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Sample records for acute cardiac death

  1. DJ-1 protects against cell death following acute cardiac ischemia–reperfusion injury

    PubMed Central

    Dongworth, R K; Mukherjee, U A; Hall, A R; Astin, R; Ong, S-B; Yao, Z; Dyson, A; Szabadkai, G; Davidson, S M; Yellon, D M; Hausenloy, D J

    2014-01-01

    Novel therapeutic targets are required to protect the heart against cell death from acute ischemia–reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia–reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1L166P and DJ-1Cys106A mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection. PMID:24577080

  2. Sudden Cardiac Death

    PubMed Central

    Weinberg, Marc

    1978-01-01

    Over the past decade, there has been a significant decrease in the hospital mortality of patients with coronary artery disease. However, sudden cardiac death, which accounts for the majority of deaths from coronary artery disease, hasbeen little affected. This report reviews the pathology, electrophysiology, demographics and clinical presentation of sudden cardiac death. Emergency care and possible preventative measures are examined. PMID:356435

  3. Sudden cardiac death after acute ST elevation myocardial infarction: insight from a developing country

    PubMed Central

    Rao, Hygriv B; Sastry, B K S; Korabathina, Radhika; Raju, Krishnam P

    2012-01-01

    Background There is no data concerning sudden cardiac death (SCD) following acute ST elevation myocardial infarction (STEMI) in India. We assessed the incidence and factors influencing SCD following STEMI. Methods Patients with STEMI admitted in our hospital from 2006 to 2009 were prospectively entered into a database. In the period 2010–2011, patients or their kin were periodically contacted and administered a questionnaire to ascertain their survival, and mode of death if applicable. Results Study population comprised of 929 patients with STEMI (mean age 55±17 years) having a mean follow-up of 41±16 months. The total number of deaths was 159, of which 78 were SCD (mean age 62.2±10 years). The cumulative incidence of total deaths and SCD at 1 month, 1, 2, 3 years and at conclusion of the study was 10.1%, 13.2%, 14.6%, 15.8%, 17.3% and 4.9%, 6.5%, 8.0%, 8.9% and 9.7%, respectively. The temporal distribution of SCD was 53.9% at first month, 19.2% at 1 month to 1 year, 15.4% in 1–2 years, 7.6% in 2–3 years and 3.8% beyond 3 years. Comparison between SCD and survivor cohorts by multivariate analysis showed five variables were found to be associated with SCD (age p=0.0163, female gender p=0.0042, severe LV dysfunction p=0.0292, absence of both reperfusion and revascularisation p=0.0373 and lack of compliance with medications p <0.0001). Conclusions SCD following STEMI accounts for about half of the total deaths. It involves younger population and most of these occur within the first month. This data has relevance in prioritising healthcare strategies in India. PMID:27326036

  4. Right ventricular dysfunction: an independent and incremental predictor of cardiac deaths late after acute myocardial infarction.

    PubMed

    Di Bella, Gianluca; Siciliano, Valeria; Aquaro, Giovanni D; De Marchi, Daniele; Rovai, Daniele; Carerj, Scipione; Molinaro, Sabrina; Lombardi, Massimo; Pingitore, Alessandro

    2015-02-01

    Prognostic implication of right ventricular dysfunction and infarction scar in the chronic phase of the myocardial infarction has been little analyzed. In 299 consecutive patients (age 63 ± 11 years) with >3 months old myocardial infarction, we quantified right and left ventricular volumes and ejection fractions by cine cardiac magnetic resonance, and right and left ventricular scar tissue by late gadolinium enhancement. During follow-up (median, 2.4 years) cardiac events (cardiac-related deaths or appropriate intra-cardiac defibrillator shocks) occurred in 21 patients. Right ventricular systolic dysfunction (ejection fraction lower the reference mean values-2 SD) was present in 67 patients (22 %), right ventricular late gadolinium enhancement was observed in 15 patients (5 %). After adjustment for left ventricular end-diastolic volume, wall motion score index, and global extent of late gadolinium enhancement, right ventricular dysfunction was an independent and incremental predictor of cardiac events (p = 0.0053), while right ventricular scar tissue extent was not. Right ventricular dysfunction is an independent and incremental predictor of cardiac events also in the chronic phase of the myocardial infarction. In these patients, right ventricular dysfunction does not necessarily mean right ventricular infarction scar, but likely reflects the effects of hemodynamic and biohumoral factors. PMID:25348657

  5. Sudden cardiac death.

    PubMed

    Sra, J; Dhala, A; Blanck, Z; Deshpande, S; Cooley, R; Akhtar, M

    1999-08-01

    SCD continues to be an important cause of death and morbidity. Despite expanding insight into the mechanisms causing SCD, the population at high risk is not being effectively identified. Although there is still much to do in the management phase of SCD (predicting the efficacy of various therapies), recent clinical trials have helped define the relative risks and benefits of therapies in preventing SCD. Trials are underway to determine whether treating other patient populations, including asymptomatic patients after MI, will improve survival rate. The approach to reducing mortality rate will always be multifaceted; primary prevention of coronary artery disease and prompt salvage of jeopardized myocardium are 2 important aspects of this approach. In addition to interventions for MI, such as myocardial revascularization when indicated, simple and easily administered therapies that are likely to remain the most effective prophylactic interventions are aspirin, ACE inhibitors, beta-blockers, and cholesterol-lowering agents. However, the MADIT and AVID data clearly demonstrate a role for ICD therapy in a subgroup of patients who have VT/VF and are at risk of cardiac arrest. Even though the absolute magnitude of benefit associated with ICDs is still to be determined, the AVID study and other recent reports provide convincing evidence that patients who have VT/VF fare better with ICDs than with antiarrhythmic drug therapy. For the high-risk population described in this article, in addition to aggressive anti-ischemic and heart failure therapy, ICDs are now a mainstay of life-saving treatment. Still to be surmounted is the challenge of identifying patients who have nonischemic substrates and of providing them with the appropriate therapy. Guided by genetic studies and new insight into the mechanisms of such problems as congenital long QT syndrome, life-saving and life-enhancing therapies may soon be available for the management of SCD. PMID:10459474

  6. Sudden Cardiac Death in Athletes.

    PubMed

    Wasfy, Meagan M; Hutter, Adolph M; Weiner, Rory B

    2016-01-01

    There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed. PMID:27486488

  7. Sudden Cardiac Death in Athletes

    PubMed Central

    Wasfy, Meagan M.; Hutter, Adolph M.; Weiner, Rory B.

    2016-01-01

    There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed. PMID:27486488

  8. Sudden cardiac death in athletes.

    PubMed

    Schmied, C; Borjesson, M

    2014-02-01

    A 'paradox of sport' is that in addition to the undisputed health benefits of physical activity, vigorous exertion may transiently increase the risk of acute cardiac events. In general, the risk of sudden cardiac death (SCD) approximately doubles during physical activity and is 2- to 3-fold higher in athletes compared to nonathletes. The incidence of SCD in young athletes is in fact very low, at around 1-3 per 100,000, but attracts much public attention. Variations in incidence figures may be explained by the methodology used for data collection and more importantly by differences between subpopulations of athletes. The incidence of SCD in older (≥ 35 years) athletes is higher and may be expected to rise, as more and older individuals take part in organized sports. SCD is often the first clinical manifestation of a potentially fatal underlying cardiovascular disorder and usually occurs in previously asymptomatic athletes. In the young (<35 years), SCD is mainly due to congenital/inherited cardiac abnormalities, whilst coronary artery disease (CAD) is the most common cause in older athletes. Cardiac screening including family/personal history, physical examination and resting electrocardiogram (ECG) may identify individuals at risk and has the potential to decrease the risk of SCD in young athletes. Screening including the ECG has a high sensitivity for underlying disease in young athletes, but the specificity needs to be improved, whereas the sensitivity of screening without the use of ECG is very low. The screening modality recommended for young athletes is of limited value in older athletes, who should receive individualized screening with cardiac stress testing for patients with high risk of underlying CAD. As cardiovascular screening will never be able to identify all athletes at risk, adequate preparedness is vital in case of a potentially fatal event at the sporting arena/facility. Firstly, we will review the magnitude of the problem of SCD in athletes of

  9. Cardiac Innervation and Sudden Cardiac Death

    PubMed Central

    Fukuda, Keiichi; Kanazawa, Hideaki; Aizawa, Yoshiyasu; Ardell, Jeffrey L.; Shivkumar, Kalyanam

    2015-01-01

    Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem and higher centers) which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes-hours) and long term (days-years). This important neurovisceral /autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death (SCD). Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extra-cardiac neural remodeling have also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provides a rational mechanistic basis for development of neuraxial therapies for preventing SCD and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention. PMID:26044253

  10. Sudden cardiac death from the perspective of coronary artery disease.

    PubMed

    Sara, Jaskanwal D; Eleid, Mackram F; Gulati, Rajiv; Holmes, David R

    2014-12-01

    Sudden cardiac death accounts for approximately 50% of all deaths attributed to cardiovascular disease in the United States. It is most commonly associated with coronary artery disease and can be its initial manifestation or may occur in the period after an acute myocardial infarction. Decreasing the rate of sudden cardiac death requires the identification and treatment of at-risk patients through evidence-based pharmacotherapy and interventional strategies aimed at primary and secondary prevention. For this review, we searched PubMed for potentially relevant articles published from January 1, 1970, through March 1, 2014, using the following key search terms: sudden cardiac death, ischemic heart disease, coronary artery disease, myocardial infarction, and cardiac arrest. Searches were enhanced by scanning bibliographies of identified articles, and those deemed relevant were selected for full-text review. This review outlines various mechanisms for sudden cardiac death in the setting of coronary artery disease, describes risk factors for sudden cardiac death, explores the management of cardiac arrest, and outlines optimal practice for the monitoring and treatment of patients after an acute ST-segment elevation myocardial infarction to decrease the risk of sudden death. PMID:25440727

  11. Sudden Cardiac Death Risk Stratification

    PubMed Central

    Deyell, Marc W.; Krahn, Andrew D.; Goldberger, Jeffrey J.

    2015-01-01

    Arrhythmic sudden cardiac death (SCD) may be due to ventricular tachycardia/fibrillation (SCD-VT/VF) or pulseless electrical activity/asystole. Effective risk stratification to identify patients at risk of arrhythmic SCD is essential for targeting our health care and research resources to tackle this important public health issue. Although our understanding of SCD due to pulseless electrical activity/asystole is growing, the overwhelming majority of research in risk stratification has focused on SCD-VT/VF. This review focuses on existing and novel risk stratification tools for SCD-VT/VF. For patients with left ventricular dysfunction and/or myocardial infarction, advances in imaging, measures of cardiac autonomic function, and measures of repolarization have shown considerable promise in refining risk. Yet the majority of SCD-VT/VF occurs in patients without known cardiac disease. Biomarkers and novel imaging techniques may provide further risk stratification in the general population beyond traditional risk stratification for coronary artery disease alone. Despite these advances, significant challenges in risk stratification remain that must be overcome before a meaningful impact on SCD can be realized. PMID:26044247

  12. [Sudden cardiac death in diabetes mellitus].

    PubMed

    Israel, C W; Lee-Barkey, Y H

    2016-05-01

    Sudden cardiac death (SCD) represents one of the most frequent causes of death in patients with diabetes. In contrast to patients without diabetes it has not been significantly reduced despite improvements in the treatment of acute myocardial infarction and long-term treatment of cardiovascular diseases as well as diabetes mellitus. Several mechanisms can be responsible for the high incidence of SCD in diabetics: 1. arrhythmogenic effects mediated via cardiac autonomic neuropathy, repolarization disturbances or sympathetic tone activation (hypoglycemia), 2. myocardial ischemia due to atherosclerosis, endothelial dysfunction, platelet aggregation or thrombophilic effects, 3. myocardial disease due to inflammation, fibrosis, associated hypertension or uremia and 4. potassium imbalance due to diabetic nephropathy or hypoglycemia. This review introduces concepts of mechanisms that are responsible for SCD in patients with diabetes. Treatment of patients with diabetes should primarily consider a systematic assessment of any deterioration of this chronic disease and of complications at an early stage. Cardiovascular drug treatment corresponds to that of non-diabetics. In antidiabetic treatment drugs with a low risk of hypoglycemia should be preferred. Treatment with implantable cardioverter defibrillators (ICD) also combined with cardiac resynchronization therapy () demonstrated a high life-saving potential particularly in patients with diabetes. PMID:27071967

  13. Radiofrequency Ablation to Prevent Sudden Cardiac Death

    PubMed Central

    Atoui, Moustapha; Gunda, Sampath; Lakkireddy, Dhanunjaya; Mahapatra, Srijoy

    2015-01-01

    Radiofrequency ablation may prevent or treat atrial and ventricular arrhythmias. Since some of these arrhythmias are associated with sudden cardiac death, it has been hypothesized that ablation may prevent sudden death in certain cases. We performed a literature search to better understand under which circumstances ablation may prevent sudden death and found little randomized data demonstrating the long-term effects of ablation. Current literature shows that ablation clearly prevents symptoms of arrhythmia and may reduce the incidence of sudden cardiac death in select patients, although data does not indicate improved mortality. Ongoing clinical trials are needed to better define the role of ablation in preventing sudden cardiac death. PMID:26306130

  14. Athletes at Risk for Sudden Cardiac Death

    ERIC Educational Resources Information Center

    Subasic, Kim

    2010-01-01

    High school athletes represent the largest group of individuals affected by sudden cardiac death, with an estimated incidence of once or twice per week. Structural cardiovascular abnormalities are the most frequent cause of sudden cardiac death. Athletes participating in basketball, football, track, soccer, baseball, and swimming were found to…

  15. Sudden cardiac death – Historical perspectives

    PubMed Central

    Abhilash, S.P.; Namboodiri, Narayanan

    2014-01-01

    Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 h of symptom onset) in a person with known or unknown cardiac disease. It is believed to be involved in nearly a quarter of human deaths, with ventricular fibrillation being the most common mechanism. It is estimated that more than 7 million lives per year are lost to SCD worldwide. Historical perspectives of SCD are analyzed with a brief description on how the developments in the management of sudden cardiac arrest evolved over time. PMID:24568828

  16. Genetics of sudden cardiac death.

    PubMed

    Refaat, Marwan M; Hotait, Mostafa; London, Barry

    2015-07-01

    Sudden cardiac death (SCD) is defined by the World Health Organization (WHO) as death within 1 h of symptom onset (witnessed) or within 24 h of being observed alive and symptom free (unwitnessed). It affects more than 3 million people annually worldwide and affects approximately 1/1000 people each year in the USA. Familial studies of syndromes with Mendelian inheritance, candidate genes analyses, and genome-wide association studies (GWAS) have helped our understanding of the genetics of SCD. We will review the genetics of arrhythmogenic hereditary syndromes with Mendelian inheritance from familial studies with structural heart disease (hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) as well as primary electrical causes (long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome). In addition, we will review the genetics of intermediate phenotypes for SCD such as coronary artery disease and electrocardiographic variables (QT interval, QRS duration, and RR interval). Finally, we will review rare and common variants that are associated with SCD in the general population and were identified from candidate gene analyses and GWAS. Our understanding of the genetics of SCD will improve by the use of next-generation sequencing/whole-exome sequencing as well as whole-genome sequencing which have the potential to discover unsuspected common and rare genetic variants that might be associated with SCD. PMID:26026997

  17. [Relevancy of sudden death of cardiac origin].

    PubMed

    Báyes de Luna, Antoni; Kotzeva, Anna; Goldwasser, Diego; Subirana, Maite; Puig, Maria Teresa; Bayés-Genis, Toni; Cinca, Juan; Vázquez, Rafael

    2007-01-01

    Sudden death (SD) is of cardiac origin in approximately 80-90% of the cases and represents one of the most important challenges of the modern cardiology. Evaluation and understanding of its epidemiological, clinical and histopathological characteristics can lead to better results in its management. In Spain was carried a multicenter study MUSA with two arms: 1/ EULALIA: histopathological aspects of SD and 2/ MUSIC: SD in heart failure with focus on identification of population groups at risk, pathophysiological mechanisms of development and clinical prognostic markers. The preliminary conclusions of both studies are the following: 1/ EULALIA trial: From the total 121 sudden deaths, 109 (90%) were of cardiac origin and of these 45% presented characteristics of myocardial hypertrophy. The histopathological findings reveled that in only 48% of cases acute ischemic heart disease was present. In the other cases of ischemic heart disease the sudden death was probably by arrhythmic origin related with the presence of old myocardial infarction. This is the most striking difference compared with Anglo-Saxon studies. In the 29 cases of ACS, 18 had eroded and combination of eroded and ruptured plaques. In the cases of non-ACS plaques were stable in 20, and combination of stable and vulnerable plaques in 7 cases. Statistically significant results as independent predictors of sudden death gave the following markers: history of MI, cephalization of vessels in thorax X-ray, left atrium size > 45 mm, high levels of NT-proBNP and PIP, LBBB on ECG recording and body mass index. PMID:18938710

  18. Cardiac Arrhythmias and Abnormal Electrocardiograms After Acute Stroke.

    PubMed

    Ruthirago, Doungporn; Julayanont, Parunyou; Tantrachoti, Pakpoom; Kim, Jongyeol; Nugent, Kenneth

    2016-01-01

    Cardiac arrhythmias and electrocardiogram (ECG) abnormalities occur frequently but are often underrecognized after strokes. Acute ischemic and hemorrhagic strokes in some particular area of brain can disrupt central autonomic control of the heart, precipitating cardiac arrhythmias, ECG abnormalities, myocardial injury and sometimes sudden death. Identification of high-risk patients after acute stroke is important to arrange appropriate cardiac monitoring and effective management of arrhythmias, and to prevent cardiac morbidity and mortality. More studies are needed to better clarify pathogenesis, localization of areas associated with arrhythmias and practical management of arrhythmias and abnormal ECGs after acute stroke. PMID:26802767

  19. Aborted sudden cardiac death: a clinical perspective

    PubMed Central

    Mazeika, P

    2001-01-01

    Sudden cardiac death in the community remains a major public health problem. The purpose of this article is to outline the epidemiology, pathophysiology, and immediate treatment of the cardiac arrest victim. The subsequent in-hospital diagnostic evaluation and management will then be discussed with an emphasis on the role of the implantable cardioverter-defibrillator. A systematic and evidence based approach should help to optimize patient care.


Keywords: cardiology; implantable cardioverter-defibrillator; resuscitation; sudden cardiac death PMID:11375448

  20. Sudden cardiac death in 2 young siblings.

    PubMed

    Kundu, Reetu; Punia, Rajpal Singh; Handa, Uma; Singh, Amandeep; Mohan, Harsh

    2014-12-01

    Hypertrophic cardiomyopathy is a disease known for exhibiting phenotypic and genetic heterogeneity. At times, sudden cardiac death may be the first and foremost manifestation of the disease. We report 2 cases of hypertrophic cardiomyopathy causing sudden death, which were diagnosed on autopsy with special emphasis on histopathological findings of this entity. The role of a pathologist cannot be undermined as the disease is a diagnostic challenge often overlooked by the neophytes in the field due to unawareness. PMID:25361060

  1. Sudden cardiac death & the Reverse Dodo Verdict.

    PubMed

    Healy, David; Howe, Gareth; Mangin, Derelie; Le Noury, Joanna

    2014-01-01

    Adverse effects of treatment on cardiac QT intervals were first reported 50 years ago. A clear link to sudden death was established, but the problem remained relatively unknown. The issue of treatment related effects on the heart, and the contribution this might make to sudden cardiac deaths in general, came more clearly into focus 20 years ago, linked to regulatory actions. In an era of polypharmacy, and mixing of prescribed and non-prescribed pharmacologically active agents it is now becoming increasingly clear that unanticipated cardiac effects may be common and a significant cause of mortality. There is likely underreporting and also underdiagnosis, as recognition requires a timely ECG. This paper proposes two methods to handle the problem. PMID:24902504

  2. Pathophysiology and prevention of sudden cardiac death.

    PubMed

    Goyal, Vineet; Jassal, Davinder S; Dhalla, Naranjan S

    2016-03-01

    Sudden cardiac death (SCD) is known to occur in individuals with diverse diseases. Each disease state has a specific etiology and pathophysiology, and is diagnosed and treated differently. Etiologies for SCD include cardiac arrhythmias, coronary artery disease, congenital coronary artery anomalies, hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, dilated cardiomyopathy, and aortic valve stenosis. A potential unifying mechanism of SCD in these diseases involves a massive stimulation of the sympathetic nervous system's stress response and the subsequent elevation of circulating catecholamines. The diagnosis of cardiac diseases that contribute to an increased risk for SCD is accomplished by a combination of different techniques including electrocardiography, echocardiography, magnetic resonance imaging, and invasive cardiac catheterization. Several therapies including anti-arrhythmic drugs, β-blockers, and antiplatelet agents may be used as medical treatment in patients for the prevention of SCD. Invasive therapies including percutaneous angioplasty, coronary artery bypass surgery, and implantable cardioverter-defibrillators are also used in the clinical management of SCD. PMID:26651385

  3. Sudden cardiac death in the older athlete.

    PubMed

    Chugh, Sumeet S; Weiss, Joseph B

    2015-02-10

    The overwhelming majority of sports-related sudden deaths occur among those older than 35 years of age. Because increasing numbers of older people are participating in organized endurance and competitive sporting events, the incidence of sports-related sudden death in older adults is expected to rise. Older athletes will approach clinical cardiologists for advice regarding their fitness for participation. It is important to recognize both that strenuous exercise is associated with a transient elevation in risk of sudden cardiac death and that appropriate training substantially reduces this risk. The approach to pre-participation screening for risk of sudden death in the older athlete is a complex issue and at present is largely focused on identifying inducible ischemia due to significant coronary disease. In this brief review, we summarize the current state of knowledge in this area with respect to epidemiology, mechanisms, and approaches to risk stratification, as viewed from the perspective of the consulting clinical cardiologist. PMID:25660928

  4. Acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Singh, Sarvesh Pal

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074

  5. Sudden cardiac death athletes: a systematic review

    PubMed Central

    2010-01-01

    Previous events evidence that sudden cardiac death (SCD) in athletes is still a reality and it keeps challenging cardiologists. Considering the importance of SCD in athletes and the requisite for an update of this matter, we endeavored to describe SCD in athletes. The Medline (via PubMed) and SciELO databases were searched using the subject keywords "sudden death, athletes and mortality". The incidence of SCD is expected at one case for each 200,000 young athletes per year. Overall it is resulted of complex dealings of factors such as arrhythmogenic substrate, regulator and triggers factors. In great part of deaths caused by heart disease in athletes younger than 35 years old investigations evidence cardiac congenital abnormalities. Athletes above 35 years old possibly die due to impairments of coronary heart disease, frequently caused by atherosclerosis. Myocardial ischemia and myocardial infarction are responsible for the most cases of SCD above this age (80%). Pre-participatory athletes' evaluation helps to recognize situations that may put the athlete's life in risk including cardiovascular diseases. In summary, cardiologic examinations of athletes' pre-competition routine is an important way to minimize the risk of SCD. PMID:20682064

  6. Sudden cardiac death: epidemiology and risk factors

    PubMed Central

    Adabag, A. Selcuk; Luepker, Russell V.; Roger, Véronique L.; Gersh, Bernard J.

    2016-01-01

    Sudden cardiac death (SCD) is an important public-health problem with multiple etiologies, risk factors, and changing temporal trends. Substantial progress has been made over the past few decades in identifying markers that confer increased SCD risk at the population level. However, the quest for predicting the high-risk individual who could be a candidate for an implantable cardioverter-defibrillator, or other therapy, continues. In this article, we review the incidence, temporal trends, and triggers of SCD, and its demographic, clinical, and genetic risk factors. We also discuss the available evidence supporting the use of public-access defibrillators. PMID:20142817

  7. Sudden cardiac death associated with methylone use.

    PubMed

    Carbone, Peter N; Carbone, David L; Carstairs, Shaun D; Luzi, Scott A

    2013-03-01

    The rise in popularity of "bath salts" as safe alternatives to MDMA (3,4-methylenedioxymethamphetamine), methamphetamine, and other illicit substances has resulted in increased scrutiny of the contents and toxicology associated with these products. We report a case of sudden death related to the synthetic cathinone methylone (3,4-methylenedioxy-N-methylcathinonmethylone) in a previously healthy 19-year-old man. Although several fatal case reports have been published involving methylone and other synthetic cathinones, this is the first reported case of sudden cardiac death associated with methylone use. Although lack of published data prevented a comparison of blood methylone concentrations between our case and existing reports, the amount of methylone we detected postmortem (0.07 mg/dL) is below those reported in MDMA-related fatalities. Our report suggests that methylone toxicity has been greatly underestimated by users of this synthetic cathinone. PMID:23403480

  8. Risk stratification for sudden cardiac death

    PubMed Central

    Cutler, Michael J; Rosenbaum, David S.

    2009-01-01

    The proportion of cardiovascular deaths attributable to sudden cardiac death (SCD) is on the rise. Herein lies the rationale for developing risk stratification strategies to predict who will benefit from prophylactic ICD implantation. Current guidelines recommend prophylactic ICD therapy in patients with reduced left ventricular ejection fraction (LVEF). However, there are clear limitations in using LVEF alone to decide who should receive an ICD. There is mounting evidence that microvolt-level T wave alternans (TWA) is an important marker of arrhythmic risk. TWA is appealing because it non-invasively probes underlying electrophysiological substrate and has been linked to cellular mechanisms for arrhythmias. This review considers the clinical role of TWA for risk stratification of SCD. PMID:19631909

  9. Donation after cardiac death in abdominal organ transplantation.

    PubMed

    Reich, David J; Guy, Stephen R

    2012-01-01

    This article reviews the field of donation after cardiac death, focusing on the history, ethicolegal issues, clinical outcomes, best practices, operative techniques, and emerging strategies to optimize utilization of this resource. Donation after cardiac death is one effective way to decrease the organ shortage and has contributed the largest recent increase in abdominal organ allografts. Currently, donation after cardiac death organs confer an increased risk of ischemic cholangiopathy after liver transplant and of delayed graft function after kidney transplant. As this field matures, risk factors for donation after cardiac death organ transplant will be further identified and clinical outcomes will improve as a result of protocol standardization and ongoing research. PMID:22678860

  10. Postmortem imaging of sudden cardiac death.

    PubMed

    Michaud, Katarzyna; Grabherr, Silke; Jackowski, Christian; Bollmann, Marc Daniel; Doenz, Franceso; Mangin, Patrice

    2014-01-01

    Postmortem imaging is increasingly used in forensic practice in cases of natural deaths related to cardiovascular diseases, which represent the most common causes of death in developed countries. While radiological examination is generally considered to be a good complement for conventional autopsy, it was thought to have limited application in cardiovascular pathology. At present, multidetector computed tomography (MDCT), CT angiography, and cardiac magnetic resonance imaging (MRI) are used in postmortem radiological investigation of cardiovascular pathologies. This review presents the actual state of postmortem imaging for cardiovascular pathologies in cases of sudden cardiac death (SCD), taking into consideration both the advantages and limitations. The radiological evaluation of ischemic heart disease (IHD), the most frequent cause of SCD in the general population of industrialized countries, includes the examination of the coronary arteries and myocardium. Postmortem CT angiography (PMCTA) is very useful for the detection of stenoses and occlusions of coronary arteries but less so for the identification of ischemic myocardium. MRI is the method of choice for the radiological investigation of the myocardium in clinical practice, but its accessibility and application are still limited in postmortem practice. There are very few reports implicating postmortem radiology in the investigation of other causes of SCD, such as cardiomyopathies, coronary artery abnormalities, and valvular pathologies. Cardiomyopathies representing the most frequent cause of SCD in young athletes cannot be diagnosed by echocardiography, the most widely available technique in clinical practice for the functional evaluation of the heart and the detection of cardiomyopathies. PMCTA and MRI have the potential to detect advanced stages of diseases when morphological substrate is present, but these methods have yet to be sufficiently validated for postmortem cases. Genetically determined

  11. Acute myocarditis presenting as cardiac tamponade.

    PubMed Central

    Nwizu, Chidi; Onwuanyi, Anekwe E.

    2004-01-01

    We report a case of acute fulminant myocarditis presenting with cardiac tamponade and shock. The patient was managed in the coronary care unit with emergency pericardiotomy, invasive hemodynamic monitoring, and supportive therapy for cardiac failure. Pleural effusion and pneumonia complicated her clinical course. She responded well to therapy with normalization of left ventricular systolic function. This case demonstrates the potential for complete recovery with appropriate management in acute myocarditis even with a fulminant course. Images Figure 1 PMID:15586655

  12. Sudden cardiac death in young athletes

    PubMed Central

    Östman-Smith, Ingegerd

    2011-01-01

    Athletic activity is associated with an increased risk of sudden death for individuals with some congenital or acquired heart disorders. This review considers in particular the causes of death affecting athletes below 35 years of age. In this age group the largest proportion of deaths are caused by diseases with autosomal dominant inheritance such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT-syndrome, and Marfan’s syndrome. A policy of early cascade-screening of all first-degree relatives of patients with these disorders will therefore detect a substantial number of individuals at risk. A strictly regulated system with preparticipation screening of all athletes following a protocol pioneered in Italy, including school-age children, can also detect cases caused by sporadic new mutations and has been shown to reduce excess mortality among athletes substantially. Recommendations for screening procedure are reviewed. It is concluded that ECG screening ought to be part of preparticipation screening, but using criteria that do not cause too many false positives among athletes. One such suggested protocol will show positive in approximately 5% of screened individuals, among whom many will be screened for these diseases. On this point further research is needed to define what kind of false-positive and false-negative rate these new criteria result in. A less formal system based on cascade-screening of relatives, education of coaches about suspicious symptoms, and preparticipation questionnaires used by athletic clubs, has been associated over time with a sizeable reduction in sudden cardiac deaths among Swedish athletes, and thus appears to be worth implementing even for junior athletes not recommended for formal preparticipation screening. It is strongly argued that in families with autosomal dominant disorders the first screening of children should be carried out no later than 6 to 7 years of age. PMID:24198575

  13. Predicting the risk of sudden cardiac death.

    PubMed

    Lerma, Claudia; Glass, Leon

    2016-05-01

    Sudden cardiac death (SCD) is the result of a change of cardiac activity from normal (typically sinus) rhythm to a rhythm that does not pump adequate blood to the brain. The most common rhythms leading to SCD are ventricular tachycardia (VT) or ventricular fibrillation (VF). These result from an accelerated ventricular pacemaker or ventricular reentrant waves. Despite significant efforts to develop accurate predictors for the risk of SCD, current methods for risk stratification still need to be improved. In this article we briefly review current approaches to risk stratification. Then we discuss the mathematical basis for dynamical transitions (called bifurcations) that may lead to VT and VF. One mechanism for transition to VT or VF involves a perturbation by a premature ventricular complex (PVC) during sinus rhythm. We describe the main mechanisms of PVCs (reentry, independent pacemakers and abnormal depolarizations). An emerging approach to risk stratification for SCD involves the development of individualized dynamical models of a patient based on measured anatomy and physiology. Careful analysis and modelling of dynamics of ventricular arrhythmia on an individual basis will be essential in order to improve risk stratification for SCD and to lay a foundation for personalized (precision) medicine in cardiology. PMID:26660287

  14. Clinical significance of lactate in acute cardiac patients

    PubMed Central

    Lazzeri, Chiara; Valente, Serafina; Chiostri, Marco; Gensini, Gian Franco

    2015-01-01

    Lactate, as a metabolite of easy and quick assessment, has been studied over time in critically ill patients in order to evaluate its prognostic ability. The present review is focused on the prognostic role of lactate levels in acute cardiac patients (that is with acute coronary syndrome, cardiogenic shock, cardiac arrest, non including post cardiac surgery patients). In patients with ST-elevation myocardial infarction treated with mechanical revascularization, hyperlactatemia identified a subset of patients at higher risk for early death and in-hospital complications, being strictly related mainly to hemodynamic derangement. The prognostic impact of hyperlactatemia on mortality has been documented in patients with cardiogenic shock and in those with cardiac arrest even if there is no cut-off value of lactate to be associated with worse outcome or to guide resuscitation or hemodynamic management. Therapeutic hypothermia seems to affect per se lactate values which have been shown to progressively decrease during hypothermia. The mechanism(s) accounting for lactate levels during hypothemia seem to be multiple ranging from the metabolic effects of reduced temperatures to the hemodynamic effects of hypothermia (i.e., reduced need of vasopressor agents). Serial lactate measurements over time, or lactate clearance, have been reported to be clinically more reliable than lactate absolute value also in acute cardiac patients. Despite differences in study design, timing of lactate measurements and type of acute cardiac conditions (i.e., cardiogenic shock, cardiac arrest, refractory cardiac arrest), available evidence strongly suggests that higher lactate levels can be observed on admission in non-survivors and that higher lactate clearance is associated with better outcome. PMID:26322188

  15. Sudden unexpected death, epilepsy and familial cardiac pathology.

    PubMed

    Eastaugh, A J; Thompson, T; Vohra, J K; O'Brien, T J; Winship, I

    2015-10-01

    We evaluated the prevalence of epilepsy in a cohort of patients who suffered a sudden unexpected death (SUDEP), and determined the proportion of the deaths that were related to an identifiable underlying familial cardiac pathology. Epilepsy is common in people who experience a sudden unexpected death, with approximately a quarter having identifiable familial electrophysiological abnormalities. Familial cardiac pathology may be an important cause of SUDEP. A retrospective evaluation was performed of 74 families that were referred to the Royal Melbourne Hospital Cardiac Genetic Clinic over a 5 year period for investigation following a family member's sudden, presumed cardiac, death. This state-wide referral clinic includes all patients who have died from a sudden unexpected death in whom the cause of death is unascertained. An epilepsy diagnosis was categorised as either definite, probable, possible or unlikely. The family members underwent comprehensive clinical evaluations and investigations in an attempt to identify a familial cardiac cause for the sudden unexpected death. Our findings suggest that systematic referral to a cardiac genetics service is warranted for the first degree relatives of people with epilepsy who experience a sudden unexplained death, for further evaluation and to identify those who are at higher risk for sudden death. Interventions may then be instituted to potentially reduce this risk. PMID:26195332

  16. [Sudden cardiac death in individuals with normal hearts: an update].

    PubMed

    González-Melchor, Laila; Villarreal-Molina, Teresa; Iturralde-Torres, Pedro; Medeiros-Domingo, Argelia

    2014-01-01

    Sudden death (SD) is a tragic event and a world-wide health problem. Every year, near 4-5 million people experience SD. SD is defined as the death occurred in 1h after the onset of symptoms in a person without previous signs of fatality. It can be named "recovered SD" when the case received medical attention, cardiac reanimation effective defibrillation or both, surviving the fatal arrhythmia. Cardiac channelopathies are a group of diseases characterized by abnormal ion channel function due to genetic mutations in ion channel genes, providing increased susceptibility to develop cardiac arrhythmias and SD. Usually the death occurs before 40 years of age and in the autopsy the heart is normal. In this review we discuss the main cardiac channelopathies involved in sudden cardiac death along with current management of cases and family members that have experienced such tragic event. PMID:25128006

  17. Heart failure therapy and sudden cardiac death prevention.

    PubMed

    Morgan, J M

    2004-12-01

    Primary prophylaxis of sudden cardiac death by implantable defibrillators is an accepted therapeutic strategy because sudden cardiac death is reduced by their use. However, many patients at risk of sudden cardiac death due to left ventricular systolic dysfunction also suffer heart failure symptoms. There is increasing evidence that the morbidity of heart failure can be alleviated by device therapy in which ventricular dysynchrony is improved by biventricular pacing. Both therapies in the same device can reduce both morbidity and mortality. Device therapy is an important new aspect in the field of heart failure management. PMID:15729212

  18. Cardiac papillary fibroelastoma presenting as acute stroke

    PubMed Central

    Abbasi, Atif Saleem; Da Costa, Mark; Hennessy, Terry; Kiernan, Thomas John

    2013-01-01

    We present a case of a young woman who was initially diagnosed with acute stroke with no obvious risk factors. Preliminary investigation with transthoracic echocardiography and subsequent advanced imaging with transoesophageal echocardiography suggested the diagnosis of a benign cardiac tumour on the anterior leaflet of mitral valve. The patient underwent urgent surgical resection. Histology confirmed the diagnosis of cardiac papillary fibroelastoma. She made complete clinical recovery with no recurrence of symptoms. PMID:23761612

  19. Acute Cardiac Tamponade: An Unusual Cause of Acute Renal Failure

    PubMed Central

    Phadke, Gautam; Whaley-Connell, Adam; Dalal, Pranavkumar; Markley, John; Rich, Andrew

    2012-01-01

    We are reporting a case of acute renal failure after cardiac surgery due to acute pericardial effusion. The patient had normal baseline renal function but developed acute oliguric renal failure with a significant increase in serum creatinine postoperatively. Pericardiotomy led to an improvement in blood pressure, immediate diuresis and quick recovery of renal function back to baseline. Pericardial tamponade should be included in the consideration of causes of the cardiorenal syndrome. PMID:22619656

  20. Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

    PubMed Central

    Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

    2014-01-01

    Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

  1. Cardiac Manifestation of Acute Lymphoblastic Leukemia.

    PubMed

    Werner, Rudolf A; Rudelius, Martina; Thurner, Annette; Higuchi, Takahiro; Lapa, Constantin

    2016-07-01

    Here, we report on a 38-year-old man with unclear right heart failure. Imaging with cardiac MRI and combined PET/CT with F-FDG revealed a hypermetabolic mass extending from the right ventricle to the atrium. In addition, intense glucose utilization throughout the bone marrow was noted. Biopsies of both bone marrow and cardiac mass were performed and revealed precursor B-cell acute lymphoblastic leukemia with gross leukemic infiltration of the myopericardium, a rare manifestation of acute lymphoblastic leukemia at initial diagnosis. PMID:27088389

  2. Strategies for the prevention of sudden cardiac death during sports.

    PubMed

    Corrado, Domenico; Drezner, Jonathan; Basso, Cristina; Pelliccia, Antonio; Thiene, Gaetano

    2011-04-01

    Sudden cardiac death of a young athlete is the most tragic event in sports and devastates the family, the sports medicine team, and the local community. Such a fatality represents the first manifestation of cardiac disease in up to 80% of young athletes who remain asymptomatic before sudden cardiac arrest occurs; this explains the limited power of screening modalities based solely on history and physical examination. The long-running Italian experience showed that electrocardiogram (ECG) screening definitively improves the sensitivity of pre-participation evaluation for heart diseases and substantially reduces the risk of death in the athletic field (primary prevention). However, some cardiac conditions, such as coronary artery diseases, present no abnormalities on 12-lead ECG. Moreover, cardiac arrest due to non-penetrating chest injury (commotio cordis) cannot be prevented by screening. This justifies the efforts for implementing programmes of early external defibrillation of unpredictable arrhythmic cardiac arrest. This article reviews the epidemiology of sudden cardiac arrest in the athlete in terms of incidence, sport-related risk, underlying causes, and the currently available prevention programmes such as pre-participation screening and early external defibrillation by using automated external defibrillators. The best strategy is to combine synergistically primary prevention of sudden cardiac death by pre-participation identification of athletes affected by at-risk cardiomyopathies and secondary prevention with back-up defibrillation of unpredictable sudden cardiac arrest on the athletic field. PMID:21567995

  3. Sudden cardiac death in 13 captive chimpanzees (Pan troglodytes).

    PubMed

    Lammey, Michael L; Lee, D Rick; Ely, John J; Sleeper, Meg M

    2008-02-01

    Sudden cardiac death (SCD), presumed secondary to fatal arrhythmias, is a common cause of mortality in captive chimpanzees at the Alamogordo Primate Facility. Over the 6-year period at the Alamogordo Primate Facility between 2001 and 2006, 13 animals were defined as sudden cardiac death (11 male and 2 female) on the basis of clinical presentation which was 38% of all deaths. All animals had annual physical exams, including electrocardiograms and serial blood pressures. Six of the 13 animals underwent a complete cardiac evaluation by a veterinary cardiologist and all six of these animals were diagnosed with various degrees of cardiomyopathy. Systemic hypertension was noted in two of the 13 cases and antemortem cardiac arrhythmias were seen in all 13 animals. Histological examination of the hearts revealed myocardial fibrosis in 12 chimpanzees. Most of the animals (10/13) that died of sudden cardiac death had cardiomegaly (increased heart weight/body weight ratio) and some degree of myocardial fibrosis noted. Additional data as well as serial diagnostic evaluations will be needed to identify the possible causes of sudden cardiac death in captive chimpanzees. PMID:18269527

  4. Mechanisms of Sudden Cardiac Death: Oxidants and Metabolism

    PubMed Central

    Yang, Kai-Chien; Kyle, John W.; Makielski, Jonathan C.; Dudley, Samuel C.

    2015-01-01

    Ventricular arrhythmia is the leading cause of sudden cardiac death (SCD). Deranged cardiac metabolism and abnormal redox state during cardiac diseases foment arrhythmogenic substrates through direct or indirect modulation of cardiac ion channel/transporter function. This review presents current evidence on the mechanisms linking metabolic derangement and excessive oxidative stress to ion channel/transporter dysfunction that predisposes to ventricular arrhythmias and SCD. As conventional anti-arrhythmic agents aiming at ion channels have proven challenging to use, targeting arrhythmogenic metabolic changes and redox imbalance may provide novel therapeutics to treat or prevent life-threatening arrhythmias and SCD. PMID:26044249

  5. Sudden cardiac death in the young: the molecular autopsy and a practical approach to surviving relatives.

    PubMed

    Semsarian, Christopher; Ingles, Jodie; Wilde, Arthur A M

    2015-06-01

    The sudden death of a young, apparently fit and healthy person is amongst the most challenging scenarios in clinical medicine. Sudden cardiac death (SCD) is a devastating and tragic outcome of a number of underlying cardiovascular diseases. While coronary artery disease and acute myocardial infarction are the most common causes of SCD in older populations, genetic (inherited) cardiac disorders comprise a substantial proportion of SCD cases aged 40 years and less. This includes the primary arrhythmogenic disorders such as long QT syndromes and inherited cardiomyopathies, namely hypertrophic cardiomyopathy. In up to 30% of young SCD, no cause of death is identified at postmortem, so-called autopsy-negative or sudden arrhythmic death syndrome (SADS). Management of families following SCD begins with a concerted effort to identify the cause of death in the decedent, based on either premorbid clinical details or the pathological findings at postmortem. Where no cause of death is identified, genetic testing of deoxyribonucleic acid extracted from postmortem blood (the molecular autopsy) may identify a cause of death in up to 30% of SADS cases. Irrespective of the genetic testing considerations, all families in which a sudden unexplained death has occurred require targeted and standardized clinical testing in an attempt to identify relatives who may be at-risk of having the same inherited heart disease and therefore also predisposed to an increased risk of SCD. Optimal care of SCD families therefore requires dedicated and appropriately trained staff in the setting of a specialized multidisciplinary cardiac genetic clinic. PMID:25765769

  6. Acute cardiac herniation following pneumonectomy.

    PubMed

    Tschersich, H U; Skorapa, V; Fleming, W H

    1976-09-01

    Pneumonectomy with partial pericardiectomy may result in herniation of the heart through the pericardial defect, leading to cardiovascular collapse and death. Awareness of this grave potential complication and familarity with its clinical and roentgenographic features should permit prompt diagnosis and facilitate lifesaving repeat thoracotomy. PMID:948585

  7. CAP2 in cardiac conduction, sudden cardiac death and eye development.

    PubMed

    Field, Jeffrey; Ye, Diana Z; Shinde, Manasi; Liu, Fang; Schillinger, Kurt J; Lu, MinMin; Wang, Tao; Skettini, Michelle; Xiong, Yao; Brice, Angela K; Chung, Daniel C; Patel, Vickas V

    2015-01-01

    Sudden cardiac death kills 180,000 to 450,000 Americans annually, predominantly males. A locus that confers a risk for sudden cardiac death, cardiac conduction disease, and a newly described developmental disorder (6p22 syndrome) is located at 6p22. One gene at 6p22 is CAP2, which encodes a cytoskeletal protein that regulates actin dynamics. To determine the role of CAP2 in vivo, we generated knockout (KO) mice. cap2(-)/cap2(-) males were underrepresented at weaning and ~70% died by 12 weeks of age, but cap2(-)/cap2(-) females survived at close to the expected levels and lived normal life spans. CAP2 knockouts resembled patients with 6p22 syndrome in that mice were smaller and they developed microphthalmia and cardiac disease. The cardiac disease included cardiac conduction disease (CCD) and, after six months of age, dilated cardiomyopathy (DCM), most noticeably in the males. To address the mechanisms underlying these phenotypes, we used Cre-mediated recombination to knock out CAP2 in cardiomyocytes. We found that the mice developed CCD, leading to sudden cardiac death from complete heart block, but no longer developed DCM or the other phenotypes, including sex bias. These studies establish a direct role for CAP2 and actin dynamics in sudden cardiac death and cardiac conduction disease. PMID:26616005

  8. CAP2 in cardiac conduction, sudden cardiac death and eye development

    PubMed Central

    Field, Jeffrey; Ye, Diana Z.; Shinde, Manasi; Liu, Fang; Schillinger, Kurt J.; Lu, MinMin; Wang, Tao; Skettini, Michelle; Xiong, Yao; Brice, Angela K.; Chung, Daniel C.; Patel, Vickas V.

    2015-01-01

    Sudden cardiac death kills 180,000 to 450,000 Americans annually, predominantly males. A locus that confers a risk for sudden cardiac death, cardiac conduction disease, and a newly described developmental disorder (6p22 syndrome) is located at 6p22. One gene at 6p22 is CAP2, which encodes a cytoskeletal protein that regulates actin dynamics. To determine the role of CAP2 in vivo, we generated knockout (KO) mice. cap2−/cap2− males were underrepresented at weaning and ~70% died by 12 weeks of age, but cap2−/cap2− females survived at close to the expected levels and lived normal life spans. CAP2 knockouts resembled patients with 6p22 syndrome in that mice were smaller and they developed microphthalmia and cardiac disease. The cardiac disease included cardiac conduction disease (CCD) and, after six months of age, dilated cardiomyopathy (DCM), most noticeably in the males. To address the mechanisms underlying these phenotypes, we used Cre-mediated recombination to knock out CAP2 in cardiomyocytes. We found that the mice developed CCD, leading to sudden cardiac death from complete heart block, but no longer developed DCM or the other phenotypes, including sex bias. These studies establish a direct role for CAP2 and actin dynamics in sudden cardiac death and cardiac conduction disease. PMID:26616005

  9. Extreme sacrifice: sudden cardiac death in the US Fire Service

    PubMed Central

    2013-01-01

    Firefighting is a hazardous profession which has claimed on average the lives of 105 US firefighters per year for the past decade. The leading cause of line-of-duty mortality is sudden cardiac death, which accounts for approximately 45% of all firefighter duty-related fatalities. Strenuous physical activity, emotional stress, and environmental pollutants all strain the cardiovascular system, and each can increase the risk of sudden cardiac events in susceptible individuals. Sudden cardiac death is more likely to occur during or shortly after emergency duties such as fire suppression, despite the fact that these duties comprise a relatively small proportion of firefighters' annual duties. Additionally, cardiac events are more likely to occur in firefighters who possess an excess of traditional risk factors for cardiovascular disease along with underlying atherosclerosis and/or structural heart disease. In this review, we propose a theoretical model for the interaction between underlying cardiovascular disease in firefighters and the multifactorial physiological strain of firefighting. PMID:23849605

  10. [Sudden cardiac death in athletes and its prevention].

    PubMed

    Tönnis, T; Tack, C; Kuck, K-H

    2015-05-01

    Athletes and especially elite athletes are predominantly young people and are not associated with high health risks, apart from traumatic injuries. Nevertheless, there is a significantly high incidence of sudden cardiac death (SCD), which ranges from 0.6 to 3.0/100,000 athletes per year. Often the SCD is the first manifestation of an underlying cardiac disease. Distinct structural cardiac disorders, such as hypertrophic cardiomyopathy, coronary artery anomalies (17 %), inflammatory disorders (6 %) and arrhythmogenic right ventricular cardiomyopathy as well as conditions without structural cardiac abnormalities, such as primary electrical diseases (channelopathies) are important causes of sudden death. A simple screening can help to identify athletes with these diseases and allow specific therapies or precautionary measures to be initiated. PMID:25963171

  11. The Spectrum of Epidemiology Underlying Sudden Cardiac Death

    PubMed Central

    Hayashi, Meiso; Shimizu, Wataru; Albert, Christine M.

    2015-01-01

    Sudden cardiac death (SCD) from cardiac arrest is a major international public health problem accounting for an estimated 15–20% of all deaths. Although resuscitation rates are generally improving throughout the world, the majority of individuals who suffer a sudden cardiac arrest will not survive. SCD most often develops in older adults with acquired structural heart disease, but it also rarely occurs in the young, where it is more commonly due to inherited disorders. Coronary heart disease (CHD) is known to be the most common pathology underlying SCD, followed by cardiomyopathies, inherited arrhythmia syndromes, and valvular heart disease. Over the past three decades, declines in SCD rates have not been as steep as for other causes of CHD deaths, and there is a growing fraction of SCDs not due to CHD and/or ventricular arrhythmias, particularly among certain subsets of the population. The growing heterogeneity of the pathologies and mechanisms underlying SCD present major challenges for SCD prevention, which are magnified further by a frequent lack of recognition of the underlying cardiac condition prior to death. Multifaceted preventative approaches, which address risk factors in seemingly low risk and known high-risk populations will be required to decrease the burden of SCD. In this Compendium, we review the wide-ranging spectrum of epidemiology underlying SCD within both the general population and in high-risk subsets with established cardiac disease placing an emphasis on recent global trends, remaining uncertainties, and potential targeted preventive strategies. PMID:26044246

  12. The spectrum of epidemiology underlying sudden cardiac death.

    PubMed

    Hayashi, Meiso; Shimizu, Wataru; Albert, Christine M

    2015-06-01

    Sudden cardiac death (SCD) from cardiac arrest is a major international public health problem accounting for an estimated 15%-20% of all deaths. Although resuscitation rates are generally improving throughout the world, the majority of individuals who experience a sudden cardiac arrest will not survive. SCD most often develops in older adults with acquired structural heart disease, but it also rarely occurs in the young, where it is more commonly because of inherited disorders. Coronary heart disease is known to be the most common pathology underlying SCD, followed by cardiomyopathies, inherited arrhythmia syndromes, and valvular heart disease. During the past 3 decades, declines in SCD rates have not been as steep as for other causes of coronary heart disease deaths, and there is a growing fraction of SCDs not due to coronary heart disease and ventricular arrhythmias, particularly among certain subsets of the population. The growing heterogeneity of the pathologies and mechanisms underlying SCD present major challenges for SCD prevention, which are magnified further by a frequent lack of recognition of the underlying cardiac condition before death. Multifaceted preventative approaches, which address risk factors in seemingly low-risk and known high-risk populations, will be required to decrease the burden of SCD. In this Compendium, we review the wide-ranging spectrum of epidemiology underlying SCD within both the general population and in high-risk subsets with established cardiac disease placing an emphasis on recent global trends, remaining uncertainties, and potential targeted preventive strategies. PMID:26044246

  13. Global burden of Sudden Cardiac Death and insights from India

    PubMed Central

    Rao, B. Hygriv

    2014-01-01

    Sudden Cardiac death (SCD) is a major clinical event causing adverse impact on global economy. This review summarizes the available epidemiological data on SCD from different parts of the world. It contrasts the Indian and global perception on the issues influencing data collection, burden of SCD and sudden deaths occurring following Myocardial Infarction. The differences in data from India and rest of the world are highlighted. PMID:24568824

  14. Donation after cardiac death and the emergency department: ethical issues.

    PubMed

    Simon, Jeremy R; Schears, Raquel M; Padela, Aasim I

    2014-01-01

    Organ donation after cardiac death (DCD) is increasingly considered as an option to address the shortage of organs available for transplantation, both in the United States and worldwide. The procedures for DCD differ from procedures for donation after brain death and are likely less familiar to emergency physicians (EPs), even as this process is increasingly involving emergency departments (EDs). This article explores the ED operational and ethical issues surrounding this procedure. PMID:24552527

  15. Genetics of channelopathies associated with sudden cardiac death

    PubMed Central

    Campuzano, Oscar; Sarquella-Brugada, Georgia; Brugada, Ramon; Brugada, Josep

    2015-01-01

    Recent technological advances in cardiology have resulted in new guidelines for the diagnosis, treatment and prevention of diseases. Despite these improvements, sudden death remains one of the main challenges to clinicians because the majority of diseases associated with sudden cardiac death are characterized by incomplete penetrance and variable expressivity. Hence, patients may be unaware of their illness, and physical activity can be the trigger for syncope as first symptom of the disease. Most common causes of sudden cardiac death are congenital alterations and structural heart diseases, although a significant number remain unexplained after comprehensive autopsy. In these unresolved cases, channelopathies are considered the first potential cause of death. Since all these diseases are of genetic origin, family members could be at risk, despite being asymptomatic. Genetics has also benefited from technological advances, and genetic testing has been incorporated into the sudden death field, identifying the cause in clinically affected patients, asymptomatic family members and post-mortem cases without conclusive diagnosis. This review focuses on recent advances in the genetics of channelopathies associated with sudden cardiac death. PMID:26566530

  16. Diagnosis of acute cardiac ischemia.

    PubMed

    Pope, J Hector; Selker, Harry P

    2003-02-01

    A better understanding of coronary syndromes allow physicians to appreciate UAP and AMI as part of a continuum of ACI. ACI is a life-threatening condition whose identification can have major economic and therapeutic importance as far as threatening dysrhythmias and preventing or limiting myocardial infarction size. The identification of ACI continues to challenge the skill of even experienced clinicians, yet physicians continue (appropriately) to admit the overwhelming majority of patients with ACI; in the process, they admit many patients without acute ischemia [2], overestimating the likelihood of ischemia in low-risk patients because of magnified concern for this diagnosis for prognostic and therapeutic reasons. Studies of admitting practices from a decade ago have yielded useful clinical information but have shown that neither clinical symptoms nor the ECG could reliably distinguish most patients with ACI from those with other conditions. Most studies have evaluated the accuracy of various technologies for diagnosing ACI, yet only a few have evaluated the clinical impact of routine use. The prehospital 12-lead ECG has moderate sensitivity and specificity for the diagnosis of ACI. It has demonstrated a reduction of the mean time to thrombolysis by 33 minutes and short-term overall mortality in randomized trials. In the general ED setting, only the ACI-TIPI has demonstrated, in a large-scale multicenter clinical trial, a reduction in unnecessary hospitalizations without decreasing the rate of appropriate admission for patients with ACI. The Goldman chest pain protocol has good sensitivity for AMI but was not shown to result in any differences in hospitalization rate, length of stay, or estimated costs in the single clinical impact study performed. The protocol's applicability to patients with UAP has not been evaluated. Single measurement of biomarkers at presentation to the ED has poor sensitivity for AMI, although most biomarkers have high specificity. Serial

  17. Sudden cardiac death secondary to antidepressant and antipsychotic drugs

    PubMed Central

    Sicouri, Serge; Antzelevitch, Charles

    2008-01-01

    A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over QT prolongation and the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. Some antidepressants and antipsychotics have been linked to QT prolongation and the development of Torsade de pointes arrhythmias, whereas others have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This review examines the mechanisms and predisposing factors underlying the development of cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and antipsychotic drugs in clinical use. PMID:18324881

  18. Aetiology of sudden cardiac death in sport: a histopathologist's perspective

    PubMed Central

    Sheppard, Mary N

    2012-01-01

    In the UK, when a young person dies suddenly, the coroner is responsible for establishing the cause of death. They will ask a consultant pathologist to carry out an autopsy in order to ascertain when, where and how that person died. Once the cause of death is established and is due to natural causes, the coroner can issue a death certificate. Importantly, the coroner is not particularly interested in the cause of death as long as it is due to natural causes, which avoids the need for an inquest (a public hearing about the death). However, if no identifiable cause is established at the initial autopsy, the coroner can refer the heart to a cardiac pathologist, since the cause of death is usually due to heart disease in most cases. Consultant histopathologists are responsible for the analysis of human tissue from both living individuals and the dead in order to make a diagnosis of disease. With recent advancements in the management protocols for routine autopsy practice and assessment following the sudden death of a young individual, this review describes the role of the consultant histopathologist in the event of a sudden death of a young athletic individual, together with the older middle-aged ‘weekend warrior’ athlete. It provides concise mechanisms for the main causes of sudden cardiac death (including coronary artery disease, cardiomyopathies, valve abnormalities, major vessel ruptures and electrical conduction abnormalities) based on detailed autopsy data from our specialised cardiac pathology laboratory. Finally, the review will discuss the role of the histopathologist in the event of a ‘negative’ autopsy. PMID:23097474

  19. Cardiac Surgery-Associated Acute Kidney Injury

    PubMed Central

    Mao, Huijuan; Katz, Nevin; Ariyanon, Wassawon; Blanca-Martos, Lourdes; Adýbelli, Zelal; Giuliani, Anna; Danesi, Tommaso Hinna; Kim, Jeong Chul; Nayak, Akash; Neri, Mauro; Virzi, Grazia Maria; Brocca, Alessandra; Scalzotto, Elisa; Salvador, Loris; Ronco, Claudio

    2013-01-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. PMID:24454314

  20. Cardiac surgery-associated acute kidney injury.

    PubMed

    Mao, Huijuan; Katz, Nevin; Ariyanon, Wassawon; Blanca-Martos, Lourdes; Adýbelli, Zelal; Giuliani, Anna; Danesi, Tommaso Hinna; Kim, Jeong Chul; Nayak, Akash; Neri, Mauro; Virzi, Grazia Maria; Brocca, Alessandra; Scalzotto, Elisa; Salvador, Loris; Ronco, Claudio

    2013-10-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. PMID:24454314

  1. Cardiac Pseudoaneurysm- A Death Defying Entity

    PubMed Central

    Gupta, Saryu

    2016-01-01

    A pseudoaneurysm refers to a contained rupture of the myocardium with a tenuous pericardium walling off the leak. It needs to be differentiated from a true aneurysm by the fact that there is lack of myocardial tissue in the wall of a pseudoaneurysm. The differentiation between the two is pertinent as true aneurysms can be treated medically while pseudoaneurysms require urgent surgical treatment. Untreated pseudoaneurysms carry a high risk of rupture and mortality. We report a case of cardiac pseudoaneurysm developing in a 46-year-old male who had suffered myocardial infarction four months back. The patient now presented with chest pain and dyspnoea. CECT chest revealed a partially thrombosed large pseudoaneurysm arising from the posterior wall of left ventricle. While the clinical diagnosis of this entity is difficult, CECT plays a pivotal role in the non-invasive detection of pseudoaneurysms. PMID:27504379

  2. Cardiac MRI of acute coronary syndrome.

    PubMed

    Akerem Khan, Shamruz; Khan, Shamruz Akarem; Williamson, Eric E; Foley, Thomas A; Cullen, Ethany L; Young, Phillip M; Araoz, Philip A

    2013-05-01

    Acute coronary syndrome (ACS) is a major cause of morbidity and mortality worldwide. New serological biomarkers, such as troponins, have improved the diagnosis of ACS; however, the diagnosis of ACS can still be difficult as there is marked heterogeneity in its presentation and significant overlap with other disorders presenting with chest pain. Evidence is accumulating that cardiac MRI provides information that can aid the detection and differential diagnosis of ACS, guide clinical decision-making and improve risk-stratification after an event. In this review, we present the relevant cardiac MRI techniques that can be used to detect ACS accurately, provide differential diagnosis, identify the sequelae of ACS, and determine prognostication after ACS. PMID:23668741

  3. The negative autopsy: sudden cardiac death or other?

    PubMed

    Cohle, S D; Sampson, B A

    2001-01-01

    One of the most frustrating challenges faced by the forensic pathologist is the inability to determine the cause of death in a young person previously thought healthy. The four steps in the investigation of a sudden death include obtaining the history and scene information, performing a gross and microscopic autopsy, performing appropriate laboratory tests, and making the diagnosis. When examining the heart grossly it is important to preserve the anatomic landmarks, section the coronary arteries closely, and recognize lethal abnormalities such as anomalous origin of the coronary arteries. Specimens useful for toxicologic analysis include whole blood, serum, vitreous humor, gastric contents, bile, urine a purple top tube of blood, and frozen myocardium and spleen. Lethal cardiac diseases with minimal or no anatomic findings include Brugada and Garg's syndromes, the long QT syndrome, and Wolff-Parkinson-White (WPW) syndrome. Consultation with other experts, including cardiac pathologists, cardiologists, electrophysiologists, and molecular biologists, may be helpful in determining a cause of death. PMID:11673059

  4. Sudden arrhythmic death syndrome: a national survey of sudden unexplained cardiac death

    PubMed Central

    Behr, E R; Casey, A; Sheppard, M; Wright, M; Bowker, T J; Davies, M J; McKenna, W J; Wood, D A

    2007-01-01

    Objective To describe the characteristics of sudden arrhythmic death syndrome (SADS) and compare its incidence with official national mortality statistics for unascertained deaths. Design and setting Sudden unexplained deaths were prospectively surveyed through 117 coroners' jurisdictions in England. Consecutive cases meeting the following criteria were included: white Caucasian, aged 4–64 years, no history of cardiac disease, last seen alive within 12 h of death, normal coroner's autopsy, cardiac pathologist's confirmation of a normal heart and negative toxicology. Main outcome measures The estimated mortality from SADS was calculated and the official mortality statistics for unascertained causes of deaths in 4–64‐year‐olds was identified for the same time period. Results 115 coroner's cases were reported and 56 (49%) SADS victims were identified: mean age 32 years, range 7–64 years and 35 (63%) male. 7 of 39 cases (18%) had a family history of other premature sudden deaths (<45). The estimated mortality from SADS was 0.16/100 000 per annum (95% CI 0.12 to 0.21), compared with an official mortality of 0.10/100 000 per annum for International Classification of Diseases 798.1 (sudden death, cause unknown—instantaneous death) or 1.34/100 000 per annum for unascertained causes of death. Conclusions Deaths from SADS occur predominantly in young males. When compared with official mortality, the incidence of SADS may be up to eight times higher than estimated: more than 500 potential SADS cases per annum in England. Families with SADS carry genetic cardiac disease, placing them at risk of further sudden deaths. SADS should therefore be a certifiable cause of death prompting specialised cardiological evaluation of families. PMID:17237131

  5. Intrapulmonary aquaporin-5 expression as a possible biomarker for discriminating smothering and choking from sudden cardiac death: a pilot study.

    PubMed

    Wang, Qi; Ishikawa, Takaki; Michiue, Tomomi; Zhu, Bao-Li; Guan, Da-Wei; Maeda, Hitoshi

    2012-07-10

    The diagnosis of mechanical asphyxia as a cause of death, especially smothering and choking lacking evident injury, is one of the most difficult tasks in forensic pathology. The present study investigated the intrapulmonary expressions of aquaporins (AQPs; AQP-1 and AQP-5), as markers of water homeostasis, in forensic autopsy cases (total n=64, within 48 h postmortem) of mechanical asphyxiation due to neck compression (strangulation, n=24), including manual/ligature strangulation (n=12) and atypical hanging (n=12), smothering (n=7) and choking (n=8), compared with sudden cardiac death (n=14) and acute brain injury (n=11). Quantification of mRNA using a Taqman real-time PCR assay system demonstrated suppressed expression of AQP-5, but not AQP-1, in smothering and choking, compared with that in strangulation as well as sudden cardiac death and acute brain injury death. Immunostaining of AQP-5 was weakly detected in a linear pattern in the type I alveolar epithelial cells in smothering and choking cases, while cardiac and brain injury death showed marked positivity, and most strangulation cases had AQP-5-positive granular aggregates and fragments in intra-alveolar spaces. These observations indicate a partial difference in pulmonary molecular pathology among these causes of death, suggesting a procedure for possible discrimination of smothering and choking from sudden cardiac death. PMID:22421325

  6. [Postmortem genetic testing in sudden cardiac death due to ion channelopathies].

    PubMed

    Guan, Da-wei; Zhao, Rui

    2010-04-01

    Sudden cardiac death accounts for majority of deaths in human. Evident cardiac lesions that may explain the cause of death can be detected in comprehensive postmortem investigation in most sudden cardiac death. However, no cardiac morphological abnormality is found in a considerable number of cases although the death is highly suspected from cardiac anomaly. With the advances in the modern molecular biology techniques, it has been discovered that many of these sudden deaths are caused by congenital ion channelopathies in myocardial cell, i.e., Brugada syndrome, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome, etc. This article presents the molecular genetics, electrocardiographic abnormalities, clinical manifestations, and mechanisms leading to sudden cardiac death with emphasis on the role of postmortem genetic testing in certification of cause of death. It may provide helpful information in investigating sudden cardiac death due to ion channelopathies in medico-legal practice. PMID:20653139

  7. Early markers for myocardial ischemia and sudden cardiac death.

    PubMed

    Sabatasso, Sara; Mangin, Patrice; Fracasso, Tony; Moretti, Milena; Docquier, Mylène; Djonov, Valentin

    2016-09-01

    The post-mortem diagnosis of acute myocardial ischemia remains a challenge for both clinical and forensic pathologists. We performed an experimental study (ligation of left anterior descending coronary artery in rats) in order to identify early markers of myocardial ischemia, to further apply to forensic and clinical pathology in cases of sudden cardiac death. Using immunohistochemistry, Western blots, and gene expression analyses, we investigated a number of markers, selected among those which are currently used in emergency departments to diagnose myocardial infarction and those which are under investigation in basic research and autopsy pathology studies on cardiovascular diseases. The study was performed on 44 adult male Lewis rats, assigned to three experimental groups: control, sham-operated, and operated. The durations of ischemia ranged between 5 min and 24 h. The investigated markers were troponins I and T, myoglobin, fibronectin, C5b-9, connexin 43 (dephosphorylated), JunB, cytochrome c, and TUNEL staining. The earliest expressions (≤30 min) were observed for connexin 43, JunB, and cytochrome c, followed by fibronectin (≤1 h), myoglobin (≤1 h), troponins I and T (≤1 h), TUNEL (≤1 h), and C5b-9 (≤2 h). By this investigation, we identified a panel of true early markers of myocardial ischemia and delineated their temporal evolution in expression by employing new technologies for gene expression analysis, in addition to traditional and routine methods (such as histology and immunohistochemistry). Moreover, for the first time in the autopsy pathology field, we identified, by immunohistochemistry, two very early markers of myocardial ischemia: dephosphorylated connexin 43 and JunB. PMID:27392959

  8. Ebstein's Anomaly, Left Ventricular Noncompaction, and Sudden Cardiac Death.

    PubMed

    McGee, Michael; Warner, Luke; Collins, Nicholas

    2015-01-01

    Ebstein's anomaly is a congenital disorder characterized by apical displacement of the septal leaflet of the tricuspid valve. Ebstein's anomaly may be seen in association with other cardiac conditions, including patent foramen ovale, atrial septal defect, and left ventricular noncompaction (LVNC). LVNC is characterized by increased trabeculation within the left ventricular apex. Echocardiography is often used to diagnose LVNC; however, magnetic resonance (MR) imaging offers superior characterization of the myocardium. We report a case of sudden cardiac death in a patient with Ebstein's anomaly with unrecognized LVNC noted on post mortem examination with screening documenting the presence of LVNC in one of the patient's twin sons. PMID:26240764

  9. Acute Kidney Injury Subsequent to Cardiac Surgery

    PubMed Central

    Kramer, Robert S.; Herron, Crystal R.; Groom, Robert C.; Brown, Jeremiah R.

    2015-01-01

    Abstract: Acute kidney injury (AKI) after cardiac surgery is a common and underappreciated syndrome that is associated with poor short- and long-term outcomes. AKI after cardiac surgery may be epiphenomenon, a signal for adverse outcomes by virtue of other affected organ systems, and a consequence of multiple factors. Subtle increases in serum creatinine (SCr) postoperatively, once considered inconsequential, have been shown to reflect a kidney injury that likely occurred in the operating room during cardiopulmonary bypass (CPB) and more often in susceptible individuals. The postoperative elevation in SCr is a delayed signal reflecting the intraoperative injury. Preoperative checklists and the conduct of CPB represent opportunities for prevention of AKI. Newer definitions of AKI provide us with an opportunity to scrutinize perioperative processes of care and determine strategies to decrease the incidence of AKI subsequent to cardiac surgery. Recognizing and mitigating risk factors preoperatively and optimizing intraoperative practices may, in the aggregate, decrease the incidence of AKI. This review explores the pathophysiology of AKI and addresses the features of patients who are the most vulnerable to AKI. Preoperative strategies are discussed with particular attention to a readiness for surgery checklist. Intraoperative strategies include minimizing hemodilution and maximizing oxygen delivery with specific suggestions regarding fluid management and plasma preservation. PMID:26390675

  10. Acute Kidney Injury Subsequent to Cardiac Surgery.

    PubMed

    Kramer, Robert S; Herron, Crystal R; Groom, Robert C; Brown, Jeremiah R

    2015-03-01

    Acute kidney injury (AKI) after cardiac surgery is a common and underappreciated syndrome that is associated with poor shortand long-term outcomes. AKI after cardiac surgery may be epiphenomenon, a signal for adverse outcomes by virtue of other affected organ systems, and a consequence of multiple factors. Subtle increases in serum creatinine (SCr) postoperatively, once considered inconsequential, have been shown to reflect a kidney injury that likely occurred in the operating room during cardiopulmonary bypass (CPB) and more often in susceptible individuals. The postoperative elevation in SCr is a delayed signal reflecting the intraoperative injury. Preoperative checklists and the conduct of CPB represent opportunities for prevention of AKI. Newer definitions of AKI provide us with an opportunity to scrutinize perioperative processes of care and determine strategies to decrease the incidence of AKI subsequent to cardiac surgery. Recognizing and mitigating risk factors preoperatively and optimizing intraoperative practices may, in the aggregate, decrease the incidence of AKI. This review explores the pathophysiology of AKI and addresses the features of patients who are the most vulnerable to AKI. Preoperative strategies are discussed with particular attention to a readiness for surgery checklist. Intraoperative strategies include minimizing hemodilution and maximizing oxygen delivery with specific suggestions regarding fluid management and plasma preservation. PMID:26390675

  11. Tissue and Animal Models of Sudden Cardiac Death

    PubMed Central

    Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; Wu, Joseph C.

    2015-01-01

    Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252

  12. Wolff-Parkinson-White syndrome and sudden cardiac death.

    PubMed

    Prystowsky, E N; Fananapazir, L; Packer, D L; Thompson, K A; German, L D

    1987-01-01

    Every year, individuals with no history of heart disease succumb to sudden cardiac death (SCD). Pathologic examination of the hearts usually reveals various forms of heart disease as hypertrophic cardiomyopathy or coronary artery disease. In other cases, however, there is no obvious structural heart disease, and it is possible that some of these individuals died because of a cardiac arrhythmia involving an accessory pathway. If this were the case, the most likely scenario would be onset of atrioventricular reciprocating tachycardia (AVRT), degeneration of the AVRT into atrial fibrillation with a rapid ventricular response over the accessory pathway, and subsequent death caused by the development of ventricular fibrillation. Although these events have been documented, albeit rarely, during intracardiac electrophysiologic studies, in reality very little is known about the natural history of asymptomatic and untreated patients with Wolff-Parkinson-White (WPW) syndrome. In fact, SCD in a previously asymptomatic patient with WPW syndrome is probably relatively rare. Whether asymptomatic WPW patients should undergo electrophysiologic or pharmacologic testing to determine their 'potential' to develop serious cardiac arrhythmias is controversial. The present paucity of data concerning the natural history of WPW syndrome in asymptomatic patients militates against successful identification of those patients who are at risk for sudden death. Long-term prospective studies are necessary to clarify which asymptomatic patients with WPW syndrome require treatment. PMID:3621280

  13. Clinical management and prevention of sudden cardiac death.

    PubMed

    Yousuf, Omair; Chrispin, Jonathan; Tomaselli, Gordon F; Berger, Ronald D

    2015-06-01

    Despite the revolutionary advancements in the past 3 decades in the treatment of ventricular tachyarrhythmias with device-based therapy, sudden cardiac death (SCD) remains an enormous public health burden. Survivors of SCD are generally at high risk for recurrent events. The clinical management of such patients requires a multidisciplinary approach from postresuscitative care to a thorough cardiovascular investigation in an attempt to identify the underlying substrate, with potential to eliminate or modify the triggers through catheter ablation and ultimately an implantable cardioverter-defibrillator (ICD) for prompt treatment of recurrences in those at risk. Early recognition of low left ventricular ejection fraction as a strong predictor of death and association of ventricular arrhythmias with sudden death led to significant investigation with antiarrhythmic drugs. The lack of efficacy and the proarrhythmic effects of drugs catalyzed the development and investigation of the ICD through several major clinical trials that proved the efficacy of ICD as a bedrock tool to detect and promptly treat life-threatening arrhythmias. The ICD therapy is routinely used for primary prevention of SCD in patients with cardiomyopathy and high risk inherited arrhythmic conditions and secondary prevention in survivors of sudden cardiac arrest. This compendium will review the clinical management of those surviving SCD and discuss landmark studies of antiarrhythmic drugs, ICD, and cardiac resynchronization therapy in the primary and secondary prevention of SCD. PMID:26044254

  14. Death due to acute tetrachloroethylene intoxication in a chronic abuser.

    PubMed

    Amadasi, Alberto; Mastroluca, Lavinia; Marasciuolo, Laura; Caligara, Marina; Sironi, Luca; Gentile, Guendalina; Zoja, Riccardo

    2015-05-01

    Volatile substances are used widespread, especially among young people, as a cheap and easily accessible drug. Tetrachloroethylene is one of the solvents exerting effects on the central nervous system with experiences of disinhibition and euphoria. The case presented is that of a 27-year-old female, found dead by her father at home with cotton swabs dipped in the nostrils. She was already known for this type of abuse and previously admitted twice to the hospital for nonfatal acute poisonings. The swabs were still soaked in tetrachloroethylene. Toxicological and histological investigations demonstrated the presence of an overlap between chronic intake of the substance (with high concentrations in sites of accumulation, e.g., the adipose tissue, and contemporary tissue damage, as histologically highlighted) and acute intoxication as final cause of death, with a concentration of 158 mg/L in cardiac blood and 4915 mg/kg in the adipose tissue. No other drugs or medicines were detected in body fluids or tissues, and to our knowledge, this is the highest concentration ever detected in forensic cases. This peculiar case confirms the toxicity of this substance and focuses on the importance of complete histological and toxicological investigations in the distinction between chronic abuse and acute intoxication. PMID:25605280

  15. [The athletes' ECG and the exercise related sudden cardiac death].

    PubMed

    Trachsel, Lukas-Daniel; Wilhelm, Matthias

    2015-05-01

    Regular physical activity induces structural, electrical and functional cardiac adaptations. The main challenge for the athletes' physician is to distinguish abnormal structural changes of the heart from training-induced adaptations (so-called “athlete's heart”). In athletes with underlying cardiac disease, physical activity may be a trigger, not the cause of exercise-induced tachyarrhythmia's and sudden cardiac death (SCD). To identify athletes with cardiac diseases and increased risk for an SCD, the European society of cardiology (ESC) recommends a pre-participation screening in elite athletes which was adopted by the Swiss society of sports medicine. The screening includes a specific medical history, cardiac auscultation and a resting ECG. Due to the high number of false-positive cases of athletes' ECGs based on traditional criteria, the ESC assessment criteria were adjusted to account for training-related changes of the ECG. The sensitivity and especially the specificity could be improved in the “revised Seattle criteria” in 2014. During the last years main attention has been shifted to the early repolarization pattern: additionally to (endurance-) training there is a clear association with male gender, ethnicity, changes in autonomic nervous system activity and high QRS-voltage criteria PMID:26098068

  16. Elevated Cardiac Troponin in Acute Stroke without Acute Coronary Syndrome Predicts Long-Term Adverse Cardiovascular Outcomes

    PubMed Central

    Bhatt, Reema; Bove, Alfred A.

    2014-01-01

    Background. Elevated cardiac troponin in acute stroke in absence of acute coronary syndrome (ACS) has unclear long-term outcomes. Methods. Retrospective analysis of 566 patients admitted to Temple University Hospital from 2008 to 2010 for acute stroke was performed. Patients were included if cardiac troponin I was measured and had no evidence of ACS and an echocardiogram was performed. Of 200 patients who met the criteria, baseline characteristics, electrocardiograms, and major adverse cardiovascular events (MACE) were reviewed. Patients were characterized into two groups with normal and elevated troponins. Primary end point was nonfatal myocardial infarction during follow-up period after discharge. The secondary end points were MACE and death from any cause. Results. For 200 patients, 17 patients had positive troponins. Baseline characteristics were as follows: age 63.1 ± 13.8, 64% African Americans, 78% with hypertension, and 22% with previous CVA. During mean follow-up of 20.1 months, 7 patients (41.2%) in elevated troponin and 6 (3.3%) patients in normal troponin group had nonfatal myocardial infarction (P = 0.0001). MACE (41.2% versus 14.2%, P = 0.01) and death from any cause (41.2% versus 14.5%, P = 0.017) were significant in the positive troponin group. Conclusions. Elevated cardiac troponin in patients with acute stroke and no evidence of ACS is strong predictor of long-term cardiac outcomes. PMID:25530906

  17. Sudden cardiac death markers in non-ischemic cardiomyopathy.

    PubMed

    Pimentel, Mauricio; Rohde, Luis Eduardo; Zimerman, André; Zimerman, Leandro Ioschpe

    2016-01-01

    Heart failure is an increasingly prevalent disease associated with high morbidity and mortality. In 30-40% of patients, the etiology is non-ischemic. In this group of patients, the implantable cardioverter-defibrillator (ICD) prevents sudden death and decreases total mortality. However, due to burden of cost, the fact that many ICD patients will never need any therapy, and possible complications involved in implant and follow-up, the device should not be implanted in every patient with non-ischemic heart failure. There is an urgent need to adequately identify patients with highest sudden death risk, in whom the implant is most cost-effective. In the present paper, the authors discuss current available tests for risk stratification of sudden cardiac death in patients with non-ischemic heart failure. PMID:27016256

  18. [Sudden cardiac death during a city marathon run].

    PubMed

    Beutler, J; Schmid, E; Fischer, S; Hürlimann, S; Konrad, C

    2015-06-01

    Sudden cardiac death (SCD) in young athletes during physical stress is a rare event with an incidence of 1-3 deaths per 100,000 athletes per year. A coronary anomaly is the second most common cause of death following hypertrophic cardiomyopathy. Symptomatic prodromes occur in 20% of cases prior to the SCD event. This case report describes a 35-year-old male who collapsed near the finishing line of a half marathon run. Despite immediate resuscitation attempts and initial return of spontaneous circulation (ROSC), a pulseless electrical activity (PEA) followed and the patient died 1 h after arrival in the resuscitation unit. The autopsy revealed an anomalous left coronary artery (ALCA), which can lead to ischemia of the respective heart muscles under severe stress. PMID:26031561

  19. Noninvasive imaging markers associated with sudden cardiac death.

    PubMed

    van der Bijl, Pieter; Delgado, Victoria; Bax, Jeroen J

    2016-05-01

    Sudden cardiac death (SCD) accounts for approximately 15-20% of all deaths worldwide. While the majority of SCDs occur in adults, children, and adults <35 years (<1%) may also be affected. Currently the most effective strategy for both primary and secondary prevention of SCD is the implantable cardioverter-defibrillator (ICD). However, identification of patients who will benefit from ICD implantation remains challenging. Left ventricular ejection fraction (LVEF) is the most frequent imaging parameter used to select patients for ICD implantation for primary prevention. However, LVEF has shown to be suboptimal for prediction of benefit. Non-invasive cardiac imaging permits characterization of the arrhythmogenic substrate, including dispersion of electromechanical activation, presence of myocardial scar, and cardiac innervation status. The arrhythmogenic substrate may change across the different underlying diseases. While in ischemic cardiomyopathy, differentiation and characterization of infarct core and peri-infarct zone have been shown to refine the risk stratification of patients, in non-ischemic cardiomyopathies, the substrate may be more heterogeneous and tissue characterization assessing focal and diffuse fibrosis and inflammation processes may be more relevant. Furthermore, in channelopathies, assessment of mechanical dispersion between myocardial layers may identify the patients with increased risk of ventricular arrhythmias. Finally, potential triggers of ventricular arrhythmias such as myocardial ischemia can be evaluated. The role of noninvasive imaging in the risk stratification of SCD and the selection of candidates for ICD will be discussed in this article. PMID:26632012

  20. Cardiac Conduction System Anomalies and Sudden Cardiac Death: Insights from Murine Models

    PubMed Central

    Aránega, Amelia; De La Rosa, Angel J.; Franco, Diego

    2012-01-01

    The cardiac conduction system (CCS) is composed of a group of myocardial tissues that control and coordinate the heart. Alterations in the CCS – especially in the His–Purkinje system, have been identified as a major cause of lethal arrhythmias. Unstable arrhythmias secondary to channelopathies significantly increase the risk of sudden cardiac death (SCD). SCD is a major contributor to mortality in industrialized countries, and most cases of SCD in the young are related to inherited ion channel diseases. In this paper, we review a series of studies with murine transgenic models that revealed that some arrhythmias are associated with the CCS and may lead to SCD PMID:22783196

  1. Genetic etiology and evaluation of sudden cardiac death.

    PubMed

    Dolmatova, Elena; Mahida, Saagar; Ellinor, Patrick T; Lubitz, Steven A

    2013-08-01

    A wide range of inherited syndromes can result in ventricular arrhythmias and sudden cardiac death (SCD). The natural histories of inherited arrhythmia syndromes are highly variable and current risk stratification techniques are limited. Thus, the management of these conditions can be difficult and often involves a combination of risk assessment, lifestyle modification, cardiac interventions, counselling, and family screening. Recent advances in high throughput sequencing have enabled routine testing in patients with a high clinical index of suspicion for an inherited arrhythmia condition, and cascade screening in relatives of mutation carriers. Given the complexity in screening and data interpretation that has been introduced by recent genomic advances, individuals with inherited arrhythmia syndromes are encouraged to seek care at specialized centers with cardiovascular genetics expertise. In this review, we discuss the etiologies of SCD syndromes and discuss strategies for the evaluation of patients at risk for SCD with a focus on the role of genetic testing and family screening. PMID:23812838

  2. Nonlinear dynamics, fractals, cardiac physiology and sudden death

    NASA Technical Reports Server (NTRS)

    Goldberger, Ary L.

    1987-01-01

    The authors propose a diametrically opposite viewpoint to the generally accepted tendency of equating healthy function with order and disease with chaos. With regard to the question of sudden cardiac death and chaos, it is suggested that certain features of dynamical chaos related to fractal structure and fractal dynamics may be important organizing principles in normal physiology and that certain pathologies, including ventricular fibrillation, represent a class of 'pathological periodicities'. Some laboratory work bearing on the relation of nonlinear analysis to physiological and pathophysiological data is briefly reviewed, with tentative theories and models described in reference to the mechanism of ventricular fibrillation.

  3. Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis.

    PubMed

    Muehlenbachs, Atis; Bollweg, Brigid C; Schulz, Thadeus J; Forrester, Joseph D; DeLeon Carnes, Marlene; Molins, Claudia; Ray, Gregory S; Cummings, Peter M; Ritter, Jana M; Blau, Dianna M; Andrew, Thomas A; Prial, Margaret; Ng, Dianna L; Prahlow, Joseph A; Sanders, Jeanine H; Shieh, Wun Ju; Paddock, Christopher D; Schriefer, Martin E; Mead, Paul; Zaki, Sherif R

    2016-05-01

    Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues. PMID:26968341

  4. Pokkuri Death Syndrome; sudden cardiac death cases without coronary atherosclerosis in South Asian young males.

    PubMed

    Nakajima, Katsuyuki; Takeichi, Sanae; Nakajima, Yasuhiro; Fujita, Masaki Q

    2011-04-15

    Sudden death is one of the major concerns in forensic medicine. Especially when the deceased is a young subject without significant history, the case will be of major interest to the authorities. Sudden unexplained cardiac death has been known as "Pokkuri Death Syndrome" (PDS) in Japan, "Lai Tai" in Thailand, "Bangungut" in the Philippines, "Dream Disease" in Hawaii, and "Sudden Unexpected Nocturnal Death Syndrome" among South Asian immigrants in the USA. However, the clinical and pathological features of these sudden death cases, especially the characteristics of no coronary atherosclerosis, are surprisingly similar and mainly occur among Southeast Asian young males during sleep in the midnight. In this manuscript, we have reviewed the pathological characteristics and the possible mechanism of death in PDS cases, which were associated with significantly elevated remnant lipoproteins in plasma as revealed from our studies during the past 15 years in Japan. Although elevated plasma remnant lipoproteins have been known to be strongly atherogenic, coronary atherosclerosis was not observed in PDS cases. PDS cases were shown to be an interesting cardiovascular disease death discovered in forensic medicine research, which may suggest the difference between the occurrence of cardiovascular events and the severity of coronary atherosclerosis as separate factors. These observations in PDS cases suggest the possibility that the intervention could be more targeted to suppress the cardiovascular events rather than to slow down the progression of atherosclerosis, which is now most extensively targeted for the therapy of cardiovascular disease in Western countries. PMID:21084168

  5. Ibogaine-associated cardiac arrest and death: case report and review of the literature

    PubMed Central

    Meisner, Jessica A.; Wilcox, Susan R.; Richards, Jeremy B.

    2016-01-01

    A naturally occurring hallucinogenic plant alkaloid, ibogaine has been used as an adjuvant for opiate withdrawal for the past 50 years. In the setting of an escalating nationwide opiate epidemic, use of substances such as ibogaine may also increase. Therefore, familiarity with the mechanisms and potential adverse effects of ibogaine is important for clinicians. We present the case report of a man whose use of ibogaine resulted in cardiac arrest and death, complemented by a review of the literature regarding ibogaine’s clinical effects. A 40-year-old man who used ibogaine for symptoms of heroin withdrawal suffered acute cardiac arrest leading to cerebral edema and brain death. His presentation was consistent with ibogaine-induced cardiotoxicity and ibogaine-induced cardiac arrest, and a review of the literature regarding the history, mechanisms, risks and clinical outcomes associated with ibogaine is presented. The case presented underscores the significant potential clinical risks of ibogaine. It is important the healthcare community be aware of the possible effects of ibogaine such that clinicians can provide informed counseling to their patients regarding the risks of attempting detoxification with ibogaine. PMID:27141291

  6. Ibogaine-associated cardiac arrest and death: case report and review of the literature.

    PubMed

    Meisner, Jessica A; Wilcox, Susan R; Richards, Jeremy B

    2016-04-01

    A naturally occurring hallucinogenic plant alkaloid, ibogaine has been used as an adjuvant for opiate withdrawal for the past 50 years. In the setting of an escalating nationwide opiate epidemic, use of substances such as ibogaine may also increase. Therefore, familiarity with the mechanisms and potential adverse effects of ibogaine is important for clinicians. We present the case report of a man whose use of ibogaine resulted in cardiac arrest and death, complemented by a review of the literature regarding ibogaine's clinical effects. A 40-year-old man who used ibogaine for symptoms of heroin withdrawal suffered acute cardiac arrest leading to cerebral edema and brain death. His presentation was consistent with ibogaine-induced cardiotoxicity and ibogaine-induced cardiac arrest, and a review of the literature regarding the history, mechanisms, risks and clinical outcomes associated with ibogaine is presented. The case presented underscores the significant potential clinical risks of ibogaine. It is important the healthcare community be aware of the possible effects of ibogaine such that clinicians can provide informed counseling to their patients regarding the risks of attempting detoxification with ibogaine. PMID:27141291

  7. Ventricular fibrillation and sudden cardiac death during myocardial infarction.

    PubMed

    Jabbari, Reza

    2016-05-01

    In this PhD thesis, we report that VF is still a common complication of STEMI, with an incidence of 11.6% in the population of Danish STEMI patients who survive to reach the hospital. In this STEMI population, we identified several risk factors associated with VF independent of MI. We identified and confirmed findings from several previous studies and found several risk factors, such as younger age, a family history of sudden death, a TIMI flow grade of 0, the absence of angina, anterior infarction (i.e., VF before PPCI), and inferior infarction (i.e., VF during PPCI) that were associated with VF in a Danish cohort. Furthermore, a history of atrial fibrillation and alcohol intake were identified as novel risk factors for VF. To the best of our knowledge, this study contains data on the largest VF cohort with the longest reported follow-up published; we found that VF mortality is significantly higher within the first 30 days for patients who experience VF before and during PPCI compared with STEMI patients without VF. However, the long-term mortality rates of the three groups are the same. Importantly, our results contradict the previous understanding that VF during PPCI is "benign"; the mortality rate within the first 30 days was as high for patients with VF during PPCI as the mortality rate of patients with VF before PPCI. Finally, although it is difficult to draw clinical implications from a descriptive study, due to the comprehensiveness of Danish death certificates, we reported a high incidence of cardiac symptoms and contact with healthcare professionals based on cardiac symptoms in young SCD patients who died due to CAD, although death was not avoided. PMID:27127021

  8. Systems Approaches to Preventing Transplanted Cell Death in Cardiac Repair

    PubMed Central

    Robey, Thomas E.; Saiget, Mark K; Reinecke, Hans; Murry, Charles E.

    2008-01-01

    Stem cell transplantation may repair the injured heart, but tissue regeneration is limited by death of transplanted cells. Most cell death occurs in the first few days post-transplantation, likely from a combination of ischemia, anoikis and inflammation. Interventions known to enhance transplanted cell survival include heat shock, over-expressing anti-apoptotic proteins, free radical scavengers, anti-inflammatory therapy and co-delivery of extracellular matrix molecules. Combinatorial use of such interventions markedly enhances graft cell survival, but death still remains a significant problem. We review these challenges to cardiac cell transplantation and present an approach to systematically address them. Most anti-death studies use histology to assess engraftment, which is time- and labor-intensive. To increase throughput, we developed two biochemical approaches to follow graft viability in the mouse heart. The first relies on LacZ enyzmatic activity to track genetically modified cells, and the second quantifies human genomic DNA content using repetitive Alu sequences. Both show linear relationships between input cell number and biochemical signal, but require correction for the time lag between cell death and loss of signal. Once optimized, they permit detection of as few as 1 graft cell in 40,000 host cells. Pro-survival effects measured biochemically at three days predict long-term histological engraftment benefits. These methods permitted identification of carbamylated erythropoietin (CEPO) as a pro-survival factor for human embryonic stem cell-derived cardiomyocyte grafts. CEPO’s effects were additive to heat shock, implying independent survival pathways. This system should permit combinatorial approaches to enhance graft viability in a fraction of the time required for conventional histology. PMID:18466917

  9. Management of Acute Regurgitation in Left-Sided Cardiac Valves

    PubMed Central

    Mokadam, Nahush A.; Stout, Karen K.; Verrier, Edward D.

    2011-01-01

    The management of acute, severe cardiac valvular regurgitation requires expeditious multidisciplinary care. Although acute, severe valvular regurgitation can be a true surgical emergency, accurate diagnosis and subsequent treatment decisions require clinical acumen, appropriate imaging, and sound judgment. An accurate and timely diagnosis is essential for successful outcomes and requires appropriate expertise and a sufficiently high degree of suspicion in a variety of settings. Whereas cardiovascular collapse is the most obvious and common presentation of acute cardiac valvular regurgitation, findings may be subtle, and the clinical presentation can often be nonspecific. Consequently, other acute conditions such as sepsis, pneumonia, or nonvalvular heart failure may be mistaken for acute valvular regurgitation. In comparison with that of the right-sided valves, regurgitation of the left-sided valves is more common and has greater clinical impact. Therefore, this review focuses on acute regurgitation of the aortic and mitral valves. PMID:21423463

  10. Overexpression of KCNN3 results in sudden cardiac death

    PubMed Central

    Mahida, Saagar; Mills, Robert W.; Tucker, Nathan R.; Simonson, Bridget; Macri, Vincenzo; Lemoine, Marc D.; Das, Saumya; Milan, David J.; Ellinor, Patrick T.

    2014-01-01

    Background A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias. Methods and results We characterized the cardiac electrophysiological phenotype of a mouse line with overexpression of the SK3 channel. We generated homozygote (SK3T/T) and heterozygote (SK3+/T) mice with overexpression of the channel and compared them with wild-type (WT) controls. We observed a high incidence of sudden death among SK3T/T mice (7 of 19 SK3T/T mice). Ambulatory monitoring demonstrated that sudden death was due to heart block and bradyarrhythmias. SK3T/T mice displayed normal body weight, temperature, and cardiac function on echocardiography; however, histological analysis demonstrated that these mice have abnormal atrioventricular node morphology. Optical mapping demonstrated that SK3T/T mice have slower ventricular conduction compared with WT controls (SK3T/T vs. WT; 0.45 ± 0.04 vs. 0.60 ± 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old SK3T/T mice demonstrated inducible atrial arrhythmias (50% of SK3T/T vs. 0% of WT mice) and also a shorter atrioventricular nodal refractory period (SK3T/T vs. WT; 43 ± 6 vs. 52 ± 9 ms, P = 0.02). Three-month-old SK3T/T mice on the other hand displayed a trend towards a more prolonged atrioventricular nodal refractory period (SK3T/T vs. WT; 61 ± 1 vs. 52 ± 6 ms, P = 0.06). Conclusion Overexpression of the SK3 channel causes an increased risk of sudden death associated with bradyarrhythmias and heart block, possibly due to atrioventricular nodal dysfunction. PMID:24296650

  11. Lactate and lactate clearance in acute cardiac care patients

    PubMed Central

    Lazzeri, Chiara; Picariello, Claudio; Dini, Carlotta Sorini; Gensini, Gian Franco; Valente, Serafina

    2012-01-01

    Hyperlactataemia is commonly used as a diagnostic and prognostic tool in intensive care settings. Recent studies documented that serial lactate measurements over time (or lactate clearance), may be clinically more reliable than lactate absolute value for risk stratification in different pathological conditions. While the negative prognostic role of hyperlactataemia in several critical ill diseases (such as sepsis and trauma) is well established, data in patients with acute cardiac conditions (i.e. acute coronary syndromes) are scarce and controversial. The present paper provides an overview of the current available evidence on the clinical role of lactic acid levels and lactate clearance in acute cardiac settings (acute coronary syndromes, cardiogenic shock, cardiac surgery), focusing on its prognostic role. PMID:24062898

  12. Cardiac and other abnormalities in the sudden infant death syndrome.

    PubMed

    Naeye, R L; Whalen, P; Ryser, M; Fisher, R

    1976-01-01

    Many victims of the sudden infant death syndrome (SIDS) have abnormally heavy cardiac right ventricles. The degree of this abnormality is directly proportional to: a) the mass of muscle about small pulmonary arteries, b) the amount of brown fat retention about adrenal glands, and c) the presence of hepatic erythropoiesis. The pulmonary arterial abnormality is probably the result of chronic alveolar hypoventilation, while brown fat retention and hepatic erythropoiesis are likely consequences of chronic hypoxemia. These abnormalities are found in both SIDS victims who die with and those who die without mild respiratory tract infections. However, there are some differences between the two SIDS groups. Infected victims die at an older age and have smaller thymus glands and larger spleens; there is a greater proportion of males in the infected victims than in the noninfected victims. PMID:1247080

  13. Arrhythmias, Sudden Cardiac Death and incapacitation of pilots

    PubMed Central

    Mantziari, L; Styliadis, C; Kourtidou-Papadeli, C; Styliadis, I

    2008-01-01

    Inflight medical emergencies occur at a rate of 20 to 100 per million passengers, with a death rate of 0.1 to 1 per million. Cardiac, neurologic, and respiratory complaints comprise the more serious emergencies, as defined by aircraft diversion or use of ground-based medical assistance. In this paper, we review changes seen in the resting electrocardiogram in normal individuals exposed to high altitude, alongside important implications for patients with heart diseases in high altitude exposures and the possible effects of high altitude to permanent cardiac pacemakers. Arrhythmias in pilots and public safety are revisited together with the guidelines of the Joint Aviation Requirements (JAR) in Europe. The situation of Military flights is also discussed. Physicians ought to become knowledgeable about the specific medical job standards for their patients when asked to render opinions regarding fitness to fly. A database must be established to obtain prospective data that defines the risk of accidents in patients who are or were being treated for arrhythmias. Current guidelines could then be updated and revised as appropriate. PMID:19050752

  14. Sudden cardiac death: ethical considerations in the return to play.

    PubMed

    Piantanida, Nicholas A; Oriscello, Ralph G; Pettrone, Frank A; O'Connor, Francis G

    2004-04-01

    The team physician-athlete relationship prompts many basic questions in medical ethics. Return-to-play decisions form many of the core responsibilities facing team physicians, and occasionally these decisions can have overriding ethical dilemmas. Therefore, a structured ethical decision-making process is a valuable skill for every successful sports medicine physician. An ethical question is confronted here in a case presentation that weighs the risk of repeat sudden cardiac death and the potential for failed cardiac resuscitation against the athlete's interest to play competitive basketball. The article applies a four-step framework for ethical decision making in sports medicine. The important first step includes gathering medical information and understanding the preferences of the athlete. Step 2 brings together the decision-making stakeholders, the team physician as a member, to define ethical issues and apply ethical principles: beneficence, non-maleficence, and patient autonomy. Step 3 selects a course of action with unbiased analysis and arrives at a good choice that merits an action plan in step 4. This decision need not be perfect, but should reinforce the team physician's responsibilities to the athlete and center on the athlete's welfare. PMID:14980137

  15. Early repolarization syndrome: A cause of sudden cardiac death

    PubMed Central

    Ali, Abdi; Butt, Nida; Sheikh, Azeem S

    2015-01-01

    Early repolarization syndrome (ERS), demonstrated as J-point elevation on an electrocardiograph, was formerly thought to be a benign entity, but the recent studies have demonstrated that it can be linked to a considerable risk of life - threatening arrhythmias and sudden cardiac death (SCD). Early repolarization characteristics associated with SCD include high - amplitude J-point elevation, horizontal and/or downslopping ST segments, and inferior and/or lateral leads location. The prevalence of ERS varies between 3% and 24%, depending on age, sex and J-point elevation (0.05 mV vs 0.1 mV) being the main determinants. ERS patients are sporadic and they are at a higher risk of having recurrent cardiac events. Implantable cardioverter-defibrillator implantation and isoproterenol are the suggested therapies in this set of patients. On the other hand, asymptomatic patients with ERS are common and have a better prognosis. The risk stratification in asymptomatic patients with ERS still remains a grey area. This review provides an outline of the up-to-date evidence associated with ERS and the risk of life - threatening arrhythmias. Further prospective studies are required to elucidate the mechanisms of ventricular arrhythmogenesis in patients with ERS. PMID:26322186

  16. Cell Death and Serum Markers of Collagen Metabolism during Cardiac Remodeling in Cavia porcellus Experimentally Infected with Trypanosoma cruzi

    PubMed Central

    Castro-Sesquen, Yagahira E.; Gilman, Robert H.; Paico, Henry; Yauri, Verónica; Angulo, Noelia; Ccopa, Fredy; Bern, Caryn

    2013-01-01

    We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV) deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP). Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response) predominated throughout the course of infection; IgG1 (Th2 response) was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively). These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection. PMID:23409197

  17. Cell death and serum markers of collagen metabolism during cardiac remodeling in Cavia porcellus experimentally infected with Trypanosoma cruzi.

    PubMed

    Castro-Sesquen, Yagahira E; Gilman, Robert H; Paico, Henry; Yauri, Verónica; Angulo, Noelia; Ccopa, Fredy; Bern, Caryn

    2013-01-01

    We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV) deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP). Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response) predominated throughout the course of infection; IgG1 (Th2 response) was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively). These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection. PMID:23409197

  18. QT dispersion as a risk factor for sudden cardiac death and fatal myocardial infarction in a coronary risk population.

    PubMed Central

    Mänttäri, M.; Oikarinen, L.; Manninen, V.; Viitasalo, M.

    1997-01-01

    OBJECTIVE: To test in a prospective study the hypothesis that increased QT dispersion in resting 12-lead ECG is a predictor of sudden cardiac death. DESIGN: A nested case-control study during a mean (SD) follow up time of 6.5 (2.8) years. SETTING: A prospective, placebo controlled, coronary prevention trial with gemfibrozil among dyslipidaemic middle aged men in primary (occupational) health care units: the Helsinki heart study. PATIENTS: 24 victims of fatal myocardial infarction, 48 victims of sudden cardiac death without acute myocardial infarction, and their matched controls. MAIN OUTCOME MEASURES: QT dispersion in baseline and pre-event electrocardiograms. RESULTS: At study baseline, QT dispersion was similar in all victims and controls. When estimated from the pre-event ECG on average 14 months before death, the risk of sudden cardiac death in the highest QTPEAK (up to the peak of the T wave) dispersion tertile (> or = 50 ms) was 6.2-fold (95% confidence interval 1.7 to 23.5) compared with the risk in the lowest tertile (< or = 30 ms), and 4.9-fold (1.2 to 19.5) after adjustment for the presence of left ventricular hypertrophy, while QTPEAK dispersion could not predict fatal myocardial infarction. QTEND dispersion (up to the end of the T wave) in pre-event ECGs could not discriminate victims of either sudden cardiac death or fatal myocardial infarction from their matched controls. CONCLUSIONS: In middle aged men with a normal conventional QT interval in 12-lead resting ECG, increased QTPEAK dispersion is an independent risk factor for sudden cardiac death, but not for fatal myocardial infarction. PMID:9391289

  19. Prevention of sudden cardiac death in hemodialysis patients.

    PubMed

    O'Shaughnessy, Michelle M; O'Regan, John A; Lavin, Peter J

    2014-01-01

    One quarter of all hemodialysis patients will succumb to sudden cardiac death (SCD), a rate far exceeding that observed in the general population. A high prevalence of atherosclerotic coronary artery disease amongst patients with end-stage kidney disease (ESKD) partly explains this exaggerated risk. However, uremia and dialysis related factors are also of critical importance. Interventions aimed at preventing SCD have been inadequately studied in patients with ESKD. Data extrapolated from non-renal populations cannot necessarily be applied to hemodialysis patients, who possess relatively unique risk factors for SCD including "uremic cardiomyopathy", electrolyte shifts, fluctuations in intravascular volume and derangements of mineral and bone metabolism. Pending data derived from proposed randomized controlled clinical trials, critical appraisal of existing evidence and the selective application of guidelines developed for the general population to dialysis patients are required if therapeutic nihilism, or excessive intervention, are to be avoided. We discuss the evidence supporting a role for medical therapies, dialysis prescription refinements, revascularization procedures and electrical therapies as potential interventions to prevent SCD amongst hemodialysis patients. Based on current best available evidence, we present suggested strategies for the prevention of arrhythmia-mediated death in this highly vulnerable patient population. PMID:24720456

  20. A New Insight Into Sudden Cardiac Death in Young People

    PubMed Central

    Wang, Yueyue; Xia, Lei; Shen, Xiaodong; Han, Guoxin; Feng, Dan; Xiao, Hongju; Zhai, Yongzhi; Chen, Xin; Miao, Yuanyuan; Zhao, Chunhong; Wang, Yingchan; Guo, Mingguang; Li, Tanshi; Zhu, Hai Yan

    2015-01-01

    Abstract Takotsubo cardiomyopathy (TTC) causes sudden cardiac death and has garnered increased attention worldwide in recent years. However, few studies have clearly classified the risk factors for this disease, including gender, race and morbidity, as well as the physical and mental stressors that can exacerbate the disease, particularly in young patients. To better analyze the characteristics of young TTC patients, we performed a systematic review of reported cases involving young patients. A computer-assisted search was performed using prominent electronic medical information sources to identify literature published between January 1965 and December 2013. Relevant studies containing clinical data of young TTC patients were included. Ninety-six records that included information about 104 cases were ultimately selected for our review. Several of the following results were noted: First, physical stress was more likely to exacerbate TTC than was mental stress in young patients. Second, more female than male TTC patients were noted among both young patients and the general population. Third, ethnicity appears to play no role in the disease, as no significant differences were noted among individuals of different races with respect to clinical characteristics, morbidity or stressors. Fourth, the clinical manifestations of TTC were similar to those of other cardiac diseases, including coronary heart disease. However, TTC may be detected using the combination of echocardiography and ventriculography. Clinicians should consider TTC if young patients present with symptoms similar to those of coronary heart disease so that harmful treatments such as coronary artery stent placement may be avoided. Moreover, the answers to questions regarding the clinical diagnostic criteria, etiology, pathophysiology, and the management of this syndrome in youth remain unclear; therefore, further research is needed. PMID:26266349

  1. Risk stratification for cardiac death in hemodialysis patients without obstructive coronary artery disease.

    PubMed

    Nishimura, Masato; Tsukamoto, Kazumasa; Tamaki, Nagara; Kikuchi, Kenjiro; Iwamoto, Noriyuki; Ono, Toshihiko

    2011-02-01

    The incidence of cardiac death is higher among patients receiving dialysis compared with the general population. Although obstructive coronary artery disease is involved in cardiac deaths in the general population, deaths in hemodialysis patients occur in the apparent absence of obstructive coronary artery disease. To study this further, we prospectively enrolled 155 patients receiving hemodialysis after angiography had confirmed the absence of obstructive coronary lesions. All patients were examined by single-photon emission computed tomography using the iodinated fatty acid analog, BMIPP, the uptake of which was graded in 17 standard myocardial segments and assessed as summed scores. Insulin resistance was determined using the homeostasis model assessment index of insulin resistance (HOMA-IR). During a mean follow-up of 5.1 years, 42 patients died of cardiac events. Stepwise Cox hazard analysis associated cardiac death with reduced BMIPP uptake and increased insulin resistance. Patients were assigned to subgroups based on BMIPP summed scores and HOMA-IR cutoff values for cardiac death of 12 and 5.1, respectively, determined by receiver operating characteristic analysis. Cardiac death-free survival rates at 5 years were the lowest (32.2%) in the subgroup with both a summed score and assessment equal to or above the cutoff values compared with any other combination (52.9-98.7%) above, equal to, or below the thresholds. Thus, impaired myocardial fatty acid metabolism and insulin resistance may be associated with cardiac death among hemodialysis patients without obstructive coronary artery disease. PMID:20944544

  2. Left Ventricular Diameter and Risk Stratification for Sudden Cardiac Death

    PubMed Central

    Narayanan, Kumar; Reinier, Kyndaron; Teodorescu, Carmen; Uy‐Evanado, Audrey; Aleong, Ryan; Chugh, Harpriya; Nichols, Gregory A.; Gunson, Karen; London, Barry; Jui, Jonathan; Chugh, Sumeet S.

    2014-01-01

    Background Left ventricular (LV) diameter is routinely measured on the echocardiogram but has not been jointly evaluated with the ejection fraction (EF) for risk stratification of sudden cardiac death (SCD). Methods and Results From a large ongoing community‐based study of SCD (The Oregon Sudden Unexpected Death Study; population ≈1 million), SCD cases were compared with geographic controls. LVEF and LV diameter, measured using the LV internal dimension in diastole (categorized as normal, mild, moderate, or severe dilatation using American Society of Echocardiography definitions) were assessed from echocardiograms prior but unrelated to the SCD event. Cases (n=418; 69.5±13.8 years), compared with controls (n=329; 67.7±11.9 years), more commonly had severe LV dysfunction (EF ≤35%; 30.5% versus 18.8%; P<0.01) and larger LV diameter (52.2±10.5 mm versus 49.7±7.9 mm; P<0.01). Moderate or severe LV dilatation (16.3% versus 8.2%; P=0.001) and severe LV dilatation (8.1% versus 2.1%; P<0.001) were significantly more frequent in cases. In multivariable analysis, severe LV dilatation was an independent predictor of SCD (odds ratio 2.5 [95% CI 1.03 to 5.9]; P=0.04). In addition, subjects with both EF ≤35% and severe LV dilatation had higher odds for SCD compared with those with low EF only (odds ratio 3.8 [95% CI 1.5 to 10.2] for both versus 1.7 [95% CI 1.2 to 2.5] for low EF only), suggesting that severe LV dilatation additively increased SCD risk. Conclusion LV diameter may contribute to risk stratification for SCD independent of the LVEF. This readily available echocardiographic measure warrants further prospective evaluation. PMID:25227407

  3. Incidence of Sudden Cardiac Death in a Young Active Population

    PubMed Central

    Farioli, Andrea; Christophi, Costas A; Quarta, Candida Cristina; Kales, Stefanos N

    2015-01-01

    Background Little is known about the burden of sudden cardiac death (SCD) among active, presumably healthy persons. We investigated the incidence of SCD among US male career firefighters. Methods and Results All on-duty SCDs among US male career firefighters between 1998 and 2012 were identified from the US Fire Administration and the US National Institute for Occupational Safety and Health databases. Age-specific incidence rates (IRs) of SCD with 95% CIs were computed. A joinpoint model was fitted to analyze the trend in IR and to help estimate the annual percentage change of SCD rates over the years. The effects of seasonality were assessed through a Poisson regression model. We identified 182 SCDs; based on 99 available autopsy reports, the leading underlying cause of death was coronary heart disease (79%). The overall IR was 18.1 SCDs per 100 000 person-years. The age-specific IRs of SCD ranged between 3.8 (for those aged 18 to 24 years) and 45.2 (for those aged 55 to 64 years) per 100 000 person-years. The annual rate of SCD steadily declined over time (annual percentage change −3.9%, 95% CI −5.8 to −2.0). SCD events were more frequent during January (peak-to-low ratio 1.70; 95% CI 1.09 to 2.65). In addition, the IR was 3 times higher during high-risk duties compared with low-risk duties. IRs among firefighters were lower than those observed among the US general population and US military personnel. Conclusions SCD risk in this active working population is overestimated using statistics from the general population. To address public health questions among these subpopulations, more specific studies of active adults should be conducted. PMID:26066031

  4. Donation after cardiac death: A 29-year experience

    PubMed Central

    Bellingham, Janet M.; Santhanakrishnan, Chandrasekar; Neidlinger, Nikole; Wai, Philip; Kim, Jim; Niederhaus, Silke; Leverson, Glen E.; Fernandez, Luis A.; Foley, David P.; Mezrich, Joshua D.; Odorico, Jon S.; Love, Robert B.; Oliveira, Nilto De; Sollinger, Hans W.; D’Alessandro, Anthony M.

    2012-01-01

    Objective To report the long-term outcomes of 1218 organs transplanted from donation after cardiac death (DCD) donors from January 1980 through December 2008. Methods One-thousand two-hundred-eighteen organs were transplanted into 1137 recipients from 577 DCD donors. This includes 1038 kidneys (RTX), 87 livers (LTX), 72 pancreas (PTX), and 21 DCD lungs. The outcomes were compared with 3470 RTX, 1157 LTX, 903 PTX, and 409 lung transplants from donors after brain death (DBD). Results Both patient and graft survival is comparable between DBD and DCD transplant recipients for kidney, pancreas, and lung after 1, 3, and 10 years. Our findings reveal a significant difference for patient and graft survival of DCD livers at each of these time points. In contrast to the overall kidney transplant experience, the most recent 16-year period (n = 396 DCD and 1,937 DBD) revealed no difference in patient and graft survival, rejection rates, or surgical complications but delayed graft function was higher (44.7% vs 22.0%; P < .001). In DCD LTX, biliary complications (51% vs 33.4%; P < .01) and retransplantation for ischemic cholangiopathy (13.9% vs 0.2%; P < .01) were increased. PTX recipients had no difference in surgical complications, rejection, and hemoglobin A1c levels. Surgical complications were equivalent between DCD and DBD lung recipients. Conclusion This series represents the largest single center experience with more than 1000 DCD transplants and given the critical demand for organs, demonstrates successful kidney, pancreas, liver, and lung allografts from DCD donors. (Surgery 2011;150:692-702.) PMID:22000181

  5. A partial defect in technetium-99m pyrophosphate image suggesting cardiac rupture following acute myocardial infarction.

    PubMed

    Tsujino, M; Hiroe, M; Sugimoto, K; Miyahara, Y; Ishii, Z; Taniguchi, K; Marumo, F

    1992-01-01

    We present the case of a 70-year-old woman with acute myocardial infarction who died of cardiac rupture on the 2nd hospital day. Dual isotope single photon emission computed tomography (SPECT) using thallium-201 chloride and technetium-99m pyrophosphate (PYP) performed on the 2nd hospital day showed a large perfusion defect in the anteroseptal wall on 201Tl image and a increased accumulation on 99mTc-PYP image in the anterior area consistent with a partial defect. Autopsy performed 1 h after death revealed a tear in the left ventricular anterior wall consistent with the defect on the 99mTc-PYP image. We propose that the finding of a partial defect in 99mTc-PYP is an interesting finding which may be associated with cardiac rupture following acute myocardial infarction. PMID:1533369

  6. History of organ donation by patients with cardiac death.

    PubMed

    DeVita, M A; Snyder, J V; Grenvik, A

    1993-06-01

    When successful solid organ transplantation was initiated almost 40 years ago, its current success rate was not anticipated. But continuous efforts were undertaken to overcome the two major obstacles to success: injury caused by interrupting nutrient supply to the organ and rejection of the implanted organ by normal host defense mechanisms. Solutions have resulted from technologic medical advances, but also from using organs from different sources. Each potential solution has raised ethical concerns and has variably resulted in societal acclaim, censure, and apathy. Transplant surgery is now well accepted, and the list of transplant candidates has grown far quicker than the availability of organs. More than 30,000 patients were awaiting organs for transplantation at the end of March 1993. While most organs came from donors declared dead by brain criteria, the increasing shortage of donated organs has prompted a reexamination of prior restrictions of donor groups. Recently, organ procurement from donors with cardiac death has been reintroduced in the United States. This practice has been mostly abandoned by the U.S. and some, though not all, other countries. Transplantation has been more successful using organs procured from heart-beating, "brain dead" cadavers than organs from non-heart-beating cadavers. However, recent advances have led to success rates with organs from non-heart-beating donors that may portend large increases in organ donation and procurement from this source. PMID:10126525

  7. Risk of sudden cardiac death in chronic kidney disease.

    PubMed

    Poulikakos, Dimitrios; Banerjee, Debasish; Malik, Marek

    2014-02-01

    The review discusses the epidemiology and the possible underlying mechanisms of sudden cardiac death (SCD) in chronic kidney disease (CKD), and highlights the unmet clinical need for noninvasive risk stratification strategies in these patients. Although renal dysfunction shares common risk factors and often coexists with atherosclerotic cardiovascular disease, the presence of renal impairment increases the risk of arrhythmic complications to an extent that cannot be explained by the severity of the atherosclerotic process. Renal impairment is an independent risk factor for SCD from the early stages of CKD; the risk increases as renal function declines and reaches very high levels in patients with end-stage renal disease on dialysis. Autonomic imbalance, uremic cardiomyopathy, and electrolyte disturbances likely play a role in increasing the arrhythmic risk and can be potential targets for treatment. Cardioverter defibrillator treatment could be offered as lifesaving treatment in selected patients, although selection strategies for this treatment mode are presently problematic in dialyzed patients. The review also examines the current experience with risk stratification tools in renal patients and suggests that noninvasive electrophysiological testing during dialysis may be of clinical value as it provides the necessary standardized environment for reproducible measurements for risk stratification purposes. PMID:24256575

  8. Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death.

    PubMed

    Feng, Qian; Leong, Wa Seng; Liu, Liang; Chan, Wai-In

    2016-01-01

    Despite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug resistance. Cardiac glycosides (CGs) have been used in treating heart failure despite its toxicity. Recently, increasing evidence has demonstrated its new usage as a potential anti-cancer drug. Ouabain, one of the CGs, specifically targeted CD34⁺CD38(-) leukemic stem-like cells, but not the more mature CD34⁺CD38⁺ leukemic cells, making this type of compounds a potential treatment for leukemia. In search of other potential anti-leukemia CGs, we found that Peruvoside, a less studied CG, is more effective than Ouabain and Digitoxin at inducing cell death in primitive myeloid leukemia cells without obvious cytotoxicity on normal blood cells. Similar to Ouabain and Digitoxin, Peruvoside also caused cell cycle arrest at G₂/M stage. It up-regulates CDKN1A expression and activated the cleavage of Caspase 3, 8 and PARP, resulting in apoptosis. Thus, Peruvoside showed potent anti-leukemia effect, which may serve as a new anti-leukemia agent in the future. PMID:27110755

  9. Does cardiac conduction pathology contribute to sudden unexpected death in epilepsy?

    PubMed

    Opeskin, K; Thomas, A; Berkovic, S F

    2000-06-01

    Heart weights have been reported to be increased in those dying suddenly and unexpectedly from epilepsy (SUDEP) and it has been suggested that cardiac pathology including cardiac conduction pathology and coronary artery atheroma may contribute to SUDEP. The purpose of this study was to perform a detailed controlled study of the microscopic pathology of the cardiac conduction system in SUDEP cases, in addition to assessing coronary artery atheroma and other cardiac pathology. The hearts of ten SUDEPs and ten control subjects (no history of epilepsy and a cause of death not primarily cardiac) were examined macroscopically and microscopically by two pathologists blinded to the patient group. Morphological abnormalities of the cardiac conduction system that could have possibly contributed to death were not increased in the SUDEP group (four cases showed such changes in the SUDEP group vs. six in the control). There was no significant difference between the maximal percentage coronary artery stenoses between the two groups and no increased prevalence of other cardiac pathology in the SUDEP group. However, since subtle abnormalities of the conduction system were identified in some of the epileptic deaths, it is still feasible that these may contribute to death by causing cardiac arrhythmia, when associated with apnoea, bradycardia or other cardiac arrhythmia related to an epileptic seizure. PMID:10771254

  10. Acute myocardial infarction and sudden death in Sioux Indians.

    PubMed Central

    Hrabovsky, S L; Welty, T K; Coulehan, J L

    1989-01-01

    While some Indian tribes have low rates of acute myocardial infarction, Northern Plains Indians, including the Sioux, have rates of morbidity and mortality from acute myocardial infarction higher than those reported for the United States population in general. In a review of diagnosed cases of acute myocardial infarction over a 3-year period in 2 hospitals serving predominantly Sioux Indians, 8% of cases were found misclassified, and 22% failed to meet rigorous diagnostic criteria, although the patients did indeed have ischemic heart disease. Patients had high frequencies of complications and risk factors and a fatality rate of 16% within a month of admission. Sudden deaths likely due to ischemic heart disease but in persons not diagnosed as having acute myocardial infarction by chart review occurred 3 times more frequently than deaths occurring within a month of clinical diagnosis. PMID:2735047

  11. Perspectives on the value of biomarkers in acute cardiac care and implications for strategic management.

    PubMed

    Kossaify, Antoine; Garcia, Annie; Succar, Sami; Ibrahim, Antoine; Moussallem, Nicolas; Kossaify, Mikhael; Grollier, Gilles

    2013-01-01

    Biomarkers in acute cardiac care are gaining increasing interest given their clinical benefits. This study is a review of the major conditions in acute cardiac care, with a focus on biomarkers for diagnostic and prognostic assessment. Through a PubMed search, 110 relevant articles were selected. The most commonly used cardiac biomarkers (cardiac troponin, natriuretic peptides, and C-reactive protein) are presented first, followed by a description of variable acute cardiac conditions with their relevant biomarkers. In addition to the conventional use of natriuretic peptides, cardiac troponin, and C-reactive protein, other biomarkers are outlined in variable critical conditions that may be related to acute cardiac illness. These include ST2 and chromogranin A in acute dyspnea and acute heart failure, matrix metalloproteinase in acute chest pain, heart-type fatty acid binding protein in acute coronary syndrome, CD40 ligand and interleukin-6 in acute myocardial infarction, blood ammonia and lactate in cardiac arrest, as well as tumor necrosis factor-alpha in atrial fibrillation. Endothelial dysfunction, oxidative stress and inflammation are involved in the physiopathology of most cardiac diseases, whether acute or chronic. In summary, natriuretic peptides, cardiac troponin, C-reactive protein are currently the most relevant biomarkers in acute cardiac care. Point-of-care testing and multi-markers use are essential for prompt diagnostic approach and tailored strategic management. PMID:24046510

  12. Roadway Proximity and Risk of Sudden Cardiac Death in Women

    PubMed Central

    Hart, Jaime E; Chiuve, Stephanie E; Laden, Francine; Albert, Christine M

    2015-01-01

    Background Sudden cardiac death (SCD) is a major source of mortality and is the first manifestation of heart disease for the majority of cases. Thus, there is a definite need to identify risk factors for SCD that can be modified on the population level. Exposure to traffic, measured by residential roadway proximity, has been shown to be associated with an increased risk of cardiovascular disease. Our objective was to determine if roadway proximity was associated with an increased risk of SCD and to compare to the risk of other coronary heart disease (CHD) outcomes. Methods and Results A total of 523 cases of SCD were identified over 26 years of follow-up among 107,130 members of the prospective Nurses’ Health Study. We calculated residential distance to roadways at all residential addresses from 1986–2012. In age- and race-adjusted models, women living within 50 meters of a major roadway had an elevated risk of SCD (HR=1.56; 95%CI: 1.18–2.05). The association was attenuated but still statistically significant after controlling for potential confounders and mediators (HR=1.38; 95%CI:1.04–1.82). The equivalent adjusted HRs for nonfatal myocardial infarction and fatal CHD were 1.08 (95%CI: 0.96–1.23) and 1.24 (95%CI: 1.03–1.50), respectively. Conclusions Among this sample of middle-aged and older women, roadway proximity was associated with an elevated and statistically significant risks of SCD and fatal CHD, even after controlling for other cardiovascular risk factors. PMID:25332277

  13. Sudden cardiac death associated with occult hypertrophic cardiomyopathy in a dog under anesthesia

    PubMed Central

    2005-01-01

    Abstract A 6-year-old, 3.0 kg, neutered female, Yorkshire terrier was referred for orthopedic surgery. Cardiac arrest followed unsuccessful treatment of bradycardia and systemic arterial hypotension under general anesthesia. Postmortem examination revealed hypertrophic cardiomyopathy. A possible relationship between treatment of bradycardia, systemic arterial hypotension, and sudden cardiac death is described. PMID:16422064

  14. State of the art in forensic investigation of sudden cardiac death.

    PubMed

    Oliva, Antonio; Brugada, Ramon; D'Aloja, Ernesto; Boschi, Ilaria; Partemi, Sara; Brugada, Josep; Pascali, Vincenzo L

    2011-03-01

    The sudden death of a young person is a devastating event for both the family and community. Over the last decade, significant advances have been made in understanding both the clinical and genetic basis of sudden cardiac death. Many of the causes of sudden death are due to genetic heart disorders, which can lead to both structural (eg, hypertrophic cardiomyopathy) and arrhythmogenic abnormalities (eg, familial long QT syndrome, Brugada syndrome). Most commonly, sudden cardiac death can be the first presentation of an underlying heart problem, leaving the family at a loss as to why an otherwise healthy young person has died. Not only is this a tragic event for those involved, but it also presents a great challenge to the forensic pathologist involved in the management of the surviving family members. Evaluation of families requires a multidisciplinary approach, which should include cardiologists, a clinical geneticist, a genetic counselor, and the forensic pathologist directly involved in the sudden death case. This multifaceted cardiac genetic service is crucial in the evaluation and management of the clinical, genetic, psychological, and social complexities observed in families in which there has been a young sudden cardiac death. The present study will address the spectrum of structural substrates of cardiac sudden death with particular emphasis given to the possible role of forensic molecular biology techniques in identifying subtle or even merely functional disorders accounting for electrical instability. PMID:20083991

  15. Thrombo-hemorrhagic deaths in acute promyelocytic leukemia.

    PubMed

    Breccia, Massimo; Lo Coco, Francesco

    2014-05-01

    Acute promyelocytic leukemia (APL) has become the most curable form of acute myeloid leukemia after the advent of all-trans retinoic acid (ATRA). However, early deaths (ED) mostly due to the disease-associated coagulopathy remain the major cause of treatment failure. In particular, hemorrhagic events account for 40-65% of ED and several prognostic factors have been identified for such hemorrhagic deaths, including poor performance status, high white blood cell (WBC) count and coagulopathy. Occurrence of thrombosis during treatment with ATRA may be associated with differentiation syndrome (DS) or represent an isolated event. Some prognostic factors have been reported to be associated with thrombosis, including increased WBC or aberrant immunophenotype of leukemic promyelocytes. Aim of this review is to report the incidence, severity, possible pathogenesis and clinical manifestations of thrombo-haemorrhagic deaths in APL. PMID:24862130

  16. Cardiac Failure 30 Years after Treatment Containing Anthracycline for Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Goldberg, John M.; Scully, Rebecca E.; Sallan, Stephen E.; Lipshultz, Steven E.

    2012-01-01

    In 1977, a 5-year-old girl diagnosed with acute lymphoblastic leukemia (ALL) was treated on DFCI Childhood ALL Protocol 77-01, receiving a cumulative doxorubicin dose of 465 mg/m2, cranial radiation, and other drugs. After being in continuous complete remission for 34 months, she developed heart failure (HF) and was treated with digoxin and furosemide. At 16, she was diagnosed and treated for dilated cardiomyopathy. Over the years she continued to have bouts of HF, which became less responsive to treatment. At 36, she received a heart transplant. Six months later, she stopped taking her medications and suffered a sudden cardiac death. PMID:22584777

  17. Child homicide or natural death? A case report of unexpected death of unusual asymptomatic acute laryngotracheobronchitis.

    PubMed

    Zhuo, Luo; Liu, Liang; Ren, Liang; Liu, Qian

    2016-07-01

    Cases involving the unexpected deaths of children are always a concern for the police and medical examiners alike. In particular, unexpected deaths due to asphyxia without obvious injuries sometimes make decisions regarding the manner of death more difficult. In the present case, a 2-year-old boy was found dead at home, and his mother was initially believed to have killed him. A complete autopsy and forensic investigation were performed, and no injuries were found on the body; however, marked laryngeal edema was observed. Histology showed extensive inflammatory infiltration of the mucosa and submucosa of the larynx, trachea, and bronchi. The cause of death was given as respiratory failure due to acute laryngotracheobronchitis; thus, the manner of death was natural. This case helps to remind the forensic community to keep an open mind and consider a broad differential diagnosis when approaching a case rather than jumping to a conclusion based solely on a preliminary investigation. PMID:26101441

  18. Motivation to Pursue Genetic Testing in Individuals with a Personal or Family History of Cardiac Events or Sudden Cardiac Death

    PubMed Central

    Erskine, Kathleen E.; Hidayatallah, Nadia Z.; Walsh, Christine A.; McDonald, Thomas V.; Cohen, Lilian; Marion, Robert W.; Dolan, Siobhan M.

    2014-01-01

    Genetic testing is becoming increasingly available for cardiac channelopathies, such as long QT syndrome and Brugada syndrome, which can lead to sudden cardiac death. Test results can be used to shape an individual’s medical management and to identify at-risk family members. In our qualitative study, all participants had a personal or family history of a diagnosed cardiac arrhythmia syndrome or sudden cardiac death. Open-ended interviews were conducted individually and in focus groups. Interviews were audio recorded, transcribed verbatim, and analyzed using a qualitative grounded-theory approach. Of 50 participants, 37 described their motivations for pursuing genetic testing for long QT syndrome or another cardiac channelopathy. Participants’ motivations included: to find an explanation for a family member’s sudden death, to relieve uncertainty regarding a diagnosis, to guide future medical management, to allay concern about children or other family members, and to comply with recommendations of physicians or family members. Perceived reasons not to pursue genetic testing included denial, fear, and lack of information. The genetic counseling and informed consent process can be enhanced by understanding and addressing an individual’s internal and external motivations either for or against pursuing genetic testing. PMID:24664857

  19. Sudden cardiac death in epilepsy disappoints, but epileptologists keep faith.

    PubMed

    Scorza, Fulvio A; Cavalheiro, Esper A; Costa, Jaderson Costa da

    2016-07-01

    Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people with intractable epilepsy. Probably, optimization of seizure control will prevent some of these deaths. Briefly, we integrated in this paper some data about the epidemiology, risk factors, etiology, and preventative measures in the management of SUDEP. PMID:27487377

  20. Decreased mRNA levels of cardiac Cx43 and ZO1 in sudden cardiac death related to coronary atherosclerosis: a pilot study.

    PubMed

    Xue, Ye; Zhao, Rui; Du, Si-Hao; Zhao, Dong; Li, Dong-Ri; Xu, Jing-Tao; Xie, Xiao-Li; Wang, Qi

    2016-07-01

    Sudden cardiac death (SCD) is the most frequent cause of sudden unexplained death in forensic practice. The most common cause of SCD is coronary artery disease related to coronary atherosclerosis. Previous study suggested the possible application of connexin 43 (Cx43) and zonula occludens-1 (ZO1) immunostaining in the early diagnosis of myocardial ischemia. However, there appears to be insufficient data with regard to their mRNA levels. The present study investigated the cardiac mRNA levels of Cx43 and ZO1, using forensic autopsy materials consisting of 41 control cases without any disease or structural abnormality of the heart (group 1), 32 deaths due to acute ischemic heart disease related to coronary atherosclerosis without apparent myocardial necrosis (group 2), and 29 traumatic deaths with coronary atherosclerosis (group 3). Ten candidate reference genes were evaluated in the left ventricles of 10 forensic autopsy cases. EEF1A1, PPIA, TPT1, and RPL13A were identified as the most stable reference genes. Using these validated reference genes, mRNA levels of Cx43 and ZO1 were examined in the bilateral ventricles and atria of the heart. Relative mRNA quantification demonstrated decreased calibrated normalized relative quantity (CNRQ) values of Cx43 and ZO1 in bilateral ventricles of group 2. When using one conventional reference gene (GAPDH or ACTB) for normalization, nearly no difference was detected among the three groups. These findings indicate that ventricular gap junction remodeling may be a key contributor to rhythm disturbances. Analysis of cardiac Cx43 and ZO1 using real-time PCR is useful in diagnosis of SCD, and validation of reference genes is crucial. PMID:26972693

  1. Donation after cardiac death: is a "paradigm shift" feasible in Italy?

    PubMed

    Fanelli, V; Geraci, P M; Mascia, L

    2013-05-01

    Donation after cardiac death (DCD) is one of the growing strategies to overcome the problem of organ shortage. Cardiac death is defined as "irreversible cessation of circulatory and respiratory function"; the time interval to define irreversibility of cardiac death, the peculiarity of consent, and the framework of end-of-life decision making are the most compelling ethical issues which have been raised with DCD. National protocols that balance medical, ethical, and social issues are mandatory to guide transplant care professionals. In Italy, the 20 min cardiac arrest demonstrated by continuous electrocardiography recording is the time interval necessary for death diagnosis based on cardiopulmonary criteria. This time negatively affects donation after cardiac death because warm ischemic time (WIT) - the most important predictor of grafts' poor outcome - is prolonged. However, this time seems to be prudential to define the irreversibility of death and to respect the "dead donor rule", as established by the National Committee of Bioethics. National reference protocols regulating DCD practice are therefore a compelling issue. PMID:23449241

  2. Facts about Sudden Cardiac Death in the Young

    MedlinePlus

    ... sports. Any young person who has experienced unexplained fainting should be tested. It is extremely important that ... arrhythmias (like LQTS) are frequently misdiagnosed as vasovagal syncope, asthma or epilepsy without any cardiac evaluation. Thus, ...

  3. Endothelial RAGE exacerbates acute postischaemic cardiac inflammation.

    PubMed

    Ziegler, Tilman; Horstkotte, Melanie; Lange, Philipp; Ng, Judy; Bongiovanni, Dario; Hinkel, Rabea; Laugwitz, Karl-Ludwig; Sperandio, Markus; Horstkotte, Jan; Kupatt, Christian

    2016-08-01

    Advanced glycation end-products (AGEs) interact with their receptor RAGE, leading to an inflammatory state. We investigated the role of RAGE in postischaemic leukocyte adhesion after myocardial infarction and its effect on postischaemic myocardial function. Wildtype (WT), ICAM-1-/-, RAGE-/- or ICAM-1/RAGE-/- mice underwent 20 minutes (min) of LAD-occlusion followed by 15 min of reperfusion. We applied in vivo fluorescence microscopy visualising Rhodamine-6G labelled leukocytes. To differentiate between endothelial and leukocyte RAGE, we generated bone marrow chimeric mice. Invasive hemodynamic measurements were performed in mice undergoing 45 min of myocardial ischaemia (via LAD-occlusion) followed by 24 hours of reperfusion. Left-ventricular developed pressure (LVDP) was assessed by insertion of a millar-tip catheter into the left ventricle. In the acute model of myocardial ischaemia, leukocyte retention (WT 68 ± 4 cells/hpf) was significantly reduced in ICAM-1-/- (40 ± 3 cells/hpf) and RAGE-/- mice (38 ± 4 cells/hpf). ICAM-1/RAGE-/- mice displayed an additive reduction of leukocyte retention (ICAM-1/RAGE-/- 15 ± 3 cells/hpf). Ly-6G+ neutrophil were predominantly reduced in ICAM-1/RAGE-/- hearts (28 %), whereas Ly-6C+ proinflammatory monocytes decreased to a lesser extent (55 %). Interestingly, PMN recruitment was not affected in chimeric mice with RAGE deficiency in BM cells (WT mice reconstituted with ICAM-1/RAGE-/- BM: 55 ± 4 cells/hpf) while in mice with global RAGE deficiency (ICAM-1/RAGE-/- mice reconstituted with ICAM-1/RAGE-/- BM) leucocyte retention was significantly reduced (13 ± 1 cells/hpf), similar to non-transplanted ICAM/RAGE-/- mice. Furthermore, postischaemic LVDP increased in ICAM-1/RAGE-/- animals (98 ± 4 mmHg vs 86 ± 4 mmHg in WT mice). In conclusion, combined deficiency of ICAM-1 and RAGE reduces leukocyte influx into infarcted myocardium and improves LV function during the acute phase after myocardial ischaemia and reperfusion

  4. A rat model of liver transplantation with a steatotic donor liver after cardiac death

    PubMed Central

    Cai, Qiucheng; Fan, Hongkai; Xiong, Rihui; Jiang, Yi

    2015-01-01

    This study aimed to establish a rat liver transplantation model with a steatotic donor liver after cardiac death, reflecting clinical conditions. Rats were fed a high-fat diet for 8 weeks to establish the fatty liver model. This model simulates liver steatosis caused by various factors before clinical donation after cardiac death. A pneumothorax was created in the donor rat to induce hypoxia and cardiac arrest before incising the liver. This simulated the processes of hypoxia and cardiac arrest caused by withdrawal of treatment in actual clinical situations. The harvested cardiac death donor liver was then transplanted using the Kamada technique. Donor operative time was 45.7 ± 4.2 min; cardiac arrest time, 9 ± 0.8 min; recipient surgery time, 40.3 ± 4.9 min; and no-liver time, 15 ± 2.5 min. Of 40 liver-transplanted rats, 2 died within 24 h, with a surgical success rate of 95%. The transaminase levels on post-transplantation days 1, 3, 5, and 7 were 835.4 ± 71.33 U/L, 1334.5 ± 102.13 U/L, 536.4 ± 65.52 U/L, and 218.2 ± 36.77 U/L, respectively. This rat liver transplantation model with a steatotic donor liver after cardiac death could improve the simulation of the pathophysiological processes of clinical donation after cardiac death, and could be used as a reliable and stable animal model. PMID:26629068

  5. [Acute liver failure after ingestion of death cap mushrooms].

    PubMed

    Zuliani, Anna-Maria; Kabar, Iyad; Mitchell, Todd; Heinzow, Hauke Sebastian

    2016-07-01

    Amatoxins, which are mainly found in Amanita phalloides, Amanita virosa, and Galerina autumnalis, are responsible for the majority of fatal intoxication with green death cap. The intoxication is associated with acute liver failure, which explains the poor prognosis. Acute liver injury is generally preceeded by a gastrointestinal phase with nausea, vomiting and diarrhea. In the course, pre-renal kidney failure due to the associated fluid deficit and fulminant liver failure may occur. General guidelines for the treatment of amatoxin poisoning are yet not available. We report on three patients who suffered from amatoxin mushroom poisoning after ingestion of green death cap mushrooms. Based on the pathophysiology of amatoxin poisoning, we discuss a potential therapeutic approach. PMID:27359312

  6. A Common Polymorphism of the Human Cardiac Sodium Channel Alpha Subunit (SCN5A) Gene Is Associated with Sudden Cardiac Death in Chronic Ischemic Heart Disease

    PubMed Central

    Marcsa, Boglárka; Dénes, Réka; Vörös, Krisztina; Rácz, Gergely; Sasvári-Székely, Mária; Rónai, Zsolt; Törő, Klára; Keszler, Gergely

    2015-01-01

    Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio = 1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association. PMID:26146998

  7. Care for the adult family members of victims of unexpected cardiac death.

    PubMed

    Zalenski, Robert; Gillum, Richard F; Quest, Tammie E; Griffith, James L

    2006-12-01

    More than 300,000 sudden coronary deaths occur annually in the United States, despite declining cardiovascular death rates. In 2000, deaths from heart disease left an estimated 190,156 new widows and 68,493 new widowers. A major unanswered question for emergency providers is whether the immediate care of the loved ones left behind by the deceased should be a therapeutic task for the staff of the emergency department in the aftermath of a fatal cardiac arrest. Based on a review of the literature, the authors suggest that more research is needed to answer this question, to assess the current immediate needs and care of survivors, and to find ways to improve care of the surviving family of unexpected cardiac death victims. This would include improving quality of death disclosure, improving care for relatives during cardiopulmonary resuscitation of their family member, and improved methods of referral for services for prevention of psychological and cardiovascular morbidity during bereavement. PMID:16946285

  8. Prognostic implications of cardiac scintigraphic parameters obtained in the early phase of acute myocardial infarction

    SciTech Connect

    Suzuki, A.; Matsushima, H.; Satoh, A.; Hayashi, H.; Sotobata, I.

    1988-06-01

    A cohort of 76 patients with acute myocardial infarction was studied with infarct-avid scan, radionuclide ventriculography, and thallium-201 myocardial perfusion scintigraphy. Infarct area, left ventricular ejection fraction, and defect score were calculated as radionuclide indices of the extent of myocardial infarction. The correlation was studied between these indices and cardiac events (death, congestive heart failure, postinfarction angina, and recurrence of myocardial infarction) in the first postinfarction year. High-risk patients (nonsurvivors and patients who developed heart failure) had a larger infarct area, a lower left ventricular ejection fraction, and a larger defect score than the others. Univariate linear discriminant analysis was done to determine the optimal threshold of these parameters for distinguishing high-risk patients from others. Radionuclide parameters obtained in the early phase of acute myocardial infarction were useful for detecting both patients with grave complications and those with poor late prognosis during a mean follow-up period of 2.6 years.

  9. Acute kidney injury following cardiac surgery: current understanding and future directions.

    PubMed

    O'Neal, Jason B; Shaw, Andrew D; Billings, Frederic T

    2016-01-01

    Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI. PMID:27373799

  10. Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death

    PubMed Central

    Campuzano, Oscar; Sanchez-Molero, Olallo; Mademont-Soler, Irene; Riuró, Helena; Allegue, Catarina; Coll, Monica; Pérez-Serra, Alexandra; Mates, Jesus; Picó, Ferran; Iglesias, Anna; Brugada, Ramon

    2015-01-01

    A leading cause of death in western countries is sudden cardiac death, and can be associated with genetic disease. Next-generation sequencing has allowed thorough analysis of genes associated with this entity, including, most recently, titin. We aimed to identify potentially pathogenic genetic variants in titin. A total of 1126 samples were analyzed using a custom sequencing panel including major genes related to sudden cardiac death. Our cohort was divided into three groups: 432 cases from patients with cardiomyopathies, 130 cases from patients with channelopathies, and 564 post-mortem samples from individuals showing anatomical healthy hearts and non-conclusive causes of death after comprehensive autopsy. None of the patients included had definite pathogenic variants in the genes analyzed by our custom cardio-panel. Retrospective analysis comparing the in-house database and available public databases also was performed. We identified 554 rare variants in titin, 282 of which were novel. Seven were previously reported as pathogenic. Of these 554 variants, 493 were missense variants, 233 of which were novel. Of all variants identified, 399 were unique and 155 were identified at least twice. No definite pathogenic variants were identified in any of genes analyzed. We identified rare, mostly novel, titin variants that seem to play a potentially pathogenic role in sudden cardiac death. Additional studies should be performed to clarify the role of these variants in sudden cardiac death. PMID:26516846

  11. Early detection of acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Jefferies, John Lynn; Devarajan, Prasad

    2016-01-01

    Acute kidney injury (AKI) is increasingly recognized as a common problem in children undergoing cardiac surgery, with well documented increases in morbidity and mortality in both the short and the long term. Traditional approaches to the identification of AKI such as changes in serum creatinine have revealed a large incidence in this population with significant negative impact on clinical outcomes. However, the traditional diagnostic approaches to AKI diagnosis have inherent limitations that may lead to under-diagnosis of this pathologic process. There is a dearth of randomized controlled trials for the prevention and treatment of AKI associated with cardiac surgery, at least in part due to the paucity of early predictive biomarkers. Novel non-invasive biomarkers have ushered in a new era that allows for earlier detection of AKI. With these new diagnostic tools, a more consistent approach can be employed across centers that may facilitate a more accurate representation of the actual prevalence of AKI and more importantly, clinical investigation that may minimize the occurrence of AKI following pediatric cardiac surgery. A thoughtful management approach is necessary to mitigate the effects of AKI after cardiac surgery, which is best accomplished in close collaboration with pediatric nephrologists. Long-term surveillance for improvement in kidney function and potential development of chronic kidney disease should also be a part of the comprehensive management strategy. PMID:27429538

  12. Postmortem mRNA Expression Patterns in Left Ventricular Myocardial Tissues and Their Implications for Forensic Diagnosis of Sudden Cardiac Death

    PubMed Central

    Son, Gi Hoon; Park, Seong Hwan; Kim, Yunmi; Kim, Ji Yeon; Kim, Jin Wook; Chung, Sooyoung; Kim, Yu-Hoon; Kim, Hyun; Hwang, Juck-Joon; Seo, Joong-Seok

    2014-01-01

    Sudden cardiac death (SCD), which is primarily caused by lethal heart disorders resulting in structural and arrhythmogenic abnormalities, is one of the prevalent modes of death in most developed countries. Myocardial ischemia, mainly due to coronary artery disease, is the most common type of heart disease leading to SCD. However, postmortem diagnosis of SCD is frequently complicated by obscure histological evidence. Here, we show that certain mRNA species, namely those encoding hemoglobin A1/2 and B (Hba1/2 and Hbb, respectively) as well as pyruvate dehydrogenase kinase 4 (Pdk4), exhibit distinct postmortem expression patterns in the left ventricular free wall of SCD subjects when compared with their expression patterns in the corresponding tissues from control subjects with non-cardiac causes of death. Hba1/2 and Hbb mRNA expression levels were higher in ischemic SCD cases with acute myocardial infarction or ischemic heart disease without recent infarction, and even in cardiac death subjects without apparent pathological signs of heart injuries, than control subjects. By contrast, Pdk4 mRNA was expressed at lower levels in SCD subjects. In conclusion, we found that altered myocardial Hba1/2, Hbb, and Pdk4 mRNA expression patterns can be employed as molecular signatures of fatal cardiac dysfunction to forensically implicate SCD as the primary cause of death. PMID:24642708

  13. [Treatment of ventricular tachyarrhythmias and prevention of sudden cardiac death: commentary on the 2016 ESC guideline].

    PubMed

    Eckardt, Lars; Köbe, Julia; Wasmer, Kristina

    2016-08-01

    The 2016 ESC guideline on prevention and therapy of ventricular tachyarrhythmias and sudden cardiac death present an excellent recommendation and summary for all forms of ventricular tachyarrhythmias in patients with and without structural or electrical heart disease. This includes cardiomyopathies as well as conditions such as proarrhythmia, neurologic/psychaitric disorders, or pregnancy. Some aspects are novel; (1) the guideline emphasizes for the first time genetic work-up in sudden cardiac death victims; (2) for prevention of sudden cardiac death systematic re-evaluation 6-12 weeks after myocardial infarction is recommended; (3) subcutaneous ICD as well as the wearable cardioverter/defibrillator are for the first time included in the guidelines; (4) automatic external defibrillators are recommended for public places; (5) for patients with recurrent ventricular tachyarrhythmias the role of catheter ablation has been upgraded. PMID:27509343

  14. Risk Stratification for Sudden Cardiac Death In Patients With Non-ischemic Dilated Cardiomyopathy

    PubMed Central

    Shekha, Karthik; Ghosh, Joydeep; Thekkoott, Deepak; Greenberg, Yisachar

    2005-01-01

    Non ischemic dilated cardiomyopathy (NIDCM) is a disorder of myocardium. It has varying etiologies. Albeit the varying etiologies of this heart muscle disorder, it presents with symptoms of heart failure, and rarely as sudden cardiac death (SCD). Manifestations of this disorder are in many ways similar to its counterpart, ischemic dilated cardiomyopathy (IDCM). A proportion of patients with NIDCM carries a grave prognosis and is prone to sudden cardiac death from sustained ventricular arrhythmias. Identification of this subgroup of patients who carry the risk of sudden cardiac death despite adequate medical management is a challenge .Yet another method is a blanket treatment of patients with this disorder with anti arrhythmic medications or anti tachyarrhythmia devices like implantable cardioverter defibrillators (ICD). However this modality of treatment could be a costly exercise even for affluent economies. In this review we try to analyze the existing data of risk stratification of NIDCM and its clinical implications in practice. PMID:16943952

  15. Alternative research funding to improve clinical outcomes: model of prediction and prevention of sudden cardiac death.

    PubMed

    Myerburg, Robert J; Ullmann, Steven G

    2015-04-01

    Although identification and management of cardiovascular risk markers have provided important population risk insights and public health benefits, individual risk prediction remains challenging. Using sudden cardiac death risk as a base case, the complex epidemiology of sudden cardiac death risk and the substantial new funding required to study individual risk are explored. Complex epidemiology derives from the multiple subgroups having different denominators and risk profiles, while funding limitations emerge from saturation of conventional sources of research funding without foreseeable opportunities for increases. A resolution to this problem would have to emerge from new sources of funding targeted to individual risk prediction. In this analysis, we explore the possibility of a research funding strategy that would offer business incentives to the insurance industries, while providing support for unresolved research goals. The model is developed for the case of sudden cardiac death risk, but the concept is applicable to other areas of the medical enterprise. PMID:25669654

  16. Cardiac computed tomography in patients with acute chest pain.

    PubMed

    Nieman, Koen; Hoffmann, Udo

    2015-04-14

    The efficient and reliable evaluation of patients with acute chest pain is one of the most challenging tasks in the emergency department. Coronary computed tomography (CT) angiography may play a major role, since it permits ruling out coronary artery disease with high accuracy if performed with expertise in properly selected and prepared patients. Several randomized trials have established early cardiac CT as a viable safe and potentially more efficient alternative to functional testing in the evaluation of acute chest pain. Ongoing investigations explore whether advanced anatomic and functional assessments such as high-risk coronary plaque, resting myocardial perfusion, and left ventricular function, or the simulation of the fractional coronary flow reserve will add information to the anatomic assessment for stenosis, which would allow expanding the benefits of cardiac CT from triage to treatment decisions. Especially, the combination of high-sensitive troponins and coronary computed tomography angiography may play a valuable role in future strategies for the management of patients presenting with acute chest pain. PMID:25687351

  17. How the 2008 stock market crash and seasons affect total and cardiac deaths in Los Angeles County.

    PubMed

    Schwartz, Bryan Glen; Pezzullo, John Christopher; McDonald, Scott Andrew; Poole, William Kenneth; Kloner, Robert Alan

    2012-05-15

    Various stressors trigger cardiac death. The objective was to investigate a possible relation between a stock market crash and cardiac death in a large population within the United States. We obtained daily stock market data (Dow Jones Industrial Average Index), death certificate data for daily deaths in Los Angeles County (LA), and annual LA population estimates for 2005 through 2008. The 4 years death rate curves (2005 through 2008) were averaged into a single curve to illustrate annual trends. Data were "deseasonalized" by subtracting from the daily observed value the average value for that day of year. There was marked seasonal variation in total and cardiac death rates. Even in the mild LA climate, death rates were higher in winter versus summer including total death (+17%), circulatory death (+24%), coronary heart disease death (+28%), and myocardial infarction death (+38%) rates (p <0.0001 for each). Absolute coronary heart disease death rates have decreased since 1985. After accounting for seasonal variation, the large stock market crash in October 2008 did not affect death rates in LA. Death rates remained at or below seasonal averages during the stock market crash. In conclusion, after correcting for seasonal variation, the stock market crash in October 2008 was not associated with an increase in total or cardiac death in LA. Annual coronary heart disease death rates continue to decrease. However, seasonal variation (specifically winter) remains a trigger for death and coronary heart disease death even in LA where winters are mild. PMID:22381159

  18. [Nursing management of a refractory cardiac death donor].

    PubMed

    Kaufmann, Marion

    2016-09-01

    The nursing management of a refractory circulatory death donor is a new procedure which forms an integral part of patient care. It comprises technical and organisational aspects, and requires a conceptual, ethical and deontological effort. PMID:27596504

  19. Brain-heart interactions. The neurocardiology of arrhythmia and sudden cardiac death.

    PubMed Central

    Davis, A M; Natelson, B H

    1993-01-01

    Neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation. Recognition and analysis of such links in the pathogenesis of malignant cardiac arrhythmia are emphasized in this review. Neurocardiac links have been shown to produce arrhythmia both experimentally and clinically; specific examples, including stroke, epilepsy, and environmental stress are presented. We hypothesize that the individual with a diseased heart has a greater likelihood of experiencing cardiac arrhythmia and sudden cardiac death when the neurocardiac axis is activated. Reviewing possible mechanisms of brain-related arrhythmias, we suggest that the nervous system directs the events leading to cardiac damage by raising catecholamine levels and potentially inducing arrhythmia. PMID:8219819

  20. Causes of sudden unexpected cardiac death in the first two decades of life.

    PubMed

    Steinberger, J; Lucas, R V; Edwards, J E; Titus, J L

    1996-05-01

    Sudden, unexpected cardiac death in the age group 1 to 21 years usually is due to myocarditis, hypertrophic cardiomyopathy, aortic valvar stenosis, and coronary arterial abnormalities. The hearts of 70 patients <21 years of age who died suddenly were reviewed. Twenty patients were <1 year of age and 50 were 1 to 21 years old. The cardiac findings were compared with those in 68 age-matched controls with known cardiac disease who did not die suddenly. Significant cardiac abnormalities were present in 13 (65%) of the 20 infants; 10 (50%) had anomalies of the aortic origin of the coronary arteries. Among the 50 older patients, cardiac abnormalities were found in 40 (80%), among whom coronary arterial anomalies existed in 12 (24%). Anomalies of aortic origin more frequently involved the left main than the right coronary artery in both groups. PMID:8644651

  1. Identifying sudden cardiac death risk and specifying its occurrence time by analyzing electrocardiograms in natural time

    NASA Astrophysics Data System (ADS)

    Varotsos, P. A.; Sarlis, N. V.; Skordas, E. S.; Lazaridou, M. S.

    2007-08-01

    Sudden cardiac death (SCD) is a frequent cause of death and may occur even if the electrocardiogram seems to be similar to that of a healthy individual. A method which not only identifies the risk but also provides an estimate of the time of an impending cardiac arrest is proposed. Analyzing 159 electrocardiograms in natural time, the authors find that the key quantity is the entropy change under time reversal. After it becomes maximum at the scale of 13 heartbeats, ventricular fibrillation starts within ˜3h in 16 out of 18 SCDs. The method also distinguishes congestive heart failure patients from SCD.

  2. Cardiac Magnetic Resonance Scar Imaging for Sudden Cardiac Death Risk Stratification in Patients with Non-Ischemic Cardiomyopathy

    PubMed Central

    Kim, Eun Kyoung; Chattranukulchai, Pairoj

    2015-01-01

    In patients with non-ischemic cardiomyopathy (NICM), risk stratification for sudden cardiac death (SCD) and selection of patients who would benefit from prophylactic implantable cardioverter-defibrillators remains challenging. We aim to discuss the evidence of cardiac magnetic resonance (CMR)-derived myocardial scar for the prediction of adverse cardiovascular outcomes in NICM. From the 15 studies analyzed, with a total of 2747 patients, the average prevalence of myocardial scar was 41%. In patients with myocardial scar, the risk for adverse cardiac events was more than 3-fold higher, and risk for arrhythmic events 5-fold higher, as compared to patients without scar. Based on the available observational, single center studies, CMR scar assessment may be a promising new tool for SCD risk stratification, which merits further investigation. PMID:26175568

  3. Overzealous cardiac massage leading to unintentional infant death.

    PubMed

    Sinani, Fatos; Ymaj, Besim; Vyshka, Gentian

    2011-01-01

    The case of an 18-month child is presented, with a picture demonstrating the thoracic trauma, caused from a hand pressure movement, perpetrated with an open right palm, in an attempt to perform an external cardiac massage. The child showed continuous episodes of 'crying spells' that the medical staff considered as benign, but an overprotective and mentally unstable mother kept on violently 'resuscitating' her son during such episodes. The last episode was characterised with a strenuous massage of the thoracic wall, causing evident bruises and leading to a cardiac contusion. The mother who perpetrated the trauma was sentenced for manslaughter, after the accidental character of the event, as well as the severity of her family situation and the precarious living environment of a socially abandoned single-acting parent, were all taken into account. The particular psychopathology of the care giver (mother) and the characteristics of the inflicted thoracic blow are described. PMID:22675032

  4. Early prediction of death in acute hypertensive intracerebral hemorrhage

    PubMed Central

    CHEN, GUOFANG; PING, LEI; ZHOU, SHENGKUI; LIU, WEIWEI; LIU, LEIJING; ZHANG, DONGMEI; LI, ZAILI; TIAN, YONGFANG; CHEN, ZHEN

    2016-01-01

    Hypertensive intracerebral hemorrhage (HICH) has been on the decline. However, mortality at long-term follow up is on the increase. The aim of the present study was to investigate early warning signals of death in patients with acute HICH. The medical records of 128 patients with acute HICH within 6 h of onset were retrospectively analyzed. For these patients, systolic blood pressure (BP) was recorded at different time points (emergency, admission, every 6 h within 24 h and twice daily after 24 h) within 1 week. Computed tomography scanning was performed at emergency and the following 24±3 h to assess the hematoma volume. Neurological impairment was evaluated using the Glasgow Coma Scale and National Institutes of Health Stroke Scale. Outcomes were death, defined as a modified Rankin scale score 6, at 90 days. The results showed that at 90 days, 15 HICH patients succumbed (mortality of 11.7%). Of the 15 patients, 1 patient (6.7%) sucumbed within 24 h and 6 patients (40%) within 1 week. HICH mortality was closely associated with age (P<0.001) but not with gender. A significant association was detected between mortality and high BP taken at 30 min, 45 min and 6 h after admission (P=0.003), albeit not at emergency and admission (P>0.05). Death was also correlated with hematoma volume at 24 h but not with the site. Results from the multivariate binary logistic regression analysis showed that age and hematoma volume were independent risk factors of death of HICH. In conclusion, age and hematoma volume may be important early predictors of death in HICH. Proactive control and management of hematoma may reduce the mortality of HICH. PMID:26889222

  5. Update: Causes and symptoms of sudden cardiac death in young athletes.

    PubMed

    Asif, Irfan M; Yim, Eugene S; Hoffman, Jacob M; Froelicher, Vic

    2015-02-01

    Abstract Sudden cardiac death (SCD) is the leading cause of death during exercise. While initial reports suggested that the most common cause of SCD in young athletes was due to hypertrophic cardiomyopathy (HCM), a critical review of investigations in several populations (athletes, non-athletes, military, national, and international) supports that the most common finding at autopsy of young individuals with SCD is actually a structurally normal heart (SNH). This information is vital for sports medicine clinicians, especially with regard to the pre-participation evaluation (PPE) since cardiac death associated with a SNH is likely attributed to disorders such as arrhythmia or ion channel diseases. This comprehensive review explores the causes of SCD, along with the symptoms preceding death, which ultimately may help refine the PPE and maximize the ability to detect potentially lethal disease prior to competition. PMID:25656358

  6. Improving Ascertainment of Sudden Cardiac Death in Patients with End Stage Renal Disease

    PubMed Central

    Pun, Patrick H.; Herzog, Charles A.; Middleton, John P.

    2012-01-01

    Summary Background and objectives Data collected by the US Renal Data System (USRDS) identify sudden cardiac death (SCD) as the leading cause of death among hemodialysis patients. However, evidence suggests that clinical events captured on the USRDS death notification form may be inaccurate. A new method for classifying SCD was recently developed to enhance the accuracy of SCD classification. This study examined the performance characteristics of this refined definition using a cohort of hemodialysis patients who experienced a witnessed SCD as the reference standard. Design, setting, participants, & measurements This is a retrospective cohort study of 363 patients who experienced a witnessed SCD in US Gambro (DaVita) outpatient dialysis clinics. Sensitivity of SCD defined by death notification forms and SCD defined using additional administrative sources was compared. Clinical data recorded near time of death were also examined. Results Existing USRDS death notification forms reported 70.8% of witnessed SCD as “cardiac arrest/cause unknown” or “arrhythmia.” The refined definition significantly improved identification to 83.8% of witnessed SCD events (P<0.001). Verified SCD cases that were not identified by either definition were more likely to be reported on the death notification form as death due to myocardial infarction, hyperkalemia, sepsis, malignancy, or unknown cause. Conclusions Compared with the death notification form alone, the refined SCD definition significantly improves the sensitivity of reporting of witnessed SCD occurring within outpatient hemodialysis clinics. More accurate reporting of cardiac events by clinicians and refinements to existing death notification forms may further improve recognition and understanding of SCD. PMID:22076878

  7. Expression of Tumor Necrosis Factor in Human Acute Cardiac Rejection

    PubMed Central

    Arbustini, Eloisa; Grasso, Maurizia; Diegoli, Marta; Bramerio, Manuela; Foglieni, Andrea Scotti; Albertario, Marco; Martinelli, Luigi; Gavazzi, Antonello; Goggi, Claudio; Campana, Carlo; Vigano, Mario

    1991-01-01

    The authors performed an immunohistochemical study on expression of tumor necrosis factor alpha (TNFα) in endomyocardial biopsies from human cardiac allografts. TNFα immunoreactivity was found in 45% biopsies with mild acute rejection, in 83% biopsies with focal moderate rejection, in 80% biopsies with diffuse moderate rejection. Biopsies with absent rejection did not show immunoreactive cells. In mild rejection, positive cells were few and scanty monocytes and macrophages (MAC-387 and LN5 positive cells) and T lymphocytes (UCHL-1/CD45 RO positive cells) (up to 20% of all infiltrating cells). Expression of major histocompatibility complex (MHC) class II antigens on infiltrating and endothelial cells occurred earlier and independent of TNFα reactivity. Number of immunoreactive cells increased in moderate rejection (up to 50%). Immunoreactivity was also present in nonpigmented macrophages in part of the biopsies with resolving rejection (45%). The authors conclude that TNFα is expressed in acute cardiac rejection by immunologically activated inflammatory cells. Immunoreactive cells increase in number with increasing severity of the reaction. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:1928295

  8. A survey of the causes of sudden cardiac death in the under 35-year-age group.

    PubMed

    Quigley, F; Greene, M; O'Connor, D; Kelly, F

    2005-09-01

    CRY (Cardiac Risk in the Young) is a registered Irish charity established by parents who are bereaved as a result of sudden cardiac death. The aim of this study is to establish the incidence and causes of sudden cardiac death in Dublin city in the 10-year period from 1st January 1993 to 31st December 2002. All sudden cardiac deaths in the under 35-year age group which were reported to the city coroner in the study period were examined. Details regarding age, sex, previous symptoms, investigations, circumstances of death and main pathological finding were recorded in each case. A total of 72 cases of sudden cardiac death in the under-35 year age group were reported. 52 were men. The median age was 26.5 years (range 12-34 years). The cause of death in 20 cases was reported as atherosclerotic Coronary Artery Disease. The second commonest cause of death (24% cases) was Hypertrophic Cardiomyopathy. Hypertrophic Cardiomyopathy was the commonest cause of death under the age of 25 years. Overall atherosclerotic coronary artery disease was the commonest cause of death in this group. The importance of Hypertrophic Cardiomyopathy is highlighted by the fact it was the commonest cause of death in the under 25-year age group. Screening those at high risk of sudden cardiac death especially the relatives of those affected by Hypertrophic Cardiomyopathy need to be discussed and implemented. PMID:16255113

  9. Acute effects of carbon monoxide on cardiac electrical stability

    SciTech Connect

    Verrier, R.L.; Mills, A.K.; Skornik, W.A. )

    1990-10-01

    The objective of this project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability. To obtain a comprehensive assessment, diverse biological models were employed. These involved cardiac electrical testing in the normal and ischemic heart in anesthetized and conscious dogs. The experimental plan was designed both to examine the direct effects of carbon monoxide exposure on the myocardium and to evaluate possible indirect influences through alterations in platelet aggregability or changes in central nervous system activity in the conscious animal. Our results indicate that exposure to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, is without significant effect on ventricular electrical stability. This appears to be the case in the acutely ischemic heart as well as in the normal heart. It is important to note that the total exposure period was in the range of 90 to 124 minutes. The possibility that longer periods of exposure or exacerbation from nicotine in cigarette smoke could have a deleterious effect cannot be excluded. We also examined whether or not alterations in platelet aggregability due to carbon monoxide exposure could be a predisposing factor for cardiac arrhythmias. A model involving partial coronary artery stenosis was used to simulate the conditions under which platelet plugs could lead to myocardial ischemia and life-threatening arrhythmias. We found no changes either in the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Thus, carbon monoxide exposure does not appear to alter platelet aggregability or its effect on coronary blood flow during stenosis. In the final series of experiments, we examined the effects of carbon monoxide exposure in the conscious state.

  10. Ion Channel Macromolecular Complexes in Cardiomyocytes: Roles in Sudden Cardiac Death

    PubMed Central

    Abriel, Hugues; Rougier, Jean-Sébastien; Jalife, José

    2015-01-01

    The movement of ions across specific channels embedded on the membrane of individual cardiomyocytes is crucial for the generation and propagation of the cardiac electrical impulse. Emerging evidence over the last 20 years strongly suggests that the normal electrical function of the heart is the result of dynamic interactions of membrane ion channels working in an orchestrated fashion as part of complex molecular networks. Such networks work together with exquisite temporal precision to generate each action potential and contraction. Macromolecular complexes play crucial roles in transcription, translation, oligomerization, trafficking, membrane retention, glycosylation, posttranslational modification, turnover, function and degradation of all cardiac ion channels known to date. In addition, the accurate timing of each cardiac beat and contraction demands, a comparable precision on the assembly and organizations of sodium, calcium and potassium channel complexes within specific subcellular microdomains, where physical proximity allows for prompt and efficient interaction. This review article, part of the Compendium on Sudden Cardiac Death, discusses the major issues related to the role of ion channel macromolecular assemblies in normal cardiac electrical function and the mechanisms of arrhythmias leading to sudden cardiac death. It provides an idea of how these issues are being addressed in the laboratory and in the clinic, which important questions remain unanswered, and what future research will be needed to improve knowledge and advance therapy. PMID:26044251

  11. Sudden Cardiac Death in Children and Adolescents: Can We Prevent It?

    ERIC Educational Resources Information Center

    Berger, Stuart

    2001-01-01

    Sudden cardiac death (SCD) can occur at any age in apparently healthy people. Early identification and intervention are essential. This article examines SCD in children and adolescents, explaining: who is at risk; the importance of training school personnel for SCD emergencies and having automated external defibrillators (AED) within the schools;…

  12. Primary Cardiac Fibroma and Cardiac Conduction System Alterations in a Case of Sudden Death of a 4-month-old Infant

    PubMed Central

    Mecchia, Donatella; Lavezzi, Anna Maria; Matturri, Luigi

    2013-01-01

    A 4-month-old female infant considered to be in good health died suddenly and unexpectedly. Post- mortem examination was requested, with clinical diagnosis of sudden infant death syndrome. At autopsy the infant was described in good health. Histo- logical examination of the heart found a cardiac fibroma compressing the atrio-ventricular node and the examination of the cardiac conduction system showed an accessory fiber of Mahaim (nodo-ventricular) and cartilaginous metaplasia of the cardiac fibrous body. Probably the concomitant presence of cardiac conduction system abnormalities and a septal fibroma, compressing the atrio-ventricular node, could have an important role in causing the sudden death. PMID:23847693

  13. Prevention of sudden cardiac death in dialysis patients: drugs, defibrillators or what else.

    PubMed

    Passman, Rod

    2013-01-01

    Death from cardiovascular disease in general and sudden cardiac arrest (SCA) in particular are exponentially proportional to declining renal function and are a major cause of mortality among those with chronic kidney disease (CKD). The greatest risk, however, is reserved for those patients on chronic dialysis. These individuals have an extraordinarily high rate of death, with cardiac disease accounting for 45% and SCA responsible for 25% of all-cause mortality. Once cardiac arrest occurs, survival is extremely poor. Thus, reducing mortality from cardiovascular disease and SCA in dialysis patients is a global health challenge. The main objectives of this review are to elucidate the nature of SCA in the dialysis population, describe possible mechanisms and risk factors, and discuss options for prevention. PMID:23343546

  14. Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

    PubMed

    Kloner, Robert A; Dai, Wangde; Hale, Sharon L; Shi, Jianru

    2016-07-01

    While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function. PMID:26612091

  15. Trigemino-cardiac reflex as lethal mechanism in a suicidal fire death case.

    PubMed

    Rossi, Riccardo; Lodise, Maria; Lancia, Massimo; Bacci, Mauro; De-Giorgio, Fabio; Cascini, Fidelia

    2014-05-01

    In the vast majority of immediate fire deaths, the mechanism of death is inhalation of toxic gases (especially carbon monoxide), direct thermal injury, or neurogenic shock due to the redistribution of the body's blood volume produced by surface heat on the skin. We present a suicidal case that is unusual because the mechanism of immediate fire death could arguably be explained in terms of a primitive autonomic reflex/the trigemino-cardiac reflex. Although this reflex is well known to surgeons and anesthetists, with possible lethal consequences in the course of invasive surgical procedures on the head and neck region, it is much less familiar to forensic pathologists. PMID:24502511

  16. How France launched its donation after cardiac death program.

    PubMed

    Antoine, C; Mourey, F; Prada-Bordenave, E

    2014-02-01

    On the basis of the literature and results presented at the 6th International Conference, donation after cardio-circulatory death provides a significant, practical, additional high quality source of transplantable organs. The vast majority of DCD are 'controlled' Maastricht category III donors. In 2010, the parliamentary information mission on the revision of the bioethics laws invited the Intensive Care Societies to debate and to make recommendations to implement controlled donation after circulatory death. They came to the conclusion that such retrieval is possible in France and insisted on the medical criteria that frame it: the writing of the medical procedures, the ethical aspects and the delay. The major recommendations of the ethics committees were firstly, The WLST decision is independent of the possibility of organ donation; secondly, the strict respect of "The dead donor and organ transplantation rule" and the updated national guidance for the WLST; thirdly, the drafting of a nationally agreed protocol defining the mandatory conditions to determine death and to perform procurement and transplantation. Organ donation after WLST will be authorised only in pilot centres with a locally agreed WLST policy including external second opinion and written transcript of the WLST decision, experienced intensive care staff, a local organ procurement coordination team familiar with DBD and DCD protocols and only in hospitals authorised for organ procurement. It is important to have an optimal and standardized national guidance to limit the known risk factors of graft failure (donor and recipient choice, warm and cold ischemia time), to increase acceptance by medical community and civil society and to improve results and allow more powerful analysis. PMID:24388490

  17. Next-Generation Sequencing in Post-mortem Genetic Testing of Young Sudden Cardiac Death Cases

    PubMed Central

    Lahrouchi, Najim; Behr, Elijah R.; Bezzina, Connie R.

    2016-01-01

    Sudden cardiac death (SCD) in the young (<40 years) occurs in the setting of a variety of rare inherited cardiac disorders and is a disastrous event for family members. Establishing the cause of SCD is important as it permits the pre-symptomatic identification of relatives at risk of SCD. Sudden arrhythmic death syndrome (SADS) is defined as SCD in the setting of negative autopsy findings and toxicological analysis. In such cases, reaching a diagnosis is even more challenging and post-mortem genetic testing can crucially contribute to the identification of the underlying cause of death. In this review, we will discuss the current achievements of “the molecular autopsy” in young SADS cases and provide an overview of key challenges in assessing pathogenicity (i.e., causality) of genetic variants identified through next-generation sequencing. PMID:27303672

  18. Sensitivity and specificity of QTc dispersion for identification of risk of cardiac death in patients with peripheral vascular disease.

    PubMed Central

    Darbar, D.; Luck, J.; Davidson, N.; Pringle, T.; Main, G.; McNeill, G.; Struthers, A. D.

    1996-01-01

    OBJECTIVE: To determine whether QTc dispersion, which is easily obtained from a standard electrocardiogram, can predict those patients with peripheral vascular disease who will subsequently suffer a cardiac death, despite having no cardiac symptoms or signs. DESIGN: Patients with peripheral vascular disease were followed up for five years after they had had coronary angiography, radionuclide ventriculography, and their QTc dispersion calculated from their 12 lead electrocardiogram. SUBJECTS: 49 such patients were then divided into three groups: survivors (34), cardiac death (12), and non-cardiac death (3). MAIN OUTCOME MEASURE: Survival. RESULTS: The mean (SD; range) ejection fractions were similar in all three groups: survivors 45.9 (11.0; 27.0-52.0), cardiac death 44.0 (7.90; 28.5-59.0), and non-cardiac death 45.3 (4.55; 39.0-50.0). QTc dispersion was significantly prolonged in the cardiac death group compared with in the survivors (86.3(23.9; 41.0-139) v 56.5 (25.4; 25.0-164); P = 0.002). A QTc dispersion > or = 60 ms had a 92% sensitivity and 81% specificity in predicting cardiac death, QTc dispersion in patients with diffuse coronary artery disease was significantly (P < 0.05) greater than in those with no disease or disease affecting one, two, or three vessels. CONCLUSIONS: There is a strong link between QTc dispersion and cardiac death in patients with peripheral vascular disease. QTc dispersion may therefore be a cheap and non-invasive way of assessing the risk of cardiac death in patients with peripheral vascular disease. PMID:8611874

  19. Cardiac troponins as indicators of acute myocardial damage in dogs.

    PubMed

    Burgener, Iwan A; Kovacevic, Alan; Mauldin, G Neal; Lombard, Christophe W

    2006-01-01

    Cardiac troponin I (cTnI) and T (cTnT) have a high sequence homology across phyla and are sensitive and specific markers of myocardial damage. The purpose of this study was to evaluate the Cardiac Reader, a human point-of-care system for the determination of cTnT and myoglobin, and the Abbott Axsym System for the determination of cTnI and creatine kinase isoenzyme MB (CK-MB) in healthy dogs and in dogs at risk for acute myocardial damage because of gastric dilatation-volvulus (GDV) and blunt chest trauma (BCT). In healthy dogs (n = 56), cTnI was below detection limits (<0.1 microg/L) in 35 of 56 dogs (reference range 0-0.7 microg/L), and cTnT was not measurable (<0.05 ng/mL) in all but 1 dog. At presentation, cTnI, CK-MB, myoglobin, and lactic acid were all significantly higher in dogs with GDV (n = 28) and BCT (n = 8) than in control dogs (P < .001), but cTnT was significantly higher only in dogs with BCT (P = .033). Increased cTnI or cTnT values were found in 26 of 28 (highest values 1.1-369 microg/L) and 16 of 28 dogs (0.1-1.7 ng/mL) with GDV, and in 6 of 8 (2.3-82.4 microg/L) and 3 of 8 dogs (0.1-0.29 ng/mL) with BCT, respectively. In dogs suffering from GDV, cTnI and cTnT increased further within the first 48 hours (P < .001). Increased cardiac troponins suggestive of myocardial damage occurred in 93% of dogs with GDV and 75% with BCT. cTnI appeared more sensitive, but cTnT may be a negative prognostic indicator in GDV. Both systems tested seemed applicable for the measurement of canine cardiac troponins, with the Cardiac Reader particularly suitable for use in emergency settings. PMID:16594583

  20. Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome

    PubMed Central

    Brunner, Michael; Peng, Xuwen; Liu, Gong Xin; Ren, Xiao-Qin; Ziv, Ohad; Choi, Bum-Rak; Mathur, Rajesh; Hajjiri, Mohammed; Odening, Katja E.; Steinberg, Eric; Folco, Eduardo J.; Pringa, Ekatherini; Centracchio, Jason; Macharzina, Roland R.; Donahay, Tammy; Schofield, Lorraine; Rana, Naveed; Kirk, Malcolm; Mitchell, Gary F.; Poppas, Athena; Zehender, Manfred; Koren, Gideon

    2008-01-01

    Long QT syndrome (LQTS) is a heritable disease associated with ECG QT interval prolongation, ventricular tachycardia, and sudden cardiac death in young patients. Among genotyped individuals, mutations in genes encoding repolarizing K+ channels (LQT1:KCNQ1; LQT2:KCNH2) are present in approximately 90% of affected individuals. Expression of pore mutants of the human genes KCNQ1 (KvLQT1-Y315S) and KCNH2 (HERG-G628S) in the rabbit heart produced transgenic rabbits with a long QT phenotype. Prolongations of QT intervals and action potential durations were due to the elimination of IKs and IKr currents in cardiomyocytes. LQT2 rabbits showed a high incidence of spontaneous sudden cardiac death (>50% at 1 year) due to polymorphic ventricular tachycardia. Optical mapping revealed increased spatial dispersion of repolarization underlying the arrhythmias. Both transgenes caused downregulation of the remaining complementary IKr and IKs without affecting the steady state levels of the native polypeptides. Thus, the elimination of 1 repolarizing current was associated with downregulation of the reciprocal repolarizing current rather than with the compensatory upregulation observed previously in LQTS mouse models. This suggests that mutant KvLQT1 and HERG interacted with the reciprocal wild-type α subunits of rabbit ERG and KvLQT1, respectively. These results have implications for understanding the nature and heterogeneity of cardiac arrhythmias and sudden cardiac death. PMID:18464931

  1. Basiliximab induction in kidney transplantation with donation after cardiac death donors

    PubMed Central

    YAO, XUPING; WENG, GUOBIN; WEI, JUNJUN; GAO, WENBO

    2016-01-01

    Basiliximab is a monoclonal antibody that binds to the α-chain of the interleukin (IL)-2 receptor. It is used as induction therapy in kidney transplantation. The objective of the present study was to evaluate induction therapy with single-dose basiliximab (Simulect®) in kidney transplantation with donation after cardiac death (DCD) donors. A total of 33 DCD kidney transplants were performed between December 2010 and July 2013 in patients who received single-dose basiliximab (20 mg) as induction therapy. The maintenance immunosuppression included calcineurin inhibitor (cyclosporine A or tacrolimus), mycophenolate mofetil and corticosteroids. The follow-up time was 1 year. The mean ages of the DCD donors and recipients were 29.3 and 41.1 years, respectively. Within the 1-year follow-up, the overall incidence of acute rejection was 9.1%. There were 10 cases of delayed graft function among the recipients. Mean serum creatinine values at 1 week and at 1, 3, 6, 9 and 12 months post-transplantation were 257.6, 238.2, 194.5, 159.3, 137.9 and 110.8 µmol/l, respectively, with a favorable trend to allograft function recovery over time. The 1-year patient and graft survival rates were 96.9 and 90.9%, respectively, with an infection rate of 24.2%. Increased alanine aminotransferase/aspartate transaminase levels in only 2 patients were considered to be associated with basiliximab. This experience with single-dose basiliximab for induction therapy in DCD kidney transplantation showed that favorable clinical outcomes were achieved in terms of graft survival and function within 1 year. PMID:27284346

  2. Life and death of a cardiac calcium spark

    PubMed Central

    Ríos, Eduardo; Maltsev, Victor A.

    2013-01-01

    Calcium sparks in cardiac myocytes are brief, localized calcium releases from the sarcoplasmic reticulum (SR) believed to be caused by locally regenerative calcium-induced calcium release (CICR) via couplons, clusters of ryanodine receptors (RyRs). How such regeneration is terminated is uncertain. We performed numerical simulations of an idealized stochastic model of spark production, assuming a RyR gating scheme with only two states (open and closed). Local depletion of calcium in the SR was inevitable during a spark, and this could terminate sparks by interrupting CICR, with or without assumed modulation of RyR gating by SR lumenal calcium. Spark termination by local SR depletion was not robust: under some conditions, sparks could be greatly and variably prolonged, terminating by stochastic attrition–a phenomenon we dub “spark metastability.” Spark fluorescence rise time was not a good surrogate for the duration of calcium release. Using a highly simplified, deterministic model of the dynamics of a couplon, we show that spark metastability depends on the kinetic relationship of RyR gating and junctional SR refilling rates. The conditions for spark metastability resemble those produced by known mutations of RyR2 and CASQ2 that cause life-threatening triggered arrhythmias, and spark metastability may be mitigated by altering the kinetics of the RyR in a manner similar to the effects of drugs known to prevent those arrhythmias. The model was unable to explain the distributions of spark amplitudes and rise times seen in chemically skinned cat atrial myocytes, suggesting that such sparks may be more complex events involving heterogeneity of couplons or local propagation among sub-clusters of RyRs. PMID:23980195

  3. Aldosterone and cortisol affect the risk of sudden cardiac death in haemodialysis patients

    PubMed Central

    Drechsler, Christiane; Ritz, Eberhard; Tomaschitz, Andreas; Pilz, Stefan; Schönfeld, Stephan; Blouin, Katja; Bidlingmaier, Martin; Hammer, Fabian; Krane, Vera; März, Winfried; Allolio, Bruno; Fassnacht, Martin; Wanner, Christoph

    2013-01-01

    Background Sudden cardiac death is common and accounts largely for the excess mortality of patients on maintenance dialysis. It is unknown whether aldosterone and cortisol increase the incidence of sudden cardiac death in dialysis patients. Methods and results We analysed data from 1255 diabetic haemodialysis patients participating in the German Diabetes and Dialysis Study (4D Study). Categories of aldosterone and cortisol were determined at baseline and patients were followed for a median of 4 years. By Cox regression analyses, hazard ratios (HRs) were determined for the effect of aldosterone, cortisol, and their combination on sudden death and other adjudicated cardiovascular outcomes. The mean age of the patients was 66 ± 8 years (54% male). Median aldosterone was <15 pg/mL (detection limit) and cortisol 16.8 µg/dL. Patients with aldosterone levels >200 pg/mL had a significantly higher risk of sudden death (HR: 1.69; 95% CI: 1.06–2.69) compared with those with an aldosterone <15 pg/mL. The combined presence of high aldosterone (>200 pg/mL) and high cortisol (>21.1 µg/dL) levels increased the risk of sudden death in striking contrast to patients with low aldosterone (<15 pg/mL) and low cortisol (<13.2 µg/dL) levels (HR: 2.86, 95% CI: 1.32–6.21). Furthermore, all-cause mortality was significantly increased in the patients with high levels of both hormones (HR: 1.62, 95% CI: 1.01–2.62). Conclusions The joint presence of high aldosterone and high cortisol levels is strongly associated with sudden cardiac death as well as all-cause mortality in haemodialysed type 2 diabetic patients. Whether a blockade of the mineralocorticoid receptor decreases the risk of sudden death in these patients must be examined in future trials. PMID:23211232

  4. Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes.

    PubMed

    Márquez, Manlio F; Cruz-Robles, David; Ines-Real, Selene; Vargas-Alarcón, Gilberto; Cárdenas, Manuel

    2015-01-01

    Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City. PMID:25661095

  5. Aborted sudden cardiac death associated with an anomalous right coronary artery.

    PubMed

    Diaz, Rienzi A; Valdés, Julio

    2015-01-01

    Coronary artery anomalies arising from the opposite sinus of Valsalva and having an interarterial course between the aorta (AO) and pulmonary artery (PA) are the second most common cause of sudden cardiac death among young athletes, after hypertrophic cardiomyopathy. The right coronary artery (RCA) originating from the AO above the left sinus of Valsalva (LSV) is an extremely rare anomaly. We report the first case of a RCA arising from the AO above the LSV that subsequently runs between the AO and the PA, discovered by a 64-slice multidetector coronary CT, in a patient who was successfully resuscitated from ventricular fibrillation (VF) cardiac arrest while running in a marathon race. PMID:26153291

  6. Bronchogenic Carcinoma with Cardiac Invasion Simulating Acute Myocardial Infarction

    PubMed Central

    Das, Anirban; Das, Sibes K.; Pandit, Sudipta; Karmakar, Rathindra Nath

    2016-01-01

    Cardiac metastases in bronchogenic carcinoma may occur due to retrograde lymphatic spread or by hematogenous dissemination of tumour cells, but direct invasion of heart by adjacent malignant lung mass is very uncommon. Pericardium is frequently involved in direct cardiac invasion by adjacent lung cancer. Pericardial effusion, pericarditis, and tamponade are common and life threatening presentation in such cases. But direct invasion of myocardium and endocardium is very uncommon. Left atrial endocardium is most commonly involved in such cases due to anatomical contiguity with pulmonary hilum through pulmonary veins, and in most cases left atrial involvement is asymptomatic. But myocardial compression and invasion by adjacent lung mass may result in myocardial ischemia and may present with retrosternal, oppressive chest pain which clinically may simulate with the acute myocardial infarction (AMI). As a result, it leads to misdiagnosis and delayed diagnosis of lung cancer. Here we report a case of non-small-cell carcinoma of right lung which was presented with asymptomatic invasion in left atrium and retrosternal chest pain simulating AMI due to myocardial compression by adjacent lung mass, in a seventy-four-year-old male smoker. PMID:27042370

  7. Acute exercise modifies titin phosphorylation and increases cardiac myofilament stiffness.

    PubMed

    Müller, Anna E; Kreiner, Matthias; Kötter, Sebastian; Lassak, Philipp; Bloch, Wilhelm; Suhr, Frank; Krüger, Martina

    2014-01-01

    Titin-based myofilament stiffness is largely modulated by phosphorylation of its elastic I-band regions N2-Bus (decreases passive stiffness, PT) and PEVK (increases PT). Here, we tested the hypothesis that acute exercise changes titin phosphorylation and modifies myofilament stiffness. Adult rats were exercised on a treadmill for 15 min, untrained animals served as controls. Titin phosphorylation was determined by Western blot analysis using phosphospecific antibodies to Ser4099 and Ser4010 in the N2-Bus region (PKG and PKA-dependent. respectively), and to Ser11878 and Ser 12022 in the PEVK region (PKCα and CaMKIIδ-dependent, respectively). Passive tension was determined by step-wise stretching of isolated skinned cardiomyocytes to sarcomere length (SL) ranging from 1.9 to 2.4 μm and showed a significantly increased PT from exercised samples, compared to controls. In cardiac samples titin N2-Bus phosphorylation was significantly decreased by 40% at Ser4099, however, no significant changes were observed at Ser4010. PEVK phosphorylation at Ser11878 was significantly increased, which is probably mediated by the observed exercise-induced increase in PKCα activity. Interestingly, relative phosphorylation of Ser12022 was substantially decreased in the exercised samples. Surprisingly, in skeletal samples from acutely exercised animals we detected a significant decrease in PEVK phosphorylation at Ser11878 and an increase in Ser12022 phosphorylation; however, PKCα activity remained unchanged. In summary, our data show that a single exercise bout of 15 min affects titin domain phosphorylation and titin-based myocyte stiffness with obviously divergent effects in cardiac and skeletal muscle tissues. The observed changes in titin stiffness could play an important role in adapting the passive and active properties of the myocardium and the skeletal muscle to increased physical activity. PMID:25477822

  8. Acute exercise modifies titin phosphorylation and increases cardiac myofilament stiffness

    PubMed Central

    Müller, Anna E.; Kreiner, Matthias; Kötter, Sebastian; Lassak, Philipp; Bloch, Wilhelm; Suhr, Frank; Krüger, Martina

    2014-01-01

    Titin-based myofilament stiffness is largely modulated by phosphorylation of its elastic I-band regions N2-Bus (decreases passive stiffness, PT) and PEVK (increases PT). Here, we tested the hypothesis that acute exercise changes titin phosphorylation and modifies myofilament stiffness. Adult rats were exercised on a treadmill for 15 min, untrained animals served as controls. Titin phosphorylation was determined by Western blot analysis using phosphospecific antibodies to Ser4099 and Ser4010 in the N2-Bus region (PKG and PKA-dependent. respectively), and to Ser11878 and Ser 12022 in the PEVK region (PKCα and CaMKIIδ-dependent, respectively). Passive tension was determined by step-wise stretching of isolated skinned cardiomyocytes to sarcomere length (SL) ranging from 1.9 to 2.4 μm and showed a significantly increased PT from exercised samples, compared to controls. In cardiac samples titin N2-Bus phosphorylation was significantly decreased by 40% at Ser4099, however, no significant changes were observed at Ser4010. PEVK phosphorylation at Ser11878 was significantly increased, which is probably mediated by the observed exercise-induced increase in PKCα activity. Interestingly, relative phosphorylation of Ser12022 was substantially decreased in the exercised samples. Surprisingly, in skeletal samples from acutely exercised animals we detected a significant decrease in PEVK phosphorylation at Ser11878 and an increase in Ser12022 phosphorylation; however, PKCα activity remained unchanged. In summary, our data show that a single exercise bout of 15 min affects titin domain phosphorylation and titin-based myocyte stiffness with obviously divergent effects in cardiac and skeletal muscle tissues. The observed changes in titin stiffness could play an important role in adapting the passive and active properties of the myocardium and the skeletal muscle to increased physical activity. PMID:25477822

  9. Chronic kidney disease and risk factors responsible for sudden cardiac death: a whiff of hope?

    PubMed Central

    Kiuchi, Márcio G.; Mion, Decio

    2015-01-01

    Several studies have shown a strong independent association between chronic kidney disease (CKD) and cardiovascular events, including death, heart failure, and myocardial infarction. Recent clinical trials extend this range of adverse cardiovascular events, also including ventricular arrhythmias and sudden cardiac death. Furthermore, other studies suggest structural remodeling of the heart and electrophysiological alterations in this population. These processes may explain the increased risk of arrhythmia in kidney disease and help to identify patients who are at increased risk of sudden cardiac death. Sympathetic hyperactivity is well known to increase cardiovascular risk in CKD patients and is a hallmark of essential hypertensive state that occurs early in the clinical course of the disease. In CKD, the sympathetic hyperactivity seems to be expressed at the earliest clinical stage of the disease, showing a direct relationship with the severity of the condition of renal failure, being more pronounced in the terminal stage of CKD. The sympathetic efferent and afferent neural activity in kidney failure is a key mediator for the maintenance and progression of the disease. The aim of this review was to show that the feedback loop of this cycle, due to adrenergic hyperactivity, also aggravates many of the risk factors responsible for causing sudden cardiac death and may be a potential target modifiable by percutaneous renal sympathetic denervation. If it is feasible and effective in end-stage renal disease, little is known. PMID:27069851

  10. Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis.

    PubMed

    Ginelliová, Alžbeta; Farkaš, Daniel; Farkašová Iannaccone, Silvia; Vyhnálková, Vlasta

    2016-09-01

    In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded. PMID:27379608

  11. Sudden cardiac death in marathons: a systematic review.

    PubMed

    Waite, Oliver; Smith, Andy; Madge, Luke; Spring, Hannah; Noret, Nathalie

    2016-02-01

    The aim of this systematic review is to summarise the results of cohort studies that examined the incidence of SCD in marathons and to assess the quality of the methods used. A search of the PROSPERO international database revealed no prospective or published systematic reviews investigating SCD in marathons. The review was conducted using studies that reported and characterised the incidence of SCD in people participating in marathons. Studies were identified via electronic database searches (Medline, CINAHL, SPORTDiscus and Google Scholar) from January 1, 1966 to October 1, 2014 and through manual literature searches. 7 studies met the inclusion criteria and were included in this review. 6 of the studies were conducted in the USA and 1 in the UK. These studies covered a 34-year period involving between 215,413 and 3,949,000 runners. The SCD of between 4 and 28 people are recorded in the papers and the reported estimates of the incidence of SCD in marathons ranged widely from 0.6 to 1.9 per 100,000 runners. The proportion of those suffering SCD who were male ranged from 57.1% to 100% and the mean age reported in the papers, ranged from 37 to 48. This review raises 4 methodological concerns over i) collating reports of SCD in marathons; ii) time of death in relation to the marathon; iii) the use of registrants rather than runners in the estimates of sample size and iv) limited detail on runners exercise history. These four concerns all threaten the reliability and interpretation of any estimate of SCD incidence rates in marathons.  This review recommends that the methods used to collect data on SCD in marathons be improved and that a central reporting system be established. PMID:26765272

  12. Sudden cardiac death and chronic kidney disease: From pathophysiology to treatment strategies.

    PubMed

    Di Lullo, L; Rivera, R; Barbera, V; Bellasi, A; Cozzolino, M; Russo, D; De Pascalis, A; Banerjee, D; Floccari, F; Ronco, C

    2016-08-15

    Chronic kidney disease (CKD) patients demonstrate higher rates of cardiovascular mortality and morbidity; and increased incidence of sudden cardiac death (SCD) with declining kidney failure. Coronary artery disease (CAD) associated risk factors are the major determinants of SCD in the general population. However, current evidence suggests that in CKD patients, traditional cardiovascular risk factors may play a lesser role. Complex relationships between CKD-specific risk factors, structural heart disease, and ventricular arrhythmias (VA) contribute to the high risk of SCD. In dialysis patients, the occurrence of VA and SCD could be exacerbated by electrolyte shifts, divalent ion abnormalities, sympathetic overactivity, inflammation and iron toxicity. As outcomes in CKD patients after cardiac arrest are poor, primary and secondary prevention of SCD and cardiac arrest could reduce cardiovascular mortality in patients with CKD. PMID:27174593

  13. Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death.

    PubMed

    Aiba, Isamu; Wehrens, Xander H T; Noebels, Jeffrey L

    2016-08-16

    Cardiorespiratory failure is the most common cause of sudden unexplained death in epilepsy (SUDEP). Genetic autopsies have detected "leaky" gain-of-function mutations in the ryanodine receptor-2 (RyR2) gene in both SUDEP and sudden cardiac death cases linked to catecholaminergic polymorphic ventricular tachycardia that feature lethal cardiac arrhythmias without structural abnormality. Here we find that a human leaky RyR2 mutation, R176Q (RQ), alters neurotransmitter release probability in mice and significantly lowers the threshold for spreading depolarization (SD) in dorsal medulla, leading to cardiorespiratory collapse. Rare episodes of sinus bradycardia, spontaneous seizure, and sudden death were detected in RQ/+ mutant mice in vivo; however, when provoked, cortical seizures frequently led to apneas, brainstem SD, cardiorespiratory failure, and death. In vitro studies revealed that the RQ mutation selectively strengthened excitatory, but not inhibitory, synapses and facilitated SD in both the neocortex as well as brainstem dorsal medulla autonomic microcircuits. These data link defects in neuronal intracellular calcium homeostasis to the vulnerability of central autonomic brainstem pathways to hypoxic stress and implicate brainstem SD as a previously unrecognized site and mechanism contributing to premature death in individuals with leaky RYR2 mutations. PMID:27482086

  14. Predicting sudden cardiac death from T wave alternans of the surface electrocardiogram: promise and pitfalls

    NASA Technical Reports Server (NTRS)

    Rosenbaum, D. S.; Albrecht, P.; Cohen, R. J.

    1996-01-01

    Sudden cardiac death remains a preeminent public health problem. Despite advances in preventative treatment for patients known to be at risk, to date we have been able to identify, and thus treat, only a small minority of these patients. Therefore, there is a major need to develop noninvasive diagnostic technologies to identify patients at risk. Recent studies have demonstrated that measurement of microvolt-level T wave alternans is a promising technique for the accurate identification of patients at risk for ventricular arrhythmias and sudden cardiac death. In this article, we review the clinical data establishing the relationship between microvolt T wave alternans and susceptibility to ventricular arrhythmias. We also review the methods and technology that have been developed to measure microvolt levels of T wave alternans noninvasively in broad populations of ambulatory patients. In particular, we examine techniques that permit the accurate measurement of T wave alternans during exercise stress testing.

  15. Sudden cardiac death while playing Australian Rules football: a retrospective 14 year review.

    PubMed

    Parsons, Sarah; Lynch, Matthew

    2016-06-01

    Australian Rules football is a sport which evolved from Gaelic football and which is played by a large number of predominantly male participants in a number of countries. The highest participation rates are in the southern states of Australia. A retrospective review over a period of 14 years identified 14 cases of sudden cardiac death that occurred in individuals while playing the sport. All were male and ranged in age from 13 to 36 years with a mean and median age of 23 years. A spectrum of cardiac causes was identified including coronary artery atherosclerosis, myocarditis, anomalous coronary artery anatomy, arrhythmogenic right ventricular cardiomyopathy, and healed Kawasaki disease. In 5 cases the heart was morphologically normal raising the possibility of a channelopathy. No traumatic deaths were identified. Some of the individuals had experienced symptoms prior to the fatal episode and the role of pre participation screening in reducing mortality is discussed. PMID:26972904

  16. UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells.

    PubMed

    Juncker, Tom; Cerella, Claudia; Teiten, Marie-Hélène; Morceau, Franck; Schumacher, Marc; Ghelfi, Jenny; Gaascht, François; Schnekenburger, Michael; Henry, Estelle; Dicato, Mario; Diederich, Marc

    2011-01-01

    Cardiac steroids are used to treat various diseases including congestive heart failure and cancer. The aim of this study was to investigate the anti-leukemic activity of UNBS1450, a hemi-synthetic cardenolide belonging to the cardiac steroid glycoside family. Here, we report that, at low nanomolar concentrations, UNBS1450 induces apoptotic cell death. Subsequently, we have investigated the molecular mechanisms leading to apoptosis activation. Our results show that UNBS1450 inhibits NF-κB transactivation and triggers apoptosis by cleavage of pro-caspases 8, 9 and 3/7, by decreasing expression of anti-apoptotic Mcl-1 and by recruitment of pro-apoptotic Bak and Bax protein eventually resulting in cell death. PMID:20849830

  17. [Liver transplant with donated graft after controlled cardiac death. Current situation].

    PubMed

    Abradelo De Usera, Manuel; Jiménez Romero, Carlos; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2013-11-01

    An increasing pressure on the liver transplant waiting list, forces us to explore new sources, in order to expand the donor pool. One of the most interesting and with a promising potential, is donation after cardiac death (DCD). Initially, this activity has developed in Spain by means of the Maastricht type II donation in the uncontrolled setting. For different reasons, donation after controlled cardiac death has been reconsidered in our country. The most outstanding circumstance involved in DCD donation is a potential ischemic stress, that could cause severe liver graft cell damage, resulting in an adverse effect on liver transplant results, in terms of complications and outcomes. The complex and particular issues related to DCD Donation will be discussed in this review. PMID:24021972

  18. A pilot programme of organ donation after cardiac death in China.

    PubMed

    Huang, Jiefu; Millis, J Michael; Mao, Yilei; Millis, M Andrew; Sang, Xinting; Zhong, Shouxian

    2012-03-01

    China's aims are to develop an ethical and sustainable organ transplantation system for the Chinese people and to be accepted as a responsible member of the international transplantation community. In 2007, China implemented the Regulation on Human Organ Transplantation, which was the first step towards the establishment of a voluntary organ donation system. Although progress has been made, several ethical and legal issues associated with transplantation in China remain, including the use of organs from executed prisoners, organ scarcity, the illegal organ trade, and transplantation tourism. In this Health Policy article we outline the standards used to define cardiac death in China and a legal and procedural framework for an organ donation system based on voluntary donation after cardiac death that adheres to both China's social and cultural principles and international transplantation standards. PMID:22078722

  19. [Assessment of risk of sudden cardiac death in patients with hypertrophic cardiomyopathy].

    PubMed

    Attanasio, Philipp; Blaschke, Florian; Pieske, Burkert; Tschöpe, Carsten; Haverkamp, Wilhelm

    2016-07-01

    Hypertrophic cardiomyopathy (HCM) is a hereditary disease characterized by left ventricular hypertrophy with or without concomitant outflow tract obstruction. Identification of patients with HCM who are at high risk of sudden cardiac death (SCD) is crucial as those patients are likely to benefit from an implantable cardioverter defibrillator (ICD). Based on the HCM Risk-SCD study published in 2013, that included 3675 HCM patients with 24 313 years of follow up, a new clinical risk prediction model for sudden cardiac death was developed. This model was included in the recently released 2014 ESC guidelines. This review summarizes the changes in the prediction model and the resulting recommendations and discusses potential risks and limitations of the new score. PMID:27404936

  20. Nonapoptotic cell death in acute kidney injury and transplantation.

    PubMed

    Linkermann, Andreas

    2016-01-01

    Acute tubular necrosis causes a loss of renal function, which clinically presents as acute kidney failure (AKI). The biochemical signaling pathways that trigger necrosis have been investigated in detail over the past 5 years. It is now clear that necrosis (regulated necrosis, RN) represents a genetically driven process that contributes to the pathophysiology of AKI. RN pathways such as necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-induced regulated necrosis (MPT-RN) may be mechanistically distinct, and the relative contributions to overall organ damage during AKI in living organisms largely remain elusive. In a synchronized manner, some necrotic programs induce the breakdown of tubular segments and multicellular functional units, whereas others are limited to killing single cells in the tubular compartment. Importantly, the means by which a renal cell dies may have implications for the subsequent inflammatory response. In this review, the recent advances in the field of renal cell death in AKI and key enzymes that might serve as novel therapeutic targets will be discussed. As a consequence of the interference with RN, the immunogenicity of dying cells in AKI in renal transplants will be diminished, rendering inhibitors of RN indirect immunosuppressive agents. PMID:26759047

  1. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome

    PubMed Central

    Martínez, Gonzalo J; Robertson, Stacy; Barraclough, Jennifer; Xia, Qiong; Mallat, Ziad; Bursill, Christina; Celermajer, David S; Patel, Sanjay

    2015-01-01

    Background Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. Methods and Results Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1β, IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively). Conclusions ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines. PMID:26304941

  2. Risk of sudden cardiac death in young athletes: which screening strategies are appropriate?

    PubMed

    Bader, Rima S; Goldberg, Linn; Sahn, David J

    2004-10-01

    Resources are not available to comprehensively evaluate all young athletes before participation in competitive sports. Therefore, the cardiovascular evaluation of young athletes needs to be targeted at high-risk areas and focus on the individuals who are at greatest possible risk: those who have suggestive, even if minor, symptoms, and those who have a family history of sudden death or premature cardiac disease. PMID:15331292

  3. Polymorphic Ventricular Tachycardia/Ventricular Fibrillation and Sudden Cardiac Death in the Normal Heart.

    PubMed

    Shah, Ashok J; Hocini, Meleze; Denis, Arnaud; Derval, Nicolas; Sacher, Frederic; Jais, Pierre; Haissaguerre, Michel

    2016-09-01

    Primary electrical diseases manifest with polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) and along with idiopathic VF contribute to about 10% of sudden cardiac deaths (SCDs) overall. These disorders include long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, and early repolarization syndrome. This article reviews the clinical electrophysiological management of PMVT/VF in a structurally normal heart affected with these disorders. PMID:27521091

  4. In Emergency Department Patients with Acute Chest Pain, Stress Cardiac MRI Observation Unit Care Reduces 1- year Cardiac-Related Health Care Expenditures: A Randomized Trial

    PubMed Central

    Miller, Chadwick D.; Hwang, Wenke; Case, Doug; Hoekstra, James W.; Lefebvre, Cedric; Blumstein, Howard; Hamilton, Craig A.; Harper, Erin N.; Hundley, W. Gregory

    2013-01-01

    Objective To compare the direct cost of medical care and clinical events during the first year after patients with intermediate risk acute chest pain were randomized to stress cardiovascular magnetic resonance (CMR) observation unit (OU) testing, versus inpatient care. Background In a recent study, randomization to OU-CMR reduced median index hospitalization cost compared to inpatient care in patients presenting to the emergency department with intermediate risk acute chest pain. Methods Emergency department patients with intermediate risk chest pain were randomized to OU-CMR (OU care, cardiac markers, stress CMR) or inpatient care (admission, care per admitting provider). This analysis reports the direct cost of cardiac-related care and clinical outcomes (MI, revascularization, cardiovascular death) during the first year of follow-up subsequent to discharge. Consistent with health economics literature, provider cost was calculated from work-related relative value units using the Medicare conversion factor; facility charges were converted to cost using departmental specific cost-to-charge ratios. Linear models were used to compare cost accumulation among study groups. Results One-hundred nine (109) randomized subjects were included in this analysis (52 OU-CMR, 57 inpatient care). The median age was 56 years; baseline characteristics were similar in both groups. At 1 year, 6% of OU-CMR and 9% of inpatient care participants experienced a major cardiac event (p=0.72) with 1 patient in each group experiencing a cardiac event after discharge. First-year cardiac-related costs were significantly lower for participants randomized to OU-CMR compared to participants receiving inpatient care (geometric mean = $3101 vs $4742 including the index visit (p = .004) and $29 vs $152 following discharge (p = .012)). During the year following randomization, 6% of OU-CMR and 9% of inpatient care participants experienced a major cardiac event (p=0.72). Conclusions An OU-CMR strategy

  5. Sudden death of an infant with cardiac, nervous system and genetic involvement – a case report

    PubMed Central

    2013-01-01

    Abstract We present a case of sudden death of a 1-month-old male infant with heart, brainstem and genetic polymorphism involvement. Previously considered quite healthy, the child died suddenly and unexpectedly during sleep. The autopsy protocol included an in-depth anatomopathological examination of both the autonomic nervous system and the cardiac conduction system, and molecular analysis of the serotonin transporter gene promoter region, in which a specific genetic condition seems to be associated with sudden infant death. Histological examination revealed the presence of congenital cardiac alterations (hypertrophic cardiomyopathy and an accessory Mahaim fiber in the cardiac conduction system), severe hypodevelopment of all the raphe nuclei and a heterozygous genotype L/S related to the serotonin transporter gene. The sudden death of this infant was the unavoidable outcome of a complex series of congenital anomalies, each predisposing to SIDS. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3480540091031788 PMID:24053176

  6. Prevention of sudden cardiac death in patients with chronic kidney disease.

    PubMed

    Franczyk-Skóra, Beata; Gluba, Anna; Banach, Maciej; Kozłowski, Dariusz; Małyszko, Jolanta; Rysz, Jacek

    2012-01-01

    Cardiovascular deaths account for about 40% of all deaths of patients with chronic kidney disease (CKD), particularly those on dialysis, while sudden cardiac death (SCD) might be responsible for as many as 60% of SCD in patients undergoing dialysis. Studies have demonstrated a number of factors occurring in hemodialysis (HD) that could lead to cardiac arrhythmias. Patients with CKD undergoing HD are at high risk of ventricular arrhythmia and SCD since changes associated with renal failure and hemodialysis-related disorders overlap. Antiarrhythmic therapy is much more difficult in patients with CKD, but the general principles are similar to those in patients with normal renal function - at first, the cause of arrhythmias should be found and eliminated. Also the choice of therapy is narrowed due to the altered pharmacokinetics of many drugs resulting from renal failure, neurotoxicity of certain drugs and their complex interactions. Cardiac pacing in elderly patients is a common method of treatment. Assessment of patients' prognosis is important when deciding whether to implant complex devices. There are reports concerning greater risk of surgical complications, which depends also on the extent of the surgical site. The decision concerning implantation of a pacing system in patients with CKD should be made on the basis of individual assessment of the patient. PMID:23206758

  7. Left ventricular apical hypoplasia: Case report on cardiomyopathy and a history of sudden cardiac death

    PubMed Central

    Alizadeh Sani, Zahra; Vojdanparast, Mohammad; Rezaeian, Nahid; Seifi, Azin; Omidvar Tehrani, Sahar; Nezafati, Pouya

    2016-01-01

    BACKGROUND Isolated left ventricular apical hypoplasia with several different unrecognized dimensions is a newly discovered congenital anomaly of the heart. CASE REPORT In this report, we describe a case of cardiomyopathy of this type occurring in a 13-year-old male with a history of mental retardation and sudden cardiac death (SCD) of second-degree relatives. The patient was referred for an evaluation of cardiac status. An echocardiography analysis demonstrated a spherical left ventricle (LV) appearance with mild mitral regurgitation. Cardiac magnetic resonance imaging (MRI) confirmed a spherical and truncated LV appearance. The right ventricle was found to have elongated and wrapped around the LV, and diverticulum was also seen in the cardiac MRI. CONCLUSION To the best of our knowledge, this is to present the first case of LV apical hypoplasia combined with LV diverticulum and a family history of SCD. As more cases featuring this cardiomyopathy type are recognized, it will be easier to elucidate the natural history and management of such cardiac anomalies. PMID:27114737

  8. Enrollment of sudden cardiac death victims into a limited cardiac autopsy study in the emergency department.

    PubMed Central

    Denninghoff, K. R.

    2000-01-01

    The lack of balanced recruitment for racial and ethnic groups in research protocols is an important ethical issue. African Americans have a history of forced participation, unethical research, and unwilling human dissection/demonstration that leads to a lack of participation in clinical research. We have embarked on a study of the pathophysiology of sudden death among African Americans which requires a limited autopsy of the heart. Our objective was to improve the recruitment rate in this study when compared with historical rates seen in clinical research and organ donation. We have screened 14 and enrolled 10 African Americans with sudden death (95% CI 0.41-0.91). By addressing the concerns of the African-American community and involving qualified input in the planning stages of the study we have been able to significantly improve the recruitment rate for this important population subgroup. PMID:10800285

  9. The cost of inpatient death associated with acute coronary syndrome

    PubMed Central

    Page, Robert L; Ghushchyan, Vahram; Van Den Bos, Jill; Gray, Travis J; Hoetzer, Greta L; Bhandary, Durgesh; Nair, Kavita V

    2016-01-01

    Background No studies have addressed the cost of inpatient mortality during an acute coronary syndrome (ACS) admission. Objective Compare ACS-related length of stay (LOS), total admission cost, and total admission cost by day of discharge/death for patients who died during an inpatient admission with a matched cohort discharged alive following an ACS-related inpatient stay. Methods Medical and pharmacy claims (2009–2012) were used to identify admissions with a primary diagnosis of ACS from patients with at least 6 months of continuous enrollment prior to an ACS admission. Patients who died during their ACS admission (deceased cohort) were matched (one-to-one) to those who survived (survived cohort) on age, sex, year of admission, Chronic Condition Index score, and prior revascularization. Mean LOS, total admission cost, and total admission cost by the day of discharge/death for the deceased cohort were compared with the survived cohort. A generalized linear model with log transformation was used to estimate the differences in the total expected incremental cost of an ACS admission and by the day of discharge/death between cohorts. A negative binomial model was used to estimate differences in the LOS between the two cohorts. Costs were inflated to 2013 dollars. Results A total of 1,320 ACS claims from patients who died (n=1,320) were identified and matched to 1,319 claims from the survived patients (n=1,319). The majority were men (68%) and mean age was 56.7±6.4 years. The LOS per claim for the deceased cohort was 47% higher (adjusted incidence rate ratio: 1.47, 95% confidence interval: 1.37–1.57) compared with claims from the survived cohort. Compared with the survived cohort, the adjusted mean incremental total cost of ACS admission claims from the deceased cohort was US$43,107±US$3,927 (95% confidence interval: US$35,411–US$50,803) higher. Conclusion Despite decreasing ACS hospitalizations, the economic burden of inpatient death remains high. PMID

  10. Cardiac Rhythm Monitoring After Acute Decompensation for Heart Failure: Results from the CARRYING ON for HF Pilot Study

    PubMed Central

    Mortara, Andrea; Diotallevi, Paolo; Gallone, Giuseppe; Mariconti, Barbara; Gronda, Edoardo; Gentili, Alessandra; Bisetti, Silvia; Botto, Giovanni Luca

    2016-01-01

    Background There’s scarce evidence about cardiovascular events (CV) in patients with hospitalization for acute heart failure (HF) and no indication for immediate device implant. Objective The CARdiac RhYthm monitorING after acute decompensatiON for Heart Failure study was designed to assess the incidence of prespecified clinical and arrhythmic events in this patient population. Methods In this pilot study, 18 patients (12 (67%) male; age 72±10; 16 (89%) NYHA II-III), who were hospitalized for HF with low left ventricular ejection fraction (LVEF) (<40%) and no immediate indication for device implant received an implantable loop recorder (ILR) before hospital discharge. Follow-up visits were scheduled at 3 and 6 months, and at every 6 months until study closure; device data were remotely reviewed monthly. CV mortality, unplanned CV hospitalization, and major arrhythmic events during follow-up were analyzed. Results During a median follow-up of 593 days, major CV occurred in 13 patients (72%); of those, 7 patients had at least 1 cardiac arrhythmic event, 2 had at least a clinical event (CV hospitalization or CV death), and 4 had both an arrhythmic and a CV event. Six (33%) patients experienced 10 major clinical events, 5 of them (50%) were HF related. During follow-up, 2 (11%) patients died due to a CV cause and 3 (16%) patients received a permanent cardiac device. Conclusions After an acute HF hospitalization, patients with LVEF<40% and who are not readily eligible for permanent cardiac device implant have a known high incidence of major CV event. In these patients, ILR allows early detection of major cardiac arrhythmias and the ability to react appropriately in a timely manner. Trial Registration ClinicalTrials.gov NCT01216670; https://clinicaltrials.gov/ct2/show/NCT01216670 PMID:27118481

  11. Finding the rhythm of sudden cardiac death: new opportunities using induced pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Sallam, Karim; Li, Yingxin; Sager, Philip T; Houser, Steven R; Wu, Joseph C

    2015-06-01

    Sudden cardiac death is a common cause of death in patients with structural heart disease, genetic mutations, or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with sudden cardiac death. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology, including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single-ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell-derived cardiomyocytes resemble, but are not identical, adult human cardiomyocytes and provide a new platform for studying arrhythmic disorders leading to sudden cardiac death. A variety of platforms exist to phenotype cellular models, including conventional and automated patch clamp, multielectrode array, and computational modeling. Induced pluripotent stem cell-derived cardiomyocytes have been used to study long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and other hereditary cardiac disorders. Although induced pluripotent stem cell-derived cardiomyocytes are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of sudden cardiac death. PMID:26044252

  12. INHALATION OF OZONE AND DIESEL EXHAUST PARTICLES (DEP) INDUCES ACUTE AND REVERSIBLE CARDIAC GENE EXPRESSION CHANGES

    EPA Science Inventory

    We have recently shown that episodic but not acute exposure to ozone or DEP induces vascular effects that are associated with the loss of cardiac mitochondrial phospholipid fatty acids (DEP 2.0 mg/m3 > ozone, 0.4 ppm). In this study we determined ozone and DEP-induced cardiac gen...

  13. A cardiac mitochondrial cAMP signaling pathway regulates calcium accumulation, permeability transition and cell death

    PubMed Central

    Wang, Z; Liu, D; Varin, A; Nicolas, V; Courilleau, D; Mateo, P; Caubere, C; Rouet, P; Gomez, A-M; Vandecasteele, G; Fischmeister, R; Brenner, C

    2016-01-01

    Although cardiac cytosolic cyclic 3′,5′-adenosine monophosphate (cAMP) regulates multiple processes, such as beating, contractility, metabolism and apoptosis, little is known yet on the role of this second messenger within cardiac mitochondria. Using cellular and subcellular approaches, we demonstrate here the local expression of several actors of cAMP signaling within cardiac mitochondria, namely a truncated form of soluble AC (sACt) and the exchange protein directly activated by cAMP 1 (Epac1), and show a protective role for sACt against cell death, apoptosis as well as necrosis in primary cardiomyocytes. Upon stimulation with bicarbonate (HCO3−) and Ca2+, sACt produces cAMP, which in turn stimulates oxygen consumption, increases the mitochondrial membrane potential (ΔΨm) and ATP production. cAMP is rate limiting for matrix Ca2+ entry via Epac1 and the mitochondrial calcium uniporter and, as a consequence, prevents mitochondrial permeability transition (MPT). The mitochondrial cAMP effects involve neither protein kinase A, Epac2 nor the mitochondrial Na+/Ca2+ exchanger. In addition, in mitochondria isolated from failing rat hearts, stimulation of the mitochondrial cAMP pathway by HCO3− rescued the sensitization of mitochondria to Ca2+-induced MPT. Thus, our study identifies a link between mitochondrial cAMP, mitochondrial metabolism and cell death in the heart, which is independent of cytosolic cAMP signaling. Our results might have implications for therapeutic prevention of cell death in cardiac pathologies. PMID:27100892

  14. Incidence, Etiology, and Comparative Frequency of Sudden Cardiac Death in NCAA Athletes: A Decade in Review

    PubMed Central

    Harmon, Kimberly G.; Asif, Irfan M.; Maleszewski, Joseph J.; Owens, David S.; Prutkin, Jordan M.; Salerno, Jack C.; Zigman, Monica L.; Ellenbogen, Rachel; Rao, Ashwin; Ackerman, Michael J.; Drezner, Jonathan A.

    2015-01-01

    Background The incidence and etiology of sudden cardiac death (SCD) in athletes is debated with hypertrophic cardiomyopathy (HCM) often reported as the most common etiology. Methods and Results A database of all NCAA deaths (2003 – 2013) was developed. Additional information and autopsy reports were obtained when possible. Cause of death was adjudicated by an expert panel. There were 4,242,519 athlete-years (AY) and 514 total student athlete deaths. Accidents were the most common cause of death (257, 50%, 1:16,508 AY) followed by medical causes (147, 29%, 1:28,861 AY). The most common medical cause of death was SCD (79, 15%, 1:53,703 AY). Males were at higher risk than females 1:37,790 AY vs. 1:121,593 AY (IRR 3.2, 95% CI, 1.9-5.5, p < .00001), and black athletes were at higher risk than white athletes 1:21,491 AY vs. 1:68,354 AY (IRR 3.2, 95% CI, 1.9-5.2, p < .00001). The incidence of SCD in Division 1 male basketball athletes was 1:5,200 AY. The most common findings at autopsy were autopsy negative sudden unexplained death (AN-SUD) in 16 (25%) and definitive evidence for HCM was seen in 5 (8%). Media reports identified more deaths in higher divisions (87%, 61%, and 44%) while percentages from the internal database did not vary (87%, 83%, and 89%). Insurance claims identified only 11% of SCDs. Conclusions The rate of SCD in NCAA athletes is high, with males, black athletes and basketball players at substantially higher risk. The most common finding at autopsy is AN-SUD. Media reports are more likely to capture high profile deaths, while insurance claims are not a reliable method for case identification. PMID:25977310

  15. MOEMS-based cardiac enzymes detector for acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Amritsar, Jeetender; Stiharu, Ion G.; Packirisamy, Muthukumaran; Balagopal, Ganesharam; Li, Xing

    2004-10-01

    Biomedical applications of MOEMS are limited only by the mankind imagination. Precision measurements on minute amounts of biological material could be performed by optical means with a remarkable accuracy. Although available in medical laboratories for general purposes, such analyzers are making their way directly to the users in the form of dedicated equipment. Such an example is a test kit to detect the existence of cardiac enzymes in the blood stream. Apart from the direct users, the medical personnel will make use of such tools given the practicality of the kit. In a large proportion of patients admitted to the hospital suspected of Acute Myocardial Infarction (AMI), the symptoms and electrocardiographic changes are inconclusive. This necessitates the use of biochemical markers of myocardial damage for correct exclusion or conformation of AMI. In this study the concept of MOEMS is applied for the detection of enzyme reaction, in which glass spectrums are scanned optically when enzyme molecules adsorb on their surface. This paper presents the optical behavior of glass spectrums under Horseradish Peroxide (HRP) enzyme reaction. The reported experimental results provide valuable information that will be useful in the development of biosensors for enzymatic detection. This paper also reports the dynamic behavior of different glass spectrums.

  16. Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery

    PubMed Central

    Shin, Su Rin; Kim, Won Ho; Kim, Dong Joon; Shin, Il-Woo; Sohn, Ju-Tae

    2016-01-01

    The incidence of acute kidney injury after cardiac surgery (CS-AKI) ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI. PMID:27419130

  17. Anhedonia Predicts Major Adverse Cardiac Events and Mortality in Patients 1 Year After Acute Coronary Syndrome

    PubMed Central

    Davidson, Karina W.; Burg, Matthew M.; Kronish, Ian M.; Shimbo, Daichi; Dettenborn, Lucia; Mehran, Roxana; Vorchheimer, David; Clemow, Lynn; Schwartz, Joseph E.; Lespérance, Francois; Rieckmann, Nina

    2010-01-01

    Context Depression is a consistent predictor of recurrent events and mortality in ACS patients, but it has 2 core diagnostic criteria with distinct biological correlates—depressed mood and anhedonia. Objective To determine if depressed mood and/or anhedonia (loss of pleasure or interest) predict 1-year medical outcomes for patients with Acute Coronary Syndrome (ACS). Design Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within one week of admission, patients underwent a structured psychiatric interview to assess clinically impairing depressed mood, anhedonia, and major depressive episode (MDE); also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity. Setting Coronary care and cardiac care step-down units of 3 university hospitals in New York and Connecticut. Participants Consecutive sample of 453 ACS patients (aged 25–93 years; 42% women). Main Outcomes Measures All-cause mortality (ACM) and documented major adverse cardiac events (MACE; myocardial infarction, hospitalization for unstable angina, or urgent revascularization) were actively surveyed for 1 year after admission. Results There were 67 events (16 deaths and 51 MACE; 14.8%). 108 (24%) and 77 (17%) patients with anhedonia and depressed mood, respectively. After controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16–2.14; P<.01) and MDE (adjusted hazard ratio, 1.48; 95% confidence interval, 1.07–2.04; P=.02) were significant predictors of combined MACE/ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes controlling for MDE diagnosis and depressive symptom severity, each of which were no longer significant. Conclusions Anhedonia identifies risk for MACE/ACM beyond that of established medical prognostic indicators

  18. An autopsy case of cardiac tamponade caused by a ruptured ventricular aneurysm associated with acute myocarditis.

    PubMed

    Kondo, Takeshi; Nagasaki, Yasushi; Takahashi, Motonori; Nakagawa, Kanako; Kuse, Azumi; Morichika, Mai; Sakurada, Makoto; Asano, Migiwa; Ueno, Yasuhiro

    2016-01-01

    We report an autopsy case of hemopericardium caused by rupture of a ventricular aneurysm associated with acute myocarditis in an infant boy aged 2 years and 10 months. Three days before his death, the patient developed fever. On the day of death, he described an urge to defecate and attempted to do so in an upright position. While straining to defecate without success for a prolonged period, he stopped breathing and collapsed. On autopsy, his heart weighed 91.7 g and cardiac tamponade was evident, the pericardial cavity being filled with 140 mL of blood that had come from a 1.5-cm-long rupture in a 2.7×1.5 cm ventricular aneurysm in the posterior left ventricular wall. Patchy grayish-white discoloration was noted in the myocardium. Histologically, CD3-positive T lymphocytic infiltration accompanied by pronounced macrophage infiltration was observed in the myocardium. Hemorrhagic necrosis was detected in the area of the ventricular aneurysm. Staining for matrix metalloproteinase (MMP) expression revealed abundant MMP-2, MMP-7, and MMP-9. Polymerase chain reaction to detect viruses failed to identify any specific causative viruses in the myocardium. In this case of lymphocytic (viral) and histiocytic myocarditis with pronounced macrophage infiltration and upregulation of MMP expression, myocardial remodeling and associated wall weakening had resulted in formation and rupture of an aneurysm. PMID:26832375

  19. Electrophysiologic testing guided risk stratification approach for sudden cardiac death beyond the left ventricular ejection fraction.

    PubMed

    Gatzoulis, Konstantinos A; Tsiachris, Dimitris; Arsenos, Petros; Tousoulis, Dimitris

    2016-01-26

    Sudden cardiac death threats ischaemic and dilated cardiomyopathy patients. Anti- arrhythmic protection may be provided to these patients with implanted cardiac defibrillators (ICD), after an efficient risk stratification approach. The proposed risk stratifier of an impaired left ventricular ejection fraction has limited sensitivity meaning that a significant number of victims will remain undetectable by this risk stratification approach because they have a preserved left ventricular systolic function. Current risk stratification strategies focus on combinations of non invasive methods like T wave alternans, late potentials, heart rate turbulence, deceleration capacity and others, with invasive methods like the electrophysiologic study. In the presence of an electrically impaired substrate with formed post myocardial infarction fibrotic zones, programmed ventricular stimulation provides important prognostic information for the selection of the patients expected to benefit from an ICD implantation, while due to its high negative predictive value, patients at low risk level may also be detected. Clustering evidence from different research groups and electrophysiologic labs support an electrophysiologic testing guided risk stratification approach for sudden cardiac death. PMID:26839662

  20. Sudden Cardiac Death Due to Deficiency of the Mitochondrial Inorganic Pyrophosphatase PPA2.

    PubMed

    Kennedy, Hannah; Haack, Tobias B; Hartill, Verity; Mataković, Lavinija; Baumgartner, E Regula; Potter, Howard; Mackay, Richard; Alston, Charlotte L; O'Sullivan, Siobhan; McFarland, Robert; Connolly, Grainne; Gannon, Caroline; King, Richard; Mead, Scott; Crozier, Ian; Chan, Wandy; Florkowski, Chris M; Sage, Martin; Höfken, Thomas; Alhaddad, Bader; Kremer, Laura S; Kopajtich, Robert; Feichtinger, René G; Sperl, Wolfgang; Rodenburg, Richard J; Minet, Jean Claude; Dobbie, Angus; Strom, Tim M; Meitinger, Thomas; George, Peter M; Johnson, Colin A; Taylor, Robert W; Prokisch, Holger; Doudney, Kit; Mayr, Johannes A

    2016-09-01

    We have used whole-exome sequencing in ten individuals from four unrelated pedigrees to identify biallelic missense mutations in the nuclear-encoded mitochondrial inorganic pyrophosphatase (PPA2) that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis, cardiac arrhythmia, and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutant PPA2-containing mitochondria from fibroblasts showed that the activity of inorganic pyrophosphatase was significantly reduced in affected individuals. Recombinant PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated with disease severity. These findings confirm the pathogenicity of PPA2 mutations and suggest that PPA2 is a cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized. PMID:27523597

  1. Application of Next Generation Sequencing for personalized medicine for sudden cardiac death

    PubMed Central

    Morini, Elena; Sangiuolo, Federica; Caporossi, Daniela; Novelli, Giuseppe; Amati, Francesca

    2015-01-01

    Sudden cardiac death (SCD) is a serious public health problem. In the United States, more than 300,000 people are affected by SCD every year. Significantly, sudden deaths represent 20% of the total mortality and 50% of cardiovascular mortality in Western countries. In addition, SCD constitutes one of the most important unsolved challenges in the practice of forensic pathology because of the failure to determine the exact cause of sudden death. In young individuals, SCD is frequently caused by cardiomyopathies and channelopathies, that have generally an autosomal dominant pattern of inheritance. The impact of genetics and genetic testing on the clinical management of these diseases is unquestioned. In particular, genetic tests are an important tool for identifying pre-symptomatic individuals carrying genetic variant that predisposes them to SCD. High-throughput sequencing technologies offer novel opportunities to deeper investigate the genetic background underlying these fatal diseases and to early identify individuals at risk for SCD. In this review, we provide an overview of the development of Next-Generation Sequencing (NGS) technologies and of guidelines useful to design an efficient sequencing protocol and to perform an accurate data analysis. We suggest a flow chart to follow for the set up of a genetic screening protocol for the prevention of cardiac pathologies, in particular SCD events, in young athletes. PMID:25784923

  2. Detection and prediction of sudden cardiac death (SCD) for personal healthcare.

    PubMed

    Shen, Tsu-Wang; Shen, Hsiao-Ping; Lin, Ching-Heng; Ou, Yi-Ling

    2007-01-01

    Sudden Cardiac Death (SCD) is one of continuing challenges to the modern clinician. It is responsible for an estimated 400,000 deaths per year in the United States and millions of deaths worldwide. This research developed a personal cardiac homecare system by sensing Lead-I ECG signals for detecting and predicting SCD events, which also builds in ECG identity verification. A MIT/BIH SCD Holter Database plus our ECG database were investigated. The system includes a self-made ECG amplifier, a NI DAQ card, a laptop computer, LabView and MatLab programs. The wavelet analysis was applied to detect SCD and the overall performance is 87.5% correct detection rate. In addition, artificial neural networks (ANN) were used to predict SCD events. The correct prediction rates by applying least mean square (LMS), decision based neural network (DBNN), and back propagation (BP) neural network were 67.44%, 58.14% and 55.81% respectively. PMID:18002521

  3. Hypothesis Holiday sudden cardiac death: food and alcohol inhibition of SULT1A enzymes as a precipitant

    PubMed Central

    Eagle, Ken

    2012-01-01

    Sudden cardiac death is a significant health issue, causing millions of deaths worldwide annually. Studies have found that the likelihood of such death is higher in winter. Further studies identified that the highest likelihood occurs on Christmas Day and New Years Day, but not the interim period. Thanksgiving, Independence Day and the Islamic holiday Eid Al-Fitr also show significant increases in the rate of cardiac events or death. A number of mechanisms have been proposed, but none have satisfactorily explained the evidence. This article reviews the data supporting the existence of a holiday cardiac death phenomenon, the involvement of catecholamines and the normal modes of human catecholamine deactivation. Further evidence is reviewed that supports a hypothesized mechanism whereby critical SULT1A catecholamine deactivation enzymes can in some patients be inhibited by naturally-occurring phenols and polyphenols in foods and alcohols. If deactivation is inhibited by holiday consumption excesses, holiday stress or excitement could lead to a buildup of catecholamines that can cause fatal arrhythmias. Awareness of this mechanism could reduce deaths, both through doctor/patient education leading to a moderation in consumption and through the potential identification of patients with a predisposition to SULT1A inhibition. This hypothesis also raises parallels between sudden cardiac death in adults and Sudden Infant Death Syndrome (SIDS). The possible involvement of SULT1A inhibition in SIDS is discussed. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22678655

  4. Hypothesis: holiday sudden cardiac death: food and alcohol inhibition of SULT1A enzymes as a precipitant.

    PubMed

    Eagle, Ken

    2012-10-01

    Sudden cardiac death is a significant health issue, causing millions of deaths worldwide annually. Studies have found that the likelihood of such death is higher in winter. Further studies identified that the highest likelihood occurs on Christmas Day and New Years Day, but not the interim period. Thanksgiving, Independence Day and the Islamic holiday Eid Al-Fitr also show significant increases in the rate of cardiac events or death. A number of mechanisms have been proposed, but none have satisfactorily explained the evidence. This article reviews the data supporting the existence of a holiday cardiac death phenomenon, the involvement of catecholamines and the normal modes of human catecholamine deactivation. Further evidence is reviewed that supports a hypothesized mechanism whereby critical SULT1A catecholamine deactivation enzymes can in some patients be inhibited by naturally-occurring phenols and polyphenols in foods and alcohols. If deactivation is inhibited by holiday consumption excesses, holiday stress or excitement could lead to a buildup of catecholamines that can cause fatal arrhythmias. Awareness of this mechanism could reduce deaths, both through doctor/patient education leading to a moderation in consumption and through the potential identification of patients with a predisposition to SULT1A inhibition. This hypothesis also raises parallels between sudden cardiac death in adults and Sudden Infant Death Syndrome (SIDS). The possible involvement of SULT1A inhibition in SIDS is discussed. PMID:22678655

  5. Risk Stratification for Sudden Cardiac Death: Current Approaches and Predictive Value

    PubMed Central

    Lopera, Gustavo; Curtis, Anne B.

    2009-01-01

    Sudden cardiac death (SCD) is a serious public health problem; the annual incidence of out-of-hospital cardiac arrest in North America is approximately 166,200. Identifying patients at risk is a difficult proposition. At the present time, left ventricular ejection fraction (LVEF) remains the single most important marker for risk stratification. According to current guidelines, most patients with LVEF <35% could benefit from prophylactic ICD implantation, particularly in the setting of symptomatic heart failure. Current risk stratification strategies fail to identify patients at risk of SCD in larger population groups encompassing a greater number of potential SCD victims. However, the best approach to identifying patients and the value of various risk stratification tools is not entirely clear. The goal of this review is to discuss the problem of SCD and the value of the different risk stratification markers and their potential clinical use either alone or in combination with other risk stratification markers. PMID:20066150

  6. Aborted Sudden Cardiac Death and a Mother with Suspected Metabolic Myopathy

    PubMed Central

    Finsterer, Josef; Stöllberger, Claudia; Keller, Hans

    2014-01-01

    Aborted sudden cardiac death (SCD) has not been reported as initial manifestation of cardiac involvement in metabolic myopathy (MM). A 20-year-old female with a previous history of three syncopes, hyperhidrosis, and recurrent tick bites experienced aborted SCD. Her mother presented with MM, and a history of pituitary adenoma, nephroptosis, arterial hypertension, depression, migraine, goiter, pancreatitis, osteoporosis, hyperhidrosis, multiple muscle ruptures, and hyperlipidemia. After a few days of disorientation and amnesia, the young female recovered completely. Clinical neurological examination was noticeable for partial ophthalmoparesis and mild hyperprolactinemia. She received an implantable cardioverter defibrillator, which did not discharge so far. Recurrent syncopes and aborted SCD may be the initial manifestation of MM with multiple organ involvement. The family history is important in cases with aborted SCD to guide the diagnostic work-up. Phenotypic heterogeneity between the family members may be an indicator of MM. PMID:25187745

  7. Contrasting effects of cardiac glycosides on cisplatin- and etoposide-induced cell death.

    PubMed

    Kulikov, Andrey V; Slobodkina, Ekaterina A; Alekseev, Andrey V; Gogvadze, Vladimir; Zhivotovsky, Boris

    2016-07-01

    Cardiac glycosides (CGs) or cardiotonic steroids, which constitute a group of naturally occurring compounds with a steroid-like structure, can act on Na+/K+-ATPase as a receptor and activate intracellular signaling messengers leading to a variety of cellular responses. Epidemiological studies have revealed that CGs, used for the treatment of cardiac disorders, may also be beneficial as anti-cancer agents. CGs, acting in combination with other chemotherapeutic agents, may significantly alter their efficiency in relation to cancer cell elimination, causing both sensitization and an increase in cancer cell death, and in some cases resistance to chemotherapy. Here we show the ability of CGs to modulate apoptotic response to conventionally used anti-cancer drugs. In combination with etoposide, CGs digoxin may enhance cytotoxic potential, thereby allowing the chemotherapeutic dose to be decreased and minimizing toxicity and adverse reactions. Mechanisms behind this event are discussed. PMID:26854291

  8. Electrocardiographic T Wave Abnormalities and the Risk of Sudden Cardiac Death: The Finnish Perspective.

    PubMed

    Tikkanen, Jani T; Kenttä, Tuomas; Porthan, Kimmo; Huikuri, Heikki V; Junttila, M Juhani

    2015-11-01

    The identification of patients at risk for sudden cardiac death (SCD) is still a significant challenge to clinicians and scientists. Noninvasive identification of high-risk patients has been of great interest, and several ventricular depolarization and repolarization abnormalities in the standard 12-lead electrocardiogram (ECG) have been associated with increased vulnerability to lethal ventricular arrhythmias. Several benign and pathological conditions can induce changes in repolarization detected as alteration of the ST segment or T wave. Changes in the ST segment and T waves can be early markers of an underlying cardiovascular disease, and even minor ST-T abnormalities have predicted reduced survival and increased risk of SCD in the adult population. In this review, we will discuss the current knowledge of the SCD risk with standard 12-lead ECG T wave abnormalities in the general population, and possible T wave changes in various cardiac conditions predisposing to SCD. PMID:26391699

  9. Usefulness of combined history, physical examination, electrocardiogram, and limited echocardiogram in screening adolescent athletes for risk for sudden cardiac death.

    PubMed

    Anderson, Jeffrey B; Grenier, Michelle; Edwards, Nicholas M; Madsen, Nicolas L; Czosek, Richard J; Spar, David S; Barnes, Allison; Pratt, Jesse; King, Eileen; Knilans, Timothy K

    2014-12-01

    Sudden cardiac death in the young (SCDY) is the leading cause of death in young athletes during sport. Screening young athletes for high-risk cardiac defects is controversial. The purpose of this study was to assess the utility and feasibility of a comprehensive cardiac screening protocol in an adolescent population. Adolescent athletes were recruited from local schools and/or sports teams. Each subject underwent a history and/or physical examination, an electrocardiography (ECG), and a limited echocardiography (ECHO). The primary outcome measure was identification of cardiac abnormalities associated with an elevated risk for sudden death. We secondarily identified cardiac abnormalities not typically associated with a short-term risk of sudden death. A total of 659 adolescent athletes were evaluated; 64% men. Five subjects had cardiac findings associated with an elevated risk for sudden death: prolonged QTc >500 ms (n = 2) and type I Brugada pattern (n = 1), identified with ECG; dilated cardiomyopathy (n = 1) and significant aortic root dilation; and z-score = +5.5 (n = 1). History and physical examination alone identified 76 (11.5%) subjects with any cardiac findings. ECG identified 76 (11.5%) subjects in which a follow-up ECHO or cardiology visit was recommended. Left ventricular mass was normal by ECHO in all but 1 patient with LVH on ECG. ECHO identified 34 (5.1%) subjects in whom a follow-up ECHO or cardiology visit was recommended. In conclusion, physical examination alone was ineffective in identification of subjects at elevated risk for SCDY. Screening ECHO identified patients with underlying cardiac disease not associated with immediate risk for SCDY. Cost of comprehensive cardiac screening is high. PMID:25307198

  10. Pre-participation screening for the prevention of sudden cardiac death in athletes

    PubMed Central

    Borrione, Paolo; Quaranta, Federico; Ciminelli, Emanuela

    2013-01-01

    Pre-partecipation screening is the systematic practice of medically evaluating large populations of athletes before participation in sport activities for the purpose of identifying abnormalities that could cause disease progression or sudden death. In order to prevent sudden cardiac death (SCD), cardiovascular screening should include a strategy for excluding high-risk subjects from athletic and vigorous exercise. There are two major screening programmes in the world. In the United States competitive athletes are screened by means of family and personal history and physical examination. In Italy there is a mandatory screening for competitive athletes, which includes a resting electrocardiogram (ECG) for the detection of cardiac abnormalities. The most important issue to be addressed is whether a screened subject is really guaranteed that she/he is not suffering from any cardiac disease or at risk for SCD. Conceivably, the introduction of echocardiogram during the pre-participation screening, could be reasonable, despite the discrete sensitivity of ECG, in raising clinical suspicions of severe cardiac alterations predisposing to SCD. It is clear that the cost-benefit ratio per saved lives of the ECG screening is a benchmark of the Public Health policy. On the contrary, the additional introduction of echocardiography in a large population screening programme seems to be too much expansive for the Public Health and for this reason not easily practicable, even if useful and not invasive. Even if we strongly believe that a saved life is more important than any cost-efficacy evaluation, the issue of the economical impact of this approach should be further assessed. PMID:25237617

  11. Pre-participation screening for the prevention of sudden cardiac death in athletes.

    PubMed

    Borrione, Paolo; Quaranta, Federico; Ciminelli, Emanuela

    2013-03-26

    Pre-partecipation screening is the systematic practice of medically evaluating large populations of athletes before participation in sport activities for the purpose of identifying abnormalities that could cause disease progression or sudden death. In order to prevent sudden cardiac death (SCD), cardiovascular screening should include a strategy for excluding high-risk subjects from athletic and vigorous exercise. There are two major screening programmes in the world. In the United States competitive athletes are screened by means of family and personal history and physical examination. In Italy there is a mandatory screening for competitive athletes, which includes a resting electrocardiogram (ECG) for the detection of cardiac abnormalities. The most important issue to be addressed is whether a screened subject is really guaranteed that she/he is not suffering from any cardiac disease or at risk for SCD. Conceivably, the introduction of echocardiogram during the pre-participation screening, could be reasonable, despite the discrete sensitivity of ECG, in raising clinical suspicions of severe cardiac alterations predisposing to SCD. It is clear that the cost-benefit ratio per saved lives of the ECG screening is a benchmark of the Public Health policy. On the contrary, the additional introduction of echocardiography in a large population screening programme seems to be too much expansive for the Public Health and for this reason not easily practicable, even if useful and not invasive. Even if we strongly believe that a saved life is more important than any cost-efficacy evaluation, the issue of the economical impact of this approach should be further assessed. PMID:25237617

  12. Use of intra-aortic balloon pump support for oozing-type cardiac rupture after acute myocardial infarction.

    PubMed

    Zhang, Zhi-Ping; Su, Xi; Liu, Cheng-Wei; Song, Dan; Peng, Jian; Wu, Ming-Xiang; Yang, Yu-Chun; Liu, Bo; Xu, Cheng-Yi; Wang, Fang

    2016-01-01

    Left ventricular free wall rupture usually leads to acute hemopericardium and sudden cardiac death resulting in cardiac tamponade. Rarely, only a few patients with subacute free wall rupture such as oozing-type ventricular rupture or left ventricular false aneurysm may permit time for pericardiocentesis and surgery. We report a 63-year-old man with ST-elevation myocardial infarction who underwent primary percutaneous coronary intervention about 12 hours from the onset, and cardiac tamponade occurred on the second day. An intra-aortic balloon pump (IABP) was immediately inserted for hemodynamic support. After 100 mL of pericardial fresh blood was drained from the percardial cavity, his hemodynamic collapse was promptly improved with IABP support. In the following 24 hours, about 600 mL of hemorrhagic pericardial fluid was drained. The most likely diagnosis was concerning for oozing-type ventricular rupture, and a conservative approach was decided. The patient survived to the acute phase under IABP support and was discharged with complete recovery. PMID:26145582

  13. Activation and modulation of cardiac poly-adenosine diphosphate ribose polymerase activity in a rat model of brain death.

    PubMed

    Brain, John G; Rostron, Anthony J; Dark, John H; Kirby, John A

    2008-05-15

    DNA damage during transplantation can activate poly-adenosine diphosphate ribose polymerase (PARP) resulting in the generation of polymers of adenosine diphosphate-ribose (PAR). Excessive linkage of PAR to nuclear proteins can induce cell death, thereby limiting the function of transplanted organs. This study uses a rat model of brain death to determine the profile of PARP activation and whether mechanisms that lead to cell death can be ameliorated by appropriate donor resuscitation. The expression of PAR-linked nuclear proteins within cardiac myocytes was greatly increased after the induction of donor brain death. Importantly, infusion of noradrenaline or vasopressin to normalize the chronic hypotension produced by brain death reduced the expression of PAR to a level below baseline. These data suggest that chronic hypotension after donor brain death has the potential to limit cardiac function through the activation of PARP; however, this early cause of graft damage can be mitigated by appropriate donor resuscitation. PMID:18475194

  14. Fat infiltration of left ventricle - a rare cause of sudden cardiac death.

    PubMed

    Kanchan, Tanuj; Acharya, Jenash; Ram, Pradhum; Khadilkar, Urmila N; Rana, Talvinder

    2016-09-01

    Cor adiposum is a rare disorder of the heart, where the normal heart tissue is replaced by fibro-fatty infiltrates. We report one such case of a middle-aged female who was declared dead shortly after a syncopal episode. At autopsy, the pericardium was intact and firmly adhered to the heart. Histopathology revealed fatty infiltrates extending into the left ventricle of the heart. A post-mortem diagnosis of Cor adiposum was made which is an uncommonly reported cause of sudden cardiac death. PMID:26975397

  15. Exercising arrhythmias and sudden cardiac death in horses: Review of the literature and comparative aspects.

    PubMed

    Navas de Solis, C

    2016-07-01

    Arrhythmias are common in equine athletes during and immediately after exercise. Many of these rhythm variations are not clinically relevant. In horses, a link between different exercising arrhythmias and poor performance or between exercising arrhythmias and sudden cardiac death (SCD) is strongly suspected but not fully understood or proven. SCD during races or competitions is rare, but has catastrophic consequences for the safety of the human partner and public perceptions of welfare during equestrian sports. This review summarises current knowledge of equine exercise arrhythmias and their implications in SCD and compares existing principles and recommendations for equine subjects with those for human athletes. PMID:27156002

  16. Sudden cardiac death: mandatory exclusion of athletes at risk is a step too far.

    PubMed

    Anderson, Lynley; Exeter, Dan; Bowyer, Lynne

    2012-04-01

    Sudden cardiac death (SCD) in young athletes is a distressing event and it is not surprising that some physicians working with sports people are proposing that preventive action should be taken. There is a push for a system similar to that established in some countries, which involves screening and mandatory exclusion of those at risk. We argue that while screening can provide useful information to at-risk athletes making decisions about their future athletic careers, mandatory exclusion of athletes is paternalistic and such decisions are not rightfully within the domain of medicine. PMID:22039216

  17. Frequency and Factors Associated with Unexpected Death in an Acute Palliative Care Unit: Expect the Unexpected

    PubMed Central

    Bruera, Sebastian; Chisholm, Gary; Santos, Renata Dos; Bruera, Eduardo; Hui, David

    2015-01-01

    Context Few studies have examined the frequency of unexpected death and its associated factors in a palliative care setting. Objectives To determine the frequency of unexpected death in two acute palliative care units (APCUs); to compare the frequency of signs of impending death between expected and unexpected deaths; and to determine the predictors associated with unexpected death. Methods In this prospective, longitudinal, observational study, consecutive patients admitted to two APCUs were enrolled and physical signs of impending death were documented twice daily until discharge or death. Physicians were asked to complete a survey within 24 hours of APCU death. The death was considered unexpected if the physician answered “yes” to the question “Were you surprised by the timing of the death?” Results In total, 193 of 203 after-death assessments (95%) were collected for analysis. Nineteen of 193 patients died unexpectedly (10%). Signs of impending death, including nonreactive pupils, inability to close eyelids, decreased response to verbal stimuli, drooping of nasolabial folds, peripheral cyanosis, pulselessness of the radial artery, and respiration with mandibular movement, were documented more frequently in expected deaths than unexpected deaths (P < 0.05). Longer disease duration was associated with unexpected death (33 months vs. 12 months, P=0.009). Conclusion Unexpected death occurred in an unexpectedly high proportion of patients in the APCU setting, and was associated with fewer signs of impending death. Our findings highlight the need for palliative care teams to be prepared for the unexpected. PMID:25499421

  18. Validity of the GRACE (Global Registry of Acute Coronary Events) acute coronary syndrome prediction model for six month post‐discharge death in an independent data set

    PubMed Central

    Bradshaw, P J; Ko, D T; Newman, A M; Donovan, L R

    2006-01-01

    Objective To determine the validity of the GRACE (Global Registry of Acute Coronary Events) prediction model for death six months after discharge in all forms of acute coronary syndrome in an independent dataset of a community based cohort of patients with acute myocardial infarction (AMI). Design Independent validation study based on clinical data collected retrospectively for a clinical trial in a community based population and record linkage to administrative databases. Setting Study conducted among patients from the EFFECT (enhanced feedback for effective cardiac treatment) study from Ontario, Canada. Patients Randomly selected men and women hospitalised for AMI between 1999 and 2001. Main outcome measure Discriminatory capacity and calibration of the GRACE prediction model for death within six months of hospital discharge in the contemporaneous EFFECT AMI study population. Results Post‐discharge crude mortality at six months for the EFFECT study patients with AMI was 7.0%. The discriminatory capacity of the GRACE model was good overall (C statistic 0.80) and for patients with ST segment elevation AMI (STEMI) (0.81) and non‐STEMI (0.78). Observed and predicted deaths corresponded well in each stratum of risk at six months, although the risk was underestimated by up to 30% in the higher range of scores among patients with non‐STEMI. Conclusions In an independent validation the GRACE risk model had good discriminatory capacity for predicting post‐discharge death at six months and was generally well calibrated, suggesting that it is suitable for clinical use in general populations. PMID:16387810

  19. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study

    PubMed Central

    Shah, Anoop S V; Anand, Atul; Sandoval, Yader; Lee, Kuan Ken; Smith, Stephen W; Adamson, Philip D; Chapman, Andrew R; Langdon, Timothy; Sandeman, Dennis; Vaswani, Amar; Strachan, Fiona E; Ferry, Amy; Stirzaker, Alexandra G; Reid, Alan; Gray, Alasdair J; Collinson, Paul O; McAllister, David A; Apple, Fred S; Newby, David E; Mills, Nicholas L

    2015-01-01

    Summary Background Suspected acute coronary syndrome is the commonest reason for emergency admission to hospital and is a large burden on health-care resources. Strategies to identify low-risk patients suitable for immediate discharge would have major benefits. Methods We did a prospective cohort study of 6304 consecutively enrolled patients with suspected acute coronary syndrome presenting to four secondary and tertiary care hospitals in Scotland. We measured plasma troponin concentrations at presentation using a high-sensitivity cardiac troponin I assay. In derivation and validation cohorts, we evaluated the negative predictive value of a range of troponin concentrations for the primary outcome of index myocardial infarction, or subsequent myocardial infarction or cardiac death at 30 days. This trial is registered with ClinicalTrials.gov (number NCT01852123). Findings 782 (16%) of 4870 patients in the derivation cohort had index myocardial infarction, with a further 32 (1%) re-presenting with myocardial infarction and 75 (2%) cardiac deaths at 30 days. In patients without myocardial infarction at presentation, troponin concentrations were less than 5 ng/L in 2311 (61%) of 3799 patients, with a negative predictive value of 99·6% (95% CI 99·3–99·8) for the primary outcome. The negative predictive value was consistent across groups stratified by age, sex, risk factors, and previous cardiovascular disease. In two independent validation cohorts, troponin concentrations were less than 5 ng/L in 594 (56%) of 1061 patients, with an overall negative predictive value of 99·4% (98·8–99·9). At 1 year, these patients had a lower risk of myocardial infarction and cardiac death than did those with a troponin concentration of 5 ng/L or more (0·6% vs 3·3%; adjusted hazard ratio 0·41, 95% CI 0·21–0·80; p<0·0001). Interpretation Low plasma troponin concentrations identify two-thirds of patients at very low risk of cardiac events who could be discharged from

  20. Rationale and design of the Pan-African Sudden Cardiac Death survey: the Pan-African SCD study

    PubMed Central

    Bonny, Aimé; Bonny, Aimé; Ngantcha, Marcus; Ndongo Amougou, Sylvie; Kane, Adama; Marrakchi, Sonia; Okello, Emmy; Taty, Georges; Gehani, Abdulrrazzak; Diakite, Mamadou; Talle, Mohammed A; Lambiase, Pier D; Houenassi, Martin; Chin, Ashley; Otieno, Harun; Temu, Gloria; Koffi Owusu, Isaac; Karaye, Kamilu M; Awad, Abdalla AM; Gregers Winkel, Bo; Priori, Silvia G; Priori, Silvia G

    2014-01-01

    Summary Background The estimated rate of sudden cardiac death (SCD) in Western countries ranges from 300 000 to 400 000 annually, which represents 0.36 to 1.28 per 1 000 inhabitants in Europe and the United States. The burden of SCD in Africa is unknown. Our aim is to assess the epidemiology of SCD in Africa. Methods The Pan-Africa SCD study is a prospective, multicentre, community-based registry monitoring all cases of cardiac arrest occurring in victims over 15 years old. We will use the definition of SCD as ‘witnessed natural death occurring within one hour of the onset of symptoms’ or ‘unwitnessed natural death within 24 hours of the onset of symptoms’. After appro val from institutional boards, we will record demographic, clinical, electrocardiographic and biological variables of SCD victims (including survivors of cardiac arrest) in several African cities. All deaths occurring in residents of districts of interest will be checked for past medical history, circumstances of death, and autopsy report (if possible). We will also analyse the employment of resuscitation attempts during the time frame of sudden cardiac arrest (SCA) in various patient populations throughout African countries. Conclusion This study will provide comprehensive, contemporary data on the epidemiology of SCD in Africa and will help in the development of strategies to prevent and manage cardiac arrest in this region of the world. PMID:25192301

  1. Kcne2 Deletion Creates a Multisystem Syndrome Predisposing to Sudden Cardiac Death

    PubMed Central

    Hu, Zhaoyang; Kant, Ritu; Anand, Marie; King, Elizabeth C.; Krogh-Madsen, Trine; Christini, David J.; Abbott, Geoffrey W.

    2014-01-01

    Background Sudden cardiac death (SCD) is the leading global cause of mortality, exhibiting increased incidence in diabetics. Ion channel gene perturbations provide a well-established ventricular arrhythmogenic substrate for SCD. However, most arrhythmia susceptibility genes - including the KCNE2 K+ channel β subunit - are expressed in multiple tissues, suggesting potential multiplex SCD substrates. Methods and Results Using “whole transcript” transcriptomics, we uncovered cardiac angiotensinogen upregulation and remodeling of cardiac angiotensinogen interaction networks in P21 Kcne2−/− mouse pups, and adrenal remodeling consistent with metabolic syndrome in adult Kcne2−/− mice. This led to the discovery that Kcne2 disruption causes multiple acknowledged SCD substrates of extracardiac origin: diabetes, hypercholesterolemia, hyperkalemia, anemia and elevated angiotensin II. Kcne2 deletion was also prerequisite for aging-dependent QT prolongation, ventricular fibrillation and SCD immediately following transient ischemia, and fasting-dependent hypoglycemia, myocardial ischemia and atrioventricular block. Conclusions Disruption of a single, widely expressed arrhythmia susceptibility gene can generate a multisystem syndrome comprising manifold electrical and systemic substrates and triggers of SCD. This paradigm is expected to apply to other arrhythmia susceptibility genes, the majority of which encode ubiquitously expressed ion channel subunits or regulatory proteins. PMID:24403551

  2. Risk stratification for sudden cardiac death: current status and challenges for the future†

    PubMed Central

    Wellens, Hein J.J.; Schwartz, Peter J.; Lindemans, Fred W.; Buxton, Alfred E.; Goldberger, Jeffrey J.; Hohnloser, Stefan H.; Huikuri, Heikki V.; Kääb, Stefan; La Rovere, Maria Teresa; Malik, Marek; Myerburg, Robert J.; Simoons, Maarten L.; Swedberg, Karl; Tijssen, Jan; Voors, Adriaan A.; Wilde, Arthur A.

    2014-01-01

    Sudden cardiac death (SCD) remains a daunting problem. It is a major public health issue for several reasons: from its prevalence (20% of total mortality in the industrialized world) to the devastating psycho-social impact on society and on the families of victims often still in their prime, and it represents a challenge for medicine, and especially for cardiology. This text summarizes the discussions and opinions of a group of investigators with a long-standing interest in this field. We addressed the occurrence of SCD in individuals apparently healthy, in patients with heart disease and mild or severe cardiac dysfunction, and in those with genetically based arrhythmic diseases. Recognizing the need for more accurate registries of the global and regional distribution of SCD in these different categories, we focused on the assessment of risk for SCD in these four groups, looking at the significance of alterations in cardiac function, of signs of electrical instability identified by ECG abnormalities or by autonomic tests, and of the progressive impact of genetic screening. Special attention was given to the identification of areas of research more or less likely to provide useful information, and thereby more or less suitable for the investment of time and of research funds. PMID:24801071

  3. Risk stratification for sudden cardiac death: current status and challenges for the future.

    PubMed

    Wellens, Hein J J; Schwartz, Peter J; Lindemans, Fred W; Buxton, Alfred E; Goldberger, Jeffrey J; Hohnloser, Stefan H; Huikuri, Heikki V; Kääb, Stefan; La Rovere, Maria Teresa; Malik, Marek; Myerburg, Robert J; Simoons, Maarten L; Swedberg, Karl; Tijssen, Jan; Voors, Adriaan A; Wilde, Arthur A

    2014-07-01

    Sudden cardiac death (SCD) remains a daunting problem. It is a major public health issue for several reasons: from its prevalence (20% of total mortality in the industrialized world) to the devastating psycho-social impact on society and on the families of victims often still in their prime, and it represents a challenge for medicine, and especially for cardiology. This text summarizes the discussions and opinions of a group of investigators with a long-standing interest in this field. We addressed the occurrence of SCD in individuals apparently healthy, in patients with heart disease and mild or severe cardiac dysfunction, and in those with genetically based arrhythmic diseases. Recognizing the need for more accurate registries of the global and regional distribution of SCD in these different categories, we focused on the assessment of risk for SCD in these four groups, looking at the significance of alterations in cardiac function, of signs of electrical instability identified by ECG abnormalities or by autonomic tests, and of the progressive impact of genetic screening. Special attention was given to the identification of areas of research more or less likely to provide useful information, and thereby more or less suitable for the investment of time and of research funds. PMID:24801071

  4. Explaining the clinical manifestations of T wave alternans in patients at risk for sudden cardiac death

    PubMed Central

    Cutler, Michael J; Rosenbaum, David S.

    2009-01-01

    The mechanisms underlying sudden cardiac death (SCD) are complex and diverse. Therefore, correct application of any marker to risk stratify patients for appropriate therapy requires knowledge regarding how the marker is reflective of a particular electro-anatomical substrate for arrhythmias. Non-invasive measurement of beat-to-beat alternation of the electrocardiographic T-wave, referred to as T-wave alternans (TWA), is an important marker of risk for sudden cardiac death (SCD). Is this relationship a mere association or is TWA mechanistically linked to SCD? Recent experimental evidence strongly supports a mechanistic relationship between TWA and SCD. This review will consider the underlying mechanisms of TWA derived from experimental studies, as they relate to clinical observations of TWA in humans, addressing the following questions derived from common clinical observations: 1) Where does TWA on the surface ECG come from? 2) Why is controlled heart rate elevation required to elicit TWA? 3) Why is TWA associated with risk for SCD? 4) Why is TWA associated with a broad range of ventricular arrhythmias? and 5) How do commonly used medications affect TWA? PMID:19168395

  5. Basis for Sudden Cardiac Death Prediction by T-Wave Alternans from an Integrative Physiology Perspective

    PubMed Central

    Verrier, Richard L.; Kumar, Kapil; Nearing, Bruce D.

    2009-01-01

    Detection of microvolt levels of T-wave alternans (TWA) has been shown to be useful in identifying individuals at heightened risk for sudden cardiac death. The mechanistic bases for TWA are complex, at the cellular level involving multiple mechanisms, particularly instabilities in membrane voltage (i.e., steep action potential duration restitution slope) and disruptions in intracellular calcium cycling dynamics. The integrative factors influencing TWA at the systemic level are also multifold. We focus on three main variables, namely, heart rate, autonomic nervous system activities, and myocardial ischemia. Clinically, there is growing interest in extending TWA testing to include ambulatory ECG monitoring as well as exercise. The former modality permits assessment of the influence of diverse provocative stimuli of daily life, including circadian factors, mental stress, and sleep-state related disturbances in respiratory and cardiovascular function. Two major emerging concepts in clinical TWA testing are discussed, namely, quantitative analysis of TWA level, to complement the current binary classification scheme, and risk stratification of patients with preserved left ventricular function, the population with the largest absolute number of sudden cardiac deaths. PMID:19251221

  6. Role of Sodium and Calcium Dysregulation in Tachyarrhythmias in Sudden Cardiac Death

    PubMed Central

    Wagner, Stefan; Maier, Lars S.; Bers, Donald M.

    2015-01-01

    Despite improvements in the therapy of underlying heart disease sudden cardiac death (SCD) is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes many ion channels and transporters, including voltage-gated Na and Ca channels, cardiac ryanodine receptors, Na/Ca-exchanger and SR Ca-ATPase are involved in this regulation. We have learned a lot about the pathophysiological relevance of disturbed ion channel function from monogenetic disorders. Changes in the gating of a single ion channel and/or the activity of an ion pump suffice to dramatically increase the propensity for arrhythmias even in structurally normal hearts. Nevertheless, patients with heart failure (HF) with acquired dysfunction in many ion channels and transporters exhibit profound dysregulation of Na and Ca handling and Ca/calmodulin dependent protein kinase, and are especially prone to arrhythmias. A deeper understanding of the underlying arrhythmic principles is mandatory if we are to improve their outcome. This review addresses basic tachy-arrhythmic mechanisms, the underlying ionic mechanisms and the consequences for ion homeostasis, and the situation in complex diseases like HF. PMID:26044250

  7. Sudden Cardiac Death in Young Athletes; a Literature Review and Special Considerations in Asia

    PubMed Central

    Halabchi, Farzin; Seif-Barghi, Tohid; Mazaheri, Reza

    2011-01-01

    Sudden cardiac death (SCD) in a young athlete is rare, but catastrophic. Exercise acts as a risk factor for SCD in people with cardiovascular disease. A diversity of cardiovascular disorders including hypertrophic cardiomyopathy, congenital coronary anomalies, arrhythmogenic right ventricular dysplasia, dilated cardiomyopathy, aortic rupture due to Marfan syndrome, myocarditis, valvular disease and electrical disorders (Wolff–Parkinson–White syndrome, long QT syndrome, Brugada syndrome), as well as commotio cordis represent the common causes of SCD in young athletes. As the outcome of lethal cardiovascular disorders is not reversible except in few cases, effective measures should be addressed to reduce the burden of sudden cardiac death in young athletes. Currently, two types of recommendations are proposed by American and European countries. It seems that there are some special considerations in Asia, entirely different from North America or Europe, which warrant more comprehensive research on epidemiology and etiology of SCD in young Asian athletes by country and evaluation of current national preventive strategies and their achievements in decreasing the risk. Using these data and considering regional restrictions, an expert group will be able to plan a practical and feasible preventive strategy. PMID:22375212

  8. The costs of a suburban paramedic program in reducing deaths due to cardiac arrest.

    PubMed

    Urban, N; Bergner, L; Eisenberg, M S

    1981-04-01

    The marginal costs per averted death of a suburban paramedic program are estimated to be approximately $42,000, when program costs are attributed entirely to cardiac arrest cases due to underlying heart disease, and indirect costs attributable to episode-related hospitalization are included, It is suggested that at $42,000 per cardiac arrest death averted the program is cost-beneficial by two criteria. First, it compares favorably with an estimate obtained from the literature of the value to the average individual of saving the life of a myocardial infarction patient. Second, the people of King County passed a cost-commensurate Paramedic Program Property Tax Levy in 1979, revealing their willingness to support the program. Results of the study should be generalized in accordance with the facts that in King County 1) the population density averages approximately 1,300 per square mile; 2) a basic emergency medical system ensures a 4-minute average response time to initiation of cardiopulmonary resuscitation; 3) a citizen-training program in cardiopulmonary resuscitation further reduces average time to initiation of basic life support; and 4) the paramedic program is designed to ensure a 10-minute average time to definitive care. PMID:6785539

  9. SPR detection of cardiac troponin T for acute myocardial infarction.

    PubMed

    Pawula, Maria; Altintas, Zeynep; Tothill, Ibtisam E

    2016-01-01

    A surface plasmon resonance (SPR) sensor developed for the rapid, sensitive and specific detection of cardiac troponin T (cTnT) in serum samples is reported in this work. An extensive optimisation of assay parameters was conducted to achieve optimal detection strategy. Both direct and sandwich immunoassay formats were investigated and optimised. The response obtained was enhanced further by the use of gold nanoparticles (AuNPs) conjugated to the anti-cTnT detection antibody. A regeneration method was developed to enable the reuse of the SPR sensor for multiple sample application. The SPR immunosensor showed good reproducibility for cTnT detection in the concentration range of 25-1000 ng mL(-1) and 5-400 ng mL(-1) for the direct and sandwich assays in buffer, respectively. The linear regression analysis was performed and R(2) value was found as 0.99 for both assays. In order to optimise the sensor for serum analysis, nonspecific binding of serum proteins was reduced through the use of additives in the dilution buffer. To achieve greater sensitivity, the performance of the cTnT immunosensor sandwich assay in human serum was evaluated using non-modified and AuNP modified detector antibodies. A detection limit (LOD) for the immunosensor in 50% serum was assessed as 5 ng mL(-1) cTnT for the standard sandwich assay and 0.5 ng mL(-1) cTnT when using AuNP conjugated detector antibodies with a linear dynamic range of 0.5-40 ng mL(-1). The dissociation constant was found as 3.28 × 10(-9) M using Langmuir binding model which indicates high affinity between cTnT and its antibody. The proposed SPR immunosensor has a promising potential to be developed for point-of-care testing for the early diagnosis of acute myocardial infarction (AMI). This method can also be used for the rapid detection of biomarkers in central nervous system diseases. PMID:26695335

  10. First experience of liver transplantation with type 2 donation after cardiac death in France.

    PubMed

    Savier, Eric; Dondero, Federica; Vibert, Eric; Eyraud, Daniel; Brisson, Hélène; Riou, Bruno; Fieux, Fabienne; Naili-Kortaia, Salima; Castaing, Denis; Rouby, Jean-Jacques; Langeron, Olivier; Dokmak, Safi; Hannoun, Laurent; Vaillant, Jean-Christophe

    2015-05-01

    Organ donation after unexpected cardiac death [type 2 donation after cardiac death (DCD)] is currently authorized in France and has been since 2006. Following the Spanish experience, a national protocol was established to perform liver transplantation (LT) with type 2 DCD donors. After the declaration of death, abdominal normothermic oxygenated recirculation was used to perfuse and oxygenate the abdominal organs until harvesting and cold storage. Such grafts were proposed to consenting patients < 65 years old with liver cancer and without any hepatic insufficiency. Between 2010 and 2013, 13 LTs were performed in 3 French centers. Six patients had a rapid and uneventful postoperative recovery. However, primary nonfunction occurred in 3 patients, with each requiring urgent retransplantation, and 4 early allograft dysfunctions were observed. One patient developed a nonanastomotic biliary stricture after 3 months, whereas 8 patients showed no sign of ischemic cholangiopathy at their 1-year follow-up. In comparison with a control group of patients receiving grafts from brain-dead donors (n = 41), donor age and cold ischemia time were significantly lower in the type 2 DCD group. Time spent on the national organ wait list tended to be shorter in the type 2 DCD group: 7.5 months [interquartile range (IQR), 4.0-11.0 months] versus 12.0 months (IQR, 6.8-16.7 months; P = 0.08. The 1-year patient survival rates were similar (85% in the type 2 DCD group versus 93% in the control group), but the 1-year graft survival rate was significantly lower in the type 2 DCD group (69% versus 93%; P = 0.03). In conclusion, to treat borderline hepatocellular carcinoma, LT with type 2 DCD donors is possible as long as strict donor selection is observed. PMID:25865077

  11. Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death.

    PubMed

    Toldo, Stefano; Quader, Mohammed; Salloum, Fadi N; Mezzaroma, Eleonora; Abbate, Antonio

    2016-01-01

    Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response. PMID:27322252

  12. Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death

    PubMed Central

    Toldo, Stefano; Quader, Mohammed; Salloum, Fadi N.; Mezzaroma, Eleonora; Abbate, Antonio

    2016-01-01

    Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response. PMID:27322252

  13. Acute myocardial infarction: the enduring challenge for cardiac protection and survival.

    PubMed

    Yasuda, Satoshi; Shimokawa, Hiroaki

    2009-11-01

    Although considerable advances have been made in the diagnosis and management of acute myocardial infarction (AMI), the disorder is still a major cause of morbidity and mortality worldwide and continues to pose significant therapeutic challenges. The use of biomarkers to aid the diagnosis of AMI is now increasing and has enabled better understanding of the pathophysiology of the disorder and identification of patients who require urgent reperfusion therapy. Early percutaneous coronary intervention (PCI) appears to be beneficial when performed in a timely manner with a door-to-balloon time <90 min. The goal of PCI is now shifting from simple revascularization of occluded coronary arteries to optimum reperfusion at the microvascular level. Effective strategies and pharmacological agents need to be developed for better cardiac protection during AMI. Most deaths resulting from AMI occur within 1 h of its onset, and half of them occur before hospital admission. Thus, an effective pre-hospital lifeline system should be an important priority, achieved through the chain of survival, including the immediate implementation of definitive resuscitative efforts and rapidly transporting the patients to the hospital. PMID:19809203

  14. Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

    PubMed

    Wang, Qingjie; Yang, Hui; Bai, Aobing; Jiang, Wei; Li, Xiuya; Wang, Xinhong; Mao, Yishen; Lu, Chao; Qian, Ruizhe; Guo, Feng; Ding, Tianling; Chen, Haiyan; Chen, Sifeng; Zhang, Jianyi; Liu, Chen; Sun, Ning

    2016-10-01

    With the advent of induced pluripotent stem cells and directed differentiation techniques, it is now feasible to derive individual-specific cardiac cells for human heart tissue engineering. Here we report the generation of functional engineered human cardiac patches using human induced pluripotent stem cells-derived cardiac cells and decellularized natural heart ECM as scaffolds. The engineered human cardiac patches can be tailored to any desired size and shape and exhibited normal contractile and electrical physiology in vitro. Further, when patching on the infarct area, these patches improved heart function of rats with acute myocardial infarction in vivo. These engineered human cardiac patches can be of great value for normal and disease-specific heart tissue engineering, drug screening, and meet the demands for individual-specific heart tissues for personalized regenerative therapy of myocardial damages in the future. PMID:27509303

  15. Hypertriglyceridemia-induced acute pancreatitis in pregnancy causing maternal death

    PubMed Central

    Jeon, Hae Rin; Cho, Yoon Jin; Chon, Seung Joo

    2016-01-01

    Acute pancreatitis in pregnancy is rare and occurs in approximately 3 in 10,000 pregnancies. It rarely complicates pregnancy, and can occur during any trimester, however over half (52%) of cases occur during the third trimester and during the post-partum period. Gallstones are the most common cause of acute pancreatitis. On the other hand, acute pancreatitis caused by hypertriglyceridemia due to increase of estrogen during the gestational period is very unusual, but complication carries a higher risk of morbidity and mortality for both the mother and the fetus. We experienced a case of pregnant woman who died of acute exacerbation of hypertriglyceridemia-induced acute pancreatitis at 23 weeks of gestation. We report on progress and management of this case along with literature reviews. PMID:27004207

  16. The Manchester Acute Coronary Syndromes (MACS) decision rule for suspected cardiac chest pain: derivation and external validation

    PubMed Central

    Body, Richard; Carley, Simon; McDowell, Garry; Pemberton, Philip; Burrows, Gillian; Cook, Gary; Lewis, Philip S; Smith, Alexander; Mackway-Jones, Kevin

    2014-01-01

    Objective We aimed to derive and validate a clinical decision rule (CDR) for suspected cardiac chest pain in the emergency department (ED). Incorporating information available at the time of first presentation, this CDR would effectively risk-stratify patients and immediately identify: (A) patients for whom hospitalisation may be safely avoided; and (B) high-risk patients, facilitating judicious use of resources. Methods In two sequential prospective observational cohort studies at heterogeneous centres, we included ED patients with suspected cardiac chest pain. We recorded clinical features and drew blood on arrival. The primary outcome was major adverse cardiac events (MACE) (death, prevalent or incident acute myocardial infarction, coronary revascularisation or new coronary stenosis >50%) within 30 days. The CDR was derived by logistic regression, considering reliable (κ>0.6) univariate predictors (p<0.05) for inclusion. Results In the derivation study (n=698) we derived a CDR including eight variables (high sensitivity troponin T; heart-type fatty acid binding protein; ECG ischaemia; diaphoresis observed; vomiting; pain radiation to right arm/shoulder; worsening angina; hypotension), which had a C-statistic of 0.95 (95% CI 0.93 to 0.97) implying near perfect diagnostic performance. On external validation (n=463) the CDR identified 27.0% of patients as ‘very low risk’ and potentially suitable for discharge from the ED. 0.0% of these patients had prevalent acute myocardial infarction and 1.6% developed MACE (n=2; both coronary stenoses without revascularisation). 9.9% of patients were classified as ‘high-risk’, 95.7% of whom developed MACE. Conclusions The Manchester Acute Coronary Syndromes (MACS) rule has the potential to safely reduce unnecessary hospital admissions and facilitate judicious use of high dependency resources. PMID:24780911

  17. Predictive Value of Beat-to-Beat QT Variability Index across the Continuum of Left Ventricular Dysfunction: Competing Risks of Non-cardiac or Cardiovascular Death, and Sudden or Non-Sudden Cardiac Death

    PubMed Central

    Tereshchenko, Larisa G.; Cygankiewicz, Iwona; McNitt, Scott; Vazquez, Rafael; Bayes-Genis, Antoni; Han, Lichy; Sur, Sanjoli; Couderc, Jean-Philippe; Berger, Ronald D.; de Luna, Antoni Bayes; Zareba, Wojciech

    2012-01-01

    Background The goal of this study was to determine the predictive value of beat-to-beat QT variability in heart failure (HF) patients across the continuum of left ventricular dysfunction. Methods and Results Beat-to-beat QT variability index (QTVI), heart rate variance (LogHRV), normalized QT variance (QTVN), and coherence between heart rate variability and QT variability have been measured at rest during sinus rhythm in 533 participants of the Muerte Subita en Insuficiencia Cardiaca (MUSIC) HF study (mean age 63.1±11.7; males 70.6%; LVEF >35% in 254 [48%]) and in 181 healthy participants from the Intercity Digital Electrocardiogram Alliance (IDEAL) database. During a median of 3.7 years of follow-up, 116 patients died, 52 from sudden cardiac death (SCD). In multivariate competing risk analyses, the highest QTVI quartile was associated with cardiovascular death [hazard ratio (HR) 1.67(95%CI 1.14-2.47), P=0.009] and in particular with non-sudden cardiac death [HR 2.91(1.69-5.01), P<0.001]. Elevated QTVI separated 97.5% of healthy individuals from subjects at risk for cardiovascular [HR 1.57(1.04-2.35), P=0.031], and non-sudden cardiac death in multivariate competing risk model [HR 2.58(1.13-3.78), P=0.001]. No interaction between QTVI and LVEF was found. QTVI predicted neither non-cardiac death (P=0.546) nor SCD (P=0.945). Decreased heart rate variability (HRV) rather than increased QT variability was the reason for increased QTVI in this study. Conclusions Increased QTVI due to depressed HRV predicts cardiovascular mortality and non-sudden cardiac death, but neither SCD nor excracardiac mortality in HF across the continuum of left ventricular dysfunction. Abnormally augmented QTVI separates 97.5% of healthy individuals from HF patients at risk. PMID:22730411

  18. Forensic Pathological Study of 1656 Cases of Sudden Cardiac Death in Southern China

    PubMed Central

    Wu, Qiuping; Zhang, Liyong; Zheng, Jinxiang; Zhao, Qianhao; Wu, Yeda; Yin, Kun; Huang, Lei; Tang, Shuangbo; Cheng, Jianding

    2016-01-01

    Abstract Sudden cardiac death (SCD) is progressively threatening the lives of young people throughout the world. We conducted a retrospective study of SCD cases identified among sudden death cases based on comprehensive autopsies and pathological examinations in the Center for Medicolegal Expertise of Sun Yat-Sen University to investigate the exact etiological distribution and epidemiological features of SCD. One thousand six hundred fifty-six cases were identified, and SCD accounted for 43.0% of these sudden death cases. The mean age of the SCD cases—where the data of definite ages were accessible—was 38.2 years, and the highest incidence occurred among the 31- to 40-year-old cases (25.6%). The male-to-female ratio among SCD cases was 4.3:1, and this ratio peaked in the 41- to 50-year-old group (7.7:1). The places of death were confirmed in 1411 cases, and predominantly in hospitals (46.3%) and at home (33.8%). SCD occurred throughout the year with a marginally increase in April and May. The major causes of SCD were coronary atherosclerotic disease (CAD, 41.6%), unexplained sudden death (15.1%), and myocarditis (11.8%). Our data indicated that in the age group of younger affected persons (below 35 years old), sudden unexplained death and myocarditis were much more prevalent than CAD. According to anatomical examinations of the CAD-related SCD cases, the proportion of cases with coronary artery stenosis exceeding 75% (grade IV) was 67.2%. Moreover, the percentages of higher grades of coronary atherosclerosis increased with age. Among all branches of the coronary arteries, the left anterior descending branch was the most prone to atherosclerosis; atherosclerosis was present in this branch in 95.4% of the cases with atherosclerosis. Additionally, lesions of multiple branches of the coronary artery were associated with ageing. This is the first study to report the causes of death and basic epidemiological data related to SCD in Southern China. PMID:26844513

  19. Acute response and chronic stimulus for cardiac structural and functional adaptation in a professional boxer.

    PubMed

    Oxborough, David; George, Keith; Utomi, Victor; Lord, Rachel; Morton, James; Jones, Nigel; Somauroo, John

    2014-06-01

    The individual response to acute and chronic changes in cardiac structure and function to intense exercise training is not fully understood and therefore evidence in this setting may help to improve the timing and interpretation of pre-participation cardiac screening. The following case report highlights an acute increase in right ventricular (RV) size and a reduction in left ventricular (LV) basal radial function with concomitant increase at the mid-level in response to a week's increase in training volume in a professional boxer. These adaptations settle by the second week; however, chronic physiological adaptation occurs over a 12-week period. Electrocardiographic findings demonstrate an acute lateral T-wave inversion at 1 week, which revert to baseline for the duration of training. It appears that a change in training intensity and volume generates an acute response within the RV that acts as a stimulus for chronic adaptation in this professional boxer. PMID:25988031

  20. Clinical investigation: thyroid function test abnormalities in cardiac arrest associated with acute coronary syndrome

    PubMed Central

    Iltumur, Kenan; Olmez, Gonul; Arıturk, Zuhal; Taskesen, Tuncay; Toprak, Nizamettin

    2005-01-01

    Introduction It is known that thyroid homeostasis is altered during the acute phase of cardiac arrest. However, it is not clear under what conditions, how and for how long these alterations occur. In the present study we examined thyroid function tests (TFTs) in the acute phase of cardiac arrest caused by acute coronary syndrome (ACS) and at the end of the first 2 months after the event. Method Fifty patients with cardiac arrest induced by ACS and 31 patients with acute myocardial infarction (AMI) who did not require cardioversion or cardiopulmonary resuscitation were enrolled in the study, as were 40 healthy volunteers. The patients were divided into three groups based on duration of cardiac arrest (<5 min, 5–10 min and >10 min). Blood samples were collected for thyroid-stimulating hormone (TSH), tri-iodothyronine (T3), free T3, thyroxine (T4), free T4, troponin-I and creatine kinase-MB measurements. The blood samples for TFTs were taken at 72 hours and at 2 months after the acute event in the cardiac arrest and AMI groups, but only once in the control group. Results The T3 and free T3 levels at 72 hours in the cardiac arrest group were significantly lower than in both the AMI and control groups (P < 0.0001). On the other hand, there were no significant differences between T4, free T4 and TSH levels between the three groups (P > 0.05). At the 2-month evaluation, a dramatic improvement was observed in T3 and free T3 levels in the cardiac arrest group (P < 0.0001). In those patients whose cardiac arrest duration was in excess of 10 min, levels of T3, free T3, T4 and TSH were significantly lower than those in patients whose cardiac arrest duration was under 5 min (P < 0.001, P < 0.001, P < 0.005 and P < 0.05, respectively). Conclusion TFTs are significantly altered in cardiac arrest induced by ACS. Changes in TFTs are even more pronounced in patients with longer periods of resuscitation. The changes in the surviving patients were characterized by euthyroid sick

  1. Effect of early bisoprolol administration on ventricular arrhythmia and cardiac death in patients with non-ST elevation myocardial infarction

    PubMed Central

    Maclean, Edd; Zheng, Sean; Nabeebaccus, Adam; O'Gallagher, Kevin; Stewart, Adrian; Webb, Ian

    2015-01-01

    Objective To investigate the impact of early oral beta blockade in patients presenting with acute non-ST elevation myocardial infarction (NSTEMI). Methods We retrospectively identified 890 consecutive patients presenting with NSTEMI to a single UK centre from 2012 to 2014. Included patients all received standardised antiplatelet therapy plus low-dose oral bisoprolol (1.25–2.5 mg) within 4 h (mean 2.2±1.36; ‘Early Group’) or within 5–24 h (mean 15.4±5.7; ‘Late Group’) of presentation. Patients were followed up for the duration of hospital stay with the incidence of major adverse cardiovascular events (MACE—defined as ventricular arrhythmia, cardiac death or repeat infarction) set as the primary outcome. Multivariate logistic regression models analysed early versus late bisoprolol administration and adjusted for potential confounders. Results 399 patients were included. Of the patient parameters, only the GRACE score was significantly different between the early (n=99, GRACE 164.5±29.6) and late (n=300, GRACE 156.7±31.4) groups (p=0.033). The early group had significantly fewer ventricular arrhythmias (1 vs 20, p=0.034), cardiac deaths (0 vs 13, p=0.044) and consequently MACE (1 vs 27, p=0.005) than the late group. After adjusting for the confounders of pulse, blood pressure, smoking and creatinine, logistic regression analysis identified early bisoprolol administration as protective for ventricular arrhythmia (p=0.038, OR 0.114, CI 0.015 to 0.885) and MACE (p=0.011, OR 0.064, CI 0.008 to 0.527). There was one episode of symptomatic bradycardia in the late group. Conclusions This study suggests that low-dose oral bisoprolol administered to patients with NSTEMI within 4 h of admission may be protective and lead to reduced inpatient MACE. PMID:27326220

  2. Palliative care consultation in the process of organ donation after cardiac death.

    PubMed

    Kelso, Catherine McVearry; Lyckholm, Laurie J; Coyne, Patrick J; Smith, Thomas J

    2007-02-01

    Palliative care consultation has been demonstrated to be useful in many situations in which expert symptom management, communication around sensitive issues, and family support may serve to enhance or improve care. The process of organ donation is an example of this concept, specifically the process of donation after cardiac death (DCD). DCD allows patients with severe, irreversible brain injuries that do not meet standard criteria for brain death to donate organs when death is declared by cardiopulmonary criteria. The DCD method of donation has been deemed an ethically appropriate means of organ donation and is supported by the organ procurement and medical communities, as well as the public. The palliative care (PC) team can make a significant contribution to the care of the patient and family in the organ donation process. In this paper we describe the controlled DCD process at one institution that utilizes the PC team to provide expert end-of-life care, including comprehensive medical management and family support. PC skills and principles applicable to the DCD process include communication, coordination of care, and skillful ventilator withdrawal. If death occurs within 90 minutes of withdrawal of life support, organs may be successfully recovered for transplantation. If the patient survives longer than 90 minutes, his or her care continues to be provided by the PC team. Palliative care can contribute to standardizing quality end-of-life care practices in the DCD process and provide education for involved personnel. Further experience, research and national discussions will be helpful in refining these practices, to make this difficult and challenging experience as gentle and supportive as possible for the courageous families who participate in this process. PMID:17298260

  3. Normothermic perfusion machine in liver transplant with cardiac death donor grafts.

    PubMed

    Pavel, Mihai-Calin; Fondevila Campo, Constantino; Calatayud Mizrahi, David; Ferrer Fabrega, Joana; Sanchez Cabus, Santiago; Molina Santos, Víctor; Fuster Obregon, Josep; Garcia-Valdecasas Salgado, Juan Carlos

    2015-10-01

    The increasing difference between the number of patients in waiting lists for liver transplantation and the number of available donors has generated a great interest in the use of non-ideal organs, like grafts obtained from cardiac death donors (DCD). However, the extreme sensibility to ischemia of these livers results in a low utilization rate and a high percentage of post-transplant complications and re-transplantation. Normothermic perfusion machines (NMP) emerged as an alternative that tries to maintain the viability of the organ and even to improve its function. This review focuses on current results of DCD liver transplantation and on the role that NMP may have in this field. PMID:26139181

  4. Potential approaches to improve the outcomes of donation after cardiac death liver grafts

    PubMed Central

    Mahboub, Paria; Bozorgzadeh, Adel; Martins, Paulo N

    2016-01-01

    There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death (DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods: (1) different ex vivo perfusion techniques; (2) persufflation with oxygen; and (3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft’s for transplantation, improve the outcomes, and decrease the mortality on the waiting list. PMID:27358776

  5. Potential approaches to improve the outcomes of donation after cardiac death liver grafts.

    PubMed

    Mahboub, Paria; Bozorgzadeh, Adel; Martins, Paulo N

    2016-06-24

    There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death (DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods: (1) different ex vivo perfusion techniques; (2) persufflation with oxygen; and (3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft's for transplantation, improve the outcomes, and decrease the mortality on the waiting list. PMID:27358776

  6. [New strategies for assessing the risk of sudden cardiac death in hypertrophic cardiomyopathy].

    PubMed

    Jaworski, Krzysztof; Możeńska, Olga; Kosior, Dariusz A

    2016-07-01

    Hypertrophic cardiomyopathy (HCM) is characterized by a primarily increased ventricular wall thickness, usually caused by the mutations in genes encoding sarcomere proteins. Thanks to the growing awareness in the medical community as well as advances in diagnostic techniques HCM can be diagnosed at earlier stages than ever before. However, in some cases the first symptom of this disease is a sudden cardiac death (SCD) and diagnosis remains unknown until post-mortem examination. Implantation of a cardioverterdefibrillator (ICD) provides the most effective method of SCD prevention. Nevertheless, due to a number of risks associated with surgery as well as the possession of such devices, predictive factors of serious ventricular arrhythmia in individual patients have been sought for many years. The aim of this review is to present the current strategies of risk assessment and prevention of SCD in patients with HCM. PMID:27590646

  7. [New strategies for assessing the risk of sudden cardiac death in hypertrophic cardiomyopathy].

    PubMed

    Jaworski, Krzysztof; Możeńska, Olga; Kosior, Dariusz A

    2016-08-01

    Hypertrophic cardiomyopathy (HCM) is characterized by a primarily increased ventricular wall thickness, usually caused by the mutations in genes encoding sarcomere proteins. Thanks to the growing awareness in the medical community as well as advances in diagnostic techniques HCM can be diagnosed at earlier stages than ever before. However, in some cases the first symptom of this disease is a sudden cardiac death (SCD) and diagnosis remains unknown until post-mortem examination. Implantation of a cardioverterdefibrillator (ICD) provides the most effective method of SCD prevention. Nevertheless, due to a number of risks associated with surgery as well as the possession of such devices, predictive factors of serious ventricular arrhythmia in individual patients have been sought for many years. The aim of this review is to present the current strategies of risk assessment and prevention of SCD in patients with HCM. PMID:27591441

  8. Is There a Role for Genetics in the Prevention of Sudden Cardiac Death?

    PubMed

    Faragli, Alessandro; Underwood, Katherine; Priori, Silvia G; Mazzanti, Andrea

    2016-09-01

    The identification of patients at risk for sudden cardiac death (SCD) is fundamental for both acquired cardiovascular diseases (such as coronary artery diseases, CAD) and inherited arrhythmia syndromes (such as the long-QT syndrome, LQTS). Genetics may play a role in both situations, although the potential to exploit this information to reduce the burden of SCD varies among these two groups. Concerning acquired cardiovascular diseases, which affect most of the general population, preliminary data suggest an association between genetics and the risk of dying suddenly. The maximal utility, instead, is reached in inherited arrhythmia syndromes, where the discovery of monogenic diseases such as LQTS tracked the way for the first genotype-phenotype correlations. The aim of this review is to provide a general overview focusing on the current genetic knowledge and on the present and future applicability for prevention in these two populations at risk for SCD. PMID:27279603

  9. A contemporary assessment of the risk for sudden cardiac death in patients with congenital heart disease.

    PubMed

    Silka, Michael J; Bar-Cohen, Yaniv

    2012-03-01

    Assessment of the risk for sudden cardiac death (SCD) after surgery for congenital heart disease (CHD) remains a difficult challenge. In the study of this problem, the focus has evolved from concern regarding late-onset heart block to a subsequent focus on ventricular and reentrant atrial arrhythmias, with the most recent emphasis on ventricular dysfunction and heart failure. Sudden cardiac death in CHD patients has been studied most extensively in tetralogy of Fallot. More than 30 risk factors have been proposed, with age at repair, QRS duration, right ventricular enlargement, and left ventricular dysfunction considered the most predictive risk factors. Additionally, SCD has been studied in patients with atrial repair for transposition of the great arteries, left heart obstructive lesions, and to a limited extent, patients with univentricular physiology. This review discusses current risk factors for SCD in CHD and the limited positive predictive value of any individual factor. The emphasis is on contemporary patients with CHD, who differ markedly from those who had repair of CHD decades earlier. This is characterized by complete repairs during the neonatal period, improved physiologic outcomes, and extended survival of patients with complex forms of CHD. Therefore, earlier data and conclusions may not be relevant to newer generations of patients with CHD. According to current perspectives, systemic ventricular dysfunction becomes a major risk factor beyond the age of 20 years. The first symptomatic arrhythmia may result in SCD, and defibrillators are increasingly implanted despite the lack of risk stratification criteria. The large number of potential risk factors and therapeutic options, in contrast to the low incidence of actual events, results in a difficult clinical challenge in the assessment of the risk for SCD in the individual patient with CHD. PMID:22311569

  10. Multiscale regularity analysis of the Heart Rate Variability: stratification of cardiac death risk.

    PubMed

    Valencia, J F; Vallverdú, M; Cygankiewicz, I; Voss, A; Vazquez, R; de Luna, A Bayés; Caminal, P

    2007-01-01

    Subjects with ischemic dilated cardiomiopathy tend to suffer episodes of sudden cardiac death, thus risk stratification is essential to establish an adequate therapy for the patients. In this work, a new methodology was proposed for the study of the heart rate variability by using a multiscale analysis based on the concept of entropy rates, for improving risk prediction in cardiac patients. Symbolic dynamics were applied to RR time series and sets of words in several scales were constructed. The multiscale regularity analysis was proposed by comparing the entropies, calculated using Shannon and Renyi definitions, of the series of words in different scales. The study considered the selection of the best parameters for the length of the words (l) and the order of the entropies (q). Statistical analysis with repeated measures and discriminant analysis revealed statistically significant differences (p-value<0.05) and a high percentage of well classified subjects in their different risk groups, with sensitivity, specificity and positive predictive values of 100%. PMID:18003368

  11. Height and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities and Cardiovascular Health Studies

    PubMed Central

    Rosenberg, Michael A.; Lopez, Faye L.; Bůžková, Petra; Adabag, SelcukPhD; Chen, Lin Y.; Sotoodehnia, Nona; Kronmal, Richard A.; Siscovick, David S.; Alonso, Alvaro; Buxton, Alfred; Folsom, Aaron R.; Mukamal, Kenneth J.

    2014-01-01

    Purpose Sudden cardiac death (SCD) is an important cause of mortality in the adult population. Height has been associated with cardiac hypertrophy and an increased risk of arrhythmias, but also with decreased risk of coronary heart disease, suggesting a complex association with SCD. Methods We examined the association of adult height with the risk of physician-adjudicated SCD in two large population-based cohorts: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study. Results Over an average follow-up time of 11.7 years in CHS, there were 199 (3.6%) cases of SCD among 5,556 participants. In ARIC, over 12.6 years, there were 227 (1.5%) cases of SCD among 15,633 participants. In both cohorts, there was a trend towards decreased SCD with taller height. In fixed effects meta-analysis, the pooled hazard ratio per 10 cm of height was 0.84 (95%CI 0.73, 0.98, p=0.03). The association of increased height with lower risk of SCD was slightly attenuated after inclusion of risk factors associated with height, such as hypertension and left ventricular hypertrophy. The association appeared stronger among men than women in both cohorts. Conclusion In two population-based prospective cohorts of different ages, greater height was associated with lower risk of SCD. PMID:24360853

  12. Plasma Fatty Acid Binding Protein 4 and Risk of Sudden Cardiac Death in Older Adults

    PubMed Central

    Djoussé, Luc; Maziarz, Marlena; Biggs, Mary L.; Ix, Joachim H.; Zieman, Susan J.; Kizer, Jorge R.; Lemaitre, Rozenn N.; Mozaffarian, Dariush; Tracy, Russell P.; Mukamal, Kenneth J.; Siscovick, David S.; Sotoodehnia, Nona

    2013-01-01

    Although fatty acid binding protein 4 (FABP4) may increase risk of diabetes and exert negative cardiac inotropy, it is unknown whether plasma concentrations of FABP4 are associated with incidence of sudden cardiac death (SCD). We prospectively analyzed data on 4,560 participants of the Cardiovascular Health Study. FABP4 was measured at baseline using ELISA, and SCD events were adjudicated through review of medical records. We used Cox proportional hazards to estimate effect measures. During a median followup of 11.8 years, 146 SCD cases occurred. In a multivariable model adjusting for demographic, lifestyle, and metabolic factors, relative risk of SCD associated with each higher standard deviation (SD) of plasma FABP4 was 1.15 (95% CI: 0.95–1.38), P = 0.15. In a secondary analysis stratified by prevalent diabetes status, FABP4 was associated with higher risk of SCD in nondiabetic participants, (RR per SD higher FABP4: 1.33 (95% CI: 1.07–1.65), P = 0.009) but not in diabetic participants (RR per SD higher FABP4: 0.88 (95% CI: 0.62–1.27), P = 0.50), P for diabetes-FABP4 interaction 0.049. In summary, a single measure of plasma FABP4 obtained later in life was not associated with the risk of SCD in older adults overall. Confirmation of our post-hoc results in nondiabetic people in other studies is warranted. PMID:24455402

  13. Unusual cause of aborted sudden cardiac death in a teen athlete: homozygosity for the 4G allele of the plasminogen activase inhibitor type 1 gene.

    PubMed

    Phillips, Susie B; Batlivala, Sarosh; Knudson, Jarrod D

    2015-10-01

    Common aetiologies of sudden cardiac death in children include coronary anomalies, channelopathies, and cardiomyopathies. Less frequently, hypercoagulable states cause sudden arrest. We report an unusual case of aborted sudden cardiac death in a teenager, ultimately found to have homozygosity for the 4G allele of the plasminogen activase inhibitor type 1 gene. PMID:25498839

  14. Incidence, prognosis, and factors associated with cardiac arrest in patients hospitalized with acute coronary syndromes (the Global Registry of Acute Coronary Events Registry)

    PubMed Central

    McManus, David D.; Aslam, Farhan; Goyal, Parag; Goldberg, Robert J.; Huang, Wei; Gore, Joel M.

    2013-01-01

    Objectives Contemporary data are lacking with respect to the incidence rates of, factors associated with, and impact of cardiac arrest from ventricular fibrillation or tachycardia (VF-CA) on hospital survival in patients admitted with an acute coronary syndrome (ACS). The objectives of this multinational study were to characterize trends in the magnitude of in-hospital VF-CA complicating an ACS and to describe its impact over time on hospital prognosis. Methods In 59 161 patients enrolled in the Global Registry of Acute Coronary Events Study between 2000 and 2007, we determined the incidence, prognosis, and factors associated with VF-CA. Results Overall, 3618 patients (6.2%) developed VF-CA during their hospitalization for an ACS. Incidence rates of VF-CA declined over time. Patients who experienced VF-CA were on average older and had a greater burden of cardiovascular disease, yet were less likely to receive evidence-based cardiac therapies than patients in whom VF-CA did not occur. Hospital death rates were 55.3% and 1.5% in patients with and without VF-CA, respectively. There was a greater than 50% decline in the hospital death rates associated with VF-CA during the years under study. Patients with a VF-CA occurring after 48 h were at especially high risk for dying during hospitalization (82.8%). Conclusion Despite reductions in the magnitude of, and short-term mortality from, VF-CA, VF-CA continues to exert an adverse effect on survival among patients hospitalized with an ACS. Opportunities exist to improve the identification and treatment of ACS patients at risk for VF-CA to reduce the incidence of, and mortality from, this serious arrhythmic disturbance. PMID:22157357

  15. The mechanism of PDT-induced electrical blockade: the dependence of time-lapse localization of talaporfin sodium on the cell death phenotypes in rat cardiac myocytes

    NASA Astrophysics Data System (ADS)

    Ito, A.; Matsuo, H.; Suenari, T.; Miyoshi, S.; Takatsuki, S.; Ogawa, S.; Arai, T.

    2009-02-01

    We have proposed a new type of atrial fibrillation treatment with the early state photodynamic therapy (PDT), in which the interval time between the photosensitizer injection and irradiation is shorter than that in conventional way. We had demonstrated the acute electrical blockade by the PDT with talaporfin sodium and a red (670 nm) diode laser in ex vivo and in vivo experiment using rat normal myocardial tissue. The previous study of intracellular Ca2+ concentration measurement in rat cardiac myocytes during the PDT indicated that Ca2+ influx induced by the plasma membrane damage might be the main cause of the acute reaction of myocardial tissue. We found that the cell damage of cardiac myocytes triggered by the PDT was mainly influenced by the site where the photosensitizer exists. In this study, we examined the relationship between the sites of talaporfin sodium existing and cell death phenotypes in response to the PDT, in order to clarify the mechanism of the acute electrical blockade induced by the PDT in myocardial tissue. The talaporfin sodium fluorescence was observed after the various incubation times to visualize the time-lapse intracellular photosensitizer localization. The distribution of the photosensitizer was dependent on the incubation time. The change in intracellular Ca2+ concentration during the PDT was examined with a fluorescent Ca2+ indicator by a high-speed Nipkow confocal laser microscope (CSU-X1, Yokogawa Electric Company). We obtained the Ca2+ dynamics during the PDT which can explain the PDT-induced cell death pathways. We concluded that the Ca2+ influx induced by plasma membrane damage is the possible mechanism of the electrical blockade by the early state PDT.

  16. Anabolic androgenic steroids abuse and cardiac death in athletes: morphological and toxicological findings in four fatal cases.

    PubMed

    Montisci, Massimo; El Mazloum, Rafi; Cecchetto, Giovanni; Terranova, Claudio; Ferrara, Santo Davide; Thiene, Gaetano; Basso, Cristina

    2012-04-10

    Anabolic androgenic steroids (AAS) are the main class of doping agents and their consumption produces adverse effects involving several organs and systems. Three cases of sudden cardiac death (SCD) and one of death due to congestive heart failure of previously healthy athletes who were AAS users are herein reported. Concentric cardiac hypertrophy with focal fibrosis (one case), dilated cardiomyopathy with patchy myocyte death (two cases) and eosinophilic myocarditis (one case) were observed and most probably relate to the final event. Molecular investigation for viral genomes was positive in one case (Ebstein virus). Our data confirm previous findings, showing that the most typical cardiac abnormality in AAS abusers is left ventricular hypertrophy, associated with fibrosis and myocytolysis. An exceptional cardiovascular substrate was represented by the case with drug induced eosinophilic myocarditis. These features are at risk of ventricular arrhythmias as well as congestive heart failure. The cause-effect relationship between AAS abuse and cardiac death can be established only by a rigorous methodology with the use of standardized protocols, including precise morphological studies of all target organs to search for chronic toxic effects. Laboratory investigations should focus on AAS searching on a wide range of biological matrices to demonstrate type, magnitude and time of exposure. PMID:22047750

  17. PULMONARY AND CARDIAC GENE EXPRESSION FOLLOWING ACUTE ULTRAFINE CARBON PARTICLE INHALATION IN HYPERTENSIVE RATS

    EPA Science Inventory

    Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and hea...

  18. Family History of Sudden Cardiac Death of the Young: Prevalence and Associated Factors

    PubMed Central

    White, Michelle J.; Duquette, Debra; Bach, Janice; Rafferty, Ann P.; Fussman, Chris; Sharangpani, Ruta; Russell, Mark W.

    2015-01-01

    Sudden cardiac death of the young (SCDY) is a devastating event for families and communities. Family history is a significant risk factor for this potentially preventable cause of death, however a complete and detailed family history is not commonly obtained during routine health maintenance visits. To estimate the proportion of adults with a family history of SCDY, the Michigan Department of Health and Human Services (MDHHS) Genomics Program included two questions within the 2007 Michigan Behavioral Risk Factor Survey (MiBRFS). Prevalence estimates and 95% confidence intervals were calculated. Among adults in Michigan, 6.3% reported a family history of SCDY, with a greater prevalence among blacks, those with lower household income, and those with less education. Among those reporting a family history of SCDY, 42.3% had at least one first-degree relative and 26.2% had multiple affected family members. This is the first study to demonstrate the prevalence of family history of SCDY while also highlighting key sociodemographic characteristics associated with increased prevalence. These findings should guide evidence-based interventions to reach those at greatest risk.

  19. Cardiac arrest triggers hippocampal neuronal death through autophagic and apoptotic pathways.

    PubMed

    Cui, Derong; Shang, Hanbing; Zhang, Xiaoli; Jiang, Wei; Jia, Xiaofeng

    2016-01-01

    The mechanism of neuronal death induced by ischemic injury remains unknown. We investigated whether autophagy and p53 signaling played a role in the apoptosis of hippocampal neurons following global cerebral ischemia-reperfusion (I/R) injury, in a rat model of 8-min asphyxial cardiac arrest (CA) and resuscitation. Increased autophagosome numbers, expression of lysosomal cathepsin B, cathepsin D, Beclin-1, and microtubule-associated protein light chain 3 (LC3) suggested autophagy in hippocampal cells. The expression of tumor suppressor protein 53 (p53) and its target genes: Bax, p53-upregulated modulator of apoptosis (PUMA), and damage-regulated autophagy modulator (DRAM) were upregulated following CA. The p53-specific inhibitor pifithrin-α (PFT-α) significantly reduced the expression of pro-apoptotic proteins (Bax and PUMA) and autophagic proteins (LC3-II and DRAM) that generally increase following CA. PFT-α also reduced hippocampal neuronal damage following CA. Similarly, 3-methyladenine (3-MA), which inhibits autophagy and bafilomycin A1 (BFA), which inhibits lysosomes, significantly inhibited hippocampal neuronal damage after CA. These results indicate that CA affects both autophagy and apoptosis, partially mediated by p53. Autophagy plays a significant role in hippocampal neuronal death induced by cerebral I/R following asphyxial-CA. PMID:27273382

  20. β-Adrenergic Regulation of Cardiac Progenitor Cell Death Versus Survival and Proliferation

    PubMed Central

    Khan, Mohsin; Mohsin, Sadia; Avitabile, Daniele; Siddiqi, Sailay; Nguyen, Jonathan; Wallach, Kathleen; Quijada, Pearl; McGregor, Michael; Gude, Natalie; Alvarez, Roberto; Tilley, Douglas G.; Koch, Walter J.; Sussman, Mark A.

    2013-01-01

    Rationale Short-term β-adrenergic stimulation promotes contractility in response to stress but is ultimately detrimental in the failing heart because of accrual of cardiomyocyte death. Endogenous cardiac progenitor cell (CPC) activation may partially offset cardiomyocyte losses, but consequences of long-term β-adrenergic drive on CPC survival and proliferation are unknown. Objective We sought to determine the relationship between β-adrenergic activity and regulation of CPC function. Methods and Results Mouse and human CPCs express only β2 adrenergic receptor (β2-AR) in conjunction with stem cell marker c-kit. Activation of β2-AR signaling promotes proliferation associated with increased AKT, extracellular signal-regulated kinase 1/2, and endothelial NO synthase phosphorylation, upregulation of cyclin D1, and decreased levels of G protein–coupled receptor kinase 2. Conversely, silencing of β2-AR expression or treatment with β2-antagonist ICI 118, 551 impairs CPC proliferation and survival. β1-AR expression in CPC is induced by differentiation stimuli, sensitizing CPC to isoproterenol-induced cell death that is abrogated by metoprolol. Efficacy of β1-AR blockade by metoprolol to increase CPC survival and proliferation was confirmed in vivo by adoptive transfer of CPC into failing mouse myocardium. Conclusions β-adrenergic stimulation promotes expansion and survival of CPCs through β2-AR, but acquisition of β1-AR on commitment to the myocyte lineage results in loss of CPCs and early myocyte precursors. PMID:23243208

  1. Experience With the Wearable Cardioverter-Defibrillator in Patients at High Risk for Sudden Cardiac Death

    PubMed Central

    Günther, Michael; Quick, Silvio; Pfluecke, Christian; Rottstädt, Fabian; Szymkiewicz, Steven J.; Ringquist, Steven; Strasser, Ruth H.; Speiser, Uwe

    2016-01-01

    Background: This study evaluated the wearable cardioverter-defibrillator (WCD) for use and effectiveness in preventing sudden death caused by ventricular tachyarrhythmia or fibrillation. Methods: From April 2010 through October 2013, 6043 German WCD patients (median age, 57 years; male, 78.5%) were recruited from 404 German centers. Deidentified German patient data were used for a retrospective, nonrandomized analysis. Results: Ninety-four patients (1.6%) were treated by the WCD in response to ventricular tachyarrhythmia/fibrillation. The incidence rate was 8.4 (95% confidence interval, 6.8–10.2) per 100 patient-years. Patients with implantable cardioverter-defibrillator explantation had an incidence rate of 19.3 (95% confidence interval, 12.2–29.0) per 100 patient-years. In contrast, an incidence rate of 8.2 (95% confidence interval, 6.4–10.3) was observed in the remaining cardiac diagnosis groups, including dilated cardiomyopathy, myocarditis, and ischemic and nonischemic cardiomyopathies. Among 120 shocked patients, 112 (93%) survived 24 hours after treatment, whereas asystole was observed in 2 patients (0.03%) with 1 resulting death. ConclusionS: This large cohort represents the first nationwide evaluation of WCD use in patients outside the US healthcare system and confirms the overall value of the WCD in German treatment pathways. PMID:27458236

  2. Sudden cardiac and sudden unexpected death related to antipsychotics: A meta-analysis of observational studies.

    PubMed

    Salvo, F; Pariente, A; Shakir, S; Robinson, P; Arnaud, M; Thomas, Shl; Raschi, E; Fourrier-Réglat, A; Moore, N; Sturkenboom, M; Hazell On Behalf Of Investigators Of The Aritmo Consortium, L

    2016-03-01

    To estimate the risk of sudden cardiac death (SCD) or sudden unexpected death (SUD) related to individual antipsychotics, a meta-analysis of observational studies was performed. Adjusted odds ratio (OR) of SCD/SUD with 95% confidence intervals (CI) were extracted and pooled; heterogeneity was studied using Q statistic and I(2) index, and its potential causes (e.g., hERG blockade potency) explored using meta-regression. Two cohort (740,306 person-years) and four case-control (2,557 cases; 17,670 controls) studies, investigating nine antipsychotics, were included. Compared with nonusers, the risk was increased for quetiapine (OR = 1.72, 95% CI: 1.33-2.23), olanzapine (OR = 2.04, 1.52-2.74), risperidone (OR = 3.04, 2.39-3.86), haloperidol (OR = 2.97, 1.59-5.54), clozapine (OR = 3.67, 1.94-6.94), and thioridazine (OR = 4.58, 2.09-10.05). Heterogeneity was found (Q = 20.0, P = 0.01; I(2) = 60.0%), and the increasing mean hERG blockade potency (P = 0.01) accounted for 43% of this. The SCD/SUD risk differed between individual antipsychotics, and mean hERG blockade potency could be an explanatory factor. This should be considered when initiating antipsychotic treatment. PMID:26272741

  3. Cardiac arrest triggers hippocampal neuronal death through autophagic and apoptotic pathways

    PubMed Central

    Cui, Derong; Shang, Hanbing; Zhang, Xiaoli; Jiang, Wei; Jia, Xiaofeng

    2016-01-01

    The mechanism of neuronal death induced by ischemic injury remains unknown. We investigated whether autophagy and p53 signaling played a role in the apoptosis of hippocampal neurons following global cerebral ischemia-reperfusion (I/R) injury, in a rat model of 8-min asphyxial cardiac arrest (CA) and resuscitation. Increased autophagosome numbers, expression of lysosomal cathepsin B, cathepsin D, Beclin-1, and microtubule-associated protein light chain 3 (LC3) suggested autophagy in hippocampal cells. The expression of tumor suppressor protein 53 (p53) and its target genes: Bax, p53-upregulated modulator of apoptosis (PUMA), and damage-regulated autophagy modulator (DRAM) were upregulated following CA. The p53-specific inhibitor pifithrin-α (PFT-α) significantly reduced the expression of pro-apoptotic proteins (Bax and PUMA) and autophagic proteins (LC3-II and DRAM) that generally increase following CA. PFT-α also reduced hippocampal neuronal damage following CA. Similarly, 3-methyladenine (3-MA), which inhibits autophagy and bafilomycin A1 (BFA), which inhibits lysosomes, significantly inhibited hippocampal neuronal damage after CA. These results indicate that CA affects both autophagy and apoptosis, partially mediated by p53. Autophagy plays a significant role in hippocampal neuronal death induced by cerebral I/R following asphyxial-CA. PMID:27273382

  4. Human Cardiac-Derived Adherent Proliferating Cells Reduce Murine Acute Coxsackievirus B3-Induced Myocarditis

    PubMed Central

    Miteva, Kapka; Haag, Marion; Peng, Jun; Savvatis, Kostas; Becher, Peter Moritz; Seifert, Martina; Warstat, Katrin; Westermann, Dirk; Ringe, Jochen; Sittinger, Michael; Schultheiss, Heinz-Peter

    2011-01-01

    Background Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs). They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3)-induced myocarditis. Methodology/Principal Findings To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR) and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. Conclusions We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis. PMID:22174827

  5. Mechanisms of cell death in acute myocardial infarction: pathophysiological implications for treatment

    PubMed Central

    de Zwaan, C.; Daemen, M.J.A.P.; Hermens, W.Th.

    2001-01-01

    The purpose of this review is to draw attention to the growing list of pathophysiological phenomena occurring in blood, the vessel wall and cardiac tissue during myocardial infarction. A further aim is to point to the complexity of factors, contributing to cardiac dysfunction and the implications for therapy, aimed at limiting myocardial cell death. Not all pathophysiological mechanisms have been elucidated yet, indicating the necessity for further research in this area. In addition we describe interventions which have shown promise in animal studies, those which may show promise in humans, and those which are accepted as therapies of choice. PMID:25696691

  6. Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure-Prone Rats

    EPA Science Inventory

    Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance...

  7. Non-invasive cardiac index monitoring during cardiopulmonary functional testing provides additional prognostic value in patients after acute heart failure.

    PubMed

    Lee, Ming-Feng; Chen, Wei-Siang; Fu, Tieh-Cheng; Liu, Min-Hui; Wang, Jong-Shyan; Hsu, Chih-Chin; Huang, Yu-Yen; Cherng, Wen-Jin; Wang, Chao-Hung

    2012-01-01

    The prognostic value of parameters derived from a cardiopulmonary exercise test (CPET) is well established in patients stabilized after acute heart failure (HF). Under multidisciplinary disease management, this study sought to test whether noninvasive cardiac output (CO) monitoring (NICOM) during the CPET provides additional prognostic value. In total, 131 patients stabilized after acute HF agreed to undergo the CPET with NICOM. Outcome follow-up focused on composite events of death and HF-related rehospitalization. Patients with a peak cardiac index (CI) of ≤ 4.5 L/minute/ m(2) (n = 32), compared to those with a peak CI of > 4.5 L/minute/m(2) (n = 99), had higher incidences of diabetes mellitus (DM) and hypertension, but had lower hemoglobin levels, estimated glomerular filtration rates (eGFR), oxygen uptake efficiency slope (OUES), and peak oxygen uptake (VO(2)). During the 1.2 ± 0.7 years of follow-up, there were 8 (6.1%) deaths, and 16 (12.2%) HF-related rehospitalizations. In a Cox univariable analysis, a lower event-free survival was associated with a history of DM, a higher Ve/VCO(2) slope, lower peak VCO(2) and eGFR, and a peak CI of ≤ 4.5 L/minute/ m(2) (P < 0.05). The Cox multivariable analysis showed that the Ve/VCO(2) slope (hazard ratio (HR) = 1.08, 95% confidence interval (CI): 1.01~1.16, P = 0.02) and peak CI of ≤ 4.5 L/minute/m(2 )(HR = 3.26, 95% CI: 1.18~9.01, P = 0.02) were significant independent predictors. In conclusion, NICOM during the CPET was demonstrated to provide prognostic information in addition to traditional risk factors, biomarkers, and other well-established CPET parameters. PMID:23258137

  8. Multi-factor analysis of failure of renal replacement therapy in acute renal failure developed after cardiac surgery

    PubMed Central

    Szwedo, Ireneusz; Tyc, Joanna; Hawrysz, Anna; Janiak, Kamila; Cichoń, Romuald

    2015-01-01

    Introduction Acute renal failure (ARF) is a rare (2-15%), but severe complication of cardiac surgery with overall mortality reaching 40-80%. In order to save patients’ lives they are treated with renal replacement therapy (RRT). The aim of our study was to assess the impact of different perioperative factors on mortality among patients treated with RRT because of acute renal failure, which occurred as a complication of a heart surgery. Material and methods Retrospective analysis included 45 patients, operated in the years 2009-2013, who underwent renal replacement therapy in order to treat postoperative ARF. The perioperative factors were analysed in two groups: group 1 – patients who died before discharge; and group 2 – those who survived until hospital discharge. Results Forty-five of 3509 cardiac surgical patients (1.25%) required RRT after the surgery. A total of 23 (51.11%) died before discharge (group 1). Patients in group 1 were characterised by older age (70.21 vs. 67 years), higher mean EuroSCORE value (9.28 vs. 7.15) (p < 0.05), higher percentage of concomitant surgery (63.63% vs. 28.57%) (p < 0.05) and of admission of catecholamines in the postoperative period (100% vs. 68.42%) (p < 0.005), and higher mean urea blood level prior to RRT initiation (156.65 vs. 102.54 mg/dl) (p < 0.05). Conclusions The statistically relevant death predictors proved to be: high EuroSCORE, concomitant surgery, and high urea level at RRT initiation and admission of catecholamines in the postoperative period. After conformation in further studies, those factors may prove useful in stratification of death risk among surgical patients requiring RRT. PMID:26702273

  9. Treatment advances have not improved the early death rate in acute promyelocytic leukemia

    PubMed Central

    McClellan, James Scott; Kohrt, Holbrook E.; Coutre, Steven; Gotlib, Jason R.; Majeti, Ravindra; Alizadeh, Ash A.; Medeiros, Bruno C.

    2012-01-01

    Early mortality in acute promyelocytic leukemia has been reported to occur in less than 10% of patients treated in clinical trials. This study reports the incidence and clinical features of acute promyelocytic leukemia patients treated at Stanford Hospital, CA, USA since March 1997, focusing on early mortality. We show that the risk of early death in acute promyelocytic leukemia patients is higher than previously reported. In a cohort of 70 patients who received induction therapy at Stanford Hospital, 19% and 26% died within seven and 30 days of admission, respectively. High early mortality was not limited to our institution as evaluation of the Surveillance, Epidemiology and End Results Database demonstrated that 30-day mortality for acute promyelocytic leukemia averaged 20% from 1977–2007 and did not improve significantly over this interval. Our findings show that early death is now the greatest contributor to treatment failure in this otherwise highly curable form of leukemia. PMID:21993679

  10. The unexpected force of acute stroke leading to patients' sudden death as described by nurses.

    PubMed

    Rejnö, Åsa; Danielson, Ella; von Post, Iréne

    2013-03-01

    Stroke occurs suddenly and unexpectedly and its consequences can mean the difference between life and death. Research into stroke is extensive but largely focused on patients who survive. The aim of the study was to describe how nurses experience the patient's death and dying, when patients are afflicted by acute stroke and whose lives cannot be saved. The study had a descriptive design with a hermeneutical approach. Interviews were carried out with ten nurses in stroke units at three hospitals. Data were interpreted using hermeneutic textual interpretation based on Gadamer's philosophy. The study shows that sudden death, when unexpected forces intervene in the lives of patients afflicted by acute stroke, was described by the main theme sudden death - the unexpected force and the following three sub-themes: death comes unexpectedly and without warning to the patient; the relatives are at the mercy of the unexpected and the nurses find themselves in demanding situations. The new understanding emphasizes that the unexpected and demanding situations the nurses are put in can be understood as ethical dilemmas and value conflicts because they are not free to give their time to preserving the dying patient's dignity and are not able to give the good care they wish to. A more flexible organization could support the nurses in making use of the creative forces in the unexpected event which an acute stroke that leads to death constitutes. PMID:22612457

  11. Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress.

    PubMed

    Logan, Suzanna J; Yin, Liya; Geldenhuys, Werner J; Enrick, Molly K; Stevanov, Kelly M; Carroll, Richard T; Ohanyan, Vahagn A; Kolz, Christopher L; Chilian, William M

    2015-03-01

    Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative environment associated with IHD. Accordingly, manipulation of stem cell mitochondrial metabolism may be an effective strategy to improve survival of stem cells under oxidative stress. MitoNEET is a redox-sensitive, mitochondrial target of thiazolidinediones (TZDs), and influences cellular oxidative capacity. Pharmacological targeting of mitoNEET with the novel TZD, mitoNEET Ligand-1 (NL-1), improved cardiac stem cell (CSC) survival compared to vehicle (0.1% DMSO) during in vitro oxidative stress (H2O2). 10 μM NL-1 also reduced CSC maximal oxygen consumption rate (OCR) compared to vehicle. Following treatment with dexamethasone, CSC maximal OCR increased compared to baseline, but NL-1 prevented this effect. Smooth muscle α-actin expression increased significantly in CSC following differentiation compared to baseline, irrespective of NL-1 treatment. When CSCs were treated with glucose oxidase for 7 days, NL-1 significantly improved cell survival compared to vehicle (trypan blue exclusion). NL-1 treatment of cells isolated from mitoNEET knockout mice did not increase CSC survival with H2O2 treatment. Following intramyocardial injection of CSCs into Zucker obese fatty rats, NL-1 significantly improved CSC survival after 24 h, but not after 10 days. These data suggest that pharmacological targeting of mitoNEET with TZDs may acutely protect stem cells following transplantation into an oxidative environment. Continued treatment or manipulation of mitochondrial metabolism may be necessary to produce long-term benefits related to stem cell therapies. PMID:25725808

  12. Sudden cardiac death associated with an extremely rare coronary anomaly of the left and right coronary arteries arising exclusively from the posterior (noncoronary) sinus of valsalva.

    PubMed

    Catanzaro, John N; Makaryus, Amgad N; Catanese, Charles

    2005-11-01

    Congenital anomalies of the coronary arteries are relatively uncommon conditions and have been associated with sudden cardiac death (SCD) in children. Although anomalous coronary artery distribution is widely reported in the literature, no articles to date address the origin of both the right (RCA) and left coronary arteries (LCA) from the posterior (noncoronary) sinus of Valsalva. This is a report of a 16-year-old black male in good health, who collapsed and was unable to be resuscitated after physical exertion while playing basketball. In this patient, postmortem evaluation revealed the LCA and RCA originating exclusively from the posterior (noncoronary) sinus with acute angle takeoff of the LCA which likely lead to ischemia, causing SCD. We discuss the incidence of coronary artery anomalies and the proposed mechanisms that led to SCD in these patients. PMID:16450799

  13. Tools for risk stratification of sudden cardiac death: A review of the literature in different patient populations

    PubMed Central

    Ragupathi, Loheetha; Pavri, Behzad B.

    2014-01-01

    While various modalities to determine risk of sudden cardiac death (SCD) have been reported in clinical studies, currently reduced left ventricular ejection fraction remains the cornerstone of SCD risk stratification. However, the absolute burden of SCD is greatest amongst populations without known cardiac disease. In this review, we summarize the evidence behind current guidelines for implantable cardioverter defibrillator (ICD) use for the prevention of SCD in patients with ischemic heart disease (IHD). We also evaluate the evidence for risk stratification tools beyond clinical guidelines in the general population, patients with IHD, and patients with other known or suspected medical conditions. PMID:24568833

  14. Anomalous Left Circumflex Coronary Artery Arising from the Right Pulmonary Artery: A Rare Cause of Aborted Sudden Cardiac Death.

    PubMed

    Liu, Bo; Fursevich, Dzmitry; O'Dell, Matthew C; Flores, Miguel; Feranec, Nicholas

    2016-01-01

    We report a case of anomalous origin of the left circumflex coronary artery arising from the right pulmonary artery resulting in stress-induced cardiac arrest. The patient collapsed after running a 5K race and was resuscitated. Subsequent workup revealed the culprit anatomy, which was successfully treated with surgical ligation. To the authors' knowledge, this is only the second case of this variant coronary anomaly resulting in aborted sudden cardiac death, subsequent surgical ligation, and recovery in a healthy young adult and is the first case treated by ligation alone without coronary bypass. PMID:27014533

  15. Sudden cardiac death in adults with congenitally corrected transposition of the great arteries

    PubMed Central

    McCombe, A; Touma, F; Jackson, D; Canniffe, C; Choudhary, P; Pressley, L; Tanous, D; Robinson, Peter J; Celermajer, D

    2016-01-01

    Background Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital heart disease. There have been only few reports of sudden cardiac death (SCD) in patients with ccTGA and reasonable ventricular function. Methods A retrospective review of the medical records of all patients attending our adult congenital heart centre, with known ccTGA. Results From a database of over 3500 adult patients with congenital heart disease, we identified 39 (∼1%) with ccTGA and ‘two-ventricle’ circulations. 65% were male. The mean age at diagnosis was 12.4±11.4 years and the mean age at last time of review was 34.3±11.3 years. 24 patients (56%) had a history of surgical intervention. 8 (19%) had had pacemaker implantation and 2 had had a defibrillator implanted for non-sustained ventricular tachycardia (NSVT). In 544 years of patient follow-up, there had been five cases of SCD in our population; 1 death per 109 patient-years. Two of these patients had had previously documented supraventricular or NSVT. However, they were all classified as New York Heart Association (NYHA) class I or II, and systemic (right) ventricular function had been recorded as normal, mildly or mildly–moderately impaired, at most recent follow-up. Conclusions Our experience suggests the need for improved risk stratification and/or surveillance for malignant arrhythmia in adults with ccTGA, even in those with reasonable functional class on ventricular function. PMID:27493760

  16. The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors

    PubMed Central

    Xu, Jin; Sayed, Blayne Amir; Casas-Ferreira, Ana Maria; Srinivasan, Parthi; Heaton, Nigel; Rela, Mohammed; Ma, Yun; Fuggle, Susan; Legido-Quigley, Cristina; Jassem, Wayel

    2016-01-01

    Background and aims The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD). The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD), we aimed to understand how ischemia/reperfusion (I/R) injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration. Methods Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13) and DBD (n = 10) livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22) and DBD (n = 13) livers. Results When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05) and C22 ceramide (p<0.05) were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST) of DCD allografts had significantly increased. Conclusion These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation. PMID:26863224

  17. Drinking to near death--acute water intoxication leading to neurogenic stunned myocardium.

    PubMed

    Losonczy, Lia I; Lovallo, Emily; Schnorr, C Daniel; Mantuani, Daniel

    2016-01-01

    Neurogenic stunned myocardium is a rare disease entity that has been typically described as a consequence of subarachnoid hemorrhage and, less commonly, seizures. Here we describe a case of a healthy young woman who drank excessive free water causing acute hyponatremia complicated by cerebral edema and seizure, leading to cardiogenic shock from neurogenic stunned myocardium. Two days later, she had complete return of her normal cardiac function. PMID:26238098

  18. The factors affecting early death after the initial therapy of acute myeloid leukemia

    PubMed Central

    Malkan, Umit Yavuz; Gunes, Gursel; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Etgul, Sezgin; Aslan, Tuncay; Yayar, Okan; Aydin, Seda; Demiroglu, Haluk; Ozcebe, Osman Ilhami; Sayinalp, Nilgun; Goker, Hakan; Aksu, Salih; Buyukasik, Yahya

    2015-01-01

    There are some improvements in management of acute myeloid leukemia (AML). However, induction-induced deaths still remain as a major problem. The aim of this study is to assess clinical parameters affecting early death in patients with AML. 199 AML patients, who were treated with intensive, non-intensive or supportive treatment between 2002 and 2014 in Hacettepe Hematology Department, were analyzed retrospectively. In our study early death rate for elderly was found to be lower than previous reports whereas it was similar for those who were under age of 60. Better ECOG performance (ECOG performance score 0 and 1) and non-intensive treatment associated with lower early death rates, however APL-type disease associated with higher early death rates. ECOG performance score at diagnosis was found to be the most related independent factor with higher rate of early death in 15 days after treatment (P<0.001). Therefore we decided to understand the factors which were related with ECOG. WBC count at diagnosis was found to be the only related parameter with ECOG performance score. Leucocyte count at diagnosis appears like to have an indirect effect on early death in AML patients. It maybe suggested that in recent years there is an improvement in early death rates of elderly AML patients. The currently reported findings require prospective validation and would encourage the incorporation of other next generation genomics for the prediction of early death and overall risk status of AML. PMID:26885243

  19. [The morphological changes in the myocardial tissue after sudden cardiac death from alcoholic cardiomyopathy].

    PubMed

    Sokolova, O V

    2016-01-01

    This paper was designed to report the results of the retrospective analysis of the protocols of 180 forensic medical autopsy sections stored in the archives of Sankt-Petersburg Bureau of Forensic Medical Expertise and the data of the histological studies of myocardial tissues obtained after sudden cardiac death from alcoholic cardiomyopathy. The study revealed the following most pathognomonic histological criteria for alcoholic heart lesions: the alternation of hypertrophic and atrophic cardiomyocytes in the state of severe parenchymatous degeneration, pronounced mesenchymal fatty dystrophy in combination with pathological changes of the vascular walls (vascular wall plasmatization), sub-endothelial accumulation of the PAS-positive tissue compounds, microcirculatory disorders in the form of erythrocyte stasis with the manifestations of the blood "sludge" phenomenon, and precapillary fibrosis. The signs of severe parenchymatous and stromal vascular dystrophy of the myocardial histohematic barrier (HHB) are supposed to reflect the toxic effects of ethanol and its metabolites that are directly involved in the mechanisms underlying the disturbances of intracellular metabolism and dyscirculatory events leading to the development of heart muscle hypoxia. PMID:27030089

  20. A case of sudden cardiac death following Domperidone self-medication.

    PubMed

    Fais, Paolo; Vermiglio, Elisa; Laposata, Chiara; Lockwood, Robert; Gottardo, Rossella; De Leo, Domenico

    2015-09-01

    The phenomenon of sudden cardiac death is usually related to the worsening of existing heart conditions leading to ventricular arrhythmia (VA). One of the well-known triggers of SCD is drug-induced prolongation of the QT interval, such as that caused by Domperidone (D). Despite its risk to prolong the QT interval and associated narrow therapeutic index, D is available as an over-the-counter (OTC) drug in many countries such as Italy, Ireland, Netherlands, China, South Africa, Mexico, New Zealand and Chile to treat gastroesophageal reflux and functional dyspepsia. The present paper reports a case of SCD that occurred some hours after D self-administration in a 47-year-old female subject with mitral valve prolapse, thus, predisposed to both VA and SCD. Despite the risks related to D administration, to the best of our knowledge, this particular issue has not been discussed in the medico-legal literature. For this reason, the forensic implications of D administration are discussed focusing on issues related to the self-administration as an OTC drug (as seen in this case), administration to incapacitated subjects, prescription to patients with contraindications and the off-label drug use of D at high and hazardous concentrations to stimulate lactation. PMID:26119456

  1. Soccer and Sudden Cardiac Death in Young Competitive Athletes: A Review

    PubMed Central

    Higgins, John P.; Andino, Aldo

    2013-01-01

    Sudden cardiac death (SCD) in young competitive athletes (<35 years old) is a tragic event that has been brought to public attention in the past few decades. The incidence of SCD is reported to be 1-2/100,000 per year, with athletes at a 2.5 times higher risk. Soccer is the most popular sport in the world, played by people of all ages. However, unfortunately it is cardiovascular diseases such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy that have subtly missed screening and claimed the lives of soccer stars such as Marc Vivien Foe and Antonio Puerta during live action on the field and on an internationally televised stage. This paper covers the physiological demands of soccer and the relationship between soccer and SCD. It also reviews the most common causes of SCD in young athletes, discusses the current guidelines in place by The Fédération Internationale de Football Association (FIFA) for screening among professional soccer players, and the precautions that have been put in place to prevent SCD on the field in professional soccer. PMID:26464886

  2. Donor Hemodynamics as a Predictor of Outcomes After Kidney Transplantation From Donors After Cardiac Death.

    PubMed

    Allen, M B; Billig, E; Reese, P P; Shults, J; Hasz, R; West, S; Abt, P L

    2016-01-01

    Donation after cardiac death is an important source of transplantable organs, but evidence suggests donor warm ischemia contributes to inferior outcomes. Attempts to predict recipient outcome using donor hemodynamic measurements have not yielded statistically significant results. We evaluated novel measures of donor hemodynamics as predictors of delayed graft function and graft failure in a cohort of 1050 kidneys from 566 donors. Hemodynamics were described using regression line slopes, areas under the curve, and time beyond thresholds for systolic blood pressure, oxygen saturation, and shock index (heart rate divided by systolic blood pressure). A logistic generalized estimation equation model showed that area under the curve for systolic blood pressure was predictive of delayed graft function (above median: odds ratio 1.42, 95% confidence interval [CI] 1.06-1.90). Multivariable Cox regression demonstrated that slope of oxygen saturation during the first 10 minutes after extubation was associated with graft failure (below median: hazard ratio 1.30, 95% CI 1.03-1.64), with 5-year graft survival of 70.0% (95%CI 64.5%-74.8%) for donors above the median versus 61.4% (95%CI 55.5%-66.7%) for those below the median. Among older donors, increased shock index slope was associated with increased hazard of graft failure. Validation of these findings is necessary to determine the utility of characterizing donor warm ischemia to predict recipient outcome. PMID:26361242

  3. Useful laboratory tests for studying thrombogenesis in acute cardiac syndromes.

    PubMed

    Fareed, J; Hoppensteadt, D A; Leya, F; Iqbal, O; Wolf, H; Bick, R

    1998-08-01

    We review laboratory tests that evaluate thrombogenesis during acute coronary syndromes. These tests have been found to be valuable research tools in more clearly understanding the pathophysiology of acute coronary syndromes. In particular, we describe tissue factor, tissue factor pathway inhibitor, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrinopeptide A, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), t-PA-PAI complex, Bbeta 15-42-related peptides, fibrinogen degradation products, fibrin degradation products, D-dimer, platelet factor 4, beta-thromboglobulin, 5-hydroxytryptamine, thromboxane B2, prostacyclin, endothelin, angiotensin-converting enzyme, soluble thrombomodulin, C1-esterase inhibitor, anaphylotoxins C3a, C4a, and C5a, bradykinin, tumor necrosis factor, leukotriene C4, platelet activating factor, anti-phospholipid antibody, and von Willebrand factor. Some of these tests may prove to be useful in clinical diagnosis and management of acute coronary syndromes. Clinical outcome studies are needed to determine which tests may be cost effective and medically useful. PMID:9702994

  4. Genetic investigations of sudden unexpected deaths in infancy using next-generation sequencing of 100 genes associated with cardiac diseases.

    PubMed

    Hertz, Christin Loeth; Christiansen, Sofie Lindgren; Larsen, Maiken Kudahl; Dahl, Morten; Ferrero-Miliani, Laura; Weeke, Peter Ejvin; Pedersen, Oluf; Hansen, Torben; Grarup, Niels; Ottesen, Gyda Lolk; Frank-Hansen, Rune; Banner, Jytte; Morling, Niels

    2016-06-01

    Sudden infant death syndrome (SIDS) is the most frequent manner of post-perinatal death among infants. One of the suggested causes of the syndrome is inherited cardiac diseases, mainly channelopathies, that can trigger arrhythmias and sudden death. The purpose of this study was to investigate cases of sudden unexpected death in infancy (SUDI) for potential causative variants in 100 cardiac-associated genes. We investigated 47 SUDI cases of which 38 had previously been screened for variants in RYR2, KCNQ1, KCNH2 and SCN5A. Using the Haloplex Target Enrichment System (Agilent) and next-generation sequencing (NGS), the coding regions of 100 genes associated with inherited channelopathies and cardiomyopathies were captured and sequenced on the Illumina MiSeq platform. Sixteen (34%) of the SUDI cases had variants with likely functional effects, based on conservation, computational prediction and allele frequency, in one or more of the genes screened. The possible effects of the variants were not verified with family or functional studies. Eight (17%) of the SUDI cases had variants in genes affecting ion channel functions. The remaining eight cases had variants in genes associated with cardiomyopathies. In total, one third of the SUDI victims in a forensic setting had variants with likely functional effect that presumably contributed to the cause of death. The results support the assumption that channelopathies are important causes of SUDI. Thus, analysis of genes associated with cardiac diseases in SUDI victims is important in the forensic setting and a valuable supplement to the clinical investigation in all cases of sudden death. PMID:26350513

  5. Effects of acute stress on cardiac endocannabinoids, lipogenesis, and inflammation in rats

    PubMed Central

    Lim, James; Piomelli, Daniele

    2014-01-01

    Objective Trauma exposure can precipitate acute/post-traumatic stress responses (AS/PTSD) and disabling cardiovascular disorders (CVD). Identifying acute stress-related physiologic changes that may increase CVD risk could inform development of early CVD-prevention strategies. The endocannabinoid system (ECS) regulates hypothalamic-pituitary-adrenal (HPA) axis response and stress-related cardiovascular function. We examine stress-related endocannabinoid system (ECS) activity and its association with cardiovascular biochemistry/function following acute stress. Methods Rodents (n=8-16/group) were exposed to predator odor or saline; elevated plus maze (EPM), blood pressure (BP), serum and cardiac tissue ECS markers, and lipid metabolism were assessed at 24h and 2wks post-exposure. Results At 24h the predator odor group demonstrated anxiety-like behavior and had (a) elevated serum markers of cardiac failure/damage (brain natriuretic peptide [BNP]: 275.1 vs. 234.6, p=0.007; troponin-I: 1.50 vs. 0.78, p=0.076), lipogenesis (triacylglycerols [TAG]: 123.5 vs. 85.93, p=0.018), and inflammation (stearoyl delta-9 desaturase activity [SCD-16]: 0.21 vs. 0.07, p<0.001); (b) significant decrease in cardiac endocannabinoid (2-arachidonoyl-sn-glycerol, 2-AG: 29.90 vs. 65.95, p<0.001) and fatty acid ethanolamides (FAE: oleoylethanolamide, OEA: 114.3 vs. 125.4, p=0.047; palmitoylethanolamide, PEA: 72.96 vs. 82.87, p=0.008); and (c) increased cardiac inflammation (IL-1β/IL-6 ratio: 19.79 vs.13.57, p=0.038; TNF-α/IL-6 ratio: 1.73 vs. 1.03, p=0.019) and oxidative stress (thiobarbituric acid reactive substances [TBARS]: 7.81 vs. 7.05, p=0.022), that were associated with cardiac steatosis (higher TAG: 1.09 vs. 0.72, p<0.001). Cardiac lipogenesis persisted, and elevated BP emerged two weeks after exposure. Conclusions Acute psychological stress elicits ECS-related cardiac responses associated with persistent, potentially-pathological changes in rat cardiovascular biochemistry

  6. National Heart Attack Alert Program position paper: chest pain centers and programs for the evaluation of acute cardiac ischemia.

    PubMed

    Zalenski, R J; Selker, H P; Cannon, C P; Farin, H M; Gibler, W B; Goldberg, R J; Lambrew, C T; Ornato, J P; Rydman, R J; Steele, P

    2000-05-01

    The National Heart Attack Alert Program (NHAAP), which is coordinated by the National Heart, Lung, and Blood Institute (NHLBI), promotes the early detection and optimal treatment of patients with acute myocardial infarction and other acute coronary ischemic syndromes. The NHAAP, having observed the development and growth of chest pain centers in emergency departments with special interest, created a task force to evaluate such centers and make recommendations pertaining to the management of patients with acute cardiac ischemia. This position paper offers recommendations to assist emergency physicians in EDs, including those with chest pain centers, in providing comprehensive care for patients with acute cardiac ischemia. PMID:10783408

  7. Fermented Brown Rice Extract Causes Apoptotic Death of Human Acute Lymphoblastic Leukemia Cells via Death Receptor Pathway.

    PubMed

    Horie, Yukiko; Nemoto, Hideyuki; Itoh, Mari; Kosaka, Hiroaki; Morita, Kyoji

    2016-04-01

    Mixture of brown rice and rice bran fermented with Aspergillus oryzae, designated as FBRA, has been reported to reveal anti-carcinogenic and anti-inflammatory effects in rodents. Then, to test its potential anti-cancer activity, the aqueous extract was prepared from FBRA powder, and the effect of this extract on human acute lymphoblastic leukemia Jurkat cells was directly examined. The exposure to FBRA extract reduced the cell viability in a concentration- and time-dependent manner. The reduction of the cell viability was accompanied by the DNA fragmentation, and partially restored by treatment with pan-caspase inhibitor. Further studies showed that FBRA extract induced the cleavage of caspase-8, -9, and -3, and decreased Bcl-2 protein expression. Moreover, the expression of tBid, DR5, and Fas proteins was enhanced by FBRA extract, and the pretreatment with caspase-8 inhibitor, but not caspase-9 inhibitor, restored the reduction of the cell viability induced by FBRA extract. These findings suggested that FBRA extract could induce the apoptotic death of human acute lymphoblastic leukemia cells probably through mainly the death receptor-mediated pathway and supplementarily through the tBid-mediated mitochondrial pathway, proposing the possibility that FBRA was a potential functional food beneficial to patients with hematological cancer. PMID:26769704

  8. Acute effects of carbon monoxide on cardiac electrical stability. Research report, Sep 85-Jul 88

    SciTech Connect

    Verrier, R.L.; Mills, A.K.; Skornik, W.A.

    1990-01-01

    The objective of the project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability in the normal and ischemic heart of anesthetized and conscious dogs. Exposure (90 to 120 minutes) to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, was without significant effect on ventricular electrical stability in laboratory dogs. This appears to be the case in the acutely ischemic heart as well as in the normal heart. Using a model involving partial coronary artery stenosis, no changes were found in either the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Also examined were the effects of carbon monoxide exposure in the conscious state in order to take into consideration possible adverse consequences mediated by the central nervous system. The study found no adverse effects on the cardiac-excitable properties in response to either a 2-hour- or 24-hour-exposure paradigm.

  9. Novel biomarkers for early diagnosis of acute kidney injury after cardiac surgery in adults

    PubMed Central

    Kališnik, Jurij Matija

    2016-01-01

    Acute kidney injury after cardiac surgery with cardiopulmonary bypass is a common and serious complication and it is associated with increased morbidity and mortality. Diagnosis of acute kidney injury is based on the serum creatinine levels which rise several hours to days after the initial injury. Thus, novel biomarkers that will enable faster diagnosis are needed in clinical practice. There are numerous urine and serum proteins that indicate kidney injury and are under extensive research. Despite promising basic research results and assembled data, which indicate superiority of some biomarkers to creatinine, we are still awaiting clinical application. PMID:27212976

  10. The Complex Role of iNOS in Acutely-Rejecting Cardiac Transplants

    PubMed Central

    Pieper, Galen M.; Roza, Allan M.

    2008-01-01

    This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutely-rejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed. PMID:18291116

  11. Polymorphism identification and cardiac gene expression analysis of the calsequestrin 2 gene in broiler chickens with sudden death syndrome.

    PubMed

    Basaki, M; Asasi, K; Tabandeh, M R; Aminlari, M

    2016-04-01

    Sudden death syndrome (SDS) in broilers is a cardiac disease associated with ventricular tachycardia (VT) and ventricular fibrillation (VF); however, its pathogenesis at the molecular level is not precisely determined. Downregulation and mutations of calsequestrin 2 (CASQ2), a major intracellular Ca(2+) buffer, have been associated with VT and sudden cardiac death (SCD) in humans but in chickens there is no report describing CASQ2 abnormalities in cardiac diseases. In order to better understand the molecular mechanisms predisposing the myocardium to fatal arrhythmia in broilers, the mRNA expression level of chicken CASQ2 gene (chCASQ2) in the left ventricle of dead broilers with SDS was determined and compared to healthy broilers using quantitative real-time PCR (qPCR). To determine the probable mutations in chCASQ2, PCR and direct sequencing were also done. Results showed a reduction in chCASQ2 expression in broilers dead by SDS. Three novel mutations (K289R, P308S, D310H) which are absent in healthy broilers were observed in chCASQ2. It is concluded that susceptibility to fatal cardiac arrhythmia in SDS may be associated with changes in intracellular Ca(2+) balance due to mutation and downregulation of chCASQ2. PMID:26953612

  12. Update on management of cardiac arrhythmias in acute coronary syndromes.

    PubMed

    Willich, T; Goette, A

    2015-04-01

    This review summarizes different types of arrhythmias in patients with acute coronary syndromes and provides an overview of the available therapeutic options for acute care and management of critical arrhythmias. The different therapeutic options are depending on the origin and type of arrhythmia. The main common dominant mechanisms are intramural re-entry in ischemia and triggered activity in reperfusion. The different forms of arrhythmia were explained in detail. Atrial arrhythmias are mainly atrial fibrillation; other forms are rare and usually self-limited. As therapeutic options antiarrhythmic drug therapy with beta-blockers or amiodarone and direct current cardioversion are suitable. Ventricular arrhythmias can be divided in premature ventricular complexes, accelerated idioventricular rhythm, non-sustained ventricular tachycardia, sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and electrical storm. As therapeutic options antiarrhythmic drug therapy, implantable cardioverter defibrillator therapy (ICD), radiofrequency catheter ablation (RFA) and stellate ganglion blockade are available. The treatment with antiarrhythmic drug is rather cautious recommended, with the exception of beta-blockers. An additional drug therapy with ranolazine may be considered. The advantage of ICD therapy for long-term primary or secondary prophylactic therapy has been well documented. ICD therapy is associated with significant reduction in mortality compared with antiarrhythmic drug therapy (mainly amiodarone), with the exception of beta-blockers. RFA and stellate ganglion blockade are rather intended as therapeutically options for incessant VT/VF or electrical storm. PMID:25612305

  13. Mood disturbance and depression in Arab women following hospitalisation from acute cardiac conditions: a cross-sectional study from Qatar

    PubMed Central

    Donnelly, Tam Truong; Al Suwaidi, Jassim Mohd; Al-Qahtani, Awad; Asaad, Nidal; Fung, Tak; Singh, Rajvir; Qader, Najlaa Abdul

    2016-01-01

    Objectives Depression is associated with increased morbidity and mortality rates among cardiovascular patients. Depressed patients have three times higher risk of death than those who are not. We sought to determine the presence of depressive symptoms, and whether gender and age are associated with depression among Arab patients hospitalised with cardiac conditions in a Middle Eastern country. Setting Using a non-probability convenient sampling technique, a cross-sectional survey was conducted with 1000 Arab patients ≥20 years who were admitted to cardiology units between 2013 and 2014 at the Heart Hospital in Qatar. Patients were interviewed 3 days after admission following the cardiac event. Surveys included demographic and clinical characteristics, and the Arabic version of the Beck Depression Inventory Second Edition (BDI-II). Depression was assessed by BDI-II clinical classification scale. Results 15% of the patients had mild mood disturbance and 5% had symptoms of clinical depression. Twice as many females than males suffered from mild mood disturbance and clinical depression symptoms, the majority of females were in the age group 50 years and above, whereas males were in the age group 40–49 years. χ2 Tests and multivariate logistic regression analyses indicated that gender and age were statistically significantly related to depression (p<0.001 for all). Conclusions Older Arab women are more likely to develop mood disturbance and depression after being hospitalised with acute cardiac condition. Gender and age differences approach, and routine screening for depression should be conducted with all cardiovascular patients, especially for females in the older age groups. Mental health counselling should be available for all cardiovascular patients who exhibit depressive symptoms. PMID:27388362

  14. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease.

    PubMed

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-08-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery. PMID:25120320

  15. [Acute mediastinitis except in a context of cardiac surgery].

    PubMed

    Doddoli, C; Trousse, D; Avaro, J-P; Djourno, X-B; Giudicelli, R; Fuentes, P; Thomas, P

    2010-02-01

    Acute mediastinitis is a life-threatening complication (20 to 40 % of mortality) secondary to oropharyngeal abscesses, neck infections or oesophageal leak spreading into the mediastium. Early diagnosis and optimal therapeutic approach are crucial for patient survival. CT scanning of the cervical and thoracic area is a useful tool for diagnosis and follow-up. Treatment is based on broad-spectrum antibiotherapy, adequate surgery, mediastinal drainage, and treatment of possible organ failure. There is no surgical standardized attitude. Mini-invasive approach could be satisfactory when prompt diagnosis is established and the thoracic drainage is effective. Repeated postoperative CT scanning and close clinical and laboratory monitoring could make an additional thoracotomy a second-line procedure. PMID:20207299

  16. Clinical presentation and in-hospital death in acute pulmonary embolism: does cancer matter?

    PubMed

    Casazza, Franco; Becattini, Cecilia; Rulli, Eliana; Pacchetti, Ilaria; Floriani, Irene; Biancardi, Marco; Scardovi, Angela Beatrice; Enea, Iolanda; Bongarzoni, Amedeo; Pignataro, Luigi; Agnelli, Giancarlo

    2016-09-01

    Cancer is one of the most common risk factors for acute pulmonary embolism (PE), but only few studies report on the short-term outcome of patients with PE and a history of cancer. The aim of the study was to assess whether a cancer diagnosis affects the clinical presentation and short-term outcome in patients hospitalized for PE who were included in the Italian Pulmonary Embolism Registry. All-cause and PE-related in-hospital deaths were also analyzed. Out of 1702 patients, 451 (26.5 %) of patients had a diagnosis of cancer: cancer was known at presentation in 365, or diagnosed during the hospital stay for PE in 86 (19 % of cancer patients). Patients with and without cancer were similar concerning clinical status at presentation. Patients with cancer less commonly received thrombolytic therapy, and more often had an inferior vena cava filter inserted. Major or intracranial bleeding was not different between groups. In-hospital all-cause death occurred in 8.4 and 5.9 % of patients with and without cancer, respectively. At multivariate analysis, cancer (OR 2.24, 95 % CI 1.27-3.98; P = 0.006) was an independent predictor of in-hospital death. Clinical instability, PE recurrence, age ≥75 years, recent bed rest ≥3 days, but not cancer, were independent predictors of in-hospital death due to PE. Cancer seems a weaker predictor of all-cause in-hospital death compared to other factors; the mere presence of cancer, without other risk factors, leads to a probability of early death of 2 %. In patients with acute PE, cancer increases the probability of in-hospital all-cause death, but does not seem to affect the clinical presentation or the risk of in-hospital PE-related death. PMID:27023066

  17. Obesity related risk of sudden cardiac death in the atherosclerosis risk in communities study

    PubMed Central

    Adabag, Selcuk; Huxley, Rachel R; Lopez, Faye L; Chen, Lin Y; Sotoodehnia, Nona; Siscovick, David; Deo, Rajat; Konety, Suma; Alonso, Alvaro; Folsom, Aaron R

    2016-01-01

    Objective To examine the association of body mass index (BMI), waist circumference (WC) and waist hip ratio (WHR) with sudden cardiac death (SCD) in community dwelling individuals. Methods Data from a multicentre, prospective, cohort study of 14 941 men and women (African American, and white), aged 45–64 years, participating in the Atherosclerosis Risk in Communities study was analysed. Obesity measures were assessed at baseline (1987–1989). SCD was adjudicated by a committee. Results At enrolment mean±SD age of the participants was 54±6 years (55% female; 26% African American). During 12.6±2.5 years of follow-up, 253 SCD occurred (incidence rate 1.34/100 person-years). The association between obesity and SCD differed by smoking status (interaction p≤0.01). In models adjusting for age, sex, race, study centre and education level, SCD risk was positively associated (p<0.001) with BMI, WC and WHR in non-smokers, but not in smokers. WHR was more strongly associated with SCD in non-smokers than was BMI or WC (HR per SD increment (95% CI) 2.00 (1.65 to 2.42); 1.34 (1.15 to 1.56) and 1.49 (1.28 to 1.74), respectively). After adjustment for potential mediators (hypertension, diabetes, lipid profile, prevalent coronary heart disease, heart failure, and LV hypertrophy), non-smokers in the highest WHR category (>0.95 in women; >1.01 in men) had double the risk of SCD (HR 2.03, 95% CI 1.19 to 3.46; incidence rate 1.43/1000 person-years) versus those with normal WHR. Conclusions General obesity is associated with increased risk of SCD in middle-aged, non-smoking individuals, mediated by traditional cardiovascular risk factors. Central obesity, however, is independently associated with SCD by pathways that remain to be elucidated. PMID:25410499

  18. Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.

    PubMed

    Deo, Rajat; Katz, Ronit; Shlipak, Michael G; Sotoodehnia, Nona; Psaty, Bruce M; Sarnak, Mark J; Fried, Linda F; Chonchol, Michel; de Boer, Ian H; Enquobahrie, Daniel; Siscovick, David; Kestenbaum, Bryan

    2011-12-01

    Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD ≥20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH ≥65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease. PMID:22068871

  19. Early allograft dysfunction in liver transplantation with donation after cardiac death donors results in inferior survival.

    PubMed

    Lee, David D; Singh, Amandeep; Burns, Justin M; Perry, Dana K; Nguyen, Justin H; Taner, C Burcin

    2014-12-01

    Donation after cardiac death (DCD) liver allografts have been associated with increased morbidity from primary nonfunction, biliary complications, early allograft failure, cost, and mortality. Early allograft dysfunction (EAD) after liver transplantation has been found to be associated with inferior patient and graft survival. In a cohort of 205 consecutive liver-only transplant patients with allografts from DCD donors at a single center, the incidence of EAD was found to be 39.5%. The patient survival rates for those with no EAD and those with EAD at 1, 3, and 5 years were 97% and 89%, 79% and 79%, and 61% and 54%, respectively (P = 0.009). Allograft survival rates for recipients with no EAD and those with EAD at 1, 3, and 5 years were 90% and 75%, 72% and 64%, and 53% and 43%, respectively (P = 0.003). A multivariate analysis demonstrated a significant association between the development of EAD and the cold ischemia time [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.01-1.56, P = 0.037] and hepatocellular cancer as a secondary diagnosis in recipients (OR = 2.26, 95% CI = 1.11-4.58, P = 0.025). There was no correlation between EAD and the development of ischemic cholangiopathy. In conclusion, EAD results in inferior patient and graft survival in recipients of DCD liver allografts. Understanding the events that cause EAD and developing preventive or early therapeutic approaches should be the focus of future investigations. PMID:25179581

  20. Radiation Therapy and Cardiac Death in Long-Term Survivors of Esophageal Cancer: An Analysis of the Surveillance, Epidemiology, and End Result Database

    PubMed Central

    Gharzai, Laila; Verma, Vivek; Denniston, Kyle A.; Bhirud, Abhijeet R.; Bennion, Nathan R.; Lin, Chi

    2016-01-01

    Objective Radiation therapy (RT) for esophageal cancer often results in unintended radiation doses delivered to the heart owing to anatomic proximity. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined late cardiac death in survivors of esophageal cancer that had or had not received RT. Methods 5,630 patients were identified that were diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (AC) from 1973–2012, who were followed for at least 5 years after therapy. Examined risk factors for cardiac death included age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/AC), esophageal location (<18cm/18-24cm/25-32cm/33-40cm from incisors), diagnosis year (1973-1992/1993-2002/2003-2012), and receipt of surgery and/or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A Cox model was used to evaluate risk factors for cardiac death in propensity score matched data. Results Patients who received RT were younger, diagnosed more recently, had more advanced disease, SCC histology, and no surgery. The RT group had higher risk of cardiac death than the no-RT group (log-rank p<0.0001). The median time to cardiac death in the RT group was 289 months (95% CI, 255–367) and was not reached in the no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.23, 95% CI 1.03–1.47, HR 1.961, 95% CI 1.466–2.624). Lower esophageal subsite (33–40 cm) was also associated with a higher risk of cardiac death. Other variables were not associated with cardiac death. Conclusions Recognizing the limitations of a SEER analysis including lack of comorbidity accountability, these data should prompt more definitive study as to whether a possible associative effect of RT on cardiac death

  1. A transgenic zebrafish model of a human cardiac sodium channel mutation exhibits bradycardia, conduction-system abnormalities and early death.

    PubMed

    Huttner, Inken G; Trivedi, Gunjan; Jacoby, Arie; Mann, Stefan A; Vandenberg, Jamie I; Fatkin, Diane

    2013-08-01

    The recent exponential increase in human genetic studies due to the advances of next generation sequencing has generated unprecedented numbers of new gene variants. Determining which of these are causative of human disease is a major challenge. In-vitro studies and murine models have been used to study inherited cardiac arrhythmias but have several limitations. Zebrafish models provide an attractive alternative for modeling human heart disease due to similarities in cardiac electrophysiology and contraction, together with ease of genetic manipulation, external development and optical transparency. Although zebrafish cardiac mutants and morphants have been widely used to study loss and knockdown of zebrafish gene function, the phenotypic effects of human dominant-negative gene mutations expressed in transgenic zebrafish have not been evaluated. The aim of this study was to generate and characterize a transgenic zebrafish arrhythmia model harboring the pathogenic human cardiac sodium channel mutation SCN5A-D1275N, that has been robustly associated with a range of cardiac phenotypes, including conduction disease, sinus node dysfunction, atrial and ventricular arrhythmias, and dilated cardiomyopathy in humans and in mice. Stable transgenic fish with cardiac expression of human SCN5A were generated using Tol2-mediated transgenesis and cardiac phenotypes were analyzed using video microscopy and ECG. Here we show that transgenic zebrafish expressing the SCN5A-D1275N mutation, but not wild-type SCN5A, exhibit bradycardia, conduction-system abnormalities and premature death. We furthermore show that SCN5A-WT, and to a lesser degree SCN5A-D1275N, are able to compensate the loss of endogenous zebrafish cardiac sodium channels, indicating that the basic pathways, through which SCN5A acts, are conserved in teleosts. This proof-of-principle study suggests that zebrafish may be highly useful in vivo models to differentiate functional from benign human genetic variants in cardiac

  2. Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving.

    PubMed

    Shiels, H A; Galli, G L J; Block, B A

    2015-02-01

    Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation-contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca(2+) transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation-contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range. PMID:25540278

  3. Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

    PubMed Central

    Shiels, H. A.; Galli, G. L. J.; Block, B. A.

    2015-01-01

    Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation–contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca2+ transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation–contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range. PMID:25540278

  4. Sensitization of acute lymphoblastic leukemia cells for LCL161-induced cell death by targeting redox homeostasis.

    PubMed

    Haß, Christina; Belz, Katharina; Schoeneberger, Hannah; Fulda, Simone

    2016-04-01

    Disturbed redox homeostasis with both elevated reactive oxygen species (ROS) levels and antioxidant defense mechanisms has been reported in acute lymphoblastic leukemia (ALL). We therefore hypothesized that inhibition of pathways responsible for ROS detoxification renders ALL cells more susceptible for cell death. Here, we report that pharmacological inhibitors of key pathways for the elimination of ROS, i.e. Erastin, buthionine sulfoximine (BSO) and Auranofin, sensitize ALL cells for cell death upon treatment with the Smac mimetic LCL161 that antagonizes Inhibitor of Apoptosis (IAP) proteins. Erastin, BSO or Auranofin significantly increase LCL161-induced cell death and also act in concert with LCL161 to profoundly suppress long-term clonogenic survival in several ALL cell lines. Erastin or BSO cooperates with LCL161 to stimulate ROS production and lipid peroxidation prior to cell death. ROS production and lipid peroxidation are required for this cotreatment-induced cell death, since ROS scavengers or pharmacological inhibition of lipid peroxidation provides significant protection against cell death. These results emphasize that inhibition of antioxidant defense mechanisms can serve as a potent approach to prime ALL cells for LCL161-induced cell death. PMID:26774450

  5. Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury

    PubMed Central

    Sancho-Martínez, Sandra M.; López-Novoa, José M.; López-Hernández, Francisco J.

    2015-01-01

    The histological substrate of many forms of intrinsic acute kidney injury (AKI) has been classically attributed to tubular necrosis. However, more recent studies indicate that necrosis is not the main form of cell death in AKI and that other forms such as apoptosis, regulated necrosis (i.e. necroptosis and parthanatos), autophagic cell death and mitotic catastrophe, also participate in AKI and that their contribution depends on the cause and stage of AKI. Herein, we briefly summarize the main characteristics of the major types of cell death and we also critically review the existing evidence on the occurrence of different types of cell death reported in the most common experimental models of AKI and human specimens. We also discuss the pathophysiological mechanisms linking tubule epithelial cell death with reduced glomerular filtration, azotaemia and hydroelectrolytic imbalance. For instance, special relevance is given to the analysis of the inflammatory component of some forms of cell death over that of others, as an important and differential pathophysiological determinant. Finally, known molecular mechanisms and signalling pathways involved in each cell death type pose appropriate targets to specifically prevent or reverse AKI, provided that further knowledge of their participation and repercussion in each AKI syndrome is progressively increased in the near future. PMID:26413280

  6. Medical neglect death due to acute lymphoblastic leukaemia: an autopsy case report.

    PubMed

    Usumoto, Yosuke; Sameshima, Naomi; Tsuji, Akiko; Kudo, Keiko; Nishida, Naoki; Ikeda, Noriaki

    2014-12-01

    We report the case of 2-year-old girl who died of precursor B-cell acute lymphoblastic leukaemia (ALL), the most common cancer in children. She had no remarkable medical history. She was transferred to a hospital because of respiratory distress and died 4 hours after arrival. Two weeks before death, she had a fever of 39 degrees C, which subsided after the administration of a naturopathic herbal remedy. She developed jaundice 1 week before death, and her condition worsened on the day of death. Laboratory test results on admission showed a markedly elevated white blood cell count. Accordingly, the cause of death was suspected to be acute leukaemia. Forensic autopsy revealed the cause of death to be precursor B-cell ALL. With advancements in medical technology, the 5-year survival rate of children with ALL is nearly 90%. However, in this case, the deceased's parents preferred complementary and alternative medicine (i.e., naturopathy) to evidence-based medicine and had not taken her to a hospital for a medical check-up or immunisation since she was an infant. Thus, if she had received routine medical care, she would have a more than 60% chance of being alive 5 years after diagnosis. Therefore, we conclude that the parents should be accused of medical neglect regardless of their motives. PMID:25895240

  7. Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.

    PubMed

    Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2016-03-01

    Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective

  8. Cardiac glycoside-induced cell death and Rho/Rho kinase pathway: Implication of different regulation in cancer cell lines.

    PubMed

    Özdemir, Aysun; Şimay, Yaprak Dilber; İbişoğlu, Burçin; Yaren, Biljana; Bülbül, Döne; Ark, Mustafa

    2016-05-01

    Previously, we demonstrated that the Rho/ROCK pathway is involved in ouabain-induced apoptosis in HUVEC. In the current work, we investigated whether the Rho/ROCK pathway is functional during cardiac glycosides-induced cytotoxic effects in cancer cell lines, as well as in non-tumor cells. For that purpose, we evaluated the role of ROCK activation in bleb formation and cell migration over upstream and downstream effectors in addition to ROCK cleavage after cardiac glycosides treatment. All three cardiac glycosides (ouabain, digoxin and bufalin) induced cell death in HeLa and HepG2 cells and increased the formation of blebbing in HeLa cells. In contrast to our previous study, ROCK inhibitor Y27632 did not prevent bleb formation. Observation of ROCK II cleavage after ouabain, digoxin and oxaliplatin treatments in HeLa and/or HepG2 cells suggested that cleavage is independent of cell type and cell death induction. While inhibiting cleavage of ROCK II by the caspase inhibitors z-VAD-fmk, z-VDVAD-fmk and z-DEVD-fmk, evaluation of caspase 2 siRNA ineffectiveness on this truncation indicated that caspase-dependent ROCK II cleavage is differentially regulated in cancer cell lines. In HeLa cells, ouabain induced the activation of ROCK, although it did not induce phosphorylation of ERM, an upstream effector. While Y27632 inhibited the migration of HeLa cells, 10nM ouabain had no effect on cell migration. In conclusion, these findings indicate that the Rho/ROCK pathway is regulated differently in cancer cell lines compared to normal cells during cardiac glycosides-induced cell death. PMID:27017918

  9. [Time costs cardiac muscle tissue--prehospital therapy of acute myocardial infarct--a case report].

    PubMed

    Eschenburg, G; Pappert, D; Ohlmeier, H

    2003-01-01

    Symptoms of an acute myocardial infarction are a common reason for calling the emergency physician. Pre-hospital mortality caused by cardiac infarction is constantly high. The main potential for decreasing infarction mortality lies in the pre-hospital period. The problems and prospects of treatment in the early period are described in the case of a 73-year-old patient with an acute anterior infarction. The diagnostic and therapeutic approach is shown and discussed in this concrete case, taking into consideration the guidelines for diagnostics and therapy of acute myocardial infarction in the pre-hospital period of the German Society for Cardiology. A particular focus is the management of pre-hospital thrombolysis, the preconditions, realization and risks of which are described. In this context, the experience and competence of the emergency physician is prerequisite for the exact diagnosis and therapy. Furthermore, the importance of a smooth transition from pre-hospital therapy to intensive care is emphasized. PMID:12666508

  10. Immediate multivessel revascularization may increase cardiac death and myocardial infarction in patients with ST-elevation myocardial infarction and multivessel coronary artery disease: data analysis from real world practice

    PubMed Central

    Chung, Woo-Young; Seo, Jae-Bin; Choi, Dong-Hyun; Cho, Young-Seok; Lee, Joo Myung; Suh, Jung-Won; Youn, Tae-Jin; Chae, In-Ho; Choi, Dong-Ju

    2016-01-01

    Background/Aims: The best revascularization strategy for patients with both acute ST-elevation myocardial infarction (STEMI) and multivessel coronary disease (MVD) is still debatable. We aimed to compare the outcomes of multivessel revascularization (MVR) with those of culprit-only revascularization (COR). Methods: A cohort of 215 consecutive patients who had received primary angioplasty for STEMI and MVD were divided into two groups according to whether angioplasty had been also performed for a stenotic nonculprit artery. The primary endpoint was one-year major adverse cardiac events defined as a composite of cardiac death, recurrent myocardial infarction, or any repeat revascularization. Results: One-year major adverse cardiac events were not significantly different between MVR (n = 107) and COR (n = 108) groups. However, the one-year composite hard endpoint of cardiac death or recurrent myocardial infarction was notably increased in the MVR group compared to the COR group (20.0% vs. 8.9%, p = 0.024). In subgroup analysis, the hard endpoint was significantly more frequent in the immediate than in the staged MVR subgroup (26.6% vs. 9.8%, p = 0.036). The propensity score-matched cohorts confirmed these findings. Conclusions: In patients with STEMI and MVD, MVR, especially immediate MVR with primary percutaneous intervention, was not beneficial and led to worse outcomes. Therefore, we conclude that COR or staged MVR would be better strategies for patients with STEMI and MVD. PMID:27048252

  11. Targeted next generation sequencing application in cardiac channelopathies: Analysis of a cohort of autopsy-negative sudden unexplained deaths.

    PubMed

    Farrugia, A; Keyser, C; Hollard, C; Raul, J S; Muller, J; Ludes, B

    2015-09-01

    Genetic testing for cardiac channelopathies in sudden unexplained death (SUD) has developed substantially over the last years. The Next Generation Sequencing (NGS) technology provides an unprecedented opportunity to screen for genetic variations underlying arrhythmogenic genes in a short period of time at a low cost. The present study aimed to perform genetic testing with NGS technologies on the Ion Torrent Personal Genome Machine™ (Ion PGM™) sequencer, in targeting a total of 23 genes reported to be associated with inherited cardiac channelopathies in order to identify the possible cause of death in a cohort of post-mortem cases. The molecular analyses focused on 16 cases of SUD, aged less than 35 years old. In all cases, the cause of death could not be determined after a rigorous autopsy associated with histopathological and toxicological analyses according to the guidelines of the Association for European Cardiovascular Pathology. DNA was extracted from fresh frozen tissue. An average of 200 variants was identified per case. However, after the prioritization process using a new scoring program (VaRank) and after the conjunction of clinical data and molecular findings, four "likely pathogenic" variants (including two undescribed variants), were identified in three cases (18.75%) of our cohort in the genes KCNH2, ANK2, SCN5A and RYR2. One case, who died during psychiatric hospitalization after administration of a QT prolonging drug, showed a double "likely pathogenic" variant in Long QT genes (ANK2 and SCN5A) which may have predisposed to drug-induced cardiac arrhythmias. Our study illustrates that the NGS approach based on AmpliSeq™ libraries and Ion Torrent PGM™ sequencing may be an efficient approach, integrated to post-mortem examination. Given the massive amount of information generated by NGS, a rigorous filtration strategy of variants coupled with multidisciplinary collaboration is crucial to determine the potential pathogenic role of identified

  12. Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons

    SciTech Connect

    Branch, C.A.; Goldberg, D.A.; Ewing, J.R.; Butt, S.S.; Gayner, J.; Fagan, S.C.

    1994-12-31

    The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 {mu}g/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%. 23 refs., 3 figs., 3 tabs.

  13. Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction

    PubMed Central

    Protti, Andrea; Mongue-Din, Heloise; Mylonas, Katie J.; Sirker, Alexander; Sag, Can Martin; Swim, Megan M.; Maier, Lars; Sawyer, Greta; Dong, Xuebin; Botnar, Rene; Salisbury, Jon; Gray, Gillian A.; Shah, Ajay M.

    2016-01-01

    Background Bone marrow transplantation (BMT) is commonly used in experimental studies to investigate the contribution of BM-derived circulating cells to different disease processes. During studies investigating the cardiac response to acute myocardial infarction (MI) induced by permanent coronary ligation in mice that had previously undergone BMT, we found that BMT itself affects the remodelling response. Methods and results Compared to matched naive mice, animals that had previously undergone BMT developed significantly less post-MI adverse remodelling, infarct thinning and contractile dysfunction as assessed by serial magnetic resonance imaging. Cardiac rupture in male mice was prevented. Histological analysis showed that the infarcts of mice that had undergone BMT had a significantly higher number of inflammatory cells, surviving cardiomyocytes and neovessels than control mice, as well as evidence of significant haemosiderin deposition. Flow cytometric and histological analyses demonstrated a higher number of alternatively activated (M2) macrophages in myocardium of the BMT group compared to control animals even before MI, and this increased further in the infarcts of the BMT mice after MI. Conclusions The process of BMT itself substantially alters tissue macrophage phenotype and the subsequent response to acute MI. An increase in alternatively activated macrophages in this setting appears to enhance cardiac recovery after MI. PMID:26688473

  14. An approach to predict Sudden Cardiac Death (SCD) using time domain and bispectrum features from HRV signal.

    PubMed

    Houshyarifar, Vahid; Chehel Amirani, Mehdi

    2016-08-12

    In this paper we present a method to predict Sudden Cardiac Arrest (SCA) with higher order spectral (HOS) and linear (Time) features extracted from heart rate variability (HRV) signal. Predicting the occurrence of SCA is important in order to avoid the probability of Sudden Cardiac Death (SCD). This work is a challenge to predict five minutes before SCA onset. The method consists of four steps: pre-processing, feature extraction, feature reduction, and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the HRV signal is extracted. In second step, bispectrum features of HRV signal and time-domain features are obtained. Six features are extracted from bispectrum and two features from time-domain. In the next step, these features are reduced to one feature by the linear discriminant analysis (LDA) technique. Finally, KNN and support vector machine-based classifiers are used to classify the HRV signals. We used two database named, MIT/BIH Sudden Cardiac Death (SCD) Database and Physiobank Normal Sinus Rhythm (NSR). In this work we achieved prediction of SCD occurrence for six minutes before the SCA with the accuracy over 91%. PMID:27567781

  15. The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication.

    PubMed

    Lee, Sun-Hyo; Park, Samel; Lee, Jung-Won; Hwang, Il-Woong; Moon, Hyung-Jun; Kim, Ki-Hwan; Park, Su-Yeon; Gil, Hyo-Wook; Hong, Sae-Yong

    2016-07-01

    Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na(+), K(+), Cl(-) HCO3 (-), Ca(++)), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication. PMID:27366016

  16. The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication

    PubMed Central

    2016-01-01

    Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na+, K+, Cl- HCO3-, Ca++), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication. PMID:27366016

  17. Upper gastrointestinal haemorrhage in the acute cardiac care setting: antiplatelets and endoscopy.

    PubMed

    Musa, S A; Brecker, S J; Rahman, T M; Kang, J Y

    2012-05-01

    Upper gastrointestinal haemorrhage (UGIH) in cardiac patients receiving antiplatelets presents a difficult management problem. The aim of this study was to describe a series of cardiac inpatients receiving antiplatelets who underwent endoscopy for an acute UGIH. Cardiac inpatients receiving antiplatelets and requiring endoscopy for UGIH over an 18-month period were followed up. Forty-one patients were studied. Most patients (25 [61%]) presented with melaena. Antiplatelets were withheld in 34 (83%) patients; predominantly in those with higher pre-endoscopy Rockall scores (median, 4; interquartile range [IQR], 3-5 versus median, 3; IQR, 2-4; P < 0.05). Positive findings were identified at endoscopy in 80%. Duodenal ulcers were the most common lesion and adrenaline the most common method of haemostasis. Median time to first endoscopy was 0 (IQR, 0-1) days. Seven (17%) patients re-bled, median Rockall score was six (IQR, 4-8). Three (7%) patients experienced procedural complications, two patients became hypoxic and one patient died. Following endoscopy, antiplatelets were restarted after a median of three (IQR, 3-5) days. On discharge, 27/28 (96%) patients continued with antiplatelet and proton-pump inhibitor therapy. Thirty-day inpatient mortality was 7% (3 patients). One patient re-bled within six months of discharge. Endoscopy helped assess the risk of re-bleeding and timing of antiplatelet re-introduction in cardiac inpatients experiencing UGIH. PMID:22555229

  18. Phenylpropenoic Acid Glucoside from Rooibos Protects Pancreatic Beta Cells against Cell Death Induced by Acute Injury

    PubMed Central

    Himpe, Eddy; Cunha, Daniel A.; Song, Imane; Bugliani, Marco; Marchetti, Piero; Cnop, Miriam; Bouwens, Luc

    2016-01-01

    Objective Previous studies demonstrated that a phenylpropenoic acid glucoside (PPAG) from rooibos (Aspalathus linearis) extract had anti-hyperglycemic activity and significant protective effects on the pancreatic beta cell mass in a chronic diet-induced diabetes model. The present study evaluated the cytoprotective effect of the phytochemical on beta cells exposed to acute cell stress. Methods Synthetically prepared PPAG was administered orally in mice treated with a single dose of streptozotocin to acutely induce beta cell death and hyperglycemia. Its effect was assessed on beta cell mass, proliferation and apoptotic cell death. Its cytoprotective effect was also studied in vitro on INS-1E beta cells and on human pancreatic islet cells. Results Treatment with the phytochemical PPAG protected beta cells during the first days after the insult against apoptotic cell death, as evidenced by TUNEL staining, and prevented loss of expression of anti-apoptotic protein BCL2 in vivo. In vitro, PPAG protected INS-1E beta cells from streptozotocin-induced apoptosis and necrosis in a BCL2-dependent and independent way, respectively, depending on glucose concentration. PPAG also protected human pancreatic islet cells against the cytotoxic action of the fatty acid palmitate. Conclusions These findings show the potential use of PPAG as phytomedicine which protects the beta cell mass exposed to acute diabetogenic stress. PMID:27299564

  19. Acute poisonings and sudden deaths in Crete: a five-year review (1991-1996).

    PubMed

    Christakis-Hampsas, M; Tutudakis, M; Tsatsakis, A M; Assithianakis, P; Alegakis, A; Katonis, P G; Michalodimitrakis, E N

    1998-08-01

    Fatal and non-fatal acute poisonings and other sudden deaths examined in the Toxicology Laboratory of University Hospital of Iraklion, Crete, from 1991 to 1996 mainly involved the abuse of drugs (heroin, flunitrazepam and other psychoactive substances), accidental poisonings or suicide attempts with pesticides (carbamates, organophosphates, paraquat), other chemicals (cyanide salts, paint thinner, chlorine), traffic accidents, drownings and violent deaths (gunshots). Many of the cases were related to poisonous gases or volatiles (carbon monoxide, methylbromide). Fatalities due to alcohol and methylene-dioxy-ethyl amphetamine were also examined. Amphetamine and alcohol-related deaths due to drowning were more recent. A significant number of cases were related to the accidental ingestion of alcohol, drugs or suicide attempts by children. Some of the cases were treated successfully in various Cretan hospitals, while others had fatal outcomes due to late hospital admission. PMID:9682411

  20. Usefulness of cardiac meta-iodobenzylguanidine imaging to identify patients with chronic heart failure and left ventricular ejection fraction <35% at low risk for sudden cardiac death.

    PubMed

    Kawai, Tsutomu; Yamada, Takahisa; Tamaki, Shunsuke; Morita, Takashi; Furukawa, Yoshio; Iwasaki, Yusuke; Kawasaki, Masato; Kikuchi, Atsushi; Kondo, Takumi; Takahashi, Satoshi; Ishimi, Masashi; Hakui, Hideyuki; Ozaki, Tatsuhisa; Sato, Yoshihiro; Seo, Masahiro; Sakata, Yasushi; Fukunami, Masatake

    2015-06-01

    Patients with chronic heart failure (CHF) at risk of sudden cardiac death (SCD) are often treated with implantable cardiac defibrillators (ICDs). However, current criteria for device use that is based largely on left ventricular ejection fraction (LVEF) lead to many patients receiving ICDs that never deliver therapy. It is of clinical significance to identify patients who do not require ICDs. Although cardiac I-123 meta-iodobenzylguanidine (MIBG) imaging provides prognostic information about CHF, whether it can identify patients with CHF who do not require an ICD remains unclear. We studied 81 patients with CHF and LVEF <35%, assessed by cardiac MIBG imaging at enrollment. The heart-to-mediastinal ratio (H/M) in delayed images and washout rates were divided into 6 grades from 0 to 5, according to the degree of deviation from control values. The study patients were classified into 3 groups: low (1 to 4), intermediate (5 to 7), and high (8 to 10), according to the MIBG scores defined as the sum of the H/M and washout rate scores. Sixteen patients died of SCD during a follow-up period. Patients with low MIBG score had a significantly lower risk of SCD than those with intermediate and high scores (low [n = 19], 0%; intermediate [n = 37], 19%; high [n = 25], 36%; p = 0.001). The positive predictive value of low MIBG score for identifying patients without SCD was 100%. In conclusion, the MIBG score can identify patients with CHF and LVEF <35% who have low risk of developing SCD. PMID:25851796

  1. Cardiac Physiologic and Genetic Predictors of Hyperoxia-Induced Acute Lung Injury in Mice

    PubMed Central

    Cho, Hye-Youn; Miller-DeGraff, Laura; Walker, Christopher; Clark, James A.; Myers, Page H.; Rouse, D. Clay; Kleeberger, Steven R.

    2012-01-01

    Exposure of mice to hyperoxia produces pulmonary toxicity similar to acute lung injury/acute respiratory distress syndrome, but little is known about the interactions within the cardiopulmonary system. This study was designed to characterize the cardiopulmonary response to hyperoxia, and to identify candidate susceptibility genes in mice. Electrocardiogram and ventilatory data were recorded continuously from 4 inbred and 29 recombinant inbred strains during 96 hours of hyperoxia (100% oxygen). Genome-wide linkage analysis was performed in 27 recombinant inbred strains against response time indices (TIs) calculated from each cardiac phenotype. Reductions in minute ventilation, heart rate (HR), low-frequency (LF) HR variability (HRV), high-frequency HRV, and total power HRV were found in all mice during hyperoxia exposure, but the lag time before these changes began was strain dependent. Significant (chromosome 9) or suggestive (chromosomes 3 and 5) quantitative trait loci were identified for the HRTI and LFTI. Functional polymorphisms in several candidate susceptibility genes were identified within the quantitative trait loci and were associated with hyperoxia susceptibility. This is the first study to report highly significant interstrain variation in hyperoxia-induced changes in minute ventilation, HR, and HRV, and to identify polymorphisms in candidate susceptibility genes that associate with cardiac responses. Results indicate that changes in HR and LF HRV could be important predictors of subsequent adverse outcome during hyperoxia exposure, specifically the pathogenesis of acute lung injury. Understanding the genetic mechanisms of these responses may have significant diagnostic clinical value. PMID:22052878

  2. Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors

    PubMed Central

    Hu, Liangshuo; Liu, Xuemin; Zhang, Xiaogang; Yu, Liang; Sha, Huanchen; Zhou, Ying; Tian, Min; Shi, Jianhua; Wang, Wanli; Liu, Chang; Guo, Kun; Lv, Yi; Wang, Bo

    2016-01-01

    Abstract Development of organ transplantation is restricted by the discrepancy between the lack of donors and increasing number of patients. The outcome of pediatric donors transplanted into adult recipients especially with donation after circulatory death (DCD) pattern has not been well studied. The aim of this paper is to describe our experience of 3 successful DCD donor child-to-adult liver transplantations lately. Three DCD donors were separately 7, 5, and 8 years old. The ratio between donor graft weight and recipient body weight was 1.42%, 1.00%, and 1.33%, respectively. Ratio between the volume of donor liver and the expected liver volume was 0.65, 0.46, and 0.60. Splenectomy was undertaken for the second recipient according to the portal vein pressure (PVP) which was observed during the operation. Two out of 3 of the recipients suffered with acute kidney injury and got recovered after renal replacement therapy. The first recipient also went through early allograft dysfunction and upper gastrointestinal bleeding. The hospital course of the third recipient was uneventful. After 1 year of follow-up visit, the first and second recipients maintain good quality of life and liver function. The third patient was followed up for 5 months until now and recovered well. DCD child-to-adult liver transplantation should only be used for comparatively matched donor and recipient. PVP should be monitored during the operation. The short-term efficacy is good, but long-term follow-up and clinical study with large sample evaluation are still needed. PMID:26886643

  3. Risk scoring for prediction of acute cardiac complications from imbalanced clinical data.

    PubMed

    Liu, Nan; Koh, Zhi Xiong; Chua, Eric Chern-Pin; Tan, Licia Mei-Ling; Lin, Zhiping; Mirza, Bilal; Ong, Marcus Eng Hock

    2014-11-01

    Fast and accurate risk stratification is essential in the emergency department (ED) as it allows clinicians to identify chest pain patients who are at high risk of cardiac complications and require intensive monitoring and early intervention. In this paper, we present a novel intelligent scoring system using heart rate variability, 12-lead electrocardiogram (ECG), and vital signs where a hybrid sampling-based ensemble learning strategy is proposed to handle data imbalance. The experiments were conducted on a dataset consisting of 564 chest pain patients recruited at the ED of a tertiary hospital. The proposed ensemble-based scoring system was compared with established scoring methods such as the modified early warning score and the thrombolysis in myocardial infarction score, and showed its effectiveness in predicting acute cardiac complications within 72 h in terms of the receiver operation characteristic analysis. PMID:25375686

  4. Geophysical variables and behavior: CIII. Days with sudden infant deaths and cardiac arrhythmias in adults share a factor with PC1 geomagnetic pulsations: implications for pursuing mechanism.

    PubMed

    Persinger, M A; O'Connor, R P

    2001-06-01

    If geomagnetic-mediated stimuli trigger many sudden infant deaths, then the days in which they and hospital admissions for cardiac arrhythmias for adults occur should share a similar source of variance. Factor analyses of the days in which a sudden infant death occurred in Ontario or adults were admitted for one of eight categories of cardiac crisis in the Sudbury (Ontario) Region for the year 1984 supported the hypothesis. This factor, with which infant deaths and adult cardiac arrhythmias each shared about 40% of their variance, also shared about 40% of the variance with a factor with which about 35% of the variance in daily occurrence of geomagnetic pulsations (0.2 Hz to 5 Hz) was associated. These results are consistent with the important role of geomagnetic variables in the occurrence of transient electrical anomalies in brain function rather than cardiac blood flow. PMID:11453188

  5. Syncope as a Warning Symptom of Sudden Cardiac Death in Athletes.

    PubMed

    Vettor, Giulia; Zorzi, Alessandro; Basso, Cristina; Thiene, Gaetano; Corrado, Domenico

    2015-08-01

    Clinical evaluation of syncope in the athlete remains a challenge. Although benign mechanisms predominate, syncope may be arrhythmic and precede SCD. Exercise-induced syncope should be regarded as an important alarming symptom of an underlying cardiac disease predisposing to arrhythmic cardiac arrest. All athletes with syncope require a focused and detailed workup for underlying cardiac causes, either structural or electrical. Major aim is to identify athletes at risk and to protect them from SCD. Athletes with potentially life-threatening etiologies of syncope should be restricted from competitive sports. PMID:26115828

  6. Selective Blockade of Periostin Exon 17 Preserves Cardiac Performance in Acute Myocardial Infarction.

    PubMed

    Taniyama, Yoshiaki; Katsuragi, Naruto; Sanada, Fumihiro; Azuma, Junya; Iekushi, Kazuma; Koibuchi, Nobutaka; Okayama, Keita; Ikeda-Iwabu, Yuka; Muratsu, Jun; Otsu, Rei; Rakugi, Hiromi; Morishita, Ryuichi

    2016-02-01

    We previously reported that overexpression of full-length periostin, Pn-1, resulted in ventricular dilation with enhanced interstitial collagen deposition in a rat model. However, other reports have documented that the short-form splice variants Pn-2 (lacking exon 17) and Pn-4 (lacking exons 17 and 21) promoted cardiac repair by angiogenesis and prevented cardiac rupture after acute myocardial infarction. The apparently differing findings from those reports prompted us to use a neutralizing antibody to selectively inhibit Pn-1 by blockade of exon 17 in a rat acute myocardial infarction model. Administration of Pn neutralizing antibody resulted in a significant decrease in the infarcted and fibrotic areas of the myocardium, which prevented ventricular wall thinning and dilatation. The inhibition of fibrosis by Pn neutralizing antibody was associated with a significant decrease in gene expression of fibrotic markers, including collagen I, collagen III, and transforming growth factor-β1. Importantly, the number of α-smooth muscle actin-positive myofibroblasts was significantly reduced in the hearts of animals treated with Pn neutralizing antibody, whereas cardiomyocyte proliferation and angiogenesis were comparable in the IgG and neutralizing antibody groups. Moreover, the level of Pn-1 expression was significantly correlated with the severity of myocardial infarction. In addition, Pn-1, but not Pn-2 or Pn-4, inhibited fibroblast and myocyte attachment, which might account for the cell slippage observed during cardiac remodeling. Collectively, these results indicate that therapeutics that specifically inhibit Pn exon-17, via a neutralizing antibody or drug, without suppressing other periostin variants might offer a new class of medication for the treatment of acute myocardial infarction patients. PMID:26644236

  7. mTOR inhibition by everolimus in childhood acute lymphoblastic leukemia induces caspase-independent cell death.

    PubMed

    Baraz, Rana; Cisterne, Adam; Saunders, Philip O; Hewson, John; Thien, Marilyn; Weiss, Jocelyn; Basnett, Jordan; Bradstock, Kenneth F; Bendall, Linda J

    2014-01-01

    Increasingly, anti-cancer medications are being reported to induce cell death mechanisms other than apoptosis. Activating alternate death mechanisms introduces the potential to kill cells that have defects in their apoptotic machinery, as is commonly observed in cancer cells, including in hematological malignancies. We, and others, have previously reported that the mTOR inhibitor everolimus has pre-clinical efficacy and induces caspase-independent cell death in acute lymphoblastic leukemia cells. Furthermore, everolimus is currently in clinical trial for acute lymphoblastic leukemia. Here we characterize the death mechanism activated by everolimus in acute lymphoblastic leukemia cells. We find that cell death is caspase-independent and lacks the morphology associated with apoptosis. Although mitochondrial depolarization is an early event, permeabilization of the outer mitochondrial membrane only occurs after cell death has occurred. While morphological and biochemical evidence shows that autophagy is clearly present it is not responsible for the observed cell death. There are a number of features consistent with paraptosis including morphology, caspase-independence, and the requirement for new protein synthesis. However in contrast to some reports of paraptosis, the activation of JNK signaling was not required for everolimus-induced cell death. Overall in acute lymphoblastic leukemia cells everolimus induces a cell death that resembles paraptosis. PMID:25014496

  8. mTOR Inhibition by Everolimus in Childhood Acute Lymphoblastic Leukemia Induces Caspase-Independent Cell Death

    PubMed Central

    Baraz, Rana; Cisterne, Adam; Saunders, Philip O.; Hewson, John; Thien, Marilyn; Weiss, Jocelyn; Basnett, Jordan; Bradstock, Kenneth F.; Bendall, Linda J.

    2014-01-01

    Increasingly, anti-cancer medications are being reported to induce cell death mechanisms other than apoptosis. Activating alternate death mechanisms introduces the potential to kill cells that have defects in their apoptotic machinery, as is commonly observed in cancer cells, including in hematological malignancies. We, and others, have previously reported that the mTOR inhibitor everolimus has pre-clinical efficacy and induces caspase-independent cell death in acute lymphoblastic leukemia cells. Furthermore, everolimus is currently in clinical trial for acute lymphoblastic leukemia. Here we characterize the death mechanism activated by everolimus in acute lymphoblastic leukemia cells. We find that cell death is caspase-independent and lacks the morphology associated with apoptosis. Although mitochondrial depolarization is an early event, permeabilization of the outer mitochondrial membrane only occurs after cell death has occurred. While morphological and biochemical evidence shows that autophagy is clearly present it is not responsible for the observed cell death. There are a number of features consistent with paraptosis including morphology, caspase-independence, and the requirement for new protein synthesis. However in contrast to some reports of paraptosis, the activation of JNK signaling was not required for everolimus-induced cell death. Overall in acute lymphoblastic leukemia cells everolimus induces a cell death that resembles paraptosis. PMID:25014496

  9. Depression and Risk of Sudden Cardiac Death and Coronary Heart Disease in Women: Results from the Nurses’ Health Study

    PubMed Central

    Whang, William; Kubzansky, Laura D.; Kawachi, Ichiro; Rexrode, Kathryn M.; Kroenke, Candyce H.; Glynn, Robert J.; Garan, Hasan; Albert, Christine M.

    2008-01-01

    Objectives We assessed the association between depression and sudden cardiac death (SCD) and cardiac events among individuals without baseline coronary heart disease (CHD). Background Depression is a risk factor for cardiac events and mortality among those with CHD, possibly from arrhythmia. Methods We studied depressive symptoms, and a proxy variable for clinical depression consisting of severe symptoms and/or antidepressant medication use, and their relationship to cardiac events in the Nurses’ Health Study. Questionnaires in 1992, 1996, and 2000 assessed symptoms with the Mental Health Index (MHI-5), and antidepressant use was assessed in 1996 and 2000. Primary endpoints included SCD, fatal CHD, and non-fatal myocardial infarction (MI). Results Among 63,469 women without prior CHD/stroke in 1992, 7.9% had MHI-5 scores (<53) previously found to predict clinical depression. Depressive symptoms were associated with CHD events, and the relationship was strongest for fatal CHD, where the association remained significant even after controlling for CHD risk factors (HR=1.49; 95% CI 1.11–2.00 for MHI-5 score<53). In models from 1996 onward, our proxy variable for clinical depression was most associated with SCD in multivariable models (HR=2.33, 95% CI 1.47–3.70), and this risk was primarily due to a specific relationship between antidepressant use and SCD (HR=3.34, 95% CI 2.03–5.50). Conclusions In this cohort of women without baseline CHD, depressive symptoms were associated with fatal CHD, and a measure of clinical depression including antidepressant use was specifically associated with SCD. Although antidepressant use may be a marker of worse depression, its specific association with SCD merits further study. CONDENSED ABSTRACT We prospectively analyzed the association between depression and cardiac events in the Nurses’ Health Study. Symptoms of depression as measured by Mental Health Index (MHI-5) score were directly associated with risk of CHD events

  10. Serum and salivary cardiac analytes in acute myocardial infarction related to oral health status

    NASA Astrophysics Data System (ADS)

    Ebersole, Jeffrey L.; Kryscio, Richard J.; Campbell, Charles; Kinane, Denis F.; McDevitt, John T.; Christodoulides, Nicolaos; Floriano, Pierre N.; Miller, Craig S.

    2014-06-01

    With the advent of an increased emphasis on the potential to utilize biomarkers in saliva for systemic diseases, the issue of existing oral disease is an important consideration that could adversely affect the interpretation of diagnostic results obtained from saliva. We addressed the question does a patient's oral inflammation status confound biomarker levels used in diagnosis of acute myocardial infarction (AMI). The results demonstrated that multiple serum biomarkers and a few salivary biomarkers reflected the cardiac event. Importantly, oral health of the individual had minimal impact on the validity of the serum or salivary biomarker effectiveness.

  11. Predictors of Acute Renal Failure During Extracorporeal Membrane Oxygenation in Pediatric Patients After Cardiac Surgery.

    PubMed

    Lv, Lin; Long, Cun; Liu, Jinping; Hei, Feilong; Ji, Bingyang; Yu, Kun; Hu, Qiang; Hu, Jinxiao; Yuan, Yuan; Gao, Guodong

    2016-05-01

    Acute renal failure (ARF) is associated with increased mortality in pediatric extracorporeal membrane oxygenation (ECMO). The aim of this study was to identify predictors of ARF during ECMO in pediatric patients after cardiac surgery. A retrospective study analyzed 42 children (≤15 years) after cardiac surgery requiring venous-arterial ECMO between December 2008 and December 2014 at Fuwai Hospital. ARF was defined as ≥300% rise in serum creatinine (SCr) concentration from baseline or application of dialysis. Multivariate logistic regression was performed to identify the predictors of ARF during ECMO. A total of 42 children (age, interquartile range [IQR], 13.0 [7.2-29.8] months; weight, IQR, 8.5 [6.7-11.0] kg) after cardiac surgery requiring ECMO were included in this study. The total survival rate was 52.4%, and the incidence of ARF was 40.5%. As the result of univariate analysis, ECMO duration, cardiopulmonary resuscitation, maximum free hemoglobin (FHB) during ECMO, lactate level, and mean blood pressure before initiation of ECMO were entered in multiple logistic regression analysis. In multiple logistic regression analysis, FHB during ECMO (OR 1.136, 95% CI 1.023-1.261) and lactate level before initiation of ECMO (OR 1.602, 95% CI 1.025-2.502) were risk factors for ARF during ECMO after pediatric cardiac surgery. There was a linear correlation between maximum SCr and maximum FHB (Pearson's r = 0.535, P = 0.001). Maximum SCr during ECMO has also a linear correlation with lactate level before initiation of ECMO (Pearson's r = 0.342, P = 0.044). Increased FHB during ECMO and high lactate level before initiation of ECMO were risk factors for ARF during ECMO in pediatric patients after cardiac surgery. PMID:26636965

  12. Inherited arrhythmia syndromes leading to sudden cardiac death in the young: A global update and an Indian perspective

    PubMed Central

    Chockalingam, Priya; Wilde, Arthur A.

    2014-01-01

    Inherited primary arrhythmias, namely congenital long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia, account for a significant proportion of sudden cardiac deaths in young and apparently healthy individuals. Genetic testing plays an integral role in the diagnosis, risk-stratification and treatment of probands and family members. It is increasingly obvious that collaborative efforts are required to understand and manage these relatively rare but potentially lethal diseases. This article aims to update readers on the recent developments in our knowledge of inherited arrhythmias and to lay the foundation for a national synergistic effort to characterize them in the Indian population. PMID:24568830

  13. [Sudden death. Role of the electrophysiologic study].

    PubMed

    Colín Lizalde, Luis

    2002-01-01

    At present, sudden death is considered a major health problem, DeBoer in 1935, recognized the clinical importance of ventricular fibrillation as the cause of sudden cardiac death. Sudden death due to cardiovascular problems has been established as one of the main causes of death in the developed countries and in developing countries as ours, where the deaths caused by cardiovascular diseases represent 15% of the total, exceeding other causes of death. The frequency of sudden death in our country is unknown, but more frequently we hear about cases of patients that have been reanimated for cardiac arrest; in the United States of America the frequency has been estimated between 400,000 at 500,000 per year although, recently, 250,000 at 300,000 events are being mentioned. It is convenient to comment that the causal arrhythmias are diverse and may vary depending on the underlying disease, although, generally, it can be pointed out that 80% of them are due to tachyarrhythmias. It's important to point out that there is a strong relationship between left ventricular dysfunction, the frequency of ventricular arrhythmias, and fatal cardiac events due to cardiac rhythm disturbances. The recommendations for electrophysiological studies are: 1) patients surviving cardiac arrest, occurring without evidence of an acute Q-wave myocardial infarction and 2) patients surviving cardiac arrest occurring more than 48 hours after the acute phase of myocardial infarction in the absence of a recurrent ischemic event. PMID:12001869

  14. Effect of Left Ventricular Dysfunction and Viral Load on Risk of Sudden Cardiac Death In Patients with Human Immunodeficiency Virus

    PubMed Central

    Moyers, Brian S.; Secemsky, Eric A.; Vittinghoff, Eric; Wong, Joseph K.; Havlir, Diane V.; Hsue, Priscilla Y.; Tseng, Zian H.

    2014-01-01

    Human Immunodeficiency Virus-infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with human immunodeficiency virus (HIV) is unknown. We sought to determine the impact of LV on SCD in patients with HIV. We previously characterized all SCDs and AIDS deaths in 2860 consecutive patients in a public HIV clinic between 2000 and 2009. Transthoracic echocardiograms (TTEs) performed during the study period were identified. The effect of ejection fraction (EF), diastolic dysfunction, pulmonary artery pressure, and LV mass on SCD and acquired immune deficiency syndrome (AIDS) death were evaluated: 423 patients had at least one TTE; 13 SCDs and 55 AIDS deaths had at least one TTE. In the propensity-adjusted analysis, EF 30–39% and EF <30% predicted SCD (HR 9.5, 95% CI 1.7–53.3, p=0.01 and HR 38.5, 95% CI 7.6–195.0, p<0.001, respectively) but not AIDS death. Diastolic dysfunction also predicted SCD (HR 14.8, 95% CI 4.0–55.4, p<0.001) but not AIDS death, even after adjusting for EF. The association between EF<40% and SCD was greater in subjects with detectable vs. undetectable HIV-RNA (adjusted HR 11.7, 95% CI 2.9–47.2, p=0.001 vs. HR 2.7, 95% CI 0.3–27.6, p=0.41; p=0.07 for interaction). In conclusion, LV systolic and diastolic dysfunction predict SCD but not AIDS death in a large HIV cohort, with greater effect in those with detectable HIV RNA. Further investigation is needed to thoroughly evaluate the effect of low EF and HIV factors on SCD incidence and the potential benefit of implantable cardioverter-defibrillator therapy in this high-risk population. PMID:24521717

  15. Effect of left ventricular dysfunction and viral load on risk of sudden cardiac death in patients with human immunodeficiency virus.

    PubMed

    Moyers, Brian S; Secemsky, Eric A; Vittinghoff, Eric; Wong, Joseph K; Havlir, Diane V; Hsue, Priscilla Y; Tseng, Zian H

    2014-04-01

    Human immunodeficiency virus (HIV)-infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with HIV is unknown. We sought to determine the impact of LV dysfunction on SCD in patients with HIV. We previously characterized all SCDs and acquired immunodeficiency syndrome (AIDS) deaths in 2,860 consecutive patients in a public HIV clinic from 2000 to 2009. Transthoracic echocardiograms (TTEs) performed during the study period were identified. The effect of ejection fraction (EF), diastolic dysfunction, pulmonary artery pressure, and LV mass on SCD and AIDS death were evaluated: 423 patients had at least 1 TTE; 13 SCDs and 55 AIDS deaths had at least 1 TTE. In the propensity-adjusted analysis, EF 30% to 39% and EF<30% predicted SCD (hazard ratio [HR] 9.5, 95% confidence interval [CI] 1.7 to 53.3, p=0.01 and HR 38.5, 95% CI 7.6 to 195.0, p<0.001, respectively) but not AIDS death. Diastolic dysfunction also predicted SCD (HR 14.8, 95% CI 4.0 to 55.4, p<0.001) but not AIDS death, even after adjusting for EF. The association between EF<40% and SCD was greater in subjects with detectable versus undetectable HIV RNA (adjusted HR 11.7, 95% CI 2.9 to 47.2, p=0.001 vs HR 2.7, 95% CI 0.3 to 27.6, p=0.41; p=0.07 for interaction). In conclusion, LV systolic dysfunction and diastolic dysfunction predict SCD but not AIDS death in a large HIV cohort, with greater effect in those with detectable HIV RNA. Further investigation is needed to thoroughly evaluate the effect of low EF and HIV factors on SCD incidence and the potential benefit of implantable cardioverter-defibrillator therapy in this high-risk population. PMID:24521717

  16. Reduction of Cardiac Cell Death after Helium Postconditioning in Rats: Transcriptional Analysis of Cell Death and Survival Pathways

    PubMed Central

    Oei, Gezina TML; Heger, Michal; van Golen, Rowan F; Alles, Lindy K; Flick, Moritz; van der Wal, Allard C; van Gulik, Thomas M; Hollmann, Markus W; Preckel, Benedikt; Weber, Nina C

    2014-01-01

    Helium, a noble gas, has been used safely in humans. In animal models of regional myocardial ischemia/reperfusion (I/R) it was shown that helium conditioning reduces infarct size. Currently, it is not known how helium exerts its cytoprotective effects and which cell death/survival pathways are affected. The objective of this study, therefore, was to investigate the cell protective effects of helium postconditioning by PCR array analysis of genes involved in necrosis, apoptosis and autophagy. Male rats were subjected to 25 min of ischemia and 5, 15 or 30 min of reperfusion. Semiquantitative histological analysis revealed that 15 min of helium postconditioning reduced the extent of I/R-induced cell damage. This effect was not observed after 5 and 30 min of helium postconditioning. Analysis of the differential expression of genes showed that 15 min of helium postconditioning mainly caused upregulation of genes involved in autophagy and inhibition of apoptosis versus I/R alone. The results suggest that the cytoprotective effects of helium inhalation may be caused by a switch from pro-cell-death signaling to activation of cell survival mechanisms, which appears to affect a wide range of pathways. PMID:25171109

  17. [Cardiac Angiosarcoma with Acute Myocardial Infarction due to Tumor Embolism;Report of a Case].

    PubMed

    Date, Yusuke; Miyazu, Katsuyuki; Ikeda, Masahiro

    2016-09-01

    We report the case of a 28-year-old man with a rare angiosarcoma complicated by acute myocardial infarction secondary to tumor embolism. He was transported to our emergency unit because of sudden onset of chest pain. The echocardiography showed a 42×60 mm mass in the left ventricle, and the coronary angiography showed embolic occlusion of the proximal left anterior descending and circumflex arteries. Emergent surgical removal of the mass was attempted under cardiopulmonary bypass, concomitant with double coronary artery bypass grafting and mitral valve replacement with a mechanical prosthesis. However, complete tumor excision was impossible. The postoperative pathological examination revealed undifferentiated angiosarcoma. Twenty days after the operation, the patient suffered acute cerebral hemorrhage from a metastatic tumor in the brain. He died at 37 days after the initial cardiac surgery. PMID:27586319

  18. Notes from the field: update on Lyme carditis, groups at high risk, and frequency of associated sudden cardiac death--United States.

    PubMed

    Forrester, Joseph D; Meiman, Jonathan; Mullins, Jocelyn; Nelson, Randall; Ertel, Starr-Hope; Cartter, Matt; Brown, Catherine M; Lijewski, Virginia; Schiffman, Elizabeth; Neitzel, David; Daly, Elizabeth R; Mathewson, Abigail A; Howe, Whitney; Lowe, Lindsay A; Kratz, Natalie R; Semple, Shereen; Backenson, P Bryon; White, Jennifer L; Kurpiel, Phillip M; Rockwell, Russell; Waller, Kirsten; Johnson, Diep Hoang; Steward, Christopher; Batten, Brigid; Blau, Dianna; DeLeon-Carnes, Marlene; Drew, Clifton; Muehlenbachs, Atis; Ritter, Jana; Sanders, Jeanine; Zaki, Sherif R; Molins, Claudia; Schriefer, Martin; Perea, Anna; Kugeler, Kiersten; Nelson, Christina; Hinckley, Alison; Mead, Paul

    2014-10-31

    On December 13, 2013, MMWR published a report describing three cases of sudden cardiac death associated with Lyme carditis. State public health departments and CDC conducted a follow-up investigation to determine 1) whether carditis was disproportionately common among certain demographic groups of patients diagnosed with Lyme disease, 2) the frequency of death among patients diagnosed with Lyme disease and Lyme carditis, and 3) whether any additional deaths potentially attributable to Lyme carditis could be identified. Lyme disease cases are reported to CDC through the Nationally Notifiable Disease Surveillance System; reporting of clinical features, including Lyme carditis, is optional. For surveillance purposes, Lyme carditis is defined as acute second-degree or third-degree atrioventricular conduction block accompanying a diagnosis of Lyme disease. During 2001-2010, a total of 256,373 Lyme disease case reports were submitted to CDC, of which 174,385 (68%) included clinical information. Among these, 1,876 (1.1%) were identified as cases of Lyme carditis. Median age of patients with Lyme carditis was 43 years (range = 1-99 years); 1,209 (65%) of the patients were male, which is disproportionately larger than the male proportion among patients with other clinical manifestations (p<0.001). Of cases with this information available, 69% were diagnosed during the months of June-August, and 42% patients had an accompanying erythema migrans, a characteristic rash. Relative to patients aged 55-59 years, carditis was more common among men aged 20-39 years, women aged 25-29 years, and persons aged ≥75 years. PMID:25356607

  19. Cell Cycle-Dependent Mechanisms Underlie Vincristine-Induced Death of Primary Acute Lymphoblastic Leukemia Cells.

    PubMed

    Kothari, Anisha; Hittelman, Walter N; Chambers, Timothy C

    2016-06-15

    Microtubule-targeting agents (MTA), such as the taxanes and vinca alkaloids, are used to treat a variety of cancers due to their ability to perturb microtubule dynamics. In cell culture, MTAs exert their anticancer effects primarily by causing mitotic arrest and cell death. However, accumulating indirect evidence suggests that MTAs may exert their cytotoxicity in human tumors by interfering with interphase microtubules. In this study, we sought to develop and characterize an experimental system in which to test the hypothesis that MTAs induce cell death during interphase. Primary adult acute lymphoblastic leukemia (ALL) cells treated with vincristine only weakly exhibited colocalization between mitotic and apoptotic markers and major characteristics of mitotic death, such as an increase in cells with 4N DNA content before the appearance of cells with <2N DNA content, suggesting a mixed response. Therefore, we separated ALL cells into distinct phases of the cell cycle by centrifugal elutriation, labeled cells with 5-ethynyl-2'-deoxyuridine (EdU), and then treated each population with vincristine. Cells isolated during G1 underwent cell death without evidence of EdU uptake, indicating that the cytotoxic effects of vincristine took place during G1 Conversely, cells isolated during S or G2-M phases underwent death following mitotic arrest. Thus, vincristine induces distinct death programs in primary ALL cells depending on cell-cycle phase, and cells in G1 are particularly susceptible to perturbation of interphase microtubules. Primary ALL cells may therefore provide a powerful model system in which to study the multimodal mechanisms underlying MTA-induced cell death. Cancer Res; 76(12); 3553-61. ©2016 AACR. PMID:27197148

  20. QT prolongation and sudden cardiac death in patients with alcoholic liver disease

    SciTech Connect

    Day, C.P.; James, O.F.W. . Dept. of Medicine); Butler, T.J. . Dept. of Medical Statistics); Campbell, R.W.F. . Dept. of Academic Cardiology)

    1993-06-05

    Cardiovascular death is the most important cause of mortality in alcoholics, yet alcohol may protect against ischemic heart disease. This could be explained if deaths were a consequence of alcohol-related arrhythmias rather than of coronary atheroma. In many conditions, abnormalities of the QT interval are markers of arrhythmia and for risk of sudden death. The authors examined the relation between QT intervals and mortality in patients with alcoholic liver disease.

  1. Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction.

    PubMed

    Maas, U; Strubelt, S

    2006-01-01

    Ibogaine is the most important alkaloid of the Central African Iboga-shrub. It is the central drug in Gabonian initiation ceremonies in which it is used to cause a near-death experience. In Western countries it is used in private clinics to treat addiction. However, in the United States and most European countries it is classified as an illegal drug because at least eight persons have died after having taken Ibogaine. These fatalities occurred in most cases several days after ingestion or following the intake of very small doses. There is no conclusive explanation at the present time for these deaths. We hypothesize, that these deaths may be a result of cardiac arrhythmias, caused by a dysregulation of the autonomic nervous system. Ibogaine affects the autonomic nervous system by influencing several neurotransmitter-systems and the fastigial nucleus. The cerebellar nucleus responds to small doses with a stimulation of the sympathetic system, leading to a fight or flight reaction. High doses, however, lead to a vagal dominance: a "feigned death". The risk of cardiac arrhythmias is increased in situations of sympathetic stimulation or coincidence of a high parasympathetic tonus and a left-sided sympathetic stimulation. This could occur under influence of small doses of ibogaine and also at times of exhaustion with a high vagal tonus, when sudden fear reactions could cause a critical left-sided sympathetic stimulation. Gabonian healers prevent these risks by isolating their patients from normal life and by inducing a trance-state with right-hemispheric and vagal dominance for several days. PMID:16698188

  2. Incidence of sudden cardiac death in Germany: results from an emergency medical service registry in Lower Saxony

    PubMed Central

    Martens, Eimo; Sinner, Moritz F.; Siebermair, Johannes; Raufhake, Carsten; Beckmann, Britt M.; Veith, Stefan; Düvel, Dieter; Steinbeck, Gerhard; Kääb, Stefan

    2014-01-01

    Aims Sudden cardiac death (SCD) is among the most common causes of death in western countries including Germany. Whereas risk stratification and primary prevention is still insufficient, we also lack accurate incidence estimates. Current estimates vary widely (18.6–128/100 000/year), but data on SCD incidence in Germany are missing. Depending on SCD definitions, death needs to occur between 1 and 24 h after the onset of symptoms. Methods and results In the district of Aurich (190 000 inhabitants, Lower Saxony, Germany), emergency medical service (EMS) is provided by a district government operated single carrier and two hospitals. To evaluate all EMS calls in this district from 2002 to 2009, we obtained EMS protocols, medical records, and death certificates for data analysis and adjudication of SCD. We defined SCD according to the definition of the World Health Organization, considering patients with cardiac arrest within ≤1 h after the onset of symptoms. We also required cardiopulmonary resuscitation being performed by EMS personnel. The overall mortality rate in the district of Aurich (1060/100 000/year) corresponded well with the average mortality rate in Germany (1030/100 000/year). During the observation period, we adjudicated 1212 SCD cases, equivalent to an annual rate of 151 SCD cases (81 cases/100 000/year). Rates remained remarkably stable over time, and affected a considerable number of individuals of working age (32/100 000/year). Conclusion Consistent with prior reports, the SCD incidence in a district of Germany is substantial. Despite an elaborate EMS system and advanced medical care, SCD rates remain stable and necessitate improved, individualized risk stratification. PMID:25061228

  3. Stress testing for risk stratification of patients with low to moderate probability of acute cardiac ischemia.

    PubMed

    Chandra, A; Rudraiah, L; Zalenski, R J

    2001-02-01

    In summary, this article focused on the use of stress testing to risk-stratify patients at the conclusion of their emergency evaluation for ACI. As discussed, those patients in the probably not ACI category require additional risk stratification prior to discharge. It should be kept in mind that patients in this category are heterogeneous, containing subgroups at both higher and lower risk of ACI and cardiac events. The patients with lower pretest probability for ACI may only need exercise testing in the ED. Patients with higher pretest probability should undergo myocardial perfusion or echocardiographic stress testing to maximize diagnostic and prognostic information. Prognostic information is the key to provocative testing in the ED. Prognostic information is the component that will help emergency physicians identify the patients who may be discharged home safely without having to worry about a 6% annual cardiac death rate and a 10% overall death rate over the next 30 months. Stress testing provides this key prognostic data, and it can be obtained in short-stay chest pain observation units in a safe, timely, and cost-effective fashion. PMID:11214405

  4. Impact of cardiac magnet resonance imaging on management of ventricular septal rupture after acute myocardial infarction

    PubMed Central

    Gassenmaier, Tobias; Gorski, Armin; Aleksic, Ivan; Deubner, Nikolas; Weidemann, Frank; Beer, Meinrad

    2013-01-01

    A 74-year-old man was admitted to the cardiac catheterization laboratory with acute myocardial infarction. After successful angioplasty and stent implantation into the right coronary artery, he developed cardiogenic shock the following day. Echocardiography showed ventricular septal rupture. Cardiac magnet resonance imaging (MRI) was performed on the critically ill patient and provided detailed information on size and localization of the ruptured septum by the use of fast MRI sequences. Moreover, the MRI revealed that the ventricular septal rupture was within the myocardial infarction area, which was substantially larger than the rupture. As the patient’s condition worsened, he was intubated and had intra-aortic balloon pump implanted, and extracorporeal membrane oxygenation was initiated. During the following days, the patient’s situation improved, and surgical correction of the ventricular septal defect could successfully be performed. To the best of our knowledge, this case report is the first description of postinfarction ventricular septal rupture by the use of cardiac MRI in an intensive care patient with cardiogenic shock and subsequent successful surgical repair. PMID:23710303

  5. Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery

    PubMed Central

    Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A.; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2016-01-01

    Abstract Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a

  6. Cardiac Autonomic Effects of Acute Exposures to Airborne Particulates in Men and Women

    NASA Technical Reports Server (NTRS)

    Howarth, M. S.; Schlegel, T. T.; Knapp, C. F.; Patwardhan, A. R.; Jenkins, R. A.; Ilgner, R. H.; Evans, J. M.

    2007-01-01

    The aim of this research was to investigate cardiac autonomic changes associated with acute exposures to airborne particulates. Methods: High fidelity 12-lead ECG (CardioSoft, Houston, TX) was acquired from 19 (10 male / 9 female) non-smoking volunteers (age 33.6 +/- 6.6 yrs) during 10 minutes pre-exposure, exposure and post-exposure to environmental tobacco smoke (ETS), cooking oil fumes, wood smoke and sham (water vapor). To control exposure levels, noise, subject activity, and temperature, all studies were conducted inside an environmental chamber. Results: The short-term fractal scaling exponent (Alpha-1) and the ratio of low frequency to high frequency Heart Rate Variability (HRV) powers (LF/HF, a purported sympathetic index) were both higher in males (p<0.017 and p<0.05, respectively) whereas approximate entropy (ApEn) and HF/(LF+HF) (a purported parasympathetic index) were both lower in males (p<0.036, and p<0.044, respectively). Compared to pre-exposure (p<0.0002) and sham exposure (p<0.047), male heart rates were elevated during early ETS post-exposure. Our data suggest that, in addition to tonic HRV gender differences, cardiac responses to some acute airborne particulates are gender related.

  7. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    SciTech Connect

    Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  8. Acute effects of intravenous dronedarone on electrocardiograms, hemodynamics and cardiac functions in anesthetized dogs

    PubMed Central

    SAENGKLUB, Nakkawee; LIMPRASUTR, Vudhiporn; SAWANGKOON, Suwanakiet; BURANAKARL, Chollada; HAMLIN, Robert L.; KIJTAWORNRAT, Anusak

    2015-01-01

    Dronedarone is a class III antiarrhythmic that has been used for management of atrial fibrillation in humans, but limited information was found in dogs. The objective of this study was to determine the acute effects of escalating concentrations of dronedarone on electrocardiograms (ECG), hemodynamics and cardiac mechanics in healthy dogs. A total of 7 beagle dogs were anesthetized with isoflurane and instrumented to obtain lead II ECG, pressures at ascending aorta, right atrium, pulmonary artery and left ventricle, and left ventricular pressure-volume relationship. Five dogs were given vehicle and followed by escalating doses of dronedarone (0.5, 1.0 and 2.5 mg/kg, 15 min for each dose), and two dogs were used as a vehicle-treated control. All parameters were measured at 15 min after the end of each dose. The results showed that all parameters in vehicle-treated dogs were unaltered. Dronedarone at 2.5 mg/kg significantly lengthened PQ interval (P<0.01), reduced cardiac output (P<0.01) and increased systemic vascular resistance (P<0.01). Dronedarone produced negative inotropy assessed by significantly lowered end-systolic pressure-volume relationship, preload recruitable stroke work, contractility index and dP/dtmax. It also impaired diastolic function by significantly increased end-diastolic pressure-volume relationship, tau and dP/dtmin. These results suggested that acute effects of dronedarone produced negative dromotropy, inotropy and lusitropy in anesthetized dogs. Care should be taken when given dronedarone to dogs, especially when the patients have impaired cardiac function. PMID:26346474

  9. Acute effects of intravenous dronedarone on electrocardiograms, hemodynamics and cardiac functions in anesthetized dogs.

    PubMed

    Saengklub, Nakkawee; Limprasutr, Vudhiporn; Sawangkoon, Suwanakiet; Buranakarl, Chollada; Hamlin, Robert L; Kijtawornrat, Anusak

    2016-03-01

    Dronedarone is a class III antiarrhythmic that has been used for management of atrial fibrillation in humans, but limited information was found in dogs. The objective of this study was to determine the acute effects of escalating concentrations of dronedarone on electrocardiograms (ECG), hemodynamics and cardiac mechanics in healthy dogs. A total of 7 beagle dogs were anesthetized with isoflurane and instrumented to obtain lead II ECG, pressures at ascending aorta, right atrium, pulmonary artery and left ventricle, and left ventricular pressure-volume relationship. Five dogs were given vehicle and followed by escalating doses of dronedarone (0.5, 1.0 and 2.5 mg/kg, 15 min for each dose), and two dogs were used as a vehicle-treated control. All parameters were measured at 15 min after the end of each dose. The results showed that all parameters in vehicle-treated dogs were unaltered. Dronedarone at 2.5 mg/kg significantly lengthened PQ interval (P<0.01), reduced cardiac output (P<0.01) and increased systemic vascular resistance (P<0.01). Dronedarone produced negative inotropy assessed by significantly lowered end-systolic pressure-volume relationship, preload recruitable stroke work, contractility index and dP/dtmax. It also impaired diastolic function by significantly increased end-diastolic pressure-volume relationship, tau and dP/dtmin. These results suggested that acute effects of dronedarone produced negative dromotropy, inotropy and lusitropy in anesthetized dogs. Care should be taken when given dronedarone to dogs, especially when the patients have impaired cardiac function. PMID:26346474

  10. Death from undetected acute myocardial infarction secondary to coronary artery dissection after blunt thoracic trauma.

    PubMed

    Puanglumyai, Supot; Thamtakerngkit, Somboon; Lekawanvijit, Suree

    2016-01-01

    Blunt thoracic trauma is a common occurrence in automobile accidents. Acute myocardial infarction (AMI) caused by coronary dissection following blunt thoracic trauma is rare. We report a case of healthy 24-year-old man with a history of blunt thoracic injury with subsequent undetected AMI who died of acute decompensated heart failure 4 days after the insult. The autopsy findings showed a 90% luminal narrowing of the left anterior descending coronary artery by dissecting hematoma, 3 cm in length. The myocardium revealed transmural myocardial infarction affecting apex, most part of left ventricular free wall, and interventricular septum. Both lungs were heavy, wet, and noncrepitant. Histological findings of the infarcted myocardium were consistent with 3-5 days post-AMI. Sections from both lungs revealed massive pulmonary edema, reflecting acute decompensated heart failure following a large AMI secondary to coronary dissection. Blunt thoracic trauma may obscure typical chest pain associated with cardiac ischemia especially in cases with a high tolerance for pain. PMID:26454807

  11. Brugada syndrome and right ventricle morphofunctional abnormalities on echocardiography in young male with family anamnesis of sudden cardiac death.

    PubMed

    Steiner, Robert; Makarovic, Sandra; Makarovic, Zorin; Bilic-Curcic, Ines

    2014-03-01

    First presented by Brugada and Brugada in 1992, Brugada Syndrome (BrS) is a primary electrical disease of the heart that causes sudden cardiac death or life-threatening ventricular arrhythmias. This disease is hereditary autosomic dominant transmitted and genetically determined. The syndrome has been linked to mutations in SCN5A, the gene encoding for the a-subunit of the sodium channel. Electrocardiogram (ECG) abnormalities indicating Brugada syndrome, include repolarization and depolarization abnormalities in the absence of identifiable structural cardiac abnormalities or other conditions or agents known to lead to ST-segment elevation in the right precordial leads (V1-V3). Intravenous administration of sodium channel blocking drugs may modify the ECG pattern. Ajmaline, flecainide, procainamide and propafenone exaggerate the ST-segment elevation or unmask it when it is initially absent. An implantable cardioverter-defibrillator (ICD) is the only proven effective device treatment for the disease. Although BrS is primary electrical disease, some authors have suggested the presence of morphological and functional abnormalities mainly located in the right ventricle (RV), notably in the outflow tract (RVOT). In this short report we will present a young male, with predisposition and positive family history of sudden cardiac death, with complete diagnostic procedure including propafenon testing unmasking Brugada syndrome. An echosonography revealed dilated apical right ventricle, suggesting BrS is not only electrical disorder, but may include morphofunctional abnormalities, described in previous reports. In addition, we reviewed the possible connection between Brugada syndrome and morphological abnormalities in RV. PMID:24851643

  12. Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes

    PubMed Central

    Zorzi, Alessandro; Perazzolo Marra, Martina; Rigato, Ilaria; De Lazzari, Manuel; Susana, Angela; Niero, Alice; Pilichou, Kalliopi; Migliore, Federico; Rizzo, Stefania; Giorgi, Benedetta; De Conti, Giorgio; Sarto, Patrizio; Serratosa, Luis; Patrizi, Giampiero; De Maria, Elia; Pelliccia, Antonio; Basso, Cristina; Schiavon, Maurizio; Bauce, Barbara; Iliceto, Sabino; Thiene, Gaetano

    2016-01-01

    Background— The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated. Methods and Results— We compared 35 athletes (80% men, age: 14–48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. Conclusions— Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography. PMID:27390211

  13. Degree Of Diminution In Vagal-Cardiac Activity Predicts Sudden Death In Familial Dysautonomia When Resting Tachycardia Is Absent

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Marthol, H.; Bucchner, S.; Tutaj, M.; Berlin, D.; Axelrod, F. B.; Hilz, M. J.

    2004-01-01

    Patients with familial dysautonomia (FD) have an increased risk of sudden death, but sensitive and specific predictors of sudden death in FD are lacking. Methods. We recorded 10-min resting high-fidelity 12-lead ECGs in 14 FD patients and in 14 age/gender-matched healthy subjects and studied 25+ different heart rate variability (HRV) indices for their ability to predict sudden death in the FD patients. Indices studied included those from 4 "nonlinear" HRV techniques (detrended fluctuation analysis, approximate entropy, correlation dimension, and PoincarC analyses). The predictive value of PR, QRS, QTc and JTc intervals, QT dispersion (QTd), beat-to-beat QT and PR interval variability indices (QTVI and PRVI) and 12- lead high frequency QRS ECG (150-250 Hz) were also studied. FD patients and controls (C) differed (Pless than 0.0l) with respect to 20+ of the HRV indices (FD less than C) and with respect to QTVI and PRVI (FDBC) and HF QRS- related root mean squared voltages (FDBC) and reduced amplitude zone counts (FD less than C). They differed less with respect to PR intervals (FD less than C) and JTc intervals (FD greater than C) (P less than 0.05 for both) and did not differ at all with respect to QRS and QTc intervals and to QTd. Within 12 months after study, 2 of the 14 patients succumbed to sudden cardiac arrest. The best predictor of sudden death was the degree of diminution in HRV vagal-cardiac (parasympathetic) parameters such as RMSSD, the SDl of Poincare plots, and HF spectral power. Excluding the two FD patients who had resting tachycardia (HR greater than 100, which confounds traditional HRV analyses), the following criteria were independently 100% sensitive and 100% specific for predicting sudden death in the remaining 12 FD patients during spontaneous breathing: RMSSD less than 13 ms and/or PoincarC SD1 less than 9 ms. In FD patients without supine tachycardia, the degree of diminution in parasympathetic HRV parameters (by high-fidelity ECG) predicts

  14. The impact of cardiac and noncardiac comorbidities on the short-term outcomes of patients hospitalized with acute myocardial infarction: a population-based perspective

    PubMed Central

    Chen, Han-Yang; Saczynski, Jane S; McManus, David D; Lessard, Darleen; Yarzebski, Jorge; Lapane, Kate L; Gore, Joel M; Goldberg, Robert J

    2013-01-01

    Objectives The objectives of our large observational study were to describe the prevalence of cardiac and noncardiac comorbidities in a community-based population of patients hospitalized with acute myocardial infarction (AMI) at all medical centers in central Massachusetts, and to examine whether multiple comorbidities were associated with in-hospital death rates and hospital length of stay. Methods The study sample consisted of 2,972 patients hospitalized with AMI at all eleven greater Worcester medical centers in central Massachusetts during the three study years of 2003, 2005, and 2007. Results The average age of this hospitalized population was 71 years, 55% were men, 93% were Caucasian, and approximately one third had developed an ST segment elevation AMI during the years under study. Hypertension (75%) was the most common cardiac condition identified in patients hospitalized with AMI whereas renal disease (22%) was the most common noncardiac comorbidity diagnosed in this study population. Approximately one in every four hospitalized patients had any four or more of the seven cardiac conditions examined, while one in 13 had any three or more of the five noncardiac conditions studied. Patients with four or more cardiac comorbidities were more than twice as likely to have died during hospitalization and have a prolonged hospital length of stay, compared to those without any cardiac comorbidities. Patients with three or more noncardiac comorbidities had markedly increased odds of dying during hospitalization and having a prolonged hospital stay compared to those with no noncardiac comorbidities previously diagnosed. Conclusion Our findings highlight the need for additional contemporary data to improve the short-term outcomes of patients hospitalized with AMI and multiple concurrent medical illnesses. PMID:24235847

  15. Vasopressin, renin, and cortisol responses to hemorrhage during acute blockade of cardiac nerves in conscious dogs

    NASA Technical Reports Server (NTRS)

    O'Donnell, C. P.; Keil, L. C.; Thrasher, T. N.

    1993-01-01

    The effect of acute cardiac nerve blockade (CNB) on the increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol in response to a 30 ml/kg hemorrhage was determined in conscious dogs (n = 9). Procaine was infused into the pericardial space to produce acute reversible CNB, or saline was infused in the control hemorrhage. Blood was removed from the inferior vena cava at a rate of 1 ml.kg-1.min-1. In the control hemorrhage, plasma AVP increased from 1.8 +/- 0.3 to 219 +/- 66 pg/ml, PRA increased from 0.63 +/- 0.20 to 3.08 +/- 0.91 ng angiotensin I (ANG I).ml-1.3 h-1, and cortisol increased from 1.4 +/- 0.2 to 4.0 +/- 0.7 micrograms/dl. When the hemorrhage was repeated during acute CNB, plasma AVP increased from 2.8 +/- 1.6 to 185 +/- 59 pg/ml, PRA increased from 0.44 +/- 0.14 to 2.24 +/- 0.27 ng ANG I.ml-1.3 h-1, and cortisol increased from 1.9 +/- 0.3 to 5.4 +/- 0.6 micrograms/dl, and none of the increases differed significantly from the responses during the control hemorrhage. Left atrial pressure fell significantly after removal of 6 ml/kg of blood, but mean arterial pressure was maintained at control levels until blood loss reached 20 ml/kg during pericardial infusion of either saline or procaine. The declines in MAP at the 30 ml/kg level of hemorrhage in both treatments were similar. These results demonstrate that acutely blocking input from cardiac receptors does not reduce the increases in plasma AVP, cortisol, and PRA in response to a 30 ml/kg hemorrhage. The results of this study do not support the hypothesis that input from cardiac receptors is required for a normal AVP response to hemorrhage and suggest that other receptors, presumably arterial baroreceptors, can stimulate AVP and cortisol secretion in the absence of signals from the heart.

  16. A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature

    PubMed Central

    Ravikumar, Sandhya; Poysophon, Poysophon; Poblete, Roy; Kim-Tenser, May

    2016-01-01

    We describe a case report of fulminant Guillain–Barré syndrome (GBS) mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy, a subtype of GBS, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler (TCD) ultrasound showed appropriate blood flow to the brain. GBS rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and TCDs when uncertainty exists about the reliability of the clinical exam. PMID:27199887

  17. Attenuation of cisplatin-induced acute renal failure is associated with less apoptotic cell death.

    PubMed

    Zhou, H; Miyaji, T; Kato, A; Fujigaki, Y; Sano, K; Hishida, A

    1999-12-01

    To clarify the pathophysiologic role of apoptosis in acute renal failure (ARF), we examined whether the attenuation of cisplatin-induced ARF is associated with the change in the degree of apoptotic cell death. The administration of cisplatin (CDDP) (6 mg/kg body weight) in rats induced ARF at day 5, as manifested by a significant increase in serum creatinine (Scr) and tubular damage. CDDP-induced apoptotic cell death was confirmed by electron microscopic examination, agarose gel electrophoresis, and increased cells positive for TaT-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) in the outer medulla of the kidney. Treatment with dimethylthiourea (DMTU)--a scavenger of hydroxyl radicals--or glycine abrogated CDDP-induced increases in Scr, the tubular damage score, and the number of TUNEL-positive cells. Pretreatment with uranyl acetate (UA) induced a significant expression of Bcl-2 in the kidney and ameliorated CDDP-induced increases in Scr, the tubular damage score, and TUNEL-positive cells in the outer stripe of the outer medulla. Our findings indicate (1) that the attenuation of CDDP-induced ARF was associated with less apoptotic cell death and (2) that the induction of the anti-apoptotic protein Bcl-2 attenuated apoptosis and tubular damage. Our results suggest that apoptotic cell death may play an important role in the development of cisplatin-induced ARF. PMID:10595794

  18. Association of Acute Interstitial Nephritis With Programmed Cell Death 1 Inhibitor Therapy in Lung Cancer Patients.

    PubMed

    Shirali, Anushree C; Perazella, Mark A; Gettinger, Scott

    2016-08-01

    Immune checkpoint inhibitors that target the programmed death 1 (PD-1) signaling pathway have recently been approved for use in advanced pretreated non-small cell lung cancer and melanoma. Clinical trial data suggest that these drugs may have adverse effects on the kidney, but these effects have not been well described. We present 6 cases of acute kidney injury in patients with lung cancer who received anti-PD-1 antibodies, with each case displaying evidence of acute interstitial nephritis (AIN) on kidney biopsy. All patients were also treated with other drugs (proton pump inhibitors and nonsteroidal anti-inflammatory drugs) linked to AIN, but in most cases, use of these drugs long preceded PD-1 inhibitor therapy. The association of AIN with these drugs in our patients raises the possibility that PD-1 inhibitor therapy may release suppression of T-cell immunity that normally permits renal tolerance of drugs known to be associated with AIN. PMID:27113507

  19. Greater Volume of Acute Normovolemic Hemodilution May Aid in Reducing Blood Transfusions After Cardiac Surgery

    PubMed Central

    Goldberg, Joshua; Paugh, Paugh; Dickinson, Timothy A.; Fuller, John; Paone, Gaetano; Theurer, Patty F.; Shann, Kenneth G.; Sundt, Thoralf M.; Prager, Richard L.; Likosky, Donald S.

    2016-01-01

    Background Perioperative red blood cell transfusions (RBC) are associated with increased morbidity and mortality after cardiac surgery. Acute normovolemic hemodilution (ANH) is recommended to reduce perioperative transfusions; however, supporting data are limited and conflicting. We describe the relationship between ANH and RBC transfusions after cardiac surgery using a multi-center registry. Methods We analyzed 13,534 patients undergoing cardiac surgery between 2010 and 2014 at any of the 26 hospitals participating in a prospective cardiovascular perfusion database. The volume of ANH (no ANH, <400mL, 400–799mL, ≥800mL) was recorded and linked to each center’s surgical data. We report adjusted relative risks reflecting the association between the use and amount of ANH and the risk of perioperative RBC transfusion. Results were adjusted for preoperative risk factors, procedure, BSA, preoperative HCT, and center. Results ANH was used in 17% of the patients. ANH was associated with a reduction in RBC transfusions (RRadj 0.74, p <0.001). Patients having ≥800mL of ANH had the most profound reduction in RBC transfusions (RRadj 0.57, p<0.001). Platelet and plasma transfusions were also significantly lower with ANH. The ANH population had superior postoperative morbidity and mortality compared to the no ANH population. Conclusions There is a significant association between ANH and reduced perioperative RBC transfusion in cardiac surgery. Transfusion reduction is most profound with larger volumes of ANH. Our findings suggest the volume of ANH, rather than just its use, may be an important feature of a center’s blood conservation strategy. PMID:26206721

  20. Treatment-related deaths in second complete remission in childhood acute myeloid leukaemia.

    PubMed

    Molgaard-Hansen, Lene; Möttönen, Merja; Glosli, Heidi; Jónmundsson, Guðmundur K; Abrahamsson, Jonas; Hasle, Henrik

    2011-03-01

    The frequency and causes of treatment-related deaths (TRD) in second complete remission (CR2) in acute myeloid leukaemia (AML) were investigated in a historical, prospective cohort study of 429 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-88 and -93 trials. Relapse occurred in 158 children (39%). Seventeen (18%) of the 96 patients entering CR2 suffered TRD. The main causes were infection (59%) and complications from graft-versus-host disease (22%). Fourteen (82%) of 17 TRDs occurred in children undergoing haematopoietic stem cell transplantations (HSCT). Optimal supportive care after HSCT is essential, and studies on risk factors for TRD are needed. PMID:21241281

  1. Electrocardiographic Screening for Prolonged QT Interval to Reduce Sudden Cardiac Death in Psychiatric Patients: A Cost-Effectiveness Analysis

    PubMed Central

    Blondon, Marc; Gex-Fabry, Marianne; Combescure, Christophe; Shah, Dipen; Schwartz, Peter J.; Besson, Marie; Girardin, François R.

    2015-01-01

    Importance Sudden cardiac death is a leading cause of mortality in psychiatric patients. Long QT (LQT) is common in this population and predisposes to Torsades-de-Pointes (TdP) and subsequent mortality. Objective To estimate the cost-effectiveness of electrocardiographic screening to detect LQT in psychiatric inpatients. Design, Setting, and Participants We built a decision analytic model based on a decision tree to evaluate the cost-effectiveness and utility of LQT screening from a health care perspective. LQT proportion parameters were derived from an in-hospital cross-sectional study. We performed experts' elicitation to estimate the risk of TdP, given extent of QT prolongation. A TdP reduction of 65% after LQT detection was based on positive drug dechallenge rate and through adequate treatment and electrolyte adjustments. The base-case model uncertainty was assessed with one-way and probabilistic sensitivity analyses. Finally, the TdP related mortality and TdP avoidance parameters were varied in a two-way sensitivity analysis to assess their effect on the Incremental Cost-Effectiveness Ratio (ICER). Main Outcomes and Measures Costs, Quality Ajusted Life Year (QALY), ICER, and probability of cost effectiveness thresholds ($ 10 000, $25 000, and $50 000 per QALY). Results In the base-case scenario, the numbers of patients needed to screen were 1128 and 2817 to avoid one TdP and one death, respectively. The ICER of systematic ECG screening was $8644 (95%CI, 3144-82 498) per QALY. The probability of cost-effectiveness was 96% at a willingness-to-pay of $50 000 for one QALY. In sensitivity analyses, results were sensitive to the case-fatality of TdP episodes and to the TdP reduction following the diagnosis of LQT. Conclusion and Relevance In psychiatric hospitals, performing systematic ECG screening at admission help reduce the number of sudden cardiac deaths in a cost-effective fashion. PMID:26070071

  2. Cardiac MR enables diagnosis in 90% of patients with acute chest pain, elevated biomarkers and unobstructed coronary arteries

    PubMed Central

    Emrich, K; Abegunewardene, N; Oberholzer, K; Dueber, C; Muenzel, T; Kreitner, K-F

    2015-01-01

    Objective: To assess the diagnostic value of cardiac MRI (CMR) in patients with acute chest pain, elevated cardiac enzymes and a negative coronary angiogram. Methods: This study included a total of 125 patients treated in the chest pain unit during a 39-month period. Each included patient underwent MRI within a median of 3 days after cardiac catheterization. The MRI protocol comprised cine, oedema-sensitive and late gadolinium-enhancement imaging. The standard of reference was a consensus diagnosis based on clinical follow-up and the synopsis of all clinical, laboratory and imaging data. Results: MRI revealed a multitude of diagnoses, including ischaemic cardiomyopathy (CM), dilated CM, myocarditis, Takotsubo CM, hypertensive heart disease, hypertrophic CM, cardiac amyloidosis and non-compaction CM. MRI-based diagnoses were the same as the final reference diagnoses in 113/125 patients (90%), with the two diagnoses differing in only 12/125 patients. In two patients, no final diagnosis could be established. Conclusion: CMR performed early after the onset of symptoms revealed a broad spectrum of diseases. CMR delivered a correct final diagnosis in 90% of patients with acute chest pain, elevated cardiac enzymes and a negative coronary angiogram. Advances in knowledge: Diagnosing patients with acute coronary syndrome but unobstructed coronary arteries remains a challenge for cardiologists. CMR performed early after catheterization reveals a broad spectrum of diseases with only a simple and quick examination protocol, and there is a high concordance between MRI-based diagnoses and final reference diagnoses. PMID:25782462

  3. Spontaneous coronary artery dissection: a neglected cause of acute myocardial ischaemia and sudden death.

    PubMed Central

    Basso, C.; Morgagni, G. L.; Thiene, G.

    1996-01-01

    Spontaneous coronary artery dissection is a rare cause of acute myocardial ischaemia. Eight consecutive fatal cases which occurred in women aged 34-54 years (mean 43) are described. The dissection involved the left anterior descending coronary artery in four, the left main trunk in two, the right coronary artery in one, and both left anterior descending and circumflex arteries in one. The clinical presentation was sudden death in six cases, and acute myocardial infarction in two. Diagnosis was made at necropsy in every case but one, in which coronary dissection was diagnosed during life by selective coronary angiography. The only ascertained risk factor was hypertension in one patient; none of the women was in the puerperium, and Marfan syndrome was excluded in all. Histology showed a haematoma between the coronary tunica media and adventitia, that flattened and occluded the lumen; a coronary intimal tear was detected in only two cases. Unusual histological findings were cystic medial necrosis in one case, eosinophilic inflammatory infiltrates in four, and angiomatosis of the tunica adventitia in one. Patients dying of spontaneous coronary dissection are usually middle aged women, with no coronary atherosclerosis and apparently no risk factors. Spontaneous coronary artery dissection is unpredictable, and sudden death is the usual mode of clinical presentation. Prompt diagnosis and life saving treatment is far from being achieved. Images PMID:8665336

  4. [Massive cardiac lipomatosis, an autopsy finding in a patient with sudden death].

    PubMed

    Zamarrón-de Lucas, Ester; García-Fernández, Eugenia; Carpio, Carlos; Alcolea, Sergio; Martínez-Abad, Yolanda; Álvarez-Sala, Rodolfo

    2016-06-17

    The fat replacement of myocardial cells is a degenerative process that usually affects the right ventricle and is found in 50% of the elderly. The problem arises when this degeneration occurs to a massive degree, a differential diagnosis with other pathologies being necessary. We present the case of a patient who died suddenly and a massive cardiac lipomatosis was found on autopsy, as the only explanation of the outcome. PMID:27143526

  5. Post-mortem whole-exome sequencing (WES) with a focus on cardiac disease-associated genes in five young sudden unexplained death (SUD) cases.

    PubMed

    Neubauer, Jacqueline; Haas, Cordula; Bartsch, Christine; Medeiros-Domingo, Argelia; Berger, Wolfgang

    2016-07-01

    Sudden death of healthy young adults in the absence of any medical reason is generally categorised as autopsy-negative sudden unexplained death (SUD). Approximately 30 % of all SUD cases can be explained by lethal sequence variants in cardiac genes causing disturbed ion channel functions (channelopathies) or minimal structural heart abnormalities (cardiomyopathies). The aim of this study was to perform whole-exome sequencing (WES) in five young SUD cases in order to identify potentially disease-causing mutations with a focus on 184 genes associated with cardiac diseases or sudden death. WES analysis enabled the identification of damaging-predicted cardiac sequence alterations in three out of five SUD cases. Two SUD victims carried disease-causing variants in long QT syndrome (LQTS)-associated genes (KCNH2, SCN5A). In a third case, WES identified variants in two genes involved in mitral valve prolapse and thoracic aortic aneurism (DCHS1, TGFβ2). The genome of a fourth case carried several minor variants involved in arrhythmia pointing to a multigene influence that might have contributed to sudden death. Our results confirm that post-mortem genetic testing in SUD cases in addition to the conventional autopsy can help to identify familial cardiac diseases and can contribute to the identification of genetic risk factors for sudden death. PMID:26846766

  6. Cardiomyocyte death: mechanisms and translational implications.

    PubMed

    Chiong, M; Wang, Z V; Pedrozo, Z; Cao, D J; Troncoso, R; Ibacache, M; Criollo, A; Nemchenko, A; Hill, J A; Lavandero, S

    2011-01-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although treatments have improved, development of novel therapies for patients with CVD remains a major research goal. Apoptosis, necrosis, and autophagy occur in cardiac myocytes, and both gradual and acute cell death are hallmarks of cardiac pathology, including heart failure, myocardial infarction, and ischemia/reperfusion. Pharmacological and genetic inhibition of autophagy, apoptosis, or necrosis diminishes infarct size and improves cardiac function in these disorders. Here, we review recent progress in the fields of autophagy, apoptosis, and necrosis. In addition, we highlight the involvement of these mechanisms in cardiac pathology and discuss potential translational implications. PMID:22190003

  7. Cardiomyocyte death: mechanisms and translational implications

    PubMed Central

    Chiong, M; Wang, Z V; Pedrozo, Z; Cao, D J; Troncoso, R; Ibacache, M; Criollo, A; Nemchenko, A; Hill, J A; Lavandero, S

    2011-01-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although treatments have improved, development of novel therapies for patients with CVD remains a major research goal. Apoptosis, necrosis, and autophagy occur in cardiac myocytes, and both gradual and acute cell death are hallmarks of cardiac pathology, including heart failure, myocardial infarction, and ischemia/reperfusion. Pharmacological and genetic inhibition of autophagy, apoptosis, or necrosis diminishes infarct size and improves cardiac function in these disorders. Here, we review recent progress in the fields of autophagy, apoptosis, and necrosis. In addition, we highlight the involvement of these mechanisms in cardiac pathology and discuss potential translational implications. PMID:22190003

  8. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia.

    PubMed

    Chen, Yu-Jen; Fang, Li-Wen; Su, Wen-Chi; Hsu, Wen-Yi; Yang, Kai-Chien; Huang, Huey-Lan

    2016-01-01

    Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR or ErbB/Her) superfamily members with anticancer activity. In this study, we examined the effects and mechanism of action of lapatinib on several human leukemia cells lines, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) cells. We found that lapatinib inhibited the growth of human AML U937, HL-60, NB4, CML KU812, MEG-01, and ALL Jurkat T cells. Among these leukemia cell lines, lapatinib induced apoptosis in HL-60, NB4, and Jurkat cells, but induced nonapoptotic cell death in U937, K562, and MEG-01 cells. Moreover, lapatinib treatment caused autophagic cell death as shown by positive acridine orange staining, the massive formation of vacuoles as seen by electronic microscopy, and the upregulation of LC3-II, ATG5, and ATG7 in AML U937 cells. Furthermore, autophagy inhibitor 3-methyladenine and knockdown of ATG5, ATG7, and Beclin-1 using short hairpin RNA (shRNA) partially rescued lapatinib-induced cell death. In addition, the induction of phagocytosis and ROS production as well as the upregulation of surface markers CD14 and CD68 was detected in lapatinib-treated U937 cells, suggesting the induction of macrophagic differentiation in AML U937 cells by lapatinib. We also noted the synergistic effects of the use of lapatinib and cytotoxic drugs in U937 leukemia cells. These results indicate that lapatinib may have potential for development as a novel antileukemia agent. PMID:27499639

  9. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia

    PubMed Central

    Chen, Yu-Jen; Fang, Li-Wen; Su, Wen-Chi; Hsu, Wen-Yi; Yang, Kai-Chien; Huang, Huey-Lan

    2016-01-01

    Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR or ErbB/Her) superfamily members with anticancer activity. In this study, we examined the effects and mechanism of action of lapatinib on several human leukemia cells lines, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) cells. We found that lapatinib inhibited the growth of human AML U937, HL-60, NB4, CML KU812, MEG-01, and ALL Jurkat T cells. Among these leukemia cell lines, lapatinib induced apoptosis in HL-60, NB4, and Jurkat cells, but induced nonapoptotic cell death in U937, K562, and MEG-01 cells. Moreover, lapatinib treatment caused autophagic cell death as shown by positive acridine orange staining, the massive formation of vacuoles as seen by electronic microscopy, and the upregulation of LC3-II, ATG5, and ATG7 in AML U937 cells. Furthermore, autophagy inhibitor 3-methyladenine and knockdown of ATG5, ATG7, and Beclin-1 using short hairpin RNA (shRNA) partially rescued lapatinib-induced cell death. In addition, the induction of phagocytosis and ROS production as well as the upregulation of surface markers CD14 and CD68 was detected in lapatinib-treated U937 cells, suggesting the induction of macrophagic differentiation in AML U937 cells by lapatinib. We also noted the synergistic effects of the use of lapatinib and cytotoxic drugs in U937 leukemia cells. These results indicate that lapatinib may have potential for development as a novel antileukemia agent. PMID:27499639

  10. Dasatinib accelerates valproic acid-induced acute myeloid leukemia cell death by regulation of differentiation capacity.

    PubMed

    Heo, Sook-Kyoung; Noh, Eui-Kyu; Yoon, Dong-Joon; Jo, Jae-Cheol; Park, Jae-Hoo; Kim, Hawk

    2014-01-01

    Dasatinib is a compound developed for chronic myeloid leukemia as a multi-targeted kinase inhibitor against wild-type BCR-ABL and SRC family kinases. Valproic acid (VPA) is an anti-epileptic drug that also acts as a class I histone deacetylase inhibitor. The aim of this research was to determine the anti-leukemic effects of dasatinib and VPA in combination and to identify their mechanism of action in acute myeloid leukemia (AML) cells. Dasatinib was found to exert potent synergistic inhibitory effects on VPA-treated AML cells in association with G1 phase cell cycle arrest and apoptosis induction involving the cleavage of poly (ADP-ribose) polymerase and caspase-3, -7 and -9. Dasatinib/VPA-induced cell death thus occurred via caspase-dependent apoptosis. Moreover, MEK/ERK and p38 MAPK inhibitors efficiently inhibited dasatinib/VPA-induced apoptosis. The combined effect of dasatinib and VPA on the differentiation capacity of AML cells was more powerful than the effect of each drug alone, being sufficiently strong to promote AML cell death through G1 cell cycle arrest and caspase-dependent apoptosis. MEK/ERK and p38 MAPK were found to control dasatinib/VPA-induced apoptosis as upstream regulators, and co-treatment with dasatinib and VPA to contribute to AML cell death through the regulation of differentiation capacity. Taken together, these results indicate that combined dasatinib and VPA treatment has a potential role in anti-leukemic therapy. PMID:24918603

  11. Acute renal failure after cardiac transplantation: a case report and review of the literature.

    PubMed Central

    Cruz, D. N.; Perazella, M. A.

    1996-01-01

    Acute renal failure (ARF) is a relatively frequent complication associated with heart transplantation. It develops in the first few days postoperatively and is characterized by oliguria with laboratory and urinary indices typical of pre-renal azotemia. Cyclosporine, especially with higher doses, is one of the many factors which play an integral part in the nephrotoxicity following cardiac transplant. Poor preoperative renal function and perioperative hemodynamic compromise may also contribute to ARF. The actual incidence of ARF now encountered by transplant centers may be lower than previously reported, the result of lower cyclosporine doses. Currently, management is entirely supportive, but novel therapeutic approaches with atrial natriuretic peptide-like substances are being explored. A case illustrating the typical clinical presentation of ARF after heart transplant will be presented and the clinical features will be reviewed. PMID:9381741

  12. Alteration in systemic vascular resistance and cardiac output during acute cellular rejection and recovery in heart transplant recipients.

    PubMed

    Garan, Arthur R; Uriel, Nir; Sayer, Gabriel; Sims, Daniel; Zahner, Doris; Farr, Maryjane; Mancini, Donna; Jorde, Ulrich P

    2010-03-01

    Coronary vascular reserve is impaired during acute cellular rejection of the orthotopically transplanted heart, but changes in the peripheral vasculature during rejection have not been well described. To investigate whether peripheral vascular compensatory mechanisms are preserved after orthotopic heart transplantation (OHT), we longitudinally observed systemic vascular resistance (SVR) and cardiac output (CO) during acute cellular rejection. CO decreased during high-grade acute cellular rejection, and maintenance of mean arterial pressure was achieved by increases in SVR, and these changes did not return to baseline until several months after histologic resolution of rejection. PMID:19875310

  13. Cost-effectiveness analysis of acute kidney injury biomarkers in pediatric cardiac surgery

    PubMed Central

    Petrovic, Stanislava; Lakic, Dragana; Peco-Antic, Amira; Vulicevic, Irena; Ivanisevic, Ivana; Kotur-Stevuljevic, Jelena; Jelic-Ivanovic, Zorana

    2015-01-01

    Introduction Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagnosis of AKI in children after cardiac surgery compared with current diagnostic method (monitoring of serum creatinine (sCr) level). Materials and methods We developed a decision analytical model to estimate incremental cost-effectiveness of different biomarker-based diagnostic strategies compared to current diagnostic strategy. The Markov model was created to compare the lifetime cost associated with using of sCysC, uNGAL, uL-FABP with monitoring of sCr level for the diagnosis of AKI. The utility measurement included in the analysis was quality-adjusted life years (QALY). The results of the analysis are presented as the incremental cost-effectiveness ratio (ICER). Results Analysed biomarker-based diagnostic strategies for AKI were cost-effective compared to current diagnostic method. However, uNGAL and sCys C strategies yielded higher costs and lower effectiveness compared to uL-FABP strategy. uL-FABP added 1.43 QALY compared to current diagnostic method at an additional cost of $8521.87 per patient. Therefore, ICER for uL-FABP compared to sCr was $5959.35/QALY. Conclusions Our results suggest that the use of uL-FABP would represent cost effective strategy for early diagnosis of AKI in children after cardiac surgery. PMID:26110039

  14. Effects of acute, intermittent exercise in hypoxic environments on the release of cardiac troponin.

    PubMed

    Li, F; Hu, Y; Nie, J; Fu, F H

    2016-04-01

    The purpose of this study was to examine the effects of acute, intermittent exercise performed in hypoxic environments on the release of cardiac troponin (cTn). Ten well-trained, male marathon runners (22.1 ± 2.6 years, 64.0 ± 4.9 kg and 177.3 ± 3.9 cm) completed three intermittent exercise protocols under normoxic (trial N) and hypoxic (trial AH and RH) conditions. In trial N, the fraction of inspiration oxygen (FIO2 ) was 21.0% and exercise intensity was 90% and 50% normoxic velocity of VO2max (vVO2max ). In trial AH, FIO2 was 14.4% (simulated altitude of 3000 m) and exercise intensity was 90% and 50% normoxic vVO2max . In trial RH, FIO2 was 14.4% and exercise intensity was 90% and 50% hypoxic vVO2max . High-sensitivity cardiac troponin T (hs-cTnT) and cardiac troponin I (cTnI) were measured pre- and 0, 2, 4, and 24 h post-exercise. Hs-cTnT was elevated in all three trials, peaking at 2 to 4 h and returning to the baseline 24 h post-exercise. CTnI increased in trial AH, peaking at 2 to 4 h and returning below the detection limit 24 h post-exercise. It is concluded that the stimulus of hypoxia did not in and of itself induce more cTn to be released, but exercise intensity could affect this response in hypoxic environments. PMID:25943765

  15. Reduction of Leukocyte Counts by Hydroxyurea Improves Cardiac Function in Rats with Acute Myocardial Infarction

    PubMed Central

    Zhu, Guiyue; Yao, Yucai; Pan, Lingyun; Zhu, Wei; Yan, Suhua

    2015-01-01

    Background This study aimed to decrease leukocytes counts by hydroxyurea (Hu) in an acute myocardial infarction (AMI) rat model and examine its effect on the inflammatory response of myocardial infarction and cardiac functions. Material/Methods AMI was successfully caused in 36 rats, and 12 control rats received sham operation. Rats in the AMI group were then randomly divided into Hu and vehicle group with 18 rats each. Rats in the Hu AMI group received Hu (200 mg/kg) intragastrically while vehicle AMI group received saline. Leukocytes counts, cardiac functions, myocardial tissue morphology, and levels of soluble intercellular adhesion molecule-1 (sICAM), P-selectin and platelet activating factor (PAF) were measured and compared among the three groups four weeks after AMI induction. Results Leukocytes, neutrophils, and leukomonocyte counts in vehicle AMI rats were significantly higher than that of the normal control group (p<0.05). However, Hu treatment decreased their counts significantly (p<0.05). sICAM, P-selectin, and PAF level in vehicle AMI group were significantly higher than those of the normal group, and their level was also decreased by Hu treatment (p<0.05). Echocardiography analysis showed that Hu treatment increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) compared to that of vehicle AMI group (p<0.05). Histopathological examination showed that Hu significantly reduced the swelling of the heart muscle fiber in necrotic foci and the number of inflammatory cells infiltrated into myocardial interstitium compared to vehicle AMI group. Conclusions Decrease leukocytes counts by Hu significantly reduced inflammatory reaction and improved cardiac functions in AMI rats. PMID:26675565

  16. Cardiac-surgery associated acute kidney injury requiring renal replacement therapy. A Spanish retrospective case-cohort study

    PubMed Central

    2009-01-01

    Background Acute kidney injury is among the most serious complications after cardiac surgery and is associated with an impaired outcome. Multiple factors may concur in the development of this disease. Moreover, severe renal failure requiring renal replacement therapy (RRT) presents a high mortality rate. Consequently, we studied a Spanish cohort of patients to assess the risk factors for RRT in cardiac surgery-associated acute kidney injury (CSA-AKI). Methods A retrospective case-cohort study in 24 Spanish hospitals. All cases of RRT after cardiac surgery in 2007 were matched in a crude ratio of 1:4 consecutive patients based on age, sex, treated in the same year, at the same hospital and by the same group of surgeons. Results We analyzed the data from 864 patients enrolled in 2007. In multivariate analysis, severe acute kidney injury requiring postoperative RRT was significantly associated with the following variables: lower glomerular filtration rates, less basal haemoglobin, lower left ventricular ejection fraction, diabetes, prior diuretic treatment, urgent surgery, longer aortic cross clamp times, intraoperative administration of aprotinin, and increased number of packed red blood cells (PRBC) transfused. When we conducted a propensity analysis using best-matched of 137 available pairs of patients, prior diuretic treatment, longer aortic cross clamp times and number of PRBC transfused were significantly associated with CSA-AKI. Patients requiring RRT needed longer hospital stays, and suffered higher mortality rates. Conclusion Cardiac-surgery associated acute kidney injury requiring RRT is associated with worse outcomes. For this reason, modifiable risk factors should be optimised and higher risk patients for acute kidney injury should be identified before undertaking cardiac surgery. PMID:19772621

  17. Preparticipation Screening for Sudden Cardiac Death in High School and College Athletes.

    ERIC Educational Resources Information Center

    Braden, David S.; Strong, William B.

    1988-01-01

    A properly performed screening history and cardiovascular examination can identify most young athletes at risk for sudden death from heart abnormalities. Warning signs and examiner response are discussed as well as appropriate use of echocardiography. Included is a sample preparticipation examination form recommended by the American Academy of…

  18. Role of caspase-10 in the death of acute leukemia cells

    PubMed Central

    Guo, Wenjian; Dong, Aishu; Pan, Xiahui; Lin, Xiaoji; Lin, Ying; He, Muqing; Zhu, Baoling; Jin, Liming; Yao, Rongxing

    2016-01-01

    Autophagy can protect cells from stress, but can also induce cancer cell death. Caspase-10 is now considered to be a factor that is associated with autophagy in cancer. The present study therefore investigated whether caspase-10 affects autophagy in acute leukemia cells. The rates of survival vs. apoptosis in acute leukemia HL-60 and Jurkat cells treated with drugs were tested using cell viability assays and flow cytometry, and the levels of caspase-3 and −10 were tested by western blotting. In HL-60 cells that were treated with chemotherapy drugs combined with a caspase-10 inhibitor, the rate of survival decreased significantly compared with HL-60 cells treated with chemotherapy drugs alone. In contrast, the rate of survival of Jurkat cells treated with chemotherapy drugs combined with the caspase-10 inhibitor increased significantly compared with Jurkat cells treated with chemotherapy drugs alone. The results of the flow cytometry and western blotting showed that the changes in the survival rate may be caused by a change in the amount of apoptosis occurring in the Jurkat cells treated with chemotherapy drugs combined with the caspase-10 inhibitor. However, in HL-60 cells undergoing this combination treatment, the change in the survival rate was not caused by a change in the rate of apoptosis. When HL-60 cells were treated with the chemotherapy drugs combined with the caspase-10 inhibitor and the autophagy inhibitor 3-methyl adenine, the survival rate increased, whereas the rate of apoptosis did not change. These results show that caspase-10 may be associated with autophagy in acute myeloid leukemia cells, but not in acute lymphatic leukemia cells. PMID:27446483

  19. Epicardial delivery of VEGF and cardiac stem cells guided by 3-dimensional PLLA mat enhancing cardiac regeneration and angiogenesis in acute myocardial infarction.

    PubMed

    Chung, Hye-Jin; Kim, Jong-Tae; Kim, Hee-Jung; Kyung, Hei-Won; Katila, Pramila; Lee, Jeong-Han; Yang, Tae-Hyun; Yang, Young-Il; Lee, Seung-Jin

    2015-05-10

    Congestive heart failure is mostly resulted in a consequence of the limited myocardial regeneration capacity after acute myocardial infarction. Targeted delivery of proangiogenic factors and/or stem cells to the ischemic myocardium is a promising strategy for enhancing their local and sustained therapeutic effects. Herein, we designed an epicardial delivery system of vascular endothelial growth factor (VEGF) and cardiac stem cells (CSCs) using poly(l-lactic acid) (PLLA) mat applied to the acutely infarcted myocardium. The fibrous VEGF-loaded PLLA mat was fabricated by an electrospinning method using PLLA solution emulsified VEGF. This mat not only allowed for sustained release of VEGF for 4weeks but boosted migration and proliferation of both endothelial cells and CSCs in vitro. Furthermore, sustained release of VEGF showed a positive effect on in vitro capillary-like network formation of endothelial cells compared with bolus treatment of VEGF. PLLA mat provided a permissive 3-dimensional (3D) substratum that led to spontaneous cardiomyogenic differentiation of CSCs in vitro. Notably, sustained stimulation by VEGF-loaded PLLA mat resulted in a substantial increase in the expression of proangiogenic mRNAs of CSCs in vitro. The epicardially implanted VEGF-loaded PLLA mat showed modest effects on angiogenesis and cardiomyogenesis in the acutely infarcted hearts. However, co-implantation of VEGF and CSCs using the PLLA mat showed meaningful therapeutic effects on angiogenesis and cardiomyogenesis compared with controls, leading to reduced cardiac remodeling and enhanced global cardiac function. Collectively, the PLLA mat allowed a smart cargo that enabled the sustained release of VEGF and the delivery of CSCs, thereby synergistically inducing angiogenesis and cardiomyogenesis in acute myocardial infarction. PMID:25681051

  20. Troponin Marker for Acute Coronary Occlusion and Patient Outcome Following Cardiac Arrest

    PubMed Central

    Pearson, David A.; Wares, Catherine M.; Mayer, Katherine A.; Runyon, Michael S.; Studnek, Jonathan R.; Ward, Shana L.; Kraft, Kathi M.; Heffner, Alan C.

    2015-01-01

    Introduction The utility of troponin as a marker for acute coronary occlusion and patient outcome after out-of-hospital cardiac arrest (OHCA) is unclear. We sought to determine whether initial or peak troponin was associated with percutaneous coronary intervention (PCI), OHCA survival or neurological outcome. Methods Single-center retrospective-cohort study of OHCA patients treated in a comprehensive clinical pathway from November 2007 to October 2012. Troponin I levels were acquired at presentation, four and eight hours after arrest, and then per physician discretion. Cardiac catheterization was at the cardiologist’s discretion. Survival and outcome were determined at hospital discharge, with cerebral performance category score 1–2 defined as a good neurological outcome. Results We enrolled 277 patients; 58% had a shockable rhythm, 44% survived, 41% good neurological outcome. Of the 107 (38%) patients who underwent cardiac catheterization, 30 (28%) had PCI. Initial ED troponin (median, ng/mL) was not different in patients requiring PCI vs no PCI (0.32 vs 0.09, p=0.06), although peak troponin was higher (4.19 versus 1.57, p=0.02). Of the 85 patients who underwent cardiac catheterization without STEMI (n=85), there was no difference in those who received PCI vs no PCI in initial troponin (0.22 vs 0.06, p=0.40) or peak troponin (2.58 vs 1.43, p=0.27). Regarding outcomes, there was no difference in initial troponin in survivors versus non-survivors (0.09 vs 0.22, p=0.11), or those with a good versus poor neurological outcome (0.09 vs 0.20, p=0.11). Likewise, there was no difference in peak troponin in survivors versus non-survivors (1.64 vs 1.23, p=0.07), or in those with a good versus poor neurological outcome (1.57 vs 1.26, p=0.14). Conclusion In our single-center patient cohort, peak troponin, but not initial troponin, was associated with higher likelihood of PCI, while neither initial nor peak troponin were associated with survival or neurological outcome in

  1. Post Cardiac Surgery Acute Kidney Injury: A Woebegone Status Rejuvenated by the Novel Biomarkers

    PubMed Central

    Jayaraman, Rajesh; Sunder, Sham; Sathi, Satyanand; Gupta, Vijay Kumar; Sharma, Neera; Kanchi, Prabhu; Gupta, Anurag; Daksh, Sunil Kumar; Ram, Pranith; Mohamed, Ashik

    2014-01-01

    Background: Acute kidney injury (AKI) is common after cardiac surgery, the incidence varying between 7.7% and 28.1%. It significantly increases morbidity and mortality. Creatinine considerably delays the diagnosis with its own attended demerits. Novel urinary biomarkers are emerging which help in rapid diagnosis thus reducing the morbidity and mortality. Biomarkers of our study were neutrophil gelatinase-associated lipocalin (NGAL) and Interleukin-18 (IL-18). Objectives: To find out the incidence of AKI in post-cardiac surgery patients in our hospital, the ability of the two biomarkers in early diagnosis in predicting the severity of AKI based on RIFLE’s criteria and their ability to discriminate pre-renal from intrinsic AKI. Patients and Methods: One-hundred patients who underwent cardiac surgery were selected. Midstream urine samples were collected at 3 time intervals (baseline before surgery, 24 hours and 7 days after surgery). Biomarkers were measured by ELISA using BIORAD processors. Fractional excretion of sodium and urea were used to discriminate pre-renal from intrinsic AKI. Results: Out of 100 patients, 31 had AKI, 11 being pre-renal and 20 intrinsic AKI. Four patients required renal replacement therapy (12.9% among AKI cases and 4% in the overall study cohort). Four among 31 expired in intensive care unit. Identifiable risk factors for AKI included insulin requiring diabetes mellitus, chronic obstructive pulmonary disease, increased cardio-pulmonary bypass time, combined valvular surgery and coronary artery bypass grafting, employment of intra-aortic balloon counter pulsation, left main coronary artery occlusion and an ejection fraction of < 40%. NGAL was extremely sensitive (area under curve-0.96) in detecting intrinsic AKI at 24 hours followed by IL-18 ratio with an area under curve of 0.89. Creatinine at 24 hours was able to detect only 31.6% of intrinsic AKI. None of the pre-renal cases showed rise in the urinary biomarker levels. Patients with

  2. Primary Prevention of Sudden Cardiac Death in Adults with Transposition of the Great Arteries: A Review of Implantable Cardioverter-Defibrillator Placement

    PubMed Central

    Cedars, Ari M.

    2015-01-01

    Transposition of the great arteries encompasses a set of structural congenital cardiac lesions that has in common ventriculoarterial discordance. Primarily because of advances in medical and surgical care, an increasing number of children born with this anomaly are surviving into adulthood. Depending upon the subtype of lesion or the particular corrective surgery that the patient might have undergone, this group of adult congenital heart disease patients constitutes a relatively new population with unique medical sequelae. Among the more common and difficult to manage are cardiac arrhythmias and other sequelae that can lead to sudden cardiac death. To date, the question of whether implantable cardioverter-defibrillators should be placed in this cohort as a preventive measure to abort sudden death has largely gone unanswered. Therefore, we review the available literature surrounding this issue. PMID:26413012

  3. Low renal oximetry correlates with acute kidney injury after infant cardiac surgery.

    PubMed

    Owens, Gabe E; King, Karen; Gurney, James G; Charpie, John R

    2011-02-01

    Acute kidney injury (AKI) is a frequent complication after cardiopulmonary bypass surgery during infancy. Standard methods for evaluating renal function are not particularly sensitive nor are proximate indicators of renal dysfunction that allow intervention in real time. Near-infrared spectroscopy (NIRS) is a newer noninvasive technology that continuously evaluates regional oximetry and may correlate with renal injury and adverse outcomes after cardiac surgery in infants. This prospective observational study enrolled 40 infants (age, <12 months) undergoing biventricular repair. Continuous renal oximetry data were collected for the first 48 postoperative hours and correlated with postoperative course, standard laboratory data, and the occurrence of acute renal injury. Subjects with low renal oximetry (below 50% for >2 h) had significantly higher postoperative peak creatinine levels by 48 h (0.8 ± 0.4 vs. 0.52 ± 0.2; p = 0.003) and a higher incidence of AKI (50 vs. 3.1%; p = 0.003) than those with normal renal oximetry. These subjects also required more ventilator days and greater vasoactive support, and they had elevated lactate levels. Prolonged low renal near-infrared oximetry appears to correlate with renal dysfunction, decreased systemic oxygen delivery, and the overall postoperative course in infants with congenital heart disease undergoing biventricular repair. PMID:21085945

  4. Role of cardiac volume receptors in the control of ADH release during acute simulated weightlessness in man

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Benjamin, B. A.; Keil, L. C.; Sandler, H.

    1984-01-01

    Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes, designed to induce central blood volume shifts in ten cardiac and one heart-lung transplant recipients, to assess the contribution of cardiac volume receptors in the control of ADH release during the initial acute phase of exposure to weightlessness. Each subject underwent 15 min of a sitting-control period (C) followed by 30 min of 6 deg headdown tilt (T) and 30 min of resumed sitting (S). Venous blood samples and cardiac dimensions were taken at 0 and 15 min of C; 5, 15, and 30 min of T; and 5, 15, and 30 min of S. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Heart rate and blood pressure were recorded every two min. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 ml in C to 106 ml in T and returned to 87 ml in S. Plasma ADH was reduced by 20 percent (P less than 0.05) with T, and returned to control levels with S. These responses were similar in six normal cardiac-innervated control subjects. These data may suggest that cardiac volume receptors are not the primary mechanism for the control of ADH release during acute central volume shifts in man.

  5. Diagnostic and Prognostic Properties of Osteoprotegerin in Patients with Acute Dyspnoea: Observations from the Akershus Cardiac Examination (ACE) 2 Study

    PubMed Central

    Pervez, Mohammed Osman; Pedersen, Marit Holmefjord; Brynildsen, Jon; Høiseth, Arne Didrik; Hagve, Tor-Arne; Røsjø, Helge; Omland, Torbjørn

    2016-01-01

    Background Circulating osteoprotegerin (OPG) levels are increased in patients with chronic heart failure (HF). The diagnostic and prognostic merit of OPG measurement in patients admitted with acute dyspnoea is unknown. Objectives To evaluate the diagnostic and prognostic value of measuring OPG in patients admitted to hospital with acute dyspnoea. Methods OPG was analysed by ELISA in 308 patients admitted due to acute dyspnoea. Investigators blinded to OPG results adjudicated the diagnosis for the index hospitalization. Clinical outcomes were obtained from hospital records. Results In total, 139 patients (45%) were hospitalized with acute HF. OPG levels on hospital admission were higher in patients with acute HF vs. no acute HF, 7.8 (5.5–10.4) vs. 5.4 (3.8–7.2) pmol/L, p<0.001. The area under the receiver operator characteristic curve (ROC AUC) of OPG to discriminate between HF vs. non-HF was 0.695 [95% CI 0.636–0.754]. OPG did not provide incremental information to the ED physician’s prediction or N-terminal pro-B-type natriuretic peptide regarding the diagnosis of acute HF. OPG levels (log transformed) were associated with mortality in crude analysis (HR (95% CI) 1.87 (1.34 to 2.61), p<0.001), but this association was attenuated and no longer significant after including established cardiac biomarkers into the model. Conclusion In patients admitted to hospital with acute dyspnoea, OPG levels are higher in patients with acute HF than in those with dyspnoea from other causes. However, OPG does not provide incremental information beyond ED physician assessment for the diagnosis of acute HF or beyond clinical risk variables and established cardiac biomarkers concerning prognosis. PMID:27463973

  6. Cardiac oxygen limitation during an acute thermal challenge in the European perch: effects of chronic environmental warming and experimental hyperoxia.

    PubMed

    Ekström, Andreas; Brijs, Jeroen; Clark, Timothy D; Gräns, Albin; Jutfelt, Fredrik; Sandblom, Erik

    2016-08-01

    Oxygen supply to the heart has been hypothesized to limit cardiac performance and whole animal acute thermal tolerance (CTmax) in fish. We tested these hypotheses by continuously measuring venous oxygen tension (Pvo2) and cardiovascular variables in vivo during acute warming in European perch (Perca fluviatilis) from a reference area during summer (18°C) and a chronically heated area (Biotest enclosure) that receives warm effluent water from a nuclear power plant and is normally 5-10°C above ambient (24°C at the time of experiments). While CTmax was 2.2°C higher in Biotest compared with reference perch, the peaks in cardiac output and heart rate prior to CTmax occurred at statistically similar Pvo2 values (2.3-4.0 kPa), suggesting that cardiac failure occurred at a common critical Pvo2 threshold. Environmental hyperoxia (200% air saturation) increased Pvo2 across temperatures in reference fish, but heart rate still declined at a similar temperature. CTmax of reference fish increased slightly (by 0.9°C) in hyperoxia, but remained significantly lower than in Biotest fish despite an improved cardiac output due to an elevated stroke volume. Thus, while cardiac oxygen supply appears critical to elevate stroke volume at high temperatures, oxygen limitation may not explain the bradycardia and arrhythmia that occur prior to CTmax Acute thermal tolerance and its thermal plasticity can, therefore, only be partially attributed to cardiac failure from myocardial oxygen limitations, and likely involves limiting factors on multiple organizational levels. PMID:27280433

  7. Acute liver failure-induced death of rats is delayed or prevented by blocking NMDA receptors in brain.

    PubMed

    Cauli, Omar; Rodrigo, Regina; Boix, Jordi; Piedrafita, Blanca; Agusti, Ana; Felipo, Vicente

    2008-09-01

    Developing procedures to delay the mechanisms of acute liver failure-induced death would increase patients' survival by allowing time for liver regeneration or to receive a liver for transplantation. Hyperammonemia is a main contributor to brain herniation and mortality in acute liver failure (ALF). Acute ammonia intoxication in rats leads to N-methyl-D-aspartate (NMDA) receptor activation in brain. Blocking these receptors prevents ammonia-induced death. Ammonia-induced activation of NMDA receptors could contribute to ALF-induced death. If this were the case, blocking NMDA receptors could prevent or delay ALF-induced death. The aim of this work was to assess 1) whether ALF leads to NMDA receptors activation in brain in vivo and 2) whether blocking NMDA receptors prevents or delays ALF-induced death of rats. It is shown, by in vivo brain microdialysis, that galactosamine-induced ALF leads to NMDA receptors activation in brain. Blocking NMDA receptors by continuous administration of MK-801 or memantine through miniosmotic pumps affords significant protection against ALF-induced death, increasing the survival time approximately twofold. Also, when liver injury is not 100% lethal (1.5 g/kg galactosamine), blocking NMDA receptors increases the survival rate from 23 to 62%. This supports that blocking NMDA receptors could have therapeutic utility to improve survival of patients with ALF. PMID:18599589

  8. Acute Auditory Stimulation with Different Styles of Music Influences Cardiac Autonomic Regulation in Men

    PubMed Central

    da Silva, Sheila Ap. F.; Guida, Heraldo L.; dos Santos Antonio, Ana Marcia; de Abreu, Luiz Carlos; Monteiro, Carlos B. M.; Ferreira, Celso; Ribeiro, Vivian F.; Barnabe, Viviani; Silva, Sidney B.; Fonseca, Fernando L. A.; Adami, Fernando; Petenusso, Marcio; Raimundo, Rodrigo D.; Valenti, Vitor E.

    2014-01-01

    Background: No clear evidence is available in the literature regarding the acute effect of different styles of music on cardiac autonomic control. Objectives: The present study aimed to evaluate the acute effects of classical baroque and heavy metal musical auditory stimulation on Heart Rate Variability (HRV) in healthy men. Patients and Methods: In this study, HRV was analyzed regarding time (SDNN, RMSSD, NN50, and pNN50) and frequency domain (LF, HF, and LF / HF) in 12 healthy men. HRV was recorded at seated rest for 10 minutes. Subsequently, the participants were exposed to classical baroque or heavy metal music for five minutes through an earphone at seated rest. After exposure to the first song, they remained at rest for five minutes and they were again exposed to classical baroque or heavy metal music. The music sequence was random for each individual. Standard statistical methods were used for calculation of means and standard deviations. Besides, ANOVA and Friedman test were used for parametric and non-parametric distributions, respectively. Results: While listening to heavy metal music, SDNN was reduced compared to the baseline (P = 0.023). In addition, the LF index (ms2 and nu) was reduced during exposure to both heavy metal and classical baroque musical auditory stimulation compared to the control condition (P = 0.010 and P = 0.048, respectively). However, the HF index (ms2) was reduced only during auditory stimulation with music heavy metal (P = 0.01). The LF/HF ratio on the other hand decreased during auditory stimulation with classical baroque music (P = 0.019). Conclusions: Acute auditory stimulation with the selected heavy metal musical auditory stimulation decreased the sympathetic and parasympathetic modulation on the heart, while exposure to a selected classical baroque music reduced sympathetic regulation on the heart. PMID:25177673

  9. Autophagy plays an important role in Sunitinib-mediated cell death in H9c2 cardiac muscle cells

    SciTech Connect

    Zhao Yuqin; Xue Tao; Yang Xiaochun; Zhu Hong; Ding Xiaofei; Lou Liming; Lu Wei; Yang Bo; He Qiaojun

    2010-10-01

    Sunitinib, which is a multitargeted tyrosine-kinase inhibitor, exhibits antiangiogenic and antitumor activity, and extends survival of patients with metastatic renal-cell carcinoma (mRCC) and gastrointestinal stromal tumors (GIST). This molecule has also been reported to be associated with cardiotoxicity at a high frequency, but the mechanism is still unknown. In the present study, we observed that Sunitinib showed high anti-proliferative effect on H9c2 cardiac muscle cells measured by PI staining and the MTT assay. But apoptotic markers (PARP cleavage, caspase 3 cleavage and chromatin condensation) were uniformly negative in H9c2 cells after Sunitinib treatment for 48 h, indicating that another cell death pathway may be involved in Sunitinib-induced cardiotoxicity. Here we found Sunitinib dramatically increased autophagic flux in H9c2 cells. Acidic vesicle fluorescence and high expression of LC3-II in H9c2 cells identified autophagy as a Sunitinib-induced process that might be associated with cytotoxicity. Furthermore, knocking down Beclin 1 by RNA-interference to block autophagy in H9c2 cells revealed that the death rate was decreased when treated with Sunitinib in comparison to control cells. These results confirmed that autophagy plays an important role in Sunitinib-mediated H9c2 cells cytotoxicity. Taken together, the data presented here strongly suggest that autophagy is associated with Sunitinib-induced cardiotoxicity, and that inhibition of autophagy constitutes a viable strategy for reducing Sunitinib-induced cardiomyocyte death thereby alleviating Sunitinib cardiotoxicity.

  10. Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

    PubMed

    Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

    2015-01-01

    Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI. PMID:26064794

  11. Central nervous system haemorrhage causing early death in acute promyelocytic leukaemia

    PubMed Central

    Borowska, Anna; Stelmaszczyk-Emmel, Anna

    2016-01-01

    Acute promyelocytic leukaemia (APL) is a rare type of paediatric leukaemia characterised by a specific genetic mutation and life-threatening coagulopathy. The discovery of all-trans retinoic acid (ATRA), which acts directly on promyelocytic locus-retinoic acid receptor α (PML-RARα) gene product, brought a revolution to the therapy of this disorder. Unfortunately, despite an improvement in the complete remission rate, the early death (ED) rate has not changed significantly, and the haemorrhages remain a major problem. The most common bleeding site, which accounts for about 65-80% of haemorrhages, is the central nervous system. Second in line are pulmonary haemorrhages (32%), while gastrointestinal bleedings are relatively rare. Haemorrhages result from thrombocytopaenia, disseminated intravascular coagulopathy (DIC), and systemic fibrinolysis. Herein we present a boy aged one year and nine months with APL. The patient was not eligible for ATRA administration due to poor clinical condition. He developed bleeding diathesis that presented as disseminated intravascular coagulation (DIC) and led to intracranial haemorrhage, which resulted in the patient's death. PMID:26862315

  12. Kidney and lung injury in irradiated rats protected from acute death by partial-body shielding

    SciTech Connect

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.; Michieli, B.M. )

    1990-04-01

    Ninety-six CD-1 male rats were exposed to gamma-ray doses (0-25 Gy) in increments of 5 Gy. One femur, the surgically exteriorized GI tract, and the oral cavity were shielded during irradiation to protect against acute mortality from injury to the hematopoietic system, small intestine, and oral cavity. In addition, the thoraxes of half of the animals from each dose group were shielded. At approximately monthly intervals from 2 to 10 months after irradiation the hematocrit, plasma urea nitrogen (PUN), and {sup 51}Cr-EDTA clearance were measured. During the study 20 thorax-shielded and 19 thorax-irradiated animals died. All rats whose thoraxes received 25 Gy irradiation and three out of seven rats whose thoraxes received 20 Gy died 1 to 3 months postirradiation with massive pleural fluid accumulation. Shielding the thoraxes prevented this mode of death at these doses. Kidney injury was judged to be the primary cause of death of all thorax-shielded animals and 15- and 20-Gy thorax-irradiated animals. Animals with kidney damage had elevated PUN and reduced {sup 51}Cr-EDTA clearance and hematocrits. The relative merits of each of these end points in assessing radiation-induced kidney injury after total-body exposure are discussed.

  13. Wild chrysanthemum extract prevents UVB radiation-induced acute cell death and photoaging.

    PubMed

    Sun, Sujiao; Jiang, Ping; Su, Weiting; Xiang, Yang; Li, Jian; Zeng, Lin; Yang, Shuangjuan

    2016-03-01

    Wild chrysanthemum (Chrysanthemum indicum L.) is traditionally used in folk medicine as an anti-inflammatory agent. It is also used in the southwest plateau region of China to prevent ultraviolet-induced skin damage. However, the role and mechanism by which wild chrysanthemum prevents UV-induced skin damage and photoaging have never been investigated in vitro. In the present study, we found that aqueous extracts from wild chrysanthemum strongly reduced high-dose UVB-induced acute cell death of human immortalized keratinocytic HaCat cells. Wild chrysanthemum extract was also demonstrated to reduce low-dose UVB-induced expression of the photoaging-related matrix metalloproteinases MMP-2 and MMP-9. The ROS level elevated by UVB irradiation was strongly attenuated by wild chrysanthemum extract. Further study revealed that wild chrysanthemum extract reduced UVB-triggered ERK1/2 and p38 MAPK phosphorylation and their protective role, which is partially dependent on inhibiting p38 activation. These results suggest that wild chrysanthemum extract can protect the skin from UVB-induced acute skin damage and photoaging by reducing the intracellular reactive oxygen species (ROS) level and inhibiting p38 MAPK phosphorylation. The present study confirmed the protective role of wild chrysanthemum against UV-induced skin disorders in vitro and indicated the possible mechanism. Further study to identify the active components in wild chrysanthemum extract would be useful for developing new drugs for preventing and treating skin diseases, including skin cancer and photoaging, induced by UV irradiation. PMID:25052044

  14. Acute pulmonary emphysema in death by hanging: a morphometric digital study.

    PubMed

    Castiglioni, Claudia; Baumann, Pia; Fracasso, Tony

    2016-09-01

    Acute pulmonary emphysema (APE) has been described in cases of mechanical asphyxia such as ligature or manual strangulation but not in cases of hanging. In this study, we wanted to verify by morphometric digital analysis of lung tissue whether APE occurs in death by hanging.We investigated 16 cases of hanging (eight complete, eight incomplete), 10 cases of freshwater drowning (positive control group), and 10 cases of acute external bleeding (negative control group). Tissue sections were obtained from each pulmonary lobe. For each slide, five fields were randomly selected. The area of every alveolar space was measured by image analysis software. The mean alveolar area (MAA) was calculated for each group.In incomplete hanging, MAA was significantly higher than that observed in complete hanging and similar to the one observed in freshwater drowning.APE in cases of incomplete hanging can be considered as a sign of vitality. The high number of conditions that can cause alveolar distension (that were excluded in this study) limits the applicability of this vital sign in the routine forensic practice. PMID:27448112

  15. Endoplasmic reticulum stress in bone marrow-derived cells prevents acute cardiac inflammation and injury in response to angiotensin II.

    PubMed

    Li, T-T; Jia, L-X; Zhang, W-M; Li, X-Y; Zhang, J; Li, Y-L; Li, H-H; Qi, Y-F; Du, J

    2016-01-01

    Inflammation plays an important role in hypertensive cardiac injury. The endoplasmic reticulum (ER) stress pathway is involved in the inflammatory response. However, the role of ER stress in elevated angiotensin II (Ang II)-induced cardiac injury remains unclear. In this study, we investigated the role of ER stress in Ang II-induced hypertensive cardiac injury. Transcriptome analysis and quantitative real-time PCR showed that Ang II infusion in mice increased ER stress-related genes expression in the heart. C/EBP homologous protein (CHOP) deficiency, a key mediator of ER stress, increased infiltration of inflammatory cells, especially neutrophils, the production of inflammatory cytokines, chemokines in Ang II-infused mouse hearts. CHOP deficiency increased Ang II-induced cardiac fibrotic injury: (1) Masson trichrome staining showed increased fibrotic areas, (2) immunohistochemistry staining showed increased expression of α-smooth muscle actin, transforming growth factor β1 and (3) quantitative real-time PCR showed increased expression of collagen in CHOP-deficient mouse heart. Bone marrow transplantation experiments indicated that CHOP deficiency in bone marrow cells was responsible for Ang II-induced cardiac fibrotic injury. Moreover, TUNEL staining and flow cytometry revealed that CHOP deficiency decreased neutrophil apoptosis in response to Ang II. Taken together, our study demonstrated that hypertension induced ER stress after Ang II infusion. ER stress in bone marrow-derived cells protected acute cardiac inflammation and injury in response to Ang II. PMID:27277680

  16. Functional characterization of CaVα2δ mutations associated with sudden cardiac death.

    PubMed

    Bourdin, Benoîte; Shakeri, Behzad; Tétreault, Marie-Philippe; Sauvé, Rémy; Lesage, Sylvie; Parent, Lucie

    2015-01-30

    L-type Ca(2+) channels play a critical role in cardiac rhythmicity. These ion channels are oligomeric complexes formed by the pore-forming CaVα1 with the auxiliary CaVβ and CaVα2δ subunits. CaVα2δ increases the peak current density and improves the voltage-dependent activation gating of CaV1.2 channels without increasing the surface expression of the CaVα1 subunit. The functional impact of genetic variants of CACNA2D1 (the gene encoding for CaVα2δ), associated with shorter repolarization QT intervals (the time interval between the Q and the T waves on the cardiac electrocardiogram), was investigated after recombinant expression of the full complement of L-type CaV1.2 subunits in human embryonic kidney 293 cells. By performing side-by-side high resolution flow cytometry assays and whole-cell patch clamp recordings, we revealed that the surface density of the CaVα2δ wild-type protein correlates with the peak current density. Furthermore, the cell surface density of CaVα2δ mutants S755T, Q917H, and S956T was not significantly different from the cell surface density of the CaVα2δ wild-type protein expressed under the same conditions. In contrast, the cell surface expression of CaVα2δ D550Y, CaVα2δ S709N, and the double mutant D550Y/Q917H was reduced, respectively, by ≈30-33% for the single mutants and by 60% for the latter. The cell surface density of D550Y/Q917H was more significantly impaired than protein stability, suggesting that surface trafficking of CaVα2δ was disrupted by the double mutation. Co-expression with D550Y/Q917H significantly decreased CaV1.2 currents as compared with results obtained with CaVα2δ wild type. It is concluded that D550Y/Q917H reduced inward Ca(2+) currents through a defect in the cell surface trafficking of CaVα2δ. Altogether, our results provide novel insight in the molecular mechanism underlying the modulation of CaV1.2 currents by CaVα2δ. PMID:25527503

  17. Incidence of cardiac events in burned patients.

    PubMed

    Meyers, David G; Hoestje, Sara M; Korentager, Richard A

    2003-06-01

    Given the increased level of adrenergic stimulation in burn patients, it would be expected that they would experience an increased incidence of cardiac arrhythmias and other cardiac events. We performed a retrospective chart review of 56 acute burn patients matched by age, length of hospital stay, and sex to 56 trauma patients, all of whom had been continuously monitored electrocardiographically. Burn and trauma patients were similar in injury severity, admission laboratory values, and prior history of cardiopulmonary diseases. Arrhythmias were noted in 34% of burn patients and 28% of trauma patients. One myocardial infarction and six deaths occurred in burn patients. No myocardial infarctions or deaths were observed in trauma patients. A past history of cardiopulmonary disease increased the risk of myocardial infarction or death by 6.6 times. Cardiac arrhythmias and other events are relatively infrequent and benign in burn patients and are similar to those experienced by other patients with acute injuries. PMID:12781616

  18. Smac mimetic primes apoptosis-resistant acute myeloid leukaemia cells for cytarabine-induced cell death by triggering necroptosis.

    PubMed

    Chromik, Joerg; Safferthal, Charlotta; Serve, Hubert; Fulda, Simone

    2014-03-01

    The prognosis for patients with acute myeloid leukaemia (AML) is still poor, thus calling for novel treatment strategies. Here, we report that the small-molecule Smac mimetic BV6, which antagonizes Inhibitor of Apoptosis (IAP) proteins, acts in concert with cytarabine (AraC) to trigger cell death in AML cells in a highly synergistic manner (combination index 0.02-0.27). Similarly, BV6 cooperates with AraC to trigger cell death in primary AML samples, underscoring the clinical relevance of our findings. Molecular studies reveal that the TNFα-blocking antibody Enbrel significantly reduces BV6/AraC-induced cell death, demonstrating that an autocrine/paracrine TNFα loop mediates cell death. Furthermore, BV6 and AraC synergize to induce loss of mitochondrial membrane potential, caspase activation and DNA fragmentation, consistent with apoptotic cell death. Nevertheless, the caspase inhibitor zVAD.fmk fails to protect against BV6/AraC-induced cell death. Intriguingly, this cell death upon caspase inhibition is significantly reduced by pharmacological inhibition of two key components of necroptosis signaling, i.e. by RIP1 kinase inhibitor Necrostatin-1 or MLKL inhibitor NSA. Thus, BV6 sensitizes AML cells to AraC-induced cell death and overcomes apoptosis resistance by triggering necroptosis as alternative form of cell death. These findings have important implications for Smac mimetic-based strategies to bypass apoptosis resistance of AML. PMID:24184825

  19. Control of breathing during acute change in cardiac preload in a patient with partial cardiopulmonary bypass.

    PubMed

    Bekteshi, Edgar; Bell, Harold J; Haouzi, Annick; El-Banayosy, Aly; Haouzi, Philippe

    2010-01-31

    We recently had the opportunity to investigate the ventilatory effects of changing the rate of venous return to the heart (and thus pulmonary gas exchange) in a patient equipped with a venous-arterial oxygenated shunt (extracorporeal membrane oxygenation (ECMO) support). The presence of the ECMO support provided a condition wherein venous return to the right heart could be increased or decreased while maintaining total aortic blood flow and arterial blood pressure (ABP) constant. The patient, who had received a heart transplant 12 years ago, was admitted for acute cardiac failure related to graft rejection. The clinical symptomatology was that of right heart failure. We studied the patient on the 4th day of ECMO support, while she was breathing spontaneously. The blood flow diverted through the ECMO system represented 2/3 of the total aortic flow (4 l min(-1)). With these ECMO settings, the baseline level of ventilation was low (3.89+/-0.99 l min(-1)), but PET(CO2) was not elevated (37+/-2 mmHg). When Pa(CO2) in the blood coming from the ECMO was increased, no stimulatory effect on ventilation was observed. However, when the diversion of the venous return to the ECMO was stopped then restored, minute ventilation respectively increased then decreased by more than twofold with opposite changes in PET(CO2). These maneuvers were associated with large changes in the size of the right atrium and ventricle and of the left atrium. This observation suggests that the change in venous return affects breathing by encoding some of the consequences of the changes in cardiac preload. The possible sites of mediation are discussed. PMID:19837189

  20. Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia.

    PubMed

    Hsu, Andrew R; Barnholt, Kimberly E; Grundmann, Nicolas K; Lin, Joseph H; McCallum, Stewart W; Friedlander, Anne L

    2006-06-01

    Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude. The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no significant effects on normoxic exercise, and 2) sildenafil would improve cardiac output, arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained men performed one practice and three experimental trials at sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test consisted of a set-work-rate portion (55% work capacity: 1 h SL, 30 min HA) followed immediately by a time trial (10 km SL, 6 km HA). Double-blinded capsules (placebo, 50, or 100 mg) were taken 1 h before exercise in a randomly counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% oxygen) 1 h before exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), cardiac output, and SaO2 during set-work-rate exercise. Sildenafil lowered 6-km time-trial time by 15% (P<0.05). SaO2 was also higher during the time trial (P<0.05) in response to sildenafil, despite higher work rates. Post hoc analyses revealed two subject groups, sildenafil responders and nonresponders, who improved time-trial performance by 39% (P<0.05) and 1.0%, respectively. No dose-response effects were observed. During cycling exercise in acute hypoxia, sildenafil can greatly improve cardiovascular function, SaO2, and performance for certain individuals. PMID:16455814

  1. Achieving better in-hospital and after-hospital care of patients with acute cardiac disease.

    PubMed

    Scott, Ian A; Denaro, Charles P; Bennett, Cameron J; Hickey, Annabel C; Mudge, Alison M; Flores, Judy L; Sanders, Daniela C J; Thiele, Justine M; Wenck, Beres; Bennett, John W; Jones, Mark A

    2004-05-17

    In patients hospitalised with acute coronary syndromes (ACS) and congestive heart failure (CHF), evidence suggests opportunities for improving in-hospital and after-hospital care, patient self-care, and hospital-community integration. A multidisciplinary quality improvement program was designed and instigated in Brisbane in October 2000 involving 250 clinicians at three teaching hospitals, 1080 general practitioners (GPs) from five Divisions of General Practice, 1594 patients with ACS and 904 patients with CHF. Quality improvement interventions were implemented over 17 months after a 6-month baseline period and included: clinical decision support (clinical practice guidelines, reminders, checklists, clinical pathways); educational interventions (seminars, academic detailing); regular performance feedback; patient self-management strategies; and hospital-community integration (discharge referral summaries; community pharmacist liaison; patient prompts to attend GPs). Using a before-after study design to assess program impact, significantly more program patients compared with historical controls received: ACS: Angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering agents at discharge, aspirin and beta-blockers at 3 months after discharge, inpatient cardiac counselling, and referral to outpatient cardiac rehabilitation. CHF: Assessment for reversible precipitants, use of prophylaxis for deep-venous thrombosis, beta-blockers at discharge, ACE inhibitors at 6 months after discharge, imaging of left ventricular function, and optimal management of blood pressure levels. Risk-adjusted mortality rates at 6 and 12 months decreased, respectively, from 9.8% to 7.4% (P = 0.06) and from 13.4% to 10.1% (P = 0.06) for patients with ACS and from 22.8% to 15.2% (P < 0.001) and from 32.8% to 22.4% (P = 0.005) for patients with CHF. Quality improvement programs that feature multifaceted interventions across the continuum of care can change clinical culture, optimise care

  2. Effect of Acute Xanthine Oxidase Inhibition on Myocardial Energetics During Basal and Very High Cardiac Workstates

    PubMed Central

    Lee, Joseph; Hu, Qingsong; Mansoor, Abdul; Kamdar, Forum

    2014-01-01

    Myocardial ischemia is associated with reduced myocardial adenosine triphosphate (ATP) and increased free adenosine diphosphate (ADP) similar to the normal heart at very high cardiac workstates (HCW). We examined whether acute xanthine oxidase inhibition (XOI) in vivo can decrease myocardial free ADP in normal hearts functioning at basal cardiac workstates (BCW) or very HCW (catecholamine-induced). Myocardial high-energy phosphate (31P magnetic resonance spectroscopy), blood flow (radioactive microspheres), and oxygen consumption (MVO2) were measured in an open-chest canine model before and after infusion of vehicle or an XO inhibitor (allopurinol or febuxostat; n= 10 in each group) during BCW and infusion of dobutamine + dopamine to induce a very HCW. During BCW, both allopurinol and febuxostat resulted in higher phosphocreatine (PCr)/ATP, corresponding to lower ADP levels. During vehicle infusion, HCW caused a decrease of PCr/ATP and an increase in myocardial free ADP. Although XOI did not prevent an increase in free ADP during catecholamine infusion, the values in the allopurinol or febuxostat groups (0.141±0.012 and 0.136±0.011 μmol/g dry wt, respectively) remained significantly less than in the vehicle group (0.180±0.017; P<0.05). Thus, at a given rate of ATP synthesis, XOI decreased the free ADP level needed to drive ATP synthesis, suggesting a more energy-efficient status. As contractile dysfunction in ischemia is characterized by increase of myocardial free ADP and energy deficiency, the data suggest that XOI might be a potential therapy for improving energy efficiency during myocardial ischemia. PMID:21584861

  3. Electrochemical aptasensor of cardiac troponin I for the early diagnosis of acute myocardial infarction.

    PubMed

    Jo, Hunho; Gu, Hyunwoo; Jeon, Weejeong; Youn, Hyungjun; Her, Jin; Kim, Seong-Kyeong; Lee, Jeongbong; Shin, Jae Ho; Ban, Changill

    2015-10-01

    Cardiac troponin I (cTnI) is well-known as a promising biomarker for the early diagnosis of acute myocardial infarction (AMI). In this work, single-stranded DNA aptamers against cTnI were identified by the Systematic Evolution of Ligands by Exponential enrichment (SELEX) method. The aptamer candidates exhibited a high selectivity and sensitivity toward both cTnI and the cardiac Troponin complex. The binding affinities of each aptamer were evaluated based on their dissociation constants (Kd) by surface plasma resonance. The Tro4 aptamer that had the highest binding capacity to cTnI showed a very low Kd value (270 pM) compared with that of a cTnI antibody (20.8 nM). Furthermore, we designed a new electrochemical aptasensor based on square wave voltammetry using ferrocene-modified silica nanoparticles. The developed aptasensor demonstrated an excellent analytical performance for cTnI with a wide linear range of 1-10 000 pM in a buffer and a detection limit of 1.0 pM (24 pg/mL; S/N = 3), which was noticeably lower than the cutoff values (70-400 pg/mL). The specificity of the aptamers was also examined using nontarget proteins, demonstrating that the proposed sensor responded to only cTnI. In addition, cTnI was successfully detected in a human serum albumin solution. On the basis of the calibration curve that was constructed, the concentrations of cTnI in a solution supplemented with human serum were effectively measured. The calculated values correlated well with the actual concentrations of cTnI. It is anticipated that the highly sensitive and selective aptasensor for cTnI could be readily applicable for the accurate diagnosis of AMI. PMID:26352249

  4. ECG risk markers for atrial fibrillation and sudden cardiac death in minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised trial

    PubMed Central

    Schlatzer, Christian; Bratton, Daniel J; Craig, Sonja E; Kohler, Malcolm; Stradling, John R

    2016-01-01

    Objective Obstructive sleep apnoea (OSA), atrial fibrillation (AF) and sudden cardiac death (SCD) may occur concomitantly, and are of considerable epidemiological interest, potentially leading to morbidity and mortality. Effective treatment of OSA with continuous positive airway pressure (CPAP) could prevent progression and/or recurrence of AF and factors leading to SCD. Recently, a randomised controlled trial showed a statistically and clinically significant prolongation of measures of cardiac repolarisation after CPAP withdrawal in symptomatic patients with moderate to severe OSA. Whether or not CPAP therapy improves ECG risk markers of AF and SCD in patients with minimally symptomatic OSA as well, is unknown. Methods 3 centres taking part in the MOSAIC (Multicentre Obstructive Sleep Apnoea Interventional Cardiovascular) trial randomisd 303 patients with minimally symptomatic OSA to receive either CPAP or standard care for 6 months. Treatment effects of CPAP on P-wave duration, P-wave dispersion, QT interval, QT dispersion, Tpeak-to-Tend (TpTe) and TpTe/QT ratio were analysed. Results Participants were primarily men (83%). Mean age was 57.8 (7.2) and mean ODI (Oxygen Desaturation Index) at baseline was 13.1/h (12.3). Full 12-lead ECG data was available in 250 patients. Mean (SD) baseline intervals of P-wave duration, P-wave dispersion, QTc interval, QT dispersion, TpTe and TpTe/QT ratio in ms were 87.4 (8.3), 42.3 (11.9), 397.8 (22.7), 43.1 (16.7), 73.5 (13.7) and 0.19 (0.0), respectively. No treatment effect of CPAP on risk markers for AF and SCD was found. Conclusions There seems to be no effect of CPAP on ECG measures of arrhythmia risk in patients with minimally symptomatic OSA. Trial registration number ISRCTN34164388; Post-results. PMID:26983946

  5. Acute and long-term renal and metabolic effects of piretanide in congestive cardiac failure.

    PubMed Central

    McNabb, W R; Noormohamed, F H; Lant, A F

    1988-01-01

    1. The renal and metabolic effects of the sulphamoylbenzoic acid diuretic, piretanide, have been studied, under controlled dietary conditions, in 39 patients with congestive cardiac failure. 2. In acute studies, peak saluresis occurred within 4 h of oral piretanide administration; saluresis was complete within 6 h, after which a significant antidiuretic effect was observed. Addition of triamterene, 50 mg, blunted the 0-6 h kaliuretic effect of piretanide. Over 24 h, piretanide, alone, caused insignificant urinary losses of potassium when compared with control. 3. In comparative studies, the piretanide dose-response curve was found to be parallel to that of frusemide over the dose range studied. The 0-6 h saluretic responses of piretanide, 6, 12 and 18 mg, were found to be equivalent to frusemide, 40, 80 and 120 mg respectively. The collective mean ratios of all the saluretic responses to each dose of piretanide with the corresponding dose of frusemide was observed to be 0.99 +/- 0.12, over 0-6 h period, and 0.86 +/- 0.09 over the 24 h period. The relative potency of piretanide, when compared with frusemide was found to be 6.18 (95% confidence limits 4.87-8.33), over the 0-6 h period, and 4.73 (95% confidence limits 3.65-6.14), over 24 h period. 4. In 15 patients in severe cardiac failure, urinary recovery of piretanide, over first 6 h, at the start of treatment was 21.2 +/- 2.1% while efficiency of the diuretic (mmol Na/mg drug) was 47.3 +/- 4.1. Long-term piretanide therapy was continued in the same group for up to and in some cases over 3 years. No other diuretics or potassium supplements were given. Piretanide dosage ranged from 6 to 24 mg day-1 according to clinical need. Plasma potassium fell significantly at 12 and 24 months, though remaining within the normal range. At these same times, significant elevations in both plasma urate and total fasting cholesterol were observed. Two patients developed overt gout on high dose piretanide therapy (24 mg day-1

  6. Sudden Cardiac Arrest

    MedlinePlus

    ... from American Heart Association Aneurysms and Dissections Angina Arrhythmia Bundle Branch Block Cardiomyopathy Carotid Artery Disease Chronic ... terms: SCA, sudden cardiac death (SCD), sudden death, arrhythmias, ... ventricular fibrillation, defibrillator, automatic cardiac defibrillator ( ...

  7. Silencer of Death Domains Controls Cell Death through Tumour Necrosis Factor-Receptor 1 and Caspase-10 in Acute Lymphoblastic Leukemia

    PubMed Central

    Khan, Naveed I.; Welschinger, Robert; Basnett, Jordan; Fung, Carina; Rizos, Helen; Bradstock, Kenneth F.; Bendall, Linda J.

    2014-01-01

    Resistance to apoptosis remains a significant problem in drug resistance and treatment failure in malignant disease. NO-aspirin is a novel drug that has efficacy against a number of solid tumours, and can inhibit Wnt signaling, and although we have shown Wnt signaling to be important for acute lymphoblastic leukemia (ALL) cell proliferation and survival inhibition of Wnt signaling does not appear to be involved in the induction of ALL cell death. Treatment of B lineage ALL cell lines and patient ALL cells with NO-aspirin induced rapid apoptotic cell death mediated via the extrinsic death pathway. Apoptosis was dependent on caspase-10 in association with the formation of the death-inducing signaling complex (DISC) incorporating pro-caspase-10 and tumor necrosis factor receptor 1 (TNF-R1). There was no measurable increase in TNF-R1 or TNF-α in response to NO-aspirin, suggesting that the process was ligand-independent. Consistent with this, expression of silencer of death domain (SODD) was reduced following NO-aspirin exposure and lentiviral mediated shRNA knockdown of SODD suppressed expansion of transduced cells confirming the importance of SODD for ALL cell survival. Considering that SODD and caspase-10 are frequently over-expressed in ALL, interfering with these proteins may provide a new strategy for the treatment of this and potentially other cancers. PMID:25061812

  8. Non-Invasive Magnetic Resonance Imaging in Rats for Prediction of the Fate of Grafted Kidneys from Cardiac Death Donors

    PubMed Central

    Kaimori, Jun-Ya; Iwai, Satomi; Hatanaka, Masaki; Teratani, Takumi; Obi, Yoshitsugu; Tsuda, Hidetoshi; Isaka, Yoshitaka; Yokawa, Takashi; Kuroda, Kagayaki; Ichimaru, Naotsugu; Okumi, Masayoshi; Yazawa, Koji; Rakugi, Hiromi; Nonomura, Norio; Takahara, Shiro; Kobayashi, Eiji

    2013-01-01

    The main objective of this study was to assess cardiac death (CD) kidney grafts before transplantation to determine whether blood oxygen level-dependent (BOLD) and diffusion MRI techniques can predict damage to these grafts after transplantation. We assessed CD kidney tissue by BOLD and diffusion MRI. We also examined pathological and gene expression changes in CD kidney grafts before and after transplantation. Although there was significantly more red cell congestion (RCC) in the inner stripe of the outer medulla (IS) in both 1 h after cardiac death (CD1h) and CD2h kidneys destined for grafts before transplantation compared with CD0h (p<0.05), CD2h, but not CD1h, kidney grafts had significantly different RCC in the IS 2 days after transplantation (p<0.05). Consistent with these pathological findings, tissue plasminogen activator (tPA) gene expression was increased only in the cortex and medulla of CD2h kidney grafts after transplantation. BOLD MRI successfully and non-invasively imaged and quantified RCC in the IS in both CD1h and CD2h kidney grafts (p<0.05). Diffusion MRI also non-invasively assessed increased the apparent diffusion coefficient in the IS and decreased it in the outer stripe (OS) of CD2h grafts, in concordance with interstitial edema in the IS and tubule cellular edema in the OS. These two types of edema in the outer medulla could explain the prolonged RCC in the IS only of CD2h kidney grafts, creating part of a vicious cycle inhibiting red cells coming out of capillary vessels in the IS. Perfusion with University of Wisconsin solution before MRI measurements did not diminish the difference in tissue damage between CD1h and CD2h kidney grafts. BOLD and diffusion MRI, which are readily available non-invasive tools for evaluating CD kidney grafts tissue damage, can predict prolonged organ damage, and therefore the outcome, of transplanted CD kidney grafts. PMID:23667641

  9. Ryanodine receptors/calcium release channels in heart failure and sudden cardiac death.

    PubMed

    Marks, A R

    2001-04-01

    Calcium (Ca2+) ions are second messengers in signaling pathways in all types of cells. They regulate muscle contraction, electrical signals which determine the cardiac rhythm and cell growth pathways in the heart. In the past decade cDNA cloning has provided clues as to the molecular structure of the intracellular Ca2+ release channels (ryanodine receptors, RyR, and inositol 1,4,5-trisphosphate receptors, IP3R) on the sarcoplasmic and endoplasmic reticulum (SR/ER) and an understanding of how these molecules regulate Ca2+ homeostasis in the heart is beginning to emerge. The intracellular Ca2+ release channels form a distinct class of ion channels distinguished by their structure, size, and function. Both RyRs and IP3Rs have gigantic cytoplasmic domains that serve as scaffolds for modulatory proteins that regulate the channel pore located in the carboxy terminal 10% of the channel sequence. The channels are tetramers comprised of four RyR or IP3R subunits. RyR2 is required for excitation-contraction (EC) coupling in the heart. Using co-sedimentation and co-immunoprecipitation we have defined a macromolecular complex comprised of RyR2, FKBP12.6, PKA, the protein phosphatases PP1 and PP2A, and an anchoring protein mAKAP. We have shown that protein kinase A (PKA) phosphorylation of RyR2 dissociates FKBP12.6 and regulates the channel open probability (P(o)). In failing human hearts RyR2 is PKA hyperphosphorylated resulting in defective channel function due to increased sensitivity to Ca2+-induced activation. PMID:11273716

  10. Peri-operative heart-type fatty acid binding protein is associated with acute kidney injury after cardiac surgery

    PubMed Central

    Schaub, Jennifer A.; Garg, Amit X.; Coca, Steven G.; Testani, Jeffrey M.; Shlipak, Michael G.; Eikelboom, John; Kavsak, Peter; McArthur, Eric; Shortt, Colleen; Whitlock, Richard; Parikh, Chirag R.

    2015-01-01

    Acute Kidney Injury (AKI) is a common complication after cardiac surgery and is associated with worse outcomes. Since heart fatty acid binding protein (H-FABP) is a myocardial protein that detects cardiac injury, we sought to determine if plasma H-FABP was associated with AKI in the TRIBE-AKI cohort; a multi-center cohort of 1219 patients at high risk for AKI who underwent cardiac surgery. The primary outcomes of interest were any AKI (Acute Kidney Injury Network (AKIN) stage 1 or higher) and severe AKI (AKIN stage 2 or higher). The secondary outcome was long-term mortality after discharge. Patients who developed AKI had higher levels of H-FABP pre- and post-operatively than patients who did not have AKI. In analyses adjusted for known AKI risk factors, first post-operative log(H-FABP) was associated with severe AKI (adjusted OR 5.39 [95% CI, 2.87-10.11] per unit increase), while pre-operative log(H-FABP) was associated with any AKI (2.07 [1.48-2.89]) and mortality (1.67 [1.17-2.37]). These relationships persisted after adjustment for change in serum creatinine (for first postoperative log(H-FABP)) and biomarkers of cardiac and kidney injury, including brain natriuretic peptide, cardiac troponin-I, interleukin-18, liver fatty acid binding protein, kidney injury molecule-1, and neutrophil gelatinase associated lipocalin. Thus, peri-operative plasma H-FABP levels may be used for risk-stratification of AKI and mortality following cardiac surgery. PMID:25830762

  11. Nitric oxide formation in acutely rejecting cardiac allografts correlates with GTP cyclohydrolase I activity

    PubMed Central

    2005-01-01

    Inducible nitric oxide synthase (iNOS) is a prominent component of the complex array of mediators in acute graft rejection. While NO production is determined by iNOS expression, BH4 (tetrahydrobiopterin), a cofactor of iNOS synthesized by GTP cyclohydrolase I, has been considered critical in sustaining NO production. In the present study, we examined time-dependent changes in iNOS and GTP cyclohydrolase I in rat cardiac allografts. The increase in iNOS protein and mRNA in allografts was similar at POD4 (post-operative day 4) and POD6. However, the peak increase in intragraft NO level at POD4 was not sustained at POD6. This disparity could not be explained by any decrease in iNOS enzyme activity measured ex vivo with optimal amounts of substrate and cofactors. Lower iNOS activity could be explained by changes in total biopterin levels in allografts at POD4 that was decreased to baseline at POD6. Changes in biopterin production correlated with lower GTP cyclohydrolase I protein levels but not by any change in GTP cyclohydrolase I mRNA. Functionally, allografts displayed bradycardia and distended diastolic and systolic dimensions at POD6 but not at POD4. Likewise, histological rejection scores were increased at POD4 but with a secondary increased stage at POD6. It is hypothesized that the dissimilar amounts of NO at early and later stages of rejection is due to uncoupling of iNOS arising from disproportionate synthesis of BH4. These findings provide insight into a potential pathway regulating NO bioactivity in graft rejection. Such knowledge may potentially assist in the design of newer strategies to prevent acute graft rejection. PMID:16000090

  12. Temporal trends in the use of invasive cardiac procedures for non-ST segment elevation acute coronary syndromes according to initial risk stratification

    PubMed Central

    Jedrzkiewicz, Sean; Goodman, Shaun G; Yan, Raymond T; Welsh, Robert C; Kornder, Jan; DeYoung, J Paul; Wong, Graham C; Rose, Barry; Grondin, François R; Gallo, Richard; Huang, Wei; Gore, Joel M; Yan, Andrew T

    2009-01-01

    BACKGROUND: Current guidelines support an early invasive strategy in the management of high-risk non-ST elevation acute coronary syndromes (NSTE-ACS). Although studies in the 1990s suggested that high-risk patients received less aggressive treatment, there are limited data on the contemporary management patterns of NSTE-ACS in Canada. OBJECTIVE: To examine the in-hospital use of coronary angiography and revascularization in relation to risk among less selected patients with NSTE-ACS. METHODS: Data from the prospective, multicentre Global Registry of Acute Coronary Events (main GRACE and expanded GRACE2) were used. Between June 1999 and September 2007, 7131 patients from across Canada with a final diagnosis of NSTE-ACS were included the study. The study population was stratified into low-, intermediate- and high-risk groups, based on their calculated GRACE risk score (a validated predictor of in-hospital mortality) and according to time of enrollment. RESULTS: While rates of in-hospital death and reinfarction were significantly (P<0.001) greater in higher-risk patients, the in-hospital use of cardiac catheterization in low- (64.7%), intermediate- (60.3%) and high-risk (42.3%) patients showed an inverse relationship (P<0.001). This trend persisted despite the increase in the overall rates of cardiac catheterization over time (47.9% in 1999 to 2003 versus 51.6% in 2004 to 2005 versus 63.8% in 2006 to 2007; P<0.001). After adjusting for confounders, intermediate-risk (adjusted OR 0.80 [95% CI 0.70 to 0.92], P=0.002) and high-risk (adjusted OR 0.38 [95% CI 0.29 to 0.48], P<0.001) patients remained less likely to undergo in-hospital cardiac catheterization. CONCLUSION: Despite the temporal increase in the use of invasive cardiac procedures, they remain paradoxically targeted toward low-risk patients with NSTE-ACS in contemporary practice. This treatment-risk paradox needs to be further addressed to maximize the benefits of invasive therapies in Canada. PMID:19898699

  13. Outcomes After Implantable Cardioverter-Defibrillator Generator Replacement for Primary Prevention of Sudden Cardiac Death

    PubMed Central

    Madhavan, Malini; Waks, Jonathan W.; Friedman, Paul A.; Kramer, Daniel B.; Buxton, Alfred E.; Noseworthy, Peter A.; Mehta, Ramila A.; Hodge, David O.; Higgins, Angela Y.; Webster, Tracy L.; Witt, Chance M.; Cha, Yong-Mei; Gersh, Bernard J.

    2016-01-01

    Background The effectiveness of implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden death in patients with an ejection fraction (EF) ≤35% and clinical heart failure is well established. However, outcomes after replacement of the ICD generator in patients with recovery of EF to >35% and no previous therapies are not well characterized. Methods and Results Between 2001 and 2011, generator replacement was performed at 2 tertiary medical centers in 253 patients (mean age, 68.3±12.7 years; 82% men) who had previously undergone ICD placement for primary prevention but subsequently never received appropriate ICD therapy. EF had recovered to >35% in 72 of 253 (28%) patients at generator replacement. During median (quartiles) follow-up of 3.3 (1.8–5.3) years after generator replacement, 68 of 253 (27%) experienced appropriate ICD therapy. Patients with EF ≤35% were more likely to experience ICD therapy compared with those with EF >35% (12% versus 5% per year; hazard ratio, 3.57; P=0.001). On multivariable analysis, low EF predicted appropriate ICD therapy after generator replacement (hazard ratio, 1.96 [1.35–2.87] per 10% decrement; P=0.001). Death occurred in 25% of patients 5 years after generator replacement. Mortality was similar in patients with EF ≤35% and >35% (7% versus 5% per year; hazard ratio, 1.10; P=0.68). Atrial fibrillation (3.24 [1.63–6.43]; P<0.001) and higher blood urea nitrogen (1.28 [1.14–1.45] per increase of 10 mg/dL; P<0.001) were associated with mortality. Conclusions Although approximately one fourth of patients with a primary prevention ICD and no previous therapy have EF >35% at the time of generator replacement, these patients continue to be at significant risk for appropriate ICD therapy (5% per year). These data may inform decisions on ICD replacement. PMID:26921377

  14. Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury

    PubMed Central

    Lee, Se-Yeon; Lee, Seahyoung; Choi, Eunhyun; Ham, Onju; Lee, Chang Youn; Lee, Jiyun; Seo, Hyang-Hee; Cha, Min-Ji; Mun, Bohyun; Lee, Yunmi; Yoon, Cheesoon; Hwang, Ki-Chul

    2016-01-01

    Genetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death. PMID:27008992

  15. Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury.

    PubMed

    Lee, Se-Yeon; Lee, Seahyoung; Choi, Eunhyun; Ham, Onju; Lee, Chang Youn; Lee, Jiyun; Seo, Hyang-Hee; Cha, Min-Ji; Mun, Bohyun; Lee, Yunmi; Yoon, Cheesoon; Hwang, Ki-Chul

    2016-01-01

    Genetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death. PMID:27008992

  16. SYSTEMIC IMBALANCE OF ESSENTIAL METALS AND CARDIAC GENE EXPRESSION IN RATS FOLLOWING ACUTE PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...

  17. Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute Coronary Syndrome

    PubMed Central

    Masrani Mehta, Shriti; Depta, Jeremiah P; Novak, Eric; Patel, Jayendrakumar S; Patel, Yogesh; Raymer, David; Facey, Gabrielle; Zajarias, Alan; Lasala, John M; Singh, Jasvindar; Bach, Richard G; Kurz, Howard I

    2015-01-01

    Background The safety of deferring revascularization based on fractional flow reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the association of FFR and adverse cardiac events among patients with coronary lesions deferred revascularization based on FFR in the setting of ACS versus non-ACS. Methods and Results The study population (674 patients; 816 lesions) was divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when revascularization was deferred based on FFR values >0.80 between October 2002 and July 2010. The association and interaction between FFR and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow-up of 4.5±2.1 years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (DLI), whereas the composite of DLI or myocardial infarction (MI) attributed to a deferred lesion was designated as deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not associated with any increase in adverse cardiac events. In the ACS group, every 0.01 decrease in FFR was associated with a significantly higher rate of cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI (HR, 1.12; 95% CI, 1.06 to 1.18). Conclusion Lower FFR values among ACS patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non-ACS patients. PMID:26289346

  18. Left Bundle Branch Block in Acute Cardiac Events: Insights From a 23-Year Registry.

    PubMed

    Alkindi, Fahad; El-Menyar, Ayman; Al-Suwaidi, Jassim; Patel, Ashfaq; Gehani, Abdurrazzak A; Singh, Rajvir; Albinali, Hajar; Arabi, Abdulrahman

    2015-10-01

    Between 1991 and 2013, we evaluated the demographics, presentations, and final diagnosis of patients hospitalized with acute cardiac events and left bundle branch block (LBBB). Of 50 992 patients, 768 (1.5%) had LBBB. Compared with non-LBBB patients, patients with LBBB were mostly older, female, diabetic, and had hypertension and chronic kidney failure (CKF; P < .001 for all). Dyspnea (P < .001) and dizziness (P = .037) were more frequent in patients with LBBB. The most frequent cause of admission with LBBB was congestive heart failure (CHF; 54.2%), followed by ST-elevation myocardial infarction (STEMI; 13.3%), valvular heart disease (9.4%), unstable angina (8.3%) and Non-STEMI (7.7%). On multivariate analysis, CKF (odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.09-3.70) and LBBB (OR: 2.96, 95% CI: 2.01-4.42) were predictors of in-hospital mortality in the entire study population. Further analysis of patients with LBBB showed that CKF (OR: 2.93, 95% CI: 1.40-6.12) was the only predictor of in-hospital mortality. Regardless the presenting symptoms, CHF was the final diagnosis in most cases with LBBB. PMID:25477500

  19. TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells

    PubMed Central

    Weeks, Robert J.; Ludgate, Jackie L.; LeMée, Gwenn; Morison, Ian M.

    2016-01-01

    Background Childhood acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity. Methods Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5’-aza-2’-deoxycytidine (decitabine) exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays. Results In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity. Conclusions These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL. PMID:26985820

  20. End-of-life discontinuation of destination therapy with cardiac and ventilatory support medical devices: physician-assisted death or allowing the patient to die?

    PubMed Central

    2010-01-01

    Background Bioethics and law distinguish between the practices of "physician-assisted death" and "allowing the patient to die." Discussion Advances in biotechnology have allowed medical devices to be used as destination therapy that are designed for the permanent support of cardiac function and/or respiration after irreversible loss of these spontaneous vital functions. For permanent support of cardiac function, single ventricle or biventricular mechanical assist devices and total artificial hearts are implanted in the body. Mechanical ventilators extrinsic to the body are used for permanent support of respiration. Clinical studies have shown that destination therapy with ventricular assist devices improves patient survival compared to medical management, but at the cost of a substantial alteration in end-of-life trajectories. The moral and legal assessment of the appropriateness and permissibility of complying with a patient's request to electively discontinue destination therapy in a life-terminating act in non-futile situations has generated controversy. Some argue that complying with this request is ethically justified because patients have the right to request withdrawal of unwanted treatment and be allowed to die of preexisting disease. Other commentators reject the argument that acceding to an elective request for death by discontinuing destination therapy is 'allowing a patient to die' because of serious flaws in interpreting the intention, causation, and moral responsibility of the ensuing death. Summary Destination therapy with cardiac and/or ventilatory medical devices replaces native physiological functions and successfully treats a preexisting disease. We posit that discontinuing cardiac and/or ventilatory support at the request of a patient or surrogate can be viewed as allowing the patient to die if--and only if--concurrent lethal pathophysiological conditions are present that are unrelated to those functions already supported by medical devices in

  1. Elevation of NT-proBNP and cardiac troponins in sepsis-related deaths: a forensic perspective.

    PubMed

    Tettamanti, Camilla; Hervet, Tania; Grabherr, Silke; Palmiere, Cristian

    2016-07-01

    In the present study, the levels of NT-proBNP, troponin T, and troponin I were measured in postmortem serum from femoral blood in a series of sepsis-related fatalities that had undergone forensic autopsies. We aimed to assess whether a possible increase in the concentrations of these biomarkers was correlated to macroscopic or microscopic observations that suggest myocardial damage or cardiac dysfunction. Two study groups were retrospectively formed, a sepsis-related fatalities group and a control group. Both groups consisted of 16 forensic autopsy cases. Unenhanced computed tomography scan, autopsy, histological, toxicological, microbiological, and biochemical analyses were performed for all cases in both groups. Levels of procalcitonin, C-reactive protein, NT-proBNP, troponin T, and troponin I were systematically measured in postmortem serum from femoral blood. The preliminary results suggest that the postmortem serum troponin I, troponin T, and NT-proBNP levels are increased in sepsis-related deaths in the absence of any relevant coronary artery disease, myocardial ischemia, or signs of heart failure. These findings corroborate clinical data from previous studies pertaining to the usefulness of troponins and natriuretic peptides as indicators of toxic and inflammatory damage to the heart in cases of severe sepsis and septic shock without concomitant underlying coronary syndromes. PMID:27002627

  2. Recovery of transplantable organs after cardiac or circulatory death: Transforming the paradigm for the ethics of organ donation

    PubMed Central

    Verheijde, Joseph L; Rady, Mohamed Y; McGregor, Joan

    2007-01-01

    Organ donation after cardiac or circulatory death (DCD) has been introduced to increase the supply of transplantable organs. In this paper, we argue that the recovery of viable organs useful for transplantation in DCD is not compatible with the dead donor rule and we explain the consequential ethical and legal ramifications. We also outline serious deficiencies in the current consent process for DCD with respect to disclosure of necessary elements for voluntary informed decision making and respect for the donor's autonomy. We compare two alternative proposals for increasing organ donation consent in society: presumed consent and mandated choice. We conclude that proceeding with the recovery of transplantable organs from decedents requires a paradigm change in the ethics of organ donation. The paradigm change to ensure the legitimacy of DCD practice must include: (1) societal agreement on abandonment of the dead donor rule, (2) legislative revisions reflecting abandonment of the dead donor rule, and (3) requirement of mandated choice to facilitate individual participation in organ donation and to ensure that decisions to participate are made in compliance with the societal values of respect for autonomy and self-determination. PMID:17519030

  3. Under-Utilization of Implantable Cardioverter Defibrillators in Patients with Heart Failure - The Current State of Sudden Cardiac Death Prophylaxis

    PubMed Central

    Pillarisetti, Jayasree; Emert, Martin; Biria, Mazda; Chotia, Rashaad; Guda, Rajeshwer; Bommana, Sudharani; Pimentel, Rhea; Vacek, James; Dendi, Raghuveer; Berenbom, Loren; Dawn, Buddhadeb; Lakkireddy, Dhanunjaya

    2016-01-01

    Background Despite ACC/AHA guidelines indicating implantable cardioverter defibrillator (ICD) as class I therapy for primary prevention of sudden cardiac death in patients with EF≤35%, ICD utilization rates in real world practice have been low. Objective To determine the rate of ICD implantation at a tertiary care academic center and to assess the reasons for under-utilization of the same. Methods Review of a prospectively collected database which included all patients diagnosed with an EF≤35% was performed to assess the rate of ICD implantation and mortality. Reasons for non-implantation of ICD were then assessed from detailed chart review. Results A total of 707 patients (age 69.4 ± 14.1 years) with mean EF of 26±7% were analyzed. Only 28% (200/707) of patients had ICDs implanted. Mortality was lower in the group with ICD (25% vs 37%, p=0.004). When patients who either died or were lost to follow-up prior to 2005 were excluded, ICD utilization rate was still low at 37.6%. The most common reason for non-implantation of ICD was physicians not discussing this option with their patients. Patient refusal was the second most common reason. Conclusions ICD Implantation rates for primary prevention of SCD in patients with EF≤35% is low. Physician and patient education should be addressed to improve the utilization rates. PMID:25852239

  4. Single-center study on transplantation of livers donated after cardiac death: A report of 6 cases

    PubMed Central

    SUN, XU-YONG; DONG, JIAN-HUI; QIN, KE; LAN, LIU-GEN; LI, HAI-BIN; HUANG, YING; CAO, SONG; LI, ZHUANG-JIANG; DAI, LONG-JUN

    2016-01-01

    Effective use of all available donated organs is critical, in order to meet the increasing demand for transplants. The present study explored liver transplantation with livers that were donated following cardiac death (DCD). According to the guidelines established by The Red Cross Society of China, 42 DCD organs were procured. Selected donors were treated with extracorporeal membrane oxygenation (ECMO) prior to the organ retrieval. The present single-center study included 6 liver transplantations of DCD organs (5 liver transplants and 1 liver-kidney combined transplant). All 6 recipients had a successful recovery without significant complications. The serum alanine transaminase, total bilirubin and international normalized ratio returned to the normal levels within a short period of time following transplantation, and the liver function remained normal during the follow-up period, which lasted up to 24 months. The present report demonstrated the feasibility of orthotopic liver transplantation using DCD livers. The pre-conditioning DCD donors and optimization of the recipient's condition using ECMO, played a crucial role in ensuring the success of transplantation. PMID:26998025

  5. Asystole to cross-clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors.

    PubMed

    Taner, C Burcin; Bulatao, Ilynn G; Perry, Dana K; Sibulesky, Lena; Willingham, Darrin L; Kramer, David J; Nguyen, Justin H

    2012-08-01

    This study sought to determine the procurement factors that lead to development of intrahepatic bile duct strictures (ITBS) and overall biliary complications in recipients of donation after cardiac death (DCD) liver grafts. Detailed information for different time points during procurement (withdrawal of support; SBP < 50 mmHg; oxygen saturation <30%; mandatory wait period; asystole; incision; aortic cross clamp) and their association with the development of ITBS and overall biliary complications were examined using logistic regression. Two hundred and fifteen liver transplants using DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Of all the time periods during procurement, only asystole-cross clamp period was significantly different between patients with ITBS versus no ITBS (P = 0.048) and between the patients who had overall biliary complications versus no biliary complications (P = 0.047). On multivariate analysis, only asystole-cross clamp period was significant predictor for development of ITBS (P = 0.015) and development of overall biliary complications (P = 0.029). Hemodynamic changes in the agonal period did not emerge as risk factors. The results of the study raise the possibility of utilizing asystole-cross-clamp period in place of or in conjunction with donor warm ischemia time in determining viability or quality of liver grafts. PMID:22703372

  6. Recovery of transplantable organs after cardiac or circulatory death: transforming the paradigm for the ethics of organ donation.

    PubMed

    Verheijde, Joseph L; Rady, Mohamed Y; McGregor, Joan

    2007-01-01

    Organ donation after cardiac or circulatory death (DCD) has been introduced to increase the supply of transplantable organs. In this paper, we argue that the recovery of viable organs useful for transplantation in DCD is not compatible with the dead donor rule and we explain the consequential ethical and legal ramifications. We also outline serious deficiencies in the current consent process for DCD with respect to disclosure of necessary elements for voluntary informed decision making and respect for the donor's autonomy. We compare two alternative proposals for increasing organ donation consent in society: presumed consent and mandated choice. We conclude that proceeding with the recovery of transplantable organs from decedents requires a paradigm change in the ethics of organ donation. The paradigm change to ensure the legitimacy of DCD practice must include: (1) societal agreement on abandonment of the dead donor rule, (2) legislative revisions reflecting abandonment of the dead donor rule, and (3) requirement of mandated choice to facilitate individual participation in organ donation and to ensure that decisions to participate are made in compliance with the societal values of respect for autonomy and self-determination. PMID:17519030

  7. PD98059 Protects Brain against Cells Death Resulting from ROS/ERK Activation in a Cardiac Arrest Rat Model

    PubMed Central

    Nguyen Thi, Phuong Anh; Chen, Meng-Hua; Li, Nuo; Zhuo, Xiao-Jun; Xie, Lu

    2016-01-01

    The clinical and experimental postcardiac arrest treatment has not reached therapeutic success. The present study investigated the effect of PD98059 (PD) in rats subjected to cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). Experimental rats were divided randomly into 3 groups: sham, CA, and PD. The rats except for sham group were subjected to CA for 5 min followed by CPR operation. Once spontaneous circulation was restored, saline and PD were injected in CA and PD groups, respectively. The survival rates and neurologic deficit scores (NDS) were observed, and the following indices of brain tissue were evaluated: ROS, MDA, SOD, p-ERK1/2/ERK1/2, caspase-3, Bax, Bcl-2, TUNEL positive cells, and double fluorescent staining of p-ERK/TUNEL. Our results indicated that PD treatment significantly reduced apoptotic neurons and improved the survival rates and NDS. Moreover, PD markedly downregulated the ROS, MDA, p-ERK, and caspase-3, Bax and upregulated SOD and Bcl-2 levels. Double staining p-ERK/TUNEL in choroid plexus and cortex showed that cell death is dependent on ERK activation. The findings in present study demonstrated that PD provides neuroprotection via antioxidant activity and antiapoptosis in rats subjected to CA/CPR. PMID:27069530

  8. Usefulness of Electrocardiographic Patterns at Presentation to Predict Long-term Risk of Cardiac Death in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Biagini, Elena; Pazzi, Chiara; Olivotto, Iacopo; Musumeci, Beatrice; Limongelli, Giuseppe; Boriani, Giuseppe; Pacileo, Giuseppe; Mastromarino, Vittoria; Bacchi Reggiani, Maria Letizia; Lorenzini, Massimiliano; Lai, Francesco; Berardini, Alessandra; Mingardi, Francesca; Rosmini, Stefania; Resciniti, Elvira; Borghi, Claudia; Autore, Camillo; Cecchi, Franco; Rapezzi, Claudio

    2016-08-01

    The objective of this study was to investigate the prognostic significance of 12-lead electrocardiogram (ECG) patterns in a large multicenter cohort of patients with hypertrophic cardiomyopathy; 1,004 consecutive patients with hypertrophic cardiomyopathy and a recorded standard ECG (64% men, mean age 50 ± 16 years) were evaluated at 4 Italian centers. The study end points were sudden cardiac death (SCD) or surrogates, including appropriate implanted cardiac defibrillator discharge and resuscitated cardiac arrest and major cardiovascular events (including SCD or surrogates and death due to heart failure, cardioembolic stroke, or heart transplantation). Prevalence of baseline electrocardiographic characteristics was: normal ECG 4%, ST-segment depression 56%, pseudonecrosis waves 33%, "pseudo-ST-segment elevation myocardial infarction (STEMI)" pattern 17%, QRS duration ≥120 ms 17%, giant inverted T waves 6%, and low QRS voltages 3%. During a mean follow-up of 7.4 ± 6.8 years, 77 patients experienced SCD or surrogates and 154 patients experienced major cardiovascular events. Independent predictors of SCD or surrogates were unexplained syncope (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.4 to 4.5, p = 0.003), left ventricular ejection fraction <50% (HR 3.5, 95% CI 1.9 to 6.7, p = 0.0001), nonsustained ventricular tachycardia (HR 1.7, 95% CI 1.1 to 2.6, p = 0.027), pseudo-STEMI pattern (HR 2.3, 95% CI 1.4 to 3.8, p = 0.001), QRS duration ≥120 ms (HR 1.8, 95% CI 1.1 to 3.0, p = 0.033), and low QRS voltages (HR 2.3, 95% CI 1.01 to 5.1, p = 0.048). Independent predictors of major cardiovascular events were age (HR 1.02, 95% CI 1.01 to 1.03, p = 0.0001), LV ejection fraction <50% (HR 3.73, 95% CI 2.39 to 5.83, p = 0.0001), pseudo-STEMI pattern (HR 1.66, 95% CI 1.13 to 2.45, p = 0.010), QRS duration ≥120 ms (HR 1.69, 95% CI 1.16 to 2.47, p = 0.007), and prolonged QTc interval (HR 1.68, 95% CI 1.21 to 2.34, p = 0.002). In conclusion, a detailed

  9. Acute alcohol intoxication and suicide: a gender-stratified analysis of the National Violent Death Reporting System

    PubMed Central

    Kaplan, Mark S; McFarland, Bentson H; Huguet, Nathalie; Conner, Kenneth; Caetano, Raul; Giesbrecht, Norman; Nolte, Kurt B

    2013-01-01

    Objectives Although it is well known that people with alcohol dependence are at a markedly elevated risk for suicide, much less is known about the role of acute alcohol use in suicidal behaviours. The primary aims of this epidemiological study were to assess the prevalence and factors associated with acute alcohol intoxication among 57 813 suicide decedents in 16 states. Methods Data from the restricted National Violent Death Reporting System 2003–2009 for male and female suicide decedents aged 18 years and older were analysed by multiple logistic regression to compare decedents with and without acute alcohol intoxication (defined as blood alcohol concentration (BAC) ≥0.08 g/dl). Results Among men, those who were younger, American Indian/Alaska Native, Hispanic, veterans, of lower educational attainment, deceased from a self-inflicted firearm injury or hanging/suffocation and residing in rural areas were more likely to have been intoxicated at the time of death. Among women, the factors associated with a BAC ≥0.08 g/dl were younger age, being American Indian/Alaska Native, and using a firearm, hanging/suffocation or falling as method of death. Conclusions In both men and women, alcohol intoxication was associated with violent methods of suicide and declined markedly with age, suggesting that addressing risks associated with acute alcohol use may be of the greatest aid in the prevention of violent suicides among young and middle age adults. PMID:22627777

  10. Predictors of hyperkalemia and death in patients with cardiac and renal disease.

    PubMed

    Jain, Nishank; Kotla, Suman; Little, Bertis B; Weideman, Rick A; Brilakis, Emmanouil S; Reilly, Robert F; Banerjee, Subhash

    2012-05-15

    Predictors of hyperkalemia in patients with cardiovascular disease (CVD; defined as patients with hypertension and heart failure) and associated chronic kidney disease (CKD) are not well established. The aim of this study was to ascertain risk factors of hyperkalemia (defined as serum potassium concentration >5.0 mEq/L) and associated all-cause mortality in patients with CVD treated with antihypertensive drugs that impair potassium homeostasis. In a retrospective analysis using a logistic regression model, risk factors for hyperkalemia and all-cause mortality were analyzed in 15,803 patients with CVD treated with antihypertensive drugs. The mean estimated glomerular filtration rate and mean serum potassium concentration were 55.55 ml/min/1.73 m(2) and 4.06 mEq/L, respectively. Hyperkalemia was observed in 24.5% of study patients and 1.7% of total hospital admissions. Compared to patients with normokalemia, those with hyperkalemia had a higher percentage of death (6.25% vs 2.92%, p = 0.0001) and admissions (7.80% vs 5.04%, p = 0.0001). Predictors of hyperkalemia were CKD stage (odds ratio [OR] 2.14, 95% confidence interval [CI] 2.02 to 2.28), diabetes mellitus (OR 1.59, 95% CI 1.47 to 1.72), coronary artery disease (OR 1.32, 95% CI 1.21 to 1.43), and peripheral vascular disease (OR 1.55, 95% CI 1.36 to 1.77). Predictors of all-cause mortality were CKD stage (OR 1.26, 95% CI 1.12 to 1.43), hyperkalemic event (OR 1.56, 95% CI 1.30 to 1.88), age (OR 1.04, 95% CI 1.03 to 1.05), and hospitalization (OR 1.04, 95% CI 1.04 to 1.05). In conclusion, hyperkalemia is encountered frequently in patients with established CVD who are taking antihypertensive drugs and is associated with increases in all-cause mortality and hospitalizations. Advanced CKD, diabetes mellitus, coronary artery disease, and peripheral vascular disease are independent predictors of hyperkalemia. PMID:22342847

  11. Sudden Cardiac Death Associated with Anomalous Origin of the Left Main Coronary Artery from the Right Sinus, with an Intramural Course

    PubMed Central

    Chang, Huai-Ren; Hsieh, Jen-Che; Chao, Shen-Feng; Wang, Ji-Hung

    2015-01-01

    Anomalous origin of the left main coronary artery from the right sinus of Valsalva is extremely rare and can lead to sudden cardiac death. We report a case in which an 18-year-old college student collapsed immediately after a long-distance run of 10 km. After cardiopulmonary resuscitation and electrical shock for ventricular fibrillation, she experienced a return of spontaneous circulation. Cardiac catheterization and cardiac computed tomographic angiography revealed an unusually long intramural course of the left main coronary artery from the right sinus of Valsalva. The young woman underwent a successful unroofing operation for coronary artery correction. She remained asymptomatic upon exercise during 2.5 years of follow-up. PMID:26664310

  12. Prognostic Role of Multiple Cardiac Biomarkers in Newly Diagnosed Acute Coronary Syndrome Patients.

    PubMed

    Rahman, M M; Alam, M M; Jahan, N A; Shila, J S; Arslam, M I

    2016-04-01

    Acute coronary syndrome includes unstable angina and myocardial infarction with or without ST-segment elevation, is life-threatening disorders that remain a source of high morbidity and mortality despite advances in treatment. The aim of the study was to evaluate the prognostic role of serum cTnI, CK-MB, hsCRP, MPO and BNP in newly diagnosed acute coronary syndrome patients. This cohort study was carried out in the Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University in cooperation with the Department of Cardiology, BSMMU and NICVD during the period of March 2013 to February 2014. A total 100 newly diagnosed acute coronary syndrome patients were purposively enrolled in this study within 24 hours of attacked, among them 30 were NSTEMI, 65 were STEMI and 5 were unstable angina. Serum cTnI, CK-MB, hsCRP, MPO and BNP concentrations were measured at enrollment and grouping of the study subjects were done on the basis of their empirical cut off values into two groups. In cTnI: Group I (n=20) having cTnI <4ng/ml and Group II (n=80) having cTnI ≥4ng/ml. In CK-MB: Group I (n=18) having CK-MB <10ng/ml and Group II (n= 82) having CK-MB ≥10ng/ml. In hsCRP: Group I (n=36) having hsCRP <5mg/L and Group II (n=64) having hsCRP ≥5mg/L. In MPO: Group I (n=30) having MPO <285.5pmol/L and Group II (n=70) having MPO ≥285.5pmol/L. In BNP: Group I (n=26) having BNP <135pg/ml and Group II (n=74) having BNP ≥135pg/ml. All the study subjects were treated and managed identically by standard management protocol and were followed up periodically up to three months from the onset of events during hospital stay and after discharge. Clinical outcomes of the study subjects such as good recovery, morbidity (recurrent ACS, heart failure, arrhythmia and revascularization) and mortality were evaluated with respect to their base line cTnI, CK-MB, hsCRP, MPO and BNP concentrations. Increased levels of base line cardiac biomarkers in Group II patients showed significantly

  13. Sirt1-Positive Lymphocytes in Acute Cellular Cardiac Allograft Rejection: Contributor to Pathogenesis and a Therapeutic Target.

    PubMed

    Welsh, Kerry J; Zhao, Bihong; Buja, L Maximilian; Brown, Robert E

    2016-01-01

    Cardiac allograft rejection remains a problem, despite advances with immunosuppressants. Understanding the mechanisms behind rejection is essential for developing targeted therapies. The goal of this investigation is to explore Sirtuin 1 (Sirt1) as a therapeutic target for cardiac allograft rejection. Thirteen endomyocardial biopsy specimens with acute cellular rejection (grade 2R or 3R) were selected. CD3, CD4, CD8, CD20, CD68, T-cell intracytoplasmic antigen (TIA-1), and Sirt1 expressions were determined by immunohistochemical stains. Comparison of Sirt1 expression was made with 10 cases of grade 0R and grade 1R. Quantitative image analysis was performed. There were 2 cases of grade 3R and 11 cases of grade 2R acute cellular rejection. Sirtuin 1 expression was present in the majority of mononuclear cells (median percentage, 73.5; interquartile range, 51.2-100%); staining was also observed in cardiomyocytes. Twelve of the 13 cases (92.3%) had an elevated CD8/FoxP3 ratio, coinciding with acute cellular rejection. Sirtuin 1 expression in the nuclei of FoxP3+ cells can lead to deacetylation and inactivation of FoxP3 rendering the T-suppressor cells inactive and promoting acute cellular rejection. The use of a Sirt1 inhibitor may be a therapeutic option in expanding the functionality of the FoxP3+ T-suppressor cells and moderating the severity of such rejection. PMID:26771391

  14. Acute death associated with Citrobacter freundii infection in an African elephant (Loxodonta africana).

    PubMed

    Ortega, Joaquín; Corpa, Juan M; Orden, José A; Blanco, Jorge; Carbonell, María D; Gerique, Amalia C; Latimer, Erin; Hayward, Gary S; Roemmelt, Andreas; Kraemer, Thomas; Romey, Aurore; Kassimi, Labib B; Casares, Miguel

    2015-09-01

    A 21-year-old male African elephant (Loxodonta africana) died suddenly with no previous medical history. Grossly, there were severe multifocal epicardial and endocardial hemorrhages of the atria and ventricles, hydropericardium, multifocal pleural hemorrhages, and severe pulmonary congestion and edema. Histologically, there was fibrinoid vasculitis and thrombosis in the heart and lung and myocardial necrosis. Citrobacter freundii was isolated in abundance in pure culture from liver and heart samples. Low levels of multiples types of elephant endotheliotropic herpesvirus (EEHV-6, EEHV-2B, and EEHV-3A) were detected in spleen samples, but not in heart samples. The levels of EEHV DNA found were much lower than those usually associated with acute EEHV hemorrhagic disease, and many other genomic loci that would normally be found in such cases were evidently below the level of detection. Therefore, these findings are unlikely to indicate lethal EEHV disease. Polymerase chain reaction for encephalomyocarditis virus (EMCV) and toxicology for oleander (Nerium oleander) were negative. Stress, resulting from recent transport, and antimicrobial therapy may have contributed to the death of this animal. PMID:26179092

  15. Acute Kidney Injury in ICU Patients Following Non-Cardiac Surgery at Masih Daneshvari Hospital: Joint Modeling Application

    PubMed Central

    Khoundabi, Batoul; Mansourian, Marjan; Kazempoor Dizaji, Mehdi; Hashemian, Seyed Mohammadreza

    2015-01-01

    Background: Admission to the intensive care unit (ICU) is often complicated by early acute kidney injury (AKI). AKI is associated with high rates of mortality and morbidity. Risk factors and incidence of AKI have been notably high following non-cardiac surgery in the past decade. The aim of this study was to determine the hazard rate of AKI, the effect of risk factors of AKI and also to assess the changes in urine output (UO) as a predictor of AKI using joint modeling in patients undergoing non-cardiac surgery. Materials and Methods: In this retrospective cohort study, 400 non-cardiac-operated patients admitted during 3 years to the ICU of Masih Daneshvari Hospital were selected according to the consecutive sample selection method. Random mixed effect model and survival model were used to assess UO changes and the effect of UO and other risk factors on the hazard rate of AKI using joint analysis. Results: AKI occurred in 8.8% of the Iranian non-cardiac-operated patients. Survival model showed that the risk of AKI in lower diastolic blood pressure (DBP), higher Acute Physiology and Chronic Health Evaluation II score (APACHE II score), emergency surgery, longer hospitalization and male patients was higher (P=0.001). Using joint modeling, an association was found between the risk of AKI and UO (−0.19, P=0.002). Conclusion: Several predictors were found to be associated with AKI in the Iranian patients after non-cardiac surgery. A relationship between longitudinal and survival responses was found in this study and joint modeling caused considerable improvement in estimations compared to separate longitudinal and survival models. PMID:26221152

  16. Rapamycin Treatment of Healthy Pigs Subjected to Acute Myocardial Ischemia-Reperfusion Injury Attenuates Cardiac Functions and Increases Myocardial Necrosis

    PubMed Central

    Lassaletta, Antonio D; Elmadhun, Nassrene Y; Zanetti, Arthus V D; Feng, Jun; Anduaga, Javier; Gohh, Reginald Y.; Sellke, Frank W; Bianchi, Cesario

    2013-01-01

    Background The Mechanistic Target of Rapamycin (mTOR) pathway is a major regulator of cell immunity and metabolism. mTOR is a well-known suppressor of tissue rejection in organ transplants, however, it has other non-immune functions including in the cardiovascular system, where it is a regulator of heart hypertrophy and locally, in coated vascular stents, inhibits vascular wall cell growth and hence neointimal formation/restenosis. Because the mTOR pathway plays major roles in normal cell growth, metabolism and survival, we hypothesized that inhibiting it with rapamycin, prior to an acute myocardial ischemia-reperfusion injury (IRI), would confer cardioprotection by virtue of slowing down cardiac function and metabolism. Methods Yorkshire pigs received orally either placebo or 4 mg/day rapamycin for 7 days before the IRI. All animals underwent median sternotomy and the mid-left anterior descending coronary artery was occluded for 60 min followed by 120 min of reperfusion. Left ventricular pressure-volume data was collected throughout the operation. The ischemic and infarcted areas were determined by monastral blue and triphenyltetrazolium chloride staining, respectively and plasma cardiac troponin I concentration. mTOR kinase activities were monitored in remote cardiac tissue by western blotting with specific antibodies against specific substrates phosphorylating sites. Results Rapamycin pre-treatement impaired endothelial-dependent vasorelaxation, attenuated cardiac function during IRI, and increased myocardial necrosis. Western blotting confirmed effective inhibition of myocardial mTOR kinase activities. Conclusions Pre-treatment of healthy pigs with rapamycin prior to acute myocardial IRI is associated with decreased cardiac function and higher myocardial necrosis. PMID:24266948

  17. Contribution of damage-associated molecular patterns to transfusion-related acute lung injury in cardiac surgery

    PubMed Central

    Müller, Marcella C.A.; Tuinman, Pieter R.; Vlaar, Alexander P.; Tuip, Anita M.; Maijoor, Kelly; Achouiti, Achmed; van t Veer, Cornelis; Vroom, Margreeth B.; Juffermans, Nicole P.

    2014-01-01

    Background The incidence of transfusion-related acute lung injury (TRALI) in cardiac surgery patients is high and this condition contributes to an adverse outcome. Damage-associated molecular pattern (DAMP) molecules, HMGB1 and S100A12, are thought to mediate inflammatory changes in acute respiratory distress syndrome. We aimed to determine whether DAMP are involved in the pathogenesis of TRALI in cardiac surgery patients. Materials and methods This was a secondary analysis of a prospective observational trial in cardiac surgery patients admitted to the Intensive Care Unit of a university hospital in the Netherlands. Fourteen TRALI cases were randomly matched with 32 transfused and non-transfused controls. Pulmonary levels of HMGB1, S100A12 and inflammatory cytokines (interleukins-1β, -6, and -8 and tumour necrosis factor-α) were determined when TRALI evolved. In addition, systemic and pulmonary levels of soluble receptor for advanced glycation end products (sRAGE) were determined. Results HMGB1 expression and levels of sRAGE in TRALI patients did not differ from those in controls. There was a trend towards higher S100A12 levels in TRALI patients compared to the controls. Furthermore, S100A12 levels were associated with increased levels of markers of pulmonary inflammation, prolonged cardiopulmonary bypass, hypoxemia and duration of mechanical ventilation. Conclusion No evidence was found that HMGB1 and sRAGE contribute to the development of TRALI. S100A12 is associated with duration of cardiopulmonary bypass, pulmonary inflammation, hypoxia and prolonged mechanical ventilation and may contribute to acute lung injury in cardiac surgery patients. PMID:24887223

  18. Impairment of antioxidant defense via glutathione depletion sensitizes acute lymphoblastic leukemia cells for Smac mimetic-induced cell death.

    PubMed

    Schoeneberger, H; Belz, K; Schenk, B; Fulda, S

    2015-07-30

    Evasion of apoptosis in pediatric acute lymphoblastic leukemia (ALL) is linked to aberrant expression of inhibitor of apoptosis (IAP) proteins and dysregulated redox homeostasis, rendering leukemic cells vulnerable to redox-targeting therapies. Here we discover that inhibition of antioxidant defenses via glutathione (GSH) depletion by buthionine sulfoximine (BSO) primes ALL cells for apoptosis induced by the Smac mimetic BV6 that antagonizes IAP proteins. Similarly, BSO cooperates with BV6 to induce cell death in patient-derived primary leukemic samples, underscoring the clinical relevance. In contrast, BSO does not sensitize non-malignant lymphohematopoietic cells from healthy donors toward BV6, pointing to some tumor selectivity. Mechanistically, both agents cooperate to stimulate reactive oxygen species (ROS) production, which is required for BSO/BV6-induced cell death, as ROS inhibitors (that is, N-acetylcysteine, MnTBAP, Trolox) significantly rescue cell death. Further, BSO and BV6 cooperate to trigger lipid peroxidation, which is necessary for cell death, as genetic or pharmacological blockage of lipid peroxidation by GSH peroxidase 4 (GPX4) overexpression or α-tocopherol significantly inhibits BSO/BV6-mediated cell death. Consistently, GPX4 knockdown or GPX4 inhibitor RSL3 enhances lipid peroxidation and cell death by BSO/BV6 cotreatment. The discovery of redox regulation of Smac mimetic-induced cell death has important implications for developing rational Smac mimetic-based combination therapies. PMID:25381820

  19. Referrals in Acute Coronary Events for CARdiac Catheterization: The RACE CAR trial

    PubMed Central

    Kreatsoulas, Catherine; Sloane, Debi; Pogue, Janice; Velianou, James L; Anand, Sonia S

    2010-01-01

    BACKGROUND: Women with acute coronary syndromes have lower rates of cardiac catheterization (CC) than men. OBJECTIVE: To determine whether sex/gender, age, risk level and patient preference influence physician decision making to refer patients for CC. METHODS: Twelve clinical scenarios controlling for sex/gender, age (55 or 75 years of age), Thrombolysis in Myocardial Infarction risk score (low, moderate or high) and patient preference for CC (agreeable or refused/no preference expressed) were designed. Scenarios were administered to specialists across Canada using a web-based computerized survey instrument. Questions were standardized using a five-point Likert scale ranging from 1 (very unlikely to benefit from CC) to 5 (very likely to benefit from CC). Outcomes were assessed using a two-tailed mixed linear regression model. RESULTS: Of 237 scenarios, physicians rated men as more likely to benefit from CC than women (mean [± SE] 4.44±0.07 versus 4.25±0.07, P=0.03), adjusted for age, risk and patient preference. Low-risk men were perceived to benefit more than low-risk women (4.20±0.13 versus 3.54±0.14, P<0.01), and low-risk younger patients were perceived to benefit more than low-risk older patients (4.52±0.17 versus 3.22±0.16, P<0.01). Regardless of risk, patients who agreed to CC were perceived as more likely to benefit from CC than patients who were disagreeable or made no comment at all (5.0±0.23, 3.67±0.21, 2.95±0.14, respectively, P<0.01). CONCLUSION: Canadian specialists’ decisions to refer patients for CC appear to be influenced by sex/gender, age and patient preference in clinical scenarios in which cardiac risk is held constant. Future investigation of possible age and sex/gender biases as proxies for risk is warranted. PMID:20931097

  20. Role of cardiac output and the autonomic nervous system in the antinatriuretic response to acute constriction of the thoracic superior vena cava.

    NASA Technical Reports Server (NTRS)

    Schrier, R. W.; Humphreys, M. H.; Ufferman, R. C.

    1971-01-01

    Study of the differential characteristics of hepatic congestion and decreased cardiac output in terms of potential afferent stimuli in the antinatriuretic effect of acute thoracic inferior vena cava (TIVC) constriction. An attempt is made to see if the autonomic nervous system is involved in the antinatriuretic effect of acute TIVC or thoracic superior vena cava constriction.

  1. Sex, Socioeconomic Status, Access to Cardiac Catheterization and Outcomes for Acute Coronary Syndromes in the Context of Universal Healthcare Coverage

    PubMed Central

    Fabreau, Gabriel E.; Leung, Alexander A.; Southern, Danielle A.; Knudtson, Merrill L.; McWilliams, J. Michael; Ayanian, John Z.; Ghali, William A.

    2015-01-01

    Background Sex and neighborhood socioeconomic status (nSES) may independently affect the care and outcomes of acute coronary syndromes (ACS), partly through barriers in timely access to cardiac catheterization. We sought to determine whether sex modifies the association between nSES, and the receipt of cardiac catheterization and mortality following an ACS in a universal healthcare system. Methods and Results We studied 14,012 ACS patients admitted to cardiology services between April 18, 2004 and December 31, 2011 in Southern Alberta, Canada. We used multivariable logistic regression to compare the odds of cardiac catheterization within 2 and 30 days of admission and the odds of 30-day and 1-year mortality for men and women by quintile of neighborhood median household income. Significant relationships between nSES and the receipt of cardiac catheterization and mortality after ACS were detected for women but not men. When examined by nSES, each incremental decrease in neighborhood income quintile for women was associated with a 6% lower odds of receiving cardiac catheterization within 30 days (p=0.01) and a 14% higher odds of 30-day mortality (p=0.03). For men, each decrease in neighborhood income quintile was associated with a 2% lower odds of receiving catheterization within 30 days (p=0.10), and a 5% higher odds of 30-day mortality (p=0.36). Conclusions Associations between nSES and receipt of cardiac catheterization and 30-day mortality were noted for women but not men in a universal healthcare system. Care protocols designed to improve equity of access to care and outcomes are required, especially for low-income women. PMID:24895450

  2. Magnolia extract (BL153) protection of heart from lipid accumulation caused cardiac oxidative damage, inflammation, and cell death in high-fat diet fed mice.

    PubMed

    Sun, Weixia; Zhang, Zhiguo; Chen, Qiang; Yin, Xia; Fu, Yaowen; Zheng, Yang; Cai, Lu; Kim, Ki-Soo; Kim, Ki Ho; Tan, Yi; Kim, Young Heui

    2014-01-01

    Magnolia as an herbal material obtained from Magnolia officinalis has been found to play an important role in anti-inflammation, antioxidative stress, and antiapoptosis. This study was designed to investigate the effect of Magnolia extract (BL153) on obesity-associated lipid accumulation, inflammation, oxidative stress, and apoptosis in the heart. C57BL/6 mice were fed a low- (10 kcal% fat) or high-fat (60 kcal% fat) diet for 24 weeks to induce obesity. These mice fed with high-fat diet (HFD) were given a gavage of vehicle, 2.5, 5, or 10 mg/kg body weight BL153 daily. The three doses of BL153 treatment slightly ameliorated insulin resistance without decrease of body weight gain induced by HFD feeding. BL153 at 10 mg/kg slightly attenuated a mild cardiac hypertrophy and dysfunction induced by HFD feeding. Both 5 mg/kg and 10 mg/kg of BL153 treatment significantly inhibited cardiac lipid accumulation measured by Oil Red O staining and improved cardiac inflammation and oxidative stress by downregulating ICAM-1, TNF-α, PAI-1, 3-NT, and 4-HNE. TUNEL staining showed that BL153 treatment also ameliorated apoptosis induced by mitochondrial caspase-3 independent cell death pathway. This study demonstrates that BL153 attenuates HFD-associated cardiac damage through prevention of HFD-induced cardiac lipid accumulation, inflammation, oxidative stress, and apoptosis. PMID:24693333

  3. Urine Output During Cardiopulmonary Bypass Predicts Acute Kidney Injury After Cardiac Surgery

    PubMed Central

    Song, Young; Kim, Dong Wook; Kwak, Young Lan; Kim, Beom Seok; Joo, Hyung Min; Ju, Jin Woo; Yoo, Young Chul

    2016-01-01

    Abstract Urine output is closely associated with renal function and has been used as a diagnostic criterion for acute kidney injury (AKI). However, urine output during cardiopulmonary bypass (CPB) has never been identified as a predictor of postoperative AKI. Considering altered renal homeostasis during CPB, we made a comprehensible approach to CPB urine output and evaluated its predictability for AKI. Patients undergoing cardiovascular surgery with the use of CPB, between January 2009 and December 2011, were retrospectively reviewed. AKI was defined as an increase in serum creatinine ≥0.3 mg/dL in the first postoperative 48 hours. We extrapolated a possible optimal amount of urine output from the plot of probability of AKI development according to CPB urine output. After separating patients by the predicted optimal value, we performed stepwise logistic regression analyses to find potential predictors of AKI in both subgroups. A total of 696 patients were analyzed. The amount of CPB urine output had a biphasic association with the incidence of AKI using 4 mL/kg/h as a boundary value. In a multivariate logistic regression to find predictors for AKI in entire patients, CPB urine output did not show statistical significance. After separating patients into subgroups with CPB urine output below and over 4 mL/kg/h, it was identified as an independent predictor for AKI with the odds ratio of 0.43 (confidence interval 0.30–0.61) and 1.11 (confidence interval 1.02–1.20), respectively. The amount of urine output during CPB with careful analysis may serve as a simple and feasible method to predict the development of AKI after cardiac surgery at an early time point. PMID:27258505

  4. Comparison of five cardiac markers in the detection of reperfusion after thrombolysis in acute myocardial infarction.

    PubMed Central

    Lavin, F.; Kane, M.; Forde, A.; Gannon, F.; Daly, K.

    1995-01-01

    OBJECTIVE--To investigate and compare the clinical usefulness of serial measurements of five cardiac marker proteins, namely creatine kinase (CK), CK-MB mass, myoglobin, troponin T, and myosin light chain 1, in the early detection of reperfusion after thrombolytic treatment. METHOD--Serial blood samples were taken from 26 patients presenting with acute myocardial infarction. Concentrations of the five markers were assayed in each sample. Thrombolytic treatment was given to the patients who were divided into those who reperfused (n = 17, group A) and those who failed to reperfuse (n = 9, group B) on the basis of clinical signs and angiography within 24 h. RESULTS--The release profiles of CK, CK-MB mass, myoglobin, and troponin T for patients in group A differed from those of patients in group B. No difference was observed in the release profile of myosin light chain 1 between the two groups. The time to peak concentration of CK, CK-MB mass, myoglobin, and troponin T occurred significantly earlier in patients of group A than in those of group B, with myoglobin peaking earlier than the other markers. An index, defined as the ratio of the concentration of each marker immediately before and 2 h after the start of thrombolytic treatment, was calculated for each marker in groups A and B. The 2 h myoglobin and troponin T indices were significantly different between groups A and B. The diagnostic efficiency of the myoglobin index, however, was best at 85%. CONCLUSIONS--These studies suggest that myoglobin has greater potential than the other markers examined in the detection of reperfusion after thrombolytic treatment. PMID:7786656

  5. [Usefulness of serum cardiac myosin light chain I for the estimation of acute myocardial infarction size].

    PubMed

    Narita, M; Kurihara, T; Murano, K; Usami, M

    1991-09-01

    To evaluate the usefulness of serum level of cardiac myosin light chain I (LC I) for the estimation of the extent of acute myocardial infarction (AMI), peak LC I level was compared with myocardial infarction weight (AMI weight) which was obtained by myocardial emission tomography with Tc-99m pyrophosphate (PYP). In 11 patients with AMI, serum LC I levels were measured once a day in most cases, and plasma CPK levels were measured serially (every 4 hours at least 48 hours after admission). Tc-99m PYP imagings were performed at second or third day of AMI, and AMI weight was calculated from the voxel numbers of myocardial hot spot in which Tc-99m PYP had accumulated. Peak LC I level correlated well with AMI weight (r = 0.72, p less than 0.02). As well as peak LC I level, peak CPK level correlated well with AMI weight (r = 0.68, p less than 0.05). But the estimation of the infarct size from peak LC I level had the following advantages over the estimation from peak CPK level. 1) We could compare peak LC I level with AMI weight in all 11 patients, but peak CPK level was able to compared with AMI weight in only 9 of them. This was because CPK level changed rapidly and reached maximum within 24 hours after the onset of AMI, while LC I level peaked after 3 to 5 days. 2) A good correlation between LC I and AMI weight was obtained by the determination of serum LC I level once a day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1836269

  6. Acute L-CPT1 Overexpression Recapitulates Reduced Palmitate Oxidation of Cardiac Hypertrophy

    PubMed Central

    Lewandowski, E. Douglas; Fischer, Susan K.; Fasano, Matthew; Banke, Natasha H.; Walker, Lori A.; Huqi, Alda; Wang, Xuerong; Lopaschuk, Gary D.; O’Donnell, J. Michael

    2012-01-01

    Rationale Muscle carnitine palmitoyltransferase I (M-CPT1) is predominant in heart, but the liver isoform (L-CPT1) is elevated in hearts with low long chain fatty acid (LCFA) oxidation, such as fetal and hypertrophied hearts. Objective This work examined the effect of acute L-CPT1 expression has on the regulation of palmitate oxidation and energy metabolism in intact functioning rat hearts for comparison to findings in hypertrophied hearts. Methods and Results L-CPT1 was expressed in vivo in rat hearts by coronary perfusion of Adv.cmv.L-CPT1 (L-CPT1, n=15) versus PBS infusion (PBS, n=7) or empty virus (EMPTY, n=5). L-CPT1 was elevated 5-fold at 72 hours after Adv.cmv.L-CPT1 infusion (P<0.05), but M-CPT1 was unaffected. Despite similar tricarboxylic acid cycle rates, palmitate oxidation rates were reduced with L-CPT1 (1.12±0.29 micromole/min/g dw, mean ± SE) vs PBS (1.6±0.34). Acetyl CoA production from palmitate was reduced with L-CPT1 (69%±0.02, P<0.05; PBS= 79%±0.01, Empty=81%±0.02), similar to what occurs in hypertrophied hearts and with no difference in malonyl CoA content. Glucose oxidation was elevated with L-CPT1 (by 60%). Surprisingly, L-CPT1 hearts contained elevated atrial natriuretic peptide, indicating induction of hypertrophic signaling. Conclusions The results link L-CPT1 expression to reduced palmitate oxidation in a non-diseased, adult heart, recapitulating the phenotype of reduced LCFA oxidation in cardiac hypertrophy. The implications are that L-CPT1 expression induces metabolic remodeling hypertrophic signaling, and that regulatory factors beyond malonyl-CoA in the heart regulate LCFA oxidation via L-CPT1. PMID:22982985

  7. Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction

    SciTech Connect

    McGhie, A.I.; Corbett, J.R.; Akers, M.S.; Kulkarni, P.; Sills, M.N.; Kremers, M.; Buja, L.M.; Durant-Reville, M.; Parkey, R.W.; Willerson, J.T. )

    1991-02-01

    The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.

  8. Body Mass Index as a Predictor of Sudden Cardiac Death and Usefulness of the Electrocardiogram for Risk Stratification.

    PubMed

    Eranti, Antti; Aro, Aapo L; Kerola, Tuomas; Tikkanen, Jani T; Rissanen, Harri A; Anttonen, Olli; Junttila, M Juhani; Knekt, Paul; Huikuri, Heikki V

    2016-02-01

    Evidence of the role of body mass index (BMI) as a risk factor for sudden cardiac death (SCD) is conflicting, and how electrocardiographic (ECG) SCD risk markers perform in subjects with different BMIs is not known. In this study, a general population cohort consisting of 10,543 middle-aged subjects (mean age 44 years, 52.7% men) was divided into groups of lean (BMI <20, n = 374), normal weight (BMI 20.0 to 24.9, n = 4,334), overweight (BMI 25.0 to 29.9, n = 4,390), and obese (BMI >30, n = 1,445) subjects. Cox proportional hazards models adjusted for confounders were used to assess the risk for SCD associated with BMI and the risk for SCD associated with ECG abnormalities in subjects with different BMIs. The overweight and obese subjects were at increased risk for SCD (hazard ratios [95% CIs] were 1.33 [1.13 to 1.56], p = 0.001 and 1.79 [1.44 to 2.23], p <0.001 for overweight and obese subjects, respectively). The risk of non-SCD had a similar relation with BMI as SCD. Hazard ratios associated with ECG abnormalities were 3.03, 1.75, 1.74, and 1.34 in groups of lean, normal weight, overweight, and obese subjects, respectively, but no statistical significance was reached in the obese. ECG abnormalities improved integrated discrimination indexes and continuous net reclassification indexes statistically significantly only in the normal weight group. In conclusion, the overweight and obese are at increased risk for SCD but also for non-SCD, and ECG abnormalities are associated with increased risk of SCD also in normal weight subjects presenting with less traditional cardiovascular risk factors. PMID:26723105

  9. Acute-phase proteins, oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin in Arabian mares affected with pyometra.

    PubMed

    El-Bahr, S M; El-Deeb, W M

    2016-09-01

    New biomarkers are essential for diagnosis of pyometra in mares. In this context, 12 subfertile Arabian mares suffered from pyometra were admitted to the Veterinary Teaching Hospital. The basis for diagnosis of pyometra was positive findings of clinical examination and rectal palpation. Blood samples were collected from diseased animals and from five Arabian healthy mares, which were considered as control group. Acute-phase proteins (APP), oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin I were estimated in the harvested sera of both groups. Clinical examination revealed purulent yellowish fluid discharged from vagina of affected animals and rectal palpation of the reproductive tract revealed uterine distention. The biochemical analysis of the serum revealed significant increase in cardiac troponin I, creatin kinase, alkaline phosphatase, malondialdehyde, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin, and serum amyloid A and significant decrease in reduced glutathione, superoxide dismutase (SOD), total antioxidant capacity, and nitric oxide (NO) of mares affected with pyometra compare to control. Cardiac troponin I was positively correlated with aspartate aminotransferase, creatin kinase, malondialdehyde, alkaline phosphatase, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin and serum amyloid A and negatively correlated with glutathione, superoxide dismutase, total antioxidant capacity and nitric oxide in serum of mares affected with pyometra. Moreover, there was high positive correlation between proinflammatory cytokines and APP in serum of mares affected with pyometra. The present study suggests cardiac troponin I together with APP, proinflammatory cytokines, and oxidative stress parameters as biomarkers for pyometra in Arabian mares. PMID:27177966

  10. Presumed consent for organ preservation in uncontrolled donation after cardiac death in the United States: a public policy with serious consequences

    PubMed Central

    Verheijde, Joseph L; Rady, Mohamed Y; McGregor, Joan

    2009-01-01

    Organ donation after cessation of circulation and respiration, both controlled and uncontrolled, has been proposed by the Institute of Medicine as a way to increase opportunities for organ procurement. Despite claims to the contrary, both forms of controlled and uncontrolled donation after cardiac death raise significant ethical and legal issues. Identified causes for concern include absence of agreement on criteria for the declaration of death, nonexistence of universal guidelines for duration before stopping resuscitation efforts and techniques, and assumption of presumed intent to donate for the purpose of initiating temporary organ-preservation interventions when no expressed consent to donate is present. From a legal point of view, not having scientifically valid criteria of cessation of circulation and respiration for declaring death could lead to a conclusion that organ procurement itself is the proximate cause of death. Although the revised Uniform Anatomical Gift Act of 2006 provides broad immunity to those involved in organ-procurement activities, courts have yet to provide an opinion on whether persons can be held liable for injuries arising from the determination of death itself. Preserving organs in uncontrolled donation after cardiac death requires the administration of life-support systems such as extracorporeal membrane oxygenation. These life-support systems can lead to return of signs of life that, in turn, have to be deliberately suppressed by the administration of pharmacological agents. Finally, allowing temporary organ-preservation interventions without expressed consent is inherently a violation of the principle of respect for a person's autonomy. Proponents of organ donation from uncontrolled donation after cardiac death, on the other hand, claim that these nonconsensual interventions enhance respect for autonomy by allowing people, through surrogate decision making, to execute their right to donate organs. However, the lack of transparency

  11. Effect of graft preservation and acute rejection on hypoxia-inducible factor-1 in rat cardiac allografts.

    PubMed

    Keränen, M A I; Nykänen, A I; Krebs, R; Tuuminen, R; Sandelin, H; Koskinen, P K; Lemström, K B

    2006-12-01

    Hypoxia plays an integral part in cardiac transplantation as prolonged graft preservation is an individual risk factor for the development of cardiac allograft vasculopathy (CAV). In this study we characterized the role of hypoxia-inducible factor-1 (HIF-1) during prolonged graft preservation, ischemia-reperfusion (I/R), acute rejection, and chronic rejection. Heart transplantations were performed from Dark Agouti (DA) to Wister-Furth (allo) or DA to DA (syn) rats, without immunosuppression (acute rejection model, harvested at day 5) or with cyclosporine (chronic rejection model, harvested at day 60). To study the effect of preservation on HIF-1 regulation, normal DA hearts were subjected to different cold ischemia times with or without 45 minutes of additional warm ischemia. The role of I/R was studied by harvesting syngrafts at different time points after reperfusion. Real-time reverse-transcriptase polymerase chain reaction quantified total HIF-1 mRNA, while enzyme-linked immunosorbent assay and immunohistochemistry quantified and localized HIF-1 protein. Our results show that HIF-1 nuclear immunoreactivity is increased during graft preservation and I/R leads to loss of nuclear HIF-1 immunoreactivity. Acute rejection induced HIF-1 in mRNA level. Our findings thus indicated that HIF-1 is activated during transplantation and suggested that manipulation of the HIF-1 pathway might reveal new therapeutic options to manage CAV. PMID:17175275

  12. Early Activation of the Kynurenine Pathway Predicts Early Death and Long‐term Outcome in Patients Resuscitated From Out‐of‐Hospital Cardiac Arrest

    PubMed Central

    Ristagno, Giuseppe; Latini, Roberto; Vaahersalo, Jukka; Masson, Serge; Kurola, Jouni; Varpula, Tero; Lucchetti, Jacopo; Fracasso, Claudia; Guiso, Giovanna; Montanelli, Alessandro; Barlera, Simona; Gobbi, Marco; Tiainen, Marjaana; Pettilä, Ville; Skrifvars, Markus B.

    2014-01-01

    Background The kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post–cardiac arrest shock, early death, and long‐term outcome. Methods and Results Plasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12‐month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3‐hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3‐hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3‐hydroxyanthranilic acid had lower 24‐hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3‐hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12‐month poor outcome and significantly improved risk reclassification. Conclusions KP is activated early after cardiac arrest and is associated with severity of post–cardiac arrest shock, early death, and poor long‐term outcome. PMID:25092787

  13. Postoperative Fluid Overload is a Useful Predictor of the Short-Term Outcome of Renal Replacement Therapy for Acute Kidney Injury After Cardiac Surgery

    PubMed Central

    Xu, Jiarui; Shen, Bo; Fang, Yi; Liu, Zhonghua; Zou, Jianzhou; Liu, Lan; Wang, Chunsheng; Ding, Xiaoqiang; Teng, Jie

    2015-01-01

    Abstract To analyze the predictive value of postoperative percent fluid overload (PFO) of renal replacement therapy (RRT) for acute kidney injury (AKI) patients after cardiac surgery. Data from 280 cardiac surgery patients between 2005 January and 2012 April were collected for retrospective analyses. A receiver operating characteristic (ROC) curve was used to compare the predictive values of cumulative PFO at different times after surgery for 90-day mortality. The cumulative PFO before RRT initiation was 7.9% ± 7.1% and the median PFO 6.1%. The cumulative PFO before and after RRT initiation in intensive care unit (ICU) was higher in the death group than in the survival group (8.8% ± 7.6% vs 6.1% ± 5.6%, P = 0.001; −0.5[−5.6, 5.1]% vs 6.9[2.2, 14.6]%, P < 0.001). The cumulative PFO during the whole ICU stay was 14.3% ± 15.8% and the median PFO was 10.7%. The areas under the ROC curves to predict the 90-day mortality by PFO at 24 hours, cumulative PFO before and after RRT initiation, and PFO during the whole ICU stay postoperatively were 0.625, 0.627, 0.731, and 0.752. PFO during the whole ICU stay ≥7.2% was determined as the cut-off point for 90-day mortality prediction with a sensitivity of 77% and a specificity of 64%. Kaplan–Meier survival estimates showed a significant difference in survival among patients with cumulative PFO ≥ 7.2% and PFO < 7.2% after cardiac surgery (log-rank P < 0.001). Postoperative cumulative PFO during the whole ICU stay ≥7.2% would have an adverse effect on 90-day short-term outcome, which may provide a strategy for the volume control of AKI-RRT patients after cardiac surgery. PMID:26287422

  14. Acute effects of chemoradiation on cardiac function in oesophageal cancer: a MUGA scan and echo-based study

    PubMed Central

    Miriyala, Raviteja; Kapoor, Rakesh; Bahl, Amit; Bhattacharya, Anish; Bahl, Ajay; Tomar, Parsee

    2015-01-01

    Objective To study the acute effects of concurrent chemoradiation on global and regional cardiac contractility and correlate with radiation dose. Methods 16 patients of locally advanced oesophageal squamous cell carcinoma were serially followed up with multiple-gated acquisition (MUGA) scans and echocardiograms during the course of concurrent chemoradiation to evaluate the ejection fractions (EFs) and pericardial status, respectively. Changes in cardiac contractility were correlated with the doses received by the heart. Results Concurrent chemoradiation resulted in a significant reduction in the contractility of both left ventricle (LV) and right ventricle (RV), with a mean reduction of LVEF by 5.6% and RVEF by 6.5% over the course of treatment, which had a significant correlation with the radiation doses received by the ventricles (p=0.001). On further analysis, correlation between radiation dose and decrease in contractility was more significant in the boost phase (16 Gy in 8 fractions over one and a half weeks; p=0.001 for LV and p=0.008 for RV) compared with the initial phase (40 Gy in 20 fractions over 4 weeks; p=0.184 for LV and p=0.269 for RV). One out of 16 patients developed mild acute pericarditis. Conclusions Concurrent chemoradiation resulted in acute decrease in EF of both ventricles in a dose-dependent manner. Correlation between cardiac doses and decrease in EF was more marked in the boost phase, suggesting a possible threshold of 40 Gy for this impairment. Nevertheless, conclusions regarding this possible threshold need to be interpreted with caution given the small sample size.

  15. From Recurrent Syncope to Sudden Cardiac Death: Clinical Characteristics in a Chinese Patient Carrying a Plakophilin-2 Gene Mutation

    PubMed Central

    Liu, Wenling; Qiu, Xiaoliang; Liu, Wen; Hu, Dayi; Zhu, Tiangang; Wang, Chunling; Beer, Dominik; Zhang, Li

    2013-01-01

    We report a case of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) which illustrates the natural progression of disease in the absence of availability of an implanted cardiac defibrillator (ICD). Electrocardiograms and cardiac imaging show the progress of ARVC and these clinical milestones of disease are presented herein. PMID:24826278

  16. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial

    PubMed Central

    Billings, Frederic T.; Hendricks, Patricia A.; Schildcrout, Jonathan S.; Shi, Yaping; Petracek, Michael R.; Byrne, John G.; Brown, Nancy J.

    2016-01-01

    Importance Hydroxy-methylglutaryl-coenzyme A reductase inhibitors affect several mechanisms underlying acute kidney injury (AKI). Objective To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery Design, Setting, Participants Double-blinded, placebo-controlled, randomized trial of adult cardiac surgery patients conducted November 2009 to October 2014 at Vanderbilt University Medical Center Intervention Statin-naïve patients (n=199) were randomly assigned 80mg atorvastatin the day before surgery, 40mg the morning of surgery, and 40mg daily following surgery (n=102) or matching placebo (n=97). Patients using statins prior to study enrollment (n=416) continued their pre-enrollment statin until the day of surgery, were randomly assigned 80mg atorvastatin the morning of surgery and 40mg the morning after (n=206) or matching placebo (n=210), and resumed their statin on postoperative day 2. Main Outcome AKI, defined as 0.3 mg/dl rise in serum creatinine within 48 hours of surgery (AKIN criteria) Results The DSMB recommended stopping the statin-naïve group due to increased AKI among statin-naïve participants with chronic kidney disease (CKD, estimated glomerular filtration rate <60 ml/min/1.73 m2) receiving atorvastatin and then recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] women, and 202 [32.8%] diabetic) completed the study. Among all participants (n=615), AKI occurred in 64 of 308 participants (20.8%) randomized to atorvastatin versus 60 of 307 participants (19.5%) randomized to placebo (risk ratio [RR], 1.06 [95% CI, 0.78–1.46]; P=0.75). Among statin-naïve participants (n=199), AKI occurred in 22 of 102 (21.6%) receiving atorvastatin versus 13 of 97 (13.4%) receiving placebo (RR, 1.61 [0.86–3.01]; P=0.15), and serum creatinine increased 0.11mg/dl (−0.11 to 0.56) (median [10th to 90th percentile]) in those randomized to atorvastatin versus 0.05 (−0

  17. Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death

    PubMed Central

    Bouilloux, Fabrice; Thireau, Jérôme; Ventéo, Stéphanie; Farah, Charlotte; Karam, Sarah; Dauvilliers, Yves; Valmier, Jean; Copeland, Neal G; Jenkins, Nancy A; Richard, Sylvain; Marmigère, Frédéric

    2016-01-01

    Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a risk factor for SCD. We report that Meis1 inactivation in the mouse neural crest leads to an altered sympatho-vagal regulation of cardiac rhythmicity in adults characterized by a chronotropic incompetence and cardiac conduction defects, thus increasing the susceptibility to SCD. We demonstrated that Meis1 is a major regulator of sympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis from early embryonic stages to perinatal stages. In addition, we showed that Meis1 regulates the transcription of key molecules necessary for the endosomal machinery. Accordingly, the traffic of Rab5+ endosomes is severely altered in Meis1-inactivated sympathetic neurons. These results suggest that Meis1 interacts with various trophic factors signaling pathways during postmitotic neurons differentiation. DOI: http://dx.doi.org/10.7554/eLife.11627.001 PMID:26857994

  18. Prognostic factors for death and survival with or without complications in cardiac arrest patients receiving CPR within 24 hours of anesthesia for emergency surgery

    PubMed Central

    Siriphuwanun, Visith; Punjasawadwong, Yodying; Lapisatepun, Worawut; Charuluxananan, Somrat; Uerpairojkit, Ketchada

    2014-01-01

    Purpose To determine prognostic factors for death and survival with or without complications in cardiac arrest patients who received cardiopulmonary resuscitation (CPR) within 24 hours of receiving anesthesia for emergency surgery. Patients and methods A retrospective cohort study approved by the Maharaj Nakorn Chiang Mai University Hospital Ethical Committee. Data used were taken from records of 751 cardiac arrest patients who received their first CPR within 24 hours of anesthesia for emergency surgery between January 1, 2003 and October 31, 2011. The reviewed data included patient characteristics, surgical procedures, American Society of Anesthesiologist (ASA) physical status classification, anesthesia information, the timing of cardiac arrest, CPR details, and outcomes at 24 hours after CPR. Univariate and polytomous logistic regression analyses were used to determine prognostic factors associated with the outcome variable. P-values of less than 0.05 were considered statistically significant. Results The outcomes at 24 hours were death (638/751, 85.0%), survival with complications (73/751, 9.7%), and survival without complications (40/751, 5.3%). The prognostic factors associated with death were: age between 13–34 years (OR =3.08, 95% CI =1.03–9.19); ASA physical status three and higher (OR =6.60, 95% CI =2.17–20.13); precardiopulmonary comorbidity (OR =3.28, 95% CI =1.09–9.90); the condition of patients who were on mechanical ventilation prior to receiving anesthesia (OR =4.11, 95% CI =1.17–14.38); surgery in the upper abdominal site (OR =14.64, 95% CI =2.83–75.82); shock prior to cardiac arrest (OR =6.24, 95% CI =2.53–15.36); nonshockable electrocardiography (EKG) rhythm (OR =5.67, 95% CI =1.93–16.62); cardiac arrest occurring in postoperative period (OR =7.35, 95% CI =2.89–18.74); and duration of CPR more than 30 minutes (OR =4.32, 95% CI =1.39–13.45). The prognostic factors associated with survival with complications were being greater

  19. Acute Cardiac Impairment Associated With Concurrent Chemoradiotherapy for Esophageal Cancer: Magnetic Resonance Evaluation

    SciTech Connect

    Hatakenaka, Masamitsu; Yonezawa, Masato; Nonoshita, Takeshi; Nakamura, Katsumasa; Yabuuchi, Hidetake; Shioyama, Yoshiyuki; Nagao, Michinobu; Matsuo, Yoshio; Kamitani, Takeshi; Higo, Taiki; Nishikawa, Kei; Setoguchi, Taro; Honda, Hiroshi

    2012-05-01

    Purpose: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT) for esophageal cancer. Methods and Materials: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. The left ventricular function (LVF) of 31 patients with esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was evaluated using cardiac cine magnetic resonance imaging. The patients were classified into two groups according to mean LV dose. The parameters related to LVF were compared between before and during (40 Gy) or between before and after CCRT using a Wilcoxon matched-pairs single rank test, and parameter ratios (during/before CCRT, after/before CCRT) were also compared between the groups with a t test. Data were expressed as mean {+-} SE. Results: In the low LV-dose group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased significantly (before vs. during vs. after CCRT; 62.7% {+-} 2.98% vs. 59.8% {+-} 2.56% vs. 60.6% {+-} 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1 {+-} 2.93 vs. 57.0 {+-} 3.23 mL/m{sup 2}), LV stroke volume index (38.6 {+-} 1.56 vs. 29.9 {+-} 1.60 mL/m{sup 2}), and LV ejection fraction (56.9% {+-} 1.79% vs. 52.8% {+-} 1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased significantly (before vs. during vs. after CCRT; 66.8 {+-} 3.05 vs. 72.4 {+-} 4.04 vs. 85.4 {+-} 3.75 beats per minute, p < 0.01). Left ventricle wall motion decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after CCRT; 6.64 {+-} 0.54 vs. 4.78 {+-} 0.43 vs. 4.79 {+-} 0.50 mm), 9 (6.88 {+-} 0.45 vs. 5.04 {+-} 0.38 vs. 5.27 {+-} 0.47 mm), and 10 (9.22 {+-} 0.48 vs. 8.08 {+-} 0.34 vs. 8.19 {+-} 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke volume index, wall motion in segment 9, and heart rate showed significant difference

  20. Molecular and Functional Effects of a Splice Site Mutation in the MYL2 Gene Associated with Cardioskeletal Myopathy and Early Cardiac Death in Infants.

    PubMed

    Zhou, Zhiqun; Huang, Wenrui; Liang, Jingsheng; Szczesna-Cordary, Danuta

    2016-01-01

    The homozygous appearance of the intronic mutation (IVS6-1) in the MYL2 gene encoding for myosin ventricular/slow-twitch skeletal regulatory light chain (RLC) was recently linked to the development of slow skeletal muscle fiber type I hypotrophy and early cardiac death. The IVS6-1 (c403-1G>C) mutation resulted from a cryptic splice site in MYL2 causing a frameshift and replacement of the last 32 codons by 19 different amino acids in the RLC mutant protein. Infants who were IVS6-1(+∕+)-positive died between 4 and 6 months of age due to cardiomyopathy and heart failure. In this report we have investigated the molecular mechanism and functional consequences associated with the IVS6-1 mutation using recombinant human cardiac IVS6-1 and wild-type (WT) RLC proteins. Recombinant proteins were reconstituted into RLC-depleted porcine cardiac muscle preparations and subjected to enzymatic and functional assays. IVS6-1-RLC showed decreased binding to the myosin heavy chain (MHC) compared with WT, and IVS6-1-reconstituted myosin displayed reduced binding to actin in rigor. The IVS6-1 myosin demonstrated a significantly lower Vmax of the actin-activated myosin ATPase activity compared with WT. In stopped-flow experiments, IVS6-1 myosin showed slower kinetics of the ATP induced dissociation of the acto-myosin complex and a significantly reduced slope of the kobs-[MgATP] relationship compared to WT. In skinned porcine cardiac muscles, RLC-depleted and IVS6-1 reconstituted muscle strips displayed a significant decrease in maximal contractile force and a significantly increased Ca(2+) sensitivity, both hallmarks of hypertrophic cardiomyopathy-associated mutations in MYL2. Our results showed that the amino-acid changes in IVS6-1 were sufficient to impose significant conformational alterations in the RLC protein and trigger a series of abnormal protein-protein interactions in the cardiac muscle sarcomere. Notably, the mutation disrupted the RLC-MHC interaction and the steady

  1. Molecular and Functional Effects of a Splice Site Mutation in the MYL2 Gene Associated with Cardioskeletal Myopathy and Early Cardiac Death in Infants

    PubMed Central

    Zhou, Zhiqun; Huang, Wenrui; Liang, Jingsheng; Szczesna-Cordary, Danuta

    2016-01-01

    The homozygous appearance of the intronic mutation (IVS6-1) in the MYL2 gene encoding for myosin ventricular/slow-twitch skeletal regulatory light chain (RLC) was recently linked to the development of slow skeletal muscle fiber type I hypotrophy and early cardiac death. The IVS6-1 (c403-1G>C) mutation resulted from a cryptic splice site in MYL2 causing a frameshift and replacement of the last 32 codons by 19 different amino acids in the RLC mutant protein. Infants who were IVS6-1+∕+-positive died between 4 and 6 months of age due to cardiomyopathy and heart failure. In this report we have investigated the molecular mechanism and functional consequences associated with the IVS6-1 mutation using recombinant human cardiac IVS6-1 and wild-type (WT) RLC proteins. Recombinant proteins were reconstituted into RLC-depleted porcine cardiac muscle preparations and subjected to enzymatic and functional assays. IVS6-1-RLC showed decreased binding to the myosin heavy chain (MHC) compared with WT, and IVS6-1-reconstituted myosin displayed reduced binding to actin in rigor. The IVS6-1 myosin demonstrated a significantly lower Vmax of the actin-activated myosin ATPase activity compared with WT. In stopped-flow experiments, IVS6-1 myosin showed slower kinetics of the ATP induced dissociation of the acto-myosin complex and a significantly reduced slope of the kobs-[MgATP] relationship compared to WT. In skinned porcine cardiac muscles, RLC-depleted and IVS6-1 reconstituted muscle strips displayed a significant decrease in maximal contractile force and a significantly increased Ca2+ sensitivity, both hallmarks of hypertrophic cardiomyopathy-associated mutations in MYL2. Our results showed that the amino-acid changes in IVS6-1 were sufficient to impose significant conformational alterations in the RLC protein and trigger a series of abnormal protein-protein interactions in the cardiac muscle sarcomere. Notably, the mutation disrupted the RLC-MHC interaction and the steady-state and

  2. Identification of a novel synergistic induction of cell death by Smac mimetic and HDAC inhibitors in acute myeloid leukemia cells.

    PubMed

    Steinwascher, Sofie; Nugues, Anne-Lucie; Schoeneberger, Hannah; Fulda, Simone

    2015-09-28

    Inhibitor of Apoptosis (IAP) proteins are expressed at high levels in acute myeloid leukemia (AML) and contribute to resistance to programmed cell death. Here, we report that inhibition of IAP proteins by the small-molecule Smac mimetic BV6 acts together with histone deacetylase (HDAC) inhibitors (HDACIs) such as MS275 or SAHA to trigger cell death in AML cell lines in a synergistic manner, as underscored by calculation of combination index (CI). Also, BV6 and HDACIs cooperate to trigger DNA fragmentation, a marker of apoptotic cell death, and to suppress long-term clonogenic survival of AML cells. In contrast, equimolar concentrations of BV6 and MS275 or SAHA do not synergize to elicit cell death in normal peripheral blood lymphocytes (PBLs), emphasizing some tumor cell selectivity of this combination treatment. Addition of the tumor necrosis factor (TNF)α-blocking antibody Enbrel significantly reduces BV6/MS275-induced cell death in the majority of AML cell lines, indicating that autocrine/paracrine TNFα signaling contributes to cell death. Remarkably, the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) fails to rescue MV4-11, Molm13 and OCI-AML3 cells and even enhances BV6/MS275-mediated cell death, whereas zVAD.fmk reduces BV6/MS275-induced cell death in NB4 cells. Annexin-V/propidium iodide (PI) double staining reveals that BV6/MS275 cotreatment predominately increases the percentage of double-positive cells. Of note, the Receptor-Interacting Protein (RIP)1 inhibitor necrostatin-1 (Nec-1) or the Mixed Lineage Kinase Domain-Like protein (MLKL) inhibitor necrosulfonamide (NSA) significantly reduce BV6/MS275-induced cell death in the presence of zVAD.fmk, suggesting that BV6/MS275 cotreatment triggers necroptosis when caspases are inhibited. Thus, BV6 acts in concert with HDACIs to induce cell death in AML cells and can bypass apoptosis resistance, at least in several AML cell lines, by engaging necroptosis as an

  3. Acute severe cardiac failure complicating myocardial infarction. Experience with 100 patients referred for consideration of mechanical left ventricular assistance.

    PubMed Central

    O'Rourke, M F; Chang, V P; Windsor, H M; Shanahan, M X; Hickie, J B; Morgan, J J; Gunning, J F; Seldon, A W; Hall, G V; Michell, G; Goldfarb, D; Harrision, D G

    1975-01-01

    One hundred patients were referred with suspected acute cardiac failure following acute myocardial infarction. The diagnosis was confirmed in 72: 31 of these patients underwent elective medical treatment, with 2 survivors (6