects, asynchrony and lead position have been addressed separately but unclear is their potential synergistic role in the clinical evolution of CRT patients. We assessed clinical and echocardiographic outcome, as well as mid-term prognosis, in a population of CHF patients submitted to CRT, stratified according to a novel asynchrony quantitation (temporal uniformity of strain: TUS) method and concordance or not between presumed LV lead position and site of latest mechanical activation. TUS was computed in 85 pts (QRS > 120 ms, EF < 0.35) in whom we measured circumferential and longitudinal strains using speckle-tracking 2D-echocardiography before and 3-6 months after CRT, together with triplane apical LV volumes. Optimal LV lead position in short axis view was defined as concordance of the segment with latest systolic circumferential strain prior-CRT and segment with assumed LV lead position. Assumed LV lead position was defined from a chest X-ray obtained 1 day after implantation and scored as anterior, lateral, posterior or inferior using 2 orthogonal views (antero-posterior and lateral). Following CRT, LV volume decreased (diastolic -8 ± 20%) and EF improved (+6 ± 9%, P < 0.001 for both). Two-way ANOVA revealed TUS improvement post-CRT (+22 ± 68%, P = 0.025), with a clear evidence for more marked asynchrony detectable at circumferential (from 0.53 ± 0.20 to 0.55 ± 0.19) as compared with longitudinal level (from 0.56 ± 0.14 to 0.62 ± 0.14) (P = 0.017). Multivariate analysis revealed that greater baseline asynchrony, as assessed circumferentially (P = 0.079), together with concordance between LV lead position and site of activation (P = 0.012), besides younger age (P = 0.051), longer QRS duration (P = 0.021) and higher baseline EF (P = 0.04),), but not longitudinal TUS (P = 0.231) did predict death from any cause or new episodes of pulmonary or systemic congestion requiring i.v. diuretics during a 529 ± 357 days clinical follow-up. We conclude that DYS indexed by circumferential TUS yields CRT benefits, supporting the idea of targeting TUS-measured DYS as the informative asynchrony quantitative measurement in CRT pts. Significant predictability in medium-term clinical follow-up of patients to be resynchronized is also associated with concordance between site of latest mechanical activation and presumed LV lead position in the present study.

Integrated Assessment of Left Ventricular Electrical Activation and Myocardial Strain Mapping in Heart Failure Patients: A Holistic Diagnostic Approach for Endocardial Cardiac Resynchronization Therapy, Ablation of Ventricular Tachycardia, and Biological Therapy.

PubMed

Maffessanti, Francesco; Prinzen, Frits W; Conte, Giulio; Regoli, François; Caputo, Maria Luce; Suerder, Daniel; Moccetti, Tiziano; Faletra, Francesco; Krause, Rolf; Auricchio, Angelo

2018-01-01

This study sought to test the accuracy of strain measurements based on anatomo-electromechanical mapping (AEMM) measurements compared with magnetic resonance imaging (MRI) tagging, to evaluate the diagnostic value of AEMM-based strain measurements in the assessment of myocardial viability, and the additional value of AEMM over peak-to-peak local voltages. The in vivo identification of viable tissue, evaluation of mechanical contraction, and simultaneous left ventricular activation is currently achieved using multiple complementary techniques. In 33 patients, AEMM maps (NOGA XP, Biologic Delivery Systems, Division of Biosense Webster, a Johnson & Johnson Company, Irwindale, California) and MRI images (Siemens 3T, Siemens Healthcare, Erlangen, Germany) were obtained within 1 month. MRI tagging was used to determine circumferential strain (E cc ) and delayed enhancement to obtain local scar extent (%). Custom software was used to measure E cc and local area strain (LAS) from the motion field of the AEMM catheter tip. Intertechnique agreement for E cc was good (R 2  = 0.80), with nonsignificant bias (0.01 strain units) and narrow limits of agreement (-0.03 to 0.06). Scar segments showed lower absolute strain amplitudes compared with nonscar segments: E cc (median [first to third quartile]: nonscar -0.10 [-0.15 to -0.06] vs. scar -0.04 [-0.06 to -0.02]) and LAS (-0.20 [-0.27 to -0.14] vs. -0.09 [-0.14 to -0.06]). AEMM strains accurately discriminated between scar and nonscar segments, in particular LAS (area under the curve: 0.84, accuracy = 0.76), which was superior to peak-to-peak voltages (nonscar 9.5 [6.5 to 13.3] mV vs. scar 5.6 [3.4 to 8.3] mV; area under the curve: 0.75). Combination of LAS and peak-to-peak voltages resulted in 86% accuracy. An integrated AEMM approach can accurately determine local deformation and correlates with the scar extent. This approach has potential immediate application in the diagnosis, delivery of intracardiac therapies, and their intraprocedural evaluation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Addressing the Global Burden of Trauma in Major Surgery

PubMed Central

Dobson, Geoffrey P.

2015-01-01

Despite a technically perfect procedure, surgical stress can determine the success or failure of an operation. Surgical trauma is often referred to as the “neglected step-child” of global health in terms of patient numbers, mortality, morbidity, and costs. A staggering 234 million major surgeries are performed every year, and depending upon country and institution, up to 4% of patients will die before leaving hospital, up to 15% will have serious post-operative morbidity, and 5–15% will be readmitted within 30 days. These percentages equate to around 1000 deaths and 4000 major complications every hour, and it has been estimated that 50% may be preventable. New frontline drugs are urgently required to make major surgery safer for the patient and more predictable for the surgeon. We review the basic physiology of the stress response from neuroendocrine to genomic systems, and discuss the paucity of clinical data supporting the use of statins, beta-adrenergic blockers and calcium-channel blockers. Since cardiac-related complications are the most common, particularly in the elderly, a key strategy would be to improve ventricular-arterial coupling to safeguard the endothelium and maintain tissue oxygenation. Reduced O2 supply is associated with glycocalyx shedding, decreased endothelial barrier function, fluid leakage, inflammation, and coagulopathy. A healthy endothelium may prevent these “secondary hit” complications, including possibly immunosuppression. Thus, the four pillars of whole body resynchronization during surgical trauma, and targets for new therapies, are: (1) the CNS, (2) the heart, (3) arterial supply and venous return functions, and (4) the endothelium. This is termed the Central-Cardio-Vascular-Endothelium (CCVE) coupling hypothesis. Since similar sterile injury cascades exist in critical illness, accidental trauma, hemorrhage, cardiac arrest, infection and burns, new drugs that improve CCVE coupling may find wide utility in civilian and military medicine. PMID:26389122

Circadian rhythms in heart rate, motility, and body temperature of wild-type C57 and eNOS knock-out mice under light-dark, free-run, and after time zone transition.

PubMed

Arraj, M; Lemmer, B

2006-01-01

The nitric oxide (NO) system is involved in the regulation of the cardiovascular system in controlling central and peripheral vascular tone and cardiac functions. It was the aim of this study to investigate in wild-type C57BL/6 and endothelial nitric oxide synthase (eNOS) knock-out mice (eNOS-/-) the contribution of NO on the circadian rhythms in heart rate (HR), motility (motor activity [MA]), and body temperature (BT) under various environmental conditions. Experiments were performed in 12:12 h of a light:dark cycle (LD), under free-run in total darkness (DD), and after a phase delay shift of the LD cycle by -6 h (i.e., under simulation of a westward time zone transition). All parameters were monitored by radiotelemetry in freely moving mice. In LD, no significant differences in the rhythms of HR and MA were observed between the two strains of mice. BT, however, was significantly lower during the light phase in eNOS-/- mice, resulting in a significantly greater amplitude. The period of the free-running rhythm in DD was slightly shorter for all variables, though not significant. In general, rhythmicity was greater in eNOS-/- than in C57 mice both in LD and DD. After a delay shift of the LD cycle, HR and BT were resynchronized to the new LD schedule within 5-6 days, and resynchronization of MA occurred within 2-3 days. The results in telemetrically instrumented mice show that complete knock-out of the endothelial NO system--though expressed in the suprachiasmatic nuclei and in peripheral tissues--did not affect the circadian organization of heart rate and motility. The circadian regulation of the body temperature was slightly affected in eNOS-/- mice.

Triple-site pacing for cardiac resynchronization in permanent atrial fibrillation - Acute phase results from a prospective observational study.

PubMed

Marques, Pedro; Nobre Menezes, Miguel; Lima da Silva, Gustavo; Bernardes, Ana; Magalhães, Andreia; Cortez-Dias, Nuno; Carpinteiro, Luís; de Sousa, João; Pinto, Fausto J

2016-06-01

Multi-site pacing is emerging as a new method for improving response to cardiac resynchronization therapy (CRT), but has been little studied, especially in patients with atrial fibrillation. We aimed to assess the effects of triple-site (Tri-V) vs. biventricular (Bi-V) pacing on hemodynamics and QRS duration. This was a prospective observational study of patients with permanent atrial fibrillation and ejection fraction <40% undergoing CRT implantation (n=40). One right ventricular (RV) lead was implanted in the apex and another in the right ventricular outflow tract (RVOT) septal wall. A left ventricular (LV) lead was implanted in a conventional venous epicardial position. Cardiac output (using the FloTrac™ Vigileo™ system), mean QRS and ejection fraction were calculated. Mean cardiac output was 4.81±0.97 l/min with Tri-V, 4.68±0.94 l/min with RVOT septal and LV pacing, and 4.68±0.94 l/min with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV). Mean pre-implantation QRS was 170±25 ms, 123±18 ms with Tri-V, 141±25 ms with RVOT septal pacing and LV pacing and 145±19 with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV and pre-implantation). Mean ejection fraction was significantly higher with Tri-V (30±11%) vs. Bi-V pacing (28±12% with RVOT septal and LV pacing and 28±11 with RV apical and LV pacing) and pre-implantation (25±8%). Tri-V pacing produced higher cardiac output and shorter QRS duration than Bi-V pacing. This may have a significant impact on the future of CRT. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

The systolic index: a noninvasive approach for the assessment of cardiac function: implications for patients with DDD and CRT devices.

PubMed

Chirife, Raul; Ruiz, G Aurora; Gayet, Enrique; Muratore, Claudio; Mazzetti, Héctor; Pellegrini, Alejandro; Tentori, M Cristina

2013-10-01

Our objective was to evaluate the systolic index (SI), the ratio between rate-corrected left ventricular ejection time (LVETc), and a preejection period surrogate (PEPsu), to assess cardiac function in patients with DDD and cardiac resynchronization therapy (CRT) pacemakers. LVETc and PEPsu were automatically measured from electrocardiogram and finger photoplethismography. Atrioventricular (AV) and mode switch (CRT to DDD) were used as hemodynamic challenges. Performance of SI, beat-by-beat systolic blood pressure (SBP), and Doppler aortic velocity/time integral (AoVTI) were compared in 36 patients, and SI's detection of CRT to DDD mode switch in nine patients, responders to CRT. AVs were changed from 30 ms to 250 ms (20 ms steps) at constant paced heart rate, alternating with a reference AV (RefAV), to reduce hemodynamic drift. The coefficient of variation (standard deviation/mean) of SI, SBP, and AoVTI during all RefAVs were used as error marker. The percentage detection of hemodynamic changes during AV transitions was a marker of sensitivity. Fifty-five patients (males 62%, age 69.6 ± 17) were studied. SI detected 441 of 544 transitions (81%) versus 361 (66%) of SBP (P = 0.005). Error during RefAVs was smaller for SI (3.4%) as compared to AoVTI (7.8%, P = 0.015) and to SBP (5.7%, P = 0.005). SIs correlated with AoVTI (R from 0.71 to 0.98, all P < 0.001). SI detected all CRT to DDD changes (P < 0.001). The noninvasive SI obtained with a simple, observer-independent hemodynamic assessment procedure has higher accuracy than SBP and AoVTI and better sensitivity than SBP. It detects mechanical resynchronization in CRT and allows programming a suitable AV delay. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

The MOnitoring Resynchronization dEvices and CARdiac patiEnts (MORE-CARE) randomized controlled trial: phase 1 results on dynamics of early intervention with remote monitoring.

PubMed

Boriani, Giuseppe; Da Costa, Antoine; Ricci, Renato Pietro; Quesada, Aurelio; Favale, Stefano; Iacopino, Saverio; Romeo, Francesco; Risi, Arnaldo; Mangoni di S Stefano, Lorenza; Navarro, Xavier; Biffi, Mauro; Santini, Massimo; Burri, Haran

2013-08-21

Remote monitoring (RM) in patients with advanced heart failure and cardiac resynchronization therapy defibrillators (CRT-D) may reduce delays in clinical decisions by transmitting automatic alerts. However, this strategy has never been tested specifically in this patient population, with alerts for lung fluid overload, and in a European setting. The main objective of Phase 1 (presented here) is to evaluate if RM strategy is able to reduce time from device-detected events to clinical decisions. In this multicenter randomized controlled trial, patients with moderate to severe heart failure implanted with CRT-D devices were randomized to a Remote group (with remote follow-up and wireless automatic alerts) or to a Control group (with standard follow-up without alerts). The primary endpoint of Phase 1 was the delay between an alert event and clinical decisions related to the event in the first 154 enrolled patients followed for 1 year. The median delay from device-detected events to clinical decisions was considerably shorter in the Remote group compared to the Control group: 2 (25(th)-75(th) percentile, 1-4) days vs 29 (25(th)-75(th) percentile, 3-51) days respectively, P=.004. In-hospital visits were reduced in the Remote group (2.0 visits/patient/year vs 3.2 visits/patient/year in the Control group, 37.5% relative reduction, P<.001). Automatic alerts were successfully transmitted in 93% of events occurring outside the hospital in the Remote group. The annual rate of all-cause hospitalizations per patient did not differ between the two groups (P=.65). RM in CRT-D patients with advanced heart failure allows physicians to promptly react to clinically relevant automatic alerts and significantly reduces the burden of in-hospital visits. Clinicaltrials.gov NCT00885677; http://clinicaltrials.gov/show/NCT00885677 (Archived by WebCite at http://www.webcitation.org/6IkcCJ7NF).

The MOnitoring Resynchronization dEvices and CARdiac patiEnts (MORE-CARE) Randomized Controlled Trial: Phase 1 Results on Dynamics of Early Intervention With Remote Monitoring

PubMed Central

Da Costa, Antoine; Ricci, Renato Pietro; Quesada, Aurelio; Favale, Stefano; Iacopino, Saverio; Romeo, Francesco; Risi, Arnaldo; Mangoni di S Stefano, Lorenza; Navarro, Xavier; Biffi, Mauro; Santini, Massimo; Burri, Haran

2013-01-01

Background Remote monitoring (RM) in patients with advanced heart failure and cardiac resynchronization therapy defibrillators (CRT-D) may reduce delays in clinical decisions by transmitting automatic alerts. However, this strategy has never been tested specifically in this patient population, with alerts for lung fluid overload, and in a European setting. Objective The main objective of Phase 1 (presented here) is to evaluate if RM strategy is able to reduce time from device-detected events to clinical decisions. Methods In this multicenter randomized controlled trial, patients with moderate to severe heart failure implanted with CRT-D devices were randomized to a Remote group (with remote follow-up and wireless automatic alerts) or to a Control group (with standard follow-up without alerts). The primary endpoint of Phase 1 was the delay between an alert event and clinical decisions related to the event in the first 154 enrolled patients followed for 1 year. Results The median delay from device-detected events to clinical decisions was considerably shorter in the Remote group compared to the Control group: 2 (25th-75th percentile, 1-4) days vs 29 (25th-75th percentile, 3-51) days respectively, P=.004. In-hospital visits were reduced in the Remote group (2.0 visits/patient/year vs 3.2 visits/patient/year in the Control group, 37.5% relative reduction, P<.001). Automatic alerts were successfully transmitted in 93% of events occurring outside the hospital in the Remote group. The annual rate of all-cause hospitalizations per patient did not differ between the two groups (P=.65). Conclusions RM in CRT-D patients with advanced heart failure allows physicians to promptly react to clinically relevant automatic alerts and significantly reduces the burden of in-hospital visits. Trial Registration Clinicaltrials.gov NCT00885677; http://clinicaltrials.gov/show/NCT00885677 (Archived by WebCite at http://www.webcitation.org/6IkcCJ7NF). PMID:23965236

Implementation of a Publish-Subscribe Protocol in Microgrid Islanding and Resynchronization with Self-Discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Starke, M.; Herron, A.; King, D.

Communications systems and protocols are becoming second nature to utilities operating distribution systems. Traditionally, centralized communication approaches are often used, while recently in microgrid applications, distributed communication and control schema emerge offering several advantages such as improved system reliability, plug-and-play operation and distributed intelligence. Still, operation and control of microgrids including distributed communication schema have been less of a discussion in the literature. To address the challenge of multiple-inverter microgrid synchronization, a publish-subscribe protocol based, Data Distribution Service (DDS), communication schema for microgrids is proposed in this paper. The communication schema is discussed in details for individual devices such asmore » generators, photovoltaic systems, energy storage systems, microgrid point of common coupling switch, and supporting applications. In conclusion, islanding and resynchronization of a microgrid are demonstrated on a test-bed utilizing this schema.« less

Implementation of a Publish-Subscribe Protocol in Microgrid Islanding and Resynchronization with Self-Discovery

DOE PAGES

Starke, M.; Herron, A.; King, D.; ...

2017-08-24

Communications systems and protocols are becoming second nature to utilities operating distribution systems. Traditionally, centralized communication approaches are often used, while recently in microgrid applications, distributed communication and control schema emerge offering several advantages such as improved system reliability, plug-and-play operation and distributed intelligence. Still, operation and control of microgrids including distributed communication schema have been less of a discussion in the literature. To address the challenge of multiple-inverter microgrid synchronization, a publish-subscribe protocol based, Data Distribution Service (DDS), communication schema for microgrids is proposed in this paper. The communication schema is discussed in details for individual devices such asmore » generators, photovoltaic systems, energy storage systems, microgrid point of common coupling switch, and supporting applications. In conclusion, islanding and resynchronization of a microgrid are demonstrated on a test-bed utilizing this schema.« less

76 FR 81513 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-28

...] Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug... meeting will be closed to the public. Name of Committee: Cellular, Tissue, and Gene Therapies Advisory... programs in the Cellular and Tissue Branch, Office of Cellular, Tissue and Gene Therapies, Center for...

Light as a chronobiologic countermeasure for long-duration space operations

NASA Technical Reports Server (NTRS)

Samel, Alexander (Editor); Gander, Philippa (Editor); Evans, Julie; Graeber, R. Curtis; Hackett, Elizabeth; Keil, Lanny; Maab, Hartmut; Raabe, Wolfgang; Rosekind, Mark; Rountree, Mike

1991-01-01

Long-duration space missions require adaptation to work-rest schedules which are substantially shifted with respect to earth. Astronauts are expected to work in two-shift operations and the environmental synchronizers (zeitgebers) in a spacecraft differ significantly from those on earth. A study on circadian rhythms, sleep, and performance was conducted by exposing four subjects to 6 deg head-down tilt bedrest (to simulate the effects of the weightless condition) and imposing a 12-h shift (6 h delay per day for two days). Bright light was tested in a cross-over design as a countermeasure for achieving faster resynchronization and regaining stable conditions for sleep and circadian rhythmicity. Data collection included objective sleep recording, temperature, heart rate, and excretion of hormones and electrolytes as well as performance and responses to questionnaires. Even without a shift in the sleep-wake cycle, the sleep quantity, circadian amplitudes and 24 h means decreased in many functions under bedrest conditions. During the shift days, sleepiness and fatigue increased, and alertness decreased. However, sleep quantity was regained, and resynchronization was completed within seven days after the shift for almost all functions, irrespective of whether light was administered during day-time or night-time hours. The time of day of light exposure surprisingly appeared not to have a discriminatory effect on the resynchronization speed under shift and bedrest conditions. The results indicate that simulated weightlessness alters circadian rhythms and sleep, and that schedule changes induce additional physiological disruption with decreased subjective alertness and increased fatigue. Because of their operational implications, these phenomena deserve additional investigation.

Identification of spinal tissues loaded by manual therapy: a robot-based serial dissection technique applied in porcine motion segments.

PubMed

Kawchuk, Gregory N; Carrasco, Alejandro; Beecher, Grayson; Goertzen, Darrell; Prasad, Narasimha

2010-10-15

Serial dissection of porcine motion segments during robotic control of vertebral kinematics. To identify which spinal tissues are loaded in response to manual therapy (manipulation and mobilization) and to what magnitude. Various theoretical constructs attempt to explain how manual therapies load specific spinal tissues. By using a parallel robot to control vertebral kinematics during serial dissection, it is possible to quantify the loads experienced by discrete spinal tissues undergoing common therapeutic procedures such as manual therapy. In 9 porcine cadavers, manual therapy was provided to L3 and the kinematic response of L3-L4 recorded. The exact kinematic trajectory experienced by L3-L4 in response to manual therapy was then replayed to the isolated segment by a parallel robot equipped with a 6-axis load cell. Discrete spinal tissues were then removed and the kinematic pathway replayed. The change in forces and moments following tissue removal were considered to be those applied to that specific tissue by manual therapy. In this study, both manual therapies affected spinal tissues. The intervertebral disc experienced the greatest forces and moments arising from both manipulation and mobilization. This study is the first to identify which tissues are loaded in response to manual therapy. The observation that manual therapy loads some tissues to a much greater magnitude than others offers a possible explanation for its modest treatment effect; only conditions involving these tissues may be influenced by manual therapy. Future studies are planned to determine if manual therapy can be altered to target (or avoid) specific spinal tissues.

Heart failure severity, inappropriate ICD therapy, and novel ICD programming: a MADIT-RIT substudy.

PubMed

Daimee, Usama A; Vermilye, Katherine; Rosero, Spencer; Schuger, Claudio D; Daubert, James P; Zareba, Wojciech; McNitt, Scott; Polonsky, Bronislava; Moss, Arthur J; Kutyifa, Valentina

2017-12-01

The effects of heart failure (HF) severity on risk of inappropriate implantable cardioverter-defibrillator (ICD) therapy have not been thoroughly investigated. We aimed to study the association between HF severity and inappropriate ICD therapy in MADIT-RIT. MADIT-RIT randomized 1,500 patients to three ICD programming arms: conventional (Arm A), high-rate cut-off (Arm B: ≥200 beats/min), and delayed therapy (Arm C: 60-second delay for ≥170 beats/min). We evaluated the association between New York Heart Association (NYHA) class III (n = 256) versus class I-II (n = 251) and inappropriate ICD therapy in Arm A patients with ICD-only and cardiac resynchronization therapy with defibrillator (CRT-D). We additionally assessed benefit of novel ICD programming in Arms B and C versus Arm A by NYHA classification. In Arm A, the risk of inappropriate therapy was significantly higher in those with NYHA III versus NYHA I-II for both ICD (hazard ratio [HR] = 2.55, confidence interval [CI]: 1.51-4.30, P < 0.001) and CRT-D patients (HR = 3.73, CI: 1.14-12.23, P = 0.030). This was consistent for inappropriate ATP and inappropriate ICD therapy < 200 beats/min, but not for inappropriate shocks. Novel ICD programming significantly reduced inappropriate therapy in patients with both NYHA III (Arm B vs Arm A: HR = 0.08, P < 0.001; Arm C vs Arm A: HR = 0.17, P < 0.001) and NYHA I-II (Arm B vs Arm A: HR = 0.25, P < 0.001; Arm C vs Arm A: HR = 0.28, P < 0.001). Patients with more severe HF are at increased risk for inappropriate ICD therapy, particularly ATP due to arrhythmias < 200 beats/min. Novel programming with high-rate cut-off or delayed detection reduces inappropriate ICD therapies in both mild and moderate HF. © 2017 Wiley Periodicals, Inc.

Relationship between mechanical dyssynchrony and intra-operative electrical delay times in patients undergoing cardiac resynchronization therapy

PubMed Central

2014-01-01

Background It is important to understand the relationship between electrical and mechanical ventricular activation in CRT patients. By measuring local electrical activation at multiple locations within the coronary veins and myocardial contraction at the same locations in the left ventricle, we determined the relationship between electrical and mechanical activation at potential left ventricular pacing locations. Methods In this study, mechanical contraction times were computed using high temporal resolution cine cardiovascular magnetic resonance (CMR) data, while electrical activation times were derived from intra-procedural local electrograms. Results In our cohort, there was a strong correlation between electrical and mechanical delay times within each patient (R2 = 0.78 ± 0.23). Additionally, the latest electrically activated location corresponded with the latest mechanically contracting location in 91% of patients. Conclusions This study provides initial evidence that our method of obtaining non-invasive mechanical activation patterns accurately reflects the underlying electromechanical substrate of intraventricular dyssynchrony. PMID:24393383

Is the epicardial left ventricular lead implantation an alternative approach to percutaneous attempt in patients with Steinert disease? A case report

PubMed Central

PAPA, ANDREA ANTONIO; RAGO, ANNA; PETILLO, ROBERTA; D’AMBROSIO, PAOLA; SCUTIFERO, MARIANNA; FEO, MARISA DE; MAIELLO, CIRO; PALLADINO, ALBERTO

2017-01-01

Steinert’s disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder characterized by myotonia, muscle and facial weakness, cataracts, cognitive, endocrine and gastrointestinal involvement, and cardiac conduction abnormalities. Although mild myocardial dysfunction may be detected in this syndrome with age, overt myocardial dysfunction with heart failure is not frequent. Cardiac resynchronization therapy is an effective treatment to improve morbidity and reduce mortality in patients with DM1 showing intra-ventricular conduction delay and/or congestive heart failure. We report the case of a patient with Steinert disease showing an early onset ventricular dysfunction due to chronic right ventricular apical pacing, in which an epicardial left ventricular lead implantation was performed following the failure of the percutaneous attempt. As no relief in symptoms of heart failure, nor an improvement of left ventricular ejection fraction and reverse remodelling was observed six months later, the patient was addressed to the heart transplantation.

Left phrenic nerve anatomy relative to the coronary venous system: Implications for phrenic nerve stimulation during cardiac resynchronization therapy.

PubMed

Spencer, Julianne H; Goff, Ryan P; Iaizzo, Paul A

2015-07-01

The objective of this study was to quantitatively characterize anatomy of the human phrenic nerve in relation to the coronary venous system, to reduce undesired phrenic nerve stimulation during left-sided lead implantations. We obtained CT scans while injecting contrast into coronary veins of 15 perfusion-fixed human heart-lung blocs. A radiopaque wire was glued to the phrenic nerve under CT, then we created three-dimensional models of anatomy and measured anatomical parameters. The left phrenic nerve typically coursed over the basal region of the anterior interventricular vein, mid region of left marginal veins, and apical region of inferior and middle cardiac veins. There was large variation associated with the average angle between nerve and veins. Average angle across all coronary sinus tributaries was fairly consistent (101.3°-111.1°). The phrenic nerve coursed closest to the middle cardiac vein and left marginal veins. The phrenic nerve overlapped a left marginal vein in >50% of specimens. © 2015 Wiley Periodicals, Inc.

Determination of Three-Dimensional Left Ventricle Motion to Analyze Ventricular Dyssyncrony in SPECT Images

NASA Astrophysics Data System (ADS)

Rebelo, Marina de Sá; Aarre, Ann Kirstine Hummelgaard; Clemmesen, Karen-Louise; Brandão, Simone Cristina Soares; Giorgi, Maria Clementina; Meneghetti, José Cláudio; Gutierrez, Marco Antonio

2009-12-01

A method to compute three-dimension (3D) left ventricle (LV) motion and its color coded visualization scheme for the qualitative analysis in SPECT images is proposed. It is used to investigate some aspects of Cardiac Resynchronization Therapy (CRT). The method was applied to 3D gated-SPECT images sets from normal subjects and patients with severe Idiopathic Heart Failure, before and after CRT. Color coded visualization maps representing the LV regional motion showed significant difference between patients and normal subjects. Moreover, they indicated a difference between the two groups. Numerical results of regional mean values representing the intensity and direction of movement in radial direction are presented. A difference of one order of magnitude in the intensity of the movement on patients in relation to the normal subjects was observed. Quantitative and qualitative parameters gave good indications of potential application of the technique to diagnosis and follow up of patients submitted to CRT.

A new electrocardiogram algorithm for diagnosing loss of ventricular capture during cardiac resynchronisation therapy.

PubMed

Ganière, Vincent; Domenichini, Giulia; Niculescu, Viviana; Cassagneau, Romain; Defaye, Pascal; Burri, Haran

2013-03-01

The prerequisite for cardiac resynchronization therapy (CRT) is ventricular capture, which may be verified by analysis of the surface electrocardiogram (ECG). Few algorithms exist to diagnose loss of ventricular capture. Electrocardiograms from 126 CRT patients were analysed during biventricular (BV), right ventricular (RV), and left ventricular (LV) pacing. An algorithm evaluating QRS narrowing in the limb leads and increasing negativity in lead I to diagnose changes in ventricular capture was devised, prospectively validated, and compared with two existing algorithms. Performance of the algorithm according to ventricular lead position was also assessed. Our algorithm had an accuracy of 88% to correctly identify the changes in ventricular capture (either loss or gain of RV or LV capture). The algorithm had a sensitivity of 94% and a specificity of 96% with an accuracy of 96% for identifying loss of LV capture (the most clinically relevant change), and compared favourably with the existing algorithms. Performance of the algorithms was not significantly affected by RV or LV lead position. A simple two-step algorithm evaluating QRS width in the limb leads and changes in negativity in lead I can accurately diagnose the lead responsible for intermittent loss of ventricular capture in CRT. This simple tool may be of particular use outside the setting of specialized device clinics.

Arrhythmia-induced cardiomyopathies: the riddle of the chicken and the egg still unanswered?

PubMed

Simantirakis, Emmanuel N; Koutalas, Emmanuel P; Vardas, Panos E

2012-04-01

The hypothesis testing of inappropriate fast, irregular, or asynchronous myocardial contraction provoking cardiomyopathy has been the primary focus of numerous research efforts, especially during the last few decades. Rapid ventricular rates resulting from supraventricular arrhythmias and atrial fibrillation (AF), irregularity of heart rhythm-basic element of AF-and asynchrony, as a consequence of right ventricular pacing, bundle branch block, or frequent premature ventricular complexes, have been established as primary causes of arrhythmia-induced cardiomyopathy. The main pathophysiological pathways involved have been clarified, including neurohumoral activation, energy stores depletion, and abnormalities in stress and strain. Unfortunately, from a clinical point of view, patients usually seek medical advice only when symptoms develop, while the causative arrhythmia may be present for months or years, resulting in myocardial remodelling, diastolic, and systolic dysfunction. In some cases, making a definite diagnosis may become a strenuous exercise for the treating physician, as the arrhythmia may not be present and, additionally, therapy must be applied for the diagnosis to be confirmed retrospectively. The diagnostic process is also hardened due to the fact that strict diagnosing criteria are still a matter of discrepancy. Therapy options include pharmaceutical agents trials, catheter-based therapies and, in the context of chronic ventricular pacing, resynchronization. For the majority of patients, partial or complete recovery is expected, although they have to be followed up thoroughly due to the risk of recurrence. Large, randomized controlled trials are more than necessary to optimize patients' stratification and therapeutic strategy choices.

75 FR 65640 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug... closed to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee. General... Branch, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, FDA...

Quality of life measured with EuroQol-five dimensions questionnaire predicts long-term mortality, response, and reverse remodelling in cardiac resynchronization therapy patients.

PubMed

Nagy, Klaudia Vivien; Széplaki, Gábor; Perge, Péter; Boros, András Mihály; Kosztin, Annamária; Apor, Astrid; Molnár, Levente; Szilágyi, Szabolcs; Tahin, Tamás; Zima, Endre; Kutyifa, Valentina; Gellér, László; Merkely, Béla

2017-11-22

There are previous studies on quality of life (QoL) in cardiac resynchronization therapy (CRT) patients; however, there are no data with the short EuroQol-five dimensions (EQ-5D) questionnaire predicting outcomes. We aimed to assess the predictive role of baseline QoL and QoL change at 6 months after CRT with EQ-5D on 5-year mortality and response. In our prospective follow-up study, 130 heart failure (HF) patients undergoing CRT were enrolled. Clinical evaluation, echocardiography, and EQ-5D were performed at baseline and at 6 months of follow-up, continued to 5 years. Primary endpoint was all-cause mortality at 5 years. Secondary endpoints were (i) clinical response with at least one class improvement in New York Heart Association without HF hospitalization and (ii) reverse remodelling with 15% reduction in left ventricular end-systolic volume at 6 months. Fifty-four (41.5%) patients died during 5 years, 85 (65.3%) clinical responders were identified, and 63 patients (48.5%) had reverse remodelling. Baseline issues with mobility were associated with lower response [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.16-0.84; P = 0.018]. Lack of reverse remodelling correlated with self-care issues at baseline (OR 0.10, 95% CI 0.01-0.94; P = 0.04). Furthermore, self-care difficulties [hazard ratio (HR) 2.39, 95% CI 1.17-4.86; P = 0.01) or more anxiety (HR 1.51, 95% CI 1.00-2.26; P = 0.04) predicted worse long-term survival. At 6 months, mobility (HR 3.95, 95% CI 1.89-8.20; P < 0.001), self-care (HR 7.69, 95% CI 2.23-25.9; P = 0.001), or ≥ 10% visual analogue scale (VAS) (HR 2.24, 95% CI 1.27-3.94; P = 0.005) improvement anticipated better survival at 5 years. EuroQol-five dimension is a simple method assessing QoL in CRT population. Mobility issues at baseline are associated with lower clinical response, whereas self-care issues predict lack of reverse remodelling. Problems with mobility or anxiety before CRT and persistent issues with mobility, self-care, and VAS scale at 6 months predict adverse outcome. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology

77 FR 65693 - Cellular, Tissue and Gene Therapies Advisory Committee; Amendment of Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

...] Cellular, Tissue and Gene Therapies Advisory Committee; Amendment of Notice AGENCY: Food and Drug... notice of a meeting of the Cellular, Tissue and Gene Therapies Advisory Committee. This meeting was... announced that a meeting of the Cellular, Tissue and Gene Therapies Advisory Committee would be held on...

Non-selective His bundle pacing with a biphasic waveform: enhancing septal resynchronization.

PubMed

Ortega, Daniel F; Barja, Luis D; Logarzo, Emilio; Mangani, Nicolas; Paolucci, Analia; Bonomini, Maria P

2018-05-01

His bundle pacing has shown to prevent detrimental effects from right ventricular apical pacing (RVA) and proved to resynchronize many conduction disturbances cases. However, the extent of His bundle pacing resynchronization is limited. An optimized stimulation waveform could expand this limit when implemented in His bundle pacing sets. In this work, we temporarily implemented RVA and Non-selective His bundle pacing with a biphasic anodal-first waveform (AF-nHB) and compared their effects against sinus rhythm (SR). Fifteen patients referred for electrophysiologic study with conduction disturbances, cardiomyopathy and ejection fraction below 35% were enrolled for the study. The following acute parameters were measured: QRS duration, left ventricular activation (RLVT), time of isovolumic contraction (IVCT), ejection fraction (EF), and dP/dtmax. QRS duration and RLVT decreased markedly under AF-nHB (SR: 169 ± 34 ms vs. nHB: 116 ± 31 ms, P < 0.0005) while RVA significantly increased QRS duration (SR: 169 ms vs. RVA: 198 ms, P < 0.05) and did not change RLVT (P = NS). Consistently, IVCT moderately decreased under AF-nHB (SR: 238 ms vs. RVA: 184 ms, P < 0.05 vs. SR) and dP/dtmax showed a 93.35 [mmHg] average increase under AF-nHB against SR. Also, T-wave inversions were observed during AF-nHB immediately after SR and RVA pacing suggesting the occurrence of cardiac memory. AF-nHB corrected bundle branch blocks in patients with severe conduction disturbances, even in those with dilated cardiomiopathy, outstanding from RVA. Also, the occurrence of cardiac memory during AF-nHB turned up as an observational finding of this study.

Circadian rhythm resynchronization improved isoflurane-induced cognitive dysfunction in aged mice.

PubMed

Song, Jia; Chu, Shuaishuai; Cui, Yin; Qian, Yue; Li, Xiuxiu; Xu, Fangxia; Shao, Xueming; Ma, Zhengliang; Xia, Tianjiao; Gu, Xiaoping

2018-04-13

Postoperative cognitive dysfunction (POCD) is a common clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery. Advanced age is a significant independent risk factor for POCD. We previously reported that in young mice, sleep-wake rhythm is involved in the isoflurane-induced memory impairment. In present study, we sought to determine whether advanced age increased the risk of POCD through aggravated and prolonged post-anesthetic circadian disruption in the elderly. We constructed POCD model by submitting the mice to 5-h 1.3% isoflurane anesthesia from Zeitgeber Time (ZT) 14 to ZT19. Under novel object recognition assay (NOR) and Morris water maze (MWM) test, We found 5-h isoflurane anesthesia impaired the cognition of young mice for early 3 days after anesthesia but damaged the aged for at least 1 week. With Mini-Mitter continuously monitoring, a 3.22 ± 0.75 h gross motor activity acrophase delay was manifested in young mice on D1, while in the aged mice, the gross motor activity phase shift lasted for 3 days, consistent with the body temperature rhythm trends of change. Melatonin has been considered as an effective remedy for circadian rhythm shift. In aged mice, melatonin was pretreated intragastrically at the dose of 10 mg/kg daily for 7 consecutive days before anesthesia. We found that melatonin prevented isoflurane-induced cognitive impairments by restoring the locomotor activity and temperature circadian rhythm via clock gene resynchronization. Overall, these results indicated that Long-term isoflurane anesthesia induced more aggravated and prolonged memory deficits and circadian rhythms disruption in aged mice. Melatonin could prevent isoflurane-induced cognitive impairments by circadian rhythm resynchronization. Copyright © 2018. Published by Elsevier Inc.

Mortality reduction in relation to implantable cardioverter defibrillator programming in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT).

PubMed

Ruwald, Anne-Christine; Schuger, Claudio; Moss, Arthur J; Kutyifa, Valentina; Olshansky, Brian; Greenberg, Henry; Cannom, David S; Estes, N A Mark; Ruwald, Martin H; Huang, David T; Klein, Helmut; McNitt, Scott; Beck, Christopher A; Goldstein, Robert; Brown, Mary W; Kautzner, Josef; Shoda, Morio; Wilber, David; Zareba, Wojciech; Daubert, James P

2014-10-01

The benefit of novel implantable cardioverter defibrillator (ICD) programming in reducing inappropriate ICD therapy and mortality was demonstrated in Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). However, the cause of mortality reduction remains incompletely evaluated. We aimed to identify factors associated with mortality, with focus on ICD therapy and programming in the MADIT-RIT population. In MADIT-RIT, 1500 patients with a primary prophylactic indication for ICD or cardiac resynchronization therapy with defibrillator were randomized to 1 of 3 different ICD programming arms: conventional programming (ventricular tachycardia zone ≥170 beats per minute), high-rate programming (ventricular tachycardia zone ≥200 beats per minute), and delayed programming (60-second delay before therapy ≥170 beats per minute). Multivariate Cox models were used to assess the influence of time-dependent appropriate and inappropriate ICD therapy (shock and antitachycardia pacing) and randomized programming arm on all-cause mortality. During an average follow-up of 1.4±0.6 years, 71 of 1500 (5%) patients died: cardiac in 40 patients (56.3%), noncardiac in 23 patients (32.4%), and unknown in 8 patients (11.3%). Appropriate shocks (hazard ratio, 6.32; 95% confidence interval, 3.13-12.75; P<0.001) and inappropriate therapy (hazard ratio, 2.61; 95% confidence interval, 1.28-5.31; P=0.01) were significantly associated with an increased mortality risk. There was no evidence of increased mortality risk in patients who experienced appropriate antitachycardia pacing only (hazard ratio, 1.02; 95% confidence interval, 0.36-2.88; P=0.98). Randomization to conventional programming was identified as an independent predictor of death when compared with patients randomized to high-rate programming (hazard ratio, 2.0; 95% confidence interval, 1.06-3.71; P=0.03). In MADIT-RIT, appropriate shocks, inappropriate ICD therapy, and randomization to conventional ICD programming were independently associated with an increased mortality risk. Appropriate antitachycardia pacing was not related to an adverse outcome. clinicaltrials.gov Unique identifier: NCT00947310. © 2014 American Heart Association, Inc.

Early Implantation of Primary Prevention Implantable Cardioverter Defibrillators for Patients with Newly Diagnosed Severe Nonischemic Cardiomyopathy.

PubMed

Voskoboinik, Aleksandr; Bloom, Jason; Taylor, Andrew; Mariani, Justin

2016-09-01

Primary prevention implantable cardioverter defibrillators (ICDs) reduce mortality in selected patients with severe systolic dysfunction. Current guidelines suggest a 3- to 6-month waiting period before implantation. We retrospectively studied 29 consecutive patients with newly diagnosed nonischemic cardiomyopathy (NICM) who underwent primary prevention ICD implantation within 6 months of diagnosis between January 2008 and April 2014. Cardiac MRI (CMR) evaluated left ventricular ejection fraction (LVEF) and regional fibrosis preimplant. The primary end point was "failure to qualify for an ICD at 12 months postimplant," either due to LVEF ≥ 35% or deterioration necessitating mechanical support or transplantation, without appropriate ICD therapy. Secondary end points were appropriate and inappropriate ICD therapy. Baseline mean age was 44.2 ± 14.8 years and median LVEF 16.4%. Median time from diagnosis to implant was 32 days. At 12 months, 17 patients (58.6%) no longer qualified for an ICD, mainly due to LVEF improvement. At follow-up (mean 32.0 ± 20.6 months), three patients received appropriate therapy (one for ventricular fibrillation). All three had CMR late gadolinium enhancement (LGE) and nonsustained ventricular tachycardia (NSVT) preimplant. Cardiac resynchronization at implant predicted LVEF improvement. Early appropriate therapy, particularly for ventricular fibrillation, is infrequent for patients with very severe NICM who have ICDs implanted within 6 months of diagnosis. The majority of these patients would not qualify for an ICD at 12 months postinsertion. In the absence of a multimodality risk score, early ICD insertion should only be considered in selected cases (presence of LGE and NSVT). Wearable cardioverter defibrillators may have a role as a bridge to ICD decision. © 2016 Wiley Periodicals, Inc.

Pre-adaptation to shiftwork in space

NASA Astrophysics Data System (ADS)

Samel, A.; Wegmann, H. M.; Vejvoda, M.

Astronauts are often required to work in shift schedules. To test pre-mission adaptation strategies and effects on the circadian system, a study was performed using microgravity simulation by head-down bedrest. Eight male subjects were studied over 4 control days, and 7 days each for pre-mission adaptation, bedrest, and readjustment. The circadian system was assessed by monitoring ECG and temperature, and by collecting urine for determination of hormones and electrolytes. Rhythms did not achieve complete adjustment within the adaptation period when the sleep-wake cycle was shortened by 1h/day, but resynchronization continued during bedrest. After the bedrest period when the time shift was reversed by a 7-h delay within 2 days, resynchronization was achieved satisfactorily only within 7 days. From the results it is concluded that a sleep-wake cycle advance as used in this study is insufficient to keep the circadian system in pace. Under operational conditions the circadian system of astronauts may become longer and more destabilized than under controlled laboratory conditions.

Functional network inference of the suprachiasmatic nucleus

PubMed Central

Abel, John H.; Meeker, Kirsten; Granados-Fuentes, Daniel; St. John, Peter C.; Wang, Thomas J.; Bales, Benjamin B.; Doyle, Francis J.; Herzog, Erik D.; Petzold, Linda R.

2016-01-01

In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data from individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure. PMID:27044085

Pre-adaptation to shiftwork in space.

PubMed

Samel, A; Wegmann, H M; Vejvoda, M

1993-08-01

Astronauts are often required to work in shift schedules. To test pre-mission adaptation strategies and effects on the circadian system, a study was performed using microgravity simulation by head-down bedrest. Eight male subjects were studied over 4 control days, and 7 days each for pre-mission adaptation, bedrest, and readjustment. The circadian system was assessed by monitoring ECG and temperature, and by collecting urine for determination of hormones and electrolytes. Rhythms did not achieve complete adjustment within the adaptation period when the sleep-wake cycle was shortened by 1 h/day, but resynchronization continued during bedrest. After the bedrest period when the time shift was reversed by a 7-h delay within 2 days, resynchronization was achieved satisfactorily only within 7 days. From the results it is concluded that a sleep-wake cycle advance as used in this study is insufficient to keep the circadian system in pace. Under operational conditions the circadian system of astronauts may become longer and more destabilized than under controlled laboratory conditions.

75 FR 66381 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide... Competent Retrovirus (RCR)/Lentivirus (RCL) in Retroviral and Lentiviral Vector Based Gene Therapy Products...

76 FR 22405 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-21

...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide... June 29, 2011, the committee will discuss cellular and gene therapy products for the treatment of...

Rationale, design, and baseline characteristics of the DANish randomized, controlled, multicenter study to assess the efficacy of Implantable cardioverter defibrillators in patients with non-ischemic Systolic Heart failure on mortality (DANISH).

PubMed

Thune, Jens Jakob; Pehrson, Steen; Nielsen, Jens Cosedis; Haarbo, Jens; Videbæk, Lars; Korup, Eva; Jensen, Gunnar; Hildebrandt, Per; Steffensen, Flemming Hald; Bruun, Niels Eske; Eiskjær, Hans; Brandes, Axel; Thøgersen, Anna Margrethe; Egstrup, Kenneth; Hastrup-Svendsen, Jesper; Høfsten, Dan Eik; Torp-Pedersen, Christian; Køber, Lars

2016-09-01

The effect of an implantable cardioverter defibrillator (ICD) in patients with symptomatic systolic heart failure (HF) caused by coronary artery disease is well documented. However, the effect of primary prophylactic ICDs in patients with systolic HF not due to coronary artery disease is much weaker. In addition, HF management has improved, since the landmark ICD trials and a large proportion of patients now receive cardiac resynchronization therapy (CRT) where the effect of ICD treatment is unknown. In the DANISH study, 1,116 patients with symptomatic systolic HF not caused by coronary artery disease have been randomized to receive an ICD or not, in addition to contemporary standard therapy. The primary outcome of the trial is time to all-cause death. Follow-up will continue until June 2016 with a median follow-up period of 5 years. Baseline characteristics show that enrolled patients are treated according to current guidelines. At baseline, 97% of patients received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 92% received a β-blocker, 58% a mineralocorticoid receptor antagonist, and 58% were scheduled to receive CRT. Median age was 63 years (range, 21-84 years) at baseline, and 28% were women. DANISH will provide pertinent information about the effect on all-cause mortality of a primary prophylactic ICD in patients with symptomatic systolic HF not caused by coronary artery disease on contemporary standard therapy including CRT. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical features and changes in epidemiology of infective endocarditis on pacemaker devices over a 27-year period (1987-2013).

PubMed

Carrasco, Francisco; Anguita, Manuel; Ruiz, Martín; Castillo, Juan Carlos; Delgado, Mónica; Mesa, Dolores; Romo, Elias; Pan, Manuel; Suárez de Lezo, Jose

2016-06-01

Use of cardiac pacing devices has grown in recent years. Our aim was to evaluate changes in epidemiology and clinical features of infective endocarditis (IE) involving pacemaker devices in a large series of IE over the last 27 years (1987-2013). From 1987 to December 2013, 413 consecutive IE cases were diagnosed in our hospital. During this period, 7424 pacemaker devices were implanted (6917 pacemakers, 239 implantable cardiac defibrillators, 158 resynchronization devices, and 110 resynchronization/defibrillator devices). All consecutive cases of IE on pacemaker devices were included and analysed. Infective endocarditis on pacemaker devices represented 6.1% of all endocarditis cases (25 patients), affecting 3.6/1000 of all implanted pacemakers. Its proportion increased from 1.25% of all endocarditis in 1987-1993 to 4.08% in 1994-2000, 7.69% in 2001-2007 and 9.32% in 2008-2013 (P < 0.01). Its incidence also increased from 1.4/1000 of all pacemaker implants in the period of 1987-1993 to 2.5/1000 in 1994-2000, 3.3/1000 in 2001-2007 and 4.5/1000 implanted devices in 2008-2013 (P < 0.05). Mean age of patients was 68 years, and 80% were male. Causative microorganisms predominantly were Staphylococci (84%: Staphylococcus aureus 48%, Staphylococcus epidermidis 36%). Rate of severe complications was high: persistent sepsis in 60% of cases, heart failure in 20%, and stroke in 12%. Device was removed in 19 patients (76%), mostly by surgery (18 of the 19 cases). Early mortality was 24% (33% of medically, 21% of surgically treated patients, P = 0.82). Infective endocarditis on pacemaker devices has shown an increasing incidence during the past decades, representing almost 10% of all IE in the last 6 years. This is a severe disease, with a high rate of severe complications and requiring removal of device in most cases. In spite of therapy, early mortality is high. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Strong resetting of the mammalian clock by constant light followed by constant darkness

PubMed Central

Chen, Rongmin; Seo, Dong-oh; Bell, Elijah; von Gall, Charlotte; Lee, Choogon

2008-01-01

The mammalian molecular circadian clock in the suprachiasmatic nuclei (SCN) regulates locomotor activity rhythms as well as clocks in peripheral tissues (Reppert and Weaver, 2002; Ko and Takahashi, 2006). Constant light (LL) can induce behavioral and physiological arrhythmicity, by desynchronizing clock cells in the SCN (Ohta et al., 2005). We examined how the disordered clock cells resynchronize by probing the molecular clock and measuring behavior in mice transferred from LL to constant darkness (DD). The circadian locomotor activity rhythms disrupted in LL become robustly rhythmic again from the beginning of DD, and the starting phase of the rhythm in DD is specific, not random, suggesting that the desynchronized clock cells are quickly reset in an unconventional manner by the L:D transition. By measuring mPERIOD protein rhythms, we showed that the SCN and peripheral tissue clocks quickly become rhythmic again in phase with the behavioral rhythms. We propose that this resetting mechanism may be different from conventional phase shifting, which involves light-induction of Period genes (Albrecht et al., 1997; Shearman et al., 1997; Shigeyoshi et al., 1997). Using our functional insights, we could shift the circadian phase of locomotor activity rhythms by 12 hours using a 15-hour LL treatment: essentially producing phase reversal by a single light pulse, a feat that has not been reported previously in wild-type mice and that has potential clinical utility. PMID:19005049

ISHNE/EHRA expert consensus on remote monitoring of cardiovascular implantable electronic devices (CIEDs).

PubMed

Dubner, Sergio; Auricchio, Angelo; Steinberg, Jonathan S; Vardas, Panos; Stone, Peter; Brugada, Josep; Piotrowicz, Ryszard; Hayes, David L; Kirchhof, Paulus; Breithardt, Günter; Zareba, Wojciech; Schuger, Claudio; Aktas, Mehmet K; Chudzik, Michal; Mittal, Suneet; Varma, Niraj

2012-02-01

We are in the midst of a rapidly evolving era of technology-assisted medicine. The field of telemedicine provides the opportunity for highly individualized medical management in a way that has never been possible before. Evolving medical technologies using cardiac implantable devices (CIEDs) with capabilities for remote monitoring permit evaluation of multiple parameters of cardiovascular physiology and risk, including cardiac rhythm, device function, blood pressure values, the presence of myocardial ischaemia, and the degree of compensation of congestive heart failure. Cardiac risk, device status, and response to therapies can now be assessed with these electronic systems of detection and reporting. This document reflects the extensive experience from investigators and innovators around the world who are shaping the evolution of this rapidly expanding field, focusing in particular on implantable pacemakers (IPGs), implantable cardioverter-defibrillators (ICDs), devices for cardiac resynchronization therapy (CRT) (both, with and without defibrillation properties), loop recorders, and haemodynamic monitoring devices. This document covers the basic methodologies, guidelines for their use, experience with existing applications, and the legal and reimbursement aspects associated with their use. To adequately cover this important emerging topic, the International Society for Holter and Noninvasive Electrocardiology (ISHNE) and the European Heart Rhythm Association (EHRA) combined their expertise in this field. We hope that the development of this field can contribute to improve care of our cardiovascular patients.

Sex Differences in Device Therapy for Heart Failure: Utilization, Outcomes, and Adverse Events

PubMed Central

Herz, Naomi D.; Engeda, Joseph; Zusterzeel, Robbert; Sanders, William E.; O'Callaghan, Kathryn M.; Strauss, David G.; Jacobs, Samantha B.; Selzman, Kimberly A.; Piña, Ileana L.

2015-01-01

Abstract Background: Multiple studies of heart failure patients demonstrated significant improvement in exercise capacity, quality of life, cardiac left ventricular function, and survival from cardiac resynchronization therapy (CRT), but the underenrollment of women in these studies is notable. Etiological and pathophysiological differences may result in different outcomes in response to this treatment by sex. The observed disproportionate representation of women suggests that many women with heart failure either do not meet current clinical criteria to receive CRT in trials or are not properly recruited and maintained in these studies. Methods: We performed a systematic literature review through May 2014 of clinical trials and registries of CRT use that stratified outcomes by sex or reported percent women included. One-hundred eighty-three studies contained sex-specific information. Results: Ninety percent of the studies evaluated included ≤35% women. Fifty-six articles included effectiveness data that reported response with regard to specific outcome parameters. When compared with men, women exhibited more dramatic improvement in specific parameters. In the studies reporting hazard ratios for hospitalization or death, women generally had greater benefit from CRT. Conclusions: Our review confirms women are markedly underrepresented in CRT trials, and when a CRT device is implanted, women have a therapeutic response that is equivalent to or better than in men, while there is no difference in adverse events reported by sex. PMID:25793483

Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure

PubMed Central

Finosh, G.T.; Jayabalan, Muthu

2012-01-01

Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed. PMID:23507781

Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure: new developments and challenges.

PubMed

Finosh, G T; Jayabalan, Muthu

2012-01-01

Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed.

Amiodarone and Catheter Ablation as Cardiac Resynchronization Therapy for Children with Dilated Cardiomyopathy and Wolff-Parkinson-White Syndrome

PubMed Central

Kim, Sung Hoon; Jeong, Soo In; Kang, I-Seok; Lee, Heung Jae

2013-01-01

Preexcitation by accessory pathways (APs) is known to cause dyssynchrony of the ventricle, related to ventricular dysfunction. Correction of ventricular dyssynchrony can improve heart failure in cases of dilated cardiomyopathy (DCMP) with preexcitation. Here, we report the first case of a child with DCMP and Wolff-Parkinson-White (WPW) syndrome treated with amiodarone and radiofrequency catheter ablation (RFCA) in Korea. A 7-year-old boy, who suffered from DCMP and WPW syndrome, showed improved left ventricular function and clinical functional class after treatment with amiodarone to eliminate preexcitation. QRS duration and left ventricular ejection fraction (LVEF) were inversely correlated with amiodarone dosage. After confirming the reduction of preexcitation effects in DCMP, successful RFCA of the right anterior AP resulted in LVEF improvement, along with the disappearance of preexcitation. Our findings suggest that ventricular dyssynchrony, caused by preexcitation in DCMP with WPW syndrome, can worsen ventricular function and amiodarone, as well as RFCA, which should be considered as a treatment option, even in young children. PMID:23407697

LDFT-based watermarking resilient to local desynchronization attacks.

PubMed

Tian, Huawei; Zhao, Yao; Ni, Rongrong; Qin, Lunming; Li, Xuelong

2013-12-01

Up to now, a watermarking scheme that is robust against desynchronization attacks (DAs) is still a grand challenge. Most image watermarking resynchronization schemes in literature can survive individual global DAs (e.g., rotation, scaling, translation, and other affine transforms), but few are resilient to challenging cropping and local DAs. The main reason is that robust features for watermark synchronization are only globally invariable rather than locally invariable. In this paper, we present a blind image watermarking resynchronization scheme against local transform attacks. First, we propose a new feature transform named local daisy feature transform (LDFT), which is not only globally but also locally invariable. Then, the binary space partitioning (BSP) tree is used to partition the geometrically invariant LDFT space. In the BSP tree, the location of each pixel is fixed under global transform, local transform, and cropping. Lastly, the watermarking sequence is embedded bit by bit into each leaf node of the BSP tree by using the logarithmic quantization index modulation watermarking embedding method. Simulation results show that the proposed watermarking scheme can survive numerous kinds of distortions, including common image-processing attacks, local and global DAs, and noninvertible cropping.

Functional network inference of the suprachiasmatic nucleus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abel, John H.; Meeker, Kirsten; Granados-Fuentes, Daniel

2016-04-04

In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data frommore » individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure.« less

Patients with left bundle branch block and left axis deviation show a specific left ventricular asynchrony pattern: Implications for left ventricular lead placement during CRT implantation.

PubMed

Sciarra, Luigi; Golia, Paolo; Palamà, Zefferino; Scarà, Antonio; De Ruvo, Ermenegildo; Borrelli, Alessio; Martino, Anna Maria; Minati, Monia; Fagagnini, Alessandro; Tota, Claudia; De Luca, Lucia; Grieco, Domenico; Delise, Pietro; Calò, Leonardo

Left bundle branch block (LBBB) and left axis deviation (LAD) patients may have poor response to resynchronization therapy (CRT). We sought to assess if LBBB and LAD patients show a specific pattern of mechanical asynchrony. CRT candidates with non-ischemic cardiomyopathy and LBBB were categorized as having normal QRS axis (within -30° and +90°) or LAD (within -30° and -90°). Patients underwent tissue Doppler imaging (TDI) to measure time interval between onset of QRS complex and peak systolic velocity in ejection period (Q-peak) at basal segments of septal, inferior, lateral and anterior walls, as expression of local timing of mechanical activation. Thirty patients (mean age 70.6years; 19 males) were included. Mean left ventricular ejection fraction was 0.28±0.06. Mean QRS duration was 172.5±13.9ms. Fifteen patients showed LBBB with LAD (QRS duration 173±14; EF 0.27±0.06). The other 15 patients had LBBB with a normal QRS axis (QRS duration 172±14; EF 0.29±0.05). Among patients with LAD, Q-peak interval was significantly longer at the anterior wall in comparison to each other walls (septal 201±46ms, inferior 242±58ms, lateral 267±45ms, anterior 302±50ms; p<0.0001). Conversely, in patients without LAD Q-peak interval was longer at lateral wall, when compared to each other (septal 228±65ms, inferior 250±64ms, lateral 328±98ms, anterior 291±86ms; p<0.0001). Patients with heart failure, presenting LBBB and LAD, show a specific pattern of ventricular asynchrony, with latest activation at anterior wall. This finding could affect target vessel selection during CRT procedures in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of ex vivo model for determining temperature distribution in tumor tissue during photothermal therapy

NASA Astrophysics Data System (ADS)

Liu, Shaojie; Doughty, Austin; Mesiya, Sana; Pettitt, Alex; Zhou, Feifan; Chen, Wei R.

2017-02-01

Temperature distribution in tissue is a crucial factor in determining the outcome of photothermal therapy in cancer treatment. In order to investigate the temperature distribution in tumor tissue during laser irradiation, we developed a novel ex vivo device to simulate the photothermal therapy on tumors. A 35°C, a thermostatic incubator was used to provide a simulation environment for body temperature of live animals. Different biological tissues (chicken breast and bovine liver) were buried inside a tissue-simulating gel and considered as tumor tissues. An 805-nm laser was used to irradiate the target tissue. A fiber with an interstitial cylindrical diffuser (10 mm) was directly inserted in the center of the tissue, and the needle probes of a thermocouple were inserted into the tissue paralleling the laser fiber at different distances to measure the temperature distribution. All of the procedures were performed in the incubator. Based on the results of this study, the temperature distribution in bovine liver is similar to that of tumor tissue under photothermal therapy with the same doses. Therefore, the developed model using bovine liver for determining temperature distribution can be used during interstitial photothermal therapy.

Distinctive Tooth-Extraction Socket Healing: Bisphosphonate Versus Parathyroid Hormone Therapy

PubMed Central

Kuroshima, Shinichiro; Mecano, Rodan B.; Tanoue, Ryuichiro; Koi, Kiyono; Yamashita, Junro

2014-01-01

Background Patients with osteoporosis who receive tooth extractions are typically on either oral bisphosphonate or parathyroid hormone (PTH) therapy. Currently, the consequence of these therapies on hard- and soft-tissue healing in the oral cavity is not clearly defined. The aim of this study is to determine the differences in the therapeutic effect on tooth-extraction wound healing between bisphosphonate and PTH therapies. Methods Maxillary second molars were extracted in Sprague Dawley rats (n = 30), and either bisphosphonate (zoledronate [Zol]), PTH, or saline (vehicle control [VC]) was administered for 10 days (n = 10 per group). Hard-tissue healing was evaluated by microcomputed tomography and histomorphometric analyses. Collagen, blood vessels, inflammatory cell infiltration, and cathepsin K expression were assessed in soft tissue using immunohistochemistry, quantitative polymerase chain reaction, and immunoblotting. Results Both therapies significantly increased bone fill and suppressed vertical bone loss. However, considerably more devital bone was observed in the sockets of rats on Zol versus VC. Although Zol increased the numbers of blood vessels, the total blood vessel area in soft tissue was significantly smaller than in VC. PTH therapy increased osteoblastic bone formation and suppressed osteoclasts. PTH therapy promoted soft-tissue maturation by suppressing inflammation and stimulating collagen deposition. Conclusion Zoledronate therapy deters whereas PTH therapy promotes hard- and soft-tissue healing in the oral cavity, and both therapies prevent vertical bone loss. PMID:23688101

Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy.

PubMed

Hoirisch-Clapauch, Silvia; Mezzasalma, Marco A U; Nardi, Antonio E

2014-02-01

Electroconvulsive therapy is an important treatment option for major depressive disorders, acute mania, mood disorders with psychotic features, and catatonia. Several hypotheses have been proposed as electroconvulsive therapy's mechanism of action. Our hypothesis involves many converging pathways facilitated by increased synthesis and release of tissue-plasminogen activator. Human and animal experiments have shown that tissue-plasminogen activator participates in many mechanisms of action of electroconvulsive therapy or its animal variant, electroconvulsive stimulus, including improved N-methyl-D-aspartate receptor-mediated signaling, activation of both brain-derived neurotrophic factor and vascular endothelial growth factor, increased bioavailability of zinc, purinergic release, and increased mobility of dendritic spines. As a result, tissue-plasminogen activator helps promote neurogenesis in limbic structures, modulates synaptic transmission and plasticity, improves cognitive function, and mediates antidepressant effects. Notably, electroconvulsive therapy seems to influence tissue-plasminogen activator metabolism. For example, electroconvulsive stimulus increases the expression of glutamate decarboxylase 65 isoform in γ-aminobutyric acid-releasing neurons, which enhances the release of tissue-plasminogen activator, and the expression of p11, a protein involved in plasminogen and tissue-plasminogen activator assembling. This paper reviews how electroconvulsive therapy correlates with tissue-plasminogen activator. We suggest that interventions aiming at increasing tissue-plasminogen activator levels or its bioavailability - such as daily aerobic exercises together with a carbohydrate-restricted diet, or normalization of homocysteine levels - be evaluated in controlled studies assessing response and remission duration in patients who undergo electroconvulsive therapy.

Gene therapy with growth factors for periodontal tissue engineering–A review

PubMed Central

Gupta, Shipra; Mahendra, Aneet

2012-01-01

The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

77 FR 73472 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug... closed to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee. General...

76 FR 64951 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

77 FR 63840 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-17

...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug... meeting will be closed to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory... to hear updates of research programs in the Gene Transfer and Immunogenicity Branch, Office of...

Negative-pressure wound therapy I: the paradox of negative-pressure wound therapy.

PubMed

Kairinos, Nicolas; Solomons, Michael; Hudson, Donald A

2009-02-01

Does negative-pressure wound therapy reduce or increase the pressure of wound tissues? This seemingly obvious question has never been addressed by a study on living tissues. The aim of this study was to evaluate the nature of tissue pressure changes in relation to negative-pressure wound therapy. Three negative-pressure wound therapy dressing configurations were evaluated-circumferential, noncircumferential, and those within a cavity-on 15 human wounds, with five wounds in each category. Tissue pressure changes were recorded (using a strain gauge sensor) for each 75-mmHg increment in suction, up to -450 mmHg. In the circumferential and noncircumferential groups, tissue pressure was also measured over a 48-hour period at a set suction pressure of -125 mmHg (n = 10). In all three groups, mean tissue pressure increased proportionately to the amount of suction applied (p < 0.0005). Mean tissue pressure increments resulting from the circumferential dressings were significantly higher than those resulting from the noncircumferential (p < 0.0005) or cavity group (p < 0.0005); however, there was no significant difference between the latter two groups (p = 0.269). Over the 48-hour period, there was a significant mean reduction in the (increased) tissue pressure (p < 0.04 for circumferential and p < 0.0005 for noncircumferential), but in only three of 10 cases did this reduce to pressures less than those before dressing application. Negative-pressure wound therapy increases tissue pressure proportionately to the amount of suction, although this becomes less pronounced over 48 hours. This suggests that negative-pressure wound therapy dressings should be used with caution on tissues with compromised perfusion, particularly when they are circumferential.

Successful Tissue Plasminogen Activator for a Patient with Stroke After Stanford Type A Aortic Dissection Treatment.

PubMed

Matsuzono, Kosuke; Suzuki, Masayuki; Arai, Naoto; Kim, Younhee; Ozawa, Tadashi; Mashiko, Takafumi; Shimazaki, Haruo; Koide, Reiji; Fujimoto, Shigeru

2018-07-01

Some stroke patients with the acute aortic dissection receiving thrombolysis treatment resulted in fatalities. Thus, the concurrent acute aortic dissection is the contraindication for the intravenous recombinant tissue-type plasminogen activator. However, the safety and the effectiveness of the intravenous recombinant tissue-type plasminogen activator therapy are not known in patients with stroke some days after acute aortic dissection treatment. Here, we first report a case of a man with a cardioembolism due to the nonvalvular atrial fibrillation, who received the intravenous recombinant tissue-type plasminogen activator therapy 117 days after the traumatic Stanford type A acute aortic dissection operation. Without the intravenous recombinant tissue-type plasminogen activator therapy, the prognosis was expected to be miserable. However, the outcome was good with no complication owing to the intravenous recombinant tissue-type plasminogen activator therapy. Our case suggests the effectiveness and the safety of the intravenous recombinant tissue-type plasminogen activator therapy to the ischemic stroke some days after acute aortic dissection treatment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Selective accumulation of PpIX and photodynamic effect after aminolevulinic acid treatment of human adenomyosis xenografts in nude mice.

PubMed

Suzuki-Kakisaka, Haruka; Murakami, Takashi; Hirano, Toru; Terada, Yukihiro; Yaegashi, Nobuo; Okamura, Kunihiro

2008-10-01

To evaluate the effect of photodynamic therapy with aminolevulinic acid (ALA) on human adenomyosis xenografts in a mouse model. Human adenomyosis tissues were implanted SC into nude mice. We measured 5-aminolevulinic acid pharmacokinetics in these mice by analyzing tissue sections 1 to 6 hours after intraperitoneal administration. Twenty-four hours after photodynamic therapy, we evaluated tissue morphologic features. Department of obstetrics and gynecology at a university hospital in Japan. Immunodeficient mice. Tissue grafts were taken from women with adenomyosis attending a university hospital. Photodynamic treatment. Peak fluorescence after intraperitoneal ALA administration and tissue histological changes 24 hours after photodynamic therapy. Peak fluorescence was observed 3 hours after intraperitoneal administration. Histological studies revealed decreased numbers of epithelial and stromal cells in adenomyosis models after therapy. Photodynamic therapy with ALA caused extensive cell death in human adenomyosis tissues implanted into nude mice. Photodynamic treatment using ALA is a potential treatment for patients with adenomyosis uteri.

Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib.

PubMed

Wodarz, Dominik; Garg, Naveen; Komarova, Natalia L; Benjamini, Ohad; Keating, Michael J; Wierda, William G; Kantarjian, Hagop; James, Danelle; O'Brien, Susan; Burger, Jan A

2014-06-26

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has excellent clinical activity in patients with chronic lymphocytic leukemia (CLL). Characteristically, ibrutinib causes CLL cell redistribution from tissue sites into the peripheral blood during the initial weeks of therapy. To better characterize the dynamics of this redistribution phenomenon, we correlated serial lymphocyte counts with volumetric changes in lymph node and spleen sizes during ibrutinib therapy. Kinetic parameters were estimated by applying a mathematical model to the data. We found that during ibrutinib therapy, 1.7% ± 1.1% of blood CLL cells and 2.7% ± 0.99% of tissue CLL cells die per day. The fraction of the tissue CLL cells that was redistributed into the blood during therapy was estimated to be 23.3% ± 17% of the total tissue disease burden. These data indicate that the reduction of tissue disease burden by ibrutinib is due more to CLL cell death and less to egress from nodal compartments. © 2014 by The American Society of Hematology.

Towards a personalized and dynamic CRT-D. A computational cardiovascular model dedicated to therapy optimization.

PubMed

Di Molfetta, A; Santini, L; Forleo, G B; Minni, V; Mafhouz, K; Della Rocca, D G; Fresiello, L; Romeo, F; Ferrari, G

2012-01-01

In spite of cardiac resynchronization therapy (CRT) benefits, 25-30% of patients are still non responders. One of the possible reasons could be the non optimal atrioventricular (AV) and interventricular (VV) intervals settings. Our aim was to exploit a numerical model of cardiovascular system for AV and VV intervals optimization in CRT. A numerical model of the cardiovascular system CRT-dedicated was previously developed. Echocardiographic parameters, Systemic aortic pressure and ECG were collected in 20 consecutive patients before and after CRT. Patient data were simulated by the model that was used to optimize and set into the device the intervals at the baseline and at the follow up. The optimal AV and VV intervals were chosen to optimize the simulated selected variable/s on the base of both echocardiographic and electrocardiographic parameters. Intervals were different for each patient and in most cases, they changed at follow up. The model can well reproduce clinical data as verified with Bland Altman analysis and T-test (p > 0.05). Left ventricular remodeling was 38.7% and left ventricular ejection fraction increasing was 11% against the 15% and 6% reported in literature, respectively. The developed numerical model could reproduce patients conditions at the baseline and at the follow up including the CRT effects. The model could be used to optimize AV and VV intervals at the baseline and at the follow up realizing a personalized and dynamic CRT. A patient tailored CRT could improve patients outcome in comparison to literature data.

Mapping cardiac fiber orientations from high-resolution DTI to high-frequency 3D ultrasound

NASA Astrophysics Data System (ADS)

Qin, Xulei; Wang, Silun; Shen, Ming; Zhang, Xiaodong; Wagner, Mary B.; Fei, Baowei

2014-03-01

The orientation of cardiac fibers affects the anatomical, mechanical, and electrophysiological properties of the heart. Although echocardiography is the most common imaging modality in clinical cardiac examination, it can only provide the cardiac geometry or motion information without cardiac fiber orientations. If the patient's cardiac fiber orientations can be mapped to his/her echocardiography images in clinical examinations, it may provide quantitative measures for diagnosis, personalized modeling, and image-guided cardiac therapies. Therefore, this project addresses the feasibility of mapping personalized cardiac fiber orientations to three-dimensional (3D) ultrasound image volumes. First, the geometry of the heart extracted from the MRI is translated to 3D ultrasound by rigid and deformable registration. Deformation fields between both geometries from MRI and ultrasound are obtained after registration. Three different deformable registration methods were utilized for the MRI-ultrasound registration. Finally, the cardiac fiber orientations imaged by DTI are mapped to ultrasound volumes based on the extracted deformation fields. Moreover, this study also demonstrated the ability to simulate electricity activations during the cardiac resynchronization therapy (CRT) process. The proposed method has been validated in two rat hearts and three canine hearts. After MRI/ultrasound image registration, the Dice similarity scores were more than 90% and the corresponding target errors were less than 0.25 mm. This proposed approach can provide cardiac fiber orientations to ultrasound images and can have a variety of potential applications in cardiac imaging.

A Clinical Feasibility Study of Atrial and Ventricular Electromechanical Wave Imaging

PubMed Central

Provost, Jean; Gambhir, Alok; Vest, John; Garan, Hasan; Konofagou, Elisa E.

2014-01-01

Background Cardiac Resynchronization Therapy (CRT) and atrial ablation currently lack a noninvasive imaging modality for reliable treatment planning and monitoring. Electromechanical Wave Imaging (EWI) is an ultrasound-based method that has previously been shown to be capable of noninvasively and transmurally mapping the activation sequence of the heart in animal studies by estimating and imaging the electromechanical wave, i.e., the transient strains occurring in response to the electrical activation, at both very high temporal and spatial resolution. Objective Demonstrate the feasibility of noninvasive transthoracic EWI for mapping the activation sequence during different cardiac rhythms in humans. Methods EWI was performed in CRT patients with a left bundle-branch block (LBBB), during sinus rhythm, left-ventricular pacing, and right-ventricular pacing and in atrial flutter (AFL) patients before intervention and correlated with results from invasive intracardiac electrical mapping studies during intervention. Additionally, the feasibility of single-heartbeat EWI at 2000 frames/s, is demonstrated in humans for the first time in a subject with both AFL and right bundle-branch-block. Results The electromechanical activation maps demonstrated the capability of EWI to localize the pacing sites and characterize the LBBB activation sequence transmurally in CRT patients. In AFL patients, the propagation patterns obtained with EWI were in agreement with results obtained from invasive intracardiac mapping studies. Conclusion Our findings demonstrate the potential capability of EWI to aid in monitoring and follow-up of patients undergoing CRT pacing therapy and atrial ablation with preliminary validation in vivo. PMID:23454060

Management of Systemic Right Ventricular Failure in Patients With Congenitally Corrected Transposition of the Great Arteries.

PubMed

Filippov, Aleksei A; Del Nido, Pedro J; Vasilyev, Nikolay V

2016-10-25

In recent decades, significant progress has been made in the diagnosis and management of congenitally corrected transposition of the great arteries (ccTGA). Nevertheless, gradual dysfunction and failure of the right ventricle (RV) in the systemic circulation remain the main contributors to mortality and disability for patients with ccTGA, especially after adolescence. Anatomic repair of ccTGA effectively resolves the problem of failure of the systemic RV and has good early and midterm results. However, this strategy is applicable primarily in infants and children up to their teens and has associated risks and limitations, and new challenges can arise in the late postoperative period. Patients with ccTGA manifesting progressive systemic RV dysfunction beyond adolescence represent the major challenge. Several palliative options such as cardiac resynchronization therapy, tricuspid valve repair or replacement, pulmonary artery banding, and implantation of an assist device into the systemic RV can be used to improve functional status and to delay the progression of ventricular dysfunction in patients who are not suitable for anatomic correction of ccTGA. For adult patients with severe systemic RV failure, heart transplantation currently remains the only long-term lifesaving procedure, although donor organ availability remains one of the most limiting factors in this type of therapy. This review focuses on current surgical and medical strategies and interventional options for the prevention and management of systemic RV failure in adults and children with ccTGA. © 2016 American Heart Association, Inc.

Left atrial booster pump function is an independent predictor of subsequent life-threatening ventricular arrhythmias in non-ischaemic cardiomyopathy.

PubMed

Negishi, Kazuaki; Negishi, Tomoko; Zardkoohi, Omeed; Ching, Elizabeth A; Basu, Nivedita; Wilkoff, Bruce L; Popović, Zoran B; Marwick, Thomas H

2016-10-01

Left atrial (LA) function helps to preserve cardiac output and to control pulmonary capillary wedge pressure in the setting of left ventricular (LV) impairment, but little is known about the contribution of the LA function to ventricular arrhythmia. We sought whether LA booster pump function was associated with arrhythmias in patients undergoing primary prevention implantable cardioverter-defibrillator (ICD) implantation for non-ischaemic dilated cardiomyopathy (NICM), independent of global longitudinal strain (GLS) and mechanical dispersion (MD). We identified 124 NICM patients (56 ± 13, 67 male) who underwent echocardiography pre-ICD implantation for primary prevention. The main outcome measure was appropriate ICD therapy (anti-tachycardia pacing or shock). The mitral A-wave was used as an LA functional marker. MD was defined as standard deviation of time to peak strain of each segment. Over a median follow-up of 3.8 ± 2.2 years, 36 patients had appropriate ICD therapy, including 23 shocks. Patients with appropriate ICD therapy had lower A-wave velocity (P < 0.001), larger LA volume (P < 0.001), and impaired circumferential MD (P = 0.006), but similar ejection fraction (EF) (P = 0.40) and GLS (P = 0.11). In sequential Cox proportional hazards models, A-wave, E/A ratio, and GLS were significantly associated with outcomes, independent of age, sex, and cardiac resynchronization therapy defibrillator or left bundle branch block. In nested Cox models, mitral A-wave had a prognostic value incremental to models with LV systolic (EF and GLS) and diastolic functional parameters (E/A, E/e', and LA volume) and MD. LA booster pump function was an independent and incremental predictor of arrhythmias in NICM over GLS and MD, and may aid better risk stratification in this population. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

TCP Resynchronization

DTIC Science & Technology

1976-01-11

Centinela and Teale Streets Culver City, CA 90230 IBM Dr. Patrick Mantey, Manager L’cer Oriented Systems International Business Machines Corp. K54...282, Monterey and Cottle Roads San Jose, CA 95193 Dr. Leonard Y. Liu, Manager Computer Science International Business Machines Corp. K51-282...Monterey and Cottle Roads San Jose, CA 95193 Mr. Harry Reinstein International Business Machines Corp. 1501 California Avenue Palo Alto, Ca 94303

Recent patents on light based therapies: photodynamic therapy, photothermal therapy and photoimmunotherapy.

PubMed

Sanchez-Barcelo, Emilio J; Mediavilla, Maria D

2014-01-01

This article reviews the more recent patents in three kinds of therapeutic strategies using the application of visible light to irradiate photosensible substances (PSs) of different natures. The light-activation of these PSs is directly responsible for the desired therapeutic effects. This group of light therapies includes photodynamic therapy (PDT), photothermal therapy (PTT) and photoimmunotherapy (PIT). Therapeutic mechanisms triggered by the activation of the PSs depend basically (though not exclusively) on the release of reactive oxygen species (ROS) and the activation of immune responses (PDT and PIT) or the local generation of heat (PTT). The main difference between PIT and PDT is that in PIT, monoclonal antibodies (MABs) are associated to PSs to improve the selective binding of the PSs to the target tissues. All these therapeutic strategies offer the possibility of destroying tumor tissue without damaging the surrounding healthy tissue, which is not achievable with chemotherapy or radiotherapy. PDT is also used as an alternative or adjuvant antimicrobial therapy together with the traditional antibiotic therapy since these organisms are unlikely to develop resistance to the ROS induced by PDT. Furthermore, PDT also induces an immune response against bacterial pathogens. The current challenge in PDT, PIT and PTT is to obtain the highest level of selectivity to act on targeted sick tissues with the minimum effects on the surrounding healthy tissue. The development of new PSs with high affinity for specific tissues, new PSs- MABs conjugates to bind to specific kinds of tumors, and new light-sensible nanoparticles with low toxicity, will increase the clinical utility of these therapies.

Optimal temperature control of tissue embedded with gold nanoparticles for enhanced thermal therapy based on two-energy equation model.

PubMed

Wang, Shen-Ling; Qi, Hong; Ren, Ya-Tao; Chen, Qin; Ruan, Li-Ming

2018-05-01

Thermal therapy is a very promising method for cancer treatment, which can be combined with chemotherapy, radiotherapy and other programs for enhanced cancer treatment. In order to get a better effect of thermal therapy in clinical applications, optimal internal temperature distribution of the tissue embedded with gold nanoparticles (GNPs) for enhanced thermal therapy was investigated in present research. The Monte Carlo method was applied to calculate the heat generation of the tissue embedded with GNPs irradiated by continuous laser. To have a better insight into the physical problem of heat transfer in tissues, the two-energy equation was employed to calculate the temperature distribution of the tissue in the process of GNPs enhanced therapy. The Arrhenius equation was applied to evaluate the degree of permanent thermal damage. A parametric study was performed to investigate the influence factors on the tissue internal temperature distribution, such as incident light intensity, the GNPs volume fraction, the periodic heating and cooling time, and the incident light position. It was found that period heating and cooling strategy can effectively avoid overheating of skin surface and heat damage of healthy tissue. Lower GNPs volume fraction will be better for the heat source distribution. Furthermore, the ring heating strategy is superior to the central heating strategy in the treatment effect. All the analysis provides theoretical guidance for optimal temperature control of tissue embedded with GNP for enhanced thermal therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Improvement in skin elasticity in the treatment of cellulite and connective tissue weakness by means of extracorporeal pulse activation therapy.

PubMed

Christ, Christophe; Brenke, Rainer; Sattler, Gerhard; Siems, Werner; Novak, Pavel; Daser, A

2008-01-01

Extracorporeal pulse activation therapy (EPAT), also called extracorporeal acoustic wave therapy, seeks to achieve effective and long-lasting improvement of age-related connective tissue weakness in the extremities, especially in the treatment of unsightly cosmetic skin defects referred to as cellulite. The objective of this study was to stimulate metabolic activity in subcutaneous fat tissue by means of EPAT in order evaluate its effectiveness in enhancing connective tissue firmness and improving skin texture and structure. Fifty-nine women with advanced cellulite were divided into 2 groups; one group of 15 patients received planar acoustic wave treatment for 6 therapy sessions within 3 weeks; a second group of 44 patients received 8 therapy sessions within 4 weeks. Changes in connective tissue were evaluated using the DermaScan C ultrasound system (Cortex Technology, Hadsund, Denmark). Skin elasticity measurements were performed using the DermaLab system (Cortex Technology). Photographs of treated areas were taken at each therapy session and at follow-up sessions. Skin elasticity values gradually improved over the course of EPAT therapy and revealed a 73% increase at the end of therapy. At 3- and 6-month follow-ups, skin elasticity had even improved by 95% and 105%, respectively. Side effects included minor pain for 3 patients during therapy and slight skin reddening. This study confirmed the effects of acoustic wave therapy on biologic tissue, including stimulation of microcirculation and improvement of cell permeability. Ultrasound evaluation demonstrated increased density and firmness in the network of collagen/elastic fibers in the dermis and subcutis. Treatment was most effective in older patients with a long history of cellulite.

A practical model for economic evaluation of tissue-engineered therapies.

PubMed

Tan, Tien-En; Peh, Gary S L; Finkelstein, Eric A; Mehta, Jodhbir S

2015-01-01

Tissue-engineered therapies are being developed across virtually all fields of medicine. Some of these therapies are already in clinical use, while others are still in clinical trials or the experimental phase. Most initial studies in the evaluation of new therapies focus on demonstration of clinical efficacy. However, cost considerations or economic viability are just as important. Many tissue-engineered therapies have failed to be impactful because of shortcomings in economic competitiveness, rather than clinical efficacy. Furthermore, such economic viability studies should be performed early in the process of development, before significant investment has been made. Cost-minimization analysis combined with sensitivity analysis is a useful model for the economic evaluation of new tissue-engineered therapies. The analysis can be performed early in the development process, and can provide valuable information to guide further investment and research. The utility of the model is illustrated with the practical real-world example of tissue-engineered constructs for corneal endothelial transplantation. The authors have declared no conflicts of interest for this article. © 2015 Wiley Periodicals, Inc.

Design control for clinical translation of 3D printed modular scaffolds.

PubMed

Hollister, Scott J; Flanagan, Colleen L; Zopf, David A; Morrison, Robert J; Nasser, Hassan; Patel, Janki J; Ebramzadeh, Edward; Sangiorgio, Sophia N; Wheeler, Matthew B; Green, Glenn E

2015-03-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion.

Design Control for Clinical Translation of 3D Printed Modular Scaffolds

PubMed Central

Hollister, Scott J.; Flanagan, Colleen L.; Zopf, David A.; Morrison, Robert J.; Nasser, Hassan; Patel, Janki J.; Ebramzadeh, Edward; Sangiorgio, Sophia N.; Wheeler, Matthew B.; Green, Glenn E.

2015-01-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion. PMID:25666115

Do women benefit equally as men from the primary prevention implantable cardioverter-defibrillator?

PubMed

Barra, Sérgio; Providência, Rui; Boveda, Serge; Narayanan, Kumar; Virdee, Munmohan; Marijon, Eloi; Agarwal, Sharad

2018-06-01

Women traditionally have been and are still underrepresented in research in many important areas of cardiology, and guideline recommendations which also encompass women are mostly based on research conducted predominantly in men. However, there is plausible cause to believe that sex may have a potential influence on the benefit derived from the implantable cardioverter-defibrillators (ICD), alone or in association with cardiac resynchronization therapy. We assessed the possible relationship between sex and outcome with ICD implantation in the setting of primary prevention, by pooling the results of MUSTT, MADIT-II, DEFINITE, COMPANION, SCD-HeFT and DANISH trials in a meta-analysis. We pooled results for female and male patients separately. The results suggest that women as a group do not seem to obtain a significant survival benefit from the primary prevention ICD, contrary to men. This in turn may also have contributed to a relative underestimation of the ICD benefit among males when looking at the results in total. It is time for the medical and research communities to actively question the presumed overarching benefit of ICDs irrespective of sex and engage in systematic scientific efforts to definitively evaluate the value of this intervention in women.

Combining computer modelling and cardiac imaging to understand right ventricular pump function.

PubMed

Walmsley, John; van Everdingen, Wouter; Cramer, Maarten J; Prinzen, Frits W; Delhaas, Tammo; Lumens, Joost

2017-10-01

Right ventricular (RV) dysfunction is a strong predictor of outcome in heart failure and is a key determinant of exercise capacity. Despite these crucial findings, the RV remains understudied in the clinical, experimental, and computer modelling literature. This review outlines how recent advances in using computer modelling and cardiac imaging synergistically help to understand RV function in health and disease. We begin by highlighting the complexity of interactions that make modelling the RV both challenging and necessary, and then summarize the multiscale modelling approaches used to date to simulate RV pump function in the context of these interactions. We go on to demonstrate how these modelling approaches in combination with cardiac imaging have improved understanding of RV pump function in pulmonary arterial hypertension, arrhythmogenic right ventricular cardiomyopathy, dyssynchronous heart failure and cardiac resynchronization therapy, hypoplastic left heart syndrome, and repaired tetralogy of Fallot. We conclude with a perspective on key issues to be addressed by computational models of the RV in the near future. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

3D and 4D echo--applications in EP laboratory procedures.

PubMed

Kautzner, Josef; Peichl, Petr

2008-08-01

3D echocardiography allows imaging and analysis of cardiovascular structures as they move in time and space, thus creating possibility for creation of 4D datasets (3D + time). Intracardiac echocardiography (ICE) further broadens the spectrum of echocardiographic techniques by allowing detailed imaging of intracardiac anatomy with 3D reconstructions. The paper reviews the current status of development of 3D and 4D echocardiography in electrophysiology. In ablation area, 3D echocardiography can enhance the performance of catheter ablation for complex arrhythmias such as atrial fibrillation. Currently, several strategies to obtain 3D reconstructions from ICE are available. One involves combination with electroanatomical mapping system; others create reconstruction from standard phased-array or single-element ICE catheter using special rotational or pull-back devices. Secondly, 3D echocardiography may be used for precise assessment of cardiac dyssynchrony before cardiac resynchronization therapy. Its reliable detection is expected to minimize number of non-responders to this treatment and optimize left ventricular lead positioning to get maximum hemodynamic benefit. The main potential benefit of 3D and 4D echocardiography in electrophysiology lie in real-time guidance of complex ablation procedures and precise assessment of cardiac dyssynchrony.

Manifold parametrization of the left ventricle for a statistical modelling of its complete anatomy

NASA Astrophysics Data System (ADS)

Gil, D.; Garcia-Barnes, J.; Hernández-Sabate, A.; Marti, E.

2010-03-01

Distortion of Left Ventricle (LV) external anatomy is related to some dysfunctions, such as hypertrophy. The architecture of myocardial fibers determines LV electromechanical activation patterns as well as mechanics. Thus, their joined modelling would allow the design of specific interventions (such as peacemaker implantation and LV remodelling) and therapies (such as resynchronization). On one hand, accurate modelling of external anatomy requires either a dense sampling or a continuous infinite dimensional approach, which requires non-Euclidean statistics. On the other hand, computation of fiber models requires statistics on Riemannian spaces. Most approaches compute separate statistical models for external anatomy and fibers architecture. In this work we propose a general mathematical framework based on differential geometry concepts for computing a statistical model including, both, external and fiber anatomy. Our framework provides a continuous approach to external anatomy supporting standard statistics. We also provide a straightforward formula for the computation of the Riemannian fiber statistics. We have applied our methodology to the computation of complete anatomical atlas of canine hearts from diffusion tensor studies. The orientation of fibers over the average external geometry agrees with the segmental description of orientations reported in the literature.

Health economics and the European Heart Rhythm Association.

PubMed

Vardas, Panos; Boriani, Giuseppe

2011-05-01

The management of healthcare is becoming extremely complex in developed countries, as a result of increasing age of the population and increasing costs of care, coupled with diminishing resources due to global financial crisis. This situation threatens access to appropriate care, and a more or less explicit rationing of some types of treatment may occur in 'real world' clinical practice. This is particularly true for those treatments or interventions with a relatively high up-front cost, such as cardioverter defibrillators, devices for cardiac resynchronization therapy or ablation procedures for atrial fibrillation. The European Heart Rhythm Association (EHRA) is strongly convinced that the skills of electrophysiologists and cardiologists responsible for the management of rhythm disorders have to evolve, also embracing the knowledge of health economics, clinical epidemiology, health-care management and outcome research. These disciplines do not belong to what is considered as the conventional cultural background of physicians, but knowledge of comparative cost effectiveness and of other economic approaches nowadays appears fundamental for a dialogue with a series of stakeholders, such as policy makers, politicians, and administrators, involved in budgeting the activity of hospitals and health-care services, as well as in approaching health technology assessment.

Heart rate turbulence.

PubMed

Cygankiewicz, Iwona

2013-01-01

Heart rate turbulence (HRT) is a baroreflex-mediated biphasic reaction of heart rate in response to premature ventricular beats. Heart rate turbulence is quantified by: turbulence onset (TO) reflecting the initial acceleration of heart rate following premature beat and turbulence slope (TS) describing subsequent deceleration of heart rate. Abnormal HRT identifies patients with autonomic dysfunction or impaired baroreflex sensitivity due to variety of disorders, but also may reflect changes in autonomic nervous system induced by different therapeutic modalities such as drugs, revascularization, or cardiac resynchronization therapy. More importantly, impaired HRT has been shown to identify patients at high risk of all-cause mortality and sudden death, particularly in postinfarction and congestive heart failure patients. It should be emphasized that abnormal HRT has a well-established role in stratification of postinfarction and heart failure patients with relatively preserved left ventricular ejection fraction. The ongoing clinical trials will document whether HRT can be used to guide implantation of cardioverter-defibrillators in this subset of patients, not covered yet by ICD guidelines. This review focuses on the current state-of-the-art knowledge regarding clinical significance of HRT in detection of autonomic dysfunction and regarding the prognostic significance of this parameter in predicting all-cause mortality and sudden death. © 2013.

Childhood Soft Tissue Sarcoma Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood soft tissue sarcoma treatment options include surgery, radiation therapy, chemotherapy, observation, targeted therapy, immunotherapy and other medications.  Learn more about the diagnosis and treatment of the many types of childhood soft tissue sarcoma in this expert-reviewed summary.

Periodontal and peri-implant wound healing following laser therapy.

PubMed

Aoki, Akira; Mizutani, Koji; Schwarz, Frank; Sculean, Anton; Yukna, Raymond A; Takasaki, Aristeo A; Romanos, Georgios E; Taniguchi, Yoichi; Sasaki, Katia M; Zeredo, Jorge L; Koshy, Geena; Coluzzi, Donald J; White, Joel M; Abiko, Yoshimitsu; Ishikawa, Isao; Izumi, Yuichi

2015-06-01

Laser irradiation has numerous favorable characteristics, such as ablation or vaporization, hemostasis, biostimulation (photobiomodulation) and microbial inhibition and destruction, which induce various beneficial therapeutic effects and biological responses. Therefore, the use of lasers is considered effective and suitable for treating a variety of inflammatory and infectious oral conditions. The CO2 , neodymium-doped yttrium-aluminium-garnet (Nd:YAG) and diode lasers have mainly been used for periodontal soft-tissue management. With development of the erbium-doped yttrium-aluminium-garnet (Er:YAG) and erbium, chromium-doped yttrium-scandium-gallium-garnet (Er,Cr:YSGG) lasers, which can be applied not only on soft tissues but also on dental hard tissues, the application of lasers dramatically expanded from periodontal soft-tissue management to hard-tissue treatment. Currently, various periodontal tissues (such as gingiva, tooth roots and bone tissue), as well as titanium implant surfaces, can be treated with lasers, and a variety of dental laser systems are being employed for the management of periodontal and peri-implant diseases. In periodontics, mechanical therapy has conventionally been the mainstream of treatment; however, complete bacterial eradication and/or optimal wound healing may not be necessarily achieved with conventional mechanical therapy alone. Consequently, in addition to chemotherapy consisting of antibiotics and anti-inflammatory agents, phototherapy using lasers and light-emitting diodes has been gradually integrated with mechanical therapy to enhance subsequent wound healing by achieving thorough debridement, decontamination and tissue stimulation. With increasing evidence of benefits, therapies with low- and high-level lasers play an important role in wound healing/tissue regeneration in the treatment of periodontal and peri-implant diseases. This article discusses the outcomes of laser therapy in soft-tissue management, periodontal nonsurgical and surgical treatment, osseous surgery and peri-implant treatment, focusing on postoperative wound healing of periodontal and peri-implant tissues, based on scientific evidence from currently available basic and clinical studies, as well as on case reports. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Maggot therapy for gangrene and osteomyelitis].

PubMed

Mumcuoglu, K Y; Lipo, M; Ioffe-Uspensky, I; Miller, J; Galun, R

1997-03-02

5 patients with diabetic-foot were treated by maggot therapy. The most serious case was in a 75-year-old man who had gangrene and osteomyelitis of the right foot. Proteus mirabilis, Enterococcus sp., Providencia stuartii and Staphylococcus spec. (coagulase positive) were isolated from lesions which did not respond to antibiotic therapy. The patient had twice refused amputation but agreed to maggot therapy. Larvae of the sheep blowfly Phoenicia (Lucilia) sericata were used for twice-weekly treatment over a period of 7 months. Sterile larvae were applied to the wound and replaced every 3-4 days. After 4 months of treatment, the necrotic tissue around the toes and on the sole of the foot detached from the healthy tissue. During the last 3 months of treatment the larvae removed the remaining infected tissue. As therapy progressed, new layers of healthy tissue covered the wound. The offensive odor associated with the necrotic tissue and the intense pain in the foot decreased significantly. At the end of therapy, during which there were no complaints of discomfort, he was able to walk. In the 4 other patients who had relatively superficial gangrene, the maggots debrided the wounds within 2-4 weeks. Thereafter treatment was continued with antibiotics. Maggot therapy can be recommended in cases of intractable gangrene and osteomyelitis, when treatment with antibiotics and surgical debridement have failed.

Biventricular pacemaker optimization guided by comprehensive echocardiography-preliminary observations regarding the effects on systolic and diastolic ventricular function and third heart sound.

PubMed

Taha, Nima; Zhang, Jing; Ranjan, Rupesh; Daneshvar, Samuel; Castillo, Edilzar; Guillen, Elizabeth; Montoya, Martha C; Velasquez, Giovanna; Naqvi, Tasneem Z

2010-08-01

Doppler echocardiography of mitral inflow or aortic outflow or both has been validated and advocated to guide biventricular (Biv) pacemaker optimization. A comprehensive and tailored Doppler echocardiographic evaluation may be required in patients with heart failure to assist with Biv pacemaker optimization. The third heart sound (S(3)), an acoustic cardiographic parameter, has been demonstrated to be a highly specific finding for hemodynamic evaluation in patients with heart failure. The aims of this study were to evaluate the use of comprehensive Doppler echocardiography as a guide during Biv pacemaker optimization in patients after cardiac resynchronization therapy and to evaluate the feasibility of S(3) intensity to be a cost-efficient parameter for Biv pacemaker optimization compared with Doppler echocardiography. Comprehensive Doppler echocardiographic evaluations were performed during Biv pacemaker optimization in 44 patients referred for pacemaker optimization (mean age, 71 + or - 12 years; mean left ventricular ejection fraction, 34 + or - 11%). Blinded assessment of S(3) intensity was performed simultaneously using acoustic cardiography. The correlation and improvement in cardiac hemodynamics were analyzed between the methods. Echocardiographically guided optimization resulted in significant improvements in the left ventricular outflow velocity-time integral (15.92 + or - 4.77 to 18.51 + or - 5.19 cm, P < .001), ejection time (278 + or - 40 to 293 + or - 40 ms, P < .001), myocardial performance index (0.57 + or - 0.19 to 0.44 + or - 0.14, P < .002), and peak pulmonary artery systolic pressure (42 + or - 13 to 36 + or - 11 mm Hg, P < .04) and decreased S(3) intensity from 4.81 + or - 1.84 at baseline to 3.96 + or - 1.22 after optimization (P < .02) for the overall study group and from 6.63 + or - 1.37 to 4.85 + or - 1.13 (P < .001) in the 18 patients with baseline S(3) intensity > 5.0. The correlation between echocardiographic and acoustic cardiographic S(3) intensity for optimal atrioventricular delay was 0.86 (P < .001) and for optimal interventricular delay was 0.64 (P < .001). Optimal atrioventricular delay was identical by echocardiographic and acoustic cardiographic S(3) intensity in 56%, and optimal interventricular delay was identical in 75% of patients. Pacemakers were permanently programmed on the basis of echocardiographic evaluation. In 35 patients available for follow up, the mean New York Heart Association class reduced from 2.55 + or - 0.81 to 1.77 + or - 0.90 (P < .001) and the mean quality-of-life score as assessed by Minnesota Living With Heart Failure Questionnaire improved from 45 + or - 28 to 32 + or - 28 (P = .08) at 2.5 + or - 2.1 months. Comprehensive echocardiographically guided Biv pacemaker optimization produces significant improvement in Doppler echocardiographic hemodynamics, a reduction in S(3) intensity, and an improvement in functional class in patients after cardiac resynchronization therapy. Copyright 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Legal basis of the Advanced Therapies Regulation.

PubMed

Jekerle, V; Schröder, C; Pedone, E

2010-01-01

Advanced therapy medicinal products consist of gene therapy, somatic cell therapy and tissue engineered products. Due to their specific manufacturing process and mode of action these products require specially tailored legislation. With Regulation (EC) No. 1394/2007, these needs have been met. Definitions of gene therapy, somatic cell therapy and tissue engineered products were laid down. A new committee, the Committee for Advanced Therapies, was founded, special procedures such as the certification procedure for small- and medium-sized enterprises were established and the technical requirements for Marketing Authorisation Applications (quality, non-clinical and clinical) were revised.

Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue.

PubMed

Jansen, H J; Stienstra, R; van Diepen, J A; Hijmans, A; van der Laak, J A; Vervoort, G M M; Tack, C J

2013-12-01

Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the insulin-associated increase in fat mass would also result in changes in the morphology of human subcutaneous adipose tissue and in increased inflammation, especially when weight gain was excessive. We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy. As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining >4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-α and IL-1β after 6 months of insulin therapy compared with those who had not gained weight. We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status. ClinicalTrials.gov: NCT00781495. The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.

Validation of electromechanical wave imaging in a canine model during pacing and sinus rhythm.

PubMed

Grondin, Julien; Costet, Alexandre; Bunting, Ethan; Gambhir, Alok; Garan, Hasan; Wan, Elaine; Konofagou, Elisa E

2016-11-01

Accurate determination of regional areas of arrhythmic triggers is of key interest to diagnose arrhythmias and optimize their treatment. Electromechanical wave imaging (EWI) is an ultrasound technique that can image the transient deformation in the myocardium after electrical activation and therefore has the potential to detect and characterize location of triggers of arrhythmias. The objectives of this study were to investigate the relationship between the electromechanical and the electrical activation of the left ventricular (LV) endocardial surface during epicardial and endocardial pacing and during sinus rhythm as well as to map the distribution of electromechanical delays. In this study, 6 canines were investigated. Two external electrodes were sutured onto the epicardial surface of the LV. A 64-electrode basket catheter was inserted through the apex of the LV. Ultrasound channel data were acquired at 2000 frames/s during epicardial and endocardial pacing and during sinus rhythm. Electromechanical and electrical activation maps were synchronously obtained from the ultrasound data and the basket catheter, respectively. The mean correlation coefficient between electromechanical and electrical activation was 0.81 for epicardial anterior pacing, 0.79 for epicardial lateral pacing, 0.69 for endocardial pacing, and 0.56 for sinus rhythm. The electromechanical activation sequence determined by EWI follows the electrical activation sequence and more specifically in the case of pacing. This finding is of key interest in the role that EWI can play in the detection of the anatomical source of arrhythmias and the planning of pacing therapies such as cardiovascular resynchronization therapy. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Validation of Electromechanical Wave Imaging in a canine model during pacing and sinus rhythm

PubMed Central

Grondin, Julien; Costet, Alexandre; Bunting, Ethan; Gambhir, Alok; Garan, Hasan; Wan, Elaine; Konofagou, Elisa E.

2016-01-01

Background Accurate determination of regional areas of arrhythmic triggers is of key interest to diagnose arrhythmias and optimize their treatment. Electromechanical wave imaging (EWI) is an ultrasound technique that can image the transient deformation in the myocardium following electrical activation and therefore has the potential to detect and characterize location of triggers of arrhythmias. Objectives The objectives of this study are to investigate the relationship between electromechanical and electrical activation of the left-ventricular (LV) endocardial surface during epicardial and endocardial pacing as well as during sinus rhythm and also to investigate the distribution of electromechanical delays. Methods In this study, six canines were investigated. Two external electrodes were sutured onto the epicardial surface of the left ventricle (LV). A 64-electrode basket catheter was inserted through the apex of the LV. Ultrasound channel data were acquired at 2000 frames/s during epicardial and endocardial pacing as well as during sinus rhythm. Electromechanical and electrical activation maps were synchronously obtained from the ultrasound data and the basket catheter respectively. Results The mean correlation coefficient between electromechanical and electrical activation was R=0.81 for epicardial anterior pacing, R=0.79 for epicardial lateral pacing, R=0.69 for endocardial pacing and R=0.56 for sinus rhythm. Conclusions The electromechanical activation sequence determined by EWI follows the electrical activation sequence and more specifically in the case of pacing. This finding is of key interest in the role that EWI can play in the detection of the anatomical source of arrhythmias and the planning of pacing therapies such as cardiovascular resynchronization therapy. PMID:27498277

Prognostic Estimation of Advanced Heart Failure With Low Left Ventricular Ejection Fraction and Wide QRS Interval.

PubMed

Oh, Changmyung; Chang, Hyuk-Jae; Sung, Ji Min; Kim, Ji Ye; Yang, Wooin; Shim, Jiyoung; Kang, Seok-Min; Ha, Jongwon; Rim, Se-Joong; Chung, Namsik

2012-10-01

Cardiac resynchronization therapy (CRT) has been known to improve the outcome of advanced heart failure (HF) but is still underutilized in clinical practice. We investigated the prognosis of patients with advanced HF who were suitable for CRT but were treated with conventional strategies. We also developed a risk model to predict mortality to improve the facilitation of CRT. Patients with symptomatic HF with left ventricular ejection fraction ≤35% and QRS interval >120 ms were consecutively enrolled at cardiovascular hospital. After excluding those patients who had received device therapy, 239 patients (160 males, mean 67±11 years) were eventually recruited. During a follow-up of 308±236 days, 56 (23%) patients died. Prior stroke, heart rate >90 bpm, serum Na ≤135 mEq/L, and serum creatinine ≥1.5 mg/dL were identified as independent factors using Cox proportional hazards regression. Based on the risk model, points were assigned to each of the risk factors proportional to the regression coefficient, and patients were stratified into three risk groups: low- (0), intermediate-(1-5), and high-risk (>5 points). The 2-year mortality rates of each risk group were 5, 31, and 64 percent, respectively. The C statistic of the risk model was 0.78, and the model was validated in a cohort from a different institution where the C statistic was 0.80. The mortality of patients with advanced HF who were managed conventionally was effectively stratified using a risk model. It may be useful for clinicians to be more proactive about adopting CRT to improve patient prognosis.

How, why, and when may atrial defibrillation find a specific role in implantable devices? A clinical viewpoint.

PubMed

Boriani, Giuseppe; Diemberger, Igor; Biffi, Mauro; Martignani, Cristian; Ziacchi, Matteo; Bertini, Matteo; Valzania, Cinzia; Bronzetti, Gabriele; Rapezzi, Claudio; Branzi, Angelo

2007-03-01

This viewpoint article discusses the potential for incorporation of atrial defibrillation capabilities in modern multi-chamber devices. In the late 1990s, the possibility of using shock-only therapy to treat selected patients with recurrent atrial fibrillation (AF) was explored in the context of the stand-alone atrial defibrillator. The failure of this strategy can be attributed to the technical limitations of the stand-alone device, low tolerance of atrial shocks, difficulties in patient selection, a lack of predictive knowledge about the evolution of AF, and, last but not least, commercial considerations. An open question is how atrial defibrillation capability may now assume a specific new role in devices implanted for sudden death prevention or cardiac resynchronization. For patients who already have indications for implantable devices, device-based atrial defibrillation appears attractive as a "backup" option for managing AF when preventive pharmacological/electrical measures fail. This and several other personalized hybrid therapeutic approaches await exploration, though assessment of their efficacy is methodologically challenging. Achievement of acceptance by patients is an essential premise for any updated atrial defibrillation strategy. Strategies that are being investigated to improve patient tolerance include waveform shaping, pharmacologic modulation of pain, and patient-activated defibrillation (patients might also perceive the problem of discomfort somewhat differently in the context of a backup therapy). The economic impact of implementing atrial defibrillation features in available devices is progressively decreasing, and financial feasibility need not be a major issue. Future studies should examine clinically relevant outcomes and not be limited (as occurred with stand-alone defibrillators) to technical or other soft endpoints.

Refusing Implantable Cardioverter Defibrillator (ICD) Replacement in Elderly Persons-The Same as Giving Up Life: A Qualitative Study.

PubMed

Svanholm, Jette Rolf; Nielsen, Jens Cosedis; Mortensen, Peter; Christensen, Charlotte Fuglesang; Birkelund, Regner

2015-11-01

More than 20% of implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) devices are implanted in the elderly population aged 80 years or older. In recent scientific literature it is suggested to consider termination of ICD therapy, rather than ICD replacement, in this patient group. The aim of this study was to explore the experiences of persons above 80 years of age concerning replacement of the ICD battery, and the shared communication and decision making with healthcare professionals. We performed a qualitative, explorative study, inspired by Ricoeur's narrative, with a phenomenological-hermeneutic approach, involving 11 ICD patients older than 80 years. The study period was 2011-2012. The meaning of the patients' experiences of living with an ICD was formulated into two themes: (1) "Feeling safe with the ICD" with the subthemes: "The ICD-a life keeper," "The battery level is important," "ICD shock-no problem." (2) "The physician is an authority" with the subthemes: "Being trustful," "Feeling fine knowing nothing," "Criminal act to deactivate the ICD." The elderly ICD recipients tended not to be aware of the option of declining replacement of their ICD. They tended to expect to have their ICD replaced and not to be involved actively in decision making concerning this. Healthcare professionals have an obligation to discuss options and ensure that every patient understands these. More research is needed to change practices and create more realistic, person-centered, ethically acceptable, and constructive healthcare for elderly persons with an ICD. © 2015 Wiley Periodicals, Inc.

A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration.

PubMed

MacIsaac, Rachael L; Khatri, Pooja; Bendszus, Martin; Bracard, Serge; Broderick, Joseph; Campbell, Bruce; Ciccone, Alfonso; Dávalos, Antoni; Davis, Stephen M; Demchuk, Andrew; Diener, Hans-Christoph; Dippel, Diederik; Donnan, Geoffrey A; Fiehler, Jens; Fiorella, David; Goyal, Mayank; Hacke, Werner; Hill, Michael D; Jahan, Reza; Jauch, Edward; Jovin, Tudor; Kidwell, Chelsea S; Liebeskind, David; Majoie, Charles B; Martins, Sheila Cristina Ouriques; Mitchell, Peter; Mocco, J; Muir, Keith W; Nogueira, Raul; Saver, Jeffrey L; Schonewille, Wouter J; Siddiqui, Adnan H; Thomalla, Götz; Tomsick, Thomas A; Turk, Aquilla S; White, Philip; Zaidat, Osama; Lees, Kennedy R

2015-10-01

Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator. This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group. This protocol will specify the primary outcome for efficacy, as 'favorable' outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: 'what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasminogen activator alone on full scale modified Rankin Scale at 3 months?' and 'to what extent do key patient characteristics influence the treatment effect of endovascular therapy?'. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow. This collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication. © 2015 World Stroke Organization.

Persistent suppression of subthalamic beta-band activity during rhythmic finger tapping in Parkinson's disease.

PubMed

Joundi, Raed A; Brittain, John-Stuart; Green, Alex L; Aziz, Tipu Z; Brown, Peter; Jenkinson, Ned

2013-03-01

The function of synchronous oscillatory activity at beta band (15-30Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement. We recorded local field potential activity from the subthalamic nuclei of 11 patients with Parkinson's disease during a synchronized tapping task at three different externally cued rates. Beta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained suppressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate. Our results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modulated by rate of finger tapping, These findings implicate consistent beta suppression in the facilitation of continuous movement sequences. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Thermal therapy techniques for skin and superficial tissue disease

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.

2000-01-01

There are numerous diseases and abnormal growths and conditions that afflict the skin and underlying superficial tissues. In addition to cancers such as primary, recurrent, and metastatic melanomas and carcinomas, there are many non-malignant conditions such as psoriasis plaques, port wine stains, warts, and superficial cut and bum wounds. Many of these clinical conditions have been shown responsive to treatment with thermal therapy - either low temperature freezing (cryotherapy),. moderate temperature warming to about 41-45°C (hyperthermia), or high temperature (>50°C) ablation or coagulation necrosis therapy. Because both very low and very high temperature therapies are for the most part non-selectively destructive in nature, they normally are used for applications where therapy can be localized precisely in the desired target and some necrosis of adjacent normal tissues is acceptable. With the exception of precision controlled cryotherapy or laser surgery (e.g. wart, mole, tattoo and port wine stain removal) or focal thermal surgery of small deep-seated nodules, it is generally preferred to use moderate thermal therapy (hyperthermia) in the treatment of skin and subcutaneous tissue disease in order to preserve the protective barrier characteristic of intact skin within the target region while inducing more subtle long term therapeutic improvement in the disease condition. This type of subtle thermal therapy is usually administered in combination with one or more other therapies such as radiation or chemotherapy - something with a differential effect on the target and surrounding normal tissues that can be magnified by the adjuvant use of heat.

Pilot study: whole body manual subcutaneous adipose tissue (SAT) therapy improved pain and SAT structure in women with lipedema.

PubMed

Herbst, Karen L; Ussery, Christopher; Eekema, Alyna

2017-09-20

Background Lipedema is a common painful subcutaneous adipose tissue (SAT) disorder in women affecting the limbs. SAT therapy is a manual therapy to improve soft tissue quality. Objective Determine if SAT therapy improves pain and structure of lipedema SAT. Design Single arm prospective pilot study. Setting Academic medical center. Patients Seven women, 46 ± 5 years, weight 90 ± 19 kg, with lipedema. Intervention Twelve 90-min SAT therapy sessions over 4 weeks. Outcomes Dual X-ray absorptiometry (DXA) scans, SAT ultrasound (Vevo 2100), leg volumetrics, skin caliper assessment, tissue exam, weight, resting metabolic rate, pain assessment, lower extremity functional scale (LEFS) and body shape questionnaire (BSQ) at baseline and end of study. Results Weight, resting metabolic rate and BSQ did not change significantly. Limb fat over total body fat mass (p = 0.08) and trunk fat over total body mass trended down from baseline (p = 0.08) by DXA. Leg volume and caliper assessments in eight of nine areas (p < 0.007), LEFS (p = 0.002) and average pain (p = 0.007) significantly decreased from baseline. Fibrosis significantly decreased in the nodules, hips and groin. Ultrasound showed improved SAT structure in some subjects. Side effects included pain, bruising, itching, swelling and gastroesophageal reflux disease. All women said they would recommend SAT therapy to other women with lipedema. Limitations Small number of subjects. Conclusion SAT therapy in 4 weeks improved tissue structure, perceived leg function, and volume although shape was not affected. While side effects of SAT therapy were common, all women felt the therapy was beneficial.

An innovative therapy for peri-implantitis based on radio frequency electric current: numerical simulation results and clinical evidence.

PubMed

Cosoli, G; Scalise, L; Tricarico, G; Tomasini, E P; Cerri, G

2016-08-01

Peri-implantitis is a severe inflammatory pathology that affects soit and hard tissues surrounding dental implants. Nowadays, only prevention is effective to contrast peri-implantitis, but, in recent years, there is the clinical evidence of the efficiency of a therapy based on the application of radio frequency electric current, reporting that 81% of the cases (66 implants, 46 patients) were successfully treated. The aim of this paper is to present the therapy mechanism, exploring the distribution of the electric currents in normal and pathologic tissues. A 3D numerical FEM model of tooth root with a dental implant screwed in the alveolar bone has been realized and the therapy has been simulated in COMSOL Multiphysics® environment. Results show that the electric current is focused in the inflamed zone around the implant, due to the fact that its conductivity is higher than the healthy tissue one. Moreover, by means of a movable return electrode, the electric current and field lines can be guided in the most inflamed area, limiting the interference on healthy tissues and improving the therapy in the area of interest. In conclusion, it can be stated that this innovative therapy would make a personalized therapy for peri-implantitis possible, also through impedance measurements, allowing the clinician to evaluate the tissue inflammation state.

Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone

NASA Astrophysics Data System (ADS)

Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Jasper, Juliana; Casagrande, Liliane Cristina Onofre; Maito, Fábio Luiz Dal Moro

2017-05-01

Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

Cell delivery in regenerative medicine: the cell sheet engineering approach.

PubMed

Yang, Joseph; Yamato, Masayuki; Nishida, Kohji; Ohki, Takeshi; Kanzaki, Masato; Sekine, Hidekazu; Shimizu, Tatsuya; Okano, Teruo

2006-11-28

Recently, cell-based therapies have developed as a foundation for regenerative medicine. General approaches for cell delivery have thus far involved the use of direct injection of single cell suspensions into the target tissues. Additionally, tissue engineering with the general paradigm of seeding cells into biodegradable scaffolds has also evolved as a method for the reconstruction of various tissues and organs. With success in clinical trials, regenerative therapies using these approaches have therefore garnered significant interest and attention. As a novel alternative, we have developed cell sheet engineering using temperature-responsive culture dishes, which allows for the non-invasive harvest of cultured cells as intact sheets along with their deposited extracellular matrix. Using this approach, cell sheets can be directly transplanted to host tissues without the use of scaffolding or carrier materials, or used to create in vitro tissue constructs via the layering of individual cell sheets. In addition to simple transplantation, cell sheet engineered constructs have also been applied for alternative therapies such as endoscopic transplantation, combinatorial tissue reconstruction, and polysurgery to overcome limitations of regenerative therapies and cell delivery using conventional approaches.

Minibeam therapy with protons and light ions: physical feasibility and potential to reduce radiation side effects and to facilitate hypofractionation.

PubMed

Dilmanian, F Avraham; Eley, John G; Krishnan, Sunil

2015-06-01

Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulations were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of photodynamic laser therapy in the treatment of marginal chronic periodontitis

NASA Astrophysics Data System (ADS)

Chifor, Radu; Badea, Iulia; Avram, Ramona; Chifor, Ioana; Badea, Mîndra Eugenia

2016-03-01

The aim of this study was to assess the effects of the antimicrobial photodynamic laser therapy performed during the treatment of deep periodontal disease by using 40 MHz high frequency ultrasonography. The periodontal data recorded during the clinical examination before each treatment session were compared with volumetric changes of the gingiva measured on periodontal ultrasound images. The results show a significant decrease of gingival tissue inflammation proved both by a significant decrease of bleeding on probing as well as by a decrease of the gingival tissues volume on sites where the laser therapy was performed. Periodontal tissues that benefit of laser therapy besides classical non-surgical treatment showed a significant clinical improvement of periodontal status. Based on these findings we were able to conclude that the antimicrobial photodynamic laser therapy applied on marginal periodontium has important anti-inflamatory effect. The periodontal ultrasonography is a method which can provide useful data for assessing the volume changes of gingival tissues, allowing a precise monitoring of marginal periodontitis.

Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy.

PubMed

Priglinger, Eleni; Schuh, Christina M A P; Steffenhagen, Carolin; Wurzer, Christoph; Maier, Julia; Nuernberger, Sylvia; Holnthoner, Wolfgang; Fuchs, Christiane; Suessner, Susanne; Rünzler, Dominik; Redl, Heinz; Wolbank, Susanne

2017-09-01

Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Redox-Modulated Phenomena and Radiation Therapy: The Central Role of Superoxide Dismutases

PubMed Central

Holley, Aaron K.; Miao, Lu; St. Clair, Daret K.

2014-01-01

Abstract Significance: Ionizing radiation is a vital component in the oncologist's arsenal for the treatment of cancer. Approximately 50% of all cancer patients will receive some form of radiation therapy as part of their treatment regimen. DNA is considered the major cellular target of ionizing radiation and can be damaged directly by radiation or indirectly through reactive oxygen species (ROS) formed from the radiolysis of water, enzyme-mediated ROS production, and ROS resulting from altered aerobic metabolism. Recent Advances: ROS are produced as a byproduct of oxygen metabolism, and superoxide dismutases (SODs) are the chief scavengers. ROS contribute to the radioresponsiveness of normal and tumor tissues, and SODs modulate the radioresponsiveness of tissues, thus affecting the efficacy of radiotherapy. Critical Issues: Despite its prevalent use, radiation therapy suffers from certain limitations that diminish its effectiveness, including tumor hypoxia and normal tissue damage. Oxygen is important for the stabilization of radiation-induced DNA damage, and tumor hypoxia dramatically decreases radiation efficacy. Therefore, auxiliary therapies are needed to increase the effectiveness of radiation therapy against tumor tissues while minimizing normal tissue injury. Future Directions: Because of the importance of ROS in the response of normal and cancer tissues to ionizing radiation, methods that differentially modulate the ROS scavenging ability of cells may prove to be an important method to increase the radiation response in cancer tissues and simultaneously mitigate the damaging effects of ionizing radiation on normal tissues. Altering the expression or activity of SODs may prove valuable in maximizing the overall effectiveness of ionizing radiation. Antioxid. Redox Signal. 20, 1567–1589. PMID:24094070

Users' manual for computer program for three-dimensional analysis of coupler-cavity traveling wave tubes

NASA Technical Reports Server (NTRS)

Omalley, T. A.

1984-01-01

The use of the coupled cavity traveling wave tube for space communications has led to an increased interest in improving the efficiency of the basic interaction process in these devices through velocity resynchronization and other methods. A flexible, three dimensional, axially symmetric, large signal computer program was developed for use on the IBM 370 time sharing system. A users' manual for this program is included.

Analysis of implantable defibrillator longevity under clinical circumstances: implications for device selection.

PubMed

Knops, Paul; Theuns, Dominic A M J; Res, Jan C J; Jordaens, Luc

2009-10-01

Information about implantable cardioverter-defibrillator (ICD) longevity is mostly calculated from measurements under ideal laboratory conditions. However, little information about longevity under clinical circumstances is available. This survey gives an overview on ICD service times and generator replacements in a cohort of consecutive ICD patients. Indications for replacement were classified as a normal end-of-service (EOS), premature EOS, system malfunction, infection and device advisory, or recall actions. From the premature and normal EOS group, longevity from single-chamber (SC), dual-chamber (DC), and cardiac resynchronization therapy defibrillator (CRT-D), rate-responsive (RR) settings, high output (HO) stimulation, and indication for ICD therapy was compared. Differences between brands were compared as well. In a total of 854 patients, 203 ICD replacements (165 patients) were recorded. Premature and normal EOS replacements consisted of 32 SC, 98 DC and 24 CRT-D systems. Longevity was significantly longer in SC systems compared to DC and CRT-D systems (54 +/- 19 vs. 40 +/- 17 and 42 +/- 15 months; P = 0.008). Longevity between non-RR (n = 143) and RR (n = 11) settings was not significantly different (43 +/- 18 vs. 45 +/- 13 months) as it also was not for HO versus non-HO stimulation (43 +/- 19 vs. 46 +/- 17 months). Longevity of ICDs was not significantly different between primary and secondary prevention (42 +/- 19 vs. 44 +/- 18 months). The average longevity on account of a device-based EOS message was 43 +/- 18 months. Average longevity for Biotronik (BIO, n = 72) was 33 +/- 10 months, for ELA Medical (ELA, n = 12) 44 +/- 17 months, for Guidant (GDT, n = 36) 49 +/- 12 months, for Medtronic (MDT, n = 29) 62 +/- 22 months, and for St. Jude Medical (SJM, n = 5) 31 +/- 9 months (P < 0.001). SC ICD generators had a longer service time compared to DC and CRT-D systems. No influence of indication for ICD therapy and HO stimulation on generator longevity was observed in this study. MDT ICDs had the longest service time.

Expediting the transition from replacement medicine to tissue engineering.

PubMed

Coury, Arthur J

2016-06-01

In this article, an expansive interpretation of "Tissue Engineering" is proposed which is in congruence with classical and recent published definitions. I further simplify the definition of tissue engineering as: "Exerting systematic control of the body's cells, matrices and fluids." As a consequence, many medical therapies not commonly considered tissue engineering are placed in this category because of their effect on the body's responses. While the progress of tissue engineering strategies is inexorable and generally positive, it has been subject to setbacks as have many important medical therapies. Medical practice is currently undergoing a transition on several fronts (academics, start-up companies, going concerns) from the era of "replacement medicine" where body parts and functions are replaced by mechanical, electrical or chemical therapies to the era of tissue engineering where health is restored by regeneration generation or limitation of the body's tissues and functions by exploiting our expanding knowledge of the body's biological processes to produce natural, healthy outcomes.

Systemic sclerosis-scleroderma.

PubMed

Haustein, U-F

2002-06-01

Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This review discusses epidemiology and survival, clinical features including subsets and internal organ involvement, pathophysiology and genetics, microvasculature, immunobiology, fibroblasts and connective tissue metabolism and environmental factors. Early diagnosis and individually tailored therapy help to manage this disorder, which is treatable, but not curable. Therapy involves immunomodulation as well as the targeting of blood vessel mechanics and fibrosis. Physical therapy and psychotherapy are also important adjunctive therapies in this multifactorial disease.

The potential value of integrated natriuretic peptide and echo-guided heart failure management

PubMed Central

2014-01-01

There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the mechanism predominant in that individual patient. A monocular, specialistic, unidimensional approach to HF can miss its pathogenetic and clinical complexity, which only can be overcome with an integrated, versatile and tailored approach. PMID:25037453

21 CFR 5.1100 - Headquarters.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Laboratories Complex Staff. Division of Engineering Services. Environment, Safety And Strategic Initiatives.... Office of Cellular, Tissue, and Gene Therapies. Regulatory Management Staff. Division of Cellular and Gene Therapies. Division of Clinical Evaluation and Pharmacology/Toxicology. Division of Human Tissues...

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

NASA Astrophysics Data System (ADS)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies.

PubMed

Santiesteban, Daniela Y; Kubelick, Kelsey; Dhada, Kabir S; Dumani, Diego; Suggs, Laura; Emelianov, Stanislav

2016-03-01

The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

Intraventricular flow alterations due to dyssynchronous wall motion

NASA Astrophysics Data System (ADS)

Pope, Audrey M.; Lai, Hong Kuan; Samaee, Milad; Santhanakrishnan, Arvind

2015-11-01

Roughly 30% of patients with systolic heart failure suffer from left ventricular dyssynchrony (LVD), in which mechanical discoordination of the ventricle walls leads to poor hemodynamics and suboptimal cardiac function. There is currently no clear mechanistic understanding of how abnormalities in septal-lateral (SL) wall motion affects left ventricle (LV) function, which is needed to improve the treatment of LVD using cardiac resynchronization therapy. We use an experimental flow phantom with an LV physical model to study mechanistic effects of SL wall motion delay on LV function. To simulate mechanical LVD, two rigid shafts were coupled to two segments (apical and mid sections) along the septal wall of the LV model. Flow through the LV model was driven using a piston pump, and stepper motors coupled to the above shafts were used to locally perturb the septal wall segments relative to the pump motion. 2D PIV was used to examine the intraventricular flow through the LV physical model. Alterations to SL delay results in a reduction in the kinetic energy (KE) of the flow field compared to synchronous SL motion. The effect of varying SL motion delay from 0% (synchronous) to 100% (out-of-phase) on KE and viscous dissipation will be presented. This research was supported by the Oklahoma Center for Advancement of Science and Technology (HR14-022).

Image based cardiac acceleration map using statistical shape and 3D+t myocardial tracking models; in-vitro study on heart phantom

NASA Astrophysics Data System (ADS)

Pashaei, Ali; Piella, Gemma; Planes, Xavier; Duchateau, Nicolas; de Caralt, Teresa M.; Sitges, Marta; Frangi, Alejandro F.

2013-03-01

It has been demonstrated that the acceleration signal has potential to monitor heart function and adaptively optimize Cardiac Resynchronization Therapy (CRT) systems. In this paper, we propose a non-invasive method for computing myocardial acceleration from 3D echocardiographic sequences. Displacement of the myocardium was estimated using a two-step approach: (1) 3D automatic segmentation of the myocardium at end-diastole using 3D Active Shape Models (ASM); (2) propagation of this segmentation along the sequence using non-rigid 3D+t image registration (temporal di eomorphic free-form-deformation, TDFFD). Acceleration was obtained locally at each point of the myocardium from local displacement. The framework has been tested on images from a realistic physical heart phantom (DHP-01, Shelley Medical Imaging Technologies, London, ON, CA) in which the displacement of some control regions was known. Good correlation has been demonstrated between the estimated displacement function from the algorithms and the phantom setup. Due to the limited temporal resolution, the acceleration signals are sparse and highly noisy. The study suggests a non-invasive technique to measure the cardiac acceleration that may be used to improve the monitoring of cardiac mechanics and optimization of CRT.

Exploring time series retrieved from cardiac implantable devices for optimizing patient follow-up

PubMed Central

Guéguin, Marie; Roux, Emmanuel; Hernández, Alfredo I; Porée, Fabienne; Mabo, Philippe; Graindorge, Laurence; Carrault, Guy

2008-01-01

Current cardiac implantable devices (ID) are equipped with a set of sensors that can provide useful information to improve patient follow-up and to prevent health deterioration in the postoperative period. In this paper, data obtained from an ID with two such sensors (a transthoracic impedance sensor and an accelerometer) are analyzed in order to evaluate their potential application for the follow-up of patients treated with a cardiac resynchronization therapy (CRT). A methodology combining spatio-temporal fuzzy coding and multiple correspondence analysis (MCA) is applied in order to: i) reduce the dimensionality of the data and provide new synthetic indices based on the “factorial axes” obtained from MCA, ii) interpret these factorial axes in physiological terms and iii) analyze the evolution of the patient’s status by projecting the acquired data into the plane formed by the first two factorial axes named “factorial plane”. In order to classify the different evolution patterns, a new similarity measure is proposed and validated on simulated datasets, and then used to cluster observed data from 41 CRT patients. The obtained clusters are compared with the annotations on each patient’s medical record. Two areas on the factorial plane are identified, one being correlated with a health degradation of patients and the other with a stable clinical state. PMID:18838359

Decision-Making Experiences of Patients with Implantable Cardioverter Defibrillators.

PubMed

Green, Ariel R; Jenkins, Amy; Masoudi, Frederick A; Magid, David J; Kutner, Jean S; Leff, Bruce; Matlock, Daniel D

2016-10-01

When patients are not adequately engaged in decision making, they may be at risk of decision regret. Our objective was to explore patients' perceptions of their decision-making experiences related to implantable cardioverter defibrillators (ICDs). Cross-sectional, mailed survey of 412 patients who received an ICD without cardiac resynchronization therapy for any indication between 2006 and 2009. Patients were asked about decision participation and decision regret. A total of 295 patients with ICDs responded (72% response rate). Overall, 79% reported that they were as involved in the decision as they wanted. However, 28% reported that they were not told of the option of not getting an ICD and 37% did not remember being asked if they wanted an ICD. In total, 19% reported not wanting their ICD at the time of implantation. Those who did not want the ICD were younger (<65 years; 74% vs 43%, P < 0.001), had higher decision regret (31/100 vs 11/100, P < 0.001), and reported less participation in decision making (the doctor "totally" made the decision, 9% vs 3%; P < 0.001). A considerable number of ICD recipients recalled not wanting their ICD at the time of implantation. While these findings may be prone to recall bias, they likely identify opportunities to improve ICD decision making. © 2016 Wiley Periodicals, Inc.

FDA's perspectives on cardiovascular devices.

PubMed

Chen, Eric A; Patel-Raman, Sonna M; O'Callaghan, Kathryn; Hillebrenner, Matthew G

2009-06-01

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, Section 903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA's review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.

Regenerative endodontics as a tissue engineering approach: past, current and future.

PubMed

Malhotra, Neeraj; Mala, Kundabala

2012-12-01

With the reported startling statistics of high incidence of tooth decay and tooth loss, the current interest is focused on the development of alternate dental tissue replacement therapies. This has led to the application of dental tissue engineering as a clinically relevant method for the regeneration of dental tissues and generation of bioengineered whole tooth. Although, tissue engineering approach requires the three main key elements of stem cells, scaffold and morphogens, a conductive environment (fourth element) is equally important for successful engineering of any tissue and/or organ. The applications of this science has evolved continuously in dentistry, beginning from the application of Ca(OH)(2) in vital pulp therapy to the development of a fully functional bioengineered tooth (mice). Thus, with advances in basic research, recent reports and studies have shown successful application of tissue engineering in the field of dentistry. However, certain practical obstacles are yet to be overcome before dental tissue regeneration can be applied as evidence-based approach in clinics. The article highlights on the past achievements, current developments and future prospects of tissue engineering and regenerative therapy in the field of endodontics and bioengineered teeth (bioteeth). © 2012 The Authors. Australian Endodontic Journal © 2012 Australian Society of Endodontology.

[Radiation therapy and redox imaging].

PubMed

Matsumoto, Ken-ichiro

2015-01-01

Radiation therapy kills cancer cells in part by flood of free radicals. Radiation ionizes and/or excites water molecules to create highly reactive species, i.e. free radicals and/or reactive oxygen species. Free radical chain reactions oxidize biologically important molecules and thereby disrupt their function. Tissue oxygen and/or redox status, which can influence the course of the free radical chain reaction, can affect the efficacy of radiation therapy. Prior observation of tissue oxygen and/or redox status is helpful for planning a safe and efficient course of radiation therapy. Magnetic resonance-based redox imaging techniques, which can estimate tissue redox status non-invasively, have been developed not only for diagnostic information but also for estimating the efficacy of treatment. Redox imaging is now spotlighted to achieve radiation theranostics.

A Dosimetric Comparison of Proton and Intensity-Modulated Photon Radiotherapy for Pediatric Parameningeal Rhabdomyosarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozak, Kevin R.; Adams, Judith; Krejcarek, Stephanie J.

Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS). Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with atmore » least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05). Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.« less

A single chip 2 Gbit/s clock recovery subsystem for digital communications

NASA Astrophysics Data System (ADS)

Hickling, Ronald M.

A self-contained clock recovery/data resynchronizer phase locked loop (PLL) for use in microwave and fiber optic digital communications has been fabricated using GaAs integrated circuit technology. The IC contains the analog and digital components for the PLL: an edge-triggered phase detector based on a 1.2 GHz phase/frequency comparator, an op amp for creating the loop filter, and a VCO based on a differential source-coupled pair amplifier.

Users' manual for computer program for one-dimensional analysis of coupled-cavity traveling wave tubes

NASA Technical Reports Server (NTRS)

Omalley, T. A.; Connolly, D. J.

1977-01-01

The use of the coupled cavity traveling wave tube for space communications has led to an increased interest in improving the efficiency of the basic interaction process in these devices through velocity resynchronization and other methods. To analyze these methods, a flexible, large signal computer program for use on the IBM 360/67 time-sharing system has been developed. The present report is a users' manual for this program.

Two complementary strategies to improve cell engraftment in mesenchymal stem cell-based therapy: Increasing transplanted cell resistance and increasing tissue receptivity.

PubMed

Ezquer, Fernando E; Ezquer, Marcelo E; Vicencio, Jose M; Calligaris, Sebastián D

2017-01-02

Over the past 2 decades, therapies based on mesenchymal stem cells (MSC) have been tested to treat several types of diseases in clinical studies, due to their potential for tissue repair and regeneration. Currently, MSC-based therapy is considered a biologically safe procedure, with the therapeutic results being very promising. However, the benefits of these therapies are not stable in the long term, and the final outcomes manifest with high inter-patient variability. The major cause of these therapeutic limitations results from the poor engraftment of the transplanted cells. Researchers have developed separate strategies to improve MSC engraftment. One strategy aims at increasing the survival of the transplanted MSCs in the recipient tissue, rendering them more resistant to the hostile microenvironment (cell-preconditioning). Another strategy aims at making the damaged tissue more receptive to the transplanted cells, favoring their interactions (tissue-preconditioning). In this review, we summarize several approaches using these strategies, providing an integral and updated view of the recent developments in MSC-based therapies. In addition, we propose that the combined use of these different conditioning strategies could accelerate the process to translate experimental evidences from pre-clinic studies to the daily clinical practice.

Insights into cell-free therapeutic approach: Role of stem cell "soup-ernatant".

PubMed

Raik, Shalini; Kumar, Ajay; Bhattacharyya, Shalmoli

2018-03-01

Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells (SCs) can be harvested from different sources for clinical therapeutics, which include fetal tissues, umbilical cord blood, embryos, and adult tissues. SCs can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large-scale therapeutic application. These include a careful approach for patient safety during SC treatments and tolerance of recipients. SC treatments are associated with a number of risk factors and require successful integration and survival of transplanted cells in the desired microenvironment with concurrent tissue regeneration. Recent studies have focused on developing alternatives that can replace the cell-based therapy using paracrine factors. The development of stem "cell free" therapies can be devoted mainly to the use of soluble factors (secretome), extracellular vesicles, and mitochondrial transfer. The present review emphasizes on the paradigms related to the use of SC-based therapeutics and the potential applications of a cell-free approach as an alternative to cell-based therapy in the area of regenerative medicine. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Minibeam Therapy With Protons and Light Ions: Physical Feasibility and Potential to Reduce Radiation Side Effects and to Facilitate Hypofractionation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilmanian, F. Avraham, E-mail: avraham.dilmanian@stonybrook.edu; Eley, John G.; Krishnan, Sunil

2015-06-01

Purpose: Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Methods and Materials: Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulationsmore » were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. Results: A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Conclusions: Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage.« less

Innovations in management of cardiac disease: drugs, treatment strategies and technology.

PubMed

Foëx, P

2017-12-01

Within the last generation, the management of patients with heart disease has been transformed by advances in drug treatments, interventions and diagnostic technologies. The management of arterial hypertension saw beta-blockers demoted from first- to third-line treatment. Recent studies suggest that the goal of treatment may have to change to lower systolic blood pressures to prevent long-term organ damage. Today less than 15% of coronary revascularizations are surgical and more than 85% are done by interventional cardiologists inserting coronary stents. Thus, managing patients on dual antiplatelet therapy has become an important issue. With new generations of coronary stents, recommendations are changing fast. In the past, decisions concerning non-cardiac surgery after acute myocardial infarction were based on the delay between infarction and non-cardiac surgery. Today, the main concern is the patient's status in respect of dual antiplatelet therapy after primary percutaneous intervention. There have been advances in the management of heart failure but new drugs (ivabradine, sacubitril/valsartan) and cardiac resynchronization are recommended only in patients with an ejection fraction below 35% on optimal medication. Heart failure remains a major perioperative risk factor. Prospective studies have shown that troponin elevations represent myocardial injury (not necessarily myocardial infarction), are mostly silent and are associated with increased 30-day mortality. Monitoring (troponin assays) for myocardial injury in non-cardiac surgery (MINS) seems increasingly justified. The treatment of MINS needs further research. Technological advances, such as intelligent, portable monitors benefit not only patients with cardiac disease but all patients who have undergone major surgery and are on the wards postoperatively. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Italian subcutaneous implantable cardioverter-defibrillator survey: S-ICD, why not?

PubMed

Botto, Giovanni Luca; Forleo, Giovanni B; Capucci, Alessandro; Solimene, Francesco; Vado, Antonello; Bertero, Giovanni; Palmisano, Pietro; Pisanò, Ennio; Rapacciuolo, Antonio; Infusino, Tommaso; Vicentini, Alessandro; Viscusi, Miguel; Ferrari, Paola; Talarico, Antonello; Russo, Giovanni; Boriani, Giuseppe; Padeletti, Luigi; Lovecchio, Mariolina; Valsecchi, Sergio; D'Onofrio, Antonio

2017-11-01

A recommendation for a subcutaneous-implantable cardioverter-defibrillator (S-ICD) has been added to recent European Society of Cardiology Guidelines. However, the S-ICD is not ideally suitable for patients who need pacing. The aim of this survey was to analyse the current practice of ICD implantation and to evaluate the actual suitability of S-ICD. The survey 'S-ICD Why Not?' was an independent initiative taken by the Italian Heart Rhythm Society (AIAC). Clinical characteristics, selection criteria, and factors guiding the choice of ICD type were collected in consecutive patients who underwent ICD implantation in 33 Italian centres from September to December 2015. A cardiac resynchronization therapy (CRT) device was implanted in 39% (369 of 947) of patients undergoing de novo ICD implantation. An S-ICD was implanted in 12% of patients with no CRT indication (62 of 510 with available data). S-ICD patients were younger than patients who received transvenous ICD, more often had channelopathies, and more frequently received their device for secondary prevention of sudden death. More frequently, the clinical reason for preferring a transvenous ICD over an S-ICD was the need for pacing (45%) or for antitachycardia pacing (36%). Nonetheless, only 7% of patients fulfilled conditions for recommending permanent pacing, and 4% of patients had a history of monomorphic ventricular tachycardia that might have been treatable with antitachycardia pacing. The vast majority of patients needing ICD therapy are suitable candidates for S-ICD implantation. Nevertheless, it currently seems to be preferentially adopted for secondary prevention of sudden death in young patients with channelopathies. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

[The subcutaneous cardioverter-defibrillator: When less is more].

PubMed

Kuschyk, J; Rudic, B; Akin, I; Borggrefe, M; Röger, S

2015-06-01

In the last few decades, defibrillator therapy has revolutionized treatment of patients at risk for sudden cardiac death. Multiple clinical trials have shown the benefit of implantable cardioverter-defibrillators (ICD) for primary and secondary prevention of sudden cardiac death. Being an entirely subcutaneous system, the S-ICD® avoids important periprocedural and long-term complications associated with transvenous implantable cardioverter-defibrillator (TV-ICD) systems as well as the need for fluoroscopy during implant surgery. In patients with challenging anatomic conditions or after infection, the S-ICD® might be reasonable. In multicenter studies and registries efficacy and safety of the S-ICD® was equal or better to transvenous implantable defibrillators. The cardiac rhythm is detected by the use of 1 of the 3 potential vectors. The S-ICD® automatically selects the most suitable vector for rhythm detection. If ventricular tachyarrhythmia is detected, the device is able to deliver up to five shocks of 80 J, while postshock pacing is available at 50 bpm for 30 s. The implantation technique is different from that of conventional ICDs, but easily learnable by experienced cardiologists. Initially observed hurdles (e.g., inappropriate shocks or infections) have been overcome by standardized implantation techniques, operator learning curves, and modification of algorithms. The S-ICD® predominately might be suitable in all patients with ICD indication except patients with pacing or cardiac resynchronization therapy (CRT) indication, ventricular tachycardia < 170 bpm, negative screening, or in the occasional patient whose arrhythmia might be suppressed by overdrive pacing. The system received CE certification in 2009 and was approved by the FDA in 2012. Currently, in Germany the S-ICD® has been integrated into the DRG system and can be reimbursed as a single chamber ICD.

Functional response to cardiac resynchronization therapy is associated with improved clinical outcome and absence of appropriate shocks.

PubMed

Van Boven, Nick; Bogaard, Kjell; Ruiter, Jaap; Kimman, Geert; Theuns, Dominic; Kardys, Isabella; Umans, Victor

2013-03-01

We evaluated clinical outcome and incidence of (in)appropriate shocks in consecutive chronic heart failure (CHF) patients treated with CRT with a defibrillator (CRT-D) according to functional response status. Furthermore, we investigated which factors predict such functional response. In a large teaching hospital, 179 consecutive CHF patients received CRT-D in 2005-2010. Patients were considered functional responders if left ventricular ejection fraction (LVEF) increased to ≥ 35% postimplantation. Analysis was performed on 142 patients, who had CRT-D as primary prevention, complete data and a baseline LVEF <35%. Endpoints consisted of all-cause mortality, heart failure (HF) hospitalizations, appropriate shocks and inappropriate shocks. Median follow-up was 3.0 years (interquartile range [IQR] 1.6-4.4) and median baseline LVEF was 20% (IQR 18-25%). The functional response-group consisted of 42 patients. In this group no patients died, none were hospitalized for HF, none received appropriate shocks and 3 patients (7.1%) received ≥ 1 inappropriate shocks. In comparison, the functional nonresponse group consisted of 100 patients, of whom 22 (22%) died (P = 0.003), 17 (17%) were hospitalized for HF (P = 0.007), 17 (17%) had ≥ 1 appropriate shocks (P = 0.003) and 8 (8.1%) received ≥ 1 inappropriate shocks (P = 0.78). Multivariable analysis showed that left bundle branch block (LBBB), QRS duration ≥ 150 milliseconds and no need for diuretics at baseline are independent predictors of functional response. Functional responders to CRT have a good prognosis and rarely need ICD therapy. LBBB, QRS duration ≥ 150 milliseconds and lack of chronic diuretic use predict functional response. © 2012 Wiley Periodicals, Inc.

Reduced left ventricular mechanical dispersion in heart failure patients undergoing cardiac resynchronisation therapy is associated with superior long-term outcome.

PubMed

van der Bijl, Pieter; Khidir, Mand Jh; Leung, Melissa; Yilmaz, Dilek; Mertens, Bart; Marsan, Nina Ajmone; Delgado, Victoria; Bax, Jeroen J

2018-05-09

In heart failure (HF) patients, left ventricular mechanical dispersion (LVMD) reflects heterogeneous mechanical activation of the left ventricle. In HF patients, LVMD can be reduced after CRT. Whether lesser LVMD is associated with improved outcome is unknown. To relate LVMD to long-term prognosis in a large cohort of HF patients after 6 months of cardiac resynchronization therapy (CRT). Clinical, echocardiographic and ventricular arrhythmia (VA) data were analyzed from an ongoing registry of HF recipients of CRT. Baseline (prior to CRT) and 6-month echocardiograms were evaluated. LVMD was calculated as the standard deviation of the time from onset of the QRS complex to the peak longitudinal strain in a 17-segment model. Patients were divided into two groups, according to the median LVMD (84 ms) at 6 months post-CRT. Of 1,185 patients (mean age 65±10 years, 76% male), 343 (29%) died during a mean follow-up of 55±36 months. Baseline LVMD was not associated with all-cause mortality and VA at follow-up. In contrast, patients with less LVMD (≤84 ms) at 6 months post-CRT had lower event rates (VA and mortality) compared to those with LVMD >84 ms. On multivariable analysis, greater LVMD at 6 months after CRT was independently associated with an increased risk of mortality (hazard ratio, 1.002; P=0.037) and VA (hazard ratio, 1.003; P=0.026) . Larger LVMD at 6 months after CRT is independently associated with all-cause mortality and VA. LVMD may be valuable in identifying patients who remain at high mortality risk after CRT implantation. Copyright © 2018. Published by Elsevier Inc.

Protocol-driven remote monitoring of cardiac resynchronization therapy as part of a heart failure disease management strategy.

PubMed

Smeets, Christophe J P; Verbrugge, Frederik H; Vranken, Julie; Van der Auwera, Jo; Mullens, Wilfried; Dupont, Matthias; Grieten, Lars; De Cannière, Hélène; Lanssens, Dorien; Vandenberk, Thijs; Storms, Valerie; Thijs, Inge M; Vandervoort, Pieter

2018-06-01

Cardiac resynchronisation therapy (CRT) is an established treatment for heart failure (HF) with reduced ejection fraction. CRT devices are equipped with remote monitoring functions, which are pivotal in the detection of device problems, but may also facilitate disease management. The aim of this study was to provide a comprehensive overview of the clinical interventions taken based on remote monitoring. This is a single centre observational study of consecutive CRT patients (n = 192) participating in protocol-driven remote follow-up. Incoming technical- and disease-related alerts were analysed together with subsequently triggered interventions. During 34 ± 13 months of follow-up, 1372 alert-containing notifications were received (2.53 per patient-year of follow-up), comprising 1696 unique alerts (3.12 per patient-year of follow-up). In 60%, notifications resulted in a phone contact. Technical alerts constituted 8% of incoming alerts (0.23 per patient-year of follow-up). Rhythm (1.43 per patient-year of follow-up) and bioimpedance alerts (0.98 per patient-year of follow-up) were the most frequent disease-related alerts. Notifications included a rhythm alert in 39%, which triggered referral to the emergency room (4%), outpatient cardiology clinic (36%) or general practitioner (7%), or resulted in medication changes (13%). Sole bioimpedance notifications resulted in a telephone contact in 91%, which triggered outpatient evaluation in 8% versus medication changes in 10%. Clinical outcome was excellent with 97% 1-year survival. Remote CRT follow-up resulted in 0.23 technical- versus 2.64 disease-related alerts annually. Rhythm and bioimpedance notifications constituted the majority of incoming notifications which triggered an actual intervention in 22% and 15% of cases, respectively.

Systemic Right Ventricle in Adults With Congenital Heart Disease: Anatomic and Phenotypic Spectrum and Current Approach to Management.

PubMed

Brida, Margarita; Diller, Gerhard-Paul; Gatzoulis, Michael A

2018-01-30

The systemic right ventricle (SRV) is commonly encountered in congenital heart disease representing a distinctly different model in terms of its anatomic spectrum, adaptation, clinical phenotype, and variable, but overall guarded prognosis. The most common clinical scenarios where an SRV is encountered are complete transposition of the great arteries with previous atrial switch repair, congenitally corrected transposition of the great arteries, double inlet right ventricle mostly with previous Fontan palliation, and hypoplastic left heart syndrome palliated with the Norwood-Fontan protocol. The reasons for the guarded prognosis of the SRV in comparison with the systemic left ventricle are multifactorial, including distinct fibromuscular architecture, shape and function, coronary artery supply mismatch, intrinsic abnormalities of the tricuspid valve, intrinsic or acquired conduction abnormalities, and varied SRV adaptation to pressure or volume overload. Management of the SRV remains an ongoing challenge because SRV dysfunction has implications on short- and long-term outcomes for all patients irrespective of underlying cardiac morphology. SRV dysfunction can be subclinical, underscoring the need for tertiary follow-up and timely management of target hemodynamic lesions. Catheter interventions and surgery have an established role in selected patients. Cardiac resynchronization therapy is increasingly used, whereas pharmacological therapy is largely empirical. Mechanical assist device and heart transplantation remain options in end-stage heart failure when other management strategies have been exhausted. The present report focuses on the SRV with its pathological subtypes, pathophysiology, clinical features, current management strategies, and long-term sequelae. Although our article touches on issues applicable to neonates and children, its main focus is on adults with SRV. © 2018 American Heart Association, Inc.

Prospective Randomized Evaluation of Implantable Cardioverter-Defibrillator Programming in Patients With a Left Ventricular Assist Device.

PubMed

Richardson, Travis D; Hale, Leslie; Arteaga, Christopher; Xu, Meng; Keebler, Mary; Schlendorf, Kelly; Danter, Matthew; Shah, Ashish; Lindenfeld, JoAnn; Ellis, Christopher R

2018-02-23

Ventricular arrhythmias are common in patients with left ventricular assist devices (LVADs) but are often hemodynamically tolerated. Optimal implantable cardioverter defibrillator (ICD) tachy-programming strategies in patients with LVAD have not been determined. We sought to determine if an ultra-conservative ICD programming strategy in patients with LVAD affects ICD shocks. Adult patients with an existing ICD undergoing continuous flow LVAD implantation were randomized to standard ICD programming by their treating physician or an ultra-conservative ICD programming strategy utilizing maximal allowable intervals to detection in the ventricular fibrillation and ventricular tachycardia zones with use of ATP. Patients with cardiac resynchronization therapy (CRT) devices were also randomized to CRT ON or OFF. Patients were followed a minimum of 6 months. The primary outcome was time to first ICD shock. Among the 83 patients studied, we found no statistically significant difference in time to first ICD shock or total ICD shocks between groups. In the ultra-conservative group 16% of patients experienced at least one shock compared with 21% in the control group ( P =0.66). There was no difference in mortality, arrhythmic hospitalization, or hospitalization for heart failure. In the 41 patients with CRT ICDs fewer shocks were observed with CRT-ON but this was not statistically significant: 10% of patients with CRT-ON (n=21) versus 38% with CRT-OFF (n=20) received shocks ( P =0.08). An ultra-conservative programming strategy did not reduce ICD shocks. Programming restrictions on ventricular tachycardia and ventricular fibrillation zone therapy should be reconsidered for the LVAD population. The role of CRT in patients with LVAD warrants further investigation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01977703. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The clinical use of regenerative therapy in COPD

PubMed Central

Lipsi, Roberto; Rogliani, Paola; Calzetta, Luigino; Segreti, Andrea; Cazzola, Mario

2014-01-01

Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation. PMID:25548520

Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy

PubMed Central

Hipp, Jason; Atala, Anthony

2004-01-01

Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure. PMID:15588286

Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy.

PubMed

Hipp, Jason; Atala, Anthony

2004-12-08

: BACKGROUND: Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

Nano scaffolds and stem cell therapy in liver tissue engineering

NASA Astrophysics Data System (ADS)

Montaser, Laila M.; Fawzy, Sherin M.

2015-08-01

Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

Predicted coreceptor usage at end-stage HIV disease in tissues derived from subjects on antiretroviral therapy with an undetectable plasma viral load.

PubMed

Lamers, S L; Fogel, G B; Liu, E S; Nolan, D J; Salemi, M; Barbier, A E; Rose, R; Singer, E J; McGrath, M S

2017-07-01

HIV cure research is increasingly focused on anatomical tissues as sites for residual HIV replication during combined antiretroviral therapy (cART). Tissue-based HIV could contribute to low-level immune activation and viral rebound over the course of infection and could also influence the development of diseases, such as atherosclerosis, neurological disorders and cancers. cART-treated subjects have a decreased and irregular presence of HIV among tissues, which has resulted in a paucity of actual evidence concerning how or if HIV persists, replicates and evolves in various anatomical sites during therapy. In this study, we pooled 1806 HIV envelope V3 loop sequences from twenty-six tissue types (seventy-one total tissues) of six pre-cART subjects, four subjects with an unknown cART history who died with profound AIDS, and five subjects who died while on cART with an undetectable plasma viral load. A computational approach was used to assess sequences for their ability to utilize specific cellular coreceptors (R5, R5 and X4, or X4). We found that autopsied tissues obtained from virally suppressed cART+ subjects harbored both integrated and expressed viruses with similar coreceptor usage profiles to subjects with no or ineffective cART therapy (i.e., significant plasma viral load at death). The study suggests that tissue microenvironments provide a sanctuary for the continued evolution of HIV despite cART. Copyright © 2017 Elsevier B.V. All rights reserved.

Negative pressure wound therapy for the treatment of infected wounds with exposed knee joint after patellar fracture.

PubMed

Lee, Sang Yang; Niikura, Takahiro; Miwa, Masahiko; Sakai, Yoshitada; Oe, Keisuke; Fukazawa, Takahiro; Kawakami, Yohei; Kurosaka, Masahiro

2011-06-14

Treatment of soft tissue defects with exposed bones and joints, resulting from trauma, infection, and surgical complications, represents a major challenge. The introduction of negative pressure wound therapy has changed many wound management practices. Negative pressure wound therapy has recently been used in the orthopedic field for management of traumatic or open wounds with exposed bone, nerve, tendon, and orthopedic implants. This article describes a case of a patient with a large soft tissue defect and exposed knee joint, in which negative pressure wound therapy markedly improved wound healing. A 50-year-old man presented with an ulceration of his left knee with exposed joint, caused by severe wound infections after open reduction and internal fixation of a patellar fracture. After 20 days of negative pressure wound therapy, a granulated wound bed covered the exposed bones and joint.To our knowledge, this is the first report of negative pressure wound therapy used in a patient with a large soft tissue defect with exposed knee joint. Despite the chronic wound secondary to infection, healing was achieved through the use of the negative pressure wound therapy, thus promoting granulation tissue formation and closing the joint. We suggest negative pressure wound therapy as an alternative option for patients with lower limb wounds containing exposed bones and joints when free flap transfer is contraindicated. Our result added to the growing evidence that negative pressure wound therapy is a useful adjunctive treatment for open wounds around the knee joint. Copyright 2011, SLACK Incorporated.

Method for estimating optimal spectral and energy parameters of laser irradiation in photodynamic therapy of biological tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lisenko, S A; Kugeiko, M M

We have solved the problem of layer-by-layer laser-light dosimetry in biological tissues and of selecting an individual therapeutic dose in laser therapy. A method is proposed for real-time monitoring of the radiation density in tissue layers in vivo, concentrations of its endogenous (natural) and exogenous (specially administered) chromophores, as well as in-depth distributions of the spectrum of light action on these chromophores. As the background information use is made of the spectrum of diffuse light reflected from a patient's tissue, measured by a fibre-optic spectrophotometer. The measured spectrum is quantitatively analysed by the method of approximating functions for fluxes ofmore » light multiply scattered in tissue and by a semi-analytical method for calculating the in-depth distribution of the light flux in a multi-layered medium. We have shown the possibility of employing the developed method for monitoring photosensitizer and oxyhaemoglobin concentrations in tissue, light power absorbed by chromophores in tissue layers at different depths and laser-induced changes in the tissue morphology (vascular volume content and ratios of various forms of haemoglobin) during photodynamic therapy. (biophotonics)« less

Solid Free-form Fabrication Technology and Its Application to Bone Tissue Engineering

PubMed Central

Lee, Jin Woo; Kim, Jong Young; Cho, Dong-Woo

2010-01-01

The development of scaffolds for use in cell-based therapies to repair damaged bone tissue has become a critical component in the field of bone tissue engineering. However, design of scaffolds using conventional fabrication techniques has limited further advancement, due to a lack of the required precision and reproducibility. To overcome these constraints, bone tissue engineers have focused on solid free-form fabrication (SFF) techniques to generate porous, fully interconnected scaffolds for bone tissue engineering applications. This paper reviews the potential application of SFF fabrication technologies for bone tissue engineering with respect to scaffold fabrication. In the near future, bone scaffolds made using SFF apparatus should become effective therapies for bone defects. PMID:24855546

Reduction of thermal damage in photodynamic therapy by laser irradiation techniques.

PubMed

Lim, Hyun Soo

2012-12-01

General application of continuous-wave (CW) laser irradiation modes in photodynamic therapy can cause thermal damage to normal tissues in addition to tumors. A new photodynamic laser therapy system using a pulse irradiation mode was optimized to reduce nonspecific thermal damage. In in vitro tissue specimens, tissue energy deposition rates were measured in three irradiation modes, CW, pulse, and burst-pulse. In addition, methods were tested for reducing variations in laser output and specific wavelength shifts using a thermoelectric cooler and thermistor. The average temperature elevation per 10 J/cm2 was 0.27°C, 0.09°C, and 0.08°C using the three methods, respectively, in pig muscle tissue. Variations in laser output were controlled within ± 0.2%, and specific wavelength shift was limited to ± 3 nm. Thus, optimization of a photodynamic laser system was achieved using a new pulse irradiation mode and controlled laser output to reduce potential thermal damage during conventional CW-based photodynamic therapy.

Maggot therapy in treatment of a complex hand injury complicated by mycotic infection.

PubMed

Bohac, M; Cambal, M; Zamborsky, R; Takac, P; Fedeles, J

2015-01-01

Complex injuries of the hand remain a therapeutic challenge for surgeons. We present the case of a male who suffered a devastating injury of the hand caused by a conveyor belt. The patient developed a progressive Absidia corymbifera infection of the affected soft tissues. Initial treatments with serial surgical debridement and topical and intravenous itraconazole were unsuccessful in eliminating the infection. We decided to use maggot debridement therapy in a new special design to debride all necrotic, devitalized tissue and preserve only healthy tissue and functioning structures. This maneuverer followed by negative pressure therapy allowed progressive healing. In such complex hand injuries, maggot debridement combined with negative pressure therapy could be considered to achieve effective and considerable results, although future functional morbidity may occur (Fig. 4, Ref. 18).

SU-D-BRC-04: Development of Proton Tissue Equivalent Materials for Calibration and Dosimetry Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olguin, E; Flampouri, S; Lipnharski, I

Purpose: To develop new proton tissue equivalent materials (PTEM), urethane and fiberglass based, for proton therapy calibration and dosimetry studies. Existing tissue equivalent plastics are applicable only for x-rays because they focus on matching mass attenuation coefficients. This study aims to create new plastics that match mass stopping powers for proton therapy applications instead. Methods: New PTEMs were constructed using urethane and fiberglass resin materials for soft, fat, bone, and lung tissue. The stoichiometric analysis method was first used to determine the elemental composition of each unknown constituent. New initial formulae were then developed for each of the 4 PTEMsmore » using the new elemental compositions and various additives. Samples of each plastic were then created and exposed to a well defined proton beam at the UF Health Proton Therapy Institute (UFHPTI) to validate its mass stopping power. Results: The stoichiometric analysis method revealed the elemental composition of the 3 components used in creating the PTEMs. These urethane and fiberglass based resins were combined with additives such as calcium carbonate, aluminum hydroxide, and phenolic micro spheres to achieve the desired mass stopping powers and densities. Validation at the UFHPTI revealed adjustments had to be made to the formulae, but the plastics eventually had the desired properties after a few iterations. The mass stopping power, density, and Hounsfield Unit of each of the 4 PTEMs were within acceptable tolerances. Conclusion: Four proton tissue equivalent plastics were developed: soft, fat, bone, and lung tissue. These plastics match each of the corresponding tissue’s mass stopping power, density, and Hounsfield Unit, meaning they are truly tissue equivalent for proton therapy applications. They can now be used to calibrate proton therapy treatment planning systems, improve range uncertainties, validate proton therapy Monte Carlo simulations, and assess in-field and out-of-field organ doses.« less

Cancer Nanotechnology: Opportunities for Prevention, Diagnosis, and Therapy.

PubMed

Zeineldin, Reema; Syoufjy, Joan

2017-01-01

Nanotechnological innovations over the last 16 years have brought about the potential to revolutionize specific therapeutic drug delivery to cancer tissue without affecting normal tissues. In addition, there are new nanotechnology-based platforms for diagnosis of cancers and for theranostics, i.e., integrating diagnosis with therapy and follow-up of effectiveness of therapy. This chapter presents an overview of these nanotechnology-based advancements in the areas of prevention, diagnosis, therapy, and theranostics for cancer. In addition, we stress the need to educate bio- and medical students in the field of nanotechnology.

New Approaches in Vital Pulp Therapy in Permanent Teeth

PubMed Central

Ghoddusi, Jamileh; Forghani, Maryam; Parisay, Iman

2014-01-01

Vitality of dental pulp is essential for long-term tooth survival. The aim of vital pulp therapy is to maintain healthy pulp tissue by eliminating bacteria from the dentin-pulp complex. There are several different treatment options for vital pulp therapy in extensively decayed or traumatized teeth. Pulp capping or pulpotomy procedures rely upon an accurate assessment of the pulp status, and careful management of the remaining pulp tissue. The purpose of this review is to provide an overview of new approaches in vital pulp therapy in permanent teeth. PMID:24396371

Current and future regenerative medicine — Principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

PubMed Central

Koch, Thomas G.; Berg, Lise C.; Betts, Dean H.

2009-01-01

This paper provides a bird’s-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine. The understanding of equine stem cell biology, biofactors, and scaffolds, and their potential therapeutic use in horses are rudimentary at present. Mesenchymal stem cell isolation has been proclaimed from several equine tissues in the past few years. Based on the criteria of the International Society for Cellular Therapy, most of these cells are more correctly referred to as multipotent mesenchymal stromal cells, unless there is proof that they exhibit the fundamental in vivo characteristics of pluripotency and the ability to self-renew. That said, these cells from various tissues hold great promise for therapeutic use in horses. The 3 components of tissue engineering — cells, biological factors, and biomaterials — are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources. The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently in controlled clinical trials in equine patients to be regarded as evidence-based medicine. In the meantime, the medical mantra “do no harm” should prevail, and the application of stem cell-based therapies in the horse should be done critically and cautiously, and treatment outcomes (good and bad) should be recorded and reported. Stem cell and tissue engineering research in the horse has exciting comparative and equine specific perspectives that most likely will benefit the health of horses and humans. Controlled, well-designed studies are needed to move this new equine research field forward. PMID:19412395

Relationships Between the Performance of Time/Frequency Standards and Navigation/Communication Systems

NASA Technical Reports Server (NTRS)

Hellwig, H.; Stein, S. R.; Walls, F. L.; Kahan, A.

1978-01-01

The relationship between system performance and clock or oscillator performance is discussed. Tradeoffs discussed include: short term stability versus bandwidth requirements; frequency accuracy versus signal acquisition time; flicker of frequency and drift versus resynchronization time; frequency precision versus communications traffic volume; spectral purity versus bit error rate, and frequency standard stability versus frequency selection and adjustability. The benefits and tradeoffs of using precise frequency and time signals are various levels of precision and accuracy are emphasized.

Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)

PubMed Central

Gao, Wenqing; Dalton, James T.

2007-01-01

Selective androgen receptor modulators (SARMs) are a novel class of androgen receptor (AR) ligands that might change the future of androgen therapy dramatically. With improved pharmacokinetic characteristics and tissue-selective pharmacological activities, SARMs are expected to greatly extend the clinical applications of androgens to osteoporosis, muscle wasting, male contraception and diseases of the prostate. Mechanistic studies with currently available SARMs will help to define the contributions of differential tissue distribution, tissue-specific expression of 5α-reductase, ligand-specific regulation of gene expression and AR interactions with tissue-specific coactivators to their observed tissue selectivity, and lead to even greater expansion of selective anabolic therapies. PMID:17331889

Nonpharmaceutical approaches to pain management.

PubMed

Corti, Lisa

2014-03-01

A nonpharmaceutical approach to managing pain is one that does not employ a medication. The use of such approaches, in conjunction with pharmaceuticals as part of multimodal methods to managing pain, is becoming more popular as evidence is emerging to support their use. Cold therapy, for one, is used to reduce the inflammation and tissue damage seen in acute injuries and can be very effective at reducing acute pain. Incorporating the use of superficial heat therapy when treating pain associated with chronic musculoskeletal conditions is often employed as heat increases blood flow, oxygen delivery, and tissue extensibility. Acupuncture is gaining acceptance in veterinary medicine. Research is confirming that release of endogenous endorphins and enkephalins from the application of needles at specific points around the body can effectively control acute and chronic pain. The use of 2 newer therapies-extracorporeal shockwave therapy and platelet-rich plasma-represent an attempt to eliminate the causes of pain at the tissue level by promoting tissue healing and regeneration. Reviewed in this article, these therapies are intended to be used in conjunction with pharmaceuticals as part of a multimodal approach to pain management. Copyright © 2014 Elsevier Inc. All rights reserved.

Resectable Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcoma: Which Patients Benefit from Adjuvant Radiation Therapy and How Much?

PubMed Central

Million, Lynn; Donaldson, Sarah S.

2012-01-01

It remains unclear which children and adolescents with resected nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) benefit from radiation therapy, as well as the optimal dose, volume, and timing of radiotherapy when used with primary surgical resection. This paper reviews the sparse literature from clinical trials and retrospective studies of resected pediatric NRSTS to discern local recurrence rates in relationship to the use of radiation therapy. PMID:22523704

Concise Review: Mind the Gap: Challenges in Characterizing and Quantifying Cell- and Tissue-Based Therapies for Clinical Translation

PubMed Central

Rayment, Erin A; Williams, David J

2010-01-01

There are many challenges associated with characterizing and quantifying cells for use in cell- and tissue-based therapies. From a regulatory perspective, these advanced treatments must not only be safe and effective but also be made by high-quality manufacturing processes that allow for on-time delivery of viable products. Although sterility assays can be adapted from conventional bioprocessing, cell- and tissue-based therapies require more stringent safety assessments, especially in relation to use of animal products, immune reaction, and potential instability due to extended culture times. Furthermore, cell manufacturers who plan to use human embryonic stem cells in their therapies need to be particularly stringent in their final purification steps, due to the unrestricted growth potential of these cells. This review summarizes the current issues in characterization and quantification for cell- and tissue-based therapies, dividing these challenges into the regulatory themes of safety, potency, and manufacturing quality. It outlines current assays in use, as well as highlights the limits of many of these product release tests. Mode of action is discussed, with particular reference to in vitro surrogate assays that can be used to provide information to correlate with proposed in vivo patient efficacy. Importantly, this review highlights the requirement for basic research to improve current knowledge on the in vivo fate of these treatments; as well as an improved stakeholder negotiation process to identify the measurement requirements that will ensure the manufacture of the best possible cell- and tissue-based therapies within the shortest timeframe for the most patient benefit. PMID:20333747

Time-Dependent Recovery of Human Synovial Membrane Mesenchymal Stem Cell Function After High-Dose Steroid Therapy: Case Report and Laboratory Study.

PubMed

Yasui, Yukihiko; Hart, David A; Sugita, Norihiko; Chijimatsu, Ryota; Koizumi, Kota; Ando, Wataru; Moriguchi, Yu; Shimomura, Kazunori; Myoui, Akira; Yoshikawa, Hideki; Nakamura, Norimasa

2018-03-01

The use of mesenchymal stem cells from various tissue sources to repair injured tissues has been explored over the past decade in large preclinical models and is now moving into the clinic. To report the case of a patient who exhibited compromised mesenchymal stem cell (MSC) function shortly after use of high-dose steroid to treat Bell's palsy, who recovered 7 weeks after therapy. Case report and controlled laboratory study. A patient enrolled in a first-in-human clinical trial for autologous implantation of a scaffold-free tissue engineered construct (TEC) derived from synovial MSCs for chondral lesion repair had a week of high-dose steroid therapy for Bell's palsy. Synovial tissue was harvested for MSC preparation after a 3-week recovery period and again at 7 weeks after therapy. The MSC proliferation rates and cell surface marker expression profiles from the 3-week sample met conditions for further processing. However, the cells failed to generate a functional TEC. In contrast, MSCs harvested at 7 weeks after steroid therapy were functional in this regard. Further in vitro studies with MSCs and steroids indicated that the effect of in vivo steroids was likely a direct effect of the drug on the MSCs. This case suggests that MSCs are transiently compromised after high-dose steroid therapy and that careful consideration regarding timing of MSC harvest is critical. The drug profiles of MSC donors and recipients must be carefully monitored to optimize opportunities to successfully repair damaged tissues.

In vivo neutron activation analysis of sodium and chlorine in tumor tissue after fast neutron therapy.

PubMed

Auberger, T; Koester, L; Knopf, K; Weissfloch, L

1996-01-01

In 12 patients with recurrences and metastases of different primaries (head and neck cancer, breast cancer, malignant melanoma, and osteosarcoma) who were treated with reactor fission neutrons the photon emission of irradiated tissue was measured after each radiotherapy fraction. Spectral analyses of the decay rates resulted in data for the exchange of sodium (Na) and chlorine (Cl) between the irradiated tissue and the body. About 60% of Na and Cl exchanged rapidly with a turnover half-life of 13 +/- 2 min. New defined mass exchange rates for Na and Cl amount to an average of 0.8 mval/min/kg of soft tissue. At the beginning of radiotherapy the turnover of the electrolytes in tissues with large tumor volumes was about twice that in tissues with small tumor volumes. Depending on the dose, neutron therapy led in all cases to variation in the metabolism. A maximum of Cl exchange and a minimum of Na exchange occurred after 10 Gy of neutrons (group of six previously untreated patients) or after 85 Gy (photon equivalent dose) of combined photon-neutron therapy. A significant increase in non-exchangeable fraction of Na from about 40 to 80% was observed in three tumors after a neutron dose of 10 Gy administered in five fractions correlated with a rapid reduction of tissue within 4 weeks after end of therapy. These results demonstrate for the first time the local response of the electrolyte metabolism to radiotherapy.

Pluripotent Stem Cells for Retinal Tissue Engineering: Current Status and Future Prospects.

PubMed

Singh, Ratnesh; Cuzzani, Oscar; Binette, François; Sternberg, Hal; West, Michael D; Nasonkin, Igor O

2018-04-19

The retina is a very fine and layered neural tissue, which vitally depends on the preservation of cells, structure, connectivity and vasculature to maintain vision. There is an urgent need to find technical and biological solutions to major challenges associated with functional replacement of retinal cells. The major unmet challenges include generating sufficient numbers of specific cell types, achieving functional integration of transplanted cells, especially photoreceptors, and surgical delivery of retinal cells or tissue without triggering immune responses, inflammation and/or remodeling. The advances of regenerative medicine enabled generation of three-dimensional tissues (organoids), partially recreating the anatomical structure, biological complexity and physiology of several tissues, which are important targets for stem cell replacement therapies. Derivation of retinal tissue in a dish creates new opportunities for cell replacement therapies of blindness and addresses the need to preserve retinal architecture to restore vision. Retinal cell therapies aimed at preserving and improving vision have achieved many improvements in the past ten years. Retinal organoid technologies provide a number of solutions to technical and biological challenges associated with functional replacement of retinal cells to achieve long-term vision restoration. Our review summarizes the progress in cell therapies of retina, with focus on human pluripotent stem cell-derived retinal tissue, and critically evaluates the potential of retinal organoid approaches to solve a major unmet clinical need-retinal repair and vision restoration in conditions caused by retinal degeneration and traumatic ocular injuries. We also analyze obstacles in commercialization of retinal organoid technology for clinical application.

Leech Therapy For The Treatment Of Venous Congestion In Flaps, Digital Re-Plants And Revascularizations - A Two-Year Review From A Regional Centre.

PubMed

Butt, Ahsan Masood; Ismail, Amir; Lawson-Smith, Matthew; Shahid, Muhammad; Webb, Jill; Chester, Darren L

2016-01-01

Leeches are a well-recognized treatment for congested tissue. This study reviewed the efficacy of leech therapy for salvage of venous congested flaps and congested replanted or revascularized hand digits over a 2-year period. All patients treated with leeches between 1 Oct 2010 and 30 Sep 2012 (two years) at Queen Elizabeth Hospital, Birmingham, UK were included in the study. Details regarding mode of injury requiring reconstruction, surgical procedure, leech therapy duration, subsequent surgery requirement and tissue salvage rates were recorded. Twenty tissues in 18 patients required leeches for tissue congestion over 2 years: 13 men and 5 women. The mean patient age was 41 years (range 17-79). The defect requiring reconstruction was trauma in 16 cases, following tumour resection in two, and two miscellaneous causes. Thirteen cases had flap reconstruction and seven digits in six patients had hand digit replantations or revascularisation. Thirteen of 20 cases (65%) had successful tissue salvage following leech therapy for congestion (77% in 10 out of 13 flaps, and 43% in 3 of 7 digits). The rate of tissue salvage in pedicled flaps was good 6/6 (100%) and so was in digital revascularizations 2/3 (67%), but poor in digital re-plants 1/4 (25%) and free flaps 0/2 (0%). Leeches are a helpful tool for congested tissue salvage and in this study, showed a greater survival benefit for pedicled flaps than for free flaps or digital replantations.

Does Proton Therapy Offer Demonstrable Clinical Advantages for Treating Thoracic Tumors?

PubMed

Liao, Zhongxing; Gandhi, Saumil J; Lin, Steven H; Bradley, Jeffrey

2018-04-01

The finite range of proton beams in tissues offers unique dosimetric advantages that theoretically allow dose to the target to be escalated while minimizing exposure of surrounding tissues and thus minimizing radiation-induced toxicity. This theoretical advantage has led to widespread adoption of proton therapy around the world for a wide variety of tumors at different anatomical sites. Many treatment-planning comparisons have shown that proton therapy has substantial dosimetric advantages over conventional radiotherapy. However, given the significant difference in cost for proton vs conventional photon therapy, thorough investigation of the evidence of proton therapy's clinical benefits in terms of toxicity and survival is warranted. Some data from retrospective studies, single-arm prospective studies, and a very few randomized clinical trials comparing these modalities are beginning to emerge. In this review, we examine the available data with regard to proton therapy for thoracic malignancies. We begin by discussing the unique challenges involved in treating moving targets with significant tissue heterogeneity and the technologic efforts underway to overcome these challenges. We then discuss the rationale for minimizing normal tissue toxicity, particularly pulmonary, cardiac, and hematologic toxicity, within the context of previously unsuccessful attempts at dose escalation for lung and esophageal cancer. Finally, we explore strategies for accelerating the development of trials aimed at measuring meaningful clinical endpoints and for maximizing the value of proton therapy by personalizing its use for individual patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Real-time three-dimensional temperature mapping in photothermal therapy with optoacoustic tomography

NASA Astrophysics Data System (ADS)

Oyaga Landa, Francisco Javier; Deán-Ben, Xosé Luís.; Sroka, Ronald; Razansky, Daniel

2017-07-01

Ablation and photothermal therapy are widely employed medical protocols where the selective destruction of tissue is a necessity as in cancerous tissue removal or vascular and brain abnormalities. Tissue denaturation takes place when the temperature reaches a threshold value while the time of exposure determines the lesion size. Therefore, the spatio-temporal distribution of temperature plays a crucial role in the outcome of these clinical interventions. We demonstrate fast volumetric temperature mapping with optoacoustic tomography based on real-time optoacoustic readings from the treated region. The performance of the method was investigated in tissue-mimicking phantom experiments. The new ability to non-invasively measure temperature volumetrically in an entire treated region with high spatial and temporal resolutions holds potential for improving safety and efficacy of thermal ablation and to advance the general applicability of laser-based therapy.

Clinical Application of Stem Cells in the Cardiovascular System

NASA Astrophysics Data System (ADS)

Stamm, Christof; Klose, Kristin; Choi, Yeong-Hoon

Regenerative medicine encompasses "tissue engineering" - the in vitro fabrication of tissues and/or organs using scaffold material and viable cells - and "cell therapy" - the transplantation or manipulation of cells in diseased tissue in vivo. In the cardiovascular system, tissue engineering strategies are being pursued for the development of viable replacement blood vessels, heart valves, patch material, cardiac pacemakers and contractile myocardium. Anecdotal clinical applications of such vessels, valves and patches have been described, but information on systematic studies of the performance of such implants is not available, yet. Cell therapy for cardiovascular regeneration, however, has been performed in large series of patients, and numerous clinical studies have produced sometimes conflicting results. The purpose of this chapter is to summarize the clinical experience with cell therapy for diseases of the cardiovascular system, and to analyse possible factors that may influence its outcome.

Negative-pressure wound therapy and early pedicle flap reconstruction of the chest wall after epirubicin extravasation.

PubMed

Papadakis, Marios; Rahmanian-Schwarz, Afshin; Bednarek, Marzena; Arafkas, Mohamed; Holschneider, Philipp; Hübner, Gunnar

2017-05-15

Accidental extravasation is a serious iatrogenic injury among patients receiving anthracycline-containing chemotherapy. The aim of this work is to present a combination therapy for chest wall reconstruction following epirubicin extravasation. Herein, we report a 68-year-old woman with massive soft tissue necrosis of the anterolateral chest wall after epirubicin extravasation from a port implanted in the subclavicular area. The necrotic tissue was resected, the port was removed, and negative-pressure wound therapy was applied. Three weeks later, a latissimus dorsi pedicle flap was successfully used to cover the defect. To the best of the authors' knowledge, this is the first report of a strategy comprising the combination of negative-pressure wound therapy and a latissimus pedicle flap for reconstruction of the chest wall after soft tissue necrosis following epirubicin extravasation.

Expression of DMP-1 in the human pulp tissue using low level laser therapy

NASA Astrophysics Data System (ADS)

Lourenço Neto, Natalino; Teixeira Marques, Nádia Carolina; Fernandes, Ana Paula; Oliveira Rodini, Camila; Cruvinel Silva, Thiago; Moreira Machado, Maria Aparecida Andrade; Marchini Oliveira, Thais

2015-09-01

This study aimed to evaluate the effects of low-level laser therapy (LLLT) on DMP-1 expression in pulp tissue repair of human primary teeth. Twenty mandibular primary molars were randomly assigned into the following groups: Group I—Buckley’s Formocresol (FC); Group II—Calcium Hydroxide (CH); Group III—LLLT + CH and Group IV—LLLT + Zinc oxide/Eugenol. The teeth at the regular exfoliation period were extracted for histological analysis and immunolocalization of DMP-1. Descriptive analysis was performed on the dentin pulp complex. Histopathological assessment showed internal resorption in group FC. Groups CH and LLLT + CH provided better pulpal repair due to the absence of inflammation and the formation of hard tissue barrier. These two groups presented odontoblastic layer expressing DMP-1. According to this study, low level laser therapy preceding the use of calcium hydroxide exhibited satisfactory bio-inductive activity on pulp tissue repair of human primary teeth. However, other histological and cellular studies are needed to confirm the laser tissue action and efficacy.

Oncologic photodynamic diagnosis and therapy: confocal Raman/fluorescence imaging of metal phthalocyanines in human breast cancer tissue in vitro.

PubMed

Abramczyk, Halina; Brozek-Pluska, Beata; Surmacki, Jakub; Musial, Jacek; Kordek, Radzislaw

2014-11-07

Raman microspectroscopy and confocal Raman imaging combined with confocal fluorescence were used to study the distribution and aggregation of aluminum tetrasulfonated phthalocyanine (AlPcS4) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and aggregation of aluminum phthalocyanine, which is a potential photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. We have observed that the distribution of aluminum tetrasulfonated phthalocyanine confined in cancerous tissue is markedly different from that in noncancerous tissue. We have concluded that Raman imaging can be treated as a new and powerful technique useful in cancer photodynamic therapy, increasing our understanding of the mechanisms and efficiency of photosensitizers by better monitoring localization in cancer cells as well as the clinical assessment of the therapeutic effects of PDT and PIT.

Acoustic pressure wound therapy to facilitate granulation tissue in sacral pressure ulcers in patients with compromised mobility: a case series.

PubMed

Schmuckler, Jo

2008-08-01

Electrical stimulation and other modalities are recommended for treatment of pressure ulcers in spinal cord injury patients but their use may be limited by clinical contraindications such as necrosis and infection. Acoustic pressure wound therapy can be used to address infection and has no known contraindications related to wound status. A retrospective nonconsecutive study was conducted involving five inpatients with sacral pressure ulcers and compromised mobility (spinal cord injury, ventilator/mobility dependency, or persistent vegetative state) treated with acoustic pressure wound therapy three times per week, 4 to 6 minutes per session, for 5 weeks to 5.5 months. Acoustic pressure wound therapy was administered until necrotic tissue was removed, granulation was complete, drainage resolved to moderate levels, and wound size was compatible with indications for high-voltage electrical stimulation. Within 1 to 4 weeks of starting acoustic pressure wound therapy, four out of five wounds with substantial yellow slough or eschar demonstrated 100% granulation tissue and wound area and volume decreased 71% to 97% and 75% to 99%, respectively. Subsequent treatments included electrical stimulation alone (three patients) or in conjunction with negative pressure wound therapy (one patient), and silver foam (one patient). Acoustic pressure wound therapy was found to be an effective option in preparing wounds for subsequent therapy.

Periodontal tissue regeneration by combined implantation of adipose tissue-derived stem cells and platelet-rich plasma in a canine model.

PubMed

Tobita, Morikuni; Uysal, Cagri A; Guo, Xin; Hyakusoku, Hiko; Mizuno, Hiroshi

2013-12-01

One goal of periodontal therapy is to regenerate periodontal tissues. Stem cells, growth factors and scaffolds and biomaterials are vital for the restoration of the architecture and function of complex tissues. Adipose tissue-derived stem cells (ASCs) are an ideal population of stem cells for practical regenerative medicine. In addition, platelet-rich plasma (PRP) can be useful for its ability to stimulate tissue regeneration. PRP contains various growth factors and may be useful as a cell carrier in stem cell therapies. The purpose of this study was to determine whether a mixture of ASCs and PRP promoted periodontal tissue regeneration in a canine model. Autologous ASCs and PRP were implanted into areas with periodontal tissue defects. Periodontal tissue defects that received PRP alone or non-implantation were also examined. Histologic, immunohistologic and x-ray studies were performed 1 or 2 months after implantation. The amount of newly formed bone and the scale of newly formed cementum in the region of the periodontal tissue defect were analyzed on tissue sections. The areas of newly formed bone and cementum were greater 2 months after implantation of ASCs and PRP than at 1 month after implantation, and the radiopacity in the region of the periodontal tissue defect increased markedly by 2 months after implantation. The ASCs and PRP group exhibited periodontal tissue with the correct architecture, including alveolar bone, cementum-like structures and periodontal ligament-like structures, by 2 months after implantation. These findings suggest that a combination of autologous ASCs and PRP promotes periodontal tissue regeneration that develops the appropriate architecture for this complex tissue. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The role of nanotechnology in induced pluripotent and embryonic stem cells research.

PubMed

Chen, Lukui; Qiu, Rong; Li, Lushen

2014-12-01

This paper reviews the recent studies on development of nanotechnology in the field of induced pluripotent and embryonic stem cells. Stem cell therapy is a promising therapy that can improve the quality of life for patients with refractory diseases. However, this option is limited by the scarcity of tissues, ethical problem, and tumorigenicity. Nanotechnology is another promising therapy that can be used to mimic the extracellular matrix, label the implanted cells, and also can be applied in the tissue engineering. In this review, we briefly introduce implementation of nanotechnology in induced pluripotent and embryonic stem cells research. Finally, the potential application of nanotechnology in tissue engineering and regenerative medicine is also discussed.

Potential for Stem Cell-Based Periodontal Therapy

PubMed Central

Bassir, Seyed Hossein; Wisitrasameewong, Wichaya; Raanan, Justin; Ghaffarigarakani, Sasan; Chung, Jamie; Freire, Marcelo; Andrada, Luciano C.; Intini, Giuseppe

2015-01-01

Periodontal diseases are highly prevalent and are linked to several systemic diseases. The goal of periodontal treatment is to halt the progression of the disease and regenerate the damaged tissue. However, achieving complete and functional periodontal regeneration is challenging because the periodontium is a complex apparatus composed of different tissues, including bone, cementum, and periodontal ligament. Stem cell-based regenerative therapy may represent an effective therapeutic tool for periodontal regeneration due to their plasticity and ability to differentiate into different cell lineages. This review presents and critically analyzes the available information on stem cell-based therapy for the regeneration of periodontal tissues and suggests new avenues for the development of more effective therapeutic protocols. PMID:26058394

[CHANGES IN THE ORGANS AND TISSUES OF THE ORAL CAVITY WITH DIGESTIVE SYSTEM DISEASES].

PubMed

Trukhan, D I; Goloshubina, V V; Trukhan, L Yu

2015-01-01

A substantial part of the pathology of organs and tissues of the oral cavity make common manifestations or systemic diseases. Accordingly, the dosage systemic therapy of these diseases can affect the condition of the eye. Changes in organs and tissues of the oral cavity and the appropriate advice a dentist can help the gastroenterologist in the diagnosis and adequate treatment of the patient. The article discusses possible changes in the organs and tissues of the oral cavity in diseases of the digestive system, as well as changes occurring under the influence of drug therapy of these diseases.

Tissue engineering therapy for cardiovascular disease.

PubMed

Nugent, Helen M; Edelman, Elazer R

2003-05-30

The present treatments for the loss or failure of cardiovascular function include organ transplantation, surgical reconstruction, mechanical or synthetic devices, or the administration of metabolic products. Although routinely used, these treatments are not without constraints and complications. The emerging and interdisciplinary field of tissue engineering has evolved to provide solutions to tissue creation and repair. Tissue engineering applies the principles of engineering, material science, and biology toward the development of biological substitutes that restore, maintain, or improve tissue function. Progress has been made in engineering the various components of the cardiovascular system, including blood vessels, heart valves, and cardiac muscle. Many pivotal studies have been performed in recent years that may support the move toward the widespread application of tissue-engineered therapy for cardiovascular diseases. The studies discussed include endothelial cell seeding of vascular grafts, tissue-engineered vascular conduits, generation of heart valve leaflets, cardiomyoplasty, genetic manipulation, and in vitro conditions for optimizing tissue-engineered cardiovascular constructs.

Photothermal lesions in soft tissue induced by optical fiber microheaters.

PubMed

Pimentel-Domínguez, Reinher; Moreno-Álvarez, Paola; Hautefeuille, Mathieu; Chavarría, Anahí; Hernández-Cordero, Juan

2016-04-01

Photothermal therapy has shown to be a promising technique for local treatment of tumors. However, the main challenge for this technique is the availability of localized heat sources to minimize thermal damage in the surrounding healthy tissue. In this work, we demonstrate the use of optical fiber microheaters for inducing thermal lesions in soft tissue. The proposed devices incorporate carbon nanotubes or gold nanolayers on the tips of optical fibers for enhanced photothermal effects and heating of ex vivo biological tissues. We report preliminary results of small size photothermal lesions induced on mice liver tissues. The morphology of the resulting lesions shows that optical fiber microheaters may render useful for delivering highly localized heat for photothermal therapy.

RADIATION THERAPY COMMUNICATION-REIRRADIATION OF A NASAL TUMOR IN A BRACHYCEPHALIC DOG USING INTENSITY MODULATED RADIATION THERAPY.

PubMed

Rancilio, Nicholas J; Custead, Michelle R; Poulson, Jean M

2016-09-01

A 5-year-old spayed female Shih Tzu was referred for evaluation of a nasal transitional carcinoma. A total lifetime dose of 117 Gy was delivered to the intranasal mass in three courses over nearly 2 years using fractionated intensity modulated radiation therapy (IMRT) to spare normal tissues. Clinically significant late normal tissue side effects were limited to bilaterally diminished tear production. The patient died of metastatic disease progression 694 days after completion of radiation therapy course 1. This case demonstrates that retreatment with radiation therapy to high lifetime doses for recurrent local disease may be well tolerated with IMRT. © 2016 American College of Veterinary Radiology.

Optoacoustic detection of thermal lesions

NASA Astrophysics Data System (ADS)

Arsenault, Michel G.; Kolios, Michael C.; Whelan, William M.

2009-02-01

Minimally invasive thermal therapy is being investigated as an alternative cancer treatment. It involves heating tissues to greater than 55°C over a period of a few minutes, which results in tissue coagulation. Optoacoustic (OA) imaging is a new imaging technique that involves exposing tissues to pulsed light and detecting the acoustic waves that are generated. In this study, adult bovine liver tissue samples were heated using continuous wave laser energy for various times, then scanned using an optoacoustic imaging system. Large optoacoustic signal variability was observed in the native tissue prior to heating. OA signal amplitude increased with maximum tissue temperature achieved, characterized by a correlation coefficient of 0.63. In this study we show that there are detectable changes in optoacoustic signal strength that arise from tissue coagulation, which demonstrates the potential of optoacoustic technology for the monitoring of thermal therapy delivery.

Spanish Pacemaker Registry. Twelfth Official Report of the Spanish Society of Cardiology Working Group on Cardiac Pacing (2014).

PubMed

Cano Pérez, Óscar; Pombo Jiménez, Marta; Coma Samartín, Raúl

2015-12-01

This report describes the results of the analysis of pacemaker implant and replacement data submitted to the Spanish Pacemaker Registry in 2014, with special reference to pacing mode selection. The report is based on the processing of information provided by the European Pacemaker Patient Identification Card. Information was received from 117 hospitals, with a total of 12 358 cards, representing 34% of estimated activity. Use of conventional generators and resynchronization devices was 784 and 64.4 units per million population, respectively. The mean age of patients receiving an implant was 77.3 years. Men received 59% of implants and 56.4% of replacements. Most patients receiving generator implants and replacements were in the age range 80 to 89 years. Most endocardial leads used were bipolar, and 84.2% had an active fixation system. Pacing was in VVI/R mode despite being in sinus rhythm in 24.7% of patients with sick sinus syndrome and 24% of those with atrioventricular block. The use of pacemaker generators and resynchronization devices per million population continued to increase. Most implanted leads had active fixation and approximately 20% had magnetic resonance imaging protection. Age and sex directly influenced pacing mode selection, which could have been improved in more than 20% of cases. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Targeting Nuclear EGFR: Strategies for Improving Cetuximab Therapy in Lung Cancer

DTIC Science & Technology

2013-09-01

has been identified in various human tumor tissues, including cancers of the breast, ovary, oropharynx, and esophagus , and has predicted poor patient...been identified in various human tumor tissues, including cancers of the breast, ovary, oropharynx, and esophagus , and has predicted...Improving Cetuximab Therapy in Lung Cancer PRINCIPAL INVESTIGATOR: Deric L Wheeler

AAV vector encoding human VEGF165-transduced pectineus muscular flaps increase the formation of new tissue through induction of angiogenesis in an in vivo chamber for tissue engineering: A technique to enhance tissue and vessels in microsurgically engineered tissue.

PubMed

Moimas, Silvia; Manasseri, Benedetto; Cuccia, Giuseppe; Stagno d'Alcontres, Francesco; Geuna, Stefano; Pattarini, Lucia; Zentilin, Lorena; Giacca, Mauro; Colonna, Michele R

2015-01-01

In regenerative medicine, new approaches are required for the creation of tissue substitutes, and the interplay between different research areas, such as tissue engineering, microsurgery and gene therapy, is mandatory. In this article, we report a modification of a published model of tissue engineering, based on an arterio-venous loop enveloped in a cross-linked collagen-glycosaminoglycan template, which acts as an isolated chamber for angiogenesis and new tissue formation. In order to foster tissue formation within the chamber, which entails on the development of new vessels, we wondered whether we might combine tissue engineering with a gene therapy approach. Based on the well-described tropism of adeno-associated viral vectors for post-mitotic tissues, a muscular flap was harvested from the pectineus muscle, inserted into the chamber and transduced by either AAV vector encoding human VEGF165 or AAV vector expressing the reporter gene β-galactosidase, as a control. Histological analysis of the specimens showed that muscle transduction by AAV vector encoding human VEGF165 resulted in enhanced tissue formation, with a significant increase in the number of arterioles within the chamber in comparison with the previously published model. Pectineus muscular flap, transduced by adeno-associated viral vectors, acted as a source of the proangiogenic factor vascular endothelial growth factor, thus inducing a consistent enhancement of vessel growth into the newly formed tissue within the chamber. In conclusion, our present findings combine three different research fields such as microsurgery, tissue engineering and gene therapy, suggesting and showing the feasibility of a mixed approach for regenerative medicine.

Protective effect of gel form of gastric gavage applicated aloe vera on ischemia reperfusion injury in renal and lung tissue.

PubMed

Sahin, Hasan; Yener, Ali Umit; Karaboga, Ihsan; Sehitoglu, Muserref Hilal; Dogu, Tugba; Altinisik, Hatice Betul; Altinisik, Ugur; Simsek, Tuncer

2017-12-30

The aloe vera plant has become increasingly popular in recent years. This study aimed to research the effect of aloe vera to prevent renal and lung tissue damage in an experimental ischemia-reperfusion (I/R) injury model. The study included 21 male Wistar Albino rats, which were categorized into control group, n = 7 (no procedures), Sham group n = 7 (I/R); and aloe vera therapy group, n = 7 (aloe vera and I/R). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were evaluated from lung and kidney tissues for biochemical investigations. As histopathological, hematoxylin and eosin and anti-iNOS were also examined. In biochemical investigations, SOD, CAT, and GPx levels of the Sham group were found to be lower compared with the other groups (P < 0.05). The aloe vera therapy group was not statistically different from control groups but significantly different compared with the Sham group. In the same way, the MDA levels of kidney and lung tissues were statistically significant in the aloe vera therapy group, compared to the Sham group. In the Sham group, the peribronchial and perialveolar edema were observed in lung parenchyma. Also, excess interstitial hemorrhage, leukocyte infiltration, and alveolar wall thickening were identified in ischemic groups. The histopathological changes were much lighter than in the aloe vera therapy group. In renal tissues, excess epithelial cell deterioration, tubular desqumination, and glomerular atrophy were observed in the Sham group. The histopathological changes were markedly reduced in the aloe vera therapy  group. In the kidney and lung tissue, the level of iNOS activity in the Sham group was significantly higher than in the control and aloe vera therapy group. This study indicated that aloe vera is protective against oxidative damage formed by I/R in distant organs like the lungs and kidneys.

Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

PubMed

Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

2015-01-01

Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

LATIS3D: The Goal Standard for Laser-Tissue-Interaction Modeling

NASA Astrophysics Data System (ADS)

London, R. A.; Makarewicz, A. M.; Kim, B. M.; Gentile, N. A.; Yang, T. Y. B.

2000-03-01

The goal of this LDRD project has been to create LATIS3D-the world's premier computer program for laser-tissue interaction modeling. The development was based on recent experience with the 2D LATIS code and the ASCI code, KULL. With LATIS3D, important applications in laser medical therapy were researched including dynamical calculations of tissue emulsification and ablation, photothermal therapy, and photon transport for photodynamic therapy. This project also enhanced LLNL's core competency in laser-matter interactions and high-energy-density physics by pushing simulation codes into new parameter regimes and by attracting external expertise. This will benefit both existing LLNL programs such as ICF and SBSS and emerging programs in medical technology and other laser applications. The purpose of this project was to develop and apply a computer program for laser-tissue interaction modeling to aid in the development of new instruments and procedures in laser medicine.

Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

PubMed Central

Yoshida, Toshiyuki; Washio, Kaoru; Iwata, Takanori; Okano, Teruo; Ishikawa, Isao

2012-01-01

It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy. PMID:22315604

Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

NASA Astrophysics Data System (ADS)

Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

Image-guided therapies for myocardial repair: concepts and practical implementation

PubMed Central

Bengel, Frank M.; George, Richard T.; Schuleri, Karl H.; Lardo, Albert C.; Wollert, Kai C.

2013-01-01

Cell- and molecule-based therapeutic strategies to support wound healing and regeneration after myocardial infarction (MI) are under development. These emerging therapies aim at sustained preservation of ventricular function by enhancing tissue repair after myocardial ischaemia and reperfusion. Such therapies will benefit from guidance with regard to timing, regional targeting, suitable candidate selection, and effectiveness monitoring. Such guidance is effectively obtained by non-invasive tomographic imaging. Infarct size, tissue characteristics, muscle mass, and chamber geometry can be determined by magnetic resonance imaging and computed tomography. Radionuclide imaging can be used for the tracking of therapeutic agents and for the interrogation of molecular mechanisms such as inflammation, angiogenesis, and extracellular matrix activation. This review article portrays the hypothesis that an integrated approach with an early implementation of structural and molecular tomographic imaging in the development of novel therapies will provide a framework for achieving the goal of improved tissue repair after MI. PMID:23720377

Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

PubMed Central

Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

2015-01-01

Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm2 for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT. PMID:26000054

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myoribers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postmitotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Telmisartan Therapy Does Not Improve Lymph Node or Adipose Tissue Fibrosis More Than Continued Antiretroviral Therapy Alone.

PubMed

Utay, Netanya S; Kitch, Douglas W; Yeh, Eunice; Fichtenbaum, Carl J; Lederman, Michael M; Estes, Jacob D; Deleage, Claire; Magyar, Clara; Nelson, Scott D; Klingman, Karen L; Bastow, Barbara; Luque, Amneris E; McComsey, Grace A; Douek, Daniel C; Currier, Judith S; Lake, Jordan E

2018-05-05

Fibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection. In this 48-week, randomized, controlled trial, adults continued HIV-suppressive ART and received telmisartan or no drug. Collagen I, fibronectin, and phosphorylated SMAD3 (pSMAD3) deposition in lymph nodes, as well as collagen I, collagen VI, and fibronectin deposition in adipose tissue, were quantified by immunohistochemical analysis at weeks 0 and 48. Two-sided rank sum and signed rank tests compared changes over 48 weeks. Forty-four participants enrolled; 35 had paired adipose tissue specimens, and 29 had paired lymph node specimens. The median change overall in the percentage of the area throughout which collagen I was deposited was -2.6 percentage points (P = 0.08) in lymph node specimens and -1.3 percentage points (P = .001) in adipose tissue specimens, with no between-arm differences. In lymph node specimens, pSMAD3 deposition changed by -0.5 percentage points overall (P = .04), with no between-arm differences. Telmisartan attenuated increases in fibronectin deposition (P = .06). In adipose tissue, changes in collagen VI deposition (-1.0 percentage point; P = .001) and fibronectin deposition (-2.4 percentage points; P < .001) were observed, with no between-arm differences. In adults with treated HIV infection, lymph node and adipose tissue fibrosis decreased with continued ART alone, with no additional fibrosis reduction with telmisartan therapy.

Comparative dosimetry of volumetric modulated arc therapy and limited-angle static intensity-modulated radiation therapy for early-stage larynx cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riegel, Adam C.; Antone, Jeffrey; Schwartz, David L., E-mail: dschwartz3@nshs.edu

2013-04-01

To compare relative carotid and normal tissue sparing using volumetric-modulated arc therapy (VMAT) or intensity-modulated radiation therapy (IMRT) for early-stage larynx cancer. Seven treatment plans were retrospectively created on 2 commercial treatment planning systems for 11 consecutive patients with T1-2N0 larynx cancer. Conventional plans consisted of opposed-wedged fields. IMRT planning used an anterior 3-field beam arrangement. Two VMAT plans were created, a full 360° arc and an anterior 180° arc. Given planning target volume (PTV) coverage of 95% total volume at 95% of 6300 cGy and maximum spinal cord dose below 2500 cGy, mean carotid artery dose was pushed asmore » low as possible for each plan. Deliverability was assessed by comparing measured and planned planar dose with the gamma (γ) index. Full-arc planning provided the most effective carotid sparing but yielded the highest mean normal tissue dose (where normal tissue was defined as all soft tissue minus PTV). Static IMRT produced next-best carotid sparing with lower normal tissue dose. The anterior half-arc produced the highest carotid artery dose, in some cases comparable with conventional opposed fields. On the whole, carotid sparing was inversely related to normal tissue dose sparing. Mean γ indexes were much less than 1, consistent with accurate delivery of planned treatment. Full-arc VMAT yields greater carotid sparing than half-arc VMAT. Limited-angle IMRT remains a reasonable alternative to full-arc VMAT, given its ability to mediate the competing demands of carotid and normal tissue dose constraints. The respective clinical significance of carotid and normal tissue sparing will require prospective evaluation.« less

Optimizing Results of Postmastectomy Radiation Therapy Utilizing the Latissimus Dorsi Flap and Tissue Expander Technique: A Single-Center Experience

PubMed Central

Chevrollier, Guillaume S.; Greaney, Patrick J.; Jenkins, Matthew P.; Copit, Steven E.

2017-01-01

Objective: Postmastectomy radiation therapy is a well-established risk factor for complications after breast reconstruction. Even if the surgeon has a suspicion that radiation therapy may be needed, it may be beneficial to place tissue expanders during the mastectomy procedure as a temporizing measure, complete radiation therapy, and then reconstruct the breast with a latissimus flap. The purpose of this study was to examine the complication rates of the latissimus dorsi flap as compared with the complication rates of implant-based reconstruction in the setting of radiation therapy. Methods: A 16-year retrospective chart review from 2000 to 2016 was conducted. All patients who underwent temporizing tissue expander placement for radiotherapy with subsequent latissimus flap reconstruction were included in the study. Patients who did not follow up for implant exchange were excluded from the study. Results: Fifty-five patients were identified with an average age of 46.0 years (range, 27-67 years) and an average body mass index of 24.2 (range, 18.9-31.9). Five patients (9.1%) developed capsular contractures amenable to surgical intervention. One patient (1.8%) developed infection of the tissue expander, requiring removal. There were no incidences of flap failure or wound dehiscence. The average follow-up after latissimus flap reconstruction was 25.3 months (range, 3.7-121.6 months). Conclusions: We feel that the latissimus dorsi flap after postmastectomy radiation therapy represents the preferred implant-based reconstruction option to consider when the need for postmastectomy radiation therapy is anticipated. The latissimus dorsi flap remains a safe, effective solution to postmastectomy radiation therapy that every plastic surgeon should offer. PMID:29308108

Optimizing Results of Postmastectomy Radiation Therapy Utilizing the Latissimus Dorsi Flap and Tissue Expander Technique: A Single-Center Experience.

PubMed

Mohiuddin, Waseem; Chevrollier, Guillaume S; Greaney, Patrick J; Jenkins, Matthew P; Copit, Steven E

2017-01-01

Objective: Postmastectomy radiation therapy is a well-established risk factor for complications after breast reconstruction. Even if the surgeon has a suspicion that radiation therapy may be needed, it may be beneficial to place tissue expanders during the mastectomy procedure as a temporizing measure, complete radiation therapy, and then reconstruct the breast with a latissimus flap. The purpose of this study was to examine the complication rates of the latissimus dorsi flap as compared with the complication rates of implant-based reconstruction in the setting of radiation therapy. Methods: A 16-year retrospective chart review from 2000 to 2016 was conducted. All patients who underwent temporizing tissue expander placement for radiotherapy with subsequent latissimus flap reconstruction were included in the study. Patients who did not follow up for implant exchange were excluded from the study. Results: Fifty-five patients were identified with an average age of 46.0 years (range, 27-67 years) and an average body mass index of 24.2 (range, 18.9-31.9). Five patients (9.1%) developed capsular contractures amenable to surgical intervention. One patient (1.8%) developed infection of the tissue expander, requiring removal. There were no incidences of flap failure or wound dehiscence. The average follow-up after latissimus flap reconstruction was 25.3 months (range, 3.7-121.6 months). Conclusions: We feel that the latissimus dorsi flap after postmastectomy radiation therapy represents the preferred implant-based reconstruction option to consider when the need for postmastectomy radiation therapy is anticipated. The latissimus dorsi flap remains a safe, effective solution to postmastectomy radiation therapy that every plastic surgeon should offer.

Recent advances in the synchronization of estrus and ovulation in dairy cows.

PubMed

Macmillan, Keith L

2010-01-01

Synchronization programs have become standard components in the current breeding management of cows in the dairy herds of most dairy industries. Many are based on protocols that allow timed inseminations (TAI) so as to circumvent the practical difficulties associated with estrus detection. These difficulties are exacerbated in modern herds of high producing cows either because of increasing herd size in which individual animal monitoring is difficult and often subjective, or because small intensively managed herds are milked in robotic systems that minimize animal: staff interactions. Additional reasons arise from high producing cows having less obvious symptoms of estrus, partly because of housing systems combined with intensive feeding and milking, partly because of higher metabolic clearance rates of reproductive hormones like estradiol and partly because of the increasing prevalence of prolonged post-partum anestrus and reproductive tract pathology. The most recently developed programs include protocols for resynchronization following first or subsequent inseminations. These re-synchronization protocols may involve selected forms of hormonal intervention during the diestrous and pro-estrous periods following TAI, or following pregnancy diagnosis by ultrasound from 28 days after TAI. The latter form of re-synchronization has become increasingly important with the recognition that late embryonic/early foetal death has become a major factor compromising the reproductive performance of high producing Holstein cows in many dairy industries. Although cows detected in estrus without any hormonal treatment before insemination have higher conception rates than those inseminated following synchronization and TAI, the low detection rates combined with embryonic death means that intervals from calving to conception (days open) are usually less when synchronization programs have been successfully implemented. One of the significant factors affecting a program's success is the compliance rate that may sometimes be less than 70%. Almost all programs involve strategically timed injections of prostaglandin F2alpha (PGF) and gonadotropin releasing hormone (GnRH). Injections of an estradiol ester and progesterone supplementation per vaginum may be included in some programs. The basic program is the "Ovsynch" regimen. Numerous variations have been tested and developed. Many involve increasingly complex protocols that increase the risk of non-compliance, none has consistently achieved conception rates that exceed 40% and few have reduced the incidence of embryonic death. These synchronization programs are the best that are currently available. They have not been able to overcome the consequences of lowered fertility associated with high levels of milk yield, forms of nutrition and environmental factors like heat stress that have profound effects on the physiology and metabolism of the high producing dairy cow.

Determining the appropriate number and duration of leech therapy in congested tissues using tissue spectrophotometry and laser Doppler flowmetry.

PubMed

Rothenberger, Jens; Petersen, Wiebke; Schaller, Hans-Eberhard; Held, Manuel

2016-11-01

A universal protocol determining the number of leeches and their application time does not exist. The aim of this study, therefore, is to quantify perfusion dynamics in venous congested tissues after leech application to get more detailed information about changes due to leech-induced skin microcirculation and to evaluate the usability of the Oxygen to See (O2C) device in terms of determining the appropriate number of leeches and the duration of therapy. Twelve patients with the need for leech therapy participated in the study. Perfusion dynamics of the congested tissue was assessed using the O2C device, which determines blood flow (BF), the relative amount of hemoglobin (rHB), and the oxygen saturation (SO2). Measurements were carried out before leech application and on various intervals like 10 minutes, one hour, and three hours after leech application. The leech application effectuated after 10 minutes a nonsignificant perfusion improvement, which further increased after one hour with a significant reduction of the relative amount of hemoglobin and a significant increase of blood flow and oxygen saturation (BF= +56.7%; rHB= -25.5%; SO2= +53.7%). After three hours, the values returned to the levels before leech administration. In two cases, in which further administration of leeches within the measurement period was necessary, no substantial perfusion changes were obtained. The results of this study forms a more precise pattern of microcirculatory changes of leech therapy in congested tissues. According to our measurements a venous drainage improvement can be expected in congested tissue one hour after leech administration. The O2C seems to be a useful method to determine the appropriate number and duration of leech therapy. © 2016 by the Wound Healing Society.

[National registry on cardiac electrophysiology (2010 and 2011)].

PubMed

Madeira, Francisco; Oliveira, Mário; Ventura, Miguel; Primo, João; Bonhorst, Daniel; Morais, Carlos

2013-02-01

Based on a survey sent to Portuguese centers that perform diagnostic and interventional electrophysiology and/or implant cardioverter-defibrillators (ICDs), the authors analyze the number and type of procedures performed during 2010 and 2011 and compare these data with previous years. In 2011, a total of 2533 diagnostic electrophysiologic procedures were performed, which were followed by ablation in 2013 cases, a steady increase over previous years. The largest share of this increase compared to 2010 was in atrial fibrillation, which is now the second most frequent indication for ablation, after atrioventricular nodal reentrant tachycardia. The total number of ICDs implanted in 2011 was 1084, of which 339 were biventricular (BiV) cardiac resynchronization devices (BiV ICDs). This represents an increase in the total number relative to previous years, 2011 being the first year in which the rate of new ICD implantations in Portugal exceeded 100 per million population. However, compared to 2010, the number of BiV ICDs implanted decreased, despite the recent publication of updated European guidelines on device therapy in heart failure, which clarified and expanded the indications for implantation of these devices. Some comments are made on the current status of cardiac electrophysiology in Portugal and on factors that may influence its development in the coming years. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Rationale and design of the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository.

PubMed

Koontz, Jason I; Haithcock, Daniel; Cumbea, Valerie; Waldron, Anthony; Stricker, Kristie; Hughes, Amy; Nilsson, Kent; Sun, Albert; Piccini, Jonathan P; Kraus, William E; Pitt, Geoffrey S; Shah, Svati H; Hranitzky, Patrick

2009-11-01

Disturbances in cardiac rhythm can lead to significant morbidity and mortality. Many arrhythmias are known to have a heritable component, but the degree to which genetic variation contributes to disease risk and morbidity is poorly understood. The EPGEN is a prospective single-center repository that archives DNA, RNA, and protein samples obtained at the time of an electrophysiologic evaluation or intervention. To identify genes and molecular variants that are associated with risk for arrhythmic phenotypes, EPGEN uses unbiased genomic screening; candidate gene analysis; and both unbiased and targeted transcript, protein, and metabolite profiling. To date, EPGEN has successfully enrolled >1,500 subjects. The median age of the study population is 62.9 years; 35% of the subjects are female and 21% are black. To this point, the study population has been composed of patients who had undergone defibrillator (implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator) implantation (45%), electrophysiology studies or ablation procedures (35%), and pacemaker implantation or other procedures (20%). The cohort has a high prevalence of comorbidities, including diabetes (33%), hypertension (73%), chronic kidney disease (26%), and peripheral vascular disease (13%). We have established a biorepository and clinical database composed of patients with electrophysiologic diseases. EPGEN will seek to (1) improve risk stratification, (2) elucidate mechanisms of arrhythmogenesis, and (3) identify novel pharmacologic targets for the treatment of heart rhythm disorders.

Initial experience with remote magnetic navigation for left ventricular lead placement.

PubMed

Mischke, Karl; Knackstedt, Christian; Schmid, Michael; Hatam, Nima; Becker, Michael; Spillner, Jan; Fache, Kerstin; Kelm, Malte; Schauerte, Patrick

2009-08-01

A novel magnetic navigation system allows remote steering of guidewires and catheters. This system may be used for left ventricular lead placement for cardiac resynchronization therapy (CRT). We sought to evaluate the feasibility and safety of magnetic guidewire navigation for CRT procedures. 123 consecutive patients underwent CRT implantation/revision procedures (including pacemaker upgrades in n=22 and left ventricular lead placement after dislocation in n=4 patients). Left ventricular lead placement in a coronary sinus side branch was performed either conventionally or using magnetic navigation. The magnetic navigation system (Niobe) consists of two permanent magnets creating a steerable magnetic field. Guidewires with integrated magnets align to the magnetic field and were used for over-the-wire implantation of pacemaker leads in the coronary sinus. Patients were assigned to conventional (n=93) or magnetic (n=30) navigation according to room availability. Venography of the coronary venous system was performed to select a target vessel for lead implantation. Guidewire access to the target vessel was achieved in 100% using magnetic navigation compared to 87% with the conventional approach (P < 0.05). Implantation success rates, total procedure and fluoroscopy times did not differ significantly between groups. No periprocedural death and no intraoperative device dysfunction occurred in either group.The magnetic guidewire ruptured in one patient. Left ventricular lead placement using magnetic guidewire navigation to engage the desired coronary sinus side branch can be successfully performed for CRT.

Heart Failure in Patients with Chronic Kidney Disease: A Systematic Integrative Review

PubMed Central

Segall, Liviu; Nistor, Ionut; Covic, Adrian

2014-01-01

Introduction. Heart failure (HF) is highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) and is strongly associated with mortality in these patients. However, the treatment of HF in this population is largely unclear. Study Design. We conducted a systematic integrative review of the literature to assess the current evidence of HF treatment in CKD patients, searching electronic databases in April 2014. Synthesis used narrative methods. Setting and Population. We focused on adults with a primary diagnosis of CKD and HF. Selection Criteria for Studies. We included studies of any design, quantitative or qualitative. Interventions. HF treatment was defined as any formal means taken to improve the symptoms of HF and/or the heart structure and function abnormalities. Outcomes. Measures of all kinds were considered of interest. Results. Of 1,439 results returned by database searches, 79 articles met inclusion criteria. A further 23 relevant articles were identified by hand searching. Conclusions. Control of fluid overload, the use of beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and optimization of dialysis appear to be the most important methods to treat HF in CKD and ESRD patients. Aldosterone antagonists and digitalis glycosides may additionally be considered; however, their use is associated with significant risks. The role of anemia correction, control of CKD-mineral and bone disorder, and cardiac resynchronization therapy are also discussed. PMID:24959595

Fluid status monitoring with a wireless network to reduce cardiovascular-related hospitalizations and mortality in heart failure: rationale and design of the OptiLink HF Study (Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink).

PubMed

Brachmann, Johannes; Böhm, Michael; Rybak, Karin; Klein, Gunnar; Butter, Christian; Klemm, Hanno; Schomburg, Rolf; Siebermair, Johannes; Israel, Carsten; Sinha, Anil-Martin; Drexler, Helmut

2011-07-01

The Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink (OptiLink HF) study is designed to investigate whether OptiVol fluid status monitoring with an automatically generated wireless CareAlert notification via the CareLink Network can reduce all-cause death and cardiovascular hospitalizations in an HF population, compared with standard clinical assessment. Methods Patients with newly implanted or replacement cardioverter-defibrillator devices with or without cardiac resynchronization therapy, who have chronic HF in New York Heart Association class II or III and a left ventricular ejection fraction ≤35% will be eligible to participate. Following device implantation, patients are randomized to either OptiVol fluid status monitoring through CareAlert notification or regular care (OptiLink 'on' vs. 'off'). The primary endpoint is a composite of all-cause death or cardiovascular hospitalization. It is estimated that 1000 patients will be required to demonstrate superiority of the intervention group to reduce the primary outcome by 30% with 80% power. The OptiLink HF study is designed to investigate whether early detection of congestion reduces mortality and cardiovascular hospitalization in patients with chronic HF. The study is expected to close recruitment in September 2012 and to report first results in May 2014.

Trajectories of perceived emotional and physical distress in patients with an implantable cardioverter defibrillator.

PubMed

van den Broek, Krista C; Kupper, Nina; van der Voort, Pepijn H; Alings, Marco; Denollet, Johan; Nyklíček, Ivan

2014-02-01

Little is known about the course of emotional and physical distress in patients with an implantable cardioverter defibrillator (ICD). We examined (1) trajectories of emotional and physical distress in the first 18 months postimplantation and (2) predictors of these trajectories, including demographical, clinical, and personality factors. Dutch patients with an ICD (N = 645) completed measures on anxiety, depression, somatic symptoms, and perceived disability at the time of implantation, and 2, 12, and 18 months postimplantation. Measures on Type D personality (tendency to inhibit the expression of negative emotions) and anxiety sensitivity (tendency to fear anxiety-related sensations) were also completed at baseline. Latent class analysis (LatentGOLD) identified six to seven distinct trajectories, varying largely in overall levels of distress, and remaining relatively stable after a small initial decline. Multinomial regression showed that Type D personality and anxiety sensitivity were the most prominent predictors, particularly of trajectories that reflected higher distress levels. Cardiac resynchronization therapy and coronary artery disease also increased the risk for distress, whereas ICD indication and shocks did not. The course of emotional and physical distress may be relatively stable after ICD implantation. In clinical practice, identification of patients with high risk of higher levels of emotional and physical distress may be warranted; as such, patients with high levels of anxiety sensitivity or a Type D personality should be identified and offered behavioral support.

Joint and Soft Tissue Injections

MedlinePlus

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Solid tumors.

PubMed

Richardson, R C

1985-05-01

Soft-tissue tumors are similar in their behavior. Benign tumors can be easily resected in most cases, whereas malignant tumors are relentless in their locally invasive characteristics. A clear understanding of the constraints of the pathologist in reaching a confirmed diagnosis and a logical plan utilizing surgery as the major modality of therapy are necessary for successful management of these tumors. It appears that radiation combined with hyperthermia is beginning to play a significant role in the local control of soft-tissue sarcomas and that single or multi-agent chemotherapy may be of benefit in treatment of nonresectable or metastatic soft-tissue sarcomas. For the immediate future, surgery remains the only nonexperimental modality of therapy, but the rapid advances in the other therapy methods are encouraging.

Long-Term Results Comparing Xenogeneic Collagen Matrix and Autogenous Connective Tissue Grafts With Coronally Advanced Flaps for Treatment of Dehiscence-Type Recession Defects.

PubMed

McGuire, Michael K; Scheyer, E Todd

2016-03-01

Although connective tissue grafts with coronally advanced flaps (CTG + CAF) have been deemed the gold standard for recession defect treatment, to provide adequate recession coverage, the periodontal profession continues to pursue lower-morbidity, patient-preferred substitutes that are more convenient and of unlimited supply. Using a randomized, controlled, and masked contralateral comparison of matched-pair, within-patient recession defects, collagen matrix (CMX) + CAF therapy was compared with CTG + CAF at 6 months and 5 years. The primary efficacy endpoint was percentage of root coverage (RC). Secondary efficacy parameters included width of keratinized tissue (KTw), probing depth (PD), clinical attachment level (CAL), clinician rating of color and texture compared with surrounding tissues, and patient esthetic satisfaction. Seventeen patients were available for the 5-year recall. Mean RC between 6 months and 5 years changed from 89.5% to 77.6% for CMX + CAF test sites and 97.5% to 95.5% for CTG + CAF control sites. KTw averaged >3 mm for both test and control sites at 5 years. PD was equivalent at all time points. The 6-month to 5-year changes for RC, KTw, and PD were not significantly different between therapies. CAL change from 6 months to 5 years was greater for CTG + CAF (0.26 mm) than CMX + CAF (-0.21 mm). Tissue color match to surrounding tissues remained similar for both therapies throughout the study. There was a difference in tissue texture at both 6 months and 5 years, with CMX + CAF sites tending to be "equally firm" and CTG + CAF sites "more firm." Patient satisfaction was high, with no statistical difference in satisfaction between therapies at any time point. When balanced with patient-reported satisfaction, clinical rankings of esthetics, and control and historical RC results reported by other investigators, CMX + CAF appears to present a viable and long-term alternative to traditional CTG + CAF therapy.

Value of MR contrast media in image-guided body interventions.

PubMed

Saeed, Maythem; Wilson, Mark

2012-01-28

In the past few years, there have been multiple advances in magnetic resonance (MR) instrumentation, in vivo devices, real-time imaging sequences and interventional procedures with new therapies. More recently, interventionists have started to use minimally invasive image-guided procedures and local therapies, which reduce the pain from conventional surgery and increase drug effectiveness, respectively. Local therapy also reduces the systemic dose and eliminates the toxic side effects of some drugs to other organs. The success of MR-guided procedures depends on visualization of the targets in 3D and precise deployment of ablation catheters, local therapies and devices. MR contrast media provide a wealth of tissue contrast and allows 3D and 4D image acquisitions. After the development of fast imaging sequences, the clinical applications of MR contrast media have been substantially expanded to include pre- during- and post-interventions. Prior to intervention, MR contrast media have the potential to localize and delineate pathologic tissues of vital organs, such as the brain, heart, breast, kidney, prostate, liver and uterus. They also offer other options such as labeling therapeutic agents or cells. During intervention, these agents have the capability to map blood vessels and enhance the contrast between the endovascular guidewire/catheters/devices, blood and tissues as well as direct therapies to the target. Furthermore, labeling therapeutic agents or cells aids in visualizing their delivery sites and tracking their tissue distribution. After intervention, MR contrast media have been used for assessing the efficacy of ablation and therapies. It should be noted that most image-guided procedures are under preclinical research and development. It can be concluded that MR contrast media have great value in preclinical and some clinical interventional procedures. Future applications of MR contrast media in image-guided procedures depend on their safety, tolerability, tissue specificity and effectiveness in demonstrating success of the interventions and therapies.

Non-invasive assessment of negative pressure wound therapy using high frequency diagnostic ultrasound: oedema reduction and new tissue accumulation.

PubMed

Young, Stephen R; Hampton, Sylvie; Martin, Robin

2013-08-01

Tissue oedema plays an important role in the pathology of chronic and traumatic wounds. Negative pressure wound therapy (NPWT) is thought to contribute to active oedema reduction, yet few studies have showed this effect. In this study, high frequency diagnostic ultrasound at 20 MHz with an axial resolution of 60 µm was used to assess the effect of NPWT at - 80 mmHg on pressure ulcers and the surrounding tissue. Wounds were monitored in four patients over a 3-month period during which changes in oedema and wound bed thickness (granulation tissue) were measured non-invasively. The results showed a rapid reduction of periwound tissue oedema in all patients with levels falling by a mean of 43% after 4 days of therapy. A 20% increase in the thickness of the wound bed was observed after 7 days due to new granulation tissue formation. Ultrasound scans through the in situ gauze NPWT filler also revealed the existence of macrodeformation in the tissue produced by the negative pressure. These preliminary studies suggest that non-invasive assessment using high frequency diagnostic ultrasound could be a valuable tool in clinical studies of NPWT. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Method for microbeam radiation therapy

DOEpatents

Slatkin, Daniel N.; Dilmanian, F. Avraham; Spanne, Per O.

1994-01-01

A method of performing radiation therapy on a patient, involving exposing a target, usually a tumor, to a therapeutic dose of high energy electromagnetic radiation, preferably X-ray radiation, in the form of at least two non-overlapping microbeams of radiation, each microbeam having a width of less than about 1 millimeter. Target tissue exposed to the microbeams receives a radiation dose during the exposure that exceeds the maximum dose that such tissue can survive. Non-target tissue between the microbeams receives a dose of radiation below the threshold amount of radiation that can be survived by the tissue, and thereby permits the non-target tissue to regenerate. The microbeams may be directed at the target from one direction, or from more than one direction in which case the microbeams overlap within the target tissue enhancing the lethal effect of the irradiation while sparing the surrounding healthy tissue.

Method for microbeam radiation therapy

DOEpatents

Slatkin, D.N.; Dilmanian, F.A.; Spanne, P.O.

1994-08-16

A method is disclosed of performing radiation therapy on a patient, involving exposing a target, usually a tumor, to a therapeutic dose of high energy electromagnetic radiation, preferably X-ray radiation. The dose is in the form of at least two non-overlapping microbeams of radiation, each microbeam having a width of less than about 1 millimeter. Target tissue exposed to the microbeams receives a radiation dose during the exposure that exceeds the maximum dose that such tissue can survive. Non-target tissue between the microbeams receives a dose of radiation below the threshold amount of radiation that can be survived by the tissue, and thereby permits the non-target tissue to regenerate. The microbeams may be directed at the target from one direction, or from more than one direction in which case the microbeams overlap within the target tissue enhancing the lethal effect of the irradiation while sparing the surrounding healthy tissue. No Drawings

Tissue engineering in urothelium regeneration.

PubMed

Vaegler, Martin; Maurer, Sabine; Toomey, Patricia; Amend, Bastian; Sievert, Karl-Dietrich

2015-03-01

The development of therapeutic treatments to regenerate urothelium, manufacture tissue equivalents or neourethras for in-vivo application is a significant challenge in the field of tissue engineering. Many studies have focused on urethral defects that, in most cases, inadequately address current therapies. This article reviews the primary tissue engineering strategies aimed at the clinical requirements for urothelium regeneration while concentrating on promising investigations in the use of grafts, cellular preparations, as well as seeded or unseeded natural and synthetic materials. Despite significant progress being made in the development of scaffolds and matrices, buccal mucosa transplants have not been replaced. Recently, graft tissues appear to have an advantage over the use of matrices. These therapies depend on cell isolation and propagation in vitro that require, not only substantial laboratory resources, but also subsequent surgical implant procedures. The choice of the correct cell source is crucial when determining an in-vivo application because of the risks of tissue changes and abnormalities that may result in donor site morbidity. Addressing an appropriately-designed animal model and relevant regulatory issues is of fundamental importance for the principal investigators when a therapy using cellular components has been developed for clinical use. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical application of cell, gene and tissue therapies in Spain.

PubMed

Gálvez-Martín, P; Ruiz, A; Clares, B

2018-05-01

Scientific and technical advances in the areas of biomedicine and regenerative medicine have enabled the development of new treatments known as "advanced therapies", which encompass cell therapy, genetics and tissue engineering. The biologic products that can be manufactured from these elements are classified from the standpoint of the Spanish Agency of Medication and Health Products in advanced drug therapies, blood products and transplants. This review seeks to provide scientific and administrative information for clinicians on the use of these biologic resources. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Manual therapy for plantar heel pain.

PubMed

Pollack, Yosefa; Shashua, Anat; Kalichman, Leonid

2018-03-01

Manual therapy employed in the treatment of plantar heel pain includes joint or soft tissue mobilizations. Efficacy of these methods is still under debate. To determine whether manual therapy, consisting of deep massage, myofascial release or joint mobilization is effective in treating plantar heel pain. A critical review of all available studies with an emphasis on randomized controlled trials (RCTs) was performed. PubMed, PEDro, and Google Scholar databases were searched for keywords relating to plantar heel pain, joint, and soft tissue mobilizations. There were no search limitations or language restrictions. The reference lists of all retrieved articles were searched. The PEDro score was used to assess the quality of the reviewed papers. A total of six relevant RCTs were found: two examined the effectiveness of joint mobilization on plantar heel pain and four the effectiveness of soft tissue techniques. Five studies showed a positive short-term effect after manual therapy treatment, mostly soft tissue mobilizations, with or without stretching exercises for patients with plantar heel pain, compared to other treatments. One study observed that adding joint mobilization to the treatment of plantar heel pain was not effective. The quality of all studies was moderate to high. According to reviewed moderate and high-quality RCTs, soft tissue mobilization is an effective modality for treating plantar heel pain. Outcomes of joint mobilizations are controversial. Further studies are needed to evaluate the short and long-term effect of different soft tissue mobilization techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Emerging Roles for Extracellular Vesicles in Tissue Engineering and Regenerative Medicine

PubMed Central

Lamichhane, Tek N.; Sokic, Sonja; Schardt, John S.; Raiker, Rahul S.; Lin, Jennifer W.

2015-01-01

Extracellular vesicles (EVs)—comprising a heterogeneous population of cell-derived lipid vesicles including exosomes, microvesicles, and others—have recently emerged as both mediators of intercellular information transfer in numerous biological systems and vehicles for drug delivery. In both roles, EVs have immense potential to impact tissue engineering and regenerative medicine applications. For example, the therapeutic effects of several progenitor and stem cell-based therapies have been attributed primarily to EVs secreted by these cells, and EVs have been recently reported to play direct roles in injury-induced tissue regeneration processes in multiple physiological systems. In addition, EVs have been utilized for targeted drug delivery in regenerative applications and possess unique potential to be harnessed as patient-derived drug delivery vehicles for personalized medicine. This review discusses EVs in the context of tissue repair and regeneration, including their utilization as drug carriers and their crucial role in cell-based therapies. Furthermore, the article highlights the growing need for bioengineers to understand, consider, and ultimately design and specifically control the activity of EVs to maximize the efficacy of tissue engineering and regenerative therapies. PMID:24957510

Deep tissue massage: What are we talking about?

PubMed

Koren, Yogev; Kalichman, Leonid

2018-04-01

Massage is a common treatment in complementary and integrative medicine. Deep tissue massage, a form of therapeutic massage, has become more and more popular in recent years. Hence, the use of massage generally and deep tissue massage specifically, should be evaluated as any other modality of therapy to establish its efficacy and safety. To determine the definitions used for deep tissue massage in the scientific literature and to review the current scientific evidence for its efficacy and safety. Narrative review. There is no commonly accepted definition of deep tissue massage in the literature. The definition most frequently used is the intention of the therapist. We suggest separating the definitions of deep massage and deep tissue massage as follows: deep massage should be used to describe the intention of the therapist to treat deep tissue by using any form of massage and deep tissue massage should be used to describe a specific and independent method of massage therapy, utilizing the specific set of principles and techniques as defined by Riggs: "The understanding of the layers of the body, and the ability to work with tissue in these layers to relax, lengthen, and release holding patterns in the most effective and energy efficient way possible within the client's parameters of comfort". Heterogeneity of techniques and protocols used in published studies have made it difficult to draw any clear conclusions. Favorable outcomes may result from deep tissue massage in pain populations and patients with decreased range of motion. In addition, several rare serious adverse events were found related to deep tissue massage, probably as a result of the forceful application of massage therapy. Future research of deep tissue massage should be based on a common definition, classification system and the use of common comparators as controls. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypoxia as a target for tissue specific gene therapy.

PubMed

Rhim, Taiyoun; Lee, Dong Yun; Lee, Minhyung

2013-12-10

Hypoxia is a hallmark of various ischemic diseases such as ischemic heart disease, ischemic limb, ischemic stroke, and solid tumors. Gene therapies for these diseases have been developed with various therapeutic genes including growth factors, anti-apoptotic genes, and toxins. However, non-specific expression of these therapeutic genes may induce dangerous side effects in the normal tissues. To avoid the side effects, gene expression should be tightly regulated in an oxygen concentration dependent manner. The hypoxia inducible promoters and enhancers have been evaluated as a transcriptional regulation tool for hypoxia inducible gene therapy. The hypoxia inducible UTRs were also used in gene therapy for spinal cord injury as a translational regulation strategy. In addition to transcriptional and translational regulations, post-translational regulation strategies have been developed using the HIF-1α ODD domain. Hypoxia inducible transcriptional, translational, and post-translational regulations are useful for tissue specific gene therapy of ischemic diseases. In this review, hypoxia inducible gene expression systems are discussed and their applications are introduced. Copyright © 2013 Elsevier B.V. All rights reserved.

Absence of Rapid Propagation through the Purkinje Network as a Potential Cause of Line Block in the Human Heart with Left Bundle Branch Block.

PubMed

Okada, Jun-Ichi; Washio, Takumi; Nakagawa, Machiko; Watanabe, Masahiro; Kadooka, Yoshimasa; Kariya, Taro; Yamashita, Hiroshi; Yamada, Yoko; Momomura, Shin-Ichi; Nagai, Ryozo; Hisada, Toshiaki; Sugiura, Seiryo

2018-01-01

Background: Cardiac resynchronization therapy is an effective device therapy for heart failure patients with conduction block. However, a problem with this invasive technique is the nearly 30% of non-responders. A number of studies have reported a functional line of block of cardiac excitation propagation in responders. However, this can only be detected using non-contact endocardial mapping. Further, although the line of block is considered a sign of responders to therapy, the mechanism remains unclear. Methods: Herein, we created two patient-specific heart models with conduction block and simulated the propagation of excitation based on a cellmodel of electrophysiology. In one model with a relatively narrow QRS width (176 ms), we modeled the Purkinje network using a thin endocardial layer with rapid conduction. To reproduce a wider QRS complex (200 ms) in the second model, we eliminated the Purkinje network, and we simulated the endocardial mapping by solving the inverse problem according to the actual mapping system. Results: We successfully observed the line of block using non-contact mapping in the model without the rapid propagation of excitation through the Purkinje network, although the excitation in the wall propagated smoothly. This model of slow conduction also reproduced the characteristic properties of the line of block, including dense isochronal lines and fractionated local electrocardiograms. Further, simulation of ventricular pacing from the lateral wall shifted the location of the line of block. By contrast, in the model with the Purkinje network, propagation of excitation in the endocardial map faithfully followed the actual propagation in the wall, without showing the line of block. Finally, switching the mode of propagation between the two models completely reversed these findings. Conclusions: Our simulation data suggest that the absence of rapid propagation of excitation through the Purkinje network is the major cause of the functional line of block recorded by non-contact endocardial mapping. The line of block can be used to identify responders as these patients loose rapid propagation through the Purkinje network.

Position paper for management of elderly patients with pacemakers and implantable cardiac defibrillators Groupe de rythmologie et stimulation cardiaque de la Société française de cardiologie et Société française de gériatrie et gérontologie.

PubMed

Fauchier, Laurent; Alonso, Christine; Anselme, Frédéric; Blangy, Hugues; Bordachar, Pierre; Boveda, Serge; Clementy, Nicolas; Defaye, Pascal; Deharo, Jean-Claude; Friocourt, Patrick; Gras, Daniel; Halimi, Franck; Klug, Didier; Mansourati, Jacques; Obadia, Benjamin; Pasquié, Jean-Luc; Pavin, Dominique; Sadoul, Nicolas; Taieb, Jérôme; Piot, Olivier; Hanon, Olivier

2016-09-01

Despite the increasingly high rate of implantation of pacemakers (PM) and cardioverter-defibrillators (ICD) in elderly patients, data supporting their clinical and cost-effectiveness in this age stratum are ambiguous and contradictory. We reviewed the data regarding the applicability, safety, and effectiveness of the conventional pacing, ICD and cardiac resynchronization therapy (CRT) in elderly patients. Although peri-procedural risk may be slightly higher in the elderly, the procedure of implantation of PMs and ICDs is still relatively safe in this age group. In older patients with sinus node disease, a general consensus is that dual chamber pacing, along with the programming of an algorithm to minimise ventricular pacing is preferred. In very old patients presenting with intermittent or suspected AV block, VVI pacing may be appropriate. In terms of correcting potentially life-threatening arrhythmias, the effectiveness of ICD therapy is comparable in older and younger individuals. However, the assumption of persistent ICD benefit in the elderly population is questionable, as any advantage of the device on arrhythmic death may be attenuated by a higher total non-arrhythmic mortality. While septuagenarians and octogenarians have higher annual all-cause mortality rates, ICD therapy may remain effective in selected patients at high risk of arrhythmic death and with minimum comorbidities despite advanced age. ICD implantation among the elderly, as a group, may not be cost-effective, but the procedure may reach cost-effectiveness in those expected to live >5-7 years after implantation. The elderly patients usually experience a significant functional improvement after CRT, similar to that observed in middle-aged patients. Management of CRT non responders remains globally the same, while considering a less aggressive approach in terms of re interventions (revision of LV lead placement, addition of a RV or LV lead, LV endocardial pacing configuration). Overall, age, comorbidities and comprehensive geriatric assessment should be the decisive factor in making a decision on device implantation selection for survival and well-being benefit in elderly patients.

"Real life" longevity of implantable cardioverter-defibrillator devices.

PubMed

Manolis, Antonis S; Maounis, Themistoklis; Koulouris, Spyridon; Vassilikos, Vassilios

2017-09-01

Manufacturers of implantable cardioverter-defibrillators (ICDs) promise a 5- to 9-year projected longevity; however, real-life data indicate otherwise. The aim of the present study was to assess ICD longevity among 685 consecutive patients over the last 20 years. Real-life longevity of ICDs may differ from that stated by the manufacturers. The study included 601 men and 84 women (mean age, 63.1 ± 13.3 years). The underlying disease was coronary (n = 396) or valvular (n = 15) disease, cardiomyopathy (n = 220), or electrical disease (n = 54). The mean ejection fraction was 35%. Devices were implanted for secondary (n = 562) or primary (n = 123) prevention. Single- (n = 292) or dual-chamber (n = 269) or cardiac resynchronization therapy (CRT) devices (n = 124) were implanted in the abdomen (n = 17) or chest (n = 668). Over 20 years, ICD pulse generator replacements were performed in 238 patients (209 men; age 63.7 ± 13.9 years; ejection fraction, 37.7% ± 14.0%) who had an ICD for secondary (n = 210) or primary (n = 28) prevention. The mean ICD longevity was 58.3 ± 18.7 months. In 20 (8.4%) patients, devices exhibited premature battery depletion within 36 months. Most (94%) patients had none, minor, or modest use of ICD therapy. Longevity was longest for single-chamber devices and shortest for CRT devices. Latest-generation devices replaced over the second decade lasted longer compared with devices replaced during the first decade. When analyzed by manufacturer, Medtronic devices appeared to have longer longevity by 13 to 18 months. ICDs continue to have limited longevity of 4.9 ± 1.6 years, and 8% demonstrate premature battery depletion by 3 years. CRT devices have the shortest longevity (mean, 3.8 years) by 13 to 17 months, compared with other ICD devices. These findings have important implications, particularly in view of the high expense involved with this type of electrical therapy. © 2017 Wiley Periodicals, Inc.

Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy

PubMed Central

Peterson, Christopher W.; Wang, Jianbin; Deleage, Claire; Reddy, Sowmya; Kaur, Jasbir; Polacino, Patricia; Reik, Andreas; Huang, Meei-Li; Holmes, Michael C.; Estes, Jacob D.

2018-01-01

Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents. PMID:29672640

Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis

PubMed Central

Darlington, Peter J; Boivin, Marie-Noëlle; Bar-Or, Amit

2011-01-01

Phase I clinical trials exploring the use of autologous mesenchymal stem cell (MSC) therapy for the treatment of multiple sclerosis (MS) have begun in a number of centers across the world. MS is a complex and chronic immune-mediated and neurodegenerative disease influenced by genetic susceptibility and environmental risk factors. The ideal treatment for MS would involve both attenuation of detrimental inflammatory responses, and induction of a degree of tissue protection/regeneration within the CNS. Preclinical studies have demonstrated that both human-derived and murine-derived MSCs are able to improve outcomes in the animal model of MS, experimental autoimmune encephalomyelitis. How MSCs ameliorate experimental autoimmune encephalomyelitis is being intensely investigated. One of the major mechanisms of action of MSC therapy is to inhibit various components of the immune system that contribute to tissue destruction. Emerging evidence now supports the idea that MSCs can access the CNS where they can provide protection against tissue damage, and may facilitate tissue regeneration through the production of growth factors. The prospect of cell-based therapy using MSCs has several advantages, including the relative ease with which they can be extracted from autologous bone marrow or adipose tissue and expanded in vitro to reach the purity and numbers required for transplantation, and the fact that MSC therapy has already been used in other human disease settings, such as graft-versus-host and cardiac disease, with initial reports indicating a good safety profile. This article will focus on the theoretical and practical issues relevant to considerations of MSC therapy in the context of MS. PMID:21864075

Tissue engineering therapies for the vocal fold lamina propria.

PubMed

Kutty, Jaishankar K; Webb, Ken

2009-09-01

The vocal folds are laryngeal connective tissues with complex matrix composition/organization that provide the viscoelastic mechanical properties required for voice production. Vocal fold injury results in alterations in tissue structure and corresponding changes in tissue biomechanics that reduce vocal quality. Recent work has begun to elucidate the biochemical changes underlying injury-induced pathology and to apply tissue engineering principles to the prevention and reversal of vocal fold scarring. Based on the extensive history of injectable biomaterials in laryngeal surgery, a major focus of regenerative therapies has been the development of novel scaffolds with controlled in vivo residence time and viscoelastic properties approximating the native tissue. Additional strategies have included cell transplantation and delivery of the antifibrotic cytokine hepatocyte growth factor, as well as investigation of the effects of the unique vocal fold vibratory microenvironment using in vitro dynamic culture systems. Recent achievements of significant reductions in fibrosis and improved recovery of native tissue viscoelasticity and vibratory/functional performance in animal models are rapidly moving vocal fold tissue engineering toward clinical application.

Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

DTIC Science & Technology

2012-02-01

10-1-0927 TITLE: Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation...immunosuppression. Bone Marrow Derived Mesenchymal stem cells (BM-MSCs) are pluripotent cells, capable of differentiation along multiple mesenchymal lineages into...As part of implemented transition from University of Pittsburgh to Johns Hopkins University, we optimized our mesenchymal stem cell (MSC) isolation

Processing ultrasound backscatter to monitor high-intensity focused ultrasound (HIFU) therapy

NASA Astrophysics Data System (ADS)

Kaczkowski, Peter J.; Anand, Ajay; Bailey, Michael R.

2005-09-01

The development of new noninvasive surgical methods such as HIFU for the treatment of cancer and internal bleeding requires simultaneous development of new sensing approaches to guide, monitor, and assess the therapy. Ultrasound imaging using echo amplitude has long been used to map tissue morphology for diagnostic interpretation by the clinician. New quantitative ultrasonic methods that rely on amplitude and phase processing for tissue characterization are being developed for monitoring of ablative therapy. We have been developing the use of full wave ultrasound backscattering for real-time temperature estimation, and to image changes in tissue backscatter spectrum as therapy progresses. Both approaches rely on differential processing of the backscatter signal in time, and precise measurement of phase differences. Noise and artifacts from motion and nonstationary speckle statistics are addressed by constraining inversions for tissue parameters with physical models. We present results of HIFU experiments with static point and scanned HIFU exposures in which temperature rise can be accurately mapped using a new heat transfer equation (HTE) model-constrained inverse approach. We also present results of a recently developed spectral imaging method that elucidates microbubble-mediated nonlinearity not visible as a change in backscatter amplitude. [Work supported by Army MRMC.

Accurate tumor localization and tracking in radiation therapy using wireless body sensor networks.

PubMed

Pourhomayoun, Mohammad; Jin, Zhanpeng; Fowler, Mark

2014-07-01

Radiation therapy is an effective method to combat cancerous tumors by killing the malignant cells or controlling their growth. Knowing the exact position of the tumor is a very critical prerequisite in radiation therapy. Since the position of the tumor changes during the process of radiation therapy due to the patient׳s movements and respiration, a real-time tumor tracking method is highly desirable in order to deliver a sufficient dose of radiation to the tumor region without damaging the surrounding healthy tissues. In this paper, we develop a novel tumor positioning method based on spatial sparsity. We estimate the position by processing the received signals from only one implantable RF transmitter. The proposed method uses less number of sensors compared to common magnetic transponder based approaches. The performance of the proposed method is evaluated in two different cases: (1) when the tissue configuration is perfectly determined (acquired beforehand by MRI or CT) and (2) when there are some uncertainties about the tissue boundaries. The results demonstrate the high accuracy and performance of the proposed method, even when the tissue boundaries are imperfectly known. Copyright © 2014 Elsevier Ltd. All rights reserved.

Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis.

PubMed

Sroussi, Herve Y; Epstein, Joel B; Bensadoun, Rene-Jean; Saunders, Deborah P; Lalla, Rajesh V; Migliorati, Cesar A; Heaivilin, Natalie; Zumsteg, Zachary S

2017-12-01

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chromophore absorbance change quantification in tissue during low-level light therapy

NASA Astrophysics Data System (ADS)

Huynh, Daniel; Chung, Christine; Qian, Li; Lilge, Lothar

2012-03-01

Low Level Light Therapy (LLLT) has been implicated to stimulate tissue, promoting healing and reducing pain. One of the potential pathways stimulated by LLLT relates to the electron transport chain, where photon quantum energy can induce a change in the biochemical reactions within the cell. The aim of this study is to assess the feasibility to exploit light additionally as a diagnostic tool to determine tissue physiological states, particularly in quantifying the changes in redox states of Cytochrome C as a result of induced LLLT biochemical reactions.

Advances in Meniscal Tissue Engineering

PubMed Central

Longo, Umile Giuseppe; Loppini, Mattia; Forriol, Francisco; Romeo, Giovanni; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Meniscal tears are the most common knee injuries and have a poor ability of healing. In the last few decades, several techniques have been increasingly used to optimize meniscal healing. Current research efforts of tissue engineering try to combine cell-based therapy, growth factors, gene therapy, and reabsorbable scaffolds to promote healing of meniscal defects. Preliminary studies did not allow to draw definitive conclusions on the use of these techniques for routine management of meniscal lesions. We performed a review of the available literature on current techniques of tissue engineering for the management of meniscal tears. PMID:25098366

Mitigation of eddy current heating during magnetic nanoparticle hyperthermia therapy.

PubMed

Stigliano, Robert V; Shubitidze, Fridon; Petryk, James D; Shoshiashvili, Levan; Petryk, Alicia A; Hoopes, P Jack

2016-11-01

Magnetic nanoparticle hyperthermia therapy is a promising technology for cancer treatment, involving delivering magnetic nanoparticles (MNPs) into tumours then activating them using an alternating magnetic field (AMF). The system produces not only a magnetic field, but also an electric field which penetrates normal tissue and induces eddy currents, resulting in unwanted heating of normal tissues. Magnitude of the eddy current depends, in part, on the AMF source and the size of the tissue exposed to the field. The majority of in vivo MNP hyperthermia therapy studies have been performed in small animals, which, due to the spatial distribution of the AMF relative to the size of the animals, do not reveal the potential toxicity of eddy current heating in larger tissues. This has posed a non-trivial challenge for researchers attempting to scale up to clinically relevant volumes of tissue. There is a relative dearth of studies focused on decreasing the maximum temperature resulting from eddy current heating to increase therapeutic ratio. This paper presents two simple, clinically applicable techniques for decreasing maximum temperature induced by eddy currents. Computational and experimental results are presented to understand the underlying physics of eddy currents induced in conducting, biological tissues and leverage these insights to mitigate eddy current heating during MNP hyperthermia therapy. Phantom studies show that the displacement and motion techniques reduce maximum temperature due to eddy currents by 74% and 19% in simulation, and by 77% and 33% experimentally. Further study is required to optimise these methods for particular scenarios; however, these results suggest larger volumes of tissue could be treated, and/or higher field strengths and frequencies could be used to attain increased MNP heating when these eddy current mitigation techniques are employed.

An end-to-end assessment of range uncertainty in proton therapy using animal tissues.

PubMed

Zheng, Yuanshui; Kang, Yixiu; Zeidan, Omar; Schreuder, Niek

2016-11-21

Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues. Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences. The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively. Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams' superior dose advantage over conventional photon-based radiation therapy.

Design of optimal hyperthermia protocols for prostate cancer by controlling HSP expression through computer modeling (Invited Paper)

NASA Astrophysics Data System (ADS)

Rylander, Marissa N.; Feng, Yusheng; Diller, Kenneth; Bass, J.

2005-04-01

Heat shock proteins (HSP) are critical components of a complex defense mechanism essential for preserving cell survival under adverse environmental conditions. It is inevitable that hyperthermia will enhance tumor tissue viability, due to HSP expression in regions where temperatures are insufficient to coagulate proteins, and would likely increase the probability of cancer recurrence. Although hyperthermia therapy is commonly used in conjunction with radiotherapy, chemotherapy, and gene therapy to increase therapeutic effectiveness, the efficacy of these therapies can be substantially hindered due to HSP expression when hyperthermia is applied prior to these procedures. Therefore, in planning hyperthermia protocols, prediction of the HSP response of the tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of overall tissue response. In this paper, we present a highly accurate, adaptive, finite element tumor model capable of predicting the HSP expression distribution and tissue damage region based on measured cellular data when hyperthermia protocols are specified. Cubic spline representations of HSP27 and HSP70, and Arrhenius damage models were integrated into the finite element model to enable prediction of the HSP expression and damage distribution in the tissue following laser heating. Application of the model can enable optimized treatment planning by controlling of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

Flexible polymer waveguides for light-activated therapy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kim, Moonseok; Kwok, Sheldon J. J.; Lin, Harvey H.; Lee, Dong Hee; Yun, Seok Hyun

2017-02-01

Conventional light-activated therapies, such as photodynamic therapy (PDT), photochemical tissue bonding (PTB), collagen crosslinking (CXL), low-level light therapy (LLLT), and antimicrobial therapy utilize external light sources and light propagation through free space, limiting treatment to accessible and superficial areas of the body. Recent progress has been made in developing biocompatible polymer waveguides to enhance light delivery to deep tissues. To further expand clinical utility, waveguides should be flexible and tough enough to enable use in anatomically difficult-to-reach regions, while having the requisite optical properties to achieve uniform and efficient illumination of the target area. Here, we present a new class of flexible polymer waveguides optimized for uniform light extraction into tissues. Our slab waveguides comprise two designs: first, a flexible polydimethylsiloxane (PDMS) based elastomer for CXL, and second, a tough polyacrylamide and alginate hydrogel for large-area phototherapies. Our waveguides are optically transparent in the visible wavelengths (400-750 nm) and a multimode fiber is used to couple light into the waveguide. We characterized the light propagation through the waveguides and light extraction into tissue, and validated our results with optical simulation. By changing the thickness and scattering properties, uniform light extraction through the length of the waveguide could be achieved. We demonstrate proof-of-concept scleral photo-crosslinking of an ex vivo porcine eyeball for prevention of myopia.

Atmospheric Pressure Photoionization Tandem Mass Spectrometry of Androgens in Prostate Cancer

PubMed Central

Lih, Fred Bjørn; Titus, Mark A.; Mohler, James L.; Tomer, Kenneth B.

2010-01-01

Androgen deprivation therapy is the most common treatment option for advanced prostate cancer. Almost all prostate cancers recur during androgen deprivation therapy, and new evidence suggests that androgen receptor activation persists despite castrate levels of circulating androgens. Quantitation of tissue levels of androgens is critical to understanding the mechanism of recurrence of prostate cancer during androgen deprivation therapy. A liquid chromatography atmospheric pressure photoionization tandem mass spectrometric method was developed for quantitation of tissue levels of androgens. Quantitation of the saturated keto-steroids dihydrotestosterone and 5-α-androstanedione required detection of a novel parent ion, [M + 15]+. The nature of this parent ion was explored and the method applied to prostate tissue and cell culture with comparison to results achieved using electrospray ionization. PMID:20560527

Progress on materials and scaffold fabrications applied to esophageal tissue engineering.

PubMed

Shen, Qiuxiang; Shi, Peina; Gao, Mongna; Yu, Xuechan; Liu, Yuxin; Luo, Ling; Zhu, Yabin

2013-05-01

The mortality rate from esophageal disease like atresia, carcinoma, tracheoesophageal fistula, etc. is increasing rapidly all over the world. Traditional therapies such as surgery, radiotherapy or chemotherapy have been met with very limited success resulting in reduced survival rate and quality of patients' life. Tissue-engineered esophagus, a novel substitute possessing structure and function similar to native tissue, is believed to be an effective therapy and a promising replacement in the future. However, research on esophageal tissue engineering is still at an early stage. Considerable research has been focused on developing ideal scaffolds with optimal materials and methods of fabrication. This article gives a review of materials and scaffold fabrications currently applied in esophageal tissue engineering research. Copyright © 2013 Elsevier B.V. All rights reserved.

Shedding Light on Nanomedicine

PubMed Central

Tong, Rong

2012-01-01

Light is electromagnetic radiation that can convert its energy into different forms (e.g., heat, chemical energy, and acoustic waves). This property has been exploited in phototherapy (e.g., photothermal therapy and photodynamic therapy) and optical imaging (e.g., fluorescence imaging) for therapeutic and diagnostic purposes. Light-controlled therapies can provide minimally or non-invasive spatiotemporal control as well as deep tissue penetration. Nanotechnology provides a numerous advantages, including selective targeting of tissues, prolongation of therapeutic effect, protection of active payloads, and improved therapeutic indices. This review explores the advances that nanotechnology can bring to light-based therapies and diagnostics, and vice versa, including photo-triggered systems, nanoparticles containing photoactive molecules, and nanoparticles that are themselves photoactive. Limitations of light-based therapies such as photic injury and phototoxicity will be discussed. PMID:22887840

Subsurface thermal behaviour of tissue mimics embedded with large blood vessels during plasmonic photo-thermal therapy.

PubMed

Paul, Anup; Narasimhan, Arunn; Das, Sarit K; Sengupta, Soujit; Pradeep, Thalappil

2016-11-01

The purpose of this study was to understand the subsurface thermal behaviour of a tissue phantom embedded with large blood vessels (LBVs) when exposed to near-infrared (NIR) radiation. The effect of the addition of nanoparticles to irradiated tissue on the thermal sink behaviour of LBVs was also studied. Experiments were performed on a tissue phantom embedded with a simulated blood vessel of 2.2 mm outer diameter (OD)/1.6 mm inner diameter (ID) with a blood flow rate of 10 mL/min. Type I collagen from bovine tendon and agar gel were used as tissue. Two different nanoparticles, gold mesoflowers (AuMS) and graphene nanostructures, were synthesised and characterised. Energy equations incorporating a laser source term based on multiple scattering theories were solved using finite element-based commercial software. The rise in temperature upon NIR irradiation was seen to vary according to the position of the blood vessel and presence of nanoparticles. While the maximum rise in temperature was about 10 °C for bare tissue, it was 19 °C for tissue embedded with gold nanostructures and 38 °C for graphene-embedded tissues. The axial temperature distribution predicted by computational simulation matched the experimental observations. A different subsurface temperature distribution has been obtained for different tissue vascular network models. The position of LBVs must be known in order to achieve optimal tissue necrosis. The simulation described here helps in predicting subsurface temperature distributions within tissues during plasmonic photo-thermal therapy so that the risks of damage and complications associated with in vivo experiments and therapy may be avoided.

Advanced therapies for the treatment of hemophilia: future perspectives.

PubMed

Liras, Antonio; Segovia, Cristina; Gabán, Aline S

2012-12-13

Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering). For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors) and cell therapy (by means of several types of target cells). Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells) in order to restore alterations in coagulation factor expression.

Regenerative periodontal therapy in mucogingival surgery for root coverage.

PubMed

Abitbol, T; Santi, E; Urbani, G

1997-02-01

This article illustrates the potential benefits of regenerative periodontal therapy in mucogingival surgery and esthetic dental treatment. Cases are described in which the treatment of soft-tissue recessions and root exposures are treated with surgical procedures where both clinical soft-tissue augmentation and the regeneration of periodontal attachment are obtained. Cases are also presented to illustrate the clinical application of guided tissue regeneration. Resorbable and nonresorbable barriers are placed over the root surface and bone and covered by the overlying flap, which allows the selective repopulation of the lesion by progenitor cells and the inhibition of a long junctional epithelium. Emphasis is placed on regenerative procedures in soft-tissue augmentation, particularly with respect to rationales, techniques, and indications.

Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: magnifying endoscopy findings.

PubMed

Law, T T; Tong, Daniel; Wong, Sam W H; Chan, S Y; Law, Simon

2015-04-01

Gastric mucosa-associated lymphoid tissue lymphoma is uncommon and most patients have an indolent clinical course. The clinical presentation and endoscopic findings can be subtle and diagnosis can be missed on white light endoscopy. Magnifying endoscopy may help identify the abnormal microstructural and microvascular patterns, and target biopsies can be performed. We describe herein the case of a 64-year-old woman with Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma diagnosed by screening magnification endoscopy. Helicobacter pylori-eradication therapy was given and she received biological therapy. She is in clinical remission after treatment. The use of magnification endoscopy in gastric mucosa-associated lymphoid tissue lymphoma and its management are reviewed.

Clinical Translation of Cell Therapy, Tissue Engineering, and Regenerative Medicine Product in Malaysia and Its Regulatory Policy.

PubMed

Bt Hj Idrus, Ruszymah; Abas, Arpah; Ab Rahim, Fazillahnor; Saim, Aminuddin Bin

2015-12-01

With the worldwide growth of cell and tissue therapy (CTT) in treating diseases, the need of a standardized regulatory policy is of paramount concern. Research in CTT in Malaysia has reached stages of clinical trials and commercialization. In Malaysia, the regulation of CTT is under the purview of the National Pharmaceutical Control Bureau (NPCB), Ministry of Health (MOH). NPCB is given the task of regulating CTT, under a new Cell and Gene Therapy Products framework, and the guidelines are currently being formulated. Apart from the laboratory accreditation, researchers are advised to follow Guidelines for Stem Cell Research and Therapy from the Medical Development Division, MOH, published in 2009.

Clinical Translation of Cell Therapy, Tissue Engineering, and Regenerative Medicine Product in Malaysia and Its Regulatory Policy

PubMed Central

Abas, Arpah; Ab Rahim, Fazillahnor; Saim, Aminuddin Bin

2015-01-01

With the worldwide growth of cell and tissue therapy (CTT) in treating diseases, the need of a standardized regulatory policy is of paramount concern. Research in CTT in Malaysia has reached stages of clinical trials and commercialization. In Malaysia, the regulation of CTT is under the purview of the National Pharmaceutical Control Bureau (NPCB), Ministry of Health (MOH). NPCB is given the task of regulating CTT, under a new Cell and Gene Therapy Products framework, and the guidelines are currently being formulated. Apart from the laboratory accreditation, researchers are advised to follow Guidelines for Stem Cell Research and Therapy from the Medical Development Division, MOH, published in 2009. PMID:26192075

Engineering organs.

PubMed

Atala, Anthony

2009-10-01

Applications of regenerative medicine technology may offer novel therapies for patients with injuries, end-stage organ failure, or other clinical problems. Currently, patients suffering from diseased and injured organs can be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly as the population ages and new cases of organ failure increase. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The stem cell field is also advancing rapidly, opening new avenues for this type of therapy. For example, therapeutic cloning and cellular reprogramming may one day provide a potentially limitless source of cells for tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors have already entered the clinical setting successfully, indicating the promise regenerative medicine holds for the future.

Using Acellular Bioactive Extracellular Matrix Scaffolds to Enhance Endogenous Cardiac Repair

PubMed Central

Svystonyuk, Daniyil A.; Mewhort, Holly E. M.; Fedak, Paul W. M.

2018-01-01

An inability to recover lost cardiac muscle following acute ischemic injury remains the biggest shortcoming of current therapies to prevent heart failure. As compared to standard medical and surgical treatments, tissue engineering strategies offer the promise of improved heart function by inducing regeneration of functional heart muscle. Tissue engineering approaches that use stem cells and genetic manipulation have shown promise in preclinical studies but have also been challenged by numerous critical barriers preventing effective clinical translational. We believe that surgical intervention using acellular bioactive ECM scaffolds may yield similar therapeutic benefits with minimal translational hurdles. In this review, we outline the limitations of cellular-based tissue engineering strategies and the advantages of using acellular biomaterials with bioinductive properties. We highlight key anatomic targets enriched with cellular niches that can be uniquely activated using bioactive scaffold therapy. Finally, we review the evolving cardiovascular tissue engineering landscape and provide critical insights into the potential therapeutic benefits of acellular scaffold therapy. PMID:29696148

Chelation of Thallium (III) in Rats Using Combined Deferasirox and Deferiprone Therapy.

PubMed

Salehi, Samie; Saljooghi, Amir Sh; Badiee, Somayeh; Moqadam, Mojtaba Mashmool

2017-10-01

Thallium and its compounds are a class of highly toxic chemicals that cause wide-ranging symptoms such as gastrointestinal disturbances; polyneuritis; encephalopathy; tachycardia; skin eruptions; hepatic, renal, cardiac, and neurological toxicities; and have mutagenic and genotoxic effects. The present research aimed to evaluate the efficacy of the chelating agents deferasirox (DFX) and deferiprone (L1) in reducing serum and tissue thallium levels after the administration of thallium (III), according to two different dosing regimens, to several groups of Wistar rats for 60 days. It was hypothesized that the two chelators might be more efficient as a combined therapy than as monotherapies in removing thallium (III) from the rats' organs. The chelators were administered orally as either single or combined therapies for a period of 14 days. Serum and tissue thallium (III) and iron concentrations were determined by flame atomic absorption spectroscopy. Serum and tissue thallium (III) levels were significantly reduced by combined therapy with DFX and L1. Additionally, iron concentrations returned to normal levels and symptoms of toxicity decreased.

Management of Facial Pyoderma Gangrenosum Using Platelet-Rich Fibrin: A Technical Report.

PubMed

Fortunato, Leonzio; Barone, Selene; Bennardo, Francesco; Giudice, Amerigo

2018-01-31

This report describes a case of local pyoderma gangrenosum that was treated with short-term immunosuppressive therapy and the topical application of platelet-rich fibrin (PRF). Medical treatment included oral corticosteroid therapy and topical treatment with PRF in solid and liquid form. This therapy initially led to the reduction of the ulcer's size and an improvement in symptoms, until the ulcer was completely healed after a few weeks. A relapse was treated with only the application of PRF to the affected tissue with excellent recovery. The efficacy of PRF as a guide for wound healing is a result of the continuous release of growth factors involved in tissue repair mechanisms. PRF has proved to be suitable for the management of facial pyoderma gangrenosum while allowing a reduction in systemic corticosteroid therapy. The ease of preparation, low cost, and outpatient use make PRF an optimal scaffold for tissue healing processes. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Boronated porhyrins and methods for their use

DOEpatents

Miura, Michiko; Shelnutt, John A.; Slatkin, Daniel N.

1999-03-02

The present invention covers boronated porphyrins containing multiple carborane cages which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies such as boron neutron capture therapy and photodynamic therapy.