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Sample records for ischemic cardiomyopathy induced

  1. Systemic lupus erythematosus presented as non-inflammatory necrotizing vasculopathy-induced ischemic glomerulopathy and small vessels-related ischemic cardiomyopathy.

    PubMed

    Sung, J M; Hsu, S C; Chen, F F; Huang, J J

    2002-01-01

    The clinical significance of lupus non-inflammatory necrotizing vasculopathy (NINV) is not well established. For example, since lupus renal NINV is usually reported to coexist with proliferative and active glomerulonephritis, it is difficult to demonstrate the role of NINV on renal pathophysiology. Here we report a 16-year-old SLE boy with renal NINV presenting as ischemic glomerulopathy and small vessels-related ischemic heart failure. The renal biopsy demonstrated mild proliferative glomerulonephritis and NINV initially, and one month later repeated renal biopsy showed NINV with ischemic glomerulopathy. These findings established that NINV, but not proliferative glomerulonephritis, was responsive for his acute renal failure (ARF). Another interesting question is about the pathophysiology of his myocardial dysfunction. This patient presented typical angina and congestive heart failure (CHF). Echocardiograms and ventriculography revealed dilatation of four chambers and low ejection fraction. Serial electrocardiograms demonstrated evolutionary ischemic changes. Coronary angiography revealed no abnormality of large vessels. These findings suggested small vascular lesions-induced myocardial ischemia was the underlying mechanism of dilated cardiomyopathy. As myocardial biopsy was not done in our case, we could only speculate, but not prove, that the NINV observed in renal biopsy may also involve in cardiac microvascular beds. Nevertheless, this interesting case emphasized the role of obliterative small vascular lesions in the pathophysiology of ARF and myocardial dysfunction. The patient was treated with high-dose corticosteroid, plasma infusion and hemodialysis. His cardiac function improved gradually, however the renal function did not recover.

  2. Non-Ischemic Cardiomyopathy Attributed to Adult Myotonic Dystrophy

    PubMed Central

    Park, Hyun Kyung; Park, Won Hyeong; Song, Dae-Geun; Kim, Tae Gyoon; Min, Bo Young; Lee, Keun

    2009-01-01

    In patients with myotonic dystrophy (MD), impairment of the conduction system is a common and progressive finding. However, only a few cases of MD with cardiomyopathy have been reported. Herein we report a case of MD with progressive non-ischemic cardiomyopathy and severe electrocardiographic abnormalities. PMID:19949641

  3. [Tachycardia-induced cardiomyopathy].

    PubMed

    Povolný, Jan

    2015-01-01

    Cardiomyopathy is a heterogeneous group of diseases of heart muscle accompanied with impaired cardiac function. Tachycardia-induced cardiomyopathy (TIC) is caused by prolonged tachycardia leading to dilatation and systolic dysfunction with clinical manifestation of heart failure. This state is reversible after normalization of heart rate. The diagnosis is usually made retrospectively after normalization of heart rate and recovery of left ventricular function (LVF). More than 100 years after the first documented case (described in 1913 in a young patient with atrial fibrillation and symptoms of heart failure [25]) is still limited knowledge of pathophysiological mechanisms. The most common arrhythmias responsible for the TIC include atrial fibrillation [1,2], atrial flutter [3], incessant supraventricular tachycardia [4], ventricular tachycardia (VT) [5] and frequent ventricular extrasystoles (VES) [6]. TIC detection and therapeutic intervention is crucial considering potential reversibility of tachycardia. Current options of treatment involve drug therapy and surgical or catheter ablation.

  4. Stress-induced cardiomyopathy

    PubMed Central

    Lisung, Fausto Gabriel; Shah, Ankit B; Levitt, Howard L; Coplan, Neil B

    2015-01-01

    A woman in her early 70s presented with chest pain, dyspnoea and diaphoresis 30 min after her husband expired in our hospital. Cardiac markers were elevated and there were acute changes in ECG suggestive for acute coronary syndrome. Echocardiogram showed apical akinesis, basal segment hyperkinesis with an ejection fraction of 30%. Cardiac catheterisation was performed showing non-obstructive coronary arteries, leading to the diagnosis of stress-induced cardiomyopathy. The patient improved with medical management. Repeat echocardiogram 2 months later showed resolution of heart failure with an ejection fraction of 65–70%. PMID:25858931

  5. Assessment of Ischemic Cardiomyopathy Using Cardiovascular Magnetic Resonance Imaging: A Pictorial Review.

    PubMed

    Olivas-Chacon, Cristina Ivette; Mullins, Carola; Solberg, Agnieszka; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Ischemic heart disease is the leading cause of death worldwide. In the last two decades, cardiovascular magnetic resonance imaging (CMRI) has emerged as the primary imaging tool in the detection and prognostic assessment of ischemic heart disease. In a single study, CMRI allows evaluation of not only myocardial wall perfusion, but also the presence, acuity, and extent of myocardial ischemia and infarction complications. Also, rest and stress perfusion imaging can accurately depict inducible ischemia secondary to significant coronary artery stenosis. We present a pictorial review of the assessment of ischemic cardiomyopathy with an emphasis on CMRI features.

  6. Assessment of Ischemic Cardiomyopathy Using Cardiovascular Magnetic Resonance Imaging: A Pictorial Review

    PubMed Central

    Olivas-Chacon, Cristina Ivette; Mullins, Carola; Solberg, Agnieszka; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Ischemic heart disease is the leading cause of death worldwide. In the last two decades, cardiovascular magnetic resonance imaging (CMRI) has emerged as the primary imaging tool in the detection and prognostic assessment of ischemic heart disease. In a single study, CMRI allows evaluation of not only myocardial wall perfusion, but also the presence, acuity, and extent of myocardial ischemia and infarction complications. Also, rest and stress perfusion imaging can accurately depict inducible ischemia secondary to significant coronary artery stenosis. We present a pictorial review of the assessment of ischemic cardiomyopathy with an emphasis on CMRI features. PMID:26085960

  7. An unusual presentation of peripartum cardiomyopathy: Recurrent transient ischemic attacks.

    PubMed

    Zehir, Regayip; Karabay, Can Yucel; Kocabay, Gonenc; Kalayci, Arzu; Akgun, Taylan; Kirma, Cevat

    2014-09-01

    Peripartum cardiomyopathy (PPCM) is a rare form of dilated cardiomyopathy that is associated with high maternal morbidity and mortality. Onset is usually between the last month of pregnancy and up to the fifth month postpartum. PPCM usually presents with signs and symptoms of heart failure and rarely with thromboembolic complications. The true incidence of thromboemboli in PPCM is unknown. Herein we report an unusual case of PPCM in a previously healthy woman who presented with recurrent transient ischemic attacks due to thrombus in the left ventricle. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  8. Trypanosomiasis, cardiomyopathy and the risk of ischemic stroke.

    PubMed

    Carod-Artal, Francisco Javier

    2010-05-01

    American (Chagas disease) and African (sleeping sickness) trypanosomiasis are neglected tropical diseases and are a heavy burden in Latin America and Africa, respectively. Chagas disease is an independent risk factor for stroke. Apical aneurysm, heart failure and cardiac arrhythmias are associated with ischemic stroke in chagasic cardiomyopathy. Not all chagasic patients who suffer an ischemic stroke have a severe cardiomyopathy, and stroke may be the first manifestation of Chagas disease. Cardioembolism affecting the middle cerebral artery is the most common stroke subtype. Risk of recurrence is high and careful evaluation of recurrence risk should be addressed. Repolarization changes, low voltage and prolonged QT interval are common electrocardiography alterations in human African trypanosomiasis, and can be found in more than 70% of patients. Epidemiological studies are needed to asses the risk of stroke in African trypanosomiasis perimyocarditis.

  9. Non-ischemic diabetic cardiomyopathy may initially exhibit a transient subclinical phase of hyperdynamic myocardial performance.

    PubMed

    Hensel, Kai O

    2016-09-01

    Cardiovascular complications are the key cause for mortality in diabetes mellitus. Besides ischemia-related cardiac malfunction there is growing evidence for non-ischemic diabetes-associated heart failure in both type 1 and type 2 diabetes mellitus. The underlying pathophysiology of non-ischemic diabetic cardiomyopathy (NIDC) is poorly understood and data on myocardial mechanics in early stages of the disease are rare. However, several studies in both human and experimental animal settings have reported prima facie unexplained features indicating myocardial hyperdynamics early in the course of the disease. The new hypothesis is that - other than previously thought - NIDC may be non-linear and initially feature an asymptomatic subclinical phase of myocardial hypercontractility that precedes the long-term development of diabetes-associated cardiac dysfunction and ultimately heart failure. Diabetes-induced metabolic imbalances may lead to a paradoxic inotropic increase and inefficient myocardial mechanics that finally result in a gradual deterioration of myocardial performance. In conclusion, diabetic patients should be screened regularly and early in the course of the disease utilizing ultra-sensitive myocardial deformation imaging in order to identify patients at risk for diabetes-associated heart failure. Moreover, hyperdynamic myocardial deformation might help distinguish non-ischemic from ischemic diabetic cardiomyopathy. Further studies are needed to illuminate the underlying pathophysiological mechanisms, the exact spatiotemporal evolvement of diabetic cardiomyopathy and its long-term relation to clinical outcome parameters.

  10. Usefulness of dipyridamole-thallium-201 perfusion scanning for distinguishing ischemic from nonischemic cardiomyopathy

    SciTech Connect

    Eichhorn, E.J.; Kosinski, E.J.; Lewis, S.M.; Hill, T.C.; Emond, L.H.; Leland, O.S.

    1988-11-01

    To determine noninvasively the etiology of left ventricular (LV) dysfunction, 22 patients with a diagnosis of cardiomyopathy determined via cardiac catheterization and 5 normal control subjects underwent radionuclide ventriculography and intravenous dipyridamole-thallium-201 perfusion scanning. Both ischemically and nonischemically induced LV dysfunction had comparable global LV ejection fractions (24 +/- 6 vs 23 +/- 8%, respectively) and extent of segmental wall motion abnormalities. Right ventricular ejection fraction was significantly better in the group with an ischemic etiology of LV dysfunction (41 +/- 26 vs 13 +/- 10%, p less than 0.005) but significant group overlap was present. However, computer-assisted analysis of dipyridamole-thallium-201 myocardial perfusion scanning demonstrated more homogeneous myocardial perfusion in idiopathic cardiomyopathy (mean perfusion defect 25 +/- 11 vs 6 +/- 6%, p less than 0.001) and successfully predicted the correct etiology of LV dysfunction in 20 of 22 (91%) patients.

  11. Incidence of appropriate cardioverter-defibrillator shocks and mortality in patients with implantable cardioverter-defibrillators with ischemic cardiomyopathy versus nonischemic cardiomyopathy at 33-month follow-up

    PubMed Central

    Gandhi, Kaushang; Aronow, Wilbert S.; Desai, Harit; Amin, Harshad; Lai, Hoang M.; Frishman, William H.; Cohen, Martin; Sorbera, Carmen

    2010-01-01

    Introduction The aim of the study was to investigate at long-term follow-up the incidence of appropriate implantable cardioverter-defibrillator (ICD) shocks and of all-cause mortality in patients with ICDs with ischemic cardiomyopathy versus nonischemic cardiomyopathy. Material and methods ICDs were implanted in 485 patients with ischemic cardiomyopathy and in 299 patients with nonischemic cardiomyopathy, all of whom had coronary angiography. Baseline characteristics were not significantly different between the 2 groups. Follow-up was 965 days in patients with ischemic cardiomyopathy versus 1039 days in patients with nonischemic cardiomyopathy (p not significant). The ICDs were interrogated every 3 months to see if shocks occurred. Results Appropriate ICD shocks occurred in 179 of 485 patients (37%) with ischemic cardiomyopathy and in 93 of 299 patients (31%) with nonischemic cardiomyopathy (p not significant). All-cause mortality occurred in 162 of 485 patients (33%) with ischemic cardiomyopathy and in 70 of 299 patients (23%) with nonischemic cardiomyopathy (p = 0.002). Conclusions The incidence of appropriate ICD shocks was not significantly different at 33-month follow-up in patients with ischemic cardiomyopathy versus nonischemic cardiomyopathy. However, patients with ischemic cardiomyopathy had a significantly higher incidence of all-cause mortality than patients with nonischemic cardiomyopathy (p = 0.002). PMID:22427764

  12. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay.

    PubMed

    Olivas-Chacon, Cristina I; Mullins, Carola; Stewart, Kevan; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features.

  13. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay

    PubMed Central

    Olivas-Chacon, Cristina I; Mullins, Carola; Stewart, Kevan; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features. PMID:26199786

  14. Electrical remodeling in a canine model of ischemic cardiomyopathy.

    PubMed

    Liu, Xian-Sheng; Jiang, Min; Zhang, Mei; Tang, Daniel; Clemo, Henry F; Higgins, Robert S D; Tseng, Gea-Ny

    2007-01-01

    The nature of electrical remodeling in a canine model of ischemic cardiomyopathy (ICM; induced by repetitive intracoronary microembolizations) that exhibits spontaneous ventricular tachycardia is not entirely clear. We used the patch-clamp technique to record action potentials and ionic currents of left ventricular myocytes isolated from the region affected by microembolizations. We also used the immunoblot technique to examine channel subunit expression in adjacent affected tissue. Ventricular myocytes and tissue isolated from the corresponding region of normal hearts served as control. ICM myocytes had prolonged action potential duration (APD) and more pronounced APD dispersion. Slow delayed rectifier current (I(Ks)) was reduced at voltages positive to 0 mV, along with a negative shift in its voltage dependence of activation. Immunoblots showed that there was no change in KCNQ1.1 (I(Ks) pore-forming or alpha-subunit), but KCNE1 (I(Ks) auxiliary or beta-subunit) was reduced, and KCNQ1.2 (a truncated KCNQ1 splice variant with a dominant-negative effect on I(Ks)) was increased. Transient outward current (I(to)) was reduced, along with an acceleration of the slow phase of recovery from inactivation. Immunoblots showed that there was no change in Kv4.3 (alpha-subunit of fast-recovering I(to) component), but KChIP2 (beta-subunit of fast-recovering component) and Kv1.4 (alpha-subunit of slow-recovering component) were reduced. Inward rectifier current was reduced. L-type Ca current was unaltered. The immunoblot data provide mechanistic insights into the observed changes in current amplitude and gating kinetics of I(Ks) and I(to). We suggest that these changes, along with the decrease in inward rectifier current, contribute to APD prolongation in ICM hearts.

  15. Can ventricular tachycardia non-inducibility after ablation predict reduced ventricular tachycardia recurrence and mortality in patients with non-ischemic cardiomyopathy? A meta-analysis of twenty-four observational studies.

    PubMed

    Hu, Jinzhu; Zeng, Shan; Zhou, Qiongqiong; Zhu, Wengen; Xu, Zhenyan; Yu, Jianhua; Hong, Kui

    2016-11-01

    At present, the role of ventricular tachycardia (VT) non-inducibility after ablation in patients with non-ischemic cardiomyopathy (NICM) remains controversial. We conducted a meta-analysis of the published literature to assess whether VT non-inducibility after ablation could predict reduced VT recurrence and mortality in patients with NICM. PubMed, ScienceDirect, and the Cochrane library were searched for studies evaluating the effects of VT non-inducibility after catheter ablation on the long-term outcome in NICM patients with sustained VT. Results were analyzed using a fixed-effect model, and the data were pooled using RevMan 5.3 software. Twenty-four observational studies were identified (736 participants, mean follow-up time: 22months). NICM patients with VT inducibility after ablation had a higher risk of VT recurrence (odds ratio [OR]=5.83, 95% confidence interval [CI] 4.07-8.37; P<0.00001) and all-cause mortality (OR=3.55, 95% CI 1.62-7.78; P=0.002) compared with VT non-inducibility. Similarly in the subgroup analysis, patients with VT inducibility showed a higher risk of VT recurrence from non-ischemic dilated cardiomyopathy (OR=3.92, 95% CI 2.36-6.50; P<0.00001) and arrhythmogenic right ventricular dysplasia/cardiomyopathy (OR=5.37, 95% CI 2.20-13.10; P=0.0002). Additionally, meta-analysis also showed that combined endo-epicardial ablation significantly reduced the risk of VT recurrence compared with endocardial-only ablation (OR=2.02, 95% CI 1.19-3.44; P=0.009; mean follow-up time: 22months). Recent evidence has shown that VT non-inducibility after ablation is a predictor for reduced VT recurrence and mortality compared with VT inducibility in NICM patients with sustained VT. In addition, endocardial plus adjuvant epicardial ablation provides better long-term arrhythmia-free survival than endocardial ablation alone. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Reversal of Dilated Cardiomyopathy After Successful Radio-Frequency Ablation of Frequent Atrial Premature Beats, a New Cause for Arrhythmia-Induced Cardiomyopathy.

    PubMed

    Vervueren, Paul Louis; Delmas, Clement; Berry, Mathieu; Rollin, Anne; Sadron, Marie; Duparc, Alexandre; Mondoly, Pierre; Honton, Benjamin; Lairez, Olivier; Maury, Philippe

    2012-12-01

    Incessant atrial premature beats as a potential cause for tachycardia-induced cardiomyopathy was suspected in a patient presenting with dilated non-ischemic cardiomyopathy and severely altered left ventricular ejection fraction. The elimination of a left atrial focus by percutaneous RF ablation led to normalization of the clinical status, of atrial and ventricular dimensions and left ventricular systolic function.

  17. Heart failure and tachycardia-induced cardiomyopathy.

    PubMed

    Ellis, Ethan R; Josephson, Mark E

    2013-12-01

    Congestive heart failure is a major health care concern affecting almost six million Americans and an estimated 23 million people worldwide, and its prevalence is increasing with time. Long-standing tachycardia is a well-recognized cause of heart failure and left ventricular dysfunction and has led to the nomenclature, tachycardia-induced cardiomyopathy. Tachycardia-induced cardiomyopathy is generally a reversible cardiomyopathy with effective treatment of the causative arrhythmia, either with medications, surgery, or catheter ablation. Tachycardia-induced cardiomyopathy remains poorly understood and is likely under-diagnosed. A better understanding of tachycardia-induced cardiomyopathy and improved recognition of its presence in clinical practice is vital to the health of patients with this disorder. The goal of this review is to discuss the pathogenesis and clinical manifestations of tachycardia-induced cardiomyopathy, as well as approaches to its diagnosis and treatment.

  18. Non-ischemic cardiomyopathy after rituximab treatment for membranous nephropathy

    PubMed Central

    Cheungpasitporn, Wisit; Kopecky, Stephen L.; Specks, Ulrich; Bharucha, Kharmen; Fervenza, Fernando C.

    2017-01-01

    Rituximab is an anti-CD20 monoclonal antibody frequently used for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), and anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis. In addition, rituximab has recently been increasingly used as an off-label treatment in a number of inflammatory and systemic autoimmune diseases. It is advised that rituximab infusion may cause infusion reactions and adverse cardiac effects including arrhythmia and angina, especially in patients with prior history of cardiovascular diseases. However, its detailed cardiotoxicity profile and effects on cardiac function were not well described. We report a 51-year-old man who developed non-ischemic cardiomyopathy after rituximab treatment for membranous nephropathy. The patient experienced reduced cardiac functions within 48 hours after the initial infusion, which remained markedly reduced at 9-month follow-up. As the utility of rituximab expands, physicians must be aware of this serious cardiovascular adverse effect. PMID:28487867

  19. Tachycardia-induced cardiomyopathy in pregnancy.

    PubMed

    Joseph, Anil C; Prapa, Matina; Pellicori, Pierpaolo; Mabote, Thato; Nasir, Mansoor; Clark, Andrew L

    2016-10-01

    Heart failure in pregnancy is rare, but usually ascribed to peripartum cardiomyopathy in the absence of other possible diagnoses. However, heart failure can develop solely due to a tachycardia, so-called 'tachycardia-induced cardiomyopathy'. The incidence of tachycardia-induced cardiomyopathy in pregnancy is unknown, but it is a treatable and potentially reversible cause of heart failure. Clinically, tachycardia-induced cardiomyopathy during pregnancy might present in a similar manner, but its management has to be individualized according to the arrhythmic substrate and usually involve multidisciplinary input from specialists in obstetrics, cardiac electrophysiology and heart failure.

  20. The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy.

    PubMed

    Wang, Xianyun; Zhang, Jun; Zhang, Fan; Li, Jing; Li, Yaqi; Tan, Zirui; Hu, Jie; Qi, Yixin; Li, Quanhai; Yan, Baoyong

    2015-01-01

    Ischemic cardiomyopathy (ICM) is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ICM. Several stem cell types including cardiac-derived stem cells (CSCs), bone marrow-derived stem cells, mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), and CD34(+) and CD 133(+) stem cells have been applied in clinical researches. The clinical effect produced by stem cell administration in ICM mainly depends on the transdifferentiation and paracrine effect. One important issue is that low survival and residential rate of transferred stem cells in the infracted myocardium blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ICM mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical condition, the particular microenvironment onto which the cells are delivered, and clinical condition remain to be addressed. Here we provide an overview of the pros and cons of these transferred cells and discuss the current state of their therapeutic potential. We believe that stem cell translation will be an ideal option for patients following ischemic heart disease in the future.

  1. Sepsis-induced Cardiomyopathy

    PubMed Central

    Romero-Bermejo, Francisco J; Ruiz-Bailen, Manuel; Gil-Cebrian, Julián; Huertos-Ranchal, María J

    2011-01-01

    Myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. During the sepsis-induced myocardial dysfunction, both ventricles can dilate and diminish its ejection fraction, having less response to fluid resuscitation and catecholamines, but typically is assumed to be reversible within 7-10 days. In the last 30 years, It´s being subject of substantial research; however no explanation of its etiopathogenesis or effective treatment have been proved yet. The aim of this manuscript is to review on the most relevant aspects of the sepsis-induced myocardial dysfunction, discuss its clinical presentation, pathophysiology, etiopathogenesis, diagnostic tools and therapeutic strategies proposed in recent years. PMID:22758615

  2. Trastuzumab-induced cardiomyopathy.

    PubMed

    Guglin, Maya; Cutro, Raymond; Mishkin, Joseph D

    2008-06-01

    Trastuzumab is a recombinant humanized monoclonal antibody used for the treatment of advanced breast cancer. It improves survival and increases response to chemotherapy. The major side effect of trastuzumab is cardiotoxicity manifesting as a reduction in left ventricular systolic function, either asymptomatic or with signs and symptoms of heart failure. Although reversible in most cases, cardiotoxicity frequently results in the discontinuation of trastuzumab. The objective of this review is to summarize facts about trastuzumab-induced cardiotoxicity and to highlight the areas of future investigations. We searched PubMed for trials involving trastuzumab used as an adjuvant therapy for breast cancer, including the metastatic breast cancer setting, and focused on cardiotoxicity.

  3. Determinants of functional mitral regurgitation severity in patients with ischemic cardiomyopathy versus nonischemic dilated cardiomyopathy.

    PubMed

    Konstantinou, Dimitrios M; Papadopoulou, Klio; Giannakoulas, George; Kamperidis, Vasilis; Dalamanga, Emmanouela G; Damvopoulou, Efthalia; Parcharidou, Despina G; Karamitsos, Theodoros D; Karvounis, Haralambos I

    2014-01-01

    Functional mitral regurgitation (MR) is prevalent among patients with left ventricular (LV) dysfunction and is associated with a poorer prognosis. Our aim was to assess the primary determinants of MR severity in patients with ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM). Patients with functional MR secondary to ICM (n = 55) and DCM (n = 48) were prospectively enrolled. Effective regurgitant orifice (ERO) area, global LV remodeling, regional wall-motion abnormalities, and mitral apparatus deformity indices were assessed utilizing conventional and tissue Doppler echocardiography. ICM patients had more severe MR compared with DCM patients despite similar ejection fraction and functional status (ERO = 0.16 ± 0.08 cm(2) vs. ERO = 0.12 ± 0.70 cm(2) , respectively, P = 0.002). Regional myocardial systolic velocities in mid-inferior and mid-lateral wall were negatively correlated with ERO in ICM and DCM patients, respectively. Multivariate analysis identified coaptation height as the only independent determinant of ERO in both groups. In a subset of ICM patients (n = 9) with relatively high ERO despite low coaptation height, a higher prevalence of left bundle branch block was detected (88.9% vs. 46.7%, P = 0.02). Functional MR severity was chiefly determined by the extent of mitral apparatus deformity, and coaptation height can provide a rapid estimation of MR severity in heart failure patients. Additional contributory mechanisms in ICM patients include depressed myocardial systolic velocities in posteromedial papillary muscle attaching site and evidence of global LV dyssynchrony. © 2013, Wiley Periodicals, Inc.

  4. Statins reduce appropriate implantable cardioverter-defibrillator shocks in ischemic cardiomyopathy with no benefit in nonischemic cardiomyopathy.

    PubMed

    Contractor, Tahmeed; Beri, Abhimanyu; Gardiner, Joseph; Ardhanari, Sivakumar; Thakur, Ranjan

    2012-11-01

    Statins have been hypothesized to decrease ventricular arrhythmias through a direct antiarrhythmic effect. Clinical studies have demonstrated a clear reduction only in populations with underlying ischemic heart disease. This study was designed to compare the effect of statins on appropriate shocks between ischemic and nonischemic cardiomyopathy. Patients with an ejection fraction 35% or less who received an implantable cardioverter-defibrillator and had follow-up for at least 1 month were included. The ischemic and nonischemic groups were divided into statin treatment and control subgroups and the occurrence of appropriate shocks was compared. The frequency of shocks was analyzed using negative binomial models to account for overdispersion of the "count" data (number of appropriate shocks) and an adjusted intensity rate ratio was calculated for statin use. A total of 676 patients were included, of which statins were used by 65% (329 of 506) of the ischemic and 42% (72 of 170) of the nonischemic groups. Occurrence of appropriate shocks was significantly reduced with statins in ischemic (13.4% vs 20.9%; relative risk 0.64, P = 0.028), but not in the patients with nonischemic cardiomyopathy. Similarly, although use of statins lowered the intensity rate of appropriate shocks in ischemic patients (intensity rate ratio, 0.23; 95% confidence interval, 0.12-0.47), no such benefit was noted in the nonischemic group (intensity rate ratio, 1.27; 95% confidence interval, 0.37-4.40). In conclusion, statins reduced the occurrence and frequency of appropriate shocks for ventricular arrhythmias in ischemic but not in nonischemic cardiomyopathy. Larger, randomized controlled trials are needed to confirm these findings.

  5. Herpes simplex virus-induced cardiomyopathy successfully treated with acyclovir.

    PubMed

    Kuchynka, Petr; Palecek, Tomas; Hrbackova, Hana; Vitkova, Ivana; Simek, Stanislav; Nemecek, Eduard; Aster, Viktor; Louch, William E; Aschermann, Michael; Linhart, Ales

    2010-10-01

    Inflammatory dilated cardiomyopathy (DCMi) represents an acquired form of dilated cardiomyopathy. Viral infection is the most common cause of DCMi. In contrast with other cardiotropic viruses, herpes simplex virus (HSV) is a very rare finding in endomyocardial biopsies of patients with dilated cardiomyopathy. We report a case of HSV-induced cardiomyopathy successfully treated with acyclovir.

  6. Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy.

    PubMed

    Velazquez, Eric J; Lee, Kerry L; Jones, Robert H; Al-Khalidi, Hussein R; Hill, James A; Panza, Julio A; Michler, Robert E; Bonow, Robert O; Doenst, Torsten; Petrie, Mark C; Oh, Jae K; She, Lilin; Moore, Vanessa L; Desvigne-Nickens, Patrice; Sopko, George; Rouleau, Jean L

    2016-04-21

    The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear. From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years. A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test). In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] Clinical

  7. Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy

    PubMed Central

    Velazquez, Eric J.; Lee, Kerry L.; Jones, Robert H.; Al-Khalidi, Hussein R.; Hill, James A.; Panza, Julio A.; Michler, Robert E.; Bonow, Robert O.; Doenst, Torsten; Petrie, Mark C.; Oh, Jae K.; She, Lilin; Moore, Vanessa L.; Desvigne-Nickens, Patrice; Sopko, George; Rouleau, Jean L.

    2016-01-01

    BACKGROUND The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear. METHODS From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years. RESULTS A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P = 0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P = 0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test). CONCLUSIONS In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of

  8. Atherosclerosis and ischemic cardiomyopathy in a captive, adult red-tailed hawk (Buteo jamaicensis).

    PubMed

    Shrubsole-Cockwill, Alana; Wojnarowicz, Chris; Parker, Dennilyn

    2008-09-01

    An adult, male, captive red-tailed hawk (Buteo jamaicensis) of at least 19 years of age presented in dorsal recumbency. The hawk was nonresponsive, and despite initial supportive care, died shortly after presentation. Gross postmortem revealed no abnormal findings. Histologic examination demonstrated atherosclerosis and ischemic cardiomyopathy. This is the first reported case of atherosclerosis in a red-tailed hawk.

  9. Feasibility and safety of catheter ablation of electrical storm in ischemic dilated cardiomyopathy.

    PubMed

    Dello Russo, Antonio; Casella, Michela; Pelargonio, Gemma; Santangeli, Pasquale; Bartoletti, Stefano; Bencardino, Gianluigi; Al-Mohani, Ghaliah; Innocenti, Ester; Di Biase, Luigi; Avella, Andrea; Pappalardo, Augusto; Carbucicchio, Corrado; Bellocci, Fulvio; Fiorentini, Cesare; Natale, Andrea; Tondo, Claudio

    2016-06-01

    Electrical storm is an emergency in 'implantation of a cardioverter defibrillator' carriers with ischemic dilated cardiomyopathy (DCM) and negatively impacts long-term prognosis. We evaluated the feasibility, safety, and effectiveness of radiofrequency catheter ablation (RFCA) in controlling electrical storm and its impact on survival and ventricular tachycardia/fibrillation recurrence. We enrolled 27 consecutive patients (25 men, age 73.1 ± 6.5 years) with ischemic DCM and an indication to RFCA for drug-refractory electrical storm. The immediate outcome was defined as failure or success, depending on whether the patient's clinical ventricular tachycardia could still be induced after RFCA; electrical storm resolution was defined as no sustained ventricular tachycardia/ventricular fibrillation in the next 7 days. Of the 27 patients, 1 died before RFCA; in the remaining 26 patients, a total of 33 RFCAs were performed. In all 26 patients, RFCA was successful, although in 6/26 patients (23.1%), repeated procedures were needed, including epicardial ablation in 3/26 (11.5%). In 23/26 patients (88.5%), electrical storm resolution was achieved. At a follow-up of 16.7 ± 8.1 months, 5/26 patients (19.2%) had died (3 nonsudden cardiac deaths, 2 noncardiac deaths) and 10/26 patients (38.5%) had ventricular tachycardia recurrence; none had electrical storm recurrence. A worse long-term outcome was associated with lower glomerular filtration rate, wider baseline QRS, and presence of atrial fibrillation before electrical storm onset. In patients with ischemic DCM, RFCA is well tolerated, feasible and effective in the acute management of drug-refractory electrical storm. It is associated with a high rate of absence of sustained ventricular tachycardia episodes over the subsequent 7 days. After successful ablation, long-term outcome was mainly predicted by baseline clinical variables.

  10. Lubiprostone induced ischemic colitis.

    PubMed

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

  11. Ischemic neuropathy and rhabdomyolysis as presenting symptoms of postpartum cardiomyopathy.

    PubMed

    Helmich, Rick C G; van Laarhoven, Hanneke W M; Schoonderwaldt, Hennie C; Janssen, Mirian C H

    2009-05-01

    Rhabdomyolysis and peripheral neuropathy are two distinct disease entities which are rarely encountered in combination. We present a woman with rhabdomyolysis and peripheral neuropathy 3 weeks postpartum. Her symptoms were caused by bilateral femoral artery thrombosis due to postpartum cardiomyopathy (PPCM). This demonstrates that PPCM may present with predominantly non-cardial symptoms and underscores the importance of rapidly recognizing this disorder.

  12. Endocardial substrate mapping for monomorphic ventricular tachycardia ablation in ischemic and non-ischemic cardiomyopathy.

    PubMed

    Fukuzawa, Koji; Yoshida, Akihiro; Kubo, Shinya; Takano, Takatsugu; Kiuchi, Kunihiko; Kanda, Gaku; Takami, Kaoru; Kumagai, Hiroyuki; Torii, Satoko; Takami, Mitsuru; Yokoyama, Mitsuhiro; Hirata, Ken-ichi

    2008-07-18

    We investigated the differences in the endocardial substrates between ischemic cardiomyopathy (ICM) and non-ICM (NICM) by using electro-anatomical mapping and pace-mapping. We studied 18 patients (ICM and NICM, 9 each) with monomorphic ventricular tachycardia (VT) documented by 12-leads ECG. Low voltage area was defined by signal amplitude <1.5 mV. A pace-map QRS morphology that matched VT in >10 of the 12-leads ECG was regarded as a pace-map match. And conduction delay during pace-mapping was defined as the stimulus to QRS interval >or=40 ms. Low voltage area was 53.8 +/- 21.5 and 20.8 +/- 16.7 cm2 in ICM and NICM patients, respectively (P = 0.002). Pace-mapping was assessed in 6 ICM and 9 NICM. Pace-map match with conduction delay were obtained in all the 6 ICM patients. But in NICM patients, pace-map match with conduction delay was obtained in 3 patients. Pace-map match sites where conduction delay was not observed were obtained in 5 patients. Pace-map match could not be obtained in 1 patient. We attempted ablation in 6 ICM and 7 NICM patients. Subsequently, VT recurrence was not observed in ICM but it was observed in 6 of 7 NICM patients (log-rank P = 0.0016). In NICM patients, the arrhythmogenic substrate that represented the abnormal electrogram and conduction delay was observed less within the endocardial surface when compared with that observed in ICM. VT recurrence rate subsequent to endocardial ablation was higher in NICM than in ICM patients.

  13. Cardiac magnetic resonance imaging and computed tomography in ischemic cardiomyopathy: an update*

    PubMed Central

    Assunção, Fernanda Boldrini; de Oliveira, Diogo Costa Leandro; Souza, Vitor Frauches; Nacif, Marcelo Souto

    2016-01-01

    Ischemic cardiomyopathy is one of the major health problems worldwide, representing a significant part of mortality in the general population nowadays. Cardiac magnetic resonance imaging (CMRI) and cardiac computed tomography (CCT) are noninvasive imaging methods that serve as useful tools in the diagnosis of coronary artery disease and may also help in screening individuals with risk factors for developing this illness. Technological developments of CMRI and CCT have contributed to the rise of several clinical indications of these imaging methods complementarily to other investigation methods, particularly in cases where they are inconclusive. In terms of accuracy, CMRI and CCT are similar to the other imaging methods, with few absolute contraindications and minimal risks of adverse side-effects. This fact strengthens these methods as powerful and safe tools in the management of patients. The present study is aimed at describing the role played by CMRI and CCT in the diagnosis of ischemic cardiomyopathies. PMID:26929458

  14. Cardiac magnetic resonance imaging and computed tomography in ischemic cardiomyopathy: an update.

    PubMed

    Assunção, Fernanda Boldrini; de Oliveira, Diogo Costa Leandro; Souza, Vitor Frauches; Nacif, Marcelo Souto

    2016-01-01

    Ischemic cardiomyopathy is one of the major health problems worldwide, representing a significant part of mortality in the general population nowadays. Cardiac magnetic resonance imaging (CMRI) and cardiac computed tomography (CCT) are noninvasive imaging methods that serve as useful tools in the diagnosis of coronary artery disease and may also help in screening individuals with risk factors for developing this illness. Technological developments of CMRI and CCT have contributed to the rise of several clinical indications of these imaging methods complementarily to other investigation methods, particularly in cases where they are inconclusive. In terms of accuracy, CMRI and CCT are similar to the other imaging methods, with few absolute contraindications and minimal risks of adverse side-effects. This fact strengthens these methods as powerful and safe tools in the management of patients. The present study is aimed at describing the role played by CMRI and CCT in the diagnosis of ischemic cardiomyopathies.

  15. Histopathological and Immunological Characteristics of Tachycardia-Induced Cardiomyopathy.

    PubMed

    Mueller, Karin A L; Heinzmann, David; Klingel, Karin; Fallier-Becker, Petra; Kandolf, Reinhard; Kilias, Antonios; Walker-Allgaier, Britta; Borst, Oliver; Kumbrink, Jörg; Kirchner, Thomas; Langer, Harald; Geisler, Tobias; Schreieck, Jürgen; Gramlich, Michael; Gawaz, Meinrad; Seizer, Peter

    2017-05-02

    Tachycardiomyopathy or tachycardia-induced cardiomyopathy (TCM) has been known for decades as a reversible form of nonischemic cardiomyopathy. However, its mechanism and properties remain poorly understood. The current study investigated endomyocardial biopsy samples from patients with TCM and compared them with samples from patients with dilated cardiomyopathy (DCM) and inflammatory cardiomyopathy (ICM). The study included 189 patients with new-onset heart failure and severely reduced ejection fraction not caused by valvular or ischemic heart disease. Nineteen patients retrospectively fulfilled common criteria of TCM, 79 patients had a diagnosis of DCM, and 91 had a diagnosis of ICM. Patients with TCM, on the basis of clinical criteria, had stronger myocardial expression of major histocompatibility complex class II molecule and enhanced infiltration of CD68(+) macrophages compared with patients with DCM. Furthermore, when compared with patients with ICM, the presence of T cells and macrophages was significantly reduced in TCM. Myocardial fibrosis was detected to a significantly lower degree in patients with TCM compared with patients with DCM and ICM. Electron microscopic examination revealed severe structural changes in patients with TCM. A disturbed distribution pattern of mitochondria was predominantly present in TCM. Quantitative assessment of myocyte morphology revealed significantly enhanced myocyte size compared with patients with ICM. Ribonucleic acid expression analysis identified changes in metabolic pathways among the patient groups. TCM is characterized by changes in cardiomyocyte and mitochondrial morphology accompanied by a macrophage-dominated cardiac inflammation. Thus, further prospective studies are warranted to characterize patients with TCM by endomyocardial biopsy more clearly. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  16. Effect of chronic sustained-release dipyridamole on myocardial blood flow and left ventricular function in patients with ischemic cardiomyopathy.

    PubMed

    Akhtar, Mateen; Ordovas, Karen; Martin, Alastair; Higgins, Charles B; Michaels, Andrew D

    2007-01-01

    Dipyridamole increases adenosine levels and augments coronary collateralization in patients with coronary ischemia. This pilot study tested whether a 6-month course of sustained-release dipyridamole/aspirin improves coronary flow reserve and left ventricular systolic function in patients with ischemic cardiomyopathy. Six outpatients with coronary artery disease and left ventricular ejection fraction (LVEF) <40% were treated with sustained-release dipyridamole 200 mg/aspirin 25 mg twice daily for 6 months. Myocardial function and perfusion, including coronary sinus flow at rest and during intravenous dipyridamole-induced hyperemia, were measured using velocity-encoded cine magnetic resonance stress perfusion studies at baseline, 3 months, and 6 months. There was no change in heart failure or angina class at 6 months. LVEF increased by 39%+/-64% (31.0%+/-13.3% at baseline vs 38.3%+/-10.7% at 6 months; P=.01), hyperemic coronary sinus flow increased more than 2-fold (219.6+/-121.3 mL/min vs 509.4+/-349.3 mL/min; P=.01), and stress-induced relative myocardial perfusion increased by 35%+/-13% (9.4%+/-3.4% vs 13.9%+/-8.5%; P=.004). Sustained-release dipyridamole improved hyperemic myocardial blood flow and left ventricular systolic function in patients with ischemic cardiomyopathy.

  17. Current Indications for Implantable Cardioverter Defibrillators in Non-Ischemic Cardiomyopathies and Channelopathies.

    PubMed

    González-Torrecilla, Esteban; Arenal, Angel; Atienza, Felipe; Datino, Tomás; Bravo, Loreto; Ruiz, Pablo; Ávila, Pablo; Fernández-Avilés, Francisco

    2015-01-01

    Current indications for implantable cardioverter defibrillators (ICDs) in patients with channelopathies and cardiomyopathies of non-ischemic origin are mainly based on non-randomized evidence. In patients with nonischemic dilated cardiomyopathy (NIDCM), there is a tendency towards a beneficial effect on total mortality of ICD therapy in patients with significant left ventricular (LV) dysfunction. Although an important reduction in sudden cardiac death (SCD) seems to be clearly demonstrated in these patients, a net beneficial effect on total mortality is unclear mostly in cases with good functional status. Risk stratification has been changing over the last two decades in patients with hypertrophic cardiomyopathy (HCM). Its risk profile has been delineated in parallel with the beneficial effect of ICD in high risk patients. Observational results based on "appropriate" ICD interventions do support its usefulness both in primary and secondary SCD prevention in these patients. Novel risk models quantify the rate of sudden cardiac death in these patients on individual basis. Less clear risk stratification is available for cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) and in other uncommon familiar cardiomyopathies. Main features of risk stratification vary among the different channelopathies (long QT syndrome -LQTS-, Brugada syndrome, etc) with great debate on the management of asymptomatic patients. For most familiar cardiomyopathies, ICD therapy is the only accepted strategy in the prevention of SCD. So far, genetic testing has a limited role in risk evaluation and management of the individual patient. This review aims to summarize these criticisms and to refine the current indications of ICD implantation in patients with cardiomyopathies and major channelopathies.

  18. What About Tachycardia-induced Cardiomyopathy?

    PubMed Central

    Ellis, Ethan R; Josephson, Mark E

    2013-01-01

    Long-standing tachycardia is a well-recognised cause of heart failure and left ventricular dysfunction, and has led to the nomenclature, tachycardia-induced cardiomyopathy (TIC). TIC is generally a reversible cardiomyopathy if the causative tachycardia can be treated effectively, either with medications, surgery or catheter ablation. The diagnosis is usually made after demonstrating recovery of left ventricular function with normalisation of heart rate in the absence of other identifiable aetiologies. One hundred years after the first reported case of TIC, our understanding of the pathophysiology of TIC in humans remains limited despite extensive work in animal models of TIC. In this review we will discuss the proposed mechanisms of TIC, the causative tachyarrhythmias and their treatment, outcomes for patients diagnosed with TIC, and future directions for research and clinical care. PMID:26835045

  19. Absence of coronary sinus tributaries in ischemic cardiomyopathy: An insight from multidetector computed tomography cardiac venographic study.

    PubMed

    Boonyasirinant, Thananya; Halliburton, Sandra S; Schoenhagen, Paul; Lieber, Michael L; Flamm, Scott D

    2016-01-01

    Cardiac resynchronization therapy (CRT) is an important therapeutic strategy in heart failure. However, there is a high incidence of lead implantation failure and suboptimal response, particularly in ischemic cardiomyopathy. This failure rate may partly be secondary to lack of suitable coronary sinus branches for lead implantation. We sought to assess the presence of coronary sinus (CS) tributaries in patients with ischemic and non-ischemic cardiomyopathy. Multidetector computed tomography (MDCT) was performed in 100 patients: 25 coronary artery bypass graft (CABG) patients with impaired left ventricular ejection fraction (LVEF), 25 CABG patients with preserved LVEF, 25 patients with non-ischemic cardiomyopathy, and 25 controls. The presence of the CS and its tributaries, including the posterior interventricular vein (PIV), posterolateral vein (PLV), left marginal vein (LMV), and the anterior interventricular vein (AIV) was assessed. The CS, PIV, and AIV were demonstrated in all patients, whereas presence of a PLV and LMV was identified in 68% and 48% of CABG patients with impaired LVEF, 96% and 68% of CABG patients with preserved LVEF, 92% and 80% of patients with non-ischemic cardiomyopathy, and 100% and 80% of controls (p = 0.001 and 0.046 for PLV and LMV, respectively). This is the first report to demonstrate that the posterolateral vein and left middle vein, branches of the coronary sinus, are detectable in a significantly smaller number of CABG patients with impaired LVEF compared to controls, CABG with preserved LVEF, and non-ischemic cardiomyopathy. The absence of CS tributary veins in ischemic cardiomyopathy potentially hinders proper lead implantation and results in suboptimal CRT response. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  20. Molecular biology of doxorubicin-induced cardiomyopathy

    PubMed Central

    Umlauf, J; Horký, M

    2002-01-01

    The anthracycline doxorubicin is an antineoplastic agent, eliciting chronic cardiac toxicity. It occurs in patients after prolonged administration of doxorubicin, leading to congestive heart failure. The pathogenesis of the doxorubicin-induced car-diomyopathy is not well understood. The present article summarizes the unique effect of doxorubicin on cardiac-specific gene expression. In addition to binding to DNA, doxorubicin directly affects the function of a variety of proteins. Free radical generation, damage to mitochondria and active cell death are also critical in the development of doxorubicin-induced cardiac toxicity. Agents providing effective cardioprotection are also reviewed. PMID:19644577

  1. Cardiomyopathy in a dish: using human inducible pluripotent stem cells to model inherited cardiomyopathies.

    PubMed

    Kamdar, Forum; Klaassen Kamdar, Andre; Koyano-Nakagawa, Naoko; Garry, Mary G; Garry, Daniel J

    2015-09-01

    Inherited cardiomyopathies, including hypertrophic cardiomyopathy, dilated cardiomyopathies, arrythmogenic right ventricular cardiomyopathy, and other inherited forms of heart failure, represent a unique set of genetically defined cardiovascular disease processes. Unraveling the molecular mechanisms of these deadly forms of human heart disease has been challenging, but recent groundbreaking scientific advances in stem cell technology have allowed for the generation of patient-specific human inducible stem cell (hiPSC)-derived cardiomyocytes (CMs). hiPSC-derived CMs retain the genetic blueprint of the patient, they can be maintained in culture, and they recapitulate the phenotypic characteristics of the disease in vitro, thus serving as a disease in a dish. This review provides an overview of in vitro modeling of inherited cardiomyopathies with the use of patient-specific hiPSC-derived CMs. Copyright © 2015. Published by Elsevier Inc.

  2. Cardiomyopathy in a dish: Using human inducible pluripotent stem cells to model inherited cardiomyopathies

    PubMed Central

    Kamdar, Forum; Kamdar, Andre Klaassen; Koyano-Nakagawa, Naoko; Garry, Mary G.; Garry, Daniel J.

    2015-01-01

    Inherited cardiomyopathies including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathies (DCM), arrythmogenic right ventricular cardiomyopathy (ARVC), and other inherited forms of heart failure represent a unique set of genetically defined cardiovascular disease processes. Unraveling the molecular mechanisms of these deadly forms of human heart disease has been challenging, however recent groundbreaking scientific advances in stem cell technology has allowed for the generation of patient-specific human inducible stem cell (hiPSC)-derived cardiomyocytes (hiPSC-derived CMs). hiPSC-derived CMs retain the genetic blueprint of the patient, they can be maintained in culture, and they recapitulate the phenotypic characteristics of the disease in vitro, thus serving as a disease in a dish. This review provides an overview of in vitro modeling of inherited cardiomyopathies using patient-specific hiPSC-derived CMs. PMID:25934595

  3. Conduction Remodeling in Human End-Stage Non-Ischemic Left Ventricular Cardiomyopathy

    PubMed Central

    Glukhov, Alexey V.; Fedorov, Vadim V.; Kalish, Paul W.; Ravikumar, Vinod K.; Lou, Qing; Janks, Deborah; Schuessler, Richard B.; Moazami, Nader; Efimov, Igor R.

    2012-01-01

    Background Several arrhythmogenic mechanisms have been inferred from animal heart failure (HF) models. However, the translation of these hypotheses is difficult due to lack of functional human data. We aimed to investigate the electrophysiological substrate for arrhythmia in human end-stage non-ischemic cardiomyopathy. Methods and Results We optically mapped the coronary-perfused left ventricular wedge preparations from human hearts with end-stage non-ischemic cardiomyopathy (HF, n=10) and non-failing hearts (NF, n=10). Molecular remodeling was studied with immunostaining, Western blotting, and histological analyses. HF produced heterogeneous prolongation of action potential duration (APD) resulting in the decrease of transmural APD dispersion (64±12 ms vs 129±15 ms in NF, P<0.005). In the failing hearts, transmural activation was significantly slowed from the endocardium (39±3 cm/s versus 49±2 cm/s in NF, P=0.008) to the epicardium (28±3 cm/s versus 40±2 cm/s in NF, P=0.008). Conduction slowing was likely due to Cx43 downregulation, decreased colocalization of Cx43 with N-cadherin (40±2% versus 52±5% in NF, P=0.02), and an altered distribution of phosphorylated Cx43 isoforms by the upregulation of the dephosphorylated Cx43 in both the subendocardium and subepicardium layers. Failing hearts further demonstrated spatially discordant conduction velocity alternans which resulted in nonuniform propagation discontinuities and wavebreaks conditioned by strands of increased interstitial fibrosis (fibrous tissue content in HF 16.4±7.7 versus 9.9±1.4% in NF, P=0.02). Conclusions Conduction disorder resulting from the anisotropic downregulation of Cx43 expression, the reduction of Cx43 phosphorylation, and increased fibrosis is likely to be a critical component of arrhythmogenic substrate in patients with non-ischemic cardiomyopathy. PMID:22412072

  4. Association of mean platelet volume with presence of non viable myocardium in ischemic cardiomyopathy.

    PubMed

    Ozturk, Semi; Gürbüz, Ahmed Seyfettin; Efe, Süleyman Çağan; Yılmaz, Mehmet Fatih; Den Hartigh, Özden Savaş; Sayın, Ferahnaz Çınaral; Kırma, Cevat

    2017-07-17

    Parameters derived from complete blood count such as mean platelet volume (MPV), neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR) are recently proposed as measures of inflammation in addition to C-reactive protein (CRP), a classical inflammatory marker. Significant association of these parameters with atherosclerosis and complications have increasingly been reported. Our aim is to evaluate relationship between these parameters and presence of myocardial viability assessed with positron emission tomography (PET) in patients with ischemic cardiomyopathy. A total of 122 ischemic cardiomyopathy patients who had undergone PET were enrolled in this study. The patients were dichotomized depending on the presence of transmural scar. Group 1 consisted of 21 patients who had transmural scar tissue, only, which were accepted as the group having non-viable myocardium. Group 2 consisted of 101 patients who had hibernation and/or non-transmural scar which were accepted as the group having viable myocardium. Hematological parameters within 30 days of PET imaging were retrospectively analyzed. There were no significant differences between two groups regarding values of WBC, neutrophil, lymphocyte, platelet, hemoglobin, RDW, CRP, PLR and NLR. Patients with non viable myocardium have significantly higher levels of MPV (p:0,002). In multiple logistic regression analysis, MPV [odds ratio (OR)=0,373, 95% confidence interval (CI) 0.20-0.69, p=0.002], was identified as independent predictor of non viable myocardium. In ROC analysis, a cut-point of 8,19 identified patients with non viable myocardium (area under curve=0.72, 95% CI 0.60-0.84). MPV value of greater than 8,19 demonstrated a sensitivity of 76%, a specificity of 55%. The present study showed that MPV is an inexpensive, clinical and routinely measurable parameter that is associated with the presence of viable myocardium in ischemic cardiomyopathy.

  5. Incessant "ventricular tachycardia" in a patient with non-ischemic cardiomyopathy. What is the tachycardia mechanism?

    PubMed

    Arora, Sandeep

    2015-01-01

    We present an uncommon and unique arrhythmia in a patient with non-ischemic cardiomyopathy and dual chamber implantable cardioverter defibrillator presenting with palpitations and dyspnea. While surface electrocardiogram suggested irregular narrow complex tachycardia, evaluation of stored electrograms from implantable cardioverter defibrillator revealed incessant episodes of non-sustained ventricular tachycardia. The patient underwent electrophysiological study and successful ablation of the arrhythmia with complete resolution of symptoms. We discuss the underlying tachycardia mechanism and challenges in the diagnosing and management of this unusual rhythm disorder. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Biventricular pacemaker/defibrillators versus biventricular pacemakers in patients with non-ischemic cardiomyopathy.

    PubMed

    Sturdivant, John Lacy; Gold, Michael R

    2015-09-01

    The decision to employ defibrillator therapy in patients with non-ischemic cardiomyopathy is driven by reduction in mortality. The strength of data supporting this therapy has led to its incorporation in medical guidelines and general practice across the world. Cardiac resynchronization therapy has also been proven to reduce heart failure hospitalization and improve quality of life. Although trends toward reduction in arrhythmic events have been observed, results in multicenter, randomized controlled trials have not been compelling for stand-alone use in most patients who currently meet criteria for defibrillator therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

    PubMed

    Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

    2014-03-01

    Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment.

  8. Cardiomyopathy

    MedlinePlus

    Cardiomyopathy is the name for diseases of the heart muscle. These diseases enlarge your heart muscle or ... tissue. Some people live long, healthy lives with cardiomyopathy. Some people don't even realize they have ...

  9. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

    PubMed Central

    Dewald, Daniela; Schmitz, Eva J.; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT−/−)-mice (n = 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT−/−-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2−/−-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT−/−-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2−/−-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  10. Computer-based assessment of left ventricular wall stiffness in patients with ischemic dilated cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Su, Y.; Teo, S. K.; Tan, R. S.; Lim, C. W.; Zhong, L.

    2013-02-01

    Ischemic dilated cardiomyopathy (IDCM) is a degenerative disease of the myocardial tissue accompanied by left ventricular (LV) structural changes such as interstitial fibrosis. This can induce increased passive stiffness of the LV wall. However, quantification of LV passive wall stiffness in vivo is extremely difficult, particularly in ventricles with complex geometry. Therefore, we sought to (i) develop a computer-based assessment of LV passive wall stiffness from cardiac magnetic resonance (CMR) imaging in terms of a nominal stiffness index (E*); and (ii) investigate whether E* can offer an insight into cardiac mechanics in IDCM. CMR scans were performed in 5 normal subjects and 5 patients with IDCM. For each data sample, an in-house software was used to generate a 1-to-1 corresponding mesh pair of the LV from the ED and ES phases. The E* values are then computed as a function of local ventricular wall strain. We found that E* in the IDCM group (40.66 - 215.12) was at least one order of magnitude larger than the normal control group (1.00 - 6.14). In addition, the IDCM group revealed much higher inhomogeneity of E* values manifested by a greater spread of E* values throughout the LV. In conclusion, there is a substantial elevated ventricular stiffness index in IDCM. This would suggest that E* could be used as discriminator for early detection of disease state. The computational performance per data sample took approximately 25 seconds, which demonstrates its clinical potential as a real-time cardiac assessment tool.

  11. Adderall induced inverted-Takotsubo cardiomyopathy.

    PubMed

    Alsidawi, Said; Muth, James; Wilkin, James

    2011-11-15

    Takotsubo Cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, was initially described in Japan in 1990. Both illicit and prescription drugs have added to the growing list of insulting stressors. We describe an interesting case of atypical TTC triggered by adderall overdose. A 19-year-old female was brought to the Emergency Department after ingesting 30 Adderall tablets. She was complaining of pressure like chest pain and shortness of breath. Her cardiac enzymes were elevated but the electrocardiogram was unremarkable. Echocardiography identified an ejection fraction (EF) of 25-30% with severe hypokinesis of the base and a preserved apex. Cardiac angiography demonstrated normal coronary arteries with an EF of 35%, hyperkinetic apex and akinetic base consistent with the diagnosis of inverted-TTC. Her symptoms resolved in 24 hrs. Repeat echocardiogram performed 3 days later showed an EF of 60% with no regional wall motion abnormalities. TTC can be identified as a rapid development of severe and reversible left ventricular dysfunction extending beyond the territory of a single epicardial coronary artery in the absence of coronary artery disease or pheochromocytoma. Clinical presentation can be challenging and very hard to distinguish from acute myocardial infarction. Medication induced-TTC has been reported. In our case, the patient overdosed on Adderall which is a sympathomimetic medication. Cardiac imaging identified wall motion abnormalities consistent with inverted type TTC. Restoration of left ventricular function within days confirms the diagnosis of TTC. In conclusion, this case offers an interesting insight into the pathophysiology of TTC. Copyright © 2011 Wiley Periodicals, Inc.

  12. Improvement of cardiac function and neurological remodeling in a patient with tachycardia-induced cardiomyopathy after catheter ablation.

    PubMed

    Omichi, Chikaya; Tanaka, Takeshi; Kakizawa, Yoshiko; Yamada, Ayako; Ishii, Yasuhiro; Nagashima, Hirotaka; Kanmatsuse, Katsuo; Endo, Masahiro

    2009-08-01

    Incessant ventricular tachycardia and long-standing ectopic beats lead to tachycardia-induced cardiomyopathy. Catheter ablation eliminates ventricular tachycardia and reverses left ventricular (LV) dysfunction. 201-Thallium ((201)Tl) scintigraphy demonstrates perfusion defects with ischemic cardiomyopathy. Reversible perfusion defects are observed even in non-ischemic cardiomyopathy, related to regional flow or metabolism derangements. 123-I-metaiodobezylguanidine ((123)I-MIBG) scintigraphy delineates regional cardiac sympathetic denervation and heterogeneity. We demonstrated the progression of tachycardia-induced cardiomyopathy in a patient with idiopathic LV outflow tract tachycardia using (201)Tl and (123)I-MIBG scintigraphic findings. Regional defects were reversed predominantly in the basal interventricular septal wall in (201)Tl scintigraphy and (123)I-MIBG scintigraphic findings. This report suggests that incessant ventricular tachycardia or long-standing ventricular ectopic beats may develop adverse myocardial remodeling and sympathetic neurological remodeling. Treatment with catheter ablation for tachycardia-induced cardiomyopathy can reverse sympathetic neurological remodeling as well as myocardial structural remodeling.

  13. Impact of ethyl pyruvate on Adriamycin-induced cardiomyopathy in rats

    PubMed Central

    Liu, Menglin; Wang, Menglong; Liu, Jianfang; Luo, Zhen; Shi, Lei; Feng, Ying; Li, Li; Xu, Lin; Wan, Jun

    2016-01-01

    Ethyl pyruvate (EP), a derivative of pyruvic acid, is known to have protective effects against ischemic cardiomyopathy and other disorders. However, little is known about its role in Adriamycin (ADR)-induced cardiomyopathy. The present study was designed to investigate the impact of EP on ADR-induced cardiomyopathy in an animal model. Sixty male Sprague-Dawley (SD) rats were divided into four groups: Normal control, EP, ADR and ADR + EP groups (n=15/group). Rats in the ADR and ADR + EP groups were treated with ADR (2.5 mg/kg/week intraperitoneally) for 6 weeks. From the eighth week, rats in the EP and ADR + EP groups received EP via gastric lavage at a dose of 50 mg/kg/day for 30 days. After completing the EP treatment, cardiac function was assessed by echocardiography and then rats were sacrificed. Hearts were harvested for subsequent analysis. Compared with rats in the normal control and EP groups (without ADR treatment), rats in the ADR and ADR + EP groups showed significant impairments in terms of cardiac function, apoptosis, severe oxidative stress and fibrosis in the heart. However, these impairments were alleviated by EP treatment in the ADR + EP group. Upon EP treatment, cardiac function was significantly improved. The levels of oxidative stress, fibrosis and apoptosis in the myocardial tissues were also significantly reduced. These findings indicated that EP treatment attenuated, at least partially, ADR-induced cardiomyopathy in rats. PMID:27882138

  14. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder

    PubMed Central

    Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

    2009-01-01

    Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure. PMID:19533818

  15. Mitochondria as a Drug Target in Ischemic Heart Disease and Cardiomyopathy

    PubMed Central

    Walters, Andrew M; Porter, George A; Brookes, Paul S.

    2012-01-01

    Ischemic heart disease (IHD) is a significant cause of morbidity and mortality in Western society. Although interventions such as thrombolysis and percutaneous coronary intervention (PCI) have proven efficacious in ischemia and reperfusion (IR) injury, the underlying pathologic process of IHD, laboratory studies suggest further protection is possible, and an expansive research effort is aimed at bringing new therapeutic options to the clinic. Mitochondrial dysfunction plays a key role in the pathogenesis of IR injury and cardiomyopathy (CM). However, despite promising mitochondria-targeted drugs emerging from the lab, very few have successfully completed clinical trials. As such, the mitochondrion is a potential untapped target for new IHD and CM therapies. Notably, there are a number of overlapping therapies for both these diseases, and as such novel therapeutic options for one condition may find use in the other. This review summarizes efforts to date in targeting mitochondria for IHD and CM therapy, and outlines emerging drug targets in this field. PMID:23065345

  16. Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

    PubMed Central

    Thoonen, Robrecht; Ernande, Laura; Cheng, Juan; Nagasaka, Yasuko; Yao, Vincent; Miranda-Bezerra, Alexandre; Chen, Chan; Chao, Wei; Panagia, Marcello; Sosnovik, David E.; Puppala, Dheeraj; Armoundas, Antonis A.; Hindle, Allyson; Bloch, Kenneth D.; Buys, Emmanuel S.; Scherrer-Crosbie, Marielle

    2015-01-01

    Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1−/−) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1−/− mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1−/− mice. UCP1−/− mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1−/− mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1−/− BAT transplanted to either UCP1−/− or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1−/− mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1−/− mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy. PMID:25968336

  17. Beta-blockade with bucindolol in heart failure caused by ischemic versus idiopathic dilated cardiomyopathy.

    PubMed

    Woodley, S L; Gilbert, E M; Anderson, J L; O'Connell, J B; Deitchman, D; Yanowitz, F G; Mealey, P C; Volkman, K; Renlund, D G; Menlove, R

    1991-12-01

    We investigated the effects of bucindolol, a nonselective, non-ISA beta-blocker with mild-vasodilatory properties, in patients with congestive heart failure from ischemic dilated cardiomyopathy (ISCDC, n = 27) and compared the results with those in subjects with heart failure from idiopathic dilated cardiomyopathy (IDC, n = 22). Patients were randomized in a double-blind fashion to receive 12 weeks' treatment with either bucindolol or placebo, with randomization stratified for IDC or ISCDC: Invasive (right heart catheterization) and noninvasive (echo, MUGA, central venous norepinephrine, exercise treadmill studies, and symptom scores) tests of heart failure severity were determined at baseline and end of the study. For all subjects (ISCDC plus IDC), relative to placebo treatment, bucindolol-treated patients had significant improvement in ejection fraction, left ventricular size and filling pressure, stroke work index, symptom score, and central venous norepinephrine. However, most of these differences could be attributed to improvement in the IDC subgroup, as the only parameter with a statistically significant degree of improvement in the bucindolol-treated ISCDC subgroup was left ventricular size. We conclude that beta-blockade may produce quantitatively different degrees of response in different kinds of heart muscle disease.

  18. Usefulness of the Agatston score = 0 to exclude ischemic cardiomyopathy in patients with heart failure.

    PubMed

    Abunassar, Joseph G; Yam, Yeung; Chen, Li; D'Mello, Nisha; Chow, Benjamin J W

    2011-02-01

    Quantification of coronary artery calcium has prognostic value and is commonly used in asymptomatic patients. Routine clinical use of coronary artery calcium in other populations remains uncertain. We sought to understand the potential application of the Agatston score in patients with heart failure (HF). For this purpose, 3 populations were identified: (1) patients with an Agatston score equal to 0, (2) patients with high-risk coronary artery disease (CAD) defined as 3-vessel, left main, or 2-vessel disease involving the proximal left anterior descending coronary artery, and (3) patients with HF symptoms and left ventricular (LV) ejection fraction <50%. Excluding patients with HF or LV dysfunction, 738 patients (mean age 52 ± 10 years, 43% men) had an Agatston score equal to 0. Of these, 18 (2%) had obstructive CAD (diameter stenosis ≥50%), 8 (1%) had diameter stenoses ≥70%, and none had high-risk CAD. The 74 patients with high-risk CAD without LV dysfunction had high Agatston scores (mean 895 ± 734, median 716, range 50 to 3,210). In total 153 patients with a history of HF and abnormal ejection fraction were identified. All 13 patients with ischemic cardiomyopathy had Agatston scores >0, whereas 46 of 140 patients (30.1%) with nonischemic causes had an Agatston score equal to 0. An Agatston score equal to 0 identified nonischemic causes with a specificity of 100% (confidence interval 90 to 100) and positive predictive value of 100% (confidence interval 90 to 100). Agatston score equal to 0 had incremental value to pretest probability for CAD. In conclusion, an Agatston score equal to 0 confers a very low likelihood of obstructive CAD, appears to rule out high-risk CAD, and thus may be used to rule out ischemic cardiomyopathy in patients with HF.

  19. Fourier amplitude and phase analysis in the clinical evaluation of patients with cardiomyopathy

    SciTech Connect

    Alcan, K.E.; Robeson, W.; Graham, M.C.; Palestro, C.; Oliver, F.H.; Benua, R.S.

    1984-06-01

    Fifty-four patients with a cardiomyopathy were studied by Radionuclide Cardangiography (RNCA) and Fourier amplitude and phase image analysis. The study group included patients with ischemic cardiomyopathy (27) and an equal number of patients with a primary cardiomyopathy: drug-induced (22), idiopathic (three), radiation-induced (one), and amyloidosis (one). Twenty-eight patients had rest studies alone and 26 had both rest and stress studies (80 total). The mean rest LVEF in the ischemic group was 27.9%, in the drug-induced group 36.5%, and in the idiopathic group 30%. The stress LVEF decreased in 92% of patients with ischemic cardiomyopathy and 45% of patients with primary (drug-induced) cardiomyopathy. Fourier amplitude and phase images were generated for each study. Amplitude and phase images were abnormal in all patients with an ischemic cardiomyopathy. LV amplitude abnormalities were regional and phase was directional. A zone of dysynergy on phase analysis was present in 44% of patients with ischemic cardiomyopathy. In the drug-induced primary cardiomyopathy group, all patients had abnormal amplitude and 86% had abnormal phase. Amplitude abnormalities were global rather than regional and phase patterns were nondirectional. Only one patient had a zone of dysynergy on the phase image. We conclude that the stress LVEF alone cannot consistently differentiate between ischemic and primary cardiomyopathies and that Fourier amplitude and phase analysis may be useful in determining the etiology of a cardiomyopathy (ischemic vs primary).

  20. [Efficacy of surgical left ventricular restoration for the patients with ischemic cardiomyopathy; comparison with the surgical treatments for ischemic heart failure (STICH) trial].

    PubMed

    Kokaji, Kiyokazu; Kudo, Mikihiko; Yozu, Ryohei

    2011-10-01

    The efficacy of surgical left ventricular restoration (LVR) for the patients with ischemic cardiomyopathy was denied by the surgical treatments for ischemic heart failure (STICH) trial. But the conclusion of the STICH trial is wrong and real message of the STICH trial is as follows. LVR is not effective procedure for the patients with poor left ventricular function and small left ventricular dilatation. In the STICH trial, volume reduction rate of the patients with LVR is too little. Based on the low of Laplace, little volume reduction rate do not contribute the improvement of the ventricular function. In our 33 cases of LVR, the survival rates at 5, 7, and 10 years after LVR were 80%, 76% and 76%. On the other hand, the corresponding cardiac event-free rates were 55%. 44%, and 44%. These discrepancies of the value suggest the importance of both the preoperative strategy and the intensive therapy during the postoperative period. We observed some cases that re-enlarged left ventricle after LVR induced heart failure or ventricular arrhythmia. The timing of operation, left ventricular reconstruction of appropriate size and shape considering the function of residual myocardium has significant effect on prognosis. Postoperative ventricular tachycardia (VT) was the major factor influenced the survival rate. After preoperative or intraoperative three-dimensional electrical mapping by CARTO system to detect focus of VT, endocardiectomy combined with cryoablation at the VT focus is performed and postoperative antiarrhythmic medication is added routinely. If LVR will be performed after appreciation of its concept, indication and method, excellent long term prognosis will be expected.

  1. Tachycardia-induced cardiomyopathy in a cat.

    PubMed

    Schober, K E; Kent, A M; Aeffner, F

    2014-03-01

    A 10-year-old male castrated Domestic Shorthair cat was evaluated for an asymptomatic tachyarrhythmia noted two weeks prior. Electrocardiography revealed a normal sinus rhythm with atrial premature complexes and paroxysms of supraventricular tachycardia with a heart rate between 300 and 400 min-1. Echocardiography was unremarkable, and concentrations of circulating cardiac troponin I, T4, and blood taurine were within reference ranges. The cat was treated with sotalol (2.1 mg/kg q12h, PO) but the arrhythmia was insufficiently controlled as determined during several re-examinations within a two-year time period. Twenty four months after initial presentation atrial fibrillation with fast ventricular response rate (200 to 300 min-1) was diagnosed, along with severe eccentric chamber remodeling and systolic dysfunction. The cat developed congestive heart failure and cardiogenic shock and was euthanized nearly 27 months after the first exam. Gross and histopathologic findings ruled out commonly seen types of primary myocardial disease in cats. The persistent nature of the tachyarrhythmia, the progressive structural and functional cardiac changes, and comparative gross and histopathologic post-mortem findings are consistent with the diagnosis of tachycardia-induced cardiomyopathy.

  2. On-pump beating heart mitral valve repair in patients with patent bypass grafts and severe ischemic cardiomyopathy.

    PubMed

    Atoui, Rony; Bittira, Bindu; Morin, Jean E; Cecere, Renzo

    2009-07-01

    Re-operative mitral valve surgery in patients with poor ventricular function can be challenging especially in the presence of patent bypass grafts. We report the case of 11 patients with severe ischemic cardiomyopathy who underwent reoperative mitral valve repair through a limited right thoracotomy approach, on a non-fibrillating beating heart. All patients had their valves successfully repaired with no operative mortality and minimal morbidity. The technical aspects of the procedure are discussed, and the pertinent literature reviewed.

  3. Left ventricular long axis strain: a new prognosticator in non-ischemic dilated cardiomyopathy?

    PubMed

    Riffel, Johannes H; Keller, Marius G P; Rost, Franziska; Arenja, Nisha; Andre, Florian; Aus dem Siepen, Fabian; Fritz, Thomas; Ehlermann, Philipp; Taeger, Tobias; Frankenstein, Lutz; Meder, Benjamin; Katus, Hugo A; Buss, Sebastian J

    2016-06-07

    Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet. In 146 subjects with non-ischemic dilated cardiomyopathy (NIDCM, LVEF ≤45 %) LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end-diastole. The final values were calculated according to the strain formula. The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > -5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, p < 0.05), presence of LGE (HR: 2.51, p < 0.05) and LAS (HR: 1.28, p < 0.05) were independent predictors for cardiac events. In a sequential cox regression analysis LAS offered significant incremental information (p < 0.05) for the prediction of outcome in addition to LGE and LVEDV/BSA. Using a dichotomous three point scoring model for risk stratification, including LVEF <35 %, LAS > -10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points. Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters.

  4. Losartan improves heart rate variability and heart rate turbulence in heart failure due to ischemic cardiomyopathy.

    PubMed

    Ozdemir, Murat; Arslan, Uğur; Türkoğlu, Sedat; Balcioğlu, Serhat; Cengel, Atiye

    2007-12-01

    Heart rate variability (HRV) and heart rate turbulence are known to be disturbed and associated with excess mortality in heart failure. The aim of this study was to investigate whether losartan, when added on top of beta-blocker and angiotensin-converting enzyme inhibitor (ACEI) therapy, could improve these indices in patients with systolic heart failure. Seventy-seven patients (mean age 60.4 +/- 8.0, 80.5% male) with ischemic cardiomyopathy (mean ejection fraction 34.5 +/- 4.4%) and New York Heart Association Class II-III heart failure symptoms, already receiving a beta-blocker and an ACEI, were randomly assigned to either open-label losartan (losartan group) or no additional drug (control group) in a 2:1 ratio and the patients were followed for 12 weeks. The HRV and heart rate turbulence indices were calculated from 24-hour Holter recordings both at the beginning and at the end of follow-up. The baseline clinical characteristics, HRV, and heart rate turbulence indices were similar in the 2 groups. At 12 weeks of follow-up, all HRV parameters except pNN50 increased (SDNN: 113.2 +/- 34.2 versus 127.8 +/- 24.1, P = .001; SDANN: 101.5 +/- 31.7 versus 115.2 +/- 22.0, P = .001; triangular index: 29.9 +/- 11.1 versus 34.2 +/- 7.9, P = .008; RMSSD: 29.1 +/- 20.2 versus 34.3 +/- 23.0, P = .009; NN50: 5015.3 +/- 5554.9 versus 6446.7 +/- 6101.1, P = .024; NN50: 5.65 +/- 6.41 versus 7.24 +/- 6.99, P = .089; SDNNi: 45.1 +/- 13.3 versus 50.3 +/- 14.5, P = .004), turbulence onset decreased (-0. 61 +/- 1.70 versus -1.24 +/- 1.31, P = .003) and turbulence slope increased (4.107 +/- 3.881 versus 5.940 +/- 4.281, P = .004) significantly in the losartan group as compared with controls. A 12-week-long losartan therapy significantly improved HRV and heart rate turbulence in patients with Class II-III heart failure and ischemic cardiomyopathy already on beta-blockers and ACEI.

  5. The effect of ICD programming on inappropriate and appropriate ICD Therapies in ischemic and nonischemic cardiomyopathy: the MADIT-RIT trial.

    PubMed

    Sedláček, Kamil; Ruwald, Anne-Christine; Kutyifa, Valentina; McNitt, Scott; Thomsen, Poul Erik Bloch; Klein, Helmut; Stockburger, Martin; Wichterle, Dan; Merkely, Bela; DE LA Concha, Joaquin Fernandez; Swissa, Moshe; Zareba, Wojciech; Moss, Arthur J; Kautzner, Josef; Ruwald, Martin H

    2015-04-01

    The MADIT-RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high-rate cut-off and 60-second-delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT-RIT ICD programming in patients with ischemic and nonischemic cardiomyopathy. First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with nonischemic cardiomyopathy. Patients with ischemic and nonischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy (HR range 0.11-0.34, P < 0.001 for all comparisons). Occurrence of total inappropriate and appropriate ICD therapies was significantly reduced by high-rate cut-off ICD programming and delayed VT therapy ICD programming in both ischemic and nonischemic cardiomyopathy patients. High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy. © 2014 Wiley Periodicals, Inc.

  6. Long-term Survival of Patients with Ischemic Cardiomyopathy Treated by CABG versus Medical Therapy

    PubMed Central

    Velazquez, Eric J.; Williams, Judson B.; Yow, Eric; Shaw, Linda K.; Lee, Kerry L.; Phillips, Harry R.; O’Connor, Christopher M.; K.Smith, Peter; Jones, Robert H.

    2013-01-01

    Background We prospectively applied the Surgical Treatment of Ischemic Cardiomyopathy (STICH) trial entry criteria to an observational database to determine whether coronary artery bypass grafting (CABG) decreases mortality compared to medical therapy (MED) for patients suffering coronary artery disease (CAD) and depressed left ventricular ejection fraction (LVEF). Methods This was a retrospective, observational, cohort study of prospectively collected data from the Duke Databank for Cardiovascular Disease. Long-term mortality was the main outcome measure. Between January 1, 1995 and July 31, 2009, 86,874 patients underwent cardiac catheterization for suspected ischemic heart disease and were evaluated for inclusion in the analysis. Results A total of 2,624 patients were found to have LVEF <35%, CAD amenable to CABG and no left main stenosis ≥50%. After exclusions including ongoing Class III angina and acute myocardial infarction, 763 patients were included for propensity score analysis including 624 who received MED and 139 CABG. Adjusted mortality curves were constructed for those patients in the three quintiles most likely to receive CABG. The curves diverged early, with risk-adjusted mortality rates at 5 years of 46% for MED versus 29% for CABG, and the survival benefit of CABG over MED continued through 10 years follow-up (hazard ratio 0.63, 95% CI 0.45 – 0.88). Conclusions Among a propensity-matched, risk-adjusted observational cohort of patients with CAD, LVEF < 35%, and no left main disease ≥ 50%, CABG is associated with a survival advantage over MED through 10 years follow-up. PMID:22269720

  7. NCAM(CD56) and RUNX1(AML1) Are Up-Regulated in Human Ischemic Cardiomyopathy and a Rat Model of Chronic Cardiac Ischemia

    PubMed Central

    Gattenlöhner, Stefan; Waller, Christiane; Ertl, Georg; Bültmann, Burkhard-Dieter; Müller-Hermelink, Hans-Konrad; Marx, Alexander

    2003-01-01

    Chronic myocardial ischemia is the leading cause of impaired myocardial contractility and heart failure. To identify differentially expressed genes in human ischemic cardiomyopathy (ICM), we constructed a subtracted cDNA library using specimens of ICM compared to normal human heart. Among 100 randomly sequenced clones, seven sequences represented recently identified candidate genes for differential expression in cardiac hypertrophy. A further clone without a known hypertrophy-association coded for the adhesion molecule NCAM(CD56). RNase protection assay, immunohistochemistry, and Western blotting revealed strong overexpression of NCAM(CD56) in all hearts with ICM (n = 14) compared to normal hearts (n = 8), whereas in congestive cardiomyopathy (CCM) (n = 8), hypertrophic obstructive cardiomyopathy (n = 2), myocarditis (n = 4), and sarcoidosis (n = 2), at most slight overexpression of NCAM(CD56) was observed. NCAM(CD56) overexpression abnormally involved the whole cell membrane and the cytoplasma of cardiomyocytes only inside and adjacent to ischemia-induced cardiac scars. Normal or hypertrophic fibers at a distance from ischemic scars were devoid of NCAM overexpression. Identical alterations were observed in an experimental rat ICM model, but not in normal nor in spontaneously hypertensive rat hearts. In search of NCAM(CD56)-related transcription factors we found RUNX1(AML1) up-regulation in ICM and detected RUNX1(AML1) binding within the NCAM(CD56) promoter by electromobility shift assay. We concluded that strong overexpression of NCAM(CD56) and RUNX1(AML1) is a constant and characteristic feature of cardiomyocytes within or adjacent to scars in ICM. PMID:12937148

  8. Opposite patterns of left ventricular remodeling after coronary revascularization in patients with ischemic cardiomyopathy: role of myocardial viability.

    PubMed

    Rizzello, Vittoria; Poldermans, Don; Boersma, Eric; Biagini, Elena; Schinkel, Arend F L; Krenning, Boudewijn; Elhendy, Abdou; Vourvouri, Eleni C; Sozzi, Fabiola B; Maat, Alexander; Crea, Filippo; Roelandt, Jos R T C; Bax, Jeroen J

    2004-10-19

    In patients with ischemic cardiomyopathy, left ventricular (LV) remodeling is an important prognostic indicator. The precise relation between viable myocardium, revascularization, and ongoing or reversed remodeling is unknown and was evaluated in the present study. A total of 100 patients with ischemic cardiomyopathy underwent dobutamine stress echocardiography to assess myocardial viability and LV geometry (volumes and shape). At a mean of 10.2 months and 4.5 years after revascularization, resting echocardiography was repeated to evaluate LV remodeling. Long-term follow-up (mean 5+/-2 years) data were obtained. According to dobutamine stress echocardiography, 44 patients (44%) were defined as viable (> or =4 viable segments) and 56 as nonviable. After revascularization, 40 patients (43%) had ongoing LV remodeling and 53 (57%) did not (in 7 patients who died early after revascularization, postoperative echocardiographic evaluation was not available). On multivariable analysis, the number of viable segments was the only predictor of ongoing LV remodeling (OR 0.60, 95% CI 0.48 to 0.75; P<0.0001). The likelihood of LV remodeling decreased as the number of viable segments increased. During the follow-up, reverse remodeling was present in viable patients, whereas in nonviable patients, LV volumes significantly increased, which indicates ongoing LV remodeling. At follow-up, viable patients also showed a persistent improvement of heart failure symptoms and fewer cardiac events than nonviable patients (P<0.05). In patients with ischemic cardiomyopathy, a substantial amount of viable myocardium prevents ongoing LV remodeling after revascularization and is associated with persistent improvement of symptoms and better outcome.

  9. Effects of sustained-release trimetazidine on chronically dysfunctional myocardium of ischemic dilated cardiomyopathy - Six months follow-up result.

    PubMed

    Momen, A; Ali, M; Karmakar, P K; Ali, M Z; Haque, A; Khan, M R; Khalil, M I; Hossain, M S; Huda, R M; Goni, M N

    Ischemic cardiomyopathy is a growing burden in third world countries. So far, benefits of trimetazidine in this group of patients have been suggested by clinical trials mainly conducted in Europe. We evaluated the effect of trimetazidine on ischemic dilated cardiomyopathy in our population. 98 patients (aged 58.5±9.2 years), admitted with decompensated heart failure with previous history of MI and/or documentation of significant CAD with previous CAG, were chosen for the study. Patients were randomized into two groups - one provided with trimetazidine 35mg sustained released tablet, twice daily and the other with a placebo, along with other conventional medications. Patients were included if they had dilated LV (LVIDd>57mm) and left ventricular ejection fraction (LVEF) ≤40%. After 6 months, significantly higher number of patients in trimetazidine group were in NYHA class I (22% vs. 8%, p=0.03) and class II (56% vs. 34%, p=0.01); higher number of patients in placebo group were in NYHA class III class IV. Anginal episodes and use of sublingual nitrate per week were significantly lower in the trimetazidine group. Left ventricular diastolic dimension (59.7±5.2 vs. 65.1±6.1, p=0.001) was significantly different in the two groups as was the increase of LVEF (11% vs. 5.6%, p=0.001). Hospitalization for worsening heart failure was significantly lower in trimetazidine group (13 vs. 22, p=0.047). Trimetazidine seems to be beneficial in patients with ischemic dilated cardiomyopathy in South Asian population and larger scale study with extended follow-up is needed. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  10. Mechanisms of bone marrow-derived cell therapy in ischemic cardiomyopathy with left ventricular assist device bridge to transplant.

    PubMed

    Stempien-Otero, April; Helterline, Deri; Plummer, Tabitha; Farris, Stephen; Prouse, Andrew; Polissar, Nayak; Stanford, Derek; Mokadam, Nahush A

    2015-04-14

    Clinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation. The goal of this study was to test the hypothesis that bone marrow stem cells (CD34+) will improve histological measurements of vascularity, fibrosis, and inflammation in human subjects undergoing left ventricular assist device (LVAD) placement as a bridge to cardiac transplantation. Subjects with ischemic cardiomyopathy who were scheduled for placement of an LVAD as a bridge to transplantation underwent bone marrow aspiration the day before surgery; the bone marrow was processed into cell fractions (bone marrow mononuclear cells, CD34+, and CD34-). At LVAD implantation, all fractions and a saline control were injected epicardially into predetermined areas and each injection site marked. At the time of transplantation, injected areas were collected. Data were analyzed by paired Student t test comparing the effect of cell fractions injected within each subject. Six subjects completed the study. There were no statistically significant differences in complications with the procedure versus control subjects. Histological analysis indicated that myocardium injected with CD34+ cells had decreased density of endothelial cells compared to saline-injected myocardium. There were no significant differences in fibrosis or inflammation between groups; however, density of activated fibroblasts was decreased in both CD34+ and CD34- injected areas. Tissue analysis does not support the hypothesis that bone marrow-derived CD34+ cells promote increased vascular tissue in humans with ischemic cardiomyopathy via direct injection. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Cardiomyopathy induced by incessant fascicular ventricular tachycardia.

    PubMed

    Velázquez-Rodríguez, Enrique; Rodríguez-Piña, Horacio; Pacheco-Bouthillier, Alex; Deras-Mejía, Luz María

    2013-01-01

    A 12-year-old girl with symptoms of fatigue, decreased exercise tolerance and progressive dyspnea (New York Heart Association functional class III) with a possible diagnosis of dilated cardiomyopathy secondary to viral myocarditis. Because of incessant wide QRS tachycardia refractory to antiarrhythmic drugs, she was referred for electrophysiological study. The diagnosis was idiopathic left ventricular tachycardia involving the posterior fascicle of the left bundle branch. After successful treatment with radiofrequency catheter ablation guided by a Purkinje potential radiological and echocardiographic evaluation showed complete reversal of left ventricular function in the first 3 months and no recurrence of arrhythmia during 2 years of follow up.

  12. Delayed-Enhanced Magnetic Resonance Imaging in Non-Ischemic Cardiomyopathy

    PubMed Central

    Bogun, Frank; Desjardins, Benoit; Good, Eric; Gupta, Sanjaya; Crawford, Thomas; Oral, Hakan; Ebinger, Matthew; Pelosi, Frank; Chugh, Aman; Jongnarangsin, Krit; Morady, Fred

    2009-01-01

    Objective The purpose of this study was to assess the value of delayed-enhanced magnetic resonance imaging (DE-MRI) to guide ablation of ventricular arrhythmias in patients with non-ischemic cardiomyopathy (NIC). Background In patients with NIC, ventricular arrhythmias often are associated with scar tissue. DE-MRI can be used to precisely define scar tissue. Methods DE-MRI was performed in 29 consecutive patients (mean age 50±15 years) with NIC (mean ejection fraction 37±9%) referred for catheter ablation of ventricular tachycardia (VT) or premature ventricular complexes (PVCs). Scar was extracted from DE-MRIs and was then integrated into the electroanatomic map. Mapping data were correlated with respect to the localization of scar tissue. Results Scar was identified by DE-MRI in 14/29 patients. Nine of these patients had VT and five had PVCs. In 5 of the patients there was predominantly endocardial scar, and mapping and ablation of arrhythmias was effectively performed from the endocardium in all 5 patients. In 2 patients scar was either intramural or epicardial with extension to the endocardium. In both patients with partial endocardial scar extension, the ablation was effective in eliminating some but not all arrhythmias. In 2 patients most of the scar tissue was confined to the epicardium; mapping identified and eliminated an epicardial origin in both patients. No effect on arrhythmias could be achieved in the other 5 patients with predominantly intramural scar. Conclusions DE-MRI in patients without prior infarctions can help to identify the arrhythmogenic substrate; furthermore it helps to plan an appropriate mapping and ablation strategy. PMID:19324259

  13. Association between High Endocardial Unipolar Voltage and Improved Left Ventricular Function in Patients with Ischemic Cardiomyopathy

    PubMed Central

    Park, Ki; Lai, Dejian; Handberg, Eileen M.; Perin, Emerson C.; Pepine, Carl J.; Anderson, R. David

    2016-01-01

    We know that endocardial mapping reports left ventricular electrical activity (voltage) and that these data can predict outcomes in patients undergoing traditional revascularization. Because the mapping data from experimental models have also been linked with myocardial viability, we hypothesized an association between increased unipolar voltage in patients undergoing intramyocardial injections and their subsequent improvement in left ventricular performance. For this exploratory analysis, we evaluated 86 patients with left ventricular dysfunction, heart-failure symptoms, possible angina, and no revascularization options, who were undergoing endocardial mapping. Fifty-seven patients received bone marrow mononuclear cell (BMC) injections and 29 patients received cell-free injections of a placebo. The average mapping site voltage was 9.7 ± 2 mV, and sites with voltage of ≥6.9 mV were engaged by needle and injected (with BMC or placebo). For all patients, at 6 months, left ventricular ejection fraction (LVEF) improved, and after covariate adjustment this improvement was best predicted by injection-site voltage. For every 2-mV increase in baseline voltage, we detected a 1.3 increase in absolute LVEF units for all patients (P=0.038). Multiple linear regression analyses confirmed that voltage and the CD34+ count present in bone marrow (but not treatment assignment) were associated with improved LVEF (P=0.03 and P=0.014, respectively). In an exploratory analysis, higher endocardial voltage and bone marrow CD34+ levels were associated with improved left ventricular function among ischemic cardiomyopathy patients. Intramyocardial needle injections, possibly through stimulation of angiogenesis, might serve as a future therapy in patients with reduced left ventricular function and warrants investigation. PMID:27547135

  14. Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy.

    PubMed

    Dib, Nabil; McCarthy, Patrick; Campbell, Ann; Yeager, Michael; Pagani, Francis D; Wright, Susan; MacLellan, W Robb; Fonarow, Gregg; Eisen, Howard J; Michler, Robert E; Binkley, Philip; Buchele, Diane; Korn, Ronald; Ghazoul, Marwan; Dinsmore, Jonathan; Opie, Shaun R; Diethrich, Edward

    2005-01-01

    Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device implantation (LVAD). In addition, we sought to gain preliminary information on graft survival and any potential improvement of cardiac function. Eighteen patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twelve patients with a history of previous myocardial infarction (MI) and a left ventricular ejection of less than 30% were enrolled in the CABG arm. In a second arm, six patients underwent LVAD implantation as a bridge to heart transplantation and were required to donate their heart for testing at the time of heart transplant. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term unexpected adverse events. Follow-up PET scans showed new areas of viability within the infarct scar in CABG patients. Echocardiography measured an average improvement in left ventricular ejection fraction (LVEF) from 25% to 34%. Histological evaluation in four out of five patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. These interim results demonstrate survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality may offer a potential therapeutic treatment for end-stage heart disease.

  15. Effects of the intramyocardial implantation of stromal vascular fraction in patients with chronic ischemic cardiomyopathy.

    PubMed

    Comella, K; Parcero, J; Bansal, H; Perez, J; Lopez, J; Agrawal, A; Ichim, T

    2016-06-02

    Stromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. We evaluated the safety and efficacy of administering SVF intra-myocardially into patients with chronic ischemic cardiomyopathy. A total of 28 patients underwent a local tumescent liposuction procedure to remove approximately 60 ml of fat tissue. The fat was separated to isolate the SVF and the cells were delivered into the akinetic myocardial scar region using a transendocardial delivery system (MyoCath(®)) in patients who had experienced a previous myocardial infarct. The subjects were then monitored for adverse events, ejection fraction via echocardiogram and six-minute walk test (6MWT) over a period of 6 months. The average EF was 29 % at baseline and significantly increased to 35 % at both 3 and 6 months. Patients walked an average of 349 m at baseline and demonstrated a statistically significant improvement at 3 and 6 months' post treatment of more than 80 m. Overall, patients were pleased with the treatment results. More importantly, the procedure demonstrated a strong safety profile with no severe adverse events or complications linked to the therapy. Trial registration NCT01502514 Name of registry: http://www.clinicaltrials.gov URL: https://www.clinicaltrials.gov/ct2/show/NCT01502514?term=adipose+cells+heart&rank=4 Date of registration: December 27, 2011 Date of enrollment: January 2012.

  16. Cardiomyopathy in neurological disorders.

    PubMed

    Finsterer, Josef; Stöllberger, Claudia; Wahbi, Karim

    2013-01-01

    According to the American Heart Association, cardiomyopathies are classified as primary (solely or predominantly confined to heart muscle), secondary (those showing pathological myocardial involvement as part of a neuromuscular disorder) and those in which cardiomyopathy is the first/predominant manifestation of a neuromuscular disorder. Cardiomyopathies may be further classified as hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or unclassified cardiomyopathy (noncompaction, Takotsubo-cardiomyopathy). This review focuses on secondary cardiomyopathies and those in which cardiomyopathy is the predominant manifestation of a myopathy. Any of them may cause neurological disease, and any of them may be a manifestation of a neurological disorder. Neurological disease most frequently caused by cardiomyopathies is ischemic stroke, followed by transitory ischemic attack, syncope, or vertigo. Neurological disease, which most frequently manifests with cardiomyopathies are the neuromuscular disorders. Most commonly associated with cardiomyopathies are muscular dystrophies, myofibrillar myopathies, congenital myopathies and metabolic myopathies. Management of neurological disease caused by cardiomyopathies is not at variance from the same neurological disorders due to other causes. Management of secondary cardiomyopathies is not different from that of cardiomyopathies due to other causes either. Patients with neuromuscular disorders require early cardiologic investigations and close follow-ups, patients with cardiomyopathies require neurological investigation and avoidance of muscle toxic medication if a neuromuscular disorder is diagnosed. Which patients with cardiomyopathy profit most from primary stroke prevention is unsolved and requires further investigations. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Role of neuropeptides in cardiomyopathies.

    PubMed

    Dvorakova, Magdalena Chottova; Kruzliak, Peter; Rabkin, Simon W

    2014-11-01

    The role of neuropeptides in cardiomyopathy-associated heart failure has been garnering more attention. Several neuropeptides--Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP) and their receptors have been studied in the various types of cardiomyopathies. The data indicate associations with the strength of the association varying depending on the kind of neuropeptide and the nature of the cardiomyopathy--diabetic, ischemic, inflammatory, stress-induced or restrictive cardiomyopathy. Several neuropeptides appear to alter regulation of genes involved in heart failure. Demonstration of an association is an essential first step in proving causality or establishing a role for a factor in a disease. Understanding the complexity of neuropeptide function should be helpful in establishing new or optimal therapeutic strategies for the treatment of heart failure in cardiomyopathies. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Determinants of Atrial Electromechanical Delay in Patients with Functional Mitral Regurgitation and Non-ischemic Dilated Cardiomyopathy.

    PubMed

    Bengi Bakal, Ruken; Hatipoglu, Suzan; Sahin, Muslum; Emiroglu, Mehmet Yunus; Bulut, Mustafa; Ozdemir, Nihal

    2014-01-01

    Atrial conduction time has important hemodynamic effects on ventricular filling and is accepted as a predictor of atrial fibrillation. In this study we assessed atrial conduction time in patients with non ischemic dilated cardiomyopathy (NIDCMP) and functional mitral regurgitation (MR) and aimed to determine factors predicting atrial conduction time prolongation. Sixty five patients with non ischemic dilated cardiomyopathy who have moderate to severe MR and 60 control subjects were included in the study. In addition to conventional echocardiographic measures used to asses left ventricle and MR, atrial electromechanical coupling (time interval from the onset of P wave on surface electrocardiogram [ECG] to the beginning of A wave interval with tissue Doppler echocardiography [PA]), intra- and interatrial electromechanical delay (intra and inter AEMD) were measured. The correlations between inter AEMD and left atrial (LA) size, MR volume, isovolumetric relaxation time (IVRT), deceleration time (DT), systolic pulmonary artery pressure (PAPs), E/A ratio and E/e' were very poor. Similarly, intra AEMD was not correlated to LA size , MR volume, IVRT, DT, PAPs, E/A ratio and E/e'. However, both inter AEMD and intra AEMD had good correlation with left ventricular mass index, tenting area (TA), tenting distance (TD), coaptation septal distance (CSD), sphericity index (SI). Prolongation of inter and intra AEMDs were found to be well correlated with parameters reflecting left ventricular and mitral annular remodeling.

  19. Macrophage Migration Inhibitory Factor Deficiency Augments Doxorubicin‐Induced Cardiomyopathy

    PubMed Central

    Xu, Xihui; Bucala, Richard; Ren, Jun

    2013-01-01

    Background Recent evidence has depicted a role of macrophage migration inhibitory factor (MIF) in cardiac homeostasis under pathological conditions. This study was designed to evaluate the role of MIF in doxorubicin‐induced cardiomyopathy and the underlying mechanism involved with a focus on autophagy. Methods and Results Wild‐type (WT) and MIF knockout (MIF−/−) mice were given saline or doxorubicin (20 mg/kg cumulative, i.p.). A cohort of WT and MIF−/− mice was given rapamycin (6 mg/kg, i.p.) with or without bafilomycin A1 (BafA1, 3 μmol/kg per day, i.p.) for 1 week prior to doxorubicin challenge. To consolidate a role for MIF in the maintenance of cardiac homeostasis following doxorubicin challenge, recombinant mouse MIF (rmMIF) was given to MIF−/− mice challenged with or without doxorubicin. Echocardiographic, cardiomyocyte function, and intracellular Ca2+ handling were evaluated. Autophagy and apoptosis were examined. Mitochondrial morphology and function were examined using transmission electron microscopy, JC‐1 staining, MitoSOX Red fluorescence, and mitochondrial respiration complex assay. DHE staining was used to evaluate reactive oxygen species (ROS) generation. MIF knockout exacerbated doxorubicin‐induced mortality and cardiomyopathy (compromised fractional shortening, cardiomyocyte and mitochondrial function, apoptosis, and ROS generation). These detrimental effects of doxorubicin were accompanied by defective autophagolysosome formation, the effect of which was exacerbated by MIF knockout. Rapamycin pretreatment rescued doxorubicin‐induced cardiomyopathy in WT and MIF−/− mice. Blocking autophagolysosome formation using BafA1 negated the cardioprotective effect of rapamycin and rmMIF. Conclusions Our data suggest that MIF serves as an indispensable cardioprotective factor against doxorubicin‐induced cardiomyopathy with an underlying mechanism through facilitating autophagolysosome formation. PMID:24334905

  20. Assessment of asynchronous relaxation in hypertrophic cardiomyopathy and ischemic heart disease

    SciTech Connect

    Kodama, S.; Tamaki, N.; Senda, M.; Yonekura, Y.; Suzuki, Y.; Nohara, R.; Tamaki, S.; Kambara, H.; Kawai, C.; Torizuka, K.

    1984-01-01

    This study is undertaken to assess cardiac performance in relation to left ventricular(LV) asynchronous wall motion. Multigated blood-pool study was performed in 67 cases, including 14 normals(N), 16 with hypertrophic cardiomyopathy(HCM), and 37 with ischemic heart disease (IHD). IHD was further divided into 2 groups: IHD(I)(EF greater than or equal to 50%), and IHD(II)(EF < 50%). Regional (pixel-by-pixel) volume curve was simulated by second order harmonics of Fourier series. Then, functional images of the following indexes were made: EF, TES(time to end-systole), PER(Peak ejection rate), TPE(Time to PER), PFR(peak filling rate), and TPF(time to PFR). The left ventricular phase distribution histograms of TES, TPE, and TPF were made to calculate the standard deviation(SD) as an asynchronous parameter of each phase. TES(SD) was higher in IHD(II)(11.3 +- 5.2 deg) than N(4.8 +- 2.5 deg). TPF(SD) was higher in HCM(11.7 +- 9.7 deg) and IHD(15.1 +- 11.3 deg) than N(5.3 +- 3.7 deg), suggesting asynchronous relaxation. In the study of global LV performance, LVEF was not significantly different in HCM(64 +- 9%) and IHD(I)(58 +- 5%) from N(60 +- 6%). However, PFR was lower in IHD(I)(2.3 +- 0.6 EDV/sec) and IHD(II) (1.6 +- 0.5 EDV/sec) than N(3.3 + 1.0 EDV/sec). PFR/PER was lower in HCM(0.7 +- 0.2), IHD(I)(0.8 +- 0.2), and IHD(II)(0.7 +- 0.3) than N(1.0 +- 0.2). Besides, TPF(SD) was inversely correlated with LVEF(r=-0.43), PFR (r=-0.45), and PFR/PER(r=-0.51). Thus, asynchronous relaxation is often seen in HCM and IHD, and it may be related to the disturbance of LV filling.

  1. Effect of levosimendan on ventriculo-arterial coupling in patients with ischemic cardiomyopathy.

    PubMed

    Guarracino, F; Cariello, C; Danella, A; Doroni, L; Lapolla, F; Stefani, M; Baldassarri, R; Vullo, C

    2007-10-01

    Levosimendan, a novel calcium sensitizer, enhances myocardial contractility without affecting intracellular calcium concentration. It also dilates peripheral arterial vessels by acting on ATP-dependent K(+) channels. Ventriculo-arterial coupling, the relationship between myocardial contractility and the arterial system, describes the efficiency of the cardiovascular system by analysing the relationship between myocardial contractility expressed by ventricular elastance (E(es)) and arterial elastance (E(a)). The aim of this prospective clinical investigation was to evaluate the effects of levosimendan on ventriculo-arterial coupling in patients with ischemic cardiomyopathy. Fifteen patients with stable angina and left ventricular dysfunction underwent elective coronary surgery. Before surgery started, ventriculo-arterial coupling and several variables of cardiovascular performance were assessed by invasive monitoring and transoesophageal echocardiography before and after administration of levosimendan (12 mug/kg bolus) in coronary patients under general anesthesia. The cardiac index and ejection fraction increased significantly [from 1.92 +/- 0.4 to 2.1 +/- 0.4 l/min/m(2) (P = 0.0004) and from 31% +/- 6 to 40% +/- 9 (P = 0.001), respectively], while mean arterial pressure and systemic vascular resistances decreased significantly [from 83 +/- 10 to 72 +/- 5 mmHg (P = 0.0016) and from 997 +/- 341 to 855 +/- 324 dyne s/cm(5) (P = 0.0002), respectively]. After administration of levosimendan, E(a) decreased significantly (from 4.3 +/- 1.8 to 3.2 +/- 1.3 mmHg/ml/m(2), P= 0.005), while E(es) significantly increased (from 2.8 +/- 1.6 to 4.4 +/- 2.3 mmHg/ml/m(2), P= 0.05); as a result, E(a)/E(es) decreased significantly (from 1.76 +/- 1 to 0.83 +/- 0.2, P= 0.002). Levosimendan improves ventriculo-arterial coupling and cardiovascular performance in coronary patients with left ventricular dysfunction by enhancing myocardial contractility and reducing arterial elastance.

  2. Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment.

    PubMed

    Yogasundaram, Haran; Putko, Brendan N; Tien, Julia; Paterson, D Ian; Cujec, Bibiana; Ringrose, Jennifer; Oudit, Gavin Y

    2014-12-01

    Drug-induced heart and vascular disease remains an important health burden. Hydroxychloroquine and its predecessor chloroquine are medications commonly used in the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disorders. Hydroxychloroquine interferes with malarial metabolites, confers immunomodulatory effects, and also affects lysosomal function. Clinical monitoring and early recognition of toxicity is an important management strategy in patients who undergo long-term treatment with hydroxychloroquine. Retinal toxicity, neuromyopathy, and cardiac disease are recognized adverse effects of hydroxychloroquine. Immediate withdrawal of hydroxychloroquine is essential if toxicity is suspected because of the early reversibility of cardiomyopathy. In addition to recommended ophthalmological screening, regular screening with 12-lead electrocardiogram and transthoracic echocardiography to detect conduction system disease and/or biventricular morphological or functional changes should be considered in hydroxychloroquine-treated patients. Cardiac magnetic resonance imaging and endomyocardial biopsy are valuable tools to provide prognostic insights and confirm the diagnosis of hydroxychloroquine-induced cardiomyopathy. In conclusion, chronic use of hydroxychloroquine can result in an acquired lysosomal storage disorder, leading to a drug-induced cardiomyopathy characterized by concentric hypertrophy and conduction abnormalities associated with increased adverse clinical outcomes and mortality.

  3. Neurogenic cardiomyopathy in rabbits with experimentally induced rabies.

    PubMed

    Kesdangsakonwut, S; Sunden, Y; Yamada, K; Nishizono, A; Sawa, H; Umemura, T

    2015-05-01

    Cardiomyopathies have been rarely described in rabbits. Here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. Myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. Neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. The myocardial lesions were characterized by degeneration and/or necrosis of myocardial cells and were accompanied by contraction band necrosis, interstitial fibrosis, and infiltration of inflammatory cells. The brain lesions due to rabies virus infection were most prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla. Rabies virus antigen was not found in the hearts of any rabbits. Based on these findings, the myocardial lesions were classified as neurogenic cardiomyopathy.

  4. Stress-induced cardiomyopathy (Takotsubo) – broken heart and mind?

    PubMed Central

    Redfors, Björn; Shao, Yangzhen; Omerovic, Elmir

    2013-01-01

    Stress-induced cardiomyopathy (SIC), also known as Takotsubo cardiomyopathy, is characterized by severe but potentially reversible regional left ventricular wall motion abnormalities, ie, akinesia, in the absence of explanatory angiographic evidence of a coronary occlusion. The typical pattern is that of an akinetic apex with preserved contractions in the base, but other variants are also common, including basal or midmyocardial akinesia with preserved apical function. The pathophysiology of SIC remains largely unknown but catecholamines are believed to play a pivotal role. The diverse array of triggering events that have been linked to SIC are arbitrarily categorized as either emotional or somatic stressors. These categories can be considered as different elements of a continuous spectrum, linked through the interface of neurology and psychiatry. This paper reviews our current knowledge of SIC, with focus on the intimate relationship between the brain and the heart. PMID:23626469

  5. Stress-induced cardiomyopathy (Takotsubo)--broken heart and mind?

    PubMed

    Redfors, Björn; Shao, Yangzhen; Omerovic, Elmir

    2013-01-01

    Stress-induced cardiomyopathy (SIC), also known as Takotsubo cardiomyopathy, is characterized by severe but potentially reversible regional left ventricular wall motion abnormalities, ie, akinesia, in the absence of explanatory angiographic evidence of a coronary occlusion. The typical pattern is that of an akinetic apex with preserved contractions in the base, but other variants are also common, including basal or midmyocardial akinesia with preserved apical function. The pathophysiology of SIC remains largely unknown but catecholamines are believed to play a pivotal role. The diverse array of triggering events that have been linked to SIC are arbitrarily categorized as either emotional or somatic stressors. These categories can be considered as different elements of a continuous spectrum, linked through the interface of neurology and psychiatry. This paper reviews our current knowledge of SIC, with focus on the intimate relationship between the brain and the heart.

  6. The Effect of Cardiac Rehabilitation Exercise Training on Cardiopulmonary Function in Ischemic Cardiomyopathy With Reduced Left Ventricular Ejection Fraction

    PubMed Central

    2016-01-01

    Objective To observe the effect and safety of cardiac rehabilitation (CR) exercise in ischemic cardiomyopathy and to compare the results between patients with preserved left ventricular ejection fraction (LVEF) and reduced LVEF. Methods Patients with ischemic cardiomyopathy with LVEF <50% were included as subjects. The patients were classified into the preserved LVEF (pLVEF; LVEF 41%–49%) group and the reduced LVEF (rLVEF; LVEF ≤40%) group. Patients underwent hourly aerobic exercise training sessions with an intensity of 60%–85% of heart rate reserve, three times a week for 6 weeks. Graded exercise test and transthoracic echocardiogram were performed in all study patients before and after completion of the CR exercise program. Results After completion of the CR exercise program, both groups (pLVEF, n=30; rLVEF, n=18) showed significant increases in LVEF and VO2max. In the pLVEF group, LVEF and VO2max increased from 45.1%±4.8% to 52.5%±9.6% (p<0.001) and from 24.1±6.3 to 28.1±8.8 mL/kg/min (p=0.002), respectively. In the rLVEF group, LVEF and VO2max increased from 29.7%±7.7% to 37.6%±10.3% (p<0.001) and from 17.6±4.7 to 21.2±5.1 mL/kg/min (p<0.001), respectively. Both groups completed their exercise program safely. Conclusion In both groups, patients with ischemic cardiomyopathy who completed a 6-week supervised CR exercise program demonstrated remarkable improvements in cardiopulmonary function. This result implies that neither of the two groups showed higher efficacy in comparison to each other, but we can conclude that CR exercise in the rLVEF group was as effective and safe as that in the pLVEF group. PMID:27606271

  7. LV Dyssynchrony Is Helpful in Predicting Ventricular Arrhythmia in Ischemic Cardiomyopathy After Cardiac Resynchronization Therapy: A Preliminary Study.

    PubMed

    Tsai, Shih-Chuan; Chang, Yu-Cheng; Chiang, Kuo-Feng; Lin, Wan-Yu; Huang, Jin-Long; Hung, Guang-Uei; Kao, Chia-Hung; Chen, Ji

    2016-02-01

    For patients with coronary artery disease, larger scar burdens are associated with higher risk of ventricular arrhythmia. Left ventricular (LV) dyssynchrony is associated with increased risk of sudden cardiac death in patients with heart failure. The purpose of this study was to assess the values of LV dyssynchrony and myocardial scar assessed by myocardial perfusion SPECT (MPS) in predicting the development of ventricular arrhythmia in ischemic cardiomyopathy. Twenty-two patients (16 males, mean age: 66 ± 13) with irreversible ischemic cardiomyopathy received cardiac resynchronization therapy (CRT) for at least 12 months were enrolled for MPS. Quantitative parameters, including LV dyssynchrony with phase standard deviation (phase SD) and bandwidth, left ventricular ejection fraction (LVEF), and scar (% of total areas), were generated by Emory Cardiac Toolbox. Ventricular tachycardia (VT) and ventricular fibrillation (VF) recorded in the CRT device during follow-up were used as the reference standard of diagnosing ventricular arrhythmia. Stepwise logistic regression analysis was performed for determining the independent predictors of VT/VF and receiver operating characteristic (ROC) curve analysis was used for generating the optimal cut-off values for predicting VT/VF. Nine (41%) of the 22 patients developed VT/VF during the follow-up periods. Patients with VT/VF had significantly lower LVEF, larger scar, larger phase SD, and larger bandwidth (all P < 0.05). Logistic regression analysis showed LVEF and bandwidth were independent predictors of VT/VF. ROC curve analysis showed the areas under the curves were 0.71 and 0.83 for LVEF and bandwidth, respectively. The optimal cut-off values were <36% and > 139° for LVEF and bandwidth, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 39%, 53%, and 100%, respectively, for LVEF; and were 78%, 92%, 88%, and 86%, respectively, for bandwidth. LV

  8. Effect of escitalopram on cardiomyopathy-induced anxiety in mice.

    PubMed

    Anwar, M J; Pillai, K K; Samad, A; Vohora, D

    2013-06-01

    The present study was aimed to evaluate the effect of escitalopram on anxiety following doxorubicin (DOX)-induced cardiomyopathy, a rodent model for heart failure (HF), in mice. The study was carried out in Swiss albino mice. DOX was used at a dose of 10 mg/kg intravenously. Escitalopram was administered at the doses of 10 and 20 mg/kg orally for 7 days pre- and 7 days post-DOX. Anxiety was measured on day 8 and on day 14 using elevated plus maze and Vogel's conflict test. On day 14, serum lactate dehydrogenase (LDH) was estimated. The mice were then killed and their hearts were dissected out for the estimation of malondialdehyde (MDA) and for the transmission electron microscopic (TEM) studies. Our results showed that the DOX administration induced cardiomyopathy in mice. This was evidenced by the increased levels of serum LDH and tissue MDA and was also confirmed by TEM. Escitalopram (20 mg/kg) not only reversed the anxiety-like effects induced by DOX but also DOX-induced increase in LDH and MDA as well as the morphological alterations induced by DOX in TEM studies. Escitalopram, thus, appears to be a good candidate for alleviating anxiety in patients with HF.

  9. Mechanisms of Functional Mitral Regurgitation in Ischemic Cardiomyopathy Determined by Transesophageal Echocardiography (From the Surgical Treatment for Ischemic Heart Failure [STICH] Trial)

    PubMed Central

    Golba, Krzysztof; Mokrzycki, Krzysztof; Drozdz, Jaroslaw; Cherniavsky, Alexander; Wrobel, Krzysztof; Roberts, Bradley J.; Haddad, Haissam; Maurer, Gerald; Yii, Michael; Asch, Federico M.; Handschumacher, Mark D.; Holly, Thomas A.; Przybylski, Roman; Kron, Irving; Schaff, Hartzell; Aston, Susan; Horton, John; Lee, Kerry L.; Velazquez, Eric J.; Grayburn, Paul A.

    2013-01-01

    The mechanisms underlying functional mitral regurgitation (MR), and the relation between mechanism and severity of MR have not been evaluated in a large multicenter randomized controlled trial. Transesophageal echocardiography (TEE) was performed in 215 patients at 17 centers in the Surgical Treatment of Ischemic Heart Failure (STICH) trial. Both two-dimensional (2D, n=215) and three-dimensional (3D, n=81) TEE were used to assess multiple quantitative measures of the mechanism and severity of MR. By 2D TEE, leaflet tenting area, anterior and posterior leaflet angles, mitral annulus diameter, left ventricular (LV) end-systolic volume index, LV ejection fraction (LVEF), and sphericity index (p<0.05 for all) were significantly different across MR grades. By 3D TEE, mitral annulus area, leaflet tenting area, LV end-systolic volume index, LVEF, and sphericity index (p<0.05 for all) were significantly different across MR grades. A multivariable analysis showed a trend for annulus area (p=0.069) and LV end-systolic volume index (p=0.071) to predict effective regurgitant orifice area (EROA) and for annulus area (p=0.018) and LV end-systolic volume index (p=0.073) to predict vena contracta area. In the STICH trial, multiple quantitative parameters of the mechanism of functional MR are related to MR severity. The mechanism of functional MR in ischemic cardiomyopathy is heterogeneous but no single variable stands out as a strong predictor of quantitative severity of MR. PMID:24035166

  10. 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

  11. Aberrant Epicardial Adipose Tissue Extracellular Matrix Remodeling in Patients with Severe Ischemic Cardiomyopathy: Insight from Comparative Quantitative Proteomics

    PubMed Central

    Jiang, Ding-Sheng; Zeng, Hao-Long; Li, Rui; Huo, Bo; Su, Yun-Shu; Fang, Jing; Yang, Qing; Liu, Li-Gang; Hu, Min; Cheng, Cai; Zhu, Xue-Hai; Yi, Xin; Wei, Xiang

    2017-01-01

    There is ample evidence indicating that epicardial adipose tissue (EAT) volume and thickness is positively associated with coronary artery disease (CAD). However, the exact pathological changes in the human EAT after myocardial ischemia remains largely unclear. In the current study, we applied a comparative quantitative proteomics to elucidate the altered biological processes in the EAT of ischemic cardiomyopathy (ICM) patients. A total of 1649 proteins were successfully quantified in our study, among which 165 proteins were significantly changed (ratio <0.8 or >1.2 fold and p < 0.05 in both repetitions) in EAT of ICM individuals. Gene ontology (GO) enrichment analysis revealed that cardiac structure and cellular metabolism were over-represented among these regulated proteins. The hypertrophic cardiomyopathy, adrenergic signaling in cardiomyocytes, extracellular matrix (ECM)-receptor interaction, phagosome, Glycolysis/Gluconeogenesis, and PPAR signaling pathway were highlighted by the KEGG PATHWAY analysis. More importantly, we found that the proteins responsible for extracellular matrix organization were dramatically increased in EAT of ICM patients. In addition, the picrosirius red (PSR) staining results showed that the collagen fiber content was prominently increased, which indicated the EAT of ICM individuals underwent extracellular matrix remodeling and ERK1/2 activation maybe responsible for these pathological changes partially. PMID:28256566

  12. The evaluation of non-ischemic dilated cardiomyopathy with T1 mapping and ECV methods using 3T cardiac MRI.

    PubMed

    Görmeli, Cemile Ayşe; Özdemir, Zeynep Maraş; Kahraman, Ayşegül Sağır; Yağmur, Jülide; Özdemir, Ramazan; Çolak, Cemil

    2017-02-01

    The aim of this study was to examine the correlation between ventricular function and the extracellular volume fraction (ECV) in patients with non-ischemic dilated cardiomyopathy (NIDCM) using 3.0 T magnetic resonance imaging (MRI). We also hypothesized that native T1 and ECV values would be increased in patients with NIDCM, independent of the left ventricular ejection fraction (LVEF). The findings of our study could lead to further studies of the follow-up protocols. In total, 53 consecutive dilated cardiomyopathy patients who had undergone cardiac MRI were functionally evaluated and underwent tissue characterization. The mean native T1 value was 1235 ± 10 ms, and the mean ECV value was 35.4 ± 2.7% in the myocardia. The LVEF values ranged from 29 to 44%. No significant correlations were observed between functional analysis measurements and native T1 or ECV values. Our results showed that myocardial fibrosis is unrelated to cardiac functional findings in NIDCM patients. Therefore, we propose that these patients should be evaluated using MRI and tissue characterization techniques, in addition to cardiac functional analysis.

  13. Incidence and predictors of appropriate therapies delivered by the implantable cardioverter defibrillator in patients with ischemic cardiomyopathy: a systematic review.

    PubMed

    Gracieux, Junève; Sanders, Gillian D; Pokorney, Sean D; Lopes, Renato D; Thomas, Kevin; Al-Khatib, Sana M

    2014-12-20

    Although the implantable cardioverter defibrillator (ICD) improves the survival of patients at increased risk of sudden cardiac death due to systolic heart failure, ICD shocks have been associated with both worse survival and quality of life. We performed a systematic review of primary prevention ICD studies to evaluate the incidence and clinical predictors of appropriate ICD shocks or anti-tachycardia pacing (ATP) in patients with ischemic cardiomyopathy. We performed a literature search in MEDLINE. Eligible studies had to be full text, written in the English language, performed in adults aged ≥ 19, and published from 1999 through April 2014. Of 289 identified studies, 9 met all our inclusion criteria. The mean length of follow up ranged from 17 to 45.5 months. The incidence of appropriate ICD therapy varied from 17% to 31%. Among those studies, only 4 included data on the clinical characteristics of appropriate ICD therapy recipients. Characteristics associated with appropriate ICD therapy included male sex, advanced New York Heart Association class, non-sustained ventricular tachycardia, and lower serum creatinine. Patients who received appropriate therapy were also less likely to be on a beta-blocker. Left ventricular ejection fraction was not significantly different between patients who received appropriate ICD therapy and those who did not. The incidence of appropriate ICD therapy is not trivial in patients with ischemic cardiomyopathy and a primary prevention ICD. Predictors of appropriate ICD therapy have not been adequately assessed in large patient populations. As such, large prospective studies of predictors of appropriate ICD therapies are needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Low-dose dobutamine gated-SPECT analysis of left ventricular segmental wall thickening in ischemic cardiomyopathy.

    PubMed

    Candell-Riera, Jaume; Romero-Farina, Guillermo; Milá, Marta; Aguadé-Bruix, Santiago

    2008-10-01

    The objective of this study was to use low-dose dobutamine (LDD) gated single-photon emission computed tomography (SPECT) to evaluate segmental thickening of the left ventricle (LV) and its relationship with changes in ejection fraction (EF) and ventricular volumes in patients with ischemic cardiomyopathy. This prospective multicenter study involved 89 patients with ischemic cardiomyopathy (i.e., EF < or =40%) who underwent LDD gated-SPECT at rest. The LV was divided into 17 segments and systolic thickening was assessed in a total of 1513 segments during LDD infusion. RESULTS; A significant increase in LVEF (33.2% vs. 30.8%; P< .001) was observed during LDD infusion and occurred at the expense of a reduction in end-systolic volume (130.5 mL vs. 136.4 mL; P=.005). The increase in EF was > or =5% in 33.7% of patients, while the EF decreased by > or =5% in 5.6% of patients. With LDD infusion, both an improvement in > or =3 segments with severely decreased baseline thickening (odds ratio [OR] = 18.3; 95% confidence interval [CI], 5.3-63) and an improvement in > or =10 segments with mild-to-moderate alterations in baseline thickening (OR = 4.53; 95% CI, 1.26-16.16) were associated with a > or =5% increase in LVEF. During the assessment of global left ventricular contractile reserve by LDD gated-SPECT, attention should be paid not only to the behavior of segments with severely decreased baseline thickening, which are generally regarded as indicating viability, but also to segments with mild-to-moderate alterations and to those in which thickening decreases.

  15. High Dose β-Blocker Therapy Triggers Additional Reverse Remodeling in Patients With Idiopathic Non-Ischemic Cardiomyopathy.

    PubMed

    Nitta, Daisuke; Kinugawa, Koichiro; Imamura, Teruhiko; Kato, Naoko P; Komuro, Issei

    2016-12-02

    Carvedilol has established its evidence to improve prognosis and facilitate left ventricular reverse remodeling (LVRR) in heart failure patients with reduced left ventricular ejection fraction (LVEF), and many studies have supported its dose-dependency. However, there are few studies demonstrating the effect of high dose carvedilol in Japan. We enrolled 23 patients with idiopathic non-ischemic cardiomyopathy, in whom LVEF remained 45% or less despite 20 mg/ day of carvedilol therapy for > 3 months. After high dose (40 mg/day) carvedilol therapy for > 3 months, LVEF improved (+9.1%, P = 0.002), and LV end-diastolic diameter (LVDd) and LV end-systolic diameter (LVDs) reduced (-4.6 and -6.9 mm, respectively, P < 0.05) compared with the baseline data. Finally, 17 patients achieved LVRR after the high dose, when LVRR was defined as 1) those with final EF > 45%, and 2) those with final EF < 45% but who attained increases in LVEF > 10%, or LVEF > 5% with a decrease in LV end-diastolic dimension index (LVDDI) > 5%. Baseline predictors for LVRR after high dose carvedilol were the change rates of log B-type natriuretic peptide (BNP), LVDd, and LVDs from the time of pre-carvedilol introduction to enrollment (P < 0.05, respectively). In conclusion, high dose carvedilol triggered additional LVRR in patients with idiopathic non-ischemic cardiomyopathy and the change rates of log BNP, LVDd, and LVDs at 20 mg carvedilol may be predictors for the additional LVRR at high dose.

  16. FOLFOX Induced Takotsubo Cardiomyopathy Treated with Impella Assist Device

    PubMed Central

    Alrifai, Abdulah; Kabach, Mohamad; Ghumman, Waqas

    2017-01-01

    Chemotherapy induced cardiotoxicity is becoming increasingly prevalent with several new agents being used recently. The incidence of Takotsubo cardiomyopathy due to 5-fluorouracil based chemotherapeutic regimens like FOLFOX is not uncommon. It is also seen with platinum based chemotherapy. Most of these patients have reversible cardiotoxicity and the cardiac function recovers within a short period with supportive treatment. Here we have a patient who presented with cardiogenic shock after 5 days of receiving FOLFOX regimen for colorectal adenocarcinoma. She was treated with a percutaneous left ventricular assist device, Impella CP, for hemodynamic support with excellent outcome. PMID:28367338

  17. Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine* **

    PubMed Central

    Ferreira, Pedro Gonçalo; Costa, Susana; Dias, Nuno; Ferreira, António Jorge; Franco, Fátima

    2014-01-01

    Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used as an antidepressant. Interindividual variability and herb-drug interactions can lead to drug-induced toxicity. We report the case of a 35-year-old female patient diagnosed with synchronous pneumonitis and acute cardiomyopathy attributed to venlafaxine. The patient sought medical attention due to dyspnea and dry cough that started three months after initiating treatment with venlafaxine for depression. The patient was concomitantly taking Centella asiatica and Fucus vesiculosus as phytotherapeutic agents. Chest CT angiography and chest X-ray revealed parenchymal lung disease (diffuse micronodules and focal ground-glass opacities) and simultaneous dilated cardiomyopathy. Ecocardiography revealed a left ventricular ejection fraction (LVEF) of 21%. A thorough investigation was carried out, including BAL, imaging studies, autoimmune testing, right heart catheterization, and myocardial biopsy. After excluding other etiologies and applying the Naranjo Adverse Drug Reaction Probability Scale, a diagnosis of synchronous pneumonitis/cardiomyopathy associated with venlafaxine was assumed. The herbal supplements taken by the patient have a known potential to inhibit cytochrome P450 enzyme complex, which is responsible for the metabolization of venlafaxine. After venlafaxine discontinuation, there was rapid improvement, with regression of the radiological abnormalities and normalization of the LVEF. This was an important case of drug-induced cardiopulmonary toxicity. The circumstantial intake of inhibitors of the CYP2D6 isoenzyme and the presence of a CYP2D6 slow metabolism phenotype might have resulted in the toxic accumulation of venlafaxine and the subsequent clinical manifestations. Here, we also discuss why macrophage-dominant phospholipidosis was the most likely mechanism of toxicity in this case. PMID:25029655

  18. Role of Interleukin-1 in Radiation-Induced Cardiomyopathy

    PubMed Central

    Mezzaroma, Eleonora; Mikkelsen, Ross B; Toldo, Stefano; Mauro, Adolfo G; Sharma, Khushboo; Marchetti, Carlo; Alam, Asim; Van Tassell, Benjamin W; Gewirtz, David A; Abbate, Antonio

    2015-01-01

    Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in the mouse. Female mice with genetic deletion of the IL-1 receptor type I (IL-1R1 knockout mice [IL-1R1 KO]) and treatment with recombinant human IL-1 receptor antagonist anakinra, 10 mg/kg twice daily for 7 d, were used as independent approaches to determine the role of IL-1. Wild-type (wt) or IL-1R1 KO mice were treated with a single session of XRT (20 or 14 gray [Gy]). Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson’s trichrome was used to assess myocardial fibrosis and pericardial thickening. After 20 Gy, the contractile reserve was impaired in wt mice at d 3, and the LV ejection fraction (EF) was reduced after 4 months when compared with sham-XRT. IL-1R1 KO mice had preserved contractile reserve at 3 d and 4 months and LVEF at 4 months after XRT. Anakinra treatment for 1 d before and 7 d after XRT prevented the impairment in contractile reserve. A significant increase in LV end-diastolic pressure, associated with increased myocardial interstitial fibrosis and pericardial thickening, was observed in wt mice, as well as in IL-1R1 KO–or anakinra-treated mice. In conclusion, induction of IL-1 by XRT mediates the development of some, such as the contractile impairment, but not all aspects of the XRT-induced cardiomyopathy, such as myocardial fibrosis or pericardial thickening. PMID:25822795

  19. Role of Interleukin-1 in Radiation-Induced Cardiomyopathy.

    PubMed

    Mezzaroma, Eleonora; Mikkelsen, Ross B; Toldo, Stefano; Mauro, Adolfo G; Sharma, Khushboo; Marchetti, Carlo; Alam, Asim; Van Tassell, Benjamin W; Gewirtz, David A; Abbate, Antonio

    2015-03-26

    Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in the mouse. Female mice with genetic deletion of the IL-1 receptor type I (IL-1R1 knockout mice [IL-1R1 KO]) and treatment with recombinant human IL-1 receptor antagonist anakinra, 10 mg/kg twice daily for 7 d, were used as independent approaches to determine the role of IL-1. Wild-type (wt) or IL-1R1 KO mice were treated with a single session of XRT (20 or 14 gray [Gy]). Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis and pericardial thickening. After 20 Gy, the contractile reserve was impaired in wt mice at d 3, and the LV ejection fraction (EF) was reduced after 4 months when compared with sham-XRT. IL-1R1 KO mice had preserved contractile reserve at 3 d and 4 months and LVEF at 4 months after XRT. Anakinra treatment for 1 d before and 7 d after XRT prevented the impairment in contractile reserve. A significant increase in LV end-diastolic pressure, associated with increased myocardial interstitial fibrosis and pericardial thickening, was observed in wt mice, as well as in IL-1R1 KO-or anakinra-treated mice. In conclusion, induction of IL-1 by XRT mediates the development of some, such as the contractile impairment, but not all aspects of the XRT-induced cardiomyopathy, such as myocardial fibrosis or pericardial thickening.

  20. Lesson of the month 2: Catecholamine-induced cardiomyopathy - pitfalls in diagnosis and medical management.

    PubMed

    Mamoojee, Yaasir; Arham, Munawar; Elsaify, Wael; Nag, Sath

    2016-04-01

    Cardiomyopathy as the initial presentation of phaeochromocytoma (PCA) is uncommon. Diagnostic work-up and perioperative management may be challenging within this context. We report three cases of PCA presenting with cardiomyopathy to illustrate the pitfalls in diagnosis and management. None of the patients had typical adrenergic symptoms and all three were established on beta-blockers prior to diagnosis. Their fractionated plasma catecholamine levels were elevated and the diagnosis of PCA was confirmed with various imaging modalities and post adrenalectomy. Interpretation of fractionated catecholamine levels in the context of established cardiomyopathy is difficult as cardiac failure of any aetiology generates an adrenergic response. Hence screening all patients with idiopathic cardiomyopathy is likely to generate a high false-positive rate. However, a high index of suspicion should prompt further diagnostic work-up in patients with idiopathic cardiomyopathy for occult PCAs. Peer-reviewed guidelines are required to guide the investigation and management of suspected catecholamine-induced cardiomyopathy.

  1. [Impact of cardiac resynchronization therapy on survival in patients with ischemic and nonischemic cardiomyopathy in clinical practice].

    PubMed

    Kuznetzov, V A; Vinogradova, T O; Enina, T N; Kolunin, G V; Kharatz, V E; Pavlov, A V; Krinochkin, D V; Belonogov, D V; Gorbatenko, E A; Efimova, Iu A

    2012-01-01

    To compare the impact of cardiac resynchronization therapy (CRT) on survival in patients with ischemic and non-ischemic cardiomyopathy (CMP) in clinical practice. The study enrolled 206 patients with NYHA Functional Class II-IV chronic heart failure (CHF) and a left ventricular ejection fraction of < or = 35, including 107 patients implanted with CRT devices in combination with continuous drug therapy (DT). Among the 107 patients, 48 were diagnosed as having non-ischemic CMP (NCMP), 59 as coronary heart disease (CHD). The other 99 patients (12 with NCMP and 87 with CHD) were on DT only. Later on the patients from both groups were divided into subgroups according to the treatment policy of CHF: CRT + DT or DT only. The mean follow-up period was 24 +/- 18.1 months. The Kaplan-Meier survival analysis revealed that overall survival in the patients on CRT + DT was significantly higher than in those on DT (70 and 49%, respectively; p = 0.004). Analysis of the chosen treatment policy in the NCMP subgroup showed no significant differences in survival rates in the patients receiving CRT + DT or DT (74 versus 78%, respectively; p = 0.5). At the same time, the survival rates in the CHD patients on CRT + DT were significantly higher than those in the DT subgroup (68 versus 44%; p = 0.04). CRT significantly reduces overall mortality in patients with CHF in clinical practice. Our findings indicated that this effect was achieved mainly in patients with CHD, rather than in those with NCMP.

  2. Impact of surgical ventricular reconstruction on sphericity index in patients with ischemic cardiomyopathy: follow-up from the STICH trial

    PubMed Central

    Choi, Jin-Oh; Daly, Richard C.; Lin, Grace; Lahr, Brian D.; Wiste, Heather J.; Beaver, Thomas M.; Iacovoni, Attilio; Malinowski, Marcin; Friedrich, Ivar; Rouleau, Jean L.; Favaloro, Roberto R.; Sopko, George; Lang, Irene M.; White, Harvey D.; Milano, Carmelo A.; Jones, Robert H.; Lee, Kerry L.; Velazquez, Eric J.; Oh, Jae K.

    2015-01-01

    Aims We sought to evaluate associations between baseline sphericity index (SI) and clinical outcome, and changes in SI after coronary artery bypass graft surgery (CABG) with or without surgical ventricular reconstruction (SVR) in ischemic cardiomyopathy patients enrolled in the SVR study (Hypothesis 2) of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Methods and results Among 1,000 patients in the STICH SVR study, we evaluated 546 patients (255 randomized to CABG alone and 291 to CABG+SVR) whose baseline SI values were available. SI was not significantly different between treatment groups at baseline. After 4 months, SI had increased in the CABG+SVR group, but was unchanged in the CABG alone group (0.69 ± 0.10 to 0.77 ± 0.12 versus 0.67 ± 0.07 to 0.66 ± 0.09, respectively; P < 0.001). SI did not significantly change from 4 months to 2 years in either group. Although LV end-systolic volume and ejection fraction improved significantly more in the CABG+SVR group compared to CABG alone, the severity of mitral regurgitation significantly improved only in the CABG alone group and estimated LV filling pressure (E/A ratio) increased only in the CABG+SVR group. Higher baseline SI was associated with worse survival after surgery (hazard ratio = 1.21, 95% confidence interval = 1.02−1.43; P = 0.026). Survival was not significantly different by treatment strategy. Conclusion Although SVR was designed to improve LV geometry, SI worsened after SVR despite improved LV ejection fraction and smaller LV volume. Survival was significantly better in patients with lower SI regardless of treatment strategy. (THE STICH TRIAL: Surgical Treatment for Ischemic Heart Failure trial; NCT00023595) PMID:25779355

  3. Direct intracardiac injection of umbilical cord-derived stromal cells and umbilical cord blood-derived endothelial cells for the treatment of ischemic cardiomyopathy

    PubMed Central

    Capriglione, Luiz Guilherme A; Barchiki, Fabiane; Miyague, Lye; Jackowski, Danielle; Fracaro, Letícia; Schittini, Andressa V; Senegaglia, Alexandra C; Rebelatto, Carmen LK; Olandoski, Márcia; Correa, Alejandro; Brofman, Paulo RS

    2015-01-01

    The development of new therapeutic strategies is necessary to reduce the worldwide social and economic impact of cardiovascular disease, which produces high rates of morbidity and mortality. A therapeutic option that has emerged in the last decade is cell therapy. The aim of this study was to compare the effect of transplanting human umbilical cord-derived stromal cells (UCSCs), human umbilical cord blood-derived endothelial cells (UCBECs) or a combination of these two cell types for the treatment of ischemic cardiomyopathy (IC) in a Wistar rat model. IC was induced by left coronary artery ligation, and baseline echocardiography was performed seven days later. Animals with a left ventricular ejection fraction (LVEF) of ≤40% were selected for the study. On the ninth day after IC was induced, the animals were randomized into the following experimental groups: UCSCs, UCBECs, UCSCs plus UCBECs, or vehicle (control). Thirty days after treatment, an echocardiographic analysis was performed, followed by euthanasia. The animals in all of the cell therapy groups, regardless of the cell type transplanted, had less collagen deposition in their heart tissue and demonstrated a significant improvement in myocardial function after IC. Furthermore, there was a trend of increasing numbers of blood vessels in the infarcted area. The median value of LVEF increased by 7.19% to 11.77%, whereas the control group decreased by 0.24%. These results suggest that UCSCs and UCBECs are promising cells for cellular cardiomyoplasty and can be an effective therapy for improving cardiac function following IC. PMID:25576340

  4. Retrospective evaluation of antibody index of human parvovirus B19 as a prognostic factor in patients with dilated and ischemic cardiomyopathy.

    PubMed

    Zedtwitz-Liebenstein, Konstantin; Robak, Oliver; Burgmann, Heinz; Frass, Michael

    2013-06-01

    Cardiotropic viral infections are important causative factors in dilated cardiomyopathy. This retrospective study examined the antibody index for human parvovirus B19 in patients suffering from dilated or ischemic cardiomyopathy as a prognostic factor for stable left ventricular function. Blood specimens from 43 patients with the diagnosis of dilated or ischemic cardiomyopathy were analyzed for human parvovirus B19 by polymerase chain reaction (PCR) and enzyme immunoassay kit for qualitative determination of IgG and IgM antibodies. To exclude patients with acute myocarditis, only patients with onset of symptoms more than 4 months previously were included. Patients with dilated cardiomyopathy and a high antibody index showed a significantly better clinical outcome when compared to patients with a low IgG antibody index (8.5 ± 2.4 vs. 3.1 ± 2.6; P = 0.006). There was no significant difference in left ventricular ejection fraction between patients with a high antibody index and patients with a lower antibody index (P = 0.59). The presence of human parvovirus B19 antibodies is associated with protective immunity. A high antibody index seems to be a good prognostic factor for the disease correlating to a relatively stable left ventricular ejection fraction.

  5. Anti-inflammatory and pro-angiogenic effects of beta blockers in a canine model of chronic ischemic cardiomyopathy: comparison between carvedilol and metoprolol

    PubMed Central

    Le, D. Elizabeth; Pascotto, Marco; Leong-Poi, Howard; Sari, Ibrahim; Micari, Antonio; Kaul, Sanjiv

    2013-01-01

    There is controversy regarding the superiority of carvedilol (C) over metoprolol (M) in congestive heart failure. We hypothesized that C is superior to M in chronic ischemic cardiomyopathy because of its better anti-inflammatory and pro-angiogenic effects. In order to test our hypothesis we used a chronic canine model of multivessel ischemic cardiomyopathy where myocardial microcatheters were placed from which interstitial fluid was collected over time to measure leukocyte count and cytokine levels. After development of left ventricular dysfunction, the animals were randomized into four groups: sham (n = 7), placebo (n = 8), M (n = 11), and C (n = 10), and followed for 3 months after treatment initiation. Tissue was examined for immunohistochemistry, oxidative stress, and capillary density. At 3 months both rest and stress wall thickening were better in C compared to the other groups. At the end of 3 months of treatment endsystolic wall stress also decreased the most in C. Similarly resting myocardial blood flow (MBF) improved the most in C as did the stress endocardial/epicardial MBF. Myocardial interstitial fluid showed greater attenuation of leukocytosis with C compared to M, which was associated with less fibrosis and oxidative stress. C also had higher IL-10 level and capillary density. In conclusion, in a chronic canine model of multivessel ischemic cardiomyopathy we found 3 months of C treatment resulted in better resting global and regional function as well as better regional function at stress compared to M. These changes were associated with higher myocardial levels of the anti-inflammatory cytokine IL-10 and less myocardial oxidative stress, leukocytosis, and fibrosis. Capillary density and MBF were almost normalized. Thus in the doses used in this study, C appears to be superior to M in a chronic canine model of ischemic cardiomyopathy from beneficial effects on inflammation and angiogenesis. Further studies are required for comparing additional doses

  6. An Alternative Way to Reach the Epicardial Focus of the Left Ventricular Tachycardia in a Patient with Non-ischemic Cardiomyopathy

    PubMed Central

    Aras, Dursun; Topaloglu, Serkan; Cay, Serkan; Ozeke, Ozcan; Cagirci, Goksel; Canpolat, Ugur

    2014-01-01

    We report a case of a 69-year-old male with non-ischemic cardiomyopathy, having drug- and antitachycardia pacing-refractory ventricular tachycardia resulted in multiple ICD shocks. The sustained and intractable ventricular arrhythmia was mapped and ablated with the aid of the three-dimensional electroanatomic mapping system, initially performed but unsuccessful from the endocardial site then performed successfully from the epicardial site via the coronary sinus. PMID:24669109

  7. Comparison of Ventricular Inducibility with Late Gadolinium Enhancement and Myocardial Inflammation in Endomyocardial Biopsy in Patients with Dilated Cardiomyopathy

    PubMed Central

    Mueller, Karin A. L.; Heck, Christian; Heinzmann, David; Schwille, Johannes; Klingel, Karin; Kandolf, Reinhard; Kramer, Ulrich; Gramlich, Michael; Geisler, Tobias; Gawaz, Meinrad P.

    2016-01-01

    Background Risk stratification of patients with non-ischemic dilated cardiomyopathy remains a matter of debate in the era of device implantation. Objective We investigated associations between histopathological findings, contrast-enhanced cardiac MRI and the inducibility of ventricular tachycardia (VT) or fibrillation (VF) in programmed ventricular stimulation. Methods 56 patients with impaired left ventricular ejection fraction (LVEF≤50%, mean 36.6±10.5%) due to non-ischemic dilated cardiomyopathy underwent cardiac MRI, programmed ventricular stimulation, and endomyocardial biopsy and were retrospectively investigated. Inducibility was defined as sustained mono- or polymorphic VT or unstable VT/VF requiring cardioversion/defibrillation. Primary study endpoint was defined as the occurrence of hemodynamically relevant VT/VF and/or adequate ICD-therapy during follow-up. Results Endomyocardial biopsy detected cardiac fibrosis in 18 (32.1%) patients. Cardiac MRI revealed 35 (62.5%) patients with positive late gadolinium enhancement. VT/VF was induced in ten (17.9%) patients during programmed ventricular stimulation. Monomorphic VT was inducible in 70%, while 20% of patients showed polymorphic VT. One patient (10%) presented with VF. Inducibility correlated significantly with the presence of positive late gadolinium enhancement in cardiac MRI (p<0.01). We could not find a significant association between inducibility and the degree of cardiac inflammation and fibrosis in non-site directed routine right ventricular endomyocardial biopsy. During a mean follow-up of 2.6 years, nine (16.1%) patients reached the primary endpoint. Monomorphic VTs were found in 66.7% patients and were terminated by antitachycardia pacing therapy. One patient with polymorphic VT and two patients with VF received adequate therapy by an ICD-shock. However, inducibility did not correlate with the occurrence of endpoints. Conclusion Inducibilty during programmed ventricular stimulation is

  8. Mid-Ventricular Variant of Dobutamine-Induced Stress Cardiomyopathy

    PubMed Central

    Chandraprakasam, Satish; Kanuri, Swapna; Hunter, Claire

    2015-01-01

    Introduction: Dobutamine stress testing is a commonly used modality in detecting and estimating the prognosis in coronary artery disease (CAD). Although it is well tolerated by most patients, adverse events have been reported. Rarely, transient wall motion abnormalities can occur in the absence of obstructive CAD to suggest stress cardiomyopathy. Case Presentation: We report a 48-year-old female with intermittent chest pain. Her physical exam, cardiac enzymes and transthoracic echocardiogram were unremarkable. She underwent dobutamine stress echocardiogram to rule out obstructive CAD. After 40 micrograms (mcg)/kg/minute and 0.5 mg atropine, she complained of intense chest pain and became hypertensive. Stress echocardiogram demonstrated mid-anterior and mid-septal hypokinesis. Emergent coronary angiogram demonstrated normal coronaries. Left ventricular angiogram in the right anterior oblique projection revealed mid-ventricular ballooning during systole with apical and basal hypercontractility. Patient demonstrated excellent recovery with expectant management. Conclusions: The mechanism of mid-variant of Dobutamine-induced stress cardiomyopathy remains unclear. We think that multiple mechanisms are involved and this risk should be considered in patients with comorbid psychiatric conditions and with use of centrally acting stimulants. PMID:26425489

  9. Transient Cardiomyopathy and Quadriplegia Induced by Ephedrine Decongestant.

    PubMed

    Snipelisky, David F; Kurklinsky, Andrew K; Chirila, Razvan

    2015-12-01

    Ephedrine decongestant products are widely used. Common side effects include palpitations, nervousness, and headache. More severe adverse reactions include cardiomyopathy and vasospasm. We report the case of an otherwise healthy 37-year-old woman who presented with acute-onset quadriplegia and heart failure. She had a normal chest radiograph on admission, but developed marked pulmonary edema and bilateral effusions the next day. Echocardiography revealed a left ventricular ejection fraction of 0.18 and no obvious intrinsic pathologic condition such as foramen narrowing on spinal imaging. Laboratory screening was positive for methamphetamines in the urine, and the patient admitted to having used, over the past several weeks, multiple ephedrine-containing products for allergy-symptom relief. She was ultimately diagnosed with an acute catecholamine-induced cardiomyopathy and spinal artery vasospasm consequential to excessive use of decongestants. Her symptoms resolved completely with supportive care and appropriate heart-failure management. An echocardiogram 2 weeks after admission showed improvement of the left ventricular ejection fraction to 0.33. Ten months after the event, the patient was entirely asymptomatic and showed further improvement of her ejection fraction to 0.45. To our knowledge, ours is the first report of spinal artery vasospasm resulting in quadriplegia in a human being after ephedrine ingestion.

  10. Transient Cardiomyopathy and Quadriplegia Induced by Ephedrine Decongestant

    PubMed Central

    Kurklinsky, Andrew K.; Chirila, Razvan

    2015-01-01

    Ephedrine decongestant products are widely used. Common side effects include palpitations, nervousness, and headache. More severe adverse reactions include cardiomyopathy and vasospasm. We report the case of an otherwise healthy 37-year-old woman who presented with acute-onset quadriplegia and heart failure. She had a normal chest radiograph on admission, but developed marked pulmonary edema and bilateral effusions the next day. Echocardiography revealed a left ventricular ejection fraction of 0.18 and no obvious intrinsic pathologic condition such as foramen narrowing on spinal imaging. Laboratory screening was positive for methamphetamines in the urine, and the patient admitted to having used, over the past several weeks, multiple ephedrine-containing products for allergy-symptom relief. She was ultimately diagnosed with an acute catecholamine-induced cardiomyopathy and spinal artery vasospasm consequential to excessive use of decongestants. Her symptoms resolved completely with supportive care and appropriate heart-failure management. An echocardiogram 2 weeks after admission showed improvement of the left ventricular ejection fraction to 0.33. Ten months after the event, the patient was entirely asymptomatic and showed further improvement of her ejection fraction to 0.45. To our knowledge, ours is the first report of spinal artery vasospasm resulting in quadriplegia in a human being after ephedrine ingestion. PMID:26664316

  11. Sites of Latest Mechanical Activation as Assessed by SPECT Myocardial Perfusion Imaging in Ischemic and Dilated Cardiomyopathy Patients with LBBB

    PubMed Central

    Lin, Xianhe; Xu, Huiqin; Zhao, Xuefeng; Chen, Ji

    2014-01-01

    Objective Sites of latest mechanical activation (SOLA) have been recognized as optimal left-ventricular (LV) lead positions for cardiac resynchronization therapy (CRT). This study was aimed to investigate SOLA in ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) patients with left bundle branch block (LBBB). Methods Sixty-four consecutive LBBB patients (47 DCM, 17 ICM), who met the standard indications for CRT and underwent resting SPECT myocardial perfusion imaging (MPI), were selected. Phase analysis was used to assess LV dyssynchrony and SOLA. The Emory Cardiac Toolbox was used to measure perfusion defects. LV dyssynchrony and SOLA were compared between the DCM patients with wide (≥150 ms) and moderate (120–150 ms) QRS durations (QRSd). The relationship between SOLA and perfusion defects was analyzed in the ICM patients. Results The DCM patients with wide QRSd had significantly more LV dyssynchrony than those with moderate QRSd. Lateral SOLA were significantly more frequent in the DCM patients with wide QRSd than those with moderate QRSd (96% vs. 62%, p=0.010). In the ICM patients, SOLA were either in the scar segments (82%) or in the segments immediately adjacent to the scar segments (18%), regardless of QRSd. Conclusion Lateral SOLA were more frequent in the DCM patients with wide QRSd than those with moderate QRSd. Such relationship was not observed in the ICM patients, where SOLA were associated with scar location rather than QRSd. These findings support the use of SPECT MPI to aid the selection of potential CRT responders and guide LV lead placement. PMID:24577952

  12. Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity.

    PubMed

    Molina-Navarro, María Micaela; Triviño, Juan Carlos; Martínez-Dolz, Luis; Lago, Francisca; González-Juanatey, Jose Ramón; Portolés, Manuel; Rivera, Miguel

    2014-01-01

    Heart failure provokes alterations in the expression of nucleocytoplasmic transport-related genes. To elucidate the nucleocytoplasmic transport-linked functional network underlying the two major causes of heart failure, ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined global transcriptome profiles of left ventricular myocardium tissue samples from 31 patients (ICM, n = 10; DCM, n = 13) undergoing heart transplantation and control donors (CNT, n = 8) using RNA-Sequencing and GeneMANIA. Comparative profiling of ICM versus control and DCM versus control showed 1081 and 2440 differentially expressed genes, respectively (>1.29-fold; P<0.05). GeneMANIA revealed differentially regulated functional networks specific to ICM and DCM. In comparison with CNT, differential expression was seen in 9 and 12 nucleocytoplasmic transport-related genes in ICM and DCM groups, respectively. DDX3X, KPNA2, and PTK2B were related to ICM, while SMURF2, NUP153, IPO5, RANBP3, NOXA1, and RHOJ were involved in DCM pathogenesis. Furthermore, the two pathologies shared 6 altered genes: XPO1, ARL4, NFKB2, FHL3, RANBP2, and RHOU showing an identical trend in expression in both ICM and DCM. Notably, the core of the derived functional networks composed of nucleocytoplasmic transport-related genes (XPO1, RANBP2, NUP153, IPO5, KPNA2, and RANBP3) branched into several pathways with downregulated genes. Moreover, we identified genes whose expression levels correlated with left ventricular mass index and left ventricular function parameters in HF patients. Collectively, our study provides a clear distinction between the two pathologies at the transcriptome level and opens up new possibilities to search for appropriate therapeutic targets for ICM and DCM.

  13. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy

    PubMed Central

    Zhang, Xiaoli; Schindler, Thomas H.; Prior, John O.; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng

    2016-01-01

    Purpose The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Methods Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25±10 %) were studied with 13N-ammonia and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to 13N-ammonia activity ratios. Results Rest MBF was reduced in viable (0.42±0.18 ml/min per g) and nonviable regions (0.32±0.09 ml/min per g) relative to remote regions (0.68±0.23 ml/min per g, p<0.001) and to normals (0.63±0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p<0.05) and stress (p<0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p>0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39±0.56 vs 1.70±0.45, p>0.05) but were significantly lower in nonviable regions (1.23±0.43, p<0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40±0.14 vs 0.90±0.20, p<0.001) and in nonviable regions (1.13±0.21, p<0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r=−0.424, p<0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions. Conclusion As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes. PMID:23287994

  14. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy.

    PubMed

    Zhang, Xiaoli; Schindler, Thomas H; Prior, John O; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng; Schelbert, Heinrich R

    2013-04-01

    The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with (13)N-ammonia and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to (13)N-ammonia activity ratios. Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p < 0.001) and to normals (0.63 ± 0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p < 0.05) and stress (p < 0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p < 0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40 ± 0.14 vs 0.90 ± 0.20, p < 0.001) and in nonviable regions (1.13 ± 0.21, p < 0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r =-0.424, p < 0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions. As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.

  15. Enhanced Therapeutic Effects of Human iPS Cell Derived-Cardiomyocyte by Combined Cell-Sheets with Omental Flap Technique in Porcine Ischemic Cardiomyopathy Model.

    PubMed

    Kawamura, Masashi; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Miki, Kenji; Funakoshi, Shunsuke; Yoshida, Yoshinori; Yamanaka, Shinya; Shimizu, Tatsuya; Okano, Teruo; Daimon, Takashi; Toda, Koichi; Sawa, Yoshiki

    2017-08-18

    Transplant of human induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs) cell-sheet is a promising approach for treating ischemic cardiomyopathy (ICM). However, poor blood supply to the transplanted cell-sheet is a concern related to the effectiveness and durability of the treatment. Herein, we hypothesized that the combined the omentum flap might enhance survival and the therapeutic effects of hiPS-CM cell-sheet transplant for ICM treatment. Treatment by Wnt signaling molecules in hiPS cells produced hiPS-CMs, which were magnetically labeled by superparamagnetic iron oxide (SPIO), followed by culture in the thermoresponsive dishes to generate hiPS-CMs cell-sheets. A porcine ICM model included 4 groups; sham operation, omentum flap only, cell-sheet only, or combination therapy. Ejection fraction (EF) was significantly greater in the cell-sheet only and combination group compared to the other groups during the follow-up period. At 3 months, the EF of the combination group was significantly greater than that of the cell-sheet only group. Consistently, the survival rate of the SPIO-labeled hiPS-CMs, as assessed by MRI, was significantly greater in the combination group than in the cell-sheet only group. This cell delivery system would be useful in optimizing the hiPS-CM cell-sheet transplant for treating severe heart failure.

  16. Prophylactic catheter ablation of ventricular tachycardia before cardioverter-defibrillator implantation in patients with non-ischemic cardiomyopathy: Clinical outcomes after a single endocardial ablation.

    PubMed

    Suzuki, Atsushi; Yoshida, Akihiro; Takei, Asumi; Fukuzawa, Koji; Kiuchi, Kunihiko; Takami, Kaoru; Itoh, Mitsuaki; Imamura, Kimitake; Fujiwara, Ryudo; Nakanishi, Tomoyuki; Yamashita, Soichiro; Matsumoto, Akinori; Shimane, Akira; Okajima, Katsunori; Hirata, Ken-Ichi

    2015-06-01

    Outcomes related to prophylactic catheter ablation (PCA) for ventricular tachycardia (VT) before implantable cardioverter-defibrillator (ICD) implantation in non-ischemic cardiomyopathy (NICM) are not well characterized. We assessed the efficacy of single endocardial PCA in NICM patients. We retrospectively analyzed 101 consecutive NICM patients with sustained VT. We compared clinical outcomes of patients who underwent PCA (ABL group) with those who did not (No ABL group). Successful PCA was defined as no inducible clinical VT. We also compared the clinical outcomes of patients with successful PCA (PCA success group) with those of the No ABL group. Endpoints were appropriate ICD therapy (shock and anti-tachycardia pacing) and the occurrence of electrical storm (ES). PCA was performed in 42 patients, and it succeeded in 20. The time to ES occurrence was significantly longer in the ABL group than in the No ABL group (p=0.04). The time to first appropriate ICD therapy and ES occurrence were significantly longer in the PCA success group than in the No ABL group (p=0.02 and p<0.01, respectively). Single endocardial PCA can decrease ES occurrence in NICM patients. However, high rates of VT recurrence and low success rates are issues to be resolved; therefore, the efficacy of single endocardial PCA is currently limited.

  17. Prophylactic catheter ablation of ventricular tachycardia before cardioverter-defibrillator implantation in patients with non-ischemic cardiomyopathy: Clinical outcomes after a single endocardial ablation

    PubMed Central

    Suzuki, Atsushi; Yoshida, Akihiro; Takei, Asumi; Fukuzawa, Koji; Kiuchi, Kunihiko; Takami, Kaoru; Itoh, Mitsuaki; Imamura, Kimitake; Fujiwara, Ryudo; Nakanishi, Tomoyuki; Yamashita, Soichiro; Matsumoto, Akinori; Shimane, Akira; Okajima, Katsunori; Hirata, Ken-ichi

    2015-01-01

    Background Outcomes related to prophylactic catheter ablation (PCA) for ventricular tachycardia (VT) before implantable cardioverter-defibrillator (ICD) implantation in non-ischemic cardiomyopathy (NICM) are not well characterized. We assessed the efficacy of single endocardial PCA in NICM patients. Methods We retrospectively analyzed 101 consecutive NICM patients with sustained VT. We compared clinical outcomes of patients who underwent PCA (ABL group) with those who did not (No ABL group). Successful PCA was defined as no inducible clinical VT. We also compared the clinical outcomes of patients with successful PCA (PCA success group) with those of the No ABL group. Endpoints were appropriate ICD therapy (shock and anti-tachycardia pacing) and the occurrence of electrical storm (ES). Results PCA was performed in 42 patients, and it succeeded in 20. The time to ES occurrence was significantly longer in the ABL group than in the No ABL group (p=0.04). The time to first appropriate ICD therapy and ES occurrence were significantly longer in the PCA success group than in the No ABL group (p=0.02 and p<0.01, respectively). Conclusion Single endocardial PCA can decrease ES occurrence in NICM patients. However, high rates of VT recurrence and low success rates are issues to be resolved; therefore, the efficacy of single endocardial PCA is currently limited. PMID:26336545

  18. Selective Serotonin–norepinephrine Reuptake Inhibitors-induced Takotsubo Cardiomyopathy

    PubMed Central

    Vasudev, Rahul; Rampal, Upamanyu; Patel, Hiten; Patel, Kunal; Bikkina, Mahesh; Shamoon, Fayez

    2016-01-01

    Context: Takotsubo translates to “octopus pot” in Japanese. Takotsubo cardiomyopathy (TTC) is characterized by a transient regional systolic dysfunction of the left ventricle. Catecholamine excess is the one most studied and favored theories explaining the pathophysiology of TTC. Case Report: We present the case of a 52-year-old Hispanic female admitted for venlafaxine-induced TTC with a review literature on all the cases of Serotonin–norepinephrine reuptake inhibitors (SNRI)-associated TTC published so far. Conclusion: SNRI inhibit the reuptake of catecholamines into the presynaptic neuron, resulting in a net gain in the concentration of epinephrine and serotonin in the neuronal synapses and causing iatrogenic catecholamine excess, ultimately leading to TTC. PMID:27583240

  19. Myocardial biochemical changes in furazolidone-induced cardiomyopathy of turkeys.

    PubMed

    Mirsalimi, S M; Qureshi, F S; Julian, R J; O'Brien, P J

    1990-02-01

    This study tested the hypothesis that membrane transport is the major biochemical system of the myocardium altered in furazolidone-induced cardiomyopathy (round heart disease), before the development of myocardial failure, and that metabolic enzymes and contractile proteins are less affected. Compared with controls, maximal percentage depression of activities of myocardium from furazolidone-treated birds were 40 for creatine kinase, 30 for glycolysis, 30 for glycogen, 20 for myofibrils, 20 for Krebs's cycle enzymes, 15 for fatty acid oxidation and 10 for total soluble protein. Sodium and potassium transport, antioxidant system activity, myosin, myosin isoenzyme patterns and amino acid aminotransferases were unaffected. In marked contrast, the calcium-transport ATPase activity of the sarcoplasmic reticulum had undergone a 60 per cent compensatory increase in activity. The pattern of biochemical changes observed is consistent with a role of ischaemia in the pathogenesis of round heart disease and indicates that calcium transport by the sarcoplasmic reticulum is the major biochemical system affected.

  20. Association of cytokines with endothelium dependent flow mediated vasodilation (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy.

    PubMed

    Vallbracht-Israng, Katja B; Kazak, Ilkay; Schwimmbeck, Peter L

    2007-12-10

    Aim of this study was to elucidate the relation between localised inflammatory heart disease and endothelial dysfunction in the peripheral circulation, considering circulating cytokines as a potential link. In 38 patients with non-ischemic heart disease, myocardial biopsies were examined for myocardial inflammation (immunohistology) and virus persistence (PCR). Cytokines (sIL-4, IFN-g, IFN-b, IFN-a, sIL-12p7, TNF-a) were measured by ELISA in venous serum. Endothelial function of the radial artery was examined by ultrasound, measuring diameter changes in response to reactive hyperemia (FMD), compared to glyceroltrinitrate (GTN-MD). Patients with EF < 35% were excluded. Age 44 +/- 14 years, 19 male, 19 female, EF 63.5[16]%. FMD 4.38 [4.82]%. 30 patients had myocardial inflammation (8 not), 23 virus persistence (15 not). FMD correlated significantly with sIL-12p7 (p = 0.024, r = -0.365), but not with other cytokines. sIL-12p7 levels were significantly higher in patients with severely impaired FMD (n = 17), compared with normal FMD (n = 21): 10.70 [10.72] vs. 4.33 [7.81] pg/ml (p = 0.002). Endothelium independent vasodilation (GTN-MD 23.67 [8.21]%) was not impaired. Endothelial dysfunction of peripheral arteries in patients with non-ischemic cardiomyopathy is associated with elevated serum concentrations of sIL-12p7, but not of other cytokines. Circulating sIL-12p7 may partly explain, that endothelial dysfunction is not restricted to the coronary circulation, but involves systemic arteries.

  1. Relationship between myocardial perfusion-gated SPECT and the performance of coronary revascularization in patients with ischemic cardiomyopathy.

    PubMed

    Romero-Farina, Guillermo; Candell-Riera, Jaume; Aguadé-Bruix, Santiago; Ferreira-Gonzalez, Ignacio; Igual, Albert; García-Dorado, David

    2012-10-01

    Ischemic cardiomyopathy (ICM) is a disease with high morbidity and mortality. There are several published studies on the evolution and prognosis of patients with ICM. However, reports on the therapeutic management in clinical practice are scarce. The aim of this study was to analyze coronary revascularization (CR) performance in patients with ICM and suitable coronary anatomy according to myocardial perfusion stress-rest gated SPECT results. Eighty-seven consecutive patients (mean age, 62.4 y; 20 women), with ischemic heart disease, left ventricular ejection fraction of 40% or less, coronary anatomy suitable for CR, and without previous CR, were evaluated by means of stress-rest gated SPECT. Sixty-four percent of patients had scintigraphic criteria of viability and 62.1% showed scintigraphic ischemia in stress-rest gated SPECT. Forty-five percent of patients were revascularized, and the remainder received medical treatment only. Coronary revascularization was more frequent in patients with scintigraphic viability (P = 0.012), in those with scintigraphic ischemia (P = 0.007), and in those with low left ventricular end-systolic volume (P = 0.006). Cox regression analysis identified multivessel disease [hazard ratio (HR), 3.3; 95% confidence interval (CI), 4-7.8], summed difference score greater than 4 (HR, 3.9; 95% CI, 1.5-9.8), and left ventricular end-systolic volume less than 120 mL (HR, 3.2; 95% CI, 1.3-8.2) as the best independent predictors of CR treatment. In patients with ICM and suitable coronary arteries who are able to perform a stress myocardial perfusion-gated SPECT, the presence of multivessel disease and myocardial ischemia and the absence of severely increased left ventricular volume were associated to a decision of CR.

  2. Late onset radiation-induced constrictive pericarditis and cardiomyopathy after radiotherapy

    PubMed Central

    Zhuang, Xiao-feng; Yang, Yan-min; Sun, Xiao-lu; Liao, Zhong-kai; Huang, Jie

    2017-01-01

    Abstract Introduction: Radiation-induced heart disease (RIHD) is a serious side effect of cancer treatment, including coronary artery disease, valvular cardiac dysfunction, cardiomyopathy, aortopathy, and chronic constrictive pericarditis. Herein, this case we present was diagnosed as radiation-induced constrictive pericarditis and cardiomyopathy by means of cardiac magnetic resonance (CMR) and transthoracic echocardiogram, finally confirmed by pathology after performing heart transplant operation. Conclusions: This case supports a notion that RIHD often causes multiple heart impairment and CMR is helpful to diagnose cardiomyopathy after radiation. PMID:28151876

  3. The Prognostic Value of Discordant T waves in Lead aVR: A Simple Risk Marker of Sudden Cardiac Arrest in Ischemic Cardiomyopathy

    PubMed Central

    Al-Zaiti, Salah S.; Fallavollita, James A.; Canty, John M.; Carey, Mary G.

    2015-01-01

    Background Simple and reliable ECG marker(s) for sudden cardiac arrest (SCA) could be very useful in assessing high-risk populations. Since ischemic repolarization abnormalities in the left ventricular (LV) apex are strongly correlated with discordant T waves in lead aVR, we sought to evaluate the clinical and prognostic significance of this feature in ischemic cardiomyopathy. Methods The PAREPET trial enrolled patients with ischemic cardiomyopathy eligible for a primary prevention implantable cardiac defibrillator (ICD). Those with persistent pacing or left bundle branch block were excluded. Amplitudes of T/aVR were automatically computed from median ECG beats at enrollment and endpoints were blindly adjudicated. Results The sample was mainly composed of older men (n=138, age 65±12, 91% male, EF 29±9%). At enrollment, amplitude of T/aVR significantly correlated with EF, indexed LV end-diastolic volume, B-type natriuretic peptide (BNP), regional scar volume, and PET-quantified denervated myocardium. After a median follow up of 4.2 years, there were 23 (17%) adjudicated SCA. In multivariate analysis, the presence of discordant T/aVR (>0mm, n=42, 30%) was a significant and independent predictor of SCA (hazard ratio 2.0 [95% CI 1.0–4.9]) and cardiac death (hazard ratio 1.9 [95% CI 1.0–3.7]). Conclusions In subjects with ischemic cardiomyopathy, discordant T waves in Lead aVR are associated with high-risk clinical parameters including lower ejection fraction, greater ventricular volume, higher BNP, and more denervated myocardium. Furthermore, discordant TaVR remained an independent predictor of SCA and cardiovascular mortality even after accounting for these prognostic factors. PMID:26233648

  4. Infarct characterization and quantification by delayed enhancement cardiac magnetic resonance imaging is a powerful independent and incremental predictor of mortality in patients with advanced ischemic cardiomyopathy.

    PubMed

    Kwon, Deborah H; Asamoto, Lisa; Popovic, Zoran B; Kusunose, Kenya; Robinson, Monique; Desai, Milind; Marwick, Thomas H; Flamm, Scott D

    2014-09-01

    Infarct heterogeneity has been shown to be independently associated with adverse outcomes in previous smaller studies. However, it is unknown whether infarct characterization is an independent predictor of all-cause mortality in patients with advanced ischemic cardiomyopathy, after adjusting for clinical risk factors, severity of ischemic mitral regurgitation, incomplete revascularization, and device therapy. A total of 362 patients with ischemic cardiomyopathy (left ventricular dysfunction with >70% stenosis in ≥1 epicardial coronary artery) underwent delayed hyperenhancement-magnetic resonance imaging and coronary angiography between 2002 and 2006. Total myocardial scar and peri-infarct (PI) area were measured using various threshold techniques. Multivariate survival analysis (primary end point of all-cause mortality) was conducted. One hundred fifty-seven deaths occurred during a mean 5.4-year follow-up (mean left ventricular ejection fraction, 23±9%; mean end-systolic volume index, 113±48 mL; mean total myocardial scar %, 25.5±16.0%; mean PI%, 5.7±2.9%). PI% (β=2.07; P<0.001) was an independent predictor of survival, independent of age, end-systolic volume, sex, mitral regurgitation, diabetes mellitus, dyslipidemia, coronary artery disease severity, implantable cardioverter defibrillator, and incomplete revascularization. PI% using 2 to 3 SD technique yielded the highest incremental prognostic power (χ(2) score 149). In advanced ischemic cardiomyopathy, PI% is a powerful independent and incremental predictor of all-cause mortality. Infarct heterogeneity offers substantial further risk stratification when compared with quantification of total myocardial scar % alone even after adjusting for clinical risk factors, end-systolic volume index, mitral regurgitation, incomplete revascularization, and implantable cardioverter defibrillator implantation. © 2014 American Heart Association, Inc.

  5. The prognostic value of discordant T waves in lead aVR: A simple risk marker of sudden cardiac arrest in ischemic cardiomyopathy.

    PubMed

    Al-Zaiti, Salah S; Fallavollita, James A; Canty, John M; Carey, Mary G

    2015-01-01

    Simple and reliable ECG marker(s) for sudden cardiac arrest (SCA) could be very useful in assessing high-risk populations. Since ischemic repolarization abnormalities in the left ventricular (LV) apex are strongly correlated with discordant T waves in lead aVR, we sought to evaluate the clinical and prognostic significance of this feature in ischemic cardiomyopathy. The PAREPET trial enrolled patients with ischemic cardiomyopathy eligible for a primary prevention implantable cardiac defibrillator (ICD). Those with persistent pacing or left bundle branch block were excluded. Amplitudes of T/aVR were automatically computed from median ECG beats at enrollment and endpoints were blindly adjudicated. The sample was mainly composed of older men (n=138, age 65±12, 91% male, EF 29±9%). At enrollment, amplitude of T/aVR significantly correlated with EF, indexed LV end-diastolic volume, B-type natriuretic peptide (BNP), regional scar volume, and PET-quantified denervated myocardium. After a median follow up of 4.2years, there were 23 (17%) adjudicated SCA. In multivariate analysis, the presence of discordant T/aVR (>0mm, n=42, 30%) was a significant and independent predictor of SCA (hazard ratio 2.0 [95% CI 1.0-4.9]) and cardiac death (hazard ratio 1.9 [95% CI 1.0-3.7]). In subjects with ischemic cardiomyopathy, discordant T waves in lead aVR are associated with high-risk clinical parameters including lower ejection fraction, greater ventricular volume, higher BNP, and more denervated myocardium. Furthermore, discordant T/aVR remained an independent predictor of SCA and cardiovascular mortality even after accounting for these prognostic factors. Copyright © 2015. Published by Elsevier Inc.

  6. Impact of Shocks on Mortality in Patients with Ischemic or Dilated Cardiomyopathy and Defibrillators Implanted for Primary Prevention

    PubMed Central

    Streitner, Florian; Herrmann, Thomas; Kuschyk, Juergen; Lang, Siegfried; Doesch, Christina; Papavassiliu, Theano; Streitner, Ines; Veltmann, Christian; Haghi, Dariusch; Borggrefe, Martin

    2013-01-01

    Background Emerging interest is seen in the paradox of defibrillator shocks for ventricular tachyarrhythmia and increased mortality risk. Particularly in patients with dilated cardiomyopathy (DCM), the prognostic importance of shocks is unclear. The purpose of this study was to compare the outcome after shocks in patients with ischemic cardiomyopathy (ICM) or DCM and defibrillators (ICD) implanted for primary prevention. Methods and Results Data of 561 patients were analyzed (mean age 68.6±10.6 years, mean left ventricular ejection fraction 28.6±7.3%). During a median follow-up of 49.3 months, occurrence of device therapies and all-cause mortality were recorded. 74 out of 561 patients (13.2%) experienced ≥1 appropriate and 51 out of 561 patients (9.1%) ≥1 inappropriate shock. All-cause mortality was 24.2% (136 out of 561 subjects). Appropriate shock was associated with a trend to higher mortality in the overall patient population (HR 1.48, 95% CI 0.96–2.28, log rank p = 0.072). The effect was significant in ICM patients (HR 1.61, 95% CI 1.00–2.59, log rank p = 0.049) but not in DCM patients (HR 1.03, 95% CI 0.36–2.96, log rank p = 0.96). Appropriate shocks occurring before the median follow-up revealed a much stronger impact on mortality (HR for the overall patient population 2.12, 95% CI 1.24–3.63, p = 0.005). The effect was driven by ICM patients (HR 2.48, 95% CI 1.41–4.37, p = 0.001), as appropriate shocks again did not influence survival of DCM patients (HR 0.63, 95% CI 0.083–4.75, p = 0.65). Appropriate shocks occurring after the median follow-up and inappropriate shocks occurring at any time revealed no impact on survival in any of the groups (p = ns). Conclusion Appropriate shocks are associated with reduced survival in patients with ICM but not in patients with DCM and ICDs implanted for primary prevention. Furthermore, the negative effect of appropriate shocks on survival in ICM patients is only evident within

  7. ECHOCARDIOGRAPHIC EVALUATION OF THE EFFECTS OF STEM CELL THERAPY ON PERFUSION AND FUNCTION IN ISCHEMIC CARDIOMYOPATHY

    PubMed Central

    Inaba, Yoichi; Davidson, Brian P.; Kim, Sajeevani; Liu, Ya Ni; Packwood, William; Belcik, Todd; Xie, Aris; Lindner, Jonathan R.

    2013-01-01

    BACKGROUND Small animal models of ischemic left ventricular (LV) dysfunction are important for the pre-clinical optimization of stem cell therapy. We hypothesized that temporal changes in LV function and regional perfusion after cell therapy can be assessed in mice using echocardiographic imaging. METHODS Wild-type mice (n=25) were studied 7 and 28 days after permanent ligation of the left anterior descending artery. Animals were randomized to receive closed-chest ultrasound-guided intramyocardial delivery of saline (n=13) or 5×105 multipotential adult progenitor cells (MAPC) (n=12) at day 7. Left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volume, left ventricular ejection fraction (LVEF), and stroke volume were measured by high-frequency echocardiography. Multiplanar assessment of perfusion and defect area size were made by myocardial contrast echocardiography (MCE). RESULTS Between day 7 and 28, MAPC-treated animals had a 40–50% reduction in defect size (p<0.001) and a 20–30% increase in total perfusion (p<0.01). Perfusion did not change in non-treated controls. Both LVEDV and LVESV increased between day 7 and 28 in both groups, however LVESV increased to a lesser degree in MAPC-treated versus control mice (+4.2±7.9 vs +19.2±22.0 μL, p<0.05). LVEF increased in the MAPC-treated mice and decreased in control mice (+3.0±4.3 vs −5.6±5.9 %, p<0.01). There was a significant linear relation between the change in LVEF and the change in either defect area size or total perfusion. CONCLUSIONS High-frequency echocardiography and MCE in murine models of ischemic LV dysfunction can be used to assess the response to stem cell therapy and to characterize the relationship between spatial flow, ventricular function and ventricular remodeling. PMID:24315764

  8. Ventricular Tachycardia and Early Fibrillation in Patients With Brugada Syndrome and Ischemic Cardiomyopathy Show Predictable Frequency-Phase Properties on the Precordial ECG Consistent With the Respective Arrhythmogenic Substrate

    PubMed Central

    Calvo, David; Atienza, Felipe; Saiz, Javier; Martínez, Laura; Ávila, Pablo; Rubín, José; Herreros, Benito; Arenal, Ángel; García-Fernández, Javier; Ferrer, Ana; Sebastián, Rafael; Martínez-Camblor, Pablo; Jalife, José

    2015-01-01

    Background— Ventricular fibrillation (VF) has been proposed to be maintained by localized high-frequency sources. We tested whether spectral-phase analysis of the precordial ECG enabled identification of periodic activation patterns generated by such sources. Methods and Results— Precordial ECGs were recorded from 15 ischemic cardiomyopathy and 15 Brugada syndrome (type 1 ECG) patients during induced VF and analyzed in the frequency-phase domain. Despite temporal variability, induced VF episodes lasting 19.6±7.9 s displayed distinctly high power at a common frequency (shared frequency, 5.7±1.1 Hz) in all leads about half of the time. In patients with Brugada syndrome, phase analysis of shared frequency showed a V1–V6 sequence as would be expected from patients displaying a type 1 ECG pattern (P<0.001). Hilbert-based phases confirmed that the most stable sequence over the whole VF duration was V1–V6. Analysis of shared frequency in ischemic cardiomyopathy patients with anteroseptal (n=4), apical (n=3), and inferolateral (n=4) myocardial infarction displayed a sequence starting at V1–V2, V3–V4, and V5–V6, respectively, consistent with an activation origin at the scar location (P=0.005). Sequences correlated with the Hilbert-based phase analysis (P<0.001). Posterior infarction (n=4) displayed no specific sequence. On paired comparison, phase sequences during monomorphic ventricular tachycardia correlated moderately with VF (P<0.001). Moreover, there was a dominant frequency gradient from precordial leads facing the scar region to the contralateral leads (5.8±0.8 versus 5.4±1.1 Hz; P=0.004). Conclusions— Noninvasive analysis of ventricular tachycardia and early VF in patients with Brugada syndrome and ischemic cardiomyopathy shows a predictable sequence in the frequency-phase domain, consistent with anatomic location of the arrhythmogenic substrate. PMID:26253505

  9. Native Myocardial T1 as a Biomarker of Cardiac Structure in Non-Ischemic Cardiomyopathy.

    PubMed

    Shah, Ravi V; Kato, Shingo; Roujol, Sebastien; Murthy, Venkatesh; Bellm, Steven; Kashem, Abyaad; Basha, Tamer; Jang, Jihye; Eisman, Aaron S; Manning, Warren J; Nezafat, Reza

    2016-01-15

    Diffuse myocardial fibrosis is involved in the pathology of nonischemic cardiomyopathy (NIC). Recently, the application of native (noncontrast) myocardial T1 measurement has been proposed as a method for characterizing diffuse interstitial fibrosis. To determine the association of native T1 with myocardial structure and function, we prospectively studied 39 patients with NIC (defined as left ventricular ejection fraction (LVEF) ≤ 50% without cardiac magnetic resonance (CMR) evidence of previous infarction) and 27 subjects with normal LVEF without known overt cardiovascular disease. T1, T2, and extracellular volume fraction (ECV) were determined over 16 segments across the base, mid, and apical left ventricular (LV). NIC participants (57 ± 15 years) were predominantly men (74%), with a mean LVEF 34 ± 10%. Subjects with NIC had a greater native T1 (1,131 ± 51 vs 1,069 ± 29 ms; p <0.0001), a greater ECV (0.28 ± 0.04 vs 0.25 ± 0.02, p = 0.002), and a longer myocardial T2 (52 ± 8 vs 47 ± 5 ms; p = 0.02). After multivariate adjustment, a lower global native T1 time in NIC was associated with a greater LVEF (β = -0.59, p = 0.0003), greater right ventricular ejection fraction (β = -0.47, p = 0.006), and smaller left atrial volume index (β = 0.51, p = 0.001). The regional distribution of native myocardial T1 was similar in patients with and without NIC. In NIC, native myocardial T1 is elevated in all myocardial segments, suggesting a global (not regional) abnormality of myocardial tissue composition. In conclusion, native T1 may represent a rapid, noncontrast alternative to ECV for delineating myocardial tissue remodeling in NIC. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Dietary Salt Exacerbates Isoproterenol-induced Cardiomyopathy in Rats

    EPA Science Inventory

    Spontaneously Hypertensive Heart Failure rats (SHHFs) take far longer to develop compensated heart failure and congestive decompensation than common surgical models of heart failure. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young SHHFs, while dietary salt loa...

  11. Dietary Salt Exacerbates Isoproterenol-induced Cardiomyopathy in Rats

    EPA Science Inventory

    Spontaneously Hypertensive Heart Failure rats (SHHFs) take far longer to develop compensated heart failure and congestive decompensation than common surgical models of heart failure. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young SHHFs, while dietary salt loa...

  12. Novel MRI-derived quantitative biomarker for cardiac function applied to classifying ischemic cardiomyopathy within a Bayesian rule learning framework

    NASA Astrophysics Data System (ADS)

    Menon, Prahlad G.; Morris, Lailonny; Staines, Mara; Lima, Joao; Lee, Daniel C.; Gopalakrishnan, Vanathi

    2014-03-01

    Characterization of regional left ventricular (LV) function may have application in prognosticating timely response and informing choice therapy in patients with ischemic cardiomyopathy. The purpose of this study is to characterize LV function through a systematic analysis of 4D (3D + time) endocardial motion over the cardiac cycle in an effort to define objective, clinically useful metrics of pathological remodeling and declining cardiac performance, using standard cardiac MRI data for two distinct patient cohorts accessed from CardiacAtlas.org: a) MESA - a cohort of asymptomatic patients; and b) DETERMINE - a cohort of symptomatic patients with a history of ischemic heart disease (IHD) or myocardial infarction. The LV endocardium was segmented and a signed phase-to-phase Hausdorff distance (HD) was computed at 3D uniformly spaced points tracked on segmented endocardial surface contours, over the cardiac cycle. An LV-averaged index of phase-to-phase endocardial displacement (P2PD) time-histories was computed at each tracked point, using the HD computed between consecutive cardiac phases. Average and standard deviation in P2PD over the cardiac cycle was used to prepare characteristic curves for the asymptomatic and IHD cohort. A novel biomarker of RMS error between mean patient-specific characteristic P2PD over the cardiac cycle for each individual patient and the cumulative P2PD characteristic of a cohort of asymptomatic patients was established as the RMS-P2PD marker. The novel RMS-P2PD marker was tested as a cardiac function based feature for automatic patient classification using a Bayesian Rule Learning (BRL) framework. The RMS-P2PD biomarker indices were significantly different for the symptomatic patient and asymptomatic control cohorts (p<0.001). BRL accurately classified 83.8% of patients correctly from the patient and control populations, with leave-one-out cross validation, using standard indices of LV ejection fraction (LV-EF) and LV end-systolic volume

  13. Long-term outcome of surgical cryoablation for refractory ventricular tachycardia in patients with non-ischemic cardiomyopathy.

    PubMed

    Liang, Jackson J; Betensky, Brian P; Muser, Daniele; Zado, Erica S; Anter, Elad; Desai, Nimesh D; Callans, David J; Deo, Rajat; Frankel, David S; Hutchinson, Mathew D; Lin, David; Riley, Michael P; Schaller, Robert D; Supple, Gregory E; Santangeli, Pasquale; Acker, Michael A; Bavaria, Joseph E; Szeto, Wilson Y; Vallabhajosyula, Prashanth; Marchlinski, Francis E; Dixit, Sanjay

    2017-04-10

    Limited data exist on the long-term outcome of patients (pts) with non-ischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) refractory to conventional therapies undergoing surgical ablation (SA). We aimed to investigate the long-term survival and VT recurrence in NICM pts with VT refractory to radiofrequency catheter ablation (RFCA) who underwent SA. Consecutive pts with NICM and VT refractory to RFCA who underwent SA were included. VT substrate was characterized in the electrophysiology lab and targeted by RFCA. During SA, previous RFCA lesions/scars were identified and targeted with cryoablation (CA; 3 min/lesion; target -150 °C). Follow-up comprised office visits, ICD interrogations and the social security death index. Twenty consecutive patients with NICM who underwent SA (age 53 ± 16 years, 18 males, LVEF 41 ± 20%; dilated CM = 9, arrhythmogenic right ventricular CM = 3, hypertrophic CM = 2, valvular CM = 4, and mixed CM = 2) were studied. Percutaneous mapping/ablation in the electrophysiology lab was performed in 18 and 2 pts had primary SA. During surgery, 4.9 ± 4.0 CA lesions/pt were delivered to the endocardium (2) and epicardium (11) or both (7). VT-free survival was 72.5% at 1 year and over 43 ± 31 months (mos) (range 1-83mos), there was only one arrhythmia-related death. There was a significant reduction in ICD shocks in the 3-mos preceding SA vs. the entire follow-up period (6.6 ± 4.9 vs. 2.3 ± 4.3 shocks/pt, P = 0.001). In select pts with NICM and VT refractory to RFCA, SA guided by pre-operative electrophysiological mapping and ablation may be a therapeutic option.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-07-06

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

  16. Biological variation of high sensitive Troponin T in stable heart failure patients with ischemic or dilated cardiomyopathy.

    PubMed

    Frankenstein, Lutz; Remppis, Andrew; Giannitis, Evangelos; Frankenstein, Joerdis; Hess, Georg; Zdunek, Dietmar; Doesch, Andreas; Zugck, Christian; Katus, Hugo A

    2011-08-01

    High sensitive Troponin (hsTn) assays enable detection of minimal marker elevation in heart failure patients previously deemed Troponin negative. Biovariability, reference change values (RCV), and index of individuality (II) have not been previously described for hsTnT although serial testing is important in interpreting low concentrations. For these values, a difference between ischemic heart disease (IHD) and dilated cardiomyopathy (dCMP) appears conceivable. Change in hsTnT was determined alongside with clinical variables in 41 patients with stable chronic systolic dysfunction at 2-week-, 1-month-, 2-month-, and 3-month-intervals (IHD n = 17; dCMP n = 24). HsTnT was detectable in all patients. Individual hsTnT-variations at 2-week, 1-month, 2-month, and 3-month follow-up were 7.2, 22.6, 28.9, and 15.7%, respectively, corresponding to RCVs of 20.1, 62.5, 80.0, and 43.3%, respectively, for crude values. For log-normalised values, individual variations were 3.2, 2.8, 2.7, and 3.5%, respectively, corresponding to RCVs of 8.8, 7.9, 7.6, and 9.7%, respectively. The II was 0.03 to 0.33 according to interval. Aetiology of heart failure was not a consistent determinant of variation (p = 0.28; p = 0.07; p = 0.98; p = 0.03 for 2-week, 1-month, 2-month, and 3-month follow-up, respectively). While short-term biological variation of hsTnT is low, it becomes relatively more important for intermediate follow-up. It is not related to aetiology of heart failure. The corresponding indices of individuality indicate high individuality of values.

  17. Effect of Enalapril on Preventing Anthracycline-Induced Cardiomyopathy.

    PubMed

    Janbabai, Ghasem; Nabati, Maryam; Faghihinia, Mohsen; Azizi, Soheil; Borhani, Samaneh; Yazdani, Jamshid

    2017-04-01

    Anthracycline (ANT) is a topoisomerase-interacting agent that is used in most malignancy treatments. We investigated the efficacy of enalapril (angiotensin-converting enzyme inhibitor) in the prevention of ANT-induced cardiomyopathy. In this randomized, single-blind, and placebo-controlled study, 69 patients with a newly diagnosed malignancy for which ANT therapy was planned were randomly assigned to either a group receiving enalapril (n = 34) or placebo (n = 35). Echocardiography studies were performed before chemotherapy and at 6 months after randomization. Additionally, troponin I and creatinine kinase-MB (CK-MB) were measured 1 month after the initiation of chemotherapy. In the enalapril group, the mean left ventricular ejection fraction (LVEF) (p = 0.58) was the same at baseline and 6 months after randomization. Conversely, LVEF significantly decreased in the control group (p < 0.001). Additionally, LV end systolic volume and left atrial diameter were significantly increased compared with the baseline measures in the control group. According to the tissue Doppler study, the mitral annuli early diastolic (e') and peak systolic (s') velocities were significantly reduced, and the E (the peak early diastolic velocity)/e' ratio was significantly increased in the control group. Furthermore, the TnI and CK-MB levels were significantly higher in the control group than in the enalapril group. Enalapril appears efficacious in preserving systolic and diastolic function in cancer patients treated with ANTs.

  18. Prediction and prognosis of ventricular tachycardia recurrence after catheter ablation with remote magnetic navigation for electrical storm in patients with ischemic cardiomyopathy.

    PubMed

    Jin, Qi; Jacobsen, Peter Karl; Pehrson, Steen; Chen, Xu

    2017-08-17

    Ventricular tachycardia (VT) recurrence after catheter ablation for electrical storm is commonly seen in patients with ischemic cardiomyopathy (ICM). We hypothesized that VT recurrence can be predicted and be related to the all-cause death after VT storm ablation guided by remote magnetic navigation (RMN) in patients with ICM. A total of 54 ICM patients (87% male; mean age, 65 ± 7.1 years) presenting with VT storm undergoing acute ablation using RMN were enrolled. Acute complete ablation success was defined as noninducibility of any sustained monomorphic VT at the end of the procedure. Early VT recurrence was defined as the occurrence of sustained VT within 1 month after the first ablation. After a mean follow-up of 17.1 months, 27 patients (50%) had freedom from VT recurrence. Sustained VT recurred in 12 patients (22%) within 1 month following the first ablation. In univariate analysis, VT recurrence was associated with incomplete procedural success (hazard ratio [HR]: 6.25, 95% confidence interval [CI]: 1.20-32.47, P = 0.029), lack of amiodarone usage before ablation (HR: 4.71, 95% CI: 1.12-19.7, P = 0.034), and a longer procedural time (HR: 1.023, 95% CI: 1.00-1.05, P = 0.05). The mortality of patients with early VT recurrence was higher than that of patients without recurrence (P < 0.01). Inducibility of any VT at the end of procedure for VT storm guided by RMN is the strongest predictor of VT recurrence. ICM patients who have early recurrences after VT storm ablation are at high risk of all-cause death. © 2017 Wiley Periodicals, Inc.

  19. Myoangiogenesis after Cell Patch Cardiomyoplasty and Omentopexy in a Patient with Ischemic Cardiomyopathy

    PubMed Central

    Taheri, Syde A.; Ashraf, Hasmat; Merhige, Michael; Miletich, Robert S.; Satchidanand, Sateesh; Malik, Chetan; Naughton, John; Zhao, Qiang

    2005-01-01

    We describe a procedure to promote angiogenesis and impregnation of skeletal myoblast into infarcted myocardium. At the completion of coronary artery bypass surgery, the midline sternotomy incision was extended to open the abdomen, and the greater omentum was tailored to reach the myocardium. Four pieces of autologous rectus muscle were applied to the infarcted left ventricle. This implantation was reinforced by the greater omentum. Incisions were closed in the usual manner. Postoperatively, the patient showed significant improvements in left ventricular ejection fraction (from 0.15 to 0.40) and in exercise tolerance (from 3 METs to 6 METs, or 100%). Computed tomographic angiography and positron emission tomography demonstrated improved myocardial viability and vascularity in the ischemic segments of the left ventricle. Omentopexy and cell patch cardiomyoplasty in conjunction with coronary artery bypass surgery may stimulate myogenesis and angiogenesis in avascular, dyskinetic scar tissue of left ventricle; in this preliminary study, this procedure appeared to improve the functional capacity of the left ventricle. PMID:16429914

  20. Patient with Eating Disorder, Carnitine Deficiency and Dilated Cardiomyopathy.

    PubMed

    Fotino, A Domnica; Sherma, A

    2015-01-01

    Dilated cardiomyopathy is characterized by a dilated and poorly functioning left ventricle and can result from several different etiologies including ischemic, infectious, metabolic, toxins, autoimmune processes or nutritional deficiencies. Carnitine deficiency-induced cardiomyopathy (CDIM) is an uncommon cause of dilated cardiomyopathy that can go untreated if not considered. Here, we describe a 30-year-old woman with an eating disorder and recent percutaneous endoscopic gastrotomy (PEG) tube placement for weight loss admitted to the hospital for possible PEG tube infection. Carnitine level was found to be low. Transthoracic echocardiogram (TTE) revealed ejection fraction 15%. Her hospital course was complicated by sepsis from a peripherally inserted central catheter (PICC). She was discharged on a beta-blocker and carnitine supplementation. One month later her cardiac function had normalized. Carnitine deficiency-induced myopathy is an unusual cause of cardiomyopathy and should be considered in adults with decreased oral intake or malabsorption who present with cardiomyopathy.

  1. Stress-induced cardiomyopathy associated with ipratropium bromide therapy in a patient with chronic obstructive pulmonary disease.

    PubMed

    Melão, Filipa; Nunes, José P L; Vasconcelos, Mariana; Dias, Paula; Almeida, Pedro B; Rodrigues, Rui; Pinho, Teresa; Madureira, António; Maciel, Maria J

    2014-03-01

    Stress-induced cardiomyopathy, also known as 'broken heart syndrome' or Takotsubo cardiomyopathy, is characterized by transient systolic dysfunction of the apical and/or mid segments of the left ventricle, in the absence of significant coronary artery disease. We report the case of a 56-year-old male patient with chronic obstructive pulmonary disease (COPD), with stress-induced cardiomyopathy associated with the use of ipratropium bromide, administered in the context of an acute exacerbation of COPD.

  2. Induced pluripotent stem cells in the inherited cardiomyopathies: From disease mechanisms to novel therapies.

    PubMed

    Ross, Samantha Barratt; Fraser, Stuart T; Semsarian, Christopher

    2016-11-01

    Inherited cardiomyopathies lead to diverse clinical outcomes including heart failure, arrhythmias, and sudden death. Mutations in over 100 genes have been implicated in the pathogenesis of genetic heart diseases, including the main inherited cardiomyopathies, such as hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathies. Understanding how these gene mutations lead to clinical disease and the various secondary genetic and environmental factors, which may modify the clinical phenotype, are key areas of research ultimately influencing diagnosis and management of patients. The emergence of patient-derived induced pluripotent stem cells (iPSCs), which can be differentiated into functional cardiomyocytes (CMs) in vitro, may provide an exciting new approach to understand disease mechanisms underpinning inherited heart diseases. This review will focus specifically on the key role of iPSC-based studies in the inherited cardiomyopathies, both in their potential utility as well as the significant challenges they present. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. CELLULAR MECHANISM OF PREMATURE VENTRICULAR CONTRACTION-INDUCED CARDIOMYOPATHY

    PubMed Central

    Wang, Youhong; Eltit, Jose M.; Kaszala, Karoly; Tan, Alex; Jiang, Min; Zhang, Mei; Tseng, Gea-Ny; Huizar, Jose F.

    2014-01-01

    Background Frequent premature ventricular contractions (PVCs) are associated with increased risk for sudden cardiac death (SCD) and can cause secondary cardiomyopathy (CM). Objective We sought to determine the mechanism(s) responsible for prolonged refractory period and LV dysfunction demonstrated in our canine model of PVC-induced CM. Methods Single myocytes were isolated from LV free wall of PVC and control canines, and used for patch clamp recording, [Ca]i measurements and immunocytochemistry/confocal microscopy. LV tissues adjacent to area of myocyte isolation were used for immunoblot quantification of protein expression. Results In PVC group, LVEF declined from 57.6±1.5% to 30.4±3.1% after ≥ 4 months of ventricular bigeminy. Compared to control myocytes, PVC myocytes had reduced densities of both outward (Ito and IK1) and inward (ICaL) currents, but no consistent changes in IKr or IKs. The reduction in Ito, IK1 and ICaL was accompanied by decreased protein levels of their channel subunits. The degrees of reduction in Ito, IK1 and ICaL varied among PVC myocytes, creating marked heterogeneity in action potential (AP) configurations and durations. PVC myocytes showed impaired Ca-induced Ca release from SR, without increase in SR Ca leak or decrease in SR Ca store. This was accompanied by a decrease in dyad scaffolding protein, junctophilin-2, and loss of Cav1.2 registry with Ca-releasing channels (RyR2). Conclusion PVCs increase dispersion of AP configuration/duration, a risk factor for SCD, due to heterogeneous reduction in Ito, IK1 and ICaL. The E-C coupling is impaired due to decrease in ICaL and Cav1.2 misalignment with respect to RyR2. PMID:25046857

  4. Short-term vs. long-term heart rate variability in ischemic cardiomyopathy risk stratification

    PubMed Central

    Voss, Andreas; Schroeder, Rico; Vallverdú, Montserrat; Schulz, Steffen; Cygankiewicz, Iwona; Vázquez, Rafael; Bayés de Luna, Antoni; Caminal, Pere

    2013-01-01

    In industrialized countries with aging populations, heart failure affects 0.3–2% of the general population. The investigation of 24 h-ECG recordings revealed the potential of nonlinear indices of heart rate variability (HRV) for enhanced risk stratification in patients with ischemic heart failure (IHF). However, long-term analyses are time-consuming, expensive, and delay the initial diagnosis. The objective of this study was to investigate whether 30 min short-term HRV analysis is sufficient for comparable risk stratification in IHF in comparison to 24 h-HRV analysis. From 256 IHF patients [221 at low risk (IHFLR) and 35 at high risk (IHFHR)] (a) 24 h beat-to-beat time series (b) the first 30 min segment (c) the 30 min most stationary day segment and (d) the 30 min most stationary night segment were investigated. We calculated linear (time and frequency domain) and nonlinear HRV analysis indices. Optimal parameter sets for risk stratification in IHF were determined for 24 h and for each 30 min segment by applying discriminant analysis on significant clinical and non-clinical indices. Long- and short-term HRV indices from frequency domain and particularly from nonlinear dynamics revealed high univariate significances (p < 0.01) discriminating between IHFLR and IHFHR. For multivariate risk stratification, optimal mixed parameter sets consisting of 5 indices (clinical and nonlinear) achieved 80.4% AUC (area under the curve of receiver operating characteristics) from 24 h HRV analysis, 84.3% AUC from first 30 min, 82.2 % AUC from daytime 30 min and 81.7% AUC from nighttime 30 min. The optimal parameter set obtained from the first 30 min showed nearly the same classification power when compared to the optimal 24 h-parameter set. As results from stationary daytime and nighttime, 30 min segments indicate that short-term analyses of 30 min may provide at least a comparable risk stratification power in IHF in comparison to a 24 h analysis period. PMID:24379785

  5. Short-term vs. long-term heart rate variability in ischemic cardiomyopathy risk stratification.

    PubMed

    Voss, Andreas; Schroeder, Rico; Vallverdú, Montserrat; Schulz, Steffen; Cygankiewicz, Iwona; Vázquez, Rafael; Bayés de Luna, Antoni; Caminal, Pere

    2013-01-01

    In industrialized countries with aging populations, heart failure affects 0.3-2% of the general population. The investigation of 24 h-ECG recordings revealed the potential of nonlinear indices of heart rate variability (HRV) for enhanced risk stratification in patients with ischemic heart failure (IHF). However, long-term analyses are time-consuming, expensive, and delay the initial diagnosis. The objective of this study was to investigate whether 30 min short-term HRV analysis is sufficient for comparable risk stratification in IHF in comparison to 24 h-HRV analysis. From 256 IHF patients [221 at low risk (IHFLR) and 35 at high risk (IHFHR)] (a) 24 h beat-to-beat time series (b) the first 30 min segment (c) the 30 min most stationary day segment and (d) the 30 min most stationary night segment were investigated. We calculated linear (time and frequency domain) and nonlinear HRV analysis indices. Optimal parameter sets for risk stratification in IHF were determined for 24 h and for each 30 min segment by applying discriminant analysis on significant clinical and non-clinical indices. Long- and short-term HRV indices from frequency domain and particularly from nonlinear dynamics revealed high univariate significances (p < 0.01) discriminating between IHFLR and IHFHR. For multivariate risk stratification, optimal mixed parameter sets consisting of 5 indices (clinical and nonlinear) achieved 80.4% AUC (area under the curve of receiver operating characteristics) from 24 h HRV analysis, 84.3% AUC from first 30 min, 82.2 % AUC from daytime 30 min and 81.7% AUC from nighttime 30 min. The optimal parameter set obtained from the first 30 min showed nearly the same classification power when compared to the optimal 24 h-parameter set. As results from stationary daytime and nighttime, 30 min segments indicate that short-term analyses of 30 min may provide at least a comparable risk stratification power in IHF in comparison to a 24 h analysis period.

  6. Premature ventricular contraction-induced cardiomyopathy: an emerging entity.

    PubMed

    Tran, Cao Thach; Calkins, Hugh

    2016-11-01

    Over the past 10-15 years, there has been an increasing amount of evidence that frequent premature ventricular contractions (PVCs) are associated with the development of a reversible cardiomyopathy. Areas covered: This review considers current evidence of the association between PVCs and the development of cardiomyopathy, risk factors, and available treatment modalities based on available published literature. Expert commentary: The field is rapidly evolving, although evidence is based primarily on observational studies. Pharmacological therapy may suppress PVCs and lead to resolution of cardiomyopathy in many patients. In addition, catheter ablation has emerged as an effective treatment modality that has compared favorably to pharmacological antiarrhythmic therapy. The excellent outcome in successfully treated patients should prompt physicians to consider whether frequent PVCs may be a contributing factor in patients with heart failure.

  7. Dilated Cardiomyopathy Induced by Chronic Starvation and Selenium Deficiency

    PubMed Central

    2016-01-01

    Protein energy malnutrition (PEM) has been rarely documented as a cause of cardiovascular abnormalities, including dilated cardiomyopathy. Selenium is responsible for antioxidant defense mechanisms in cardiomyocytes, and its deficiency in the setting of PEM and disease related malnutrition (DRM) may lead to exacerbation of the dilated cardiomyopathy. We report a rare case of a fourteen-year-old boy who presented with symptoms of congestive heart failure due to DRM and PEM (secondary to chronic starvation) along with severe selenium deficiency. An initial echocardiogram showed severely depressed systolic function consistent with dilated cardiomyopathy. Aggressive nutritional support and replacement of selenium and congestive heart failure medications that included diuretics and ACE inhibitors with the addition of carvedilol led to normalization of the cardiac function within four weeks. He continues to have significant weight gain and is currently completely asymptomatic from a cardiovascular standpoint. PMID:27994905

  8. Role of implantable cardioverter defibrillator in non-ischemic cardiomyopathy: a systematic review and meta-analysis of prospective randomized clinical trials.

    PubMed

    Romero, Jorge; Chaudhary, Rahul; Garg, Jalaj; Lupercio, Florentino; Shah, Neeraj; Gupta, Rahul; Nazir, Talha; Bozorgnia, Babak; Natale, Andrea; Di Biase, Luigi

    2017-09-01

    A mortality benefit in patients with implantable cardioverter defibrillator (ICD) in ischemic cardiomyopathy is well established. However, the benefit of ICD implantation in non-ischemic cardiomyopathy (NICM) on total mortality remains uncertain. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) evaluating the role of primary prevention ICD in NICM patients. We performed a systematic review on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through February 2017 to identify RCT evaluating the role of ICD in NICM patients. Mantel-Haenszel risk ratio (RR) fixed effects model was used to summarize data across treatment arms. If heterogeneity (I (2)) ≥25, random effects model was used instead. We analyzed a total of 2573 patients from five RCTs comparing ICD with medical therapy in patients with NICM. The mean follow up for the trials was 48 ± 22 months. There was a significant reduction in (a) all-cause mortality (RR 0.84, 95% CI 0.71-0.99, p = 0.03) and (b) sudden cardiac death (RR 0.47, 95% CI 0.30-0.73, p < 0.001) in ICD group versus medical therapy. Our analysis demonstrates that the use of ICD for primary prevention is associated with a reduction in all-cause mortality and SCD in patients with NICM.

  9. Prevalence and risk factors of sepsis-induced cardiomyopathy

    PubMed Central

    Sato, Ryota; Kuriyama, Akira; Takada, Tadaaki; Nasu, Michitaka; Luthe, Sarah Kyuragi

    2016-01-01

    Abstract The aim of the study is to evaluate the epidemiology and clinical features of sepsis-induced cardiomyopathy (SICM). A retrospective cohort study was conducted. A total of 210 adult patients with sepsis or septic shock admitted to a Japanese tertiary care hospital from January 1, 2013, to December 31, 2015, who underwent transthoracic echocardiography (TTE) on admission. The definition of SICM was ejection fraction (EF) < 50% and a ≥10% decrease compared to the baseline EF which recovered within 2 weeks, in sepsis or septic shock patients. Our primary outcome was the incidence rate of SICM. Our secondary outcomes were the in-hospital mortality rate and length of intensive care unit (ICU) stay according to the presence or absence of SICM. In total, 29 patients (13.8%) were diagnosed with SICM. The prevalence rate of SICM was significantly higher in male than in female (P = 0.02). Multivariate logistic regression analyses revealed that the incidence of SICM was associated with younger age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95–0.99), higher lactate level on admission (OR, 1.18; 95% CI, 1.05–1.32) and history of heart failure (HF) (OR, 3.77; 95% CI, 1.37–10.40). There were no significant differences in the in-hospital and 30-day mortality between patients with and without SICM (24.1% vs 12.7%, P = 0.15; 20.7% vs 12.1%, P = 0.23). Lengths of hospital and ICU stay were significantly longer in patients with SICM than in those without SICM (median, 43 vs 26 days, P = 0.04; 9 vs 5 days, P < 0.01). SICM developed in 13.8% of patients with sepsis and septic shock. A younger age, higher lactate levels on admission and history of HF were risk factors. PMID:27684877

  10. Acute and Chronic Pheochromocytoma-Induced Cardiomyopathies: Different Prognoses?

    PubMed Central

    Batisse-Lignier, Marie; Pereira, Bruno; Motreff, Pascal; Pierrard, Romain; Burnot, Christelle; Vorilhon, Charles; Maqdasy, Salwan; Roche, Béatrice; Desbiez, Francoise; Clerfond, Guillaume; Citron, Bernard; Lusson, Jean-René; Tauveron, Igor; Eschalier, Romain

    2015-01-01

    Abstract Pheochromocytoma and paraganglioma (PPG) are rare and late-diagnosed catecholamine secreting tumors, which may be associated with unrecognized and/or severe cardiomyopathies. We performed a computer-assisted systematic search of the electronic Medline databases using the MESH terms “myocarditis,” “myocardial infarction,” “Takotsubo,” “stress cardiomyopathy,” “cardiogenic shock”, or “dilated cardiomyopathy,” and “pheochromocytoma” or “paraganglioma” from 1961 to August 2012. All detailed case reports of cardiomyopathy due to a PPG, without coronary stenosis, and revealed by acute symptoms were included and analyzed. A total of 145 cases reports were collected (49 Takotsubo Cardiomyopathies [TTC] and 96 other Catecholamine Cardiomyopathies [CC]). At initial presentation, prevalence of high blood pressure (87.7%), chest pain (49.0%), headaches (47.6%), palpitations (46.9%), sweating (39.3%), and shock (51.0%) were comparable between CC and TTC. Acute pulmonary edema (58.3% vs 38.8%, P = 0.03) was more frequent in CC. There was no difference in proportion of patients with severe left ventricular systolic dysfunction (LV Ejection Fraction [LVEF] < 30%) at initial presentation between both groups (P = 0.15). LVEF recovery before (64.9% vs 40.8%, P = 0.005) and after surgical resection (97.7% vs73.3%, P = 0.001) was higher in the TTC group. Death occurred in 11 cases (7.6%). In multivariate analysis, only TTC was associated with a better LV recovery (0.15 [0.03–0.67], P = 0.03). Pheochromocytoma and paraganglioma can lead to different cardiomyopathies with the same brutal and life-threatening initial clinical presentation but with a different recovery rate. Diagnosis of unexplained dilated cardiomyopathy or TTC should lead clinicians to a specific search for PPG. PMID:26683930

  11. An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy

    PubMed Central

    Talavera, Jesús; Fernández-Del-Palacio, María Josefa; García-Nicolás, Obdulio; Seva, Juan; Brooks, Gavin; Moraleda, Jose M.

    2015-01-01

    Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality. PMID:26788502

  12. An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy.

    PubMed

    Talavera, Jesús; Giraldo, Alejandro; Fernández-Del-Palacio, María Josefa; García-Nicolás, Obdulio; Seva, Juan; Brooks, Gavin; Moraleda, Jose M

    2015-01-01

    Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality.

  13. Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Qin, J. X.; Shiota, T.; McCarthy, P. M.; Firstenberg, M. S.; Greenberg, N. L.; Tsujino, H.; Bauer, F.; Travaglini, A.; Hoercher, K. J.; Buda, T.; Smedira, N. G.; Thomas, J. D.

    2000-01-01

    BACKGROUND: Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. METHODS AND RESULTS: Thirty patients who underwent IE (mean age 61+/-8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42+/-67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99+/-40, 67+/-26, and 71+/-31 mL/m(2), respectively; ESVI 72+/-37, 40+/-21, and 42+/-22 mL/m(2), respectively; P:<0.05). LV ejection fraction increased significantly and remained higher (0.29+/-0.11, 0.43+/-0.13, and 0.42+/-0.09, respectively, P:<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22+/-12, 53+/-24, and 58+/-21 mL, respectively, P:<0.005). New York Heart Association functional class at an average 285+/-144 days of clinical follow-up significantly improved from 3.0+/-0.8 to 1.8+/-0.8 (P:<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman's rho=0.58 and 0.60, respectively). CONCLUSIONS: RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.

  14. Echocardiographic and hemodynamic determinants of right coronary artery flow reserve and phasic flow pattern in advanced non-ischemic cardiomyopathy

    PubMed Central

    Graziosi, Pedro; Ianni, Barbara; Ribeiro, Expedito; Perin, Marco; Beck, Leonardo; Meneghetti, Claudio; Mady, Charles; Filho, Eulogio Martinez; Ramires, Jose AF

    2007-01-01

    Background In patients with advanced non-ischemic cardiomyopathy (NIC), right-sided cardiac disturbances has prognostic implications. Right coronary artery (RCA) flow pattern and flow reserve (CFR) are not well known in this setting. The purpose of this study was to assess, in human advanced NIC, the RCA phasic flow pattern and CFR, also under right-sided cardiac disturbances, and compare with left coronary circulation. As well as to investigate any correlation between the cardiac structural, mechanical and hemodynamic parameters with RCA phasic flow pattern or CFR. Methods Twenty four patients with dilated severe NIC were evaluated non-invasively, even by echocardiography, and also by cardiac catheterization, inclusive with Swan-Ganz catheter. Intracoronary Doppler (Flowire) data was obtained in RCA and left anterior descendent coronary artery (LAD) before and after adenosine. Resting RCA phasic pattern (diastolic/systolic) was compared between subgroups with and without pulmonary hypertension, and with and without right ventricular (RV) dysfunction; and also with LAD. RCA-CFR was compared with LAD, as well as in those subgroups. Pearson's correlation analysis was accomplished among echocardiographic (including LV fractional shortening, mass index, end systolic wall stress) more hemodynamic parameters with RCA phasic flow pattern or RCA-CFR. Results LV fractional shortening and end diastolic diameter were 15.3 ± 3.5 % and 69.4 ± 12.2 mm. Resting RCA phasic pattern had no difference comparing subgroups with vs. without pulmonary hypertension (1.45 vs. 1.29, p = NS) either with vs. without RV dysfunction (1.47 vs. 1.23, p = NS); RCA vs. LAD was 1.35 vs. 2.85 (p < 0.001). It had no significant correlation among any cardiac mechanical or hemodynamic parameter with RCA-CFR or RCA flow pattern. RCA-CFR had no difference compared with LAD (3.38 vs. 3.34, p = NS), as well as in pulmonary hypertension (3.09 vs. 3.10, p = NS) either in RV dysfunction (3.06 vs. 3.22, p

  15. Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Qin, J. X.; Shiota, T.; McCarthy, P. M.; Firstenberg, M. S.; Greenberg, N. L.; Tsujino, H.; Bauer, F.; Travaglini, A.; Hoercher, K. J.; Buda, T.; hide

    2000-01-01

    BACKGROUND: Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. METHODS AND RESULTS: Thirty patients who underwent IE (mean age 61+/-8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42+/-67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99+/-40, 67+/-26, and 71+/-31 mL/m(2), respectively; ESVI 72+/-37, 40+/-21, and 42+/-22 mL/m(2), respectively; P:<0.05). LV ejection fraction increased significantly and remained higher (0.29+/-0.11, 0.43+/-0.13, and 0.42+/-0.09, respectively, P:<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22+/-12, 53+/-24, and 58+/-21 mL, respectively, P:<0.005). New York Heart Association functional class at an average 285+/-144 days of clinical follow-up significantly improved from 3.0+/-0.8 to 1.8+/-0.8 (P:<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman's rho=0.58 and 0.60, respectively). CONCLUSIONS: RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.

  16. Psychology of earthquake-induced stress cardiomyopathy, myocardial infarction and non-cardiac chest pain.

    PubMed

    Zarifeh, J A; Mulder, R T; Kerr, A J; Chan, C W; Bridgman, P G

    2012-04-01

    To compare psychological factors in patients presenting to hospital with earthquake-induced stress cardiomyopathy, myocardial infarction (MI) and non-cardiac chest pain. We hypothesised that patients with stress cardiomyopathy and non-cardiac chest pain would be more psychologically vulnerable than those with MI. Cardiology admitting staff in the week following the September 2010 Christchurch earthquake prospectively identified patients with earthquake-precipitated chest pain. Males were excluded. All consenting women met diagnostic criteria for one of the three conditions. Patients underwent a semistructured interview with a senior clinical psychologist who was blind to the cardiac diagnosis. Premorbid psychological factors, experience of the earthquake and psychological response were assessed using a range of validated tools. Seventeen women were included in the study, six with stress cardiomyopathy, five with MI and six with non-cardiac chest pain. Earthquake experiences were notably similar across the groups. Patients with non-cardiac chest pain scored high on the hospital anxiety and depression scale, the health anxiety questionnaire, the Eysenck neuroticism scale and the Impact of Event scale. Women with stress cardiomyopathy scored as the most psychologically robust. Depression and extroversion scores were the same across groups. Our hypothesis was incorrect. Women with non-cardiac chest pain following an earthquake have higher anxiety and neuroticism scores than women with either MI or stress cardiomyopathy. Stress cardiomyopathy following an earthquake is not specific to psychologically vulnerable women. The psychology of natural disaster-induced stress cardiomyopathy may differ from that of sporadic cases. © 2012 The Authors. Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

  17. SENP5, a SUMO isopeptidase, induces apoptosis and cardiomyopathy.

    PubMed

    Kim, Eun Young; Zhang, Yi; Beketaev, Ilimbek; Segura, Ana Maria; Yu, Wei; Xi, Yutao; Chang, Jiang; Wang, Jun

    2015-01-01

    Cardiomyopathy presents a major health issue and is a leading cause of heart failure. Although a subset of familial cardiomyopathy is associated with genetic mutations, over 50% of cardiomyopathy is defined as idiopathic, the mechanisms underlying which are under intensive investigation. SUMO conjugation is a dynamic posttranslational modification that can be readily reversed by the activity of sentrin-specific proteases (SENPs). However, whether SENPs are implicated in heart disease pathophysiology remains unexplored. We observed a significant increase in the level of SENP5, a SUMO isopeptidase, in human idiopathic failing hearts. To reveal whether it plays a role in the pathogenesis of cardiac muscle disorders, we used a gain-of-function approach to overexpress SENP5 in murine cardiomyocytes (SENP5 transgenic, SENP5-Tg). Overexpression of SENP5 led to cardiac dysfunction, accompanied by decreased cardiomyocyte proliferation and elevated apoptosis. The increase in apoptosis preceded other detectable pathological changes, suggesting its causal link to cardiomyopathy. Further examination of SENP5-Tg hearts unveiled a decrease in SUMO attachment to dynamin related protein (Drp1), a factor critical for mitochondrial fission. Correspondingly, the mitochondria of SENP5-Tg hearts at an early developmental stage were significantly larger compared with those in the control hearts, suggesting that desumoylation of Drp1 at least partially accounts for the cardiac phenotypes observed in the SENP5-Tg mice. Finally, overexpression of Bcl2 in SENP5-Tg hearts improved cardiac function of SENP5-Tg mice, further supporting the notion that SENP5 mainly targets mitochondrial function in vivo. Our findings demonstrate an important role of the desumoylation enzyme SENP5 in the development of cardiac muscle disorders, and point to the SUMO conjugation pathway as a potential target in the prevention/treatment of cardiomyopathy. This article is part of a Special Issue entitled

  18. Metabolic stress–induced activation of FoxO1 triggers diabetic cardiomyopathy in mice

    PubMed Central

    Battiprolu, Pavan K.; Hojayev, Berdymammet; Jiang, Nan; Wang, Zhao V.; Luo, Xiang; Iglewski, Myriam; Shelton, John M.; Gerard, Robert D.; Rothermel, Beverly A.; Gillette, Thomas G.; Lavandero, Sergio; Hill, Joseph A.

    2012-01-01

    The leading cause of death in diabetic patients is cardiovascular disease; diabetic cardiomyopathy is typified by alterations in cardiac morphology and function, independent of hypertension or coronary disease. However, the molecular mechanism that links diabetes to cardiomyopathy is incompletely understood. Insulin resistance is a hallmark feature of diabetes, and the FoxO family of transcription factors, which regulate cell size, viability, and metabolism, are established targets of insulin and growth factor signaling. Here, we set out to evaluate a possible role of FoxO proteins in diabetic cardiomyopathy. We found that FoxO proteins were persistently activated in cardiac tissue in mice with diabetes induced either genetically or by high-fat diet (HFD). FoxO activity was critically linked with development of cardiomyopathy: cardiomyocyte-specific deletion of FoxO1 rescued HFD-induced declines in cardiac function and preserved cardiomyocyte insulin responsiveness. FoxO1-depleted cells displayed a shift in their metabolic substrate usage, from free fatty acids to glucose, associated with decreased accumulation of lipids in the heart. Furthermore, we found that FoxO1-dependent downregulation of IRS1 resulted in blunted Akt signaling and insulin resistance. Together, these data suggest that activation of FoxO1 is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease. PMID:22326951

  19. Incidence and risk factors for clozapine-induced myocarditis and cardiomyopathy at a regional mental health service in Australia.

    PubMed

    Youssef, Daniel L; Narayanan, Pradeep; Gill, Neeraj

    2016-04-01

    To determine the incidence of clozapine-induced myocarditis and cardiomyopathy and identify risk factors. A cohort of 129 patients initiated on clozapine at Toowoomba Mental Health Service from year 2000 until 2011 was examined to evaluate cases of myocarditis and cardiomyopathy. Risk factors were analysed using multivariable logistic regression. The incidence of clozapine-induced myocarditis and cardiomyopathy was 3.88% and 4.65% (or 2.26 per 100 patient years), respectively. A significant association was identified between clozapine-induced myocarditis and SSRI use (p = 0.043). Subclinical cardiomyopathy was identified in the absence of symptoms in the majority of cases. These results illustrate a high incidence of clozapine-induced myocarditis as well as cardiomyopathy, reinforcing the need for a standardised, mandatory monitoring scheme. Concomitant SSRI use as one such potential predictor merits further study. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  20. The role of HIF in cobalt-induced ischemic tolerance.

    PubMed

    Jones, S M; Novak, A E; Elliott, J P

    2013-11-12

    Understanding the endogenous survival pathways induced by ischemic tolerance may yield targets for neuroprotection from stroke. One well-studied pathway reported to be evoked by preconditioning stimuli is the transcription factor HIF (hypoxia-inducible factor). However, whether HIF induction by ischemic insults is neuroprotective or toxic is still unclear. We examined the ability of three prolyl-hydroxylase inhibitors, which induce HIF, to protect hippocampal cultures from oxygen-glucose deprivation. Hippocampal cultures were exposed to ischemic preconditioning or various concentrations of cobalt chloride, deferoxamine (DFO) or dimethyloxylalyglycine (DMOG), prior to lethal oxygen-glucose deprivation (OGD). Cell survival of neurons and astrocytes was determined with dual-label immunocytochemistry. The induction of HIF targets was assessed in mixed as well as astrocyte-enriched cultures. Ischemic preconditioning, as well as low concentrations of cobalt and DFO, enhanced the survival of neurons following OGD. However, DMOG exacerbates OGD-induced neuronal death. At low concentrations, all three prolyl-hydroxylase (PHD) inhibitors increased the survival of astrocytes. Neuroprotective concentrations of cobalt induced the transcription of the cytokine erythropoietin (EPO) in astrocyte cultures. In addition, pretreatment with recombinant human erythropoietin (rH-EPO) also protected neurons from OGD. Our data suggest that HIF-induced EPO, released from astrocytes, protects neurons from OGD. However, the three PHD inhibitors each exhibited different neuroprotective profiles at low concentrations, suggesting that not all PHD inhibitors are created equal. The protective effects at low doses is reminiscent of HIF involvement in ischemic tolerance, in which sub-lethal insults induce HIF pathways resulting in neuroprotection, whereas the high-dose toxicity suggests that over-activation of HIF is not always protective. Therefore, the choice of inhibitor and dose may determine

  1. Effect of dl-sotalol on mortality and recurrence of ventricular tachyarrhythmias: ischemic compared to nonischemic cardiomyopathy.

    PubMed

    Furushima, Hiroshi; Chinushi, Masaomi; Okamura, Kazuki; Komura, Satoru; Tanabe, Yasutaka; Sato, Akinori; Izumi, Daisuke; Aizawa, Yoshifusa

    2007-09-01

    We compared the effectiveness of sotalol on mortality and the recurrence of ventricular tachyarrhythmia (VTA) between idiopathic dilated cardiomyopathy (IDCM) and coronary artery disease (CAD). Forty patients with spontaneous VTA and induced VTA associated with CAD (n = 23) and IDCM (n = 17) were studied. In all patients, sotalol was prescribed and an electrophysiologic study (EPS) was performed to evaluate its effect on the induction of VTA. There were no significant differences in left ventricular ejection fraction (LVEF) between CAD and IDCM (35%+/- 10% vs. 35%+/- 12%). After sotalol, there were no significant differences in the QTc interval on electrocardiogram (ECG) or in the effective refractory period in the apex of the right ventricle between the two groups, but sotalol was more effective in preventing the induction of VTA in CAD than in IDCM (65% vs. 29%; P < 0.05). During a mean follow-up period of 47 +/- 27 months, the overall VTA recurrence rate was significantly lower in CAD than in IDCM (P < 0.01). The all-cause mortality rate tended to be lower in CAD than in IDCM, but the difference was not significant (P = 0.07). Electrical storm (ES) occurred more frequently in IDCM than in CAD, (41% vs. 13%; P < 0.05), and all patients with ES (n = 10) failed to respond to sotalol as assessed by EPS. Sotalol reduced the overall VTA recurrence rate and all-cause mortality more in CAD than in IDCM.

  2. Reversal of Ischemic Cardiomyopathy with Sca-1+ Stem Cells Modified with Multiple Growth Factors

    PubMed Central

    Li, Ning; Pasha, Zeeshan; Ashraf, Muhammad

    2014-01-01

    Background We hypothesized that bone marrow derived Sca-1+ stem cells (BM Sca-1+) transduced with multiple therapeutic cytokines with diverse effects will induce faster angiomyogenic differentiation in the infarcted myocardium. Methods and Results BM Sca-1+ were purified from transgenic male mice expressing GFP. Plasmids encoding for select quartet of growth factors, i.e., human IGF-1, VEGF, SDF-1α and HGF were prepared and used for genetic modification of Sca-1+ cells (GFSca-1+). Scramble transfected cells (ScSca-1+) were used as a control. RT-PCR and western blotting showed significantly higher expression of the growth factors in GFSca-1+. Besides the quartet of the therapeutic growth factors, PCR based growth factor array showed upregulation of multiple angiogenic and prosurvival factors such as Ang-1, Ang-2, MMP9, Cx43, BMP2, BMP5, FGF2, and NGF in GFSca-1+ (p<0.01 vs ScSca-1+). LDH and TUNEL assays showed enhanced survival of GFSca-1+ under lethal anoxia (p<0.01 vs ScSca-1+). MTS assay showed significant increased cell proliferation in GFSca-1+ (p<0.05 vs ScSca-1+). For in vivo study, female mice were grouped to receive the intramyocardial injection of 15 μl DMEM without cells (group-1) or containing 2.5×105 ScSca-1+ (group-2) or GFSca-1+ (group-3) immediately after coronary artery ligation. As indicated by Sry gene, a higher survival of GFSca-1+ in group-3 on day4 (2.3 fold higher vs group-2) was observed with massive mobilization of stem and progenitor cells (cKit+, Mdr1+, Cxcr4+ cells). Heart tissue sections immunostained for actinin and Cx43 at 4 weeks post engraftment showed extensive myofiber formation and expression of gap junctions. Immunostaining for vWF showed increased blood vessel density in both peri-infarct and infarct regions in group-3. Infarct size was attenuated and the global heart function was improved in group-3 as compared to group-2. Conclusions Administration of BM Sca-1+ transduced with multiple genes is a novel approach to treat

  3. Comparison of Transesophageal and Transthoracic Echocardiographic Measurements of Mechanism and Severity of Mitral Regurgitation in Ischemic Cardiomyopathy (From the STICH trial)

    PubMed Central

    Grayburn, Paul A.; She, Lilin; Roberts, Brad J.; Golba, Krzysztof S.; Mokrzycki, Krzysztof; Drozdz, Jaroslaw; Cherniavsky, Alexander; Przybylski, Roman; Wrobel, Krzysztof; Asch, Federico M.; Holly, Thomas A.; Haddad, Haissam; Yii, Michael; Maurer, Gerald; Kron, Irving; Schaff, Hartzell; Velazquez, Eric J.; Oh, Jae K.

    2015-01-01

    Mitral regurgitation (MR) is common in ischemic heart disease and contributes to symptoms and mortality. This report compares the results of baseline transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) imaging of the mechanism and severity of functional MR in patients with ischemic cardiomyopathy in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Independent core labs measured both TTE and TEE images on 196 STICH patients. Common measurements to both modalities included MR grade, mitral valve tenting height and tenting area, and mitral annular diameter. For each parameter, correlations were assessed using Spearman rank correlation coefficients. A modest correlation (figure) was present between TEE and TTE for overall MR grade (n=176, r=0.52). For mechanism of MR, modest correlations were present for long-axis tenting height (n=152, r=0.35), tenting area (n=128, r=0.27), and long-axis mitral annulus diameter (n=123, r=0.41). For each measurement, there was significant scatter. Potential explanations for the scatter include different orientation of the imaging planes between TEE and TTE, a mean temporal delay of 6 days between TEE and TTE, and statistically significant differences in heart rate and blood pressure and weight between studies. In conclusion, TEE and TTE measurements of MR mechanism and severity correlate only modestly with enough scatter in the data that they are not interchangeable. PMID:26170249

  4. Nightmare-induced atypical midventricular tako-tsubo cardiomyopathy.

    PubMed

    Fibbi, Veronica; Ballo, Piercarlo; Nannini, Marco; Consoli, Lorenzo; Chechi, Tania; Bribani, Andrea; Fiorentino, Francesca; Chiodi, Leandro; Zuppiroli, Alfredo

    2015-01-01

    Tako-Tsubo cardiomyopathy (TTC) is a reversible cardiomyopathy characterized by acute left ventricular segmental dysfunction, whose clinical presentation resembles that of acute myocardial infarction. The syndrome often follows a psychophysical stressful event and is characterized by echocardiographic evidence of akinesia of the left ventricular mid-apical segments. Atypical echocardiographic patterns of TTC have recently been described, often triggered by emotional stressors, rather than physical. In this report, we describe a case of atypical TTC triggered by an unusual stressor (recurrent nightmare) in a 45-year-old woman, with peculiar clinical presentation and evolution characterized by persistent loss of consciousness, neurological deterioration, absence of typical symptoms of TTC, and features suggestive of a hysterical crisis.

  5. Nightmare-Induced Atypical Midventricular Tako-Tsubo Cardiomyopathy

    PubMed Central

    Fibbi, Veronica; Ballo, Piercarlo; Nannini, Marco; Consoli, Lorenzo; Chechi, Tania; Bribani, Andrea; Fiorentino, Francesca; Chiodi, Leandro; Zuppiroli, Alfredo

    2015-01-01

    Tako-Tsubo cardiomyopathy (TTC) is a reversible cardiomyopathy characterized by acute left ventricular segmental dysfunction, whose clinical presentation resembles that of acute myocardial infarction. The syndrome often follows a psychophysical stressful event and is characterized by echocardiographic evidence of akinesia of the left ventricular mid-apical segments. Atypical echocardiographic patterns of TTC have recently been described, often triggered by emotional stressors, rather than physical. In this report, we describe a case of atypical TTC triggered by an unusual stressor (recurrent nightmare) in a 45-year-old woman, with peculiar clinical presentation and evolution characterized by persistent loss of consciousness, neurological deterioration, absence of typical symptoms of TTC, and features suggestive of a hysterical crisis. PMID:25788945

  6. Gemcitabine induced cardiomyopathy: a case of multiple hit cardiotoxicity.

    PubMed

    Mohebali, Donya; Matos, Jason; Chang, James Ducksoon

    2017-02-01

    Gemcitabine is a commonly used antineoplastic agent used to treat a variety of cancers with rarely reported cardiac side effects. We describe a case of a 67-year-old woman with follicular lymphoma who experienced a rarely reported side effect of gemcitabine: cardiomyopathy. This case highlights a multiple hit mechanism of myocyte damage that may occur following the use of multiple cardio-toxic agents despite their administration in doses not associated with cardiotoxicity.

  7. Intravenously Delivered Mesenchymal Stem Cells: Systemic Anti-Inflammatory Effects Improve Left Ventricular Dysfunction in Acute Myocardial Infarction and Ischemic Cardiomyopathy.

    PubMed

    Luger, Dror; Lipinski, Michael J; Westman, Peter C; Glover, David K; Dimastromatteo, Julien; Frias, Juan C; Albelda, M Teresa; Sikora, Sergey; Kharazi, Alex; Vertelov, Grigory; Waksman, Ron; Epstein, Stephen E

    2017-05-12

    Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O2, were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10(6)) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10(6) MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were

  8. Persimmon leaf flavonoid induces brain ischemic tolerance in mice☆

    PubMed Central

    Miao, Mingsan; Zhang, Xuexia; Wang, Linan

    2013-01-01

    The persimmon leaf has been shown to improve cerebral ischemic outcomes; however, its mechanism of action remains unclear. In this study, mice were subjected to 10 minutes of ischemic preconditioning, and persimmon leaf flavonoid was orally administered for 5 days. Results showed that the persimmon leaf flavonoid significantly improved the content of tissue type plasminogen activator and 6-keto prostaglandin-F1 α in the cerebral cortex, decreased the content of thromboxane B2, and reduced the content of plasminogen activator inhibitor-1 in mice. Following optical microscopy, persimmon leaf flavonoid was also shown to reduce cell swelling and nuclear hyperchromatism in the cerebral cortex and hippocampus of mice. These results suggested that persimmon leaf flavonoid can effectively inhibit brain thrombosis, improve blood supply to the brain, and relieve ischemia-induced pathological damage, resulting in brain ischemic tolerance. PMID:25206432

  9. Frequency and predictors of tachycardia-induced cardiomyopathy in patients with persistent atrial flutter

    PubMed Central

    Pizzale, Stephen; Lemery, Robert; Green, Martin S; Gollob, Michael H; Tang, Anthony SL; Birnie, David H

    2009-01-01

    BACKGROUND There are few data on the frequency and predictors of tachycardia-induced cardiomyopathy (TICM) in patients with persistent atrial flutter. OBJECTIVES To examine the incidence of TICM in patients undergoing ablation for persistent atrial flutter, and to examine predictors for the development of TICM. METHODS AND RESULTS One hundred eleven patients met the inclusion criteria for the present study. Twenty-eight of 111 (25%) patients had cardiomyopathy before ablation. Sixteen of 28 (57%) patients showed significant improvement in their left ventricular (LV) function postablation. LV function improved to normal in 12 of 16 (75%) patients. Nineteen of 28 (68%) cardiomyopathy patients had preablation LV function in the range in which they would be considered for an implantable cardioverter defibrillator for primary prevention of sudden cardiac death. In nine of 19 (47%) patients, the ejection fraction improved such that an implantable cardioverter defibrillator was no longer indicated. In multivariate analysis, average ventricular rate during atrial flutter was the only independent predictor of reversibility of cardiomyopathy (P=0.013). CONCLUSIONS Sixteen of 28 (57%) cardiomyopathy patients with persistent atrial flutter had significantly improved LV function postablation. In 75% of these patients, LV function improved to normal. PMID:19668781

  10. Metabolic stress-induced cardiomyopathy is caused by mitochondrial dysfunction due to attenuated Erk5 signaling.

    PubMed

    Liu, Wei; Ruiz-Velasco, Andrea; Wang, Shoubao; Khan, Saba; Zi, Min; Jungmann, Andreas; Dolores Camacho-Muñoz, Maria; Guo, Jing; Du, Guanhua; Xie, Liping; Oceandy, Delvac; Nicolaou, Anna; Galli, Gina; Müller, Oliver J; Cartwright, Elizabeth J; Ji, Yong; Wang, Xin

    2017-09-08

    The prevalence of cardiomyopathy from metabolic stress has increased dramatically; however, its molecular mechanisms remain elusive. Here, we show that extracellular signal-regulated protein kinase 5 (Erk5) is lost in the hearts of obese/diabetic animal models and that cardiac-specific deletion of Erk5 in mice (Erk5-CKO) leads to dampened cardiac contractility and mitochondrial abnormalities with repressed fuel oxidation and oxidative damage upon high fat diet (HFD). Erk5 regulation of peroxisome proliferator-activated receptor γ co-activator-1α (Pgc-1α) is critical for cardiac mitochondrial functions. More specifically, we show that Gp91phox activation of calpain-1 degrades Erk5 in free fatty acid (FFA)-stressed cardiomyocytes, whereas the prevention of Erk5 loss by blocking Gp91phox or calpain-1 rescues mitochondrial functions. Similarly, adeno-associated virus 9 (AAV9)-mediated restoration of Erk5 expression in Erk5-CKO hearts prevents cardiomyopathy. These findings suggest that maintaining Erk5 integrity has therapeutic potential for treating metabolic stress-induced cardiomyopathy.The mechanistic link between metabolic stress and associated cardiomyopathy is unknown. Here the authors show that high fat diet causes calpain-1-dependent degradation of ERK5 leading to mitochondrial dysfunction, suggesting the maintenance of cardiac ERK5 as a therapeutic approach for cardiomyopathy prevention and/or treatment.

  11. Doxorubicin-induced dilated cardiomyopathy for modified radical mastectomy: A case managed under cervical epidural anaesthesia

    PubMed Central

    Jain, Anuj; Kishore, Kamal

    2013-01-01

    Doxorubicin (Dox) is an antineoplastic agent used in a wide variety of malignancies. Its use is limited because of a cumulative, dose-dependent irreversible cardiomyopathy. We report a case of Dox induced cardiomyopathy, posted for modified radical mastectomy. The patient had poor LV function along with moderate pulmonary hypertension. Regional anaesthesia was planned as the risk associated with general anaesthesia was more. A cervical epidural was placed and a block adequate for surgery could be achived. The haemodynamic parameters as measured by esophageal doppler showed a stable trend. The surgery could be managed well under cervical epidural and also provided a good postoperative pain relief. PMID:23825820

  12. Molecular pathogenetic mechanisms and new therapeutic perspectives in anthracycline-induced cardiomyopathy

    PubMed Central

    2009-01-01

    Anthracyclines are among the most powerful drugs for the treatment of oncologic diseases both in childhood and in adulthood. Nevertheless, their major antineoplastic efficacy can be seriously impaired by collateral toxic cardiac effects causing cardiomyopathy with chronic heart failure that is refractory to conventional medical therapy. This article reports possible subcellular molecular alterations of anthracycline-induced cardiomyopathy (reactive oxygen species formation, apoptosis, inflammatory signalling, altered expression of cardiomyocytes specific genes, etc) and indicates some new therapeutic perspectives resulting from a better understanding of the molecular pathogenetic mechanisms. PMID:19930562

  13. Molecular pathogenetic mechanisms and new therapeutic perspectives in anthracycline-induced cardiomyopathy.

    PubMed

    Distefano, Giuseppe

    2009-11-20

    Anthracyclines are among the most powerful drugs for the treatment of oncologic diseases both in childhood and in adulthood. Nevertheless, their major antineoplastic efficacy can be seriously impaired by collateral toxic cardiac effects causing cardiomyopathy with chronic heart failure that is refractory to conventional medical therapy.This article reports possible subcellular molecular alterations of anthracycline-induced cardiomyopathy (reactive oxygen species formation, apoptosis, inflammatory signalling, altered expression of cardiomyocytes specific genes, etc) and indicates some new therapeutic perspectives resulting from a better understanding of the molecular pathogenetic mechanisms.

  14. An Unusual Case of Loffler Endomyocarditis after Takotsubo Cardiomyopathy Induced by Deep Neck Infection

    PubMed Central

    Kundi, Harun; Cetin, Mustafa; Kızıltunç, Emrullah; Cetin, Zehra Guven; Çiçekçioğlu, Hülya; Ornek, Ender

    2015-01-01

    In this case, we herein have described a 72-year-old female patient with deep neck infection induced Takotsubo cardiomyopathy and idiopathic hypereosinophilic syndrome with Loffler endocarditis characterized by right atrial thrombus and right ventricular fibrothrombotic obliteration within two months. PMID:27122907

  15. Acute left ventricular failure in a patient with hydroxychloroquine-induced cardiomyopathy.

    PubMed

    Hartmann, M; Meek, I L; van Houwelingen, G K; Lambregts, H P C M; Toes, G J; van der Wal, A C; von Birgelen, C

    2011-11-01

    We present the case of a 75-year-old woman with a medical history of rheumatoid arthritis treated with hydroxychloroquine, who was admitted with acute left-sided heart failure due to a hydroxychloroquine-induced cardiomyopathy as supported by endomyocardial biopsy.

  16. Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy

    PubMed Central

    Das, Bidyut Kumar

    2011-01-01

    Azithromycin is a widely used macrolide derivative and has generally been considered to be a very safe medication. Though gastrointestinal symptoms and reversible hearing loss are common, potentially serious side effects including angioedema and cholestatic jaundice occurred in less than one percent of patients. We report a case of asymptomatic dilated cardiomyopathy with Azithromycin induced severe hepatocellular toxicity and hepatic encephalopathy. PMID:22144789

  17. Prevention of exercised induced cardiomyopathy following Pip-PMO treatment in dystrophic mdx mice.

    PubMed

    Betts, Corinne A; Saleh, Amer F; Carr, Carolyn A; Hammond, Suzan M; Coenen-Stass, Anna M L; Godfrey, Caroline; McClorey, Graham; Varela, Miguel A; Roberts, Thomas C; Clarke, Kieran; Gait, Michael J; Wood, Matthew J A

    2015-03-11

    Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder caused by mutations in the Dmd gene. In addition to skeletal muscle wasting, DMD patients develop cardiomyopathy, which significantly contributes to mortality. Antisense oligonucleotides (AOs) are a promising DMD therapy, restoring functional dystrophin protein by exon skipping. However, a major limitation with current AOs is the absence of dystrophin correction in heart. Pip peptide-AOs demonstrate high activity in cardiac muscle. To determine their therapeutic value, dystrophic mdx mice were subject to forced exercise to model the DMD cardiac phenotype. Repeated peptide-AO treatments resulted in high levels of cardiac dystrophin protein, which prevented the exercised induced progression of cardiomyopathy, normalising heart size as well as stabilising other cardiac parameters. Treated mice also exhibited significantly reduced cardiac fibrosis and improved sarcolemmal integrity. This work demonstrates that high levels of cardiac dystrophin restored by Pip peptide-AOs prevents further deterioration of cardiomyopathy and pathology following exercise in dystrophic DMD mice.

  18. Prevention of exercised induced cardiomyopathy following Pip-PMO treatment in dystrophic mdx mice

    PubMed Central

    Betts, Corinne A.; Saleh, Amer F.; Carr, Carolyn A.; Hammond, Suzan M.; Coenen-Stass, Anna M. L.; Godfrey, Caroline; McClorey, Graham; Varela, Miguel A.; Roberts, Thomas C.; Clarke, Kieran; Gait, Michael J.; Wood, Matthew J. A.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder caused by mutations in the Dmd gene. In addition to skeletal muscle wasting, DMD patients develop cardiomyopathy, which significantly contributes to mortality. Antisense oligonucleotides (AOs) are a promising DMD therapy, restoring functional dystrophin protein by exon skipping. However, a major limitation with current AOs is the absence of dystrophin correction in heart. Pip peptide-AOs demonstrate high activity in cardiac muscle. To determine their therapeutic value, dystrophic mdx mice were subject to forced exercise to model the DMD cardiac phenotype. Repeated peptide-AO treatments resulted in high levels of cardiac dystrophin protein, which prevented the exercised induced progression of cardiomyopathy, normalising heart size as well as stabilising other cardiac parameters. Treated mice also exhibited significantly reduced cardiac fibrosis and improved sarcolemmal integrity. This work demonstrates that high levels of cardiac dystrophin restored by Pip peptide-AOs prevents further deterioration of cardiomyopathy and pathology following exercise in dystrophic DMD mice. PMID:25758104

  19. Initial clinical experience of real-time three-dimensional echocardiography in patients with ischemic and idiopathic dilated cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Shiota, T.; McCarthy, P. M.; White, R. D.; Qin, J. X.; Greenberg, N. L.; Flamm, S. D.; Wong, J.; Thomas, J. D.

    1999-01-01

    The geometry of the left ventricle in patients with cardiomyopathy is often sub-optimal for 2-dimensional ultrasound when assessing left ventricular (LV) function and localized abnormalities such as a ventricular aneurysm. The aim of this study was to report the initial experience of real-time 3-D echocardiography for evaluating patients with cardiomyopathy. A total of 34 patients were evaluated with the real-time 3D method in the operating room (n = 15) and in the echocardiographic laboratory (n = 19). Thirteen of 28 patients with cardiomyopathy and 6 other subjects with normal LV function were evaluated by both real-time 3-D echocardiography and magnetic resonance imaging (MRI) for obtaining LV volumes and ejection fractions for comparison. There were close relations and agreements for LV volumes (r = 0.98, p <0.0001, mean difference = -15 +/- 81 ml) and ejection fractions (r = 0.97, p <0.0001, mean difference = 0.001 +/- 0.04) between the real-time 3D method and MRI when 3 cardiomyopathy cases with marked LV dilatation (LV end-diastolic volume >450 ml by MRI) were excluded. In these 3 patients, 3D echocardiography significantly underestimated the LV volumes due to difficulties with imaging the entire LV in a 60 degrees x 60 degrees pyramidal volume. The new real-time 3D echocardiography is feasible in patients with cardiomyopathy and may provide a faster and lower cost alternative to MRI for evaluating cardiac function in patients.

  20. Initial clinical experience of real-time three-dimensional echocardiography in patients with ischemic and idiopathic dilated cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Shiota, T.; McCarthy, P. M.; White, R. D.; Qin, J. X.; Greenberg, N. L.; Flamm, S. D.; Wong, J.; Thomas, J. D.

    1999-01-01

    The geometry of the left ventricle in patients with cardiomyopathy is often sub-optimal for 2-dimensional ultrasound when assessing left ventricular (LV) function and localized abnormalities such as a ventricular aneurysm. The aim of this study was to report the initial experience of real-time 3-D echocardiography for evaluating patients with cardiomyopathy. A total of 34 patients were evaluated with the real-time 3D method in the operating room (n = 15) and in the echocardiographic laboratory (n = 19). Thirteen of 28 patients with cardiomyopathy and 6 other subjects with normal LV function were evaluated by both real-time 3-D echocardiography and magnetic resonance imaging (MRI) for obtaining LV volumes and ejection fractions for comparison. There were close relations and agreements for LV volumes (r = 0.98, p <0.0001, mean difference = -15 +/- 81 ml) and ejection fractions (r = 0.97, p <0.0001, mean difference = 0.001 +/- 0.04) between the real-time 3D method and MRI when 3 cardiomyopathy cases with marked LV dilatation (LV end-diastolic volume >450 ml by MRI) were excluded. In these 3 patients, 3D echocardiography significantly underestimated the LV volumes due to difficulties with imaging the entire LV in a 60 degrees x 60 degrees pyramidal volume. The new real-time 3D echocardiography is feasible in patients with cardiomyopathy and may provide a faster and lower cost alternative to MRI for evaluating cardiac function in patients.

  1. [Cardiomyopathies. I: classification of cardiomyopathies--dilated cardiomyopathy].

    PubMed

    Schultheiss, H P; Noutsias, M; Kühl, U; Lassner, D; Gross, U; Poller, W; Pauschinger, M

    2005-11-01

    Cardiomyopathies are common causes of heart failure and sudden cardiac death. According to the WHO classification, "specific" cardiomyopathies are differentiated from "idiopathic" cardiomyopathies. Thus, this classification is primarily based on pathophysiological characteristics. The diagnostic spectrum in cardiomyopathies comprises the entire spectrum of non-invasive and invasive cardiological examination techniques. The exact verification of certain cardiomyopathies necessitates additionally investigations. For example, immunohistological and molecular biological investigations of endomyocardial biopsies may confirm inflammatory cardiomyopathy, which is often induced by viruses. Several studies have shown that specific immunomodulatory treatment options can halt the progressive course of the disease. Several gene mutations have been identified in genetic/familial dilated cardiomyopathy. First-degree relatives should be screened for early stages. Primary prevention of sudden cardiac death shows increasing superiority of the implantable defibrillator compared with pharmacological approaches (i.e. amiodarone).

  2. Unique preferential conduction within the isolated septal substrate in a patient with ventricular tachycardia complicated with non-ischemic dilated cardiomyopathy.

    PubMed

    Watanabe, Masaya; Yokoshiki, Hisashi; Mitsuyama, Hirofumi; Mizukami, Kazuya; Tsutsui, Hiroyuki

    2013-01-01

    We describe the case of a 67-year-old woman with non-ischemic dilated cardiomyopathy who underwent successful radiofrequency catheter ablation for ventricular tachycardia (VT) originated from the isolated ventricular septal substrate. Pacemapping exhibited either left, identical to clinical VT, or right bundle branch block like wide QRS morphology. Time interval from the stimulus to QRS onset (St-QRS) was prolonged at the center of the substrate, while St-QRS at the border was shortened. Difference in the morphology of pacemapping was dependent on whether or not the pacing stimulus could propagate directly into the right ventricle due to the possible intramural conduction disturbance. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. New insight into scar-related ventricular tachycardia circuits in ischemic cardiomyopathy: Fat deposition after myocardial infarction on computed tomography--A pilot study.

    PubMed

    Sasaki, Takeshi; Calkins, Hugh; Miller, Christopher F; Zviman, Menekhem M; Zipunnikov, Vadim; Arai, Tomio; Sawabe, Motoji; Terashima, Masashiro; Marine, Joseph E; Berger, Ronald D; Nazarian, Saman; Zimmerman, Stefan L

    2015-07-01

    Myocardial fat deposition (FAT-DEP) has been frequently observed in regions of chronic myocardial infarction in patients with ischemic cardiomyopathy. The role of FAT-DEP within scar-related ventricular tachycardia (VT) circuits has not been investigated. This pilot study aimed to assess the impact of myocardial FAT-DEP on local electrograms and VT circuits in patients with ischemic cardiomyopathy. Contrast-enhanced computed tomography was performed in 22 patients with ischemic VT. Electroanatomic map points were registered to the corresponding contrast-enhanced computed tomography images. Myocardial FAT-DEP was identified and characterized using a postprocessing image overlay that highlighted areas below 0 Hounsfield units (HU). The mean attenuation of local myocardial regions corresponding to sampled electrograms was measured on short-axis images. The associations of mean attenuation with bipolar and unipolar amplitudes, left ventricular wall thickness, and VT circuit sites were investigated. Of 1801 electroanatomic map points, 519 (28.8%) were located in regions with FAT-DEP. Significant differences were observed in mean intensity (23.2 ± 35.6 HU vs 81.7 ± 21.9 HU; P < .001), bipolar (0.75 ± 0.83 mV vs 2.9 ± 2.4 mV; P < .001) and unipolar (3.1 ± 1.7 mV vs 7.4 ± 4.3 mV; P < .001) amplitudes, and left ventricular wall thickness (5.2 ± 1.7 mm vs 8.2 ± 2.5 mm; P < .001) between regions with and without FAT-DEP. Lower HU was strongly associated with lower bipolar and unipolar amplitudes (P < .0001, respectively). Importantly, FAT-DEP was associated with critical VT circuit sites with fractionated or isolated potentials. FAT-DEP was associated with electrogram characteristics and VT circuit sites. Further work will be needed to determine whether FAT-DEP plays a causal role in the generation of ischemic scar-related VT circuits. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  4. Cardioprotective effect of ammonium glycyrrhizinate against doxorubicin-induced cardiomyopathy in experimental animals

    PubMed Central

    Garg, Munish; Singhal, Tinku; Sharma, Hitender

    2014-01-01

    Objective: The objective of this study was to evaluate the cardioprotective effect of herbal bioactive compound ammonium glycyrrhizinate against doxorubicin-induced cardiomyopathy, in experimental animals. Materials and Methods: Ammonium glycyrrhizinate (50, 100, 200 mg/kg, p.o.) was administered for four weeks in albino rats. Cardiomyopathy was induced with a dose of 2.5 mg/kg i.p. of doxorubicin on 1th, 7th, 14th, 21th, 28th day in the experimental animals. At the end of the experiment, on 29th day, serum and heart tissues were collected and hemodynamic, biochemical and histopathological studies were carried out. Results: Administration of doxorubicin in normal rats showed significant (P < 0.001) changes in body weight, feed intake, urine output, hemodynamic parameters like (blood pressure, heart rate, cardiac output) and in lipid profile (cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein) indicating cardiomyopathy symptoms. Animals treated with ammonium glycyrrhizinate significantly (P < 0.05) decreased triglyceride, cholesterol, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels. Moreover, high density lipoprotein (HDL) levels increased in rats treated with ammonium glycyrrhizinate as compared with the normal group. Conclusion: Ammonium glycyrrhizinate is effective in controlling serum lipid profile and cardiac complications in experimentally induced cardiomyopathy in animals. PMID:25298583

  5. Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality.

    PubMed

    Fallavollita, James A; Dare, Jonathan D; Carter, Randolph L; Baldwa, Sunil; Canty, John M

    2017-08-01

    Previous studies have identified multiple risk factors that are associated with total cardiac mortality. Nevertheless, identifying specific factors that distinguish patients at risk of arrhythmic death versus heart failure could better target patients likely to benefit from implantable cardiac defibrillators, which have no impact on nonsudden cardiac death. We performed a pilot competing risks analysis of the National Institutes of Health-sponsored PAREPET trial (Prediction of Arrhythmic Events with Positron Emission Tomography). Death from cardiac causes was ascertained in subjects with ischemic cardiomyopathy (n=204) eligible for an implantable cardiac defibrillator for the primary prevention of sudden cardiac arrest after baseline clinical evaluation and imaging at enrollment (positron emission tomography and 2-dimensional echo). Mean age was 67±11 years with an ejection fraction of 27±9%, and 90% were men. During 4.1 years of follow-up, there were 33 sudden cardiac arrests (arrhythmic death or implantable cardiac defibrillator discharge for ventricular fibrillation or ventricular tachycardia >240 bpm) and 36 nonsudden cardiac deaths. Sudden cardiac arrest was correlated with a greater volume of denervated myocardium (defect of the positron emission tomography norepinephrine analog (11)C-hydroxyephedrine), lack of angiotensin inhibition therapy, elevated B-type natriuretic peptide, and larger left ventricular end-diastolic volume index. In contrast, nonsudden cardiac death was associated with a higher resting heart rate, older age, elevated creatinine, larger left atrial volume index, and larger left ventricular end-diastolic volume index. Distinct clinical, laboratory, and imaging variables are associated with cause-specific cardiac mortality in primary-prevention candidates with ischemic cardiomyopathy. If prospectively validated, these multivariable associations may help target specific therapies to those at the greatest risk of sudden and nonsudden cardiac

  6. Conventional Coronary Angiography Induced Takotsubo Cardiomyopathy Complicated with Cardiac Tamponade

    PubMed Central

    Kang, Min Gyu; Kim, Kye-Hwan; Koh, Jin-Sin; Jeong, Young-Hoon; Hwang, Jin-Yong

    2017-01-01

    Takotsubo cardiomyopathy (TCM) is a transient left ventricular dysfunction that typically occurs after emotional or physical stress. TCM has a benign prognosis and serious complications are uncommon. However, though very rarely reported, cardiac tamponade has occurred on some occasions. We hereby report the case of a 70-year-old woman who underwent coronary angiography with an ergonovine provocation test to evaluate recurrent chest pain and was readmitted 7 days later presenting with TCM, followed by left ventricular outflow tract obstruction and cardiac tamponade.

  7. Association between left atrial myocardial function and exercise capacity in patients with either idiopathic or ischemic dilated cardiomyopathy: a two-dimensional speckle strain study.

    PubMed

    D'Andrea, Antonello; Caso, Pio; Romano, Silvio; Scarafile, Raffaella; Cuomo, Sergio; Salerno, Gemma; Riegler, Lucia; Limongelli, Giuseppe; Di Salvo, Giovanni; Romano, Massimo; Liccardo, Biagio; Iengo, Raffaele; Ascione, Luigi; Del Viscovo, Luca; Calabrò, Paolo; Calabrò, Raffaele

    2009-03-06

    In patients with idiopathic dilated cardiomyopathy (DCM) a more depressed left atrial (LA) booster pump function has been observed compared to ischemic patients although under similar loading conditions, and attributed both to altered LA overload and to LA larger involvement in the myopathic process. To detect by speckle-tracking two-dimensional strain (2DSE) LA systolic dysfunction in patients with either idiopathic or ischemic DCM, and to assess in these patients possible correlation between LA myocardial function and exercise capacity during cardiopulmonary test. Three-hundred-fourteen patients (52.4+/-11.2 years) with either idiopathic (160 patients) or ischemic (154 patients) DCM underwent cardiopulmonary stress test, standard Doppler echo and 2DSE analysis of atrial longitudinal strain in the basal segments of LA septum and LA lateral wall, and in LA roof. The two groups were comparable for most of clinical variables. LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler transmitral inflow measurements. Also LA diameter and maximal volume were similar between the two groups. Conversely, LA active empting volume and fraction were both lower in patients with idiopathic DCM (<0.001). Peak systolic myocardial atrial strain was significantly reduced in patients with idiopathic DCM compared with ischemic DCM at the level of all the analyzed atrial segments (p<0.0001). By multivariable analysis, in the overall population, ischemic aetiology of DCM (p<0.0001) and LA volume (p<0.001) were the only independent determinants of LA lateral wall systolic strain. On the other hand, LA lateral wall systolic strain (p<0.0001) and LA volume (p<0.001) were powerful independent predictors of peak oxygen consumption during cardiopulmonary exercise testing. Two-dimensional strain represents a promising non-invasive technique to assess LA atrial

  8. Mitochondrial cardiomyopathy and related arrhythmias.

    PubMed

    Montaigne, David; Pentiah, Anju Duva

    2015-06-01

    Mitochondrial dysfunction has been shown to be involved in the pathophysiology of arrhythmia, not only in inherited cardiomyopathy due to specific mutations in the mitochondrial DNA but also in acquired cardiomyopathy such as ischemic or diabetic cardiomyopathy. This article briefly discusses the basics of mitochondrial physiology and details the mechanisms generating arrhythmias due to mitochondrial dysfunction. The clinical spectrum of inherited and acquired cardiomyopathies associated with mitochondrial dysfunction is discussed followed by general aspects of the management of mitochondrial cardiomyopathy and related arrhythmia. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Effect of alprazolam on anxiety and cardiomyopathy induced by doxorubicin in mice.

    PubMed

    Anwar, Md Jamir; Pillai, Krishna K; Khanam, Razia; Akhtar, Mohammad; Vohora, Divya

    2012-06-01

    Anxiety following heart failure (HF) and/or myocardial infarction (MI) can impede recovery and constitute a major risk factor for further cardiac events. The present study was aimed to evaluate anxiety following doxorubicin (DOX)-induced cardiomyopathy, a rodent model for HF, in mice. Furthermore, the study investigated the effect of alprazolam on anxiety and cardiomyopathy in this model. The study was carried out in Swiss albino mice. DOX was used at a dose of 10 mg/kg i.v. Alprazolam was administered at doses of 0.5, 1 and 2 mg/kg po for 7 days' pre- and 7 days' post-DOX. Anxiety was measured on day 8 and on day 14 using elevated plus maze and Vogel's conflict test. On 14th day, serum lactate dehydrogenase (LDH) was estimated. The mice were then killed and hearts were dissected out for estimation of thiobarbituric acid reactive substance and Transmission Electron Microscopy (TEM) studies. Our results showed that DOX administration induced cardiomyopathy in mice. This was evidenced by an increased serum LDH and tissue malondialdehyde (MDA) and was confirmed by TEM studies. Alprazolam treatment for 14 days dose dependently reversed DOX-induced increase in LDH and MDA as well as the morphological alterations induced by DOX in TEM studies. Furthermore, alprazolam also reversed the anxiety-like effects induced by DOX in both the tests for anxiety. Thus, alprazolam appears to be a good candidate for alleviating anxiety in patients following MI or HF.

  10. Comparative Efficacy of Nebivolol and Metoprolol to Prevent Tachycardia-Induced Cardiomyopathy in a Porcine Model.

    PubMed

    Nazeri, Alireza; Elayda, MacArthur A; Segura, Ana Maria; Stainback, Raymond F; Nathan, Joanna; Lee, Vei-Vei; Bove, Christina; Sampaio, Luiz; Grace, Brian; Massumi, Ali; Razavi, Mehdi

    2016-12-01

    Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model. Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were obtained at baseline and at the end of the study. At the end of week 8, the pigs were euthanized, and complete histopathologic studies were performed. All the pigs developed left ventricular cardiomyopathy but remained hemodynamically stable and survived to the end of the study. The mean left ventricular ejection fraction decreased from baseline by 34%, 20%, and 20% in the nebivolol, metoprolol, and placebo groups, respectively. These changes did not differ significantly among the 3 groups (P =0.51). Histopathologic analysis revealed mild left ventricular perivascular fibrosis with cardiomyocyte hypertrophy in 14 of the 15 pigs. Both nebivolol and metoprolol failed to prevent cardiomyopathy in our animal model of persistent tachycardia and a high catecholamine state.

  11. Comparative Efficacy of Nebivolol and Metoprolol to Prevent Tachycardia-Induced Cardiomyopathy in a Porcine Model

    PubMed Central

    Nazeri, Alireza; Elayda, MacArthur A.; Segura, Ana Maria; Stainback, Raymond F.; Nathan, Joanna; Lee, Vei-Vei; Bove, Christina; Sampaio, Luiz; Grace, Brian; Massumi, Ali

    2016-01-01

    Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model. Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were obtained at baseline and at the end of the study. At the end of week 8, the pigs were euthanized, and complete histopathologic studies were performed. All the pigs developed left ventricular cardiomyopathy but remained hemodynamically stable and survived to the end of the study. The mean left ventricular ejection fraction decreased from baseline by 34%, 20%, and 20% in the nebivolol, metoprolol, and placebo groups, respectively. These changes did not differ significantly among the 3 groups (P =0.51). Histopathologic analysis revealed mild left ventricular perivascular fibrosis with cardiomyocyte hypertrophy in 14 of the 15 pigs. Both nebivolol and metoprolol failed to prevent cardiomyopathy in our animal model of persistent tachycardia and a high catecholamine state. PMID:28100964

  12. Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

    PubMed Central

    Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun

    2015-01-01

    Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis. PMID:26689945

  13. Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun

    2015-12-01

    Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

  14. Sepsis-Induced Takotsubo Cardiomyopathy Leading to Torsades de Pointes

    PubMed Central

    Kamran, Haroon; El-Sherif, Nabil

    2016-01-01

    Background. Takotsubo cardiomyopathy (TCM) is sudden and reversible myocardial dysfunction often attributable to physical or emotional triggers. Case Report. We describe a 51-year-old man presented to emergency department with sepsis from urinary tract infection (UTI). He was placed on cefepime for UTI and non-ST-elevation myocardial infarction protocol given elevated troponins with chest pain. Subsequently, patient was pulseless with torsades de pointes (TdP) and then converted to sinus rhythm with cardioversion. An echocardiogram revealed low ejection fraction with hypokinesis of the apical wall. Over 48 hours, the patient was extubated and stable on 3 L/min nasal cannula. He underwent a cardiac catheterization to evaluate coronary artery disease (CAD) and was found to have mild nonobstructive CAD with no further findings. Conclusion. TCM is a rare disorder presenting with symptoms similar to acute coronary syndrome. Though traditionally elicited by physical and emotional triggers leading to transient left ventricular dysfunction, our case suggests that it may also be triggered by a urinary tract infection and lead to severe QT prolongation and a malignant ventricular arrhythmia in TdP. PMID:27525128

  15. Impact of T wave amplitude in lead aVR on predicting cardiac events in ischemic and nonischemic cardiomyopathy patients with an implantable cardioverter defibrillator.

    PubMed

    Tanaka, Yoshihiro; Konno, Tetsuo; Tamura, Yudai; Tsuda, Toyonobu; Furusho, Hiroshi; Takamura, Masayuki; Sakata, Kenji; Yamagishi, Masakazu; Hayashi, Kenshi

    2017-04-25

    T wave amplitudes during ventricular repolarization in the lead aVR (TAaVR) are shown to be associated with adverse cardiac events in patients with several cardiovascular diseases, such as postmyocardial infarction. However, the utility of TAaVR has not been previously evaluated in patients with cardiomyopathy who have received implantable cardioverter defibrillators (ICD). Patients with ischemic or nonischemic cardiomyopathy (ICM or NICM, respectively) and who received an ICD may experience worsening of their condition due to the introduction of electric shock during treatment. This study aimed to investigate the utility of TAaVR in the prediction of cardiac events in ICM or NICM patients with ICD. Ninety-three consecutive ICM or NICM patients with ICD were retrospectively analyzed (median age: 64 years; male: 77.4%; ICD for secondary prevention: 76.3%; NICM: 64.5%). The median follow-up period was 31 months. The primary endpoint was defined as composite cardiac events, including cardiac death, major ventricular arrhythmic events (MVAE), or hospitalization due to heart failure (HHF). Multivariate Cox regression analysis demonstrated that less negative TAaVR (-0.1 mV ≤ TAaVR <0 mV and 0 mV ≤ TAaVR) was independently associated with the primary endpoint (HR: 3.75; 95% confidence interval [CI]: 1.09-23.7; p = .04). Kaplan-Meier curve also revealed that the event free survival rate in the less negative TAaVR group was significantly lower than that in the normal TAaVR group (<-0.1 mV) (p < .01). TAaVR is useful in risk stratification for cardiac events in ICM or NICM patients with ICD. © 2017 Wiley Periodicals, Inc.

  16. Cardiovascular Magnetic Resonance to Predict Appropriate Implantable Cardioverter Defibrillator Therapy in Ischemic and Nonischemic Cardiomyopathy Patients Using Late Gadolinium Enhancement Border Zone: Comparison of Four Analysis Methods.

    PubMed

    Jablonowski, Robert; Chaudhry, Uzma; van der Pals, Jesper; Engblom, Henrik; Arheden, Håkan; Heiberg, Einar; Wu, Katherine C; Borgquist, Rasmus; Carlsson, Marcus

    2017-09-01

    Late gadolinium enhancement (LGE) border zone on cardiac magnetic resonance imaging has been proposed as an independent predictor of ventricular arrhythmias. The purpose was to determine whether size and heterogeneity of LGE predict appropriate implantable cardioverter defibrillator (ICD) therapy in ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM) patients and to evaluate 4 LGE border-zone algorithms. ICM and NICM patients who underwent LGE cardiac magnetic resonance imaging prior to ICD implantation were retrospectively included. Two semiautomatic algorithms, expectation maximization, weighted intensity, a priori information and a weighted border zone algorithm, were compared with a modified full-width half-maximum and a 2-3SD threshold-based algorithm (2-3SD). Hazard ratios were calculated per 1% increase in LGE. A total of 74 ICM and 34 NICM were followed for 63 months (1-140) and 52 months (0-133), respectively. ICM patients had 27 appropriate ICD events, and NICM patients had 7 ICD events. In ICM patients with primary prophylactic ICD, LGE border zone predicted ICD therapy in univariable and multivariable analysis measured by the expectation maximization, weighted intensity, a priori information, weighted border zone, and modified full-width half-maximum algorithms (hazard ratios 1.23, 1.22, and 1.05, respectively; P<0.05; negative predictive value 92%). For NICM, total LGE by all 4 methods was the strongest predictor (hazard ratios, 1.03-1.04; P<0.05), though the number of events was small. Appropriate ICD therapy can be predicted in ICM patients with primary prevention ICD by quantifying the LGE border zone. In NICM patients, total LGE but not LGE border zone had predictive value for ICD therapy. However, the algorithms used affects the predictive value of these measures. © 2017 American Heart Association, Inc.

  17. Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation: real-time three-dimensional echocardiography study

    NASA Technical Reports Server (NTRS)

    Kwan, Jun; Shiota, Takahiro; Agler, Deborah A.; Popovic, Zoran B.; Qin, Jian Xin; Gillinov, Marc A.; Stewart, William J.; Cosgrove, Delos M.; McCarthy, Patrick M.; Thomas, James D.

    2003-01-01

    BACKGROUND: This study was conducted to elucidate the geometric differences of the mitral apparatus in patients with significant mitral regurgitation caused by ischemic cardiomyopathy (ICM-MR) and by idiopathic dilated cardiomyopathy (DCM-MR) by use of real-time 3D echocardiography (RT3DE). METHODS AND RESULTS: Twenty-six patients with ICM-MR caused by posterior infarction, 18 patients with DCM-MR, and 8 control subjects were studied. With the 3D software, commissure-commissure plane and 3 perpendicular anteroposterior (AP) planes were generated for imaging the medial, central, and lateral sides of the mitral valve (MV) during mid systole. In 3 AP planes, the angles between the annular plane and each leaflet (anterior, Aalpha; posterior, Palpha) were measured. In ICM-MR, Aalpha measured in the medial and central planes was significantly larger than that in the lateral plane (39+/-5 degrees, 34+/-6 degrees, and 27+/-5 degrees, respectively; P<0.01), whereas Palpha showed no significant difference in any of the 3 AP planes (61+/-7 degrees, 57+/-7 degrees, and 56+/-7 degrees, P>0.05). In DCM-MR, both Aalpha (38+/-8 degrees, 37+/-9 degrees, and 36+/-7 degrees, P>0.05) and Palpha (59+/-6 degrees, 58+/-5 degrees, and 57+/-6 degrees, P>0.05) revealed no significant differences in the 3 planes. CONCLUSIONS: The pattern of MV deformation from the medial to the lateral side was asymmetrical in ICM-MR, whereas it was symmetrical in DCM-MR. RT3DE is a helpful tool for differentiating the geometry of the mitral apparatus between these 2 different types of functional mitral regurgitation.

  18. Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation: real-time three-dimensional echocardiography study

    NASA Technical Reports Server (NTRS)

    Kwan, Jun; Shiota, Takahiro; Agler, Deborah A.; Popovic, Zoran B.; Qin, Jian Xin; Gillinov, Marc A.; Stewart, William J.; Cosgrove, Delos M.; McCarthy, Patrick M.; Thomas, James D.

    2003-01-01

    BACKGROUND: This study was conducted to elucidate the geometric differences of the mitral apparatus in patients with significant mitral regurgitation caused by ischemic cardiomyopathy (ICM-MR) and by idiopathic dilated cardiomyopathy (DCM-MR) by use of real-time 3D echocardiography (RT3DE). METHODS AND RESULTS: Twenty-six patients with ICM-MR caused by posterior infarction, 18 patients with DCM-MR, and 8 control subjects were studied. With the 3D software, commissure-commissure plane and 3 perpendicular anteroposterior (AP) planes were generated for imaging the medial, central, and lateral sides of the mitral valve (MV) during mid systole. In 3 AP planes, the angles between the annular plane and each leaflet (anterior, Aalpha; posterior, Palpha) were measured. In ICM-MR, Aalpha measured in the medial and central planes was significantly larger than that in the lateral plane (39+/-5 degrees, 34+/-6 degrees, and 27+/-5 degrees, respectively; P<0.01), whereas Palpha showed no significant difference in any of the 3 AP planes (61+/-7 degrees, 57+/-7 degrees, and 56+/-7 degrees, P>0.05). In DCM-MR, both Aalpha (38+/-8 degrees, 37+/-9 degrees, and 36+/-7 degrees, P>0.05) and Palpha (59+/-6 degrees, 58+/-5 degrees, and 57+/-6 degrees, P>0.05) revealed no significant differences in the 3 planes. CONCLUSIONS: The pattern of MV deformation from the medial to the lateral side was asymmetrical in ICM-MR, whereas it was symmetrical in DCM-MR. RT3DE is a helpful tool for differentiating the geometry of the mitral apparatus between these 2 different types of functional mitral regurgitation.

  19. A bioengineered hydrogel system enables targeted and sustained intramyocardial delivery of neuregulin, activating the cardiomyocyte cell cycle and enhancing ventricular function in a murine model of ischemic cardiomyopathy.

    PubMed

    Cohen, Jeffrey E; Purcell, Brendan P; MacArthur, John W; Mu, Anbin; Shudo, Yasuhiro; Patel, Jay B; Brusalis, Christopher M; Trubelja, Alen; Fairman, Alexander S; Edwards, Bryan B; Davis, Mollie S; Hung, George; Hiesinger, William; Atluri, Pavan; Margulies, Kenneth B; Burdick, Jason A; Woo, Y Joseph

    2014-07-01

    Neuregulin-1β (NRG) is a member of the epidermal growth factor family possessing a critical role in cardiomyocyte development and proliferation. Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal models, leading to clinical trials using daily NRG infusions. This approach is hindered by requiring daily infusions and off-target exposure. Therefore, this study aimed to encapsulate NRG in a hydrogel to be directly delivered to the myocardium, accomplishing sustained localized NRG delivery. NRG was encapsulated in hydrogel, and release over 14 days was confirmed by ELISA in vitro. Sprague-Dawley rats were used for cardiomyocyte isolation. Cells were stimulated by PBS, NRG, hydrogel, or NRG-hydrogel (NRG-HG) and evaluated for proliferation. Cardiomyocytes demonstrated EdU (5-ethynyl-2'-deoxyuridine) and phosphorylated histone H3 positivity in the NRG-HG group only. For in vivo studies, 2-month-old mice (n=60) underwent left anterior descending coronary artery ligation and were randomized to the 4 treatment groups mentioned. Only NRG-HG-treated mice demonstrated phosphorylated histone H3 and Ki67 positivity along with decreased caspase-3 activity compared with all controls. NRG was detected in myocardium 6 days after injection without evidence of off-target exposure in NRG-HG animals. At 2 weeks, the NRG-HG group exhibited enhanced left ventricular ejection fraction, decreased left ventricular area, and augmented borderzone thickness. Targeted and sustained delivery of NRG directly to the myocardial borderzone augments cardiomyocyte mitotic activity, decreases apoptosis, and greatly enhances left ventricular function in a model of ischemic cardiomyopathy. This novel approach to NRG administration avoids off-target exposure and represents a clinically translatable strategy in myocardial regenerative therapeutics. © 2014 American Heart Association, Inc.

  20. Direct intramyocardial transthoracic transplantation of bone marrow mononuclear cells for non-ischemic dilated cardiomyopathy: INTRACELL, a prospective randomized controlled trial

    PubMed Central

    Sant'Anna, Roberto T.; Fracasso, James; Valle, Felipe H.; Castro, Iran; Nardi, Nance B.; Sant'Anna, João Ricardo M.; Nesralla, Ivo Abrahão; Kalil, Renato A. K.

    2014-01-01

    Objective We tested the hypothesis that direct intramyocardial injection of bone marrow mononuclear cells in patients with non-ischemic dilated cardiomyopathy can improve left ventricular function and physical capacity. Methods Thirty non-ischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% were randomized at a 1:2 ratio into two groups, control and treated. The bone marrow mononuclear cells group received 1.06±108 bone marrow mononuclear cells through mini-thoracotomy. There was no intervention in the control group. Assessment was carried out through clinical evaluations as well as a 6-min walk test, nuclear magnectic resonance imaging and echocardiogram. Results The bone marrow mononuclear cells group showed a trend toward left ventricular ejection fraction improvement, with magnectic resonance imaging - at 3 months, showing an increase from 27.80±6.86% to 30.13±9.06% (P=0.08) and returning to baseline at 9 months (28.78%, P=0.77). Magnectic resonance imaging showed no changes in left ventricular ejection fraction during follow-up of the control group (28.00±4.32%, 27.42±7.41%, and 29.57±4.50%). Echocardiogram showed left ventricular ejection fraction improved in the bone marrow mononuclear cells group at 3 months, 25.09±3.98 to 30.94±9.16 (P=0.01), and one year, 30.07±7.25% (P=0.001). The control group showed no change (26.1±4.4 vs 26.5±4.7 and 30.2±7.39%, P=0.25 and 0.10, respectively). Bone marrow mononuclear cells group showed improvement in New York Heart Association functional class, from 3.40±0.50 to 2.41±0.79 (P=0.002); patients in the control group showed no change (3.37±0.51 to 2.71±0.95; P=0.17). Six-minute walk test improved in the bone marrow mononuclear cells group (348.00±93.51m at baseline to 370.41±91.56m at 12 months, P=0.66) and there was a non-significant decline in the control group (361.25±90.78m to 330.00±123.42m after 12 months, P=0.66). Group comparisons were non-significant. Conclusion

  1. Ketogenic diet prevents cardiac arrest-induced cerebral ischemic neurodegeneration.

    PubMed

    Tai, K-K; Nguyen, N; Pham, L; Truong, D D

    2008-07-01

    Ketogenic diet (KD) is an effective treatment for intractable epilepsies. We recently found that KD can prevent seizure and myoclonic jerk in a rat model of post-hypoxic myoclonus. In the present study, we tested the hypothesis that KD can prevent the cerebral ischemic neurodegeneration in this animal model. Rats fed a standard diet or KD for 25 days were being subjected to mechanically induced cardiac arrest brain ischemia for 8 min 30 s. Nine days after cardiac arrest, frozen rat brains were sectioned for evaluation of ischemia-induced neurodegeneration using fluoro-jade (FJ) staining. The FJ positive degenerating neurons were counted manually. Cardiac arrest-induced cerebral ischemia in rats fed the standard diet exhibited extensive neurodegeneration in the CA1 region of the hippocampus, the number of FJ positive neurons was 822+/-80 (n=4). They also showed signs of neurodegeneration in the Purkinje cells of the cerebellum and in the thalamic reticular nucleus, the number of FJ positive neurons in the cerebellum was 55+/-27 (n=4), the number of FJ positive neurons in the thalamic reticular nucleus was 22+/-5 (n=4). In contrast, rats fed KD showed no evidence of neurodegeneration, the number of FJ positive neurons in these areas were zero. The results demonstrate that KD can prevent cardiac arrest-induced cerebral ischemic neurodegeneration in selected brain regions.

  2. Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young male patient.

    PubMed

    Shamloul, Reham Mohammed; Aborayah, Ahmed Fathy; Hashad, Assem; Abd-Allah, Foad

    2014-02-26

    We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects.

  3. Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young male patient

    PubMed Central

    Shamloul, Reham Mohammed; Aborayah, Ahmed Fathy; Hashad, Assem; Abd-Allah, Foad

    2014-01-01

    We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects. PMID:24574525

  4. Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy

    PubMed Central

    Kannan, Sankaranarayanan; Muthusamy, Vasanthi R.; Whitehead, Kevin J.; Wang, Li; Gomes, Aldrin V.; Litwin, Sheldon E.; Kensler, Thomas W.; Abel, E. Dale; Hoidal, John R.; Rajasekaran, Namakkal S.

    2013-01-01

    Aims Mutant protein aggregation (PA) cardiomyopathy (MPAC) is characterized by reductive stress (RS), PA (of chaperones and cytoskeletal components), and ventricular dysfunction in transgenic mice expressing human mutant CryAB (hmCryAB). Sustained activation of nuclear erythroid-2 like factor-2 (Nrf2) causes RS, which contributes to proteotoxic cardiac disease. The goals of this pre-clinical study were to (i) investigate whether disrupting Nrf2-antioxidant signalling prevents RS and rescues redox homeostasis in hearts expressing the mutant chaperone and (ii) elucidate mechanisms that could delay proteotoxic cardiac disease. Methods and results Non-transgenic (NTG), transgenic (TG) with MPAC and MPAC-TG:Nrf2-deficient (Nrf2-def) mice were used in this study. The effects of Nrf2 diminution (Nrf2±) on RS mediated MPAC in TG mice were assessed at 6–7 and 10 months of age. The diminution of Nrf2 prevented RS and prolonged the survival of TG mice (∼50 weeks) by an additional 20–25 weeks. The TG:Nrf2-def mice did not exhibit cardiac hypertrophy at even 60 weeks, while the MPAC-TG mice developed pathological hypertrophy and heart failure starting at 24–28 weeks of age. Aggregation of cardiac proteins was significantly reduced in TG:Nrf2-def when compared with TG mice at 7 months. Preventing RS and maintaining redox homeostasis in the TG:Nrf2-def mice ameliorated PA, leading to decreased ubiquitination of proteins. Conclusion Nrf2 deficiency rescues redox homeostasis, which reduces aggregation of mutant proteins, thereby delaying the proteotoxic pathological cardiac remodelling caused by RS and toxic protein aggregates. PMID:23761402

  5. Pheochromocytoma-induced acute pulmonary edema and reversible catecholamine cardiomyopathy mimicking acute myocardial infarction.

    PubMed

    Pineda Pompa, Luis Ramón; Barrera-Ramírez, Carlos Felipe; Martínez-Valdez, Jesús; Rodríguez, Pedro Domínguez; Guzmán, Carlos E

    2004-04-01

    Acute noncardiogenic pulmonary edema and catecholamine-induced cardiomyopathy as the first presentations of pheochromocytoma are uncommon events, but usually rapidly fatal. A 36-year-old man presented acute pulmonary edema in a setting of hypertensive emergency after arthroscopy, later developing catecholamine-induced cardiotoxicity mimicking an acute myocardial infarction, with elevation of cardiac damage markers, normal coronary arteries, and with full recovery from electrical abnormalities. Magnetic resonance imaging revealed a right adrenal mass. Elevated levels of catecholamines and metanephrines, and a positive 131I-metaiodobenzylguanidine scan confirmed a pheochromocytoma. Once the patient had been hemodynamically stabilized, he was successfully operated.

  6. Matricellular protein CCN1 mediates doxorubicin-induced cardiomyopathy in mice.

    PubMed

    Hsu, Pei-Ling; Mo, Fan-E

    2016-06-14

    Doxorubicin (DOX) is an effective chemotherapeutic agent however its clinical use is limited by its cumulative cardiotoxicity. Matricellular protein CCN1 mediates work-overload-induced cardiac injury. We aimed to assess the role of CCN1 in DOX-associated cardiomyopathy. Here we discovered CCN1 expression in the myocardium 1 day after DOX treatment (15 mg/kg; i.p.) in mice. Whereas CCN1 synergizes with Fas ligand (FasL) to induce cardiomyocyte apoptosis, we found that FasL was also induced by DOX in the heart. To assess the function of CCN1 in vivo, knockin mice (Ccn1dm/dm) expressing an a6β1-binding defective CCN1 mutant were treated with a single dose of DOX (15 mg/kg; i.p.). Compared with wild-type mice, Ccn1dm/dm mice were resistant to DOX-induced cardiac injury and dysfunction 14 days after injection. Using rat cardiomyoblast H9c2 cells, we demonstrated that DOX induced reactive oxygen species accumulation to upregulate CCN1 and FasL expression. CCN1 mediated DOX cardiotoxicity by engaging integrin a6β1 to promote p38 mitogen-activated protein kinase activation and the release of mitochondrial Smac and HtrA2 to cytosol, thereby counteracting the inhibition of XIAP and facilitating apoptosis. In summary, CCN1 critically mediates DOX-induced cardiotoxicity. Disrupting CCN1/a6β1 engagement abolishes DOX-associated cardiomyopathy in mice.

  7. Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold intolerance

    PubMed Central

    Xiong, Dingding; He, Huamei; James, Jeanne; Tokunaga, Chonan; Powers, Corey; Huang, Yan; Osinska, Hanna; Towbin, Jeffrey A.; Purevjav, Enkhsaikhan; Balschi, James A.; Javadov, Sabzali; McGowan, Francis X.; Strauss, Arnold W.

    2013-01-01

    The very long-chain acyl-CoA dehydrogenase (VLCAD) enzyme catalyzes the first step of mitochondrial β-oxidation. Patients with VLCAD deficiency present with hypoketotic hypoglycemia and cardiomyopathy, which can be exacerbated by fasting and/or cold stress. Global VLCAD knockout mice recapitulate these phenotypes: mice develop cardiomyopathy, and cold exposure leads to rapid hypothermia and death. However, the contribution of different tissues to development of these phenotypes has not been studied. We generated cardiac-specific VLCAD-deficient (cVLCAD−/−) mice by Cre-mediated ablation of the VLCAD in cardiomyocytes. By 6 mo of age, cVLCAD−/− mice demonstrated increased end-diastolic and end-systolic left ventricular dimensions and decreased fractional shortening. Surprisingly, selective VLCAD gene ablation in cardiomyocytes was sufficient to evoke severe cold intolerance in mice who rapidly developed severe hypothermia, bradycardia, and markedly depressed cardiac function in response to fasting and cold exposure (+5°C). We conclude that cardiac-specific VLCAD deficiency is sufficient to induce cold intolerance and cardiomyopathy and is associated with reduced ATP production. These results provide strong evidence that fatty acid oxidation in myocardium is essential for maintaining normal cardiac function under these stress conditions. PMID:24285112

  8. Recurrence of Postoperative Stress-Induced Cardiomyopathy Resulting from Status Epilepticus

    PubMed Central

    Ahmed, Yousef M.; Tarant, Nicki S.

    2017-01-01

    Introduction. Classically, stress-induced cardiomyopathy (SIC), also known as takotsubo cardiomyopathy, displays the pathognomonic feature of reversible left ventricular apical ballooning without coronary artery stenosis following stressful event(s). Temporary reduction in ejection fraction (EF) resolves spontaneously. Variants of SIC exhibiting mid-ventricular regional wall motion abnormalities have been identified. Recent case series present SIC as a finding in association with sudden unexplained death in epilepsy (SUDEP). This case presents a patient who develops recurrence of nonapical cardiomyopathy secondary to status epilepticus. Case Report. Involving a postoperative, postmenopausal woman having two distinct episodes of status epilepticus (SE) preceding two incidents of SIC. Preoperative transthoracic echocardiogram (TTE) confirms the patient's baseline EF of 60% prior to the second event. Postoperatively, SE occurs, and the initial electrocardiogram exhibits T-wave inversions with subsequent elevation of troponin I. Postoperative TTE shows an EF of 30% with mid-ventricular wall akinesia restoring baseline EF rapidly. Conclusion. This case identifies the need to understand SIC and its diagnostic criteria, especially when cardiac catheterization is neither indicated nor available. Sudden cardiac death should be considered as a possible complication of refractory status epilepticus. The pathophysiology in SUDEP is currently unknown; yet a correlation between SUDEP and SIC is hypothesized to exist. PMID:28210509

  9. The differences in left atrial function between ischemic and idiopathic dilated cardiomyopathy patients: A two-dimensional speckle tracking imaging study.

    PubMed

    Cao, Sheng; Zhou, Qing; Chen, Jin-Ling; Hu, Bo; Guo, Rui-Qiang

    2016-09-01

    To evaluate left atrial (LA) function in patients with ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy via two-dimensional speckle-tracking imaging. We measured the LA maximum volume, minimum volume, and volume before the atrial systole, and calculated total emptying volume, expansion index, active emptying volume, and fraction. We measured strain and strain rate during systole and late diastole using two-dimensional speckle-tracking imaging, and analyzed correlations between variables. We found no significant differences in LA size, left ventricle (LV) end-diastole diameter, LV ejection fraction (EF), E/A, E/e', deceleration time of the E wave, and effective mitral regurgitant orifice area between the DCM and the ICM group. However, the LA expansion index, active EF, systolic and late diastolic strain, and strain rate were lower in the ICM group (p < 0.05). The expansion index and active EF were positively correlated with the systolic strain rate and the absolute value of the late diastolic strain rate, respectively. LA basic echocardiographic variables did not reflect the differences between ICM and DCM patients, but the systolic and late diastolic strain, as well as the strain rate, were lower in DCM patients. Two-dimensional speckle-tracking imaging is a promising method to differentiate these patients. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:437-445, 2016. © 2016 Wiley Periodicals, Inc.

  10. Heart-Derived Stem Cells in Miniature Swine with Coronary Microembolization: Novel Ischemic Cardiomyopathy Model to Assess the Efficacy of Cell-Based Therapy

    PubMed Central

    Young, Rebeccah F.; Leiker, Merced M.; Suzuki, Takayuki

    2016-01-01

    A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 106 microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 106, n = 5) or saline (untreated, n = 6). Four weeks after therapy myocardial function, myocyte proliferation (Ki67), mitosis (phosphor-Histone H3; pHH3), apoptosis, infarct size (TTC), myocyte nuclear density, and cell size were evaluated. CDCs injected into infarcted and remodeled remote myocardium (global infusion) increased regional function and global function contrasting no change in untreated animals. CDCs reduced infarct volume and stimulated Ki67 and pHH3 positive myocytes in infarct and remote regions. As a result, myocyte number (nuclear density) increased and myocyte cell diameter decreased in both infarct and remote regions. Coronary microembolization produces stable long-term ischemic cardiomyopathy. Global infusion of CDCs stimulates myocyte regeneration and improves left ventricular ejection fraction. Thus, global infusion of CDCs could become a new therapy to reverse LV dysfunction in patients with asymptomatic heart failure. PMID:27738436

  11. Heart-Derived Stem Cells in Miniature Swine with Coronary Microembolization: Novel Ischemic Cardiomyopathy Model to Assess the Efficacy of Cell-Based Therapy.

    PubMed

    Suzuki, Gen; Young, Rebeccah F; Leiker, Merced M; Suzuki, Takayuki

    2016-01-01

    A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 10(6) microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 10(6), n = 5) or saline (untreated, n = 6). Four weeks after therapy myocardial function, myocyte proliferation (Ki67), mitosis (phosphor-Histone H3; pHH3), apoptosis, infarct size (TTC), myocyte nuclear density, and cell size were evaluated. CDCs injected into infarcted and remodeled remote myocardium (global infusion) increased regional function and global function contrasting no change in untreated animals. CDCs reduced infarct volume and stimulated Ki67 and pHH3 positive myocytes in infarct and remote regions. As a result, myocyte number (nuclear density) increased and myocyte cell diameter decreased in both infarct and remote regions. Coronary microembolization produces stable long-term ischemic cardiomyopathy. Global infusion of CDCs stimulates myocyte regeneration and improves left ventricular ejection fraction. Thus, global infusion of CDCs could become a new therapy to reverse LV dysfunction in patients with asymptomatic heart failure.

  12. Sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia.

    PubMed

    Pinto, M C X; Simão, F; da Costa, F L P; Rosa, D V; de Paiva, M J N; Resende, R R; Romano-Silva, M A; Gomez, M V; Gomez, R S

    2014-06-20

    Brain ischemic tolerance is an endogenous protective mechanism activated by a preconditioning stimulus that is closely related to N-methyl-d-aspartate receptor (NMDAR). Glycine transporter type 1 (GlyT-1) inhibitors potentiate NMDAR and suggest an alternative strategy for brain preconditioning. The aim of this work was to evaluate the effects of brain preconditioning induced by sarcosine, a GlyT-1 inhibitor, against global cerebral ischemia and its relation to NMDAR. Sarcosine was administered over 7 days (300 or 500 mg/kg/day, ip) before the induction of a global cerebral ischemia model in Wistar rats (male, 8-week-old). It was observed that sarcosine preconditioning reduced cell death in rat hippocampi submitted to cerebral ischemia. Hippocampal levels of glycine were decreased in sarcosine-treated animals, which was associated with a reduction of [(3)H] glycine uptake and a decrease in glycine transporter expression (GlyT-1 and GlyT-2). The expression of glycine receptors and the NR1 and NR2A subunits of NMDAR were not affected by sarcosine preconditioning. However, sarcosine preconditioning reduced the expression of the NR2B subunits of NMDAR. In conclusion, these data demonstrate that sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia and this neuroprotective state is associated with changes in glycine transport and reduction of NR2B-containing NMDAR expression. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. New Insight into Scar-related Ventricular Tachycardia Circuits in Ischemic Cardiomyopathy: Fat Deposition after Myocardial Infarction on Computed Tomography: A Pilot Study

    PubMed Central

    Sasaki, Takeshi; Calkins, Hugh; Miller, Christopher F.; Zviman, Menekhem M.; Zipunnikov, Vadim; Arai, Tomio; Sawabe, Motoji; Terashima, Masashiro; Marine, Joseph E.; Berger, Ronald D.; Nazarian, Saman; Zimmerman, Stefan L.

    2015-01-01

    Background Myocardial fat deposition (FAT-DEP) has been frequently observed in regions of chronic myocardial infarction in patients with ischemic cardiomyopathy (ICM). The role of FAT-DEP within scar-related ventricular tachycardia (VT) circuits has not been investigated. Objective This pilot study aimed to assess the impact of myocardial FAT-DEP on local electrograms and VT circuits in patients with ICM. Methods Contrast-enhanced computed tomography (CE-CT) was performed in 22 patients with ischemic VT. Electroanatomic map (EAM) points were registered to corresponding CE-CT images. Myocardial FAT-DEP were identified and characterized using a post-processing image overlay that highlighted areas below 0 Hounsfield units (HU). The mean attenuation of local myocardial regions corresponding to sampled electrograms was measured on short axis images. The associations of mean attenuation with bipolar and unipolar amplitudes, left ventricular (LV) wall thickness and VT circuit sites were investigated. Results Of 1801 EAM points, 519 (28.8%) were located in regions with FAT-DEP. Significant differences were observed in mean intensity (23.2±35.6 vs. 81.7±21.9 HU, P<0.001), bipolar (0.75±0.83 vs 2.9±2.4 mV, P<0.001) and unipolar (3.1±1.7 vs. 7.4±4.3 mV, P<0.001) amplitudes and LV wall thickness (5.2±1.7 vs. 8.2±2.5 mm, P<0.001) between regions with and without FAT-DEP. Lower HU was strongly associated with lower bipolar and unipolar amplitude (P<0.0001, respectively). Importantly, FAT-DEP was associated with critical VT circuit sites with fractionated or isolated potentials. Conclusions FAT-DEP was associated with electrogram features and VT circuit sites. Further work will be needed to determine whether FAT-DEP plays a causal role in the generation of ischemic scar-related VT circuits. PMID:25814415

  14. Right ventricular scar-related ventricular tachycardia in non-ischemic cardiomyopathy: Electrophysiological characteristics, mapping and ablation of underlying heart disease.

    PubMed

    Kumar, Saurabh; Baldinger, Samuel H; Kapur, Sunil; Romero, Jorge; Mehta, Nishaki K; Mahida, Saagar; Fujii, Akira; Tedrow, Usha B; Stevenson, William G

    2017-09-21

    Right ventricular (RV)-scar related ventricular tachycardia (VT) is often due to arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) or cardiac sarcoidosis (CS), but some patients whose clinical course has not been described do not fulfill diagnostic criteria for these diseases. We sought to characterize the electrophysiologic substrate and catheter ablation outcomes of such patients, termed RV cardiomyopathy of unknown source (RCUS). Data of 100 consecutive patients who presented with RV cardiomyopathy and/or RV-related VT for ablation was reviewed (51 ARVC/D, 22 CS; 27 RCUS). Compared to ARVC/D, RCUS patients were older (P = 0.001), less commonly had RV dilatation (P = 0.001) or dysfunction (P = 0.01) and fragmented QRS, parietal block, and T wave inversion. Compared to CS, R-CUS patients had less severe LV dysfunction. Extent and distribution of endocardial/epicardial scar and inducible VTs in RCUS patients were comparable with ARVC/D and CS patients. At a median follow-up of 23 months, RCUS patients had more favorable VT-free survival (RCUS 71%, ARVC/D 60%, CS 41%, P = 0.03) and survival free of death or cardiac transplant (RCUS 92%, ARVC/D 92%, CS 62%, P = 0.01). No RCUS patients developed new criteria for ARVC/D or CS in follow-up. Up to one-third of patients with RV scar-related VT are not be classifiable as ARVC/D or CS. These patients had a somewhat better prognosis than ARVC/D or sarcoid and did not develop evidence of these diseases during the initial 2 years of follow-up. The extent to which this population is comprised of mild ARVC/D, CS or other diseases is not clear. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Reversible Cardiomyopathies

    PubMed Central

    Patel, Harsh; Madanieh, Raef; Kosmas, Constantine E; Vatti, Satya K; Vittorio, Timothy J

    2015-01-01

    Cardiomyopathies (CMs) have many etiological factors that can result in severe structural and functional dysregulation. Fortunately, there are several potentially reversible CMs that are known to improve when the root etiological factor is addressed. In this article, we discuss several of these reversible CMs, including tachycardia-induced, peripartum, inflammatory, hyperthyroidism, Takotsubo, and chronic illness–induced CMs. Our discussion also includes a review on their respective pathophysiology, as well as possible management solutions. PMID:26052233

  16. Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline.

    PubMed

    Ashida, Terunao; Takato, Tetsuya; Matsuzaki, Gen; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

    2014-01-01

    We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 μg and the large-dose group (group L, n = 23) received 15-60 μg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.

  17. An animal model of stress-induced cardiomyopathy utilizing the social defeat paradigm.

    PubMed

    Wideman, Cyrilla H; Cierniak, Kayla H; Sweet, Wendy E; Moravec, Christine S; Murphy, Helen M

    2013-08-15

    Stress-induced cardiomyopathy (SIC) is a form of acute heart disease triggered by extreme psychological stress. In patients who develop SIC, the outward symptoms are almost indistinguishable from acute myocardial infarction (AMI). However, some important criteria differentiate patients with SIC from those with AMI. Patients with SIC: (1) experience some form of extreme psychological stress from minutes to hours before developing heart disease, (2) do not suffer from atherosclerosis or coronary artery obstruction, and 3) exhibit abnormal ballooning of the left ventricle. In the present study, the resident-intruder (RI) social defeat test was investigated as a potential rat model for stressed-induced cardiomyopathy. Adult Long-Evans rats were implanted with a biotelemetry transmitter for ECG recordings and habituated for two weeks. An intruder rat was placed in the cage of a resident rat behind a wire-mesh partition for 5 min. The partition was then removed for 5 min to allow direct contact between the intruder and resident rats. After this interval, the wire-mesh partition was replaced and the intruder rat remained behind the partition for an additional 50 min. Behavioral responses were noted and ECG recordings were collected during the entire 60-min testing period. Upon completion of the test, the intruder rat was removed from the cage of the resident rat and sacrificed. The heart was examined and blood was collected. Heart weight/body weight ratio, left ventricle/body weight ratio, heart length, plasma corticosterone levels, and plasma troponin I levels of intruder rats were significantly higher as compared to control rats. Intruder rats significantly increased their heart rate during the first 5 min of the RI test. It is concluded that the RI test to induce social defeat is a novel rodent paradigm for modeling stress-induced cardiomyopathy in the human.

  18. Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy.

    PubMed

    Zhang, Bin; Shen, Qiang; Chen, Yaping; Pan, Ruile; Kuang, Shihuan; Liu, Guiyan; Sun, Guibo; Sun, Xiaobo

    2017-03-13

    Diabetic cardiomyopathy (DCM) has been increasingly considered as a main cause of heart failure and death in diabetic patients. At present, no effective treatment exists to prevent its development. In the present study, we describe the potential protective effects and mechanisms of myricitrin (Myr) on the cardiac function of streptozotosin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with Myr significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy in H9c2 cells. These effects are correlated with Nrf2 activation and NF-κB inhibition. In vivo investigation demonstrated that oral administration of Myr at 300 mg/kg/day for 8 weeks remarkably decreased the expression of enzymes associated with cardiomyopathy, as well as the expression of inflammatory cytokines and apoptotic proteins. Finally, Myr improved diastolic dysfunction and attenuated histological abnormalities. Mechanistically, Myr attenuated diabetes-induced Nrf2 inhibition via the regulation of Akt and ERK phosphorylation in the diabetic heart. Collectively, these results strongly indicate that Myr exerts cardioprotective effects against DCM through the blockage of inflammation, oxidative stress, and apoptosis. This suggests that Myr might be a potential therapeutic agent for the treatment of DCM.

  19. Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

    PubMed Central

    Zhang, Bin; Shen, Qiang; Chen, Yaping; Pan, Ruile; Kuang, Shihuan; Liu, Guiyan; Sun, Guibo; Sun, Xiaobo

    2017-01-01

    Diabetic cardiomyopathy (DCM) has been increasingly considered as a main cause of heart failure and death in diabetic patients. At present, no effective treatment exists to prevent its development. In the present study, we describe the potential protective effects and mechanisms of myricitrin (Myr) on the cardiac function of streptozotosin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with Myr significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy in H9c2 cells. These effects are correlated with Nrf2 activation and NF-κB inhibition. In vivo investigation demonstrated that oral administration of Myr at 300 mg/kg/day for 8 weeks remarkably decreased the expression of enzymes associated with cardiomyopathy, as well as the expression of inflammatory cytokines and apoptotic proteins. Finally, Myr improved diastolic dysfunction and attenuated histological abnormalities. Mechanistically, Myr attenuated diabetes-induced Nrf2 inhibition via the regulation of Akt and ERK phosphorylation in the diabetic heart. Collectively, these results strongly indicate that Myr exerts cardioprotective effects against DCM through the blockage of inflammation, oxidative stress, and apoptosis. This suggests that Myr might be a potential therapeutic agent for the treatment of DCM. PMID:28287141

  20. Intrathecal Clonidine Pump Failure Causing Acute Withdrawal Syndrome With 'Stress-Induced' Cardiomyopathy.

    PubMed

    Lee, Hwee Min D; Ruggoo, Varuna; Graudins, Andis

    2016-03-01

    Clonidine is a central alpha(2)-agonist antihypertensive used widely for opioid/alcohol withdrawal, attention deficit hyperactivity disorder and chronic pain management. We describe a case of clonidine withdrawal causing life-threatening hypertensive crisis and stress-induced cardiomyopathy. A 47-year-old man with chronic back pain, treated with clonidine for many years via intrathecal pump (550 mcg/24 h), presented following a collapse and complaining of sudden worsening of back pain, severe headache, diaphoresis, nausea and vomiting. A few hours prior to presentation, his subcutaneous pump malfunctioned. On presentation, vital signs included pulse 100 bpm, BP 176/103 mmHg, temperature 37.8 °C and O2 saturation 100 % (room air). Acute clonidine withdrawal with hypertensive crisis was suspected. Intravenous clonidine loading dose and a 50 mcg/h infusion were commenced. Five hours later, severe chest pain, dyspnoea, tachycardia, hypoxia, with BP 180/120 mmHg and pulmonary edema ensued. ECG showed sinus tachycardia with no ST elevation. Repeated intravenous clonidine doses were given (25 mcg every 5-10 min), with ongoing clonidine infusion to control blood pressure. Glyceryl trinitrate infusion, positive pressure ventilation and intravenous benzodiazepines were added. Bedside echocardiogram showed stress-induced cardiomyopathy pattern. Serum troponin-I was markedly elevated. His coronary angiography showed minor irregularities in the major vessels. Over the next 3 days in the ICU, drug infusions were weaned. Discharge was 12 days later on oral clonidine, metoprolol, perindopril, aspirin and oxycodone-SR. Two months later, his echocardiogram was normal. The intrathecal pump was removed. We report a case of stress-induced cardiomyopathy resulting from the sudden cessation of long-term intrathecal clonidine. This was managed by re-institution of clonidine and targeted organ-specific therapies.

  1. Clinical recognition of pure premature ventricular complex-induced cardiomyopathy at presentation.

    PubMed

    Penela, Diego; Fernández-Armenta, Juan; Aguinaga, Luis; Tercedor, Luis; Ordoñez, Augusto; Bisbal, Felipe; Acosta, Juan; Rossi, Luca; Borras, Roger; Doltra, Adelina; Ortiz-Pérez, José T; Bosch, Xavier; Perea, Rosario J; Prat-González, Susana; Soto-Iglesias, David; Tolosana, Jose M; Vassanelli, Francesca; Cabrera, Mario; Linhart, Markus; Martinez, Mikel; Mont, Lluis; Berruezo, Antonio

    2017-07-27

    Frequent premature ventricular complexes (PVCs) can induce or worsen left ventricular (LV) systolic dysfunction. The purpose of this study was to identify the clinical pattern of patients having a "pure PVC-induced" cardiomyopathy at presentation. This prospective multicenter study included 155 consecutive patients (age 55 ± 12 years, 96 men [62%], 23% ±12% mean PVC burden) with LV dysfunction and frequent PVCs submitted for ablation and followed up for at least 12 months. Patients with a previously diagnosed structural heart disease (50 [32%]) and those without complete PVC abolition during follow-up who did not normalize LV ejection fraction (LVEF) (24 [15%]) were excluded from the analysis. Of the remaining 81 patients, 41 (51%) had a successful sustained ablation, did not have normalized LVEF, and were classified as having PVC-worsened nonischemic cardiomyopathy, and 40 (49%) who had normalized LVEF were considered as having pure PVC-induced cardiomyopathy. The latter group had higher baseline PVC burden (27% ± 12% vs 12% ± 8%; P <.001), smaller LV end-diastolic diameter (58 ± 5 mm vs 60 ± 6 mm; P = .05), and shorter intrinsic QRS (105 ± 12 vs 129 ± 24 ms; P <.001). Any of the following baseline characteristics accurately identified patients who will not normalize LVEF after PVC ablation (85% sensitivity, 98% specificity): intrinsic QRS >130 ms, baseline PVC burden <17%, and LV end-diastolic diameter >63 mm. Almost half of patients with frequent PVCs and low LVEF of unknown origin normalize LVEF after sustained PVC abolition, and these patients can be identified before ablation. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  2. A Drosophila Model of High Sugar Diet-Induced Cardiomyopathy

    PubMed Central

    Na, Jianbo; Musselman, Laura Palanker; Pendse, Jay; Baranski, Thomas J.; Bodmer, Rolf; Ocorr, Karen; Cagan, Ross

    2013-01-01

    Diets high in carbohydrates have long been linked to progressive heart dysfunction, yet the mechanisms by which chronic high sugar leads to heart failure remain poorly understood. Here we combine diet, genetics, and physiology to establish an adult Drosophila melanogaster model of chronic high sugar-induced heart disease. We demonstrate deterioration of heart function accompanied by fibrosis-like collagen accumulation, insulin signaling defects, and fat accumulation. The result was a shorter life span that was more severe in the presence of reduced insulin and P38 signaling. We provide evidence of a role for hexosamine flux, a metabolic pathway accessed by glucose. Increased hexosamine flux led to heart function defects and structural damage; conversely, cardiac-specific reduction of pathway activity prevented sugar-induced heart dysfunction. Our data establish Drosophila as a useful system for exploring specific aspects of diet-induced heart dysfunction and emphasize enzymes within the hexosamine biosynthetic pathway as candidate therapeutic targets. PMID:23326243

  3. Reversal of Pacing-Induced Cardiomyopathy by Normal QRS Axis Pacing

    PubMed Central

    Yang, Ji Hyun; Kim, Ju Youn; Kim, Sung-Hwan

    2016-01-01

    Right ventricular apical pacing has been a commonly used method for placement of permanent pacemaker, but it is known to be associated with ventricular dyssynchrony and may lead to heart failure. Septal pacing could be an alternative method to improve this complication but the results have been conflicting; hence, other strategies are needed. This case is about a patient with pacing-induced cardiomyopathy who showed much improvement after repositioning the leads to a site different from that of normally paced QRS axis. PMID:27275181

  4. Young at Heart: Pioneering Approaches to Model Nonischaemic Cardiomyopathy with Induced Pluripotent Stem Cells

    PubMed Central

    Gowran, Aoife; Rasponi, Marco; Perrucci, Gianluca L.; Righetti, Stefano; Zanobini, Marco; Pompilio, Giulio

    2016-01-01

    A mere 9 years have passed since the revolutionary report describing the derivation of induced pluripotent stem cells from human fibroblasts and the first in-patient translational use of cells obtained from these stem cells has already been achieved. From the perspectives of clinicians and researchers alike, the promise of induced pluripotent stem cells is alluring if somewhat beguiling. It is now evident that this technology is nascent and many areas for refinement have been identified and need to be considered before induced pluripotent stem cells can be routinely used to stratify, treat and cure patients, and to faithfully model diseases for drug screening purposes. This review specifically addresses the pioneering approaches to improve induced pluripotent stem cell based models of nonischaemic cardiomyopathy. PMID:27110250

  5. Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase

    PubMed Central

    Liu, Yan; Asnani, Aarti; Zou, Lin; Bentley, Victoria L.; Yu, Min; Wang, You; Dellaire, Graham; Sarkar, Kumar S.; Dai, Matthew; Chen, Howard H.; Sosnovik, David E.; Shin, Jordan T.; Haber, Daniel A.; Berman, Jason N.; Chao, Wei; Peterson, Randall T.

    2015-01-01

    Doxorubicin is a highly effective anti-cancer chemotherapy agent, but its usage is limited by its cardiotoxicity. To develop a drug that prevents the cardiac toxicity of doxorubicin while preserving its anti-tumor potency, we established a doxorubicin-induced cardiomyopathy model in zebrafish that recapitulated the cardiomyocyte apoptosis and contractility decline observed in patients. Using this model, we screened 3000 compounds and discovered that visnagin (VIS) and diphenylurea (DPU) rescue cardiac performance and circulatory defects caused by doxorubicin treatment in zebrafish. VIS and DPU reduced doxorubicin-induced apoptosis in cultured cardiomyocytes and in vivo in zebrafish and mouse hearts. Furthermore, VIS treatment improved cardiac contractility in doxorubicin-treated mice. Importantly, VIS and DPU caused no reduction in the chemotherapeutic efficacy of doxorubicin in several cultured tumor lines or in zebrafish and mouse xenograft models. Using affinity chromatography, we discovered that VIS binds to mitochondrial malate dehydrogenase (MDH2), one of the key enzymes in the tricarboxylic acid cycle. As with VIS, treatment with the MDH2 inhibitors mebendazole, thyroxine, and iodine prevented doxorubicin cardiotoxicity, as did treatment with malate itself, suggesting that modulation of MDH2 activity is responsible for VIS’s cardioprotective effects. Taken together, this study identified VIS and DPU as potent cardioprotective compounds and implicates MDH2 as a previously undescribed, druggable target for doxorubicin-induced cardiomyopathy. PMID:25504881

  6. Dimethyl α-ketoglutarate inhibits maladaptive autophagy in pressure overload-induced cardiomyopathy.

    PubMed

    Mariño, Guillermo; Pietrocola, Federico; Kong, Yongli; Eisenberg, Tobias; Hill, Joseph A; Madeo, Frank; Kroemer, Guido

    2014-05-01

    It has been a longstanding problem to identify specific and efficient pharmacological modulators of autophagy. Recently, we found that depletion of acetyl-coenzyme A (AcCoA) induced autophagic flux, while manipulations designed to increase cytosolic AcCoA efficiently inhibited autophagy. Thus, the cell permeant ester dimethyl α-ketoglutarate (DMKG) increased the cytosolic concentration of α-ketoglutarate, which was converted into AcCoA through a pathway relying on either of the 2 isocitrate dehydrogenase isoforms (IDH1 or IDH2), as well as on ACLY (ATP citrate lyase). DMKG inhibited autophagy in an IDH1-, IDH2- and ACLY-dependent fashion in vitro, in cultured human cells. Moreover, DMKG efficiently prevented autophagy induced by starvation in vivo, in mice. Autophagy plays a maladaptive role in the dilated cardiomyopathy induced by pressure overload, meaning that genetic inhibition of autophagy by heterozygous knockout of Becn1 suppresses the pathological remodeling of heart muscle responding to hemodynamic stress. Repeated administration of DMKG prevents autophagy in heart muscle responding to thoracic aortic constriction (TAC) and simultaneously abolishes all pathological and functional correlates of dilated cardiomyopathy: hypertrophy of cardiomyocytes, fibrosis, dilation of the left ventricle, and reduced contractile performance. These findings indicate that DMKG may be used for therapeutic autophagy inhibition.

  7. Results of radiofrequency ablation in children with tachycardia-induced cardiomyopathy.

    PubMed

    Aykan, Hayrettin Hakan; Karagöz, Tevfik; Akın, Alper; İrdem, Ahmet; Özer, Sema; Çeliker, Alpay

    2014-11-01

    Tachycardia-induced cardiomyopathy (TIC) is a rare but potentially curable cause of dilated cardiomyopathy. Data on radiofrequency ablation (RFA) for TIC is limited. The aim of this study is to present our experience with RFA in children with TIC, retrospectively. The medical records of patients with TIC and those underwent RFA between 2000-2011 were systematically reviewed. Demographics and echocardiographic features were recorded. Tachycardia-induced cardiomyopathy is defined as dilatation of the heart chambers or heart failure with chronic or very frequent cardiac arrhythmia. Diagnosis was confirmed with normalization of functions after sinus rhythm has been achieved. A total of 12 patients with a mean age of 6.3±4.1 years (in utero-11.5 years) at diagnosis were enrolled in the study consisting of 7 patients with permanent junctional reciprocating tachycardia and 5 patients with focal atrial tachycardia. The mean pre-RFA left ventricular end-diastolic diameter and left ventricular ejection fraction (LVEF) values were 49.1±9.6 mm (32-66) and 40.8±13.4% (23-57%), respectively. One month after RFA, the mean LVEF value was 62±4.9% (52-69), with only 2 out of 12 patients' LVEF values were still lower than 58%. Tachycardia recurrence was observed in 4 patients, 3 of which had successful repeated RFA procedure. Overall, cure for arrhythmia was achieved in 11 patients (92%), while reversal of heart failure achieved in all patients. In 1 patient permanent complete AV block was developed after the procedure. Treatment of tachycardia with RFA, particularly in patients with arrhythmia refractory to medical therapy, is a feasible and effective treatment option regardless of age.

  8. Restrictive cardiomyopathy

    MedlinePlus

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy; Idiopathic myocardial fibrosis ... In a case of restrictive cardiomyopathy, the heart muscle is of normal size or slightly enlarged. Most of the time, it also pumps normally. However, it does ...

  9. Beriberi Induced Cardiomyopathy Requiring Salvage Venoarterial Extracorporeal Membrane Oxygenation

    PubMed Central

    Patel, Samir; Kothari, Sorabh; Denk, Jennifer

    2016-01-01

    Beriberi refers to a constellation of symptoms caused primarily by thiamine (vitamin B1) deficiency. An acute and fulminant presentation of this rare condition has been described in the literature as “Shoshin” beriberi which is characterized by catastrophic cardiovascular collapse. Early recognition and treatment lead to dramatic improvements of symptoms. We present a case of thiamine deficiency-induced acute heart failure in a malnourished patient leading to cardiac arrest necessitating VA-ECMO (venoarterial extracorporeal membrane oxygenation) with improvement in heart function secondary to thiamine administration. PMID:28050289

  10. Dilated cardiomyopathy-induced disruption of basement membrane alters the lever systems acting on the heart.

    PubMed

    Mohamed, Iman A; El-Badri, Nagwa; Zaher, Amr

    2017-06-01

    Dilated cardiomyopathy (DCM) is considered the most common form of non-ischemic heart diseases. DCM, occurs in response to both non-genetic and genetic factors, and has been associated with cytoskeletal protein mutations, impairing the contractile apparatus of cardiac myocytes. However, the pathology underlying the marked left ventricular dilatation remains unclear. Moreover, patients with end-stage DCM show alterations in the composition of the extracellular matrix (ECM), and myocardial fibrosis even when the cardiac myocytes are intact. Therefore we hypothesize that DCM is a disease of basement membrane, which functions to support sarcomeric interactions with the ECM, and not only impaired cardiac contractility. We propose that under physiological conditions, the heart could be considered a second-class lever system. Disruption of the basement membrane in DCM would cause disarray in the alignment of cardiac myocytes and alteration in the second-class lever system of the heart. Thus, current inotropic agents show minimal or no effect on therapy as they target cardiac contractility rather than cardiac architecture and the lever systems of the heart. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Intracoronary autologous bone marrow-derived mononuclear cell transplantation improves coronary collateral vessel formation and recruitment capacity in patients with ischemic cardiomyopathy: a combined hemodynamic and scintigraphic approach.

    PubMed

    Tayyareci, Yelda; Sezer, Murat; Umman, Berrin; Besisik, Sevgi; Mudun, Ayse; Sanli, Yasemin; Oncul, Aytac; Gurses, Nuray; Sargin, Deniz; Meric, Mehmet; Nisanci, Yilmaz

    2008-01-01

    This study investigated the effects of intracoronary autologous bone marrow-derived mononuclear cell (BMC) transplantation on coronary microcirculation. Fifteen patients with ischemic cardiomyopathy were treated by intracoronary infusion of BMCs via the patent infarct-related artery. The thermodilution-derived coronary flow reserve, index of microvascular resistance, pressure-derived collateral flow index, and coronary wedge pressure were measured at baseline and at 6 months. Successive balloon inflations during BMC transplantation were performed to observe the recruitment in pressure-derived collateral flow index and coronary wedge pressure, and the percentage changes between baseline and 6 months were calculated. The mean (SD) coronary flow reserve increased from 1.3 (0.4) to 2.1 (0.5), and the mean (SD) index of microvascular resistance decreased from 44.9 (24.4) to 21.2 (14.1) (P = .001 for both). The mean (SD) improvement in pressure-derived collateral flow index (from 0.14 [0.05] to 0.22 [0.08]) was also statistically significant (P = .001). Similarly, the percentage improvements in pressure-derived collateral flow index and coronary wedge pressure were statistically significant (P = .01 for both). The percentage improvement in perfusion assessed by single-photon emission computed tomography strongly correlated with the percentage changes in pressure-derived collateral flow index (r = 0.88, P = .001) and coronary wedge pressure (r = 0.69, P = .01). These results demonstrate for the first time (to our knowledge) that intracoronary autologous BMC transplantation improves coronary collateral vessel formation and recruitment capacity in human subjects.

  12. The IMPACT-CABG trial: A multicenter, randomized clinical trial of CD133(+) stem cell therapy during coronary artery bypass grafting for ischemic cardiomyopathy.

    PubMed

    Noiseux, Nicolas; Mansour, Samer; Weisel, Richard; Stevens, Louis-Mathieu; Der Sarkissian, Shant; Tsang, Katherine; Crean, Andrew M; Larose, Eric; Li, Shu-Hong; Wintersperger, Bernd; Vu, Minh Quan; Prieto, Ignacio; Li, Ren-Ke; Roy, Denis Claude; Yau, Terrence M

    2016-12-01

    The IMPACT-CABG trial is the first North American multicenter phase II randomized study of intramyocardial delivery of autologous CD133(+) stem cells in patients with chronic ischemic cardiomyopathy undergoing coronary artery bypass grafting. The primary objective was to demonstrate safety, including freedom from major adverse cardiac events. The secondary objective was to evaluate feasibility of same-day autologous cell preparation. Although the trial was not powered to evaluate LV function, exploratory data were collected. After 7 open-label patients who received cells, patients randomly received stem cells or placebo (N = 40 total, 20 per center). After completion of coronary anastomoses, up to 10 million CD133(+), CD34(+), CD45(+) triple-positive cells or placebo were injected into the infarct and border zones. Patients were followed up clinically and underwent magnetic resonance imaging preoperatively and after 6 months. There were no procedural complications from bone marrow isolation and cell injection, no in-hospital mortality, and no protocol-related complications. Four patients had transient renal insufficiency, with 1 death during 6-month follow-up. Magnetic resonance imaging revealed that left ventricular volumes and ejection fractions improved in all patients (no difference between groups). The trial successfully met both primary and secondary objectives, demonstrating that same-day isolation and autologous CD133(+) cell delivery with coronary artery bypass grafting is safe and feasible. The positive findings support a larger randomized, multicenter trial, with higher numbers of transplanted cells to demonstrate beneficial effects. The upcoming IMPACT-CABG II trial will evaluate higher cell doses and pharmacologic enhancement to determine whether these cells improve perfusion and myocardial function. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  13. High-frequency power within the QRS complex in ischemic cardiomyopathy patients with ventricular arrhythmias: Insights from a clinical study and computer simulation of cardiac fibrous tissue.

    PubMed

    Tsutsumi, Takeshi; Okamoto, Yoshiwo; Takano, Nami; Wakatsuki, Daisuke; Tomaru, Takanobu; Nakajima, Toshiaki

    2017-08-01

    The distribution of frequency power (DFP) within the QRS complex (QRS) is unclear. This study aimed to investigate the DFP within the QRS in ischemic cardiomyopathy (ICM) with lethal ventricular arrhythmias (L-VA). A computer simulation was performed to explore the mechanism of abnormal frequency power. The study included 31 ICM patients with and without L-VA (n = 10 and 21, respectively). We applied the continuous wavelet transform to measure the time-frequency power within the QRS. Integrated time-frequency power (ITFP) was measured within the frequency range of 5-300 Hz. The simulation model consisted of two-dimensional myocardial tissues intermingled with fibroblasts. We examined the relation between frequency power calculated from the simulated QRS and the fibroblast-to-myocyte ratio (r) of the model. The frequency powers significantly increased from 180 to 300 Hz and from 5 to 15 Hz, and also decreased from 45 to 80 Hz in patients with ICM and L-VA compared with the normal individuals. They increased from 110 Hz to 250 Hz in ICM alone. In the simulation, the high-frequency power increased when the ratio (r) were 2.0-2.5. Functional reentry was initiated if the ratio (r) increased to 2.0. Abnormal higher-frequency power (180-300 Hz) may provide arrhythmogenic signals in ICM with L-VA that may be associated with the fibrous tissue proliferation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Effects of Transendocardial Stem Cell Injection on Ventricular Proarrhythmia in Patients with Ischemic Cardiomyopathy: Results from the POSEIDON and TAC-HFT Trials.

    PubMed

    Ramireddy, Archana; Brodt, Chad R; Mendizabal, Adam M; DiFede, Darcy L; Healy, Chris; Goyal, Vishal; Alansari, Yahya; Coffey, James O; Viles-Gonzalez, Juan F; Heldman, Alan W; Goldberger, Jeffrey J; Myerburg, Robert J; Hare, Joshua M; Mitrani, Raul D

    2017-03-02

    Transendocardial stem cell injection in patients with ischemic cardiomyopathy (ICM) improves left ventricular function and structure but has ill-defined effects on ventricular arrhythmias. We hypothesized that mesenchymal stem cell (MSC) implantation is not proarrhythmic. Post hoc analyses were performed on ambulatory ECGs collected from the POSEIDON and TAC-HFT trials. Eighty-eight subjects (mean age 61 ± 10 years) with ICM (mean EF 32.2% ± 9.8%) received treatment with MSC (n = 48), Placebo (n = 21), or bone marrow mononuclear cells (BMC) (n = 19). Heart rate variability (HRV) and ventricular ectopy (VE) were evaluated over 12 months. VE did not change in any group following MSC implantation. However, in patients with ≥ 1 VE run (defined as ≥ 3 consecutive premature ventricular complexes in 24 hours) at baseline, there was a decrease in VE runs at 12 months in the MSC group (p = .01), but not in the placebo group (p = .07; intergroup comparison: p = .18). In a subset of the MSC group, HRV measures of standard deviation of normal intervals was 75 ± 30 msec at baseline and increased to 87 ± 32 msec (p =.02) at 12 months, and root mean square of intervals between successive complexes was 36 ± 30 msec and increased to 58.2 ± 50 msec (p = .01) at 12 months. In patients receiving MSCs, there was no evidence for ventricular proarrhythmia, manifested by sustained or nonsustained ventricular ectopy or worsened HRV. Signals of improvement in ventricular arrhythmias and HRV in the MSC group suggest a need for further studies of the antiarrhythmic potential of MSCs. © Stem Cells Translational Medicine 2017.

  15. Extracellular Volume Fraction Is More Closely Associated With Altered Regional Left Ventricular Velocities Than Left Ventricular Ejection Fraction in Non-Ischemic Cardiomyopathy

    PubMed Central

    Collins, Jeremy; Sommerville, Cort; Magrath, Patrick; Spottiswoode, Bruce; Freed, Benjamin H; Benzuly, Keith H; Gordon, Robert; Vidula, Himabindu; Lee, Dan C; Yancy, Clyde; Carr, James; Markl, Michael

    2014-01-01

    Background Non-ischemic cardiomyopathy (NICM) is a common cause of left ventricular (LV) dysfunction and myocardial fibrosis. The purpose of this study was to non-invasively evaluate changes in segmental LV extracellular volume fraction (ECV), LV velocities, myocardial scar, and wall motion in NICM patients. Methods and Results Cardiac MRI including pre- and post-contrast myocardial T1-mapping and velocity quantification (tissue phase mapping, TPM) of the LV (basal, mid-ventricular, apical short axis) was applied in 31 patients with NICM (50±18years). Analysis based on the 16-segment AHA model was employed to evaluate the segmental distribution of ECV, peak systolic and diastolic myocardial velocities, scar determined by late gadolinium enhancement (LGE), and wall motion abnormalities. LV segments with scar or impaired wall motion were significantly associated with elevated ECV (r=0.26, p<0.001) and reduced peak systolic radial velocities (r=−0.43, p<0.001). Regional myocardial velocities and ECV were similar for patients with reduced (n=12, ECV=0.28±0.06) and preserved LV ejection fraction (LVEF) (n=19, ECV=0.30±0.09). Patients with preserved LVEF showed significant relationships between increasing ECV and reduced systolic (r=−0.19, r=−0.30) and diastolic (r=0.34, r=0.26) radial and long-axis peak velocities (p<0.001). Even after excluding myocardial segments with LGE, significant relationships between ECV and segmental LV velocities were maintained indicating the potential of elevated ECV to identify regional diffuse fibrosis not visible by LGE which was associated with impaired regional LV function Conclusions Regionally elevated ECV negatively impacted myocardial velocities. The association of elevated regional ECV with reduced myocardial velocities independent of LVEF suggests a structure-function relationship between altered ECV and segmental myocardial function in NICM. PMID:25552491

  16. Importance of mitral valve repair associated with left ventricular reconstruction for patients with ischemic cardiomyopathy: a real-time three-dimensional echocardiographic study

    NASA Technical Reports Server (NTRS)

    Qin, Jian Xin; Shiota, Takahiro; McCarthy, Patrick M.; Asher, Craig R.; Hail, Melanie; Agler, Deborah A.; Popovic, Zoran B.; Greenberg, Neil L.; Smedira, Nicholas G.; Starling, Randall C.; Young, James B.; Thomas, James D.

    2003-01-01

    BACKGROUND: Left ventricular (LV) reconstruction surgery leads to early improvement in LV function in ischemic cardiomyopathy (ICM) patients. This study was designed to evaluate the impact of mitral valve (MV) repair associated with LV reconstruction on LV function 1-year after surgery in ICM patients assessed by real-time 3-dimensional echocardiography (3DE). METHODS AND RESULTS: Sixty ICM patients who underwent the combination surgery (LV reconstruction in 60, MV repair in 30, and revascularization in 52 patients) were studied. Real-time 3DE was performed and LV volumes were obtained at baseline, discharge, 6-month and >or=12-month follow-up. Reduction in end-diastolic volumes (EDV) by 29% and in end-systolic volumes by 38% were demonstrated immediately after surgery and remained at subsequent follow-up (P<0.0001). The LV ejection fraction significantly increased by about 10% at discharge and was maintained >or=12-month (P<0.0001). Although the LV volumes were significantly larger in patients with MV repair before surgery (EDV, 235+/-87 mL versus 193+/-67 mL, P<0.05), they were similar to LV volumes of the patients without MV repair at subsequent follow-ups. However, the EDV increased from 139+/-24 mL to 227+/-79 mL (P<0.01) in 7 patients with recurrent mitral regurgitation (MR). Improvement in New York Heart Association functional class occurred in 81% patients during late follow-up. CONCLUSIONS: Real-time 3DE demonstrates that LV reconstruction provides significant reduction in LV volumes and improvement in LV function which is sustained throughout the 1-year follow-up with 84% cardiac event free survival. If successful, MV repair may prevent LV redilation, while recurrent MR is associated with increased LV volumes.

  17. Importance of mitral valve repair associated with left ventricular reconstruction for patients with ischemic cardiomyopathy: a real-time three-dimensional echocardiographic study

    NASA Technical Reports Server (NTRS)

    Qin, Jian Xin; Shiota, Takahiro; McCarthy, Patrick M.; Asher, Craig R.; Hail, Melanie; Agler, Deborah A.; Popovic, Zoran B.; Greenberg, Neil L.; Smedira, Nicholas G.; Starling, Randall C.; hide

    2003-01-01

    BACKGROUND: Left ventricular (LV) reconstruction surgery leads to early improvement in LV function in ischemic cardiomyopathy (ICM) patients. This study was designed to evaluate the impact of mitral valve (MV) repair associated with LV reconstruction on LV function 1-year after surgery in ICM patients assessed by real-time 3-dimensional echocardiography (3DE). METHODS AND RESULTS: Sixty ICM patients who underwent the combination surgery (LV reconstruction in 60, MV repair in 30, and revascularization in 52 patients) were studied. Real-time 3DE was performed and LV volumes were obtained at baseline, discharge, 6-month and >or=12-month follow-up. Reduction in end-diastolic volumes (EDV) by 29% and in end-systolic volumes by 38% were demonstrated immediately after surgery and remained at subsequent follow-up (P<0.0001). The LV ejection fraction significantly increased by about 10% at discharge and was maintained >or=12-month (P<0.0001). Although the LV volumes were significantly larger in patients with MV repair before surgery (EDV, 235+/-87 mL versus 193+/-67 mL, P<0.05), they were similar to LV volumes of the patients without MV repair at subsequent follow-ups. However, the EDV increased from 139+/-24 mL to 227+/-79 mL (P<0.01) in 7 patients with recurrent mitral regurgitation (MR). Improvement in New York Heart Association functional class occurred in 81% patients during late follow-up. CONCLUSIONS: Real-time 3DE demonstrates that LV reconstruction provides significant reduction in LV volumes and improvement in LV function which is sustained throughout the 1-year follow-up with 84% cardiac event free survival. If successful, MV repair may prevent LV redilation, while recurrent MR is associated with increased LV volumes.

  18. Novel rat model reveals important roles of β-adrenoreceptors in stress-induced cardiomyopathy.

    PubMed

    Shao, Yangzhen; Redfors, Bjorn; Scharin Täng, Margareta; Möllmann, Helge; Troidl, Christian; Szardien, Sebastian; Hamm, Christian; Nef, Holger; Borén, Jan; Omerovic, Elmir

    2013-10-03

    Stress-induced cardiomyopathy (SIC), also known as Takotsubo cardiomyopathy, is an acute cardiac syndrome with substantial morbidity and mortality. The unique hallmark of SIC is extensive ventricular akinesia involving apical segments with preserved function in basal segments. Adrenergic overstimulation plays an important role in initiating SIC but the pathophysiological pathways and receptors involved are unknown. Sprague Dawley rats (~300 g) were injected with a single dose of the β-adrenergic agonist isoprenaline (ISO, i.p.) and echocardiography was used to study cardiac function. The akinetic part of the left ventricle was biopsied in six SIC patients. Amount of intracellular lipid and glycogen as well as degree of permanent cardiac damage were assessed by histology. In rats, ISO at doses ≥ 50 mg/kg induced severe SIC-like regional akinesia that completely resolved within seven days. Intracellular lipid content was higher in akinetic, but not in normokinetic myocardium in both SIC patients and rats. β2-receptor blockade or Gi-pathway inhibition was associated with less widespread akinesia and low lipid accumulation but significantly increased acute mortality. We provide a novel rat model of SIC that supports the hypothesis of circulating catecholamines as initiators of SIC. We propose that the β-adrenoreceptor pathway is important in the setting of severe catecholamine overstimulation and that perturbations of cardiac metabolism occur in SIC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Statin Induced Regression of Cardiomyopathy Trial: A Randomized, Placebo-controlled Double-blind Trial

    PubMed Central

    Hersi, Ahmad; Giannoccaro, J. Peter; Howarth, Andrew; Exner, Derek; Weeks, Sarah; Eitel, Ingo; Herman, R. Cameron; Duff, Henry; Ritchie, Debbie; Mcrae, Maureen; Sheldon, Robert

    2016-01-01

    Background: Hypertrophic cardiomyopathy (HCM), characterized by a thickened, fibrotic myocardium, remains the most common cause of sudden cardiac death in young adults. Based on animal and clinical data, we hypothesized that atorvastatin would induce left ventricular (LV) mass regression. Methods: Statin Induced Regression of Cardiomyopathy Trial (SIRCAT) was a randomized, placebo-controlled study. The primary endpoint was change in LV mass measured by cardiac magnetic resonance imaging 12 months after treatment with once-daily atorvastatin 80 mg or placebo. A key secondary endpoint was diastolic dysfunction measured echocardiographically by transmitral flow velocities. SIRCAT is registered with www.clinicaltrials.gov (NCT00317967). Results: Of 222 screened patients, 22 were randomized evenly to atorvastatin and placebo. The mean age was 47 ± 10 years, and 15 (68%) were male. All subjects completed the protocol. At baseline, LV masses were 197 ± 76 g and 205 ± 82 g in the placebo and atorvastatin groups, respectively. After 12 months treatment, the LV masses in the placebo and atorvastatin groups were 196 ± 80 versus 206 ± 92 g (P = 0.80), respectively. Echocardiographic indices were not different in the two groups at baseline. After 12 months, diastolic dysfunction as assessed using transmitral flow velocities E/E', A/A', and peak systolic mitral velocity showed no benefit from atorvastatin. Conclusions: In patients with HCM, atorvastatin did not cause LV mass regression or improvements in LV diastolic function. PMID:28400935

  20. Types of Cardiomyopathy

    MedlinePlus

    ... page from the NHLBI on Twitter. Types of Cardiomyopathy The types of cardiomyopathy include: Hypertrophic cardiomyopathy Dilated ... cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy Unclassified ... Cardiomyopathy Hypertrophic cardiomyopathy is very common and can affect ...

  1. Matricellular protein CCN1 mediates doxorubicin-induced cardiomyopathy in mice

    PubMed Central

    Hsu, Pei-Ling; Mo, Fan-E

    2016-01-01

    Doxorubicin (DOX) is an effective chemotherapeutic agent however its clinical use is limited by its cumulative cardiotoxicity. Matricellular protein CCN1 mediates work-overload-induced cardiac injury. We aimed to assess the role of CCN1 in DOX-associated cardiomyopathy. Here we discovered CCN1 expression in the myocardium 1 day after DOX treatment (15 mg/kg; i.p.) in mice. Whereas CCN1 synergizes with Fas ligand (FasL) to induce cardiomyocyte apoptosis, we found that FasL was also induced by DOX in the heart. To assess the function of CCN1 in vivo, knockin mice (Ccn1dm/dm) expressing an β6β1-binding defective CCN1 mutant were treated with a single dose of DOX (15 mg/kg; i.p.). Compared with wild-type mice, Ccn1dm/dm mice were resistant to DOX-induced cardiac injury and dysfunction 14 days after injection. Using rat cardiomyoblast H9c2 cells, we demonstrated that DOX induced reactive oxygen species accumulation to upregulate CCN1 and FasL expression. CCN1 mediated DOX cardiotoxicity by engaging integrin β6β1 to promote p38 mitogen-activated protein kinase activation and the release of mitochondrial Smac and HtrA2 to cytosol, thereby counteracting the inhibition of XIAP and facilitating apoptosis. In summary, CCN1 critically mediates DOX-induced cardiotoxicity. Disrupting CCN1/β6β1 engagement abolishes DOX-associated cardiomyopathy in mice. PMID:27167338

  2. Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis.

    PubMed

    Hao, Enkui; Mukhopadhyay, Partha; Cao, Zongxian; Erdélyi, Katalin; Holovac, Eileen; Liaudet, Lucas; Lee, Wen-Shin; Haskó, György; Mechoulam, Raphael; Pacher, Pál

    2015-01-06

    Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX's cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may

  3. Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis

    PubMed Central

    Hao, Enkui; Mukhopadhyay, Partha; Cao, Zongxian; Erdélyi, Katalin; Holovac, Eileen; Liaudet, Lucas; Lee, Wen-Shin; Haskó, György; Mechoulam, Raphael; Pacher, Pál

    2015-01-01

    Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX’s cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may

  4. Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice

    PubMed Central

    2011-01-01

    Background Cardiomyopathy in Duchenne muscular dystrophy (DMD) is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy. Methods Three month old female mdx mice were exposed to the β1 receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188) (460 mg/kg/dose i.p. daily). Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD) and picrosirius red staining. Results BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p < 0.02) and cardiac fibrosis (p < 0.01) over 4 weeks compared to unexposed controls. P188 treatment of mdx mice significantly increased heart rate (median 593 vs. 667 bpm; p < 0.001) after 2 weeks and prevented a decrease in cardiac function in isoproterenol exposed mice (Shortening Fraction = 46 ± 6% vs. 35 ± 6%; p = 0.007) after 4 weeks. P188 treated mdx mice did not show significant differences in cardiac fibrosis, but demonstrated significantly increased EBD positive fibers. Conclusions This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice. PMID:21575230

  5. A Clinical Risk Score to Improve the Diagnosis of Tachycardia-Induced Cardiomyopathy in Childhood.

    PubMed

    Moore, Jeremy P; Wang, Shuo; Albers, Erin L; Salerno, Jack C; Stephenson, Elizabeth A; Shah, Maully J; Pflaumer, Andreas; Czosek, Richard J; Garnreiter, Jason M; Collins, Kathryn; Papez, Andrew L; Sanatani, Shubhayan; Cain, Nicole B; Kannankeril, Prince J; Perry, James C; Mandapati, Ravi; Silva, Jennifer N A; Balaji, Seshadri; Shannon, Kevin M

    2016-10-01

    Tachycardia-induced cardiomyopathy (TIC) is a treatable cause of heart failure in children, but there is little information as to which clinical variables best discriminate TIC from other forms of cardiomyopathy. TIC cases with dilated cardiomyopathy (DC) from 16 participating centers were identified and compared with controls with other forms of DC. Presenting clinical, echocardiographic, and electrocardiographic characteristics were collected. Heart rate (HR) percentile was defined as HR/median HR for age, and PR index as the PR/RR interval. P-wave morphology (PWM) was defined as possible sinus or nonsinus based on a predefined algorithm. Eighty TIC cases and 135 controls were identified. Cases demonstrated lower LV end-diastolic diameter and LV end-systolic diameter than DC controls (4.3 vs 6.5, p <0.001; 7.4 vs 10.9, p <0.001) and were less likely to receive inotropic medication at presentation (p <0.001 for both). Multivariable logistic regression identified HR percentile (OR 2.1 per 10% increase, CI 1.3 to 4.6; p = 0.014), PR index (OR 1.2, CI 1.1 to 1.4; p = 0.004), and nonsinus PWM (OR 104.9, CI 15.2 to 1,659.8; p <0.001) as predictive of TIC status. A risk score using HR percentile >130%, PR index >30%, and nonsinus PWM was associated with a sensitivity of 100% and specificity of 87% for the diagnosis of TIC. Model training and validation area under the curves were similar at 0.97 and 0.94, respectively. In conclusion, pediatric TIC may be accurately discriminated from other forms of DC using simple electrocardiographic parameters. This may allow for rapid diagnosis and early treatment of this condition.

  6. [Comparison of preoperative and postoperative hemodynamic parameters in replacement or reconstruction of the mitral valve in ischemic dilated cardiomyopathy].

    PubMed

    Mijatov, M; Jonjev, Z; Konstantinović, Z; Golubović, M; Radovanović, N

    2000-01-01

    Ischemic mitral insufficiency is a clinical syndrome described as a consequence of the coronary artery disease where the basic problem is blood regurgitation between the left ventricle and left atrium following mitral annulus dilatation. Mitral regurgitation occurs in different degrees during the natural evolution of the ischemic heart disease. The main reason for the existence of mitral regurgitation is global deterioration in the left ventricle geometry as a consequence of myocardial infarction or/and left ventricle dilatation. Surgical correction of this problem is possible by simultaneous correction of mitral insufficiency (repair or replacement) and complete myocardial revascularisation. Complete hemodynamic monitoring was followed by Swan-Ganz catheter including: central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, cardiac index and pulmonary vascular resistance. All surgical procedures were performed in extracorporeal circulation (ECC) with membrane oxygenator using moderate systemic hypothermia and transseptal surgical approach to mitral valve. Hemodynamic parameters were followed before and after ECC, immediately after surgery and during the first 48 hours after operation in the intensive care unit. In 88 patients posterior semicircular annuloplasty by N. Radovanović was performed whereas in 13 patients mitral valve replacement was done. There is a great, statistically significant hemodynamic improvement after the surgical procedure and during the continuous 48 hours monitoring in the intensive care unit no matter if mitral repair or replacement was done. No statistically significant difference was recorded between these two groups considering that the hemodynamic improvement is very similar. Simultaneous surgical procedures, including myocardial revascularization, mitral and usually consecutive tricuspid insufficiency correction, are a very common surgical problem with higher operative risk than

  7. Cardiogenic Shock due to Psychosis-Induced Inverted Takotsubo Cardiomyopathy Bridged-to-Recovery with a Percutaneous Left Ventricular Assist Device

    PubMed Central

    Abel, Warren; Labovitz, Arthur

    2016-01-01

    Inverted Takotsubo cardiomyopathy, a less common variant in the spectrum of stress-induced cardiomyopathy, is increasingly being reported. This report describes an acute psychiatric illness leading to the onset of this syndrome. The patient presented here developed cardiogenic shock but successfully recovered with the use of a percutaneous left ventricular assist device. PMID:28058119

  8. Mitochondrial Peroxiredoxin-3 protects against hyperglycemia induced myocardial damage in Diabetic cardiomyopathy.

    PubMed

    Arkat, Silpa; Umbarkar, Prachi; Singh, Sarojini; Sitasawad, Sandhya L

    2016-08-01

    Mitochondrial oxidative stress has emerged as a key contributor towards the development of diabetic cardiomyopathy. Peroxiredoxin-3 (Prx-3), a mitochondrial antioxidant, scavenges H2O2 and offers protection against ROS related pathologies. We observed a decrease in the expression of Prx-3 in the hearts of streptozotocin (STZ) induced diabetic rats, and also high glucose treated H9c2 cardiac cells, which may augment oxidative stress mediated damage. Hence we hypothesized that overexpression of Prx-3 could prevent the cardiac damage associated with diabetes. In this study we used quercetin (QUE) to achieve Prx-3 induction in vivo, while a Prx-3 overexpressing H9c2 cell line was employed for carrying out in vitro studies. Diabetes was induced in Wistar rats by a single intraperitoneal injection of STZ. Quercetin (50mg/kg body weight) was delivered orally to hyperglycemic and age matched control rats for 2 months. Quercetin treatment induced the myocardial expression of Prx-3 but not Prx-5 both in control and STZ rats. Prx-3 induction by quercetin prevented diabetes induced oxidative stress as confirmed by decrease in expression of markers such as 4-HNE and mitochondrial uncoupling protein, UCP-3. It was also successful in reducing cardiac cell apoptosis, hypertrophy and fibrosis leading to amelioration of cardiac contractility defects. Overexpression of Prx-3 in cultured H9c2 cardiac cells could significantly diminish high glucose inflicted mitochondrial oxidative damage and apoptosis, thus strengthening our hypothesis. These results suggest that diabetes induced cardiomyopathy can be prevented by elevating Prx-3 levels thereby providing extensive protection to the diabetic heart.

  9. Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model.

    PubMed

    Martínez-Morentin, Leticia; Martínez, Lidia; Piloto, Sarah; Yang, Hua; Schon, Eric A; Garesse, Rafael; Bodmer, Rolf; Ocorr, Karen; Cervera, Margarita; Arredondo, Juan J

    2015-07-01

    The heart is a muscle with high energy demands. Hence, most patients with mitochondrial disease produced by defects in the oxidative phosphorylation (OXPHOS) system are susceptible to cardiac involvement. The presentation of mitochondrial cardiomyopathy includes hypertrophic, dilated and left ventricular noncompaction, but the molecular mechanisms involved in cardiac impairment are unknown. One of the most frequent OXPHOS defects in humans frequently associated with cardiomyopathy is cytochrome c oxidase (COX) deficiency caused by mutations in COX assembly factors such as Sco1 and Sco2. To investigate the molecular mechanisms that underlie the cardiomyopathy associated with Sco deficiency, we have heart specifically interfered scox expression, the single Drosophila Sco orthologue. Cardiac-specific knockdown of scox reduces fly lifespan, and it severely compromises heart function and structure, producing dilated cardiomyopathy. Cardiomyocytes with low levels of scox have a significant reduction in COX activity and they undergo a metabolic switch from OXPHOS to glycolysis, mimicking the clinical features found in patients harbouring Sco mutations. The major cardiac defects observed are produced by a significant increase in apoptosis, which is dp53-dependent. Genetic and molecular evidence strongly suggest that dp53 is directly involved in the development of the cardiomyopathy induced by scox deficiency. Remarkably, apoptosis is enhanced in the muscle and liver of Sco2 knock-out mice, clearly suggesting that cell death is a key feature of the COX deficiencies produced by mutations in Sco genes in humans.

  10. Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model

    PubMed Central

    Martínez-Morentin, Leticia; Martínez, Lidia; Piloto, Sarah; Yang, Hua; Schon, Eric A.; Garesse, Rafael; Bodmer, Rolf; Ocorr, Karen; Cervera, Margarita; Arredondo, Juan J.

    2015-01-01

    The heart is a muscle with high energy demands. Hence, most patients with mitochondrial disease produced by defects in the oxidative phosphorylation (OXPHOS) system are susceptible to cardiac involvement. The presentation of mitochondrial cardiomyopathy includes hypertrophic, dilated and left ventricular noncompaction, but the molecular mechanisms involved in cardiac impairment are unknown. One of the most frequent OXPHOS defects in humans frequently associated with cardiomyopathy is cytochrome c oxidase (COX) deficiency caused by mutations in COX assembly factors such as Sco1 and Sco2. To investigate the molecular mechanisms that underlie the cardiomyopathy associated with Sco deficiency, we have heart specifically interfered scox expression, the single Drosophila Sco orthologue. Cardiac-specific knockdown of scox reduces fly lifespan, and it severely compromises heart function and structure, producing dilated cardiomyopathy. Cardiomyocytes with low levels of scox have a significant reduction in COX activity and they undergo a metabolic switch from OXPHOS to glycolysis, mimicking the clinical features found in patients harbouring Sco mutations. The major cardiac defects observed are produced by a significant increase in apoptosis, which is dp53-dependent. Genetic and molecular evidence strongly suggest that dp53 is directly involved in the development of the cardiomyopathy induced by scox deficiency. Remarkably, apoptosis is enhanced in the muscle and liver of Sco2 knock-out mice, clearly suggesting that cell death is a key feature of the COX deficiencies produced by mutations in Sco genes in humans. PMID:25792727

  11. Ventricular Rhythm and Hypotension in a Patient with Pheochromocytoma-induced Myocardial Damage and Reverse Takotsubo Cardiomyopathy.

    PubMed

    Tagawa, Minoru; Nanba, Hitomi; Suzuki, Hiromi; Nakamura, Yuichi; Uchiyama, Hiroko; Ochiai, Sachie; Terunuma, Masahiro; Yahata, Kazuaki; Minamino, Tohru

    2015-01-01

    A 33-year-old woman experienced near-syncope at a hospital. Electrocardiography revealed an intermittent ventricular rhythm. The echocardiogram at admission indicated mild hypokinesis and severe diffuse hypokinesis with reverse takotsubo cardiomyopathy on the following day. The patient experienced abdominal pain on the admission day, and computed tomography identified a large left adrenal mass. Her catecholamine levels increased remarkably on the third day. The wall motion improved on the twelfth day. The tumor was successfully resected and the patient was diagnosed with an ectopic pheochromocytoma. The ventricular rhythm with myocardial damage and hypotension induced by the reverse takotsubo cardiomyopathy masked the characteristic symptoms of pheochromocytoma.

  12. Are the different patterns of stress-induced (Takotsubo) cardiomyopathy explained by regional mechanical overload and demand: supply mismatch in selected ventricular regions?

    PubMed

    Redfors, Bjorn; Shao, Yangzhen; Ali, Anwar; Omerovic, Elmir

    2013-11-01

    Takotsubo cardiomyopathy (TCM) or stress-induced cardiomyopathy is an increasingly recognized syndrome characterized by severe regional left ventricular dysfunction in the absence of an explanatory coronary lesion. TCM may lead to lethal complications but is completely reversible if the patient survives the acute phase. The pathogenesis of TCM and the mechanism behind this remarkable recovery are unknown. Plasma levels of catecholamine are elevated in many TCM patients and exogenously administered catecholamine induces TCM-like cardiac dysfunction in both humans and rats. A catecholamine excess increases myocardial metabolic demand by increasing the force of contraction as well as the heart rate, and also alters cardiac depolarization patterns. We propose that an altered spatiotemporal pattern of cardiac contraction and excessive force of contraction may lead to a redistribution of wall stresses in the left ventricle. This redistribution of wall stress causes regional mechanical overload of regions where wall tension becomes disproportionately great and renders these cardiomyocytes "metabolically insufficient". In other words, these cardiomyocytes experience a demand: supply mismatch on the basis of excessive metabolic demand. In order to prevent the death of these cardiomyocytes and to prevent excessive wall tension from developing in neighboring regions, a protective metabolic shutdown occurs in the affected cardiomyocytes. This metabolic shutdown, i.e., acute down regulation of non-vital cellular functions, serves to protect the affected regions from necrosis and explains the apparently complete recovery observed in TCM. We propose that this phenomenon may share important characteristics with phenomena such as ischemic conditioning, stunning and hibernation. In this manuscript, we discuss our hypothesis in the context of available knowledge and discuss important experiments that would help to corroborate or refute the hypothesis. Copyright © 2013 Elsevier Ltd

  13. Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy.

    PubMed

    Zhang, Ning; Yang, Zheng; Xiang, Shi-Zhao; Jin, Ya-Ge; Wei, Wen-Ying; Bian, Zhou-Yan; Deng, Wei; Tang, Qi-Zhu

    2016-06-01

    Diabetic cardiomyopathy, characterized by the presence of diastolic and/or systolic myocardial dysfunction, is one of the major causes of heart failure. Nobiletin, which is extracted from the fruit peel of citrus, is reported to possess anti-inflammatory, anti-oxidative, and hypolipidemic properties. The purpose of this study was to investigate whether nobiletin exerts the therapeutic effect on streptozotocin-induced diabetic cardiomyopathy (DCM) in mice. 80 experimental male C57BL mice were randomly assigned into four groups: sham + vehicle (VEH/SH), sham + nobiletin (NOB/SH), DCM + vehicle (VEH/DM), and DCM + nobiletin (NOB/DM). Nobiletin treatment ameliorated cardiac dysfunction in the DCM group, as shown by the result of echocardiography and hemodynamic measurements. Nobiletin treatment also blunted the mRNA expression of NADPH oxidase isoforms p67(phox), p22(phox), and p91(phox), and abated oxidative stress. Although administration of diabetic mice with nobiletin did not significantly effect the level of blood glucose, it decreased the TGF-β1, CTGF, fibronectin, and collagen Iα expressions and blunted cardiac fibrosis. In addition, nobiletin inhibited the activation of c-Jun NH2-terminal kinase (JNK), P38, and NF-κB in the cardiac tissue of diabetic mice. Collectively, our study indicates that treatment with nobiletin mitigates cardiac dysfunction and interstitial fibrosis, and these beneficial of nobiletin may belong to the suppression of JNK, P38, and NF-κB signaling pathways.

  14. Positive feedback induced memory effect in ischemic preconditioning.

    PubMed

    Shi, Jichen; Xu, Jian; Zhang, Xiaorong; Yang, Ling

    2012-05-07

    The memory of ischemic preconditioning remains a great mystery. Brief preconditioning (several sequential regional ischemia/reperfusion in minutes) can induce a two-phase protection that lasts up to 3 days. Thus comes the so-called memory of preconditioning. This memory effect has been attributed to a feed-forward signaling cascade. But recent experimental observations suggest that intra-mitochondrial positive feedback may be responsible for sustaining the protective effect. The link between positive feedback and memory is yet to be determined. In this study, we used a mathematical model to describe the way in which positive feedback induces memory in the first window of cardioprotection, and we derived an explicit relationship between the memory duration and the strength of the positive feedback. Our major findings are: (1) that positive feedback relying on a hysteresis response provides an effective way of prolonging protection up to any length; and (2) that the stronger the positive feedback, the longer the memory duration. Furthermore, compared with the feed-forward signaling cascade, positive feedback may be more favored by natural systems because of its robustness and high efficiency. The mechanisms described in this study have important implications for developments of experimental approaches as well as therapeutic strategies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Widespread Myocardial Delivery of Heart-Derived Stem Cells by Nonocclusive Triple-Vessel Intracoronary Infusion in Porcine Ischemic Cardiomyopathy: Superior Attenuation of Adverse Remodeling Documented by Magnetic Resonance Imaging and Histology

    PubMed Central

    Tseliou, Eleni; Kanazawa, Hideaki; Dawkins, James; Gallet, Romain; Kreke, Michelle; Smith, Rachel; Middleton, Ryan; Valle, Jackelyn; Marbán, Linda; Kar, Saibal; Makkar, Rajendra; Marbán, Eduardo

    2016-01-01

    Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients. PMID:26784932

  16. Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis.

    PubMed

    Fang, Qilu; Wang, Jingying; Zhang, Yali; Wang, Lintao; Li, Weixin; Han, Jibo; Huang, Weijian; Liang, Guang; Wang, Yi

    2017-09-28

    Obesity causes cardiovascular diseases, including cardiac hypertrophy and remodeling, via chronic tissue inflammation. Myeloid differentiation factor-2 (MD2), a binding protein of lipopolysaccharide, is functionally essential for the activation of proinflammatory pathways in endotoxin-induced acute inflammatory diseases. Here we tested the hypothesis that MD2 plays a central role in obesity-induced cardiomyopathy. Wildtype or MD2 knockout mice were fed with a high fat diet (HFD) or normal diet (Control) for total 16weeks, and MD2 inhibitor L6H21 (20mg/kg) or vehicle (1% CMC-Na) were administered from the beginning of the 9th week. HFD induced significant weight gain and cardiac hypertrophy, with increased cardiac fibrosis and inflammation. L6H21 administration or MD2 knockout attenuated HFD-induced obesity, inflammation and cardiac remodeling. In vitro exposure of H9C2 cells to high lipids induced cell hypertrophy with activated JNK/ERK and NF-κB pathways, which was abolished by pretreatment of MD2 inhibitor L6H21. Our results demonstrate that MD2 is essential to obesity-related cardiac hypertrophy through activating JNK/ERK and NF-κB-dependent cardiac inflammatory pathways. Targeting MD2 would be a therapeutic approach to prevent obesity-induced cardiac injury and remodeling. Copyright © 2017. Published by Elsevier B.V.

  17. Inducible pluripotent stem cells for the treatment of ischemic stroke: current status and problems.

    PubMed

    Zhu, Yu; Wan, Shu; Zhan, Ren-ya

    2012-01-01

    Despite dramatic advancements in medical and surgical care, effective clinical therapies for ischemic stroke are limited. Stem-cell transplantation has emerged as a potential therapeutic approach for cell replacement in ischemic brain injuries. Inducible pluripotent stem cells (iPSCs) have become an alternative cell source for transplantation. They possess efficient capacities for neural differentiation without ethical and immune-rejection concerns. Substantial function of iPSCs in pre-clinical models of ischemic brain injury has been observed. However, several problems remain regarding the treatment of ischemic stroke with iPSCs: tumorigenicity, poor iPSC derivation methods, and undefined delivery variables. With the development of iPSC research, safer and more effective strategies will be achieved for highly effective and tumor-free cell treatment of ischemic stroke.

  18. [Biochemical predictors of anthracyclin and trastuzumab induced cardiotoxicity in early diagnostics of cardiomyopathy].

    PubMed

    Słowik, Agnieszka; Lelakowska-Pieła, Maria; Konduracka, Ewa

    2016-01-01

    The treatment based on athracyclines and trastuzumab may lead to heart failure in oncological setting. Assessment of the heart function is conducted using radiological examinations, especially echocardiography. Biochemical diagnostics enables to depict clinically silent cardiac dysfunction at an earlier stage. Biomarkers that showed to be the most promising in predicting the development of deterioration of systolic and/or diastolic function in course of chemotherapy are troponins and NT-pro-BNP. However, no cut-off point had been yet determined, especially in terms of cardiotoxicity induced by oncological therapy. Biomarkers serum level may be dependent on many conditions, mostly comorbidities, what makes the interpretation of the results difficult. Trials involving mikro RNA particles, which depict the molecular level of the pathological changes, also those involved in the development of cardiomyopathy, are underway. © 2016 MEDPRESS.

  19. Distribution of myocardial glycogen in turkey poults during development of furazolidone-induced cardiomyopathy.

    PubMed

    Czarnecki, C M; Evanson, O A

    1980-07-01

    Furazolidone (FZ) at 700 ppm was added to feed mixtures fed turkey poults two weeks posthatching to induce experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. From ECG data obtained at weekly intervals, poults were selected for sacrifice at 3, 4, and 5 weeks of age. Myocardial samples from the right and left ventricular free walls were analyzed for glycogen by biochemical assay technics. Levels of glycogen were significantly (p less than .01) elevated in the FZ-treated poults at 3, 4, and 5 weeks of age. At all ages, the increase occurred in both the acid-soluble (TCA) and acid-insoluble (KOH) fractions with a proportionately greater increase in the TCA fraction. Results suggest that the effect of FZ on myocardial glycogen metabolism occurs very early and is more pronounced in the right ventricle than in the left ventricle even though both chambers may exhibit similar gross changes.

  20. Impact of repeated intravenous bone marrow mesenchymal stem cells infusion on myocardial collagen network remodeling in a rat model of doxorubicin-induced dilated cardiomyopathy.

    PubMed

    Yu, Qin; Li, Qianxiao; Na, Rongmei; Li, Xiaofei; Liu, Baiting; Meng, Lili; Liutong, Hanyu; Fang, Weiyi; Zhu, Ning; Zheng, Xiaoqun

    2014-02-01

    Bone marrow mesenchymal stem cells (MSCs) transplantation improved cardiac function and reduced myocardial fibrosis in both ischemic and non-ischemic cardiomyopathies. We evaluated the effects of repeated peripheral vein injection of MSCs on collagen network remodeling and myocardial TGF-β1, AT1, CYP11B2 (aldosterone synthase) gene expressions in a rat model of doxorubicin (DOX)-induced dilated cardiomyopathy (DCM). Thirty-eight out of 53 SD rats survived at 10 weeks post-DOX injection (2.5 mg/kg/week for 6 weeks, i.p.) were divided into DCM blank (without treatment, n = 12), DCM placebo (intravenous tail injection of 0.5 mL serum-free culture medium every other day for ten times, n = 13), and DCM plus MSCs group (intravenous tail injection of 5 × 10(6) MSCs dissolved in 0.5 mL serum-free culture medium every other day for 10 times, n = 13). Ten untreated rats served as normal controls. At 20 weeks after DOX injection, echocardiography, myocardial collagen content, myocardial expressions of types I and III collagen, TGF-β1, AT1, and CYP11B2 were compared among groups. At 20 weeks post-DOX injection, 8 rats (67%) survived in DCM blank group, 9 rats (69%) survived in DCM placebo group while 13 rats (100 %) survived in DCM plus MSCs group. Left ventricular end-diastolic diameter was significantly higher and ejection fraction was significantly lower in DCM blank and DCM placebo groups compared to normal control rats, which were significantly improved in DCM plus MSCs group (all p < 0.05 vs. DCM blank and DCM placebo groups). Moreover, myocardial collagen volume fraction, types I and III collagen, myocardial mRNA expressions of TGF-β1, AT1, CYP11B2, and collagen I/III ratio were all significantly lower in DCM plus MSCs group compared to DCM blank and DCM placebo groups (all p < 0.05). Repeated intravenous MSCs transplantation could improve cardiac function by attenuating myocardial collagen network remodeling possibly through downregulating renin

  1. Adenosine A2(A) receptor gene polymorphism (1976C>T) affects coronary flow reserve response during vasodilator stress testing in patients with non ischemic-dilated cardiomyopathy.

    PubMed

    Andreassi, Maria Grazia; Laghi Pasini, Franco; Picano, Eugenio; Capecchi, Pier Leopoldo; Pompella, Gerarda; Foffa, Ilenia; Borghini, Andrea; Sicari, Rosa

    2011-08-01

    Patients with non ischemic-dilated cardiomyopathy (DCM) are characterized by an activation of the adenosinergic system and reduced coronary flow reserve (CFR) evaluated by transthoracic Doppler echocardiography during vasodilator adenosinergic stress (dipyridamole administration). The aim of this study was to assess whether genetic polymorphisms (263C>T and 1976C>T) of the A2(A) receptor gene affect CFR response in patients with DCM. We enrolled a group of 80 patients with DCM (55 male; age, 62±10.3 years) and 162 healthy volunteers (55 male; age, 45.1±9.5 years). Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was determined in DCM. A2(A) receptor genotyping was determined in all patients by polymerase chain reaction-restriction fragment length polymorphism analysis. The expression of A2(A) protein and mRNA was also assessed in healthy controls. The genotype distribution of the 263C>T (P=0.5) and 1976C>T (P=0.8) polymorphisms was not significantly different between patients and controls. Patients with 1976TT genotype had significantly lower CFR value than 1976CC patients (2.3±0.7, 2.0±0.5 and 1.9±0.4, P<0.05 for CC, CT and TT genotypes, respectively). Controls who were heterozygous (P=0.02) or homozygous (P=0.001) for the T1976 allele showed a significant increase in A2(A) receptor protein. These data demonstrate that A2(A) 1976C>T polymorphism is associated with a blunted coronary vasodilatory response in patients with DCM, and support a direct consequences of this single nucleotide polymorphism for protein expression. Additional studies are needed to better define the functional role of this genetic variant as well as to clarify the potential clinical impact of genetics during pharmacological stress cardiac imaging.

  2. Relationship between native papillary muscle T1 time and severity of functional mitral regurgitation in patients with non-ischemic dilated cardiomyopathy.

    PubMed

    Kato, Shingo; Nakamori, Shiro; Roujol, Sébastien; Delling, Francesca N; Akhtari, Shadi; Jang, Jihye; Basha, Tamer; Berg, Sophie; Kissinger, Kraig V; Goddu, Beth; Manning, Warren J; Nezafat, Reza

    2016-11-16

    Functional mitral regurgitation is one of the severe complications of non-ischemic dilated cardiomyopathy (DCM). Non-contrast native T1 mapping has emerged as a non-invasive method to evaluate myocardial fibrosis. We sought to evaluate the potential relationship between papillary muscle T1 time and mitral regurgitation in DCM patients. Forty DCM patients (55 ± 13 years) and 20 healthy adult control subjects (54 ± 13 years) were studied. Native T1 mapping was performed using a slice interleaved T1 mapping sequence (STONE) which enables acquisition of 5 slices in the short-axis plane within a 90 s free-breathing scan. We measured papillary muscle diameter, length and shortening. DCM patients were allocated into 2 groups based on the presence or absence of functional mitral regurgitation. Papillary muscle T1 time was significantly elevated in DCM patients with mitral regurgitation (n = 22) in comparison to those without mitral regurgitation (n = 18) (anterior papillary muscle: 1127 ± 36 msec vs 1063 ± 16 msec, p < 0.05; posterior papillary muscle: 1124 ± 30 msec vs 1062 ± 19 msec, p < 0.05), but LV T1 time was similar (1129 ± 38 msec vs 1134 ± 58 msec, p = 0.93). Multivariate linear regression analysis showed that papillary muscle native T1 time (β = 0.10, 95 % CI: 0.05-0.17, p < 0.05) is significantly correlated with mitral regurgitant fraction. Elevated papillary muscle T1 time was associated with larger diameter, longer length and decreased papillary muscle shortening (all p values <0.05). In DCM, papillary muscle native T1 time is significantly elevated and related to mitral regurgitant fraction.

  3. Myocardial Expression Analysis of Osteopontin and Its Splice Variants in Patients Affected by End-Stage Idiopathic or Ischemic Dilated Cardiomyopathy

    PubMed Central

    Cabiati, Manuela; Svezia, Benedetta; Matteucci, Marco; Botta, Luca; Pucci, Angela; Rinaldi, Mauro; Caselli, Chiara; Lionetti, Vincenzo; Del Ry, Silvia

    2016-01-01

    Osteopontin (OPN) is a phosphoglycoprotein of cardiac extracellular matrix and it is still poorly defined whether its expression changes in failing heart of different origin. The full-length OPN-a and its isoforms (OPN-b, OPN-c) transcriptomic profile were evaluated in myocardium of patients with dilated or ischemic cardiomyopathy (DCM n = 8; LVEF% = 17.5±3; ICM n = 8; LVEF% = 19.5±5.2) and in auricle of valvular patients (VLP n = 5; LVEF%≥50), by Real-time PCR analysis. OPN-a and thrombin mRNA levels resulted significantly higher in DCM compared to ICM patients (DCM:31.3±7.4, ICM:2.7±1.1, p = 0.0002; DCM:19.1±4.9, ICM:5.4±2.2, p = 0.007, respectively). Although both genes’ mRNA levels increased in patients with LVEF<50% (DCM+ICM) with respect to VLP with LVEF>50%, a significant increase in OPN (p = 0.0004) and thrombin (p = 0.001) expression was observed only in DCM. In addition, a correlation between OPN-a and thrombin was found in patients with LVEF<50% (r = 0.6; p = 0.003). The mRNA pattern was confirmed by OPN-a cardiac protein concentration (VLP:1.127±0.26; DCM:1.29±0.22; ICM:1.00±0.077 ng/ml). The OPN splice variants expression were detectable only in ICM (OPN-b: 0.357±0.273; OPN-c: 0.091±0.033) and not in DCM patients. A significant correlation was observed between collagen type I, evaluated by immunohistochemistry analysis, and both OPN-a mRNA expression (r = 0.87, p = 0.002) and OPN protein concentrations (r = 0.77, p = 0.016). Concluding, OPN-a and thrombin mRNA resulted dependent on the origin of heart failure while OPN-b and OPN-c highlighted a different expression for DCM and ICM patients, suggesting their correlation with different clinical-pathophysiological setting. PMID:27479215

  4. Prediction of Appropriate Shocks Using 24-Hour Holter Variables and T-Wave Alternans After First Implantable Cardioverter-Defibrillator Implantation in Patients With Ischemic or Nonischemic Cardiomyopathy.

    PubMed

    Seegers, Joachim; Bergau, Leonard; Expósito, Pascal Muñoz; Bauer, Axel; Fischer, Thomas H; Lüthje, Lars; Hasenfuß, Gerd; Friede, Tim; Zabel, Markus

    2016-07-01

    In patients treated with implantable cardioverter defibrillator (ICD), prediction of both overall survival and occurrence of shocks is important if improved patient selection is desired. We prospectively studied the predictive value of biomarkers and indexes of cardiac and renal function and spectral microvolt T-wave alternans testing and 24-hour Holter variables in a population who underwent first ICD implantation. Consecutive patients in sinus rhythm with ischemic or dilated cardiomyopathy scheduled for primary or secondary prophylactic ICD implantation were enrolled. Exercise microvolt T-wave alternans and 24-hour Holter for number of ventricular premature contractions (VPCs), deceleration capacity, heart rate variability, and heart rate turbulence were done. Death of any cause and first appropriate ICD shock were defined as end points. Over 33 ± 15 months of follow-up, 36 of 253 patients (14%) received appropriate shocks and 39 of 253 patients (15%) died. Only 3 of 253 patients (1%) died after receiving at least 1 appropriate shock. In univariate analyses, New York Heart Association class, ejection fraction, N-terminal pro brain-type natriuretic peptide (NT-proBNP), renal function, ICD indication, deceleration capacity, heart rate variability, and heart rate turbulence were predictive of all-cause mortality and VPC number and deceleration capacity predicted first appropriate shock. NT-proBNP (≥1,600 pg/ml) was identified as the only independent predictor of all-cause mortality (hazard ratio 3.0, confidence interval 1.3 to 7.3, p = 0.014). In contrast, VPC number predicted appropriate shocks (hazard ratio 2.3, confidence interval 1.0 to 5.5, p = 0.047) as the only independent risk marker. In conclusion, NT-proBNP is a strong independent predictor of mortality in a typical prospective cohort of newly implanted patients with ICD, among many electrocardiographic and clinical variables studied. Number of VPCs was identified as a predictor of appropriate shocks

  5. Ranolazine versus placebo in patients with ischemic cardiomyopathy and persistent chest pain or dyspnea despite optimal medical and revascularization therapy: randomized, double-blind crossover pilot study

    PubMed Central

    Shammas, Nicolas W; Shammas, Gail A; Keyes, Kathleen; Duske, Shawna; Kelly, Ryan; Jerin, Michael

    2015-01-01

    Background Patients with ischemic cardiomyopathy (ICM) may continue to experience persistent chest pain and/or dyspnea despite pharmacologic therapy and revascularization. We hypothesized that ranolazine would reduce anginal symptoms or dyspnea in optimally treated ICM patients. Methods In this randomized, double-blind, crossover-design pilot study, 28 patients with ICM (ejection fraction less or equal 40%) were included after providing informed consent. A total of 24 patients completed both placebo and ranolazine treatments and were analyzed. All patients were on treatment with a beta blocker, an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker), and at least one additional antianginal drug. After randomization, patients received up to 1,000 mg ranolazine orally twice a day, as tolerated, versus placebo. The primary end point was change in angina as assessed by the Seattle Angina Questionnaire (SAQ), or in dyspnea as assessed by the Rose Dyspnea Scale (RDS). Change in the RDS and SAQ score from baseline was compared, for ranolazine and placebo, using the Wilcoxon signed rank test or paired t-test. Results Patients had the following demographic and clinical variables: mean age of 71.5 years; male (82.1%); prior coronary bypass surgery (67.9%); prior coronary percutaneous intervention (85.7%); prior myocardial infarction (82.1%); diabetes (67.9%); and mean ejection fraction of 33.1%. No statistical difference was seen between baseline RDS score and that after placebo or ranolazine (n=20) (P≥0.05). There was however, an improvement in anginal frequency (8/10 patients) (P=0.058), quality of life (8/10 patients) (P=0.048), and mean score of all components of the SAQ questionnaire (n=10) (P=0.047) with ranolazine compared with placebo. Conclusion In optimally treated ICM patients with continued chest pain or dyspnea, ranolazine possibly had a positive impact on quality of life, a reduction in anginal frequency, and an overall improvement in the

  6. Metallothionein as a compensatory component prevents intermittent hypoxia-induced cardiomyopathy in mice

    SciTech Connect

    Yin, Xia; Zhou, Shanshan; Zheng, Yang; Tan, Yi; Kong, Maiying; Wang, Bo; Feng, Wenke; Epstein, Paul N.; Cai, Jun; Cai, Lu

    2014-05-15

    Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (IH) to induce cardiovascular disease, which may be related to oxidative damage. Metallothionein (MT) has been extensively proved to be an endogenous and highly inducible antioxidant protein expressed in the heart. Therefore, we tested the hypotheses that oxidative stress plays a critical role in OSA induced cardiac damage and MT protects the heart from OSA-induced cardiomyopathy. To mimic hypoxia/reoxygenation events that occur in adult OSA patients, mice were exposed to IH for 3 days to 8 weeks. The IH paradigm consisted of alternating cycles of 20.9% O{sub 2}/8% O{sub 2} F{sub I}O{sub 2} (30 episodes per hour) with 20 s at the nadir F{sub I}O{sub 2} for 12 h a day during daylight. IH significantly increased the ratio of heart weight to tibia length at 4 weeks with a decrease in cardiac function from 4 to 8 weeks. Cardiac oxidative damage and fibrosis were observed after 4 and 8 weeks of IH exposures. Endogenous MT expression was up-regulated in response to 3-day IH, but significantly decreased at 4 and 8 weeks of IH. In support of MT as a major compensatory component, mice with cardiac overexpression of MT gene and mice with global MT gene deletion were completely resistant, and highly sensitive, respectively, to chronic IH induced cardiac effects. These findings suggest that chronic IH induces cardiomyopathy characterized by oxidative stress-mediated cardiac damage and the antioxidant MT protects the heart from such pathological and functional changes. - Highlights: • The effect of intermittent hypoxia (IH) on cardiac metallothionein (MT) • Cardiac MT expression was up-regulated in response to 3-day IH. • Exposure to 4- or 8-week IH downregulated cardiac MT expression. • Overexpression of cardiac MT protects from IH-induced cardiac damage. • Global deletion of MT gene made the heart more sensitive to IH damage.

  7. [Genetic diagnostics for cardiomyopathies].

    PubMed

    Czepluch, Frauke; Wollnik, Bernd; Hasenfuß, Gerd

    2017-05-01

    Cardiomyopathies often have a genetic etiology. New genetic diagnostic strategies based on next generation sequencing (NGS)-approaches will continuously increase our knowledge about the genetic basis of cardiomyopathies within the following years. Diagnostics and therapy of rare, genetically-induced cardiac diseases increasingly require special cardiac and genetic knowledge. Interestingly, mutations in the same gene or even identical gene mutations can be associated with different cardiomyopathy phenotypes and can exhibit incomplete penetrance or variable expressivity. In the future, the correct interpretation and classification of novel gene variants identified in patients with inherited cardiomyopathy forms will represent a great challenge. Genetic counselling and - if appropriate - subsequent genetic testing for cardiomyopathy patients and their asymptomatic relatives is essential for an early diagnosis of the disease, a prognostic evaluation and possibly for the start of preventive or therapeutic measures. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Thrombin induces ischemic LTP (iLTP): implications for synaptic plasticity in the acute phase of ischemic stroke

    PubMed Central

    Stein, Efrat Shavit; Itsekson-Hayosh, Zeev; Aronovich, Anna; Reisner, Yair; Bushi, Doron; Pick, Chaim G.; Tanne, David; Chapman, Joab; Vlachos, Andreas; Maggio, Nicola

    2015-01-01

    Acute brain ischemia modifies synaptic plasticity by inducing ischemic long-term potentiation (iLTP) of synaptic transmission through the activation of N-Methyl-D-aspartate receptors (NMDAR). Thrombin, a blood coagulation factor, affects synaptic plasticity in an NMDAR dependent manner. Since its activity and concentration is increased in brain tissue upon acute stroke, we sought to clarify whether thrombin could mediate iLTP through the activation of its receptor Protease-Activated receptor 1 (PAR1). Extracellular recordings were obtained in CA1 region of hippocampal slices from C57BL/6 mice. In vitro ischemia was induced by acute (3 minutes) oxygen and glucose deprivation (OGD). A specific ex vivo enzymatic assay was employed to assess thrombin activity in hippocampal slices, while OGD-induced changes in prothrombin mRNA levels were assessed by (RT)qPCR. Upon OGD, thrombin activity increased in hippocampal slices. A robust potentiation of excitatory synaptic strength was detected, which occluded the ability to induce further LTP. Inhibition of either thrombin or its receptor PAR1 blocked iLTP and restored the physiological, stimulus induced LTP. Our study provides important insights on the early changes occurring at excitatory synapses after ischemia and indicates the thrombin/PAR1 pathway as a novel target for developing therapeutic strategies to restore synaptic function in the acute phase of ischemic stroke. PMID:25604482

  9. Rationale and design of the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy.

    PubMed

    Mushtaq, Muzammil; DiFede, Darcy L; Golpanian, Samuel; Khan, Aisha; Gomes, Samirah A; Mendizabal, Adam; Heldman, Alan W; Hare, Joshua M

    2014-12-01

    While accumulating clinical trials have focused on the impact of cell therapy in patients with acute myocardial infarction (MI) and ischemic cardiomyopathy, there are fewer efforts to examine cell-based therapy in patients with non-ischemic cardiomyopathy (NICM). We hypothesized that cell therapy could have a similar impact in NICM. The POSEIDON-DCM trial is a phase I/II trial designed to address autologous vs. allogeneic bone marrow-derived mesenchymal stem cells (MSCs) in patients with NICM. In this study, cells will be administered transendocardially with the NOGA injection-catheter system to patients (n = 36) randomly allocated to two treatment groups: group 1 (n = 18 auto-human mesenchymal stem cells (hMSC)) and group 2 (n = 18 allo-hMSCs). The primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCS vs. auto-hMSCs in patients with NICM. This study will establish safety of transendocardial injection of stem cells (TESI), compare phenotypic outcomes, and offer promising advances in the field of cell-based therapy in patients with NICM.

  10. Astragalus polysaccharide improves cardiac function in doxorubicin-induced cardiomyopathy through ROS-p38 signaling

    PubMed Central

    Zhou, Liangliang; Chen, Lanping; Wang, Jing; Deng, Yijun

    2015-01-01

    Doxorubicin (DOX) is widely used as an antitumor agent, but it is significantly challenged by clinical workers due to the severe and acute cardiotoxitity. Astragalus polysaccharide (APS) is characterized by an anti-inflammation and anti-oxidant features. In the current study, we explored the effects and specific mechanisms of APS on DOX-induced-cardiomyopathy in mouse primary myocardial cells. To explore the effect of DOX on ROS production, DHE staining and flow cytometry analysis were used in primary cardiomyocytes treated with 1 μM DOX for 24 h. MTT assay was applied to determine the effect of DOX on cell viability. The effects of DOX on rat cardiomyocytes apoptosis by Hoechst staining and annexin V-PI staining, while caspase3 activity was determined using an assay kit. Two-dimensional echocardiography of rats was performed to determine left ventricular fraction and relative wall thickness. Activation of p38 and Akt was analyzed using western blot. ROS production was significantly enhanced by DOX stimulation in primary cardiomyocytes. DOX reduced rat cardiomyocytes viability in a time- and dose-dependent manner. DOX induced apoptosis in rat cardiomyocytes via activation of caspase-3. Cardiac function was significantly impaired by enhanced p38 activation. APS treatment reduced DOX-induced rat cardiomyocytes apoptosis by decreasing ROS production. To conclude, APS reduced DOX-induced cell apoptosis and ROS production by reduced activation of p38 signaling pathway. PMID:26885153

  11. Astragalus polysaccharide improves cardiac function in doxorubicin-induced cardiomyopathy through ROS-p38 signaling.

    PubMed

    Zhou, Liangliang; Chen, Lanping; Wang, Jing; Deng, Yijun

    2015-01-01

    Doxorubicin (DOX) is widely used as an antitumor agent, but it is significantly challenged by clinical workers due to the severe and acute cardiotoxitity. Astragalus polysaccharide (APS) is characterized by an anti-inflammation and anti-oxidant features. In the current study, we explored the effects and specific mechanisms of APS on DOX-induced-cardiomyopathy in mouse primary myocardial cells. To explore the effect of DOX on ROS production, DHE staining and flow cytometry analysis were used in primary cardiomyocytes treated with 1 μM DOX for 24 h. MTT assay was applied to determine the effect of DOX on cell viability. The effects of DOX on rat cardiomyocytes apoptosis by Hoechst staining and annexin V-PI staining, while caspase3 activity was determined using an assay kit. Two-dimensional echocardiography of rats was performed to determine left ventricular fraction and relative wall thickness. Activation of p38 and Akt was analyzed using western blot. ROS production was significantly enhanced by DOX stimulation in primary cardiomyocytes. DOX reduced rat cardiomyocytes viability in a time- and dose-dependent manner. DOX induced apoptosis in rat cardiomyocytes via activation of caspase-3. Cardiac function was significantly impaired by enhanced p38 activation. APS treatment reduced DOX-induced rat cardiomyocytes apoptosis by decreasing ROS production. To conclude, APS reduced DOX-induced cell apoptosis and ROS production by reduced activation of p38 signaling pathway.

  12. Activation of NR2A receptors induces ischemic tolerance through CREB signaling.

    PubMed

    Terasaki, Yasukazu; Sasaki, Tsutomu; Yagita, Yoshiki; Okazaki, Shuhei; Sugiyama, Yukio; Oyama, Naoki; Omura-Matsuoka, Emi; Sakoda, Saburo; Kitagawa, Kazuo

    2010-08-01

    Previous exposure to a nonlethal ischemic insult protects the brain against subsequent harmful ischemia. N-methyl-D-aspartate (NMDA) receptors are a highly studied target of neuroprotection after ischemia. Recently, NMDA receptor subtypes were implicated in neuronal survival and death. We focused on the contribution of NR2A and cyclic-AMP response element (CRE)-binding protein (CREB) signaling to ischemic tolerance using primary cortical neurons. Ischemia in vitro was modeled by oxygen-glucose deprivation (OGD). Ischemic tolerance was induced by applying 45-mins OGD 24 h before 180-mins OGD. Sublethal OGD also induced cross-tolerance against lethal glutamate and hydrogen peroxide. After sublethal OGD, expression of phosphorylated CREB and CRE transcriptional activity were significantly increased. When CRE activity was inhibited by CREB-S133A, a mutant CREB, ischemic tolerance was abolished. Inhibiting NR2A using NVP-AAM077 attenuated preconditioning-induced neuroprotection and correlated with decreased CRE activity levels. Activating NR2A using bicuculline and 4-aminopiridine induced resistance to lethal ischemia accompanied by elevated CRE activity levels, and this effect was abolished by NVP-AAM077. Elevated brain-derived neurotrophic factor (BDNF) transcriptional activities were observed after sublethal OGD and administration of bicuculline and 4-aminopiridine. NR2A-containing NMDA receptors and CREB signaling have important functions in the induction of ischemic tolerance. This may provide potential novel therapeutic strategies to treat ischemic stroke.

  13. Treatment of refractory ischemic pain from chemotherapy-induced Raynaud's syndrome with spinal cord stimulation.

    PubMed

    Ting, Joseph C; Fukshansky, Mikhail; Burton, Allen W

    2007-06-01

    We report the successful treatment of refractory ischemic pain from cisplatin-induced Raynaud's syndrome with spinal cord stimulation after failed pharmacologic management and surgical sympathectomy. A 48-year-old man developed ischemic pain of the hands while undergoing cisplatin and gemcitabine chemotherapy for metastatic pancreatic carcinoma. After extensive pharmacologic management and surgical sympathectomy failed to provide adequate analgesia, the patient underwent a percutaneous spinal cord stimulation trial followed by permanent implantation and received significant pain relief prior to succumbing to his illness. Spinal cord stimulation provided effective therapy for refractory ischemic pain, even after failed sympathectomy.

  14. Transgenic expression of replication-restricted enteroviral genomes in heart muscle induces defective excitation-contraction coupling and dilated cardiomyopathy.

    PubMed Central

    Wessely, R; Klingel, K; Santana, L F; Dalton, N; Hongo, M; Jonathan Lederer, W; Kandolf, R; Knowlton, K U

    1998-01-01

    Numerous studies have implicated Coxsackievirus in acute and chronic heart failure. Although enteroviral nucleic acids have been detected in selected patients with dilated cardiomyopathy, the significance of such persistent nucleic acids is unknown. To investigate the mechanisms by which restricted viral replication with low level expression of Coxsackieviral proteins may be able to induce cardiomyopathy, we generated transgenic mice which express a replication-restricted full-length Coxsackievirus B3 (CVB3) cDNA mutant (CVB3DeltaVP0) in the heart driven by the cardiac myocyte-specific myosin light chain-2v (MLC-2v) promoter. CVB3DeltaVP0 was generated by mutating infectious CVB3 cDNA at the VP4/VP2 autocatalytic cleavage site from Asn-Ser to Lys-Ala. Cardiac-specific expression of this cDNA leads to synthesis of positive- and negative-strand viral RNA in the heart without formation of infectious viral progeny. Histopathologic analysis of transgenic hearts revealed typical morphologic features of myocardial interstitial fibrosis and in some cases degeneration of myocytes, thus resembling dilated cardiomyopathy in humans. There was also an increase in ventricular atrial natriuretic factor mRNA levels, demonstrating activation of the embryonic program of gene expression typical of ventricular hypertrophy and failure. Echocardiographic analysis demonstrated the presence of left ventricular dilation and decreased systolic function in the transgenic mice compared with wild-type littermates, evidenced by increased ventricular end-diastolic and end-systolic dimensions and decreased fractional shortening. Analysis of isolated myocytes from transgenic mice demonstrate that there is defective excitation-contraction coupling and a decrease in the magnitude of isolated cell shortening. These data demonstrate that restricted replication of enteroviral genomes in the heart can induce dilated cardiomyopathy with excitation-contraction coupling abnormalities similar to pressure

  15. S-diclofenac Protects against Doxorubicin-Induced Cardiomyopathy in Mice via Ameliorating Cardiac Gap Junction Remodeling

    PubMed Central

    Zhang, Huili; Zhang, Alian; Guo, Changfa; Shi, Chunzhi; Zhang, Yang; Liu, Qing; Sparatore, Anna; Wang, Changqian

    2011-01-01

    Hydrogen sulfide (H2S), as a novel gaseous mediator, plays important roles in mammalian cardiovascular tissues. In the present study, we investigated the cardioprotective effect of S-diclofenac (2-[(2,6-dichlorophenyl)amino] benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester), a novel H2S-releasing derivative of diclofenac, in a murine model of doxorubicin-induced cardiomyopathy. After a single dose injection of doxorubicin (15 mg/kg, i.p.), male C57BL/6J mice were given daily treatment of S-diclofenac (25 and 50 µmol/kg, i.p.), diclofenac (25 and 50 µmol/kg, i.p.), NaHS (50 µmol/kg, i.p.), or same volume of vehicle. The cardioprotective effect of S-diclofenac was observed after 14 days. It showed that S-diclofenac, but not diclofenac, dose-dependently inhibited the doxorubicin-induced downregulation of cardiac gap junction proteins (connexin 43 and connexin 45) and thus reversed the remodeling of gap junctions in hearts. It also dose-dependently suppressed doxorubicin-induced activation of JNK in hearts. Furthermore, S-diclofenac produced a dose-dependent anti-inflammatory and anti-oxidative effect in this model. As a result, S-diclofenac significantly attenuated doxorubicin-related cardiac injury and cardiac dysfunction, and improved the survival rate of mice with doxorubicin-induced cardiomyopathy. These effects of S-diclofenac were mimicked in large part by NaHS. Therefore, we propose that H2S released from S-diclofenac in vivo contributes to the protective effect in doxorubicin-induced cardiomyopathy. These data also provide evidence for a critical role of H2S in the pathogenesis of doxorubicin-induced cardiomyopathy. PMID:22039489

  16. Ischemic Preconditioning Blunts Muscle Damage Responses Induced by Eccentric Exercise.

    PubMed

    Franz, Alexander; Behringer, Michael; Harmsen, Jan-Frieder; Mayer, Constantin; Krauspe, Rüdiger; Zilkens, Christoph; Schumann, Moritz

    2017-08-22

    Ischemic preconditioning (IPC) is known to reduce muscle damage induced by ischemia and reperfusion-injury (I/R-Injury) during surgery. Due to similarities between the pathophysiological formation of I/R-injury and eccentric exercise-induced muscle damage (EIMD), as characterized by an intracellular accumulation of Ca, an increased production of reactive oxygen species and increased pro-inflammatory signaling, the purpose of the present study was to investigate whether IPC performed prior to eccentric exercise may also protect against EIMD. Nineteen healthy men were matched to an eccentric only (ECC) (n=9) or eccentric proceeded by IPC group (IPC+ECC) (n=10). The exercise protocol consisted of bilateral biceps curls (3x10 repetitions at 80% of the concentric 1RM). In IPC+ECC, IPC was applied bilaterally at the upper arms by a tourniquet (200 mmHg) immediately prior to the exercise (3x5 minutes of occlusion, separated by 5 minutes of reperfusion). Creatine Kinase (CK), arm circumference, subjective pain (VAS score) and radial displacement (Tensiomyography, Dm) were assessed before IPC, pre-exercise, post-exercise, 20 minutes-, 2 hours-, 24 hours-, 48 hours- and 72 hours post-exercise. CK differed from baseline only in ECC at 48h (p<0.001) and 72h (p<0.001) post-exercise. After 24h, 48h and 72h, CK was increased in ECC compared to IPC+ECC (between groups: 24h: p=0.004, 48h: p<0.001, 72h: p<0.001). VAS was significantly higher in ECC at 24-72 h post-exercise, when compared to IPC+ECC (between groups: all p<0.001). Dm was decreased on all post-exercise days in ECC (all p<0.001) but remained statistically unchanged in IPC+ECC (between-groups p<0.01). These findings indicate that IPC performed prior to a bout of eccentric exercise of the elbow flexors blunts EIMD and exercise-induced pain, while maintaining the contractile properties of the muscle.

  17. Medicinal chemistry of drugs used in diabetic cardiomyopathy.

    PubMed

    Adeghate, E; Kalasz, H; Veress, G; Teke, K

    2010-01-01

    Diabetes mellitus is a common disease and contributes to a high degree of morbidity and mortality. Cardiovascular complications, including diabetic cardiomyopathy are major causes of morbidity and mortality in diabetic patients. Diabetic cardiomyopathy is a condition that affects the myocardium, primarily. It is not necessarily associated with ischemic heart disease, high blood pressure, valvular or congenital anomalies. The pathology of diabetic cardiomyopathy includes interstitial fibrosis, apoptosis of cardiomyocytes, abnormal energy utilization, small vessel disease and cardiac neuropathy. These pathologies are induced by hyperglycemia and oxidative stress. Biochemical as well as electrolyte changes, especially reduced calcium availability also occurs in the myocardium of diabetic patients. The abnormal structure and biochemistry of the myocardium result in functional problems such as diastolic and systolic dysfunctions, which may cause symptoms of dyspnea and inability to tolerate exercise. No single specific therapeutic agent can treat diabetic cardiomyopathy because once the disease is overt, the management may require a variety of approaches such as risk factors and lifestyle modification, glucose control (insulin, alpha glucosidase inhibitors, sulfonylureas, biguanides, meglitinides, thiazolidinediones and dipeptidyl peptidase 4 (DPP-4) inhibitors); hormones (IGF-1); ACE inhibitors (captopril, enalapril); angiotensin II receptor antagonists (losartan, olmesartan); beta adrenoreceptor antagonists (acebutolol, carvedilol); peptides (adrenomedullin); endothelin-1 receptor antagonists (bosentan, tezosentan); calcium channel blockers (amlodipine, verapamil); antioxidants (methalothionein, alpha tocopherol, alpha lipoic acid) and antihyperlipidemic drugs (simvastatin, fenofibrate, ezetimibe) to effectively treat patients with diabetic cardiomyopathy.

  18. Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

    PubMed Central

    Aulakh, Amritpal Singh; Randhawa, Puneet Kaur; Singh, Nirmal

    2017-01-01

    Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection. PMID:28280407

  19. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis

    PubMed Central

    Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P.; De Geest, Bart

    2017-01-01

    Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05) in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64) during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold (p < 0.01) higher in coconut oil mice than in standard chow mice. Myocardial capillary density (p < 0.001) was decreased, interstitial fibrosis was 1.88-fold (p < 0.001) higher, and systolic and diastolic function was worse in coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold (p < 0.001) higher in coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower (p < 0.05) in coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy. PMID:28718833

  20. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis.

    PubMed

    Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P; De Geest, Bart

    2017-07-18

    Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05) in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64) during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold (p < 0.01) higher in coconut oil mice than in standard chow mice. Myocardial capillary density (p < 0.001) was decreased, interstitial fibrosis was 1.88-fold (p < 0.001) higher, and systolic and diastolic function was worse in coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold (p < 0.001) higher in coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower (p < 0.05) in coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy.

  1. What's Cardiomyopathy

    MedlinePlus

    ... people in the U.S. with children under 12 accounting for less than 10% of all cases. According ... RCM) is the least common type of cardiomyopathy accounting for only 5% of patients with cardiomyopathy. It ...

  2. Peripartum cardiomyopathy.

    PubMed

    Grixti, Sarah; Magri, Caroline J; Xuereb, Robert; Fava, Stephen

    2015-02-01

    Peripartum cardiomyopathy is a form of dilated cardiomyopathy of indeterminate aetiology occurring in late pregnancy or the months following delivery. This article reviews current knowledge of its pathophysiology, therapeutic strategies and prognosis, as well as new treatments and future directions.

  3. Structural and biochemical remodelling in catecholamine-induced cardiomyopathy: comparative and ontogenetic aspects.

    PubMed

    Ostádal, B; Pelouch, V; Ostádalová, I; Nováková, O

    Excessive release or administration of beta-mimetic catecholamines may induce cardiomegaly, necrotic lesions and accumulation of connective tissue in the heart of adult homoiotherms. It was examined here whether similar changes can also be observed at different stages of evolution of the cardiovascular system, i.e. in poikilotherms and in homoiotherms during embryonic life. Sensitivity of the poikilothermic hearts (carp, frog, turtle) to isoproterenol (IPRO) was significantly lower than in the homoiotherms. Necrotic lesions, if present, were localized in the inner spongious musculature which has no vascular supply but which exhibits higher activities of enzymes connected with aerobic oxidation. Moreover, the IPRO-induced decrease of the phospholipid content was also significantly more expressed in the spongious layer. IPRO treatment did not influence the total weight of the fish heart but the proportion of the outer compact layer was significantly higher. These changes were accompanied by an increase of collagen, higher water content and an increase of isomyosin with a lower ATPase activity. The response of the poikilothermic heart to IPRO-induced overload thus differs significantly from that in the homoiotherms. The administration of IPRO during embryonic life of homoiotherms (chick) induces serious cardiovascular disturbances, including cardiomegaly and cellular oedema. Necroses of myofibrils, characteristic of IPRO-induced lesions of adults, were, however, rather exceptional. IPRO did not elevate the concentration of 85Sr (as a calcium homologue) in the immature myocardium; it seems, therefore, that IPRO-induced changes of the embryonic heart are not necessarily due to an intracellular calcium overload. It may be concluded that the character of catecholamine-induced cardiomyopathy is not uniform and depends strictly on the stage of cardiac development.

  4. Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure

    PubMed Central

    Maier, Harald J.; Schips, Tobias G.; Wietelmann, Astrid; Krüger, Marcus; Brunner, Cornelia; Sauter, Martina; Klingel, Karin; Böttger, Thomas; Braun, Thomas; Wirth, Thomas

    2012-01-01

    Inflammation is a major factor in heart disease. IκB kinase (IKK) and its downstream target NF-κB are regulators of inflammation and are activated in cardiac disorders, but their precise contributions and targets are unclear. We analyzed IKK/NF-κB function in the heart by a gain-of-function approach, generating an inducible transgenic mouse model with cardiomyocyte-specific expression of constitutively active IKK2. In adult animals, IKK2 activation led to inflammatory dilated cardiomyopathy and heart failure. Transgenic hearts showed infiltration with CD11b+ cells, fibrosis, fetal reprogramming, and atrophy of myocytes with strong constitutively active IKK2 expression. Upon transgene inactivation, the disease was reversible even at an advanced stage. IKK-induced cardiomyopathy was dependent on NF-κB activation, as in vivo expression of IκBα superrepressor, an inhibitor of NF-κB, prevented the development of disease. Gene expression and proteomic analyses revealed enhanced expression of inflammatory cytokines, and an IFN type I signature with activation of the IFN-stimulated gene 15 (ISG15) pathway. In that respect, IKK-induced cardiomyopathy resembled Coxsackievirus-induced myocarditis, during which the NF-κB and ISG15 pathways were also activated. Vice versa, in cardiomyocytes lacking the regulatory subunit of IKK (IKKγ/NEMO), the induction of ISG15 was attenuated. We conclude that IKK/NF-κB activation in cardiomyocytes is sufficient to cause cardiomyopathy and heart failure by inducing an excessive inflammatory response and myocyte atrophy. PMID:22753500

  5. NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats

    SciTech Connect

    Park, Joonghoon; Park, Eok; Ahn, Bong-Hyun; Kim, Hyoung Jin; Park, Ji-hoon; Koo, Sun Young; Kwak, Hyo-Shin; Park, Heui Sul; Kim, Dong Wook; Song, Myoungsub; Yim, Hyeon Joo; Seo, Dong Ook; Kim, Soon Ha

    2012-08-15

    Oxidative stress is one of the causes of cardiomyopathy. In the present study, NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for cardioprotection in in vitro and in vivo model, and the putative mechanism of the cardioprotection of NecroX-7 was investigated by global gene expression profiling and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced death of H9C2 rat cardiomyocytes at EC{sub 50} = 0.057 μM. In doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) which were increased by DOX treatment (p < 0.05). Microarray analysis revealed that 21 genes differentially expressed in tBHP-treated H9C2 cells were involved in ‘Production of reactive oxygen species’ (p = 0.022), and they were resolved by concurrent NecroX-7 treatment. Gene-to-gene networking also identified that NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity by 53.3% (p < 0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. -- Highlights: ► NecroX-7 prevented tert-butyl hydroperoxide-induced in vitro cardiac cell death. ► NecroX-7 ameliorated doxorubicin-induced in vivo cardiomyopathy. ► NecroX-7 prevented oxidative stress and necrosis-enriched transcriptional changes. ► NecroX-7 effectively inhibited NADPH oxidase activation. ► Cardioprotection of Necro-7 was brought on by modulation of NADPH oxidase activity.

  6. Stress-related cardiomyopathies

    PubMed Central

    2011-01-01

    Stress-related cardiomyopathies can be observed in the four following situations: Takotsubo cardiomyopathy or apical ballooning syndrome; acute left ventricular dysfunction associated with subarachnoid hemorrhage; acute left ventricular dysfunction associated with pheochromocytoma and exogenous catecholamine administration; acute left ventricular dysfunction in the critically ill. Cardiac toxicity was mediated more by catecholamines released directly into the heart via neural connection than by those reaching the heart via the bloodstream. The mechanisms underlying the association between this generalized autonomic storm secondary to a life-threatening stress and myocardial toxicity are widely discussed. Takotsubo cardiomyopathy has been reported all over the world and has been acknowledged by the American Heart Association as a form of reversible cardiomyopathy. Four "Mayo Clinic" diagnostic criteria are required for the diagnosis of Takotsubo cardiomyopathy: 1) transient left ventricular wall motion abnormalities involving the apical and/or midventricular myocardial segments with wall motion abnormalities extending beyond a single epicardial coronary artery distribution; 2) absence of obstructive epicardial coronary artery disease that could be responsible for the observed wall motion abnormality; 3) ECG abnormalities, such as transient ST-segment elevation and/or diffuse T wave inversion associated with a slight troponin elevation; and 4) the lack of proven pheochromocytoma and myocarditis. ECG changes and LV dysfunction occur frequently following subarachnoid hemorrhage and ischemic stroke. This entity, referred as neurocardiogenic stunning, was called neurogenic stress-related cardiomyopathy. Stress-related cardiomyopathy has been reported in patients with pheochromocytoma and in patients receiving intravenous exogenous catecholamine administration. The role of a huge increase in endogenous and/or exogenous catecholamine level in critically ill patients

  7. Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan mice

    PubMed Central

    MacFarlane, Elena Gallo; Takimoto, Eiki; Chaudhary, Rahul; Nagpal, Varun; Rainer, Peter P.; Bindman, Julia G.; Gerber, Elizabeth E.; Bedja, Djahida; Schiefer, Christopher; Miller, Karen L.; Zhu, Guangshuo; Myers, Loretha; Amat-Alarcon, Nuria; Lee, Dong I.; Koitabashi, Norimichi; Judge, Daniel P.; Dietz, Harry C.

    2017-01-01

    Among children with the most severe presentation of Marfan syndrome (MFS), an inherited disorder of connective tissue caused by a deficiency of extracellular fibrillin-1, heart failure is the leading cause of death. Here, we show that, while MFS mice (Fbn1C1039G/+ mice) typically have normal cardiac function, pressure overload (PO) induces an acute and severe dilated cardiomyopathy in association with fibrosis and myocyte enlargement. Failing MFS hearts show high expression of TGF-β ligands, with increased TGF-β signaling in both nonmyocytes and myocytes; pathologic ERK activation is restricted to the nonmyocyte compartment. Informatively, TGF-β, angiotensin II type 1 receptor (AT1R), or ERK antagonism (with neutralizing antibody, losartan, or MEK inhibitor, respectively) prevents load-induced cardiac decompensation in MFS mice, despite persistent PO. In situ analyses revealed an unanticipated axis of activation in nonmyocytes, with AT1R-dependent ERK activation driving TGF-β ligand expression that culminates in both autocrine and paracrine overdrive of TGF-β signaling. The full compensation seen in wild-type mice exposed to mild PO correlates with enhanced deposition of extracellular fibrillin-1. Taken together, these data suggest that fibrillin-1 contributes to cardiac reserve in the face of hemodynamic stress, critically implicate nonmyocytes in disease pathogenesis, and validate ERK as a therapeutic target in MFS-related cardiac decompensation. PMID:28768908

  8. Depletion of T lymphocytes ameliorates cardiac fibrosis in streptozotocin-induced diabetic cardiomyopathy.

    PubMed

    Abdullah, Chowdhury S; Li, Zhao; Wang, Xiuqing; Jin, Zhu-Qiu

    2016-10-01

    T cell infiltration has been associated with increased coronary heart disease risk in patients with diabetes mellitus. Effect of modulation of T cell trafficking on diabetes-induced cardiac fibrosis has yet to be determined. Therefore, our aim was to investigate the circulatory T cell depletion-mediated cardioprotection in streptozotocin-induced diabetic cardiomyopathy. Fingolimod (FTY720), an immunomodulatory drug, was tested in wild-type (WT) C57BL/6 and recombination activating gene 1 (Rag1) knockout (KO) mice without mature lymphocytes in streptozotocin-induced type 1 diabetic model. FTY720 (0.3mg/kg/day) was administered intraperitoneally daily for the first 4weeks with interim 3weeks then resumed for another 4weeks in 11weeks study period. T lymphocyte counts, cardiac histology, function, and fibrosis were examined in diabetic both WT and KO mice. FTY720 reduced both CD4(+) and CD8(+) T cells in diabetic WT mice. FTY720-treated diabetic WT mouse myocardium showed reduction in CD3 T cell infiltration and decreased expression of S1P1 and TGF-β1 in cardiac tissue. Fibrosis was reduced after FTY720 treatment in diabetic WT mice. Rag1 KO mice exhibited no CD4(+) and CD8(+) T cells in the blood and CD3 T cells in the heart. Diabetic Rag1 KO mouse hearts appeared no fibrosis and exhibited preserved myocardial contractility. FTY720-induced antifibrosis was abolished in diabetic Rag1 KO mice. These findings demonstrate that chronic administration with FTY720 induces lymphopenia and protects diabetic hearts in WT mice whereas FTY720 increases cardiac fibrosis and myocardial dysfunction in diabetic Rag1 KO mice without mature lymphocytes.

  9. Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis

    PubMed Central

    Maya, Lisandro; Villarreal, Francisco J.

    2009-01-01

    In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies is termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, it is imperative the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in cardiac function are typically manifested as abnormal diastolic function that with time leads to loss of contractile function. Echocardiography based methods currently stands as the preferred diagnostic approach for diabetic cardiomyopathy, due to its wide availability and economical use. In addition to conventional techniques, magnetic resonance imaging and spectroscopy along with contrast agents are now leading new approaches in the diagnosis of myocardial fibrosis, and cardiac and hepatic metabolic changes. These strategies can be complemented with serum biomarkers so they can offer a clear picture as to diabetes-induced changes in cardiac structure/function even at very early stages of the disease. This review article intends to provide a summary of experimental and routine tools currently available to diagnose diabetic cardiomyopathy induced changes in cardiac structure/function. These tools can be reliably used in either experimental models of diabetes or for clinical applications. PMID:19595694

  10. Fragmented QRS as a Marker of Electrical Dyssynchrony to Predict Inter-Ventricular Conduction Defect by Subsequent Echocardiographic Assessment in Symptomatic Patients of Non-Ischemic Dilated Cardiomyopathy

    PubMed Central

    Sinha, Santosh Kumar; Bhagat, Kush; Asif, Mohammad; Singh, Karandeep; Sachan, Mohit; Mishra, Vikas; Afdaali, Nasar; Jha, Mukesh Jitendra; Kumar, Ashutosh; Singh, Shravan; Sinha, Rupesh; Khanra, Dibbendhu; Thakur, Ramesh; Varma, Chandra Mohan; Krishna, Vinay; Pandey, Umeshwar

    2016-01-01

    Background Left ventricular (LV) dyssynchrony frequently occurs in patients with heart failure (HF). QRS ≥ 120 ms is a surrogate marker of electrical dyssynchrony, which occurs in only 30% of HF patients. In contrary, in those with normal QRS (nQRS) duration, LV dyssynchrony has been reported in 20-50%. This study was carried out to investigate the role of fragmented QRS (fQRS) on the surface electrocardiography (ECG) as a marker of electrical dyssynchrony to predict the presence of significant intraventricular dyssynchrony (IVD) by subsequent echocardiographic assessment. Methods A total of 226 consecutive patients with non-ischemic cardiomyopathy were assessed for fQRS on surface ECG as defined by presence of an additional R wave (R prime), notching in nadir of the S wave, notching of R wave, or the presence of more than one R prime (fragmentation) in two contiguous leads corresponding to a major myocardial segment. Tissue Doppler imaging (TDI) was performed in the apical views (four-chamber, two-chamber and long-axis) to analyze all 12 segments at both basal and middle levels. Time-to-peak myocardial sustained systolic (Ts) velocities were calculated. Significant systolic IVD was defined as Ts-SD > 32.6 ms as known as “Yu index”. Result Of the total patients, 112 had fQRS (49.5%), while 114 had nQRS (50.5%) with male dominance (M/F = 71:29). Majority of patients were in NYHA class II (n = 122, 54%) followed by class III (n = 83; 37%), and class IV (n = 21; 9%). There were no significant differences among both groups for baseline parameters except higher QRS duration (102.42 ± 14.05 vs. 91.10 ± 13.75 ms; P = 0.001), higher Yu index (35.64 ± 12.79 vs. 20.45 ± 11.17; P = 0.01) and number of patients with positive Yu index (78.6% vs. 21.1%; P = 0.04) in group with fQRS compared with group with nQRS. fQRS complexes had 84.61% sensitivity and 80.32% specificity with positive predictive value of 78.6% and negative predictive value of 85.9% to detect IVD. On

  11. Fragmented QRS as a Marker of Electrical Dyssynchrony to Predict Inter-Ventricular Conduction Defect by Subsequent Echocardiographic Assessment in Symptomatic Patients of Non-Ischemic Dilated Cardiomyopathy.

    PubMed

    Sinha, Santosh Kumar; Bhagat, Kush; Asif, Mohammad; Singh, Karandeep; Sachan, Mohit; Mishra, Vikas; Afdaali, Nasar; Jha, Mukesh Jitendra; Kumar, Ashutosh; Singh, Shravan; Sinha, Rupesh; Khanra, Dibbendhu; Thakur, Ramesh; Varma, Chandra Mohan; Krishna, Vinay; Pandey, Umeshwar

    2016-08-01

    Left ventricular (LV) dyssynchrony frequently occurs in patients with heart failure (HF). QRS ≥ 120 ms is a surrogate marker of electrical dyssynchrony, which occurs in only 30% of HF patients. In contrary, in those with normal QRS (nQRS) duration, LV dyssynchrony has been reported in 20-50%. This study was carried out to investigate the role of fragmented QRS (fQRS) on the surface electrocardiography (ECG) as a marker of electrical dyssynchrony to predict the presence of significant intraventricular dyssynchrony (IVD) by subsequent echocardiographic assessment. A total of 226 consecutive patients with non-ischemic cardiomyopathy were assessed for fQRS on surface ECG as defined by presence of an additional R wave (R prime), notching in nadir of the S wave, notching of R wave, or the presence of more than one R prime (fragmentation) in two contiguous leads corresponding to a major myocardial segment. Tissue Doppler imaging (TDI) was performed in the apical views (four-chamber, two-chamber and long-axis) to analyze all 12 segments at both basal and middle levels. Time-to-peak myocardial sustained systolic (Ts) velocities were calculated. Significant systolic IVD was defined as Ts-SD > 32.6 ms as known as "Yu index". Of the total patients, 112 had fQRS (49.5%), while 114 had nQRS (50.5%) with male dominance (M/F = 71:29). Majority of patients were in NYHA class II (n = 122, 54%) followed by class III (n = 83; 37%), and class IV (n = 21; 9%). There were no significant differences among both groups for baseline parameters except higher QRS duration (102.42 ± 14.05 vs. 91.10 ± 13.75 ms; P = 0.001), higher Yu index (35.64 ± 12.79 vs. 20.45 ± 11.17; P = 0.01) and number of patients with positive Yu index (78.6% vs. 21.1%; P = 0.04) in group with fQRS compared with group with nQRS. fQRS complexes had 84.61% sensitivity and 80.32% specificity with positive predictive value of 78.6% and negative predictive value of 85.9% to detect IVD. On detailed segmental analysis for

  12. Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes

    SciTech Connect

    Saygili, Erol; Noor-Ebad, Fawad; Schröder, Jörg W.; Mischke, Karl; Saygili, Esra; Rackauskas, Gediminas; Marx, Nikolaus; Kelm, Malte; Rana, Obaida R.

    2015-09-11

    Background: Autoantibodies have been identified as major predisposing factors for dilated cardiomyopathy (DCM). Patients with DCM show elevated serum levels of vascular endothelial growth factor (VEGF) whose source is unknown. Besides its well-investigated effects on angiogenesis, evidence is present that VEGF signaling is additionally involved in fibroblast proliferation and cardiomyocyte hypertrophy, hence in cardiac remodeling. Whether autoimmune effects in DCM impact cardiac VEGF signaling needs to be elucidated. Methods: Five DCM patients were treated by the immunoadsorption (IA) therapy on five consecutive days. The eluents from the IA columns were collected and prepared for cell culture. Cardiomyocytes from neonatal rats (NRCM) were incubated with increasing DCM-immunoglobulin-G (IgG) concentrations for 48 h. Polyclonal IgG (Venimmun N), which was used to restore IgG plasma levels in DCM patients after the IA therapy was additionally used for control cell culture purposes. Results: Elevated serum levels of VEGF decreased significantly after IA (Serum VEGF (ng/ml); DCM pre-IA: 45 ± 9.1 vs. DCM post–IA: 29 ± 6.7; P < 0.05). In cell culture, pretreatment of NRCM by DCM-IgG induced VEGF expression in a time and dose dependent manner. Biologically active VEGF that was secreted by NRCM significantly increased BNP mRNA levels in control cardiomyocytes and induced cell-proliferation of cultured cardiac fibroblast (Fibroblast proliferation; NRCM medium/HC-IgG: 1 ± 0.0 vs. NRCM medium/DCM-IgG 100 ng/ml: 5.6 ± 0.9; P < 0.05). Conclusion: The present study extends the knowledge about the possible link between autoimmune signaling in DCM and VEGF induction. Whether this observation plays a considerable role in cardiac remodeling during DCM development needs to be further elucidated. - Highlights: • Mechanisms of remodeling in dilated cardiomyopathy (DCM) are not fully understood. • Autoantibodies have been identified as major predisposing factors

  13. Pediatric Cardiomyopathies.

    PubMed

    Lee, Teresa M; Hsu, Daphne T; Kantor, Paul; Towbin, Jeffrey A; Ware, Stephanie M; Colan, Steven D; Chung, Wendy K; Jefferies, John L; Rossano, Joseph W; Castleberry, Chesney D; Addonizio, Linda J; Lal, Ashwin K; Lamour, Jacqueline M; Miller, Erin M; Thrush, Philip T; Czachor, Jason D; Razoky, Hiedy; Hill, Ashley; Lipshultz, Steven E

    2017-09-15

    Pediatric cardiomyopathies are rare diseases with an annual incidence of 1.1 to 1.5 per 100 000. Dilated and hypertrophic cardiomyopathies are the most common; restrictive, noncompaction, and mixed cardiomyopathies occur infrequently; and arrhythmogenic right ventricular cardiomyopathy is rare. Pediatric cardiomyopathies can result from coronary artery abnormalities, tachyarrhythmias, exposure to infection or toxins, or secondary to other underlying disorders. Increasingly, the importance of genetic mutations in the pathogenesis of isolated or syndromic pediatric cardiomyopathies is becoming apparent. Pediatric cardiomyopathies often occur in the absence of comorbidities, such as atherosclerosis, hypertension, renal dysfunction, and diabetes mellitus; as a result, they offer insights into the primary pathogenesis of myocardial dysfunction. Large international registries have characterized the epidemiology, cause, and outcomes of pediatric cardiomyopathies. Although adult and pediatric cardiomyopathies have similar morphological and clinical manifestations, their outcomes differ significantly. Within 2 years of presentation, normalization of function occurs in 20% of children with dilated cardiomyopathy, and 40% die or undergo transplantation. Infants with hypertrophic cardiomyopathy have a 2-year mortality of 30%, whereas death is rare in older children. Sudden death is rare. Molecular evidence indicates that gene expression differs between adult and pediatric cardiomyopathies, suggesting that treatment response may differ as well. Clinical trials to support evidence-based treatments and the development of disease-specific therapies for pediatric cardiomyopathies are in their infancy. This compendium summarizes current knowledge of the genetic and molecular origins, clinical course, and outcomes of the most common phenotypic presentations of pediatric cardiomyopathies and highlights key areas where additional research is required. URL: http

  14. Cardiomyopathy Induced by Pulmonary Sequestration in a 50-Year-Old Man

    PubMed Central

    Chatelain, Shaun; Comp, Robert A.; Grace, R. Randal

    2015-01-01

    A 50-year-old black man presented at the emergency department with midsternal, nonradiating chest pressure and chronic dyspnea on exertion. Four years before the current admission, he had been diagnosed with nonischemic cardiomyopathy at another facility. After our complete evaluation, we suspected that his symptoms arose from left-to-left shunting in association with pulmonary sequestration, a congenital malformation. Our preliminary diagnosis of secondary dilated cardiomyopathy was confirmed by normalization of the patient's ventricular size and function after lobectomy. To our knowledge, this patient is the oldest on record to present with cardiomyopathy consequent to pulmonary sequestration. His case is highly unusual because of his age and the rapid resolution of his symptoms after lobectomy. We believe that pulmonary sequestration should be included in the differential diagnosis of dilated cardiomyopathy. PMID:25873803

  15. Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy

    EPA Science Inventory

    Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were...

  16. Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy

    EPA Science Inventory

    Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were...

  17. BPA-induced DNA hypermethylation of the master mitochondrial gene PGC-1α contributes to cardiomyopathy in male rats.

    PubMed

    Jiang, Ying; Xia, Wei; Yang, Jie; Zhu, Yingshuang; Chang, Huailong; Liu, Juan; Huo, Wenqian; Xu, Bing; Chen, Xi; Li, Yuanyuan; Xu, Shunqing

    2015-03-02

    Implication of environmental endocrine disruptors, such as bisphenol A (BPA), on the development of cardiopathy has been poorly investigated. The aim of the study was to investigate the effects of long-term exposure to BPA at the reference dose on the myocardium of rats, and the underlying mechanisms. Male rats received corn oil or 50 μg/kg/day of BPA since delactation. At 24 and 48 weeks (wk), cardiac function and mitochondrial function were examined. The mRNA expression and the methylation status of PCG-1α, a major regulator of mitochondrial biogenesis in cardiac muscle, were also tested. At 48 wk, BPA-exposed rats displayed cardiomyopathy, characterized by myocardium hypertrophy, cardiomyocyte enlargement, and impairment of cardiac function. At 24 wk, significantly reduced ATP production, dissipated mitochondrial membrane potential (Ψm) and declined mitochondrial respiratory complex (MRC) activity in cardiomyocytes were observed in BPA-exposed rats compared with the control rats, indicating a decrease in mitochondrial function occurs before the development of cardiomyopathy. Additionally, BPA exposure decreased the expression of PGC-1α and induced hypermethylation of PGC-1 α in heart tissue in 24- and 48-week-old rats. The change in methylation of PGC-1α was observed more pronounced in BPA-exposed rats at 48 wk. Overall, long-term BPA exposure induces cardiomyopathy in male rats, and the underlying mechanism may involve the impairment of cardiac mitochondrial function and the disturbance of methylation of PGC-1α.

  18. Dendrobium officinale Kimura et Migo attenuates diabetic cardiomyopathy through inhibiting oxidative stress, inflammation and fibrosis in streptozotocin-induced mice.

    PubMed

    Zhang, Zhihao; Zhang, Duoduo; Dou, Mengmeng; Li, Zhubo; Zhang, Jie; Zhao, Xiaoyan

    2016-12-01

    Dendrobium officinale Kimura et Migo (Dendrobium catenatum Lindley), a prized traditional Chinese Medicine, has been used in China and Southeast Asian countries for centuries. The present study was aimed to investigate the effects and the possible mechanisms of the Dendrobium officinale extracts (DOE) on diabetic cardiomyopathy in mice. The diabetic model was induced by intraperitoneal injection of streptozotocin at the dose of 50mg/kg body weight for 5 consecutive days. After 8 weeks treatment of DOE, mice were sacrificed, blood sample and heart tissues were collected. Our results showed that Streptozotocin-induced diabetic model was effectively achieved and serum CK and LDH levels were significantly increased in mice with diabetic cardiomyopathy. Pretreatment with DOE decreased the heart-to-body weight ratio (HW/BW) and showed an evident hypoglycemic effect. DOE pretreatment significantly decreased CK, LDH, TC and TG levels, limited the production of MDA and increased the activities of T-SOD. The histological analysis of Oil red O staining and Sirius red staining showed an obvious amelioration of cardiac injury, inhibition of cardiac lipid accumulation and deposition of collagen when pretreatment with DOE. In addition, Western blot detection and analysis showed that DOE down-regulated the expression of TGF-β, collegan-1, fibronectin, NF-κB, TNF-α and IL-1β. In conclusion, our study suggested that DOE possesses the cardioprotective potential against diabetic cardiomyopathy, which may be due to the inhibition of oxidative stress, cardiac lipid accumulation, pro-inflammatory cytokines and cardiac fibrosis.

  19. Stress-induced cardiomyopathy following infection of the upper respiratory tract in an elderly female patient: A case report

    PubMed Central

    Ding, Huaiyu; Huang, Rongchong; Shi, Xiaoli; Wu, Baolin

    2016-01-01

    Stress-induced cardiomyopathy (SIC), also known as takotsubo cardiomyopathy (TTC), is a relatively newly-described condition, which has been increasingly reported in the literature. It is characterized by acute onset of symptoms and electrocardiogram changes mimicking myocardial infarction, with transient but completely reversible left ventricular (LV) dysfunction. SIC commonly occurs following physical or emotional stress. The present study discusses the case of a 68-year-old female patient who had suffered from infection of the upper respiratory tract for 10 days before admission to the hospital with symptoms of chest stuffiness and dyspnea that persisted for 2 days. Coronary angiography showed normal coronary artery function, while LV angiography demonstrated systolic apical ballooning. Based on these observed characteristics, the patient was diagnosed with SIC and was successfully treated. PMID:27882121

  20. Acute and Chronic Pheochromocytoma-Induced Cardiomyopathies: Different Prognoses?: A Systematic Analytical Review.

    PubMed

    Batisse-Lignier, Marie; Pereira, Bruno; Motreff, Pascal; Pierrard, Romain; Burnot, Christelle; Vorilhon, Charles; Maqdasy, Salwan; Roche, Béatrice; Desbiez, Francoise; Clerfond, Guillaume; Citron, Bernard; Lusson, Jean-René; Tauveron, Igor; Eschalier, Romain

    2015-12-01

    Pheochromocytoma and paraganglioma (PPG) are rare and late-diagnosed catecholamine secreting tumors, which may be associated with unrecognized and/or severe cardiomyopathies. We performed a computer-assisted systematic search of the electronic Medline databases using the MESH terms "myocarditis," "myocardial infarction," "Takotsubo," "stress cardiomyopathy," "cardiogenic shock", or "dilated cardiomyopathy," and "pheochromocytoma" or "paraganglioma" from 1961 to August 2012. All detailed case reports of cardiomyopathy due to a PPG, without coronary stenosis, and revealed by acute symptoms were included and analyzed. A total of 145 cases reports were collected (49 Takotsubo Cardiomyopathies [TTC] and 96 other Catecholamine Cardiomyopathies [CC]). At initial presentation, prevalence of high blood pressure (87.7%), chest pain (49.0%), headaches (47.6%), palpitations (46.9%), sweating (39.3%), and shock (51.0%) were comparable between CC and TTC. Acute pulmonary edema (58.3% vs 38.8%, P = 0.03) was more frequent in CC. There was no difference in proportion of patients with severe left ventricular systolic dysfunction (LV Ejection Fraction [LVEF] < 30%) at initial presentation between both groups (P = 0.15). LVEF recovery before (64.9% vs 40.8%, P = 0.005) and after surgical resection (97.7% vs 73.3%, P = 0.001) was higher in the TTC group. Death occurred in 11 cases (7.6%). In multivariate analysis, only TTC was associated with a better LV recovery (0.15 [0.03-0.67], P = 0.03). Pheochromocytoma and paraganglioma can lead to different cardiomyopathies with the same brutal and life-threatening initial clinical presentation but with a different recovery rate. Diagnosis of unexplained dilated cardiomyopathy or TTC should lead clinicians to a specific search for PPG.

  1. The right heart in athletes. Evidence for exercise-induced arrhythmogenic right ventricular cardiomyopathy.

    PubMed

    Heidbüchel, H; La Gerche, A

    2012-06-01

    Although 'athlete's heart' usually constitutes a balanced dilation and hypertrophy of all four chambers, there is increasing evidence that intense endurance activity may particularly tax the right ventricle (RV), both acutely and chronically. We review the evidence that the high wall stress of the RV during intense sports may explain observed B-type natriuretic peptide (BNP) elevations immediately after a race, may lead to cellular disruption and leaking of cardiac enzymes, and may even result in transient RV dilatation and dysfunction. Over time, this could lead to chronic remodelling and a pro-arrhythmic state resembling arrhythmogenic RV cardiomyopathy (ARVC) in some cases. ARVC in high-endurance athletes most often develops in the absence of underlying desmosomal abnormalities, probably only as a result of excessive RV wall stress during exercise. Therefore, we have labelled this syndrome 'exercise-induced ARVC'. Sports cardiologists should be aware that excessive sports activity can lead to cardiac sports injuries in some individuals, just like orthopaedic specialists are familiar with musculoskeletal sports injuries. This does not negate the fact that moderate exercise has positive cardiovascular effects and should be encouraged.

  2. [Myocardial pseudo-infarction: "stress"-associated catecholamine-induced acute cardiomyopathy or coronary spasm?].

    PubMed

    Boulmier, D; Bazin, P

    2000-12-01

    As well as pheochromocytoma, in which it has been established that an excess of circulating catecholamines is responsible for the development of catecholamine-induced acute myopathy, some rare cases have been reported of a similar cardiac incident following intense emotional stress. In this study, the case has been examined of a 56-year old female with no history of cardiovascular disorder who presented with intense, nitro-resistant prolonged chest pain mimicking an acute coronary syndrome immediately following a situation involving major psychological stress. The admission electrocardiogram revealed a sharp decrease in R-wave amplitude in the right chest leads associated with an extended QT interval, and secondarily with subepicardiac ischemia in the lower leads. However, a few days after admission the electrical signs and septo-apical akinesia that had initially been observed by echocardiography completely disappeared. The clinical examination ruled out a diagnosis of myocardial necrosis, acute myocarditis, or pheochromocytoma. Moreover, no direct evidence of coronary spasm was found. The outcome was positive, with complete reversibility of all clinical signs and no organic sequelae. It is considered that this was probably a case of catecholaminergic acute cardiomyopathy triggered by intense emotional stress, a rare occurrence that should nevertheless be systematically taken into account in cases with similar clinical signs.

  3. Layer-specific quantification of myocardial deformation in sepsis-induced Takotsubo cardiomyopathy

    PubMed Central

    Hung, Ming-Jui; Kao, Yu-Cheng; Chen, Wei-Siang; Mao, Chun-Tai; Chen, Tien-Hsing; Yang, Ning-I.; Ko, Ta; Liang, Chung-Yu

    2016-01-01

    Abstract Introduction: Little is known about the time-course changes in left ventricular myocardial deformation in patients with Takotsubo cardiomyopathy (TC) using layer-specific quantification of myocardial deformation assessed by 2-dimensional speckle tracking echocardiography (2DSTE). Case summary: In this retrospective 2DSTE follow-up study of 3 female patients with sepsis-induced TC, we examined changes in strain among the 3 myocardial layers, and examined the changes in left ventricular diastolic function and right ventricular systolic function. In all 3 patients, there was improvement of at least 15% in left ventricular ejection fractions, and improvement in left ventricular longitudinal and circumferential strains. The absolute differences in left ventricular global strains between the endocardium and epicardium, and between the first and the third 2DSTE studies reflect the following: a decrease in all 3 myocardial layers in patients with acute TC; and a slower improvement in mid-myocardial and epicardial function during recovery of TC. In addition, the right ventricular free wall strains were also impaired in the acute stage of TC with gradual improvement during recovery. Conclusions: Left ventricular strains did not fully recover even 1 month after acute TC. In addition, right ventricular free wall strains were also impaired in all 3 patients initially. In this case series, we found that layer-specific 2DSTE is a more sensitive method for myocardial function assessment than standard echocardiography. PMID:27858884

  4. Pituitary metastasis presenting as ischemic pituitary apoplexy following heparin-induced thrombocytopenia.

    PubMed

    Kruljac, Ivan; Cerina, Vatroslav; Pećina, Hrvoje Ivan; Pažanin, Leo; Matić, Tomas; Božikov, Velimir; Vrkljan, Milan

    2012-12-01

    Pituitary apoplexy (PA) typically results from infarction or hemorrhage in a pituitary adenoma, while PA in nonadenomatous pituitary gland is uncommon. Prothrombotic states have never been recognized as precipitating factors for PA. The authors report a case of an elderly female who received prophylactic fractionated heparin therapy due to sepsis, consequent rhabdomyolysis, and overt disseminated intravascular coagulation. On the seventh day of heparin therapy, she reported sudden vision loss, ptosis, diplopia, and severe headache. Severe thrombocytopenia and positive antibodies to the complex of platelet factor 4 and heparin confirmed heparin-induced thrombocytopenia type 2 (HIT). Magnetic resonance imaging disclosed a homogenous pituitary tumor mass with pronounced sphenoid sinus mucosa thickening and two hypointense zones within the tumor mass on contrast-enhanced images consistent with focal ischemic necrosis. The tumor was confirmed to be squamous cell carcinoma with no signs of necrosis. Ischemic necrosis was found within marginal pituitary tissue. This is the first reported case of ischemic PA associated with pituitary metastasis and the first case in which HIT triggered PA. Our case demonstrates that prothrombotic states such as HIT can precipitate ischemic PA. Pituitary metastasis can present with ischemic PA, but radiological features differ from those described in pituitary adenomas. Segregated low-signal intensity zones within the tumor mass on postcontrast images indicate partial infarction of the tumor, which could be a special feature of ischemic PA in pituitary metastasis and has never been described in pituitary adenomas. These are all novel findings and might enlighten the pathogenesis of PA.

  5. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage.

    PubMed

    Bae, Ok-Nam; Majid, Arshad

    2013-08-21

    Urgent need exists for new therapeutic options in ischemic stroke. We recently demonstrated that carnosine, an endogenous dipeptide consisting of alanine and histidine, is robustly neuroprotective in ischemic brain injury and has a wide clinically relevant therapeutic time window. The precise mechanistic pathways that mediate this neuroprotective effect are not known. Following in vivo administration, carnosine is hydrolyzed into histidine, a precursor of histamine. It has been hypothesized that carnosine may exert its neuroprotective activities through the histidine/histamine pathway. Herein, we investigated whether the neuroprotective effect of carnosine is mediated by the histidine/histamine pathway using in vitro primary astrocytes and cortical neurons, and an in vivo rat model of ischemic stroke. In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death. In primary neuronal cultures, carnosine was found to be neuroprotective but histamine receptor antagonists had no effect on the extent of neuroprotection. The in vivo effect of histidine and carnosine was compared using a rat model of ischemic stroke; only carnosine exhibited neuroprotection. Taken together, our data demonstrate that although the protective effects of carnosine may be partially mediated by activity at the histamine type 1 receptor on astrocytes, the histidine/histamine pathway does not appear to play a critical role in carnosine induced neuroprotection.

  6. PACAP38/PAC1 Signaling Induces Bone Marrow-Derived Cells Homing to Ischemic Brain

    PubMed Central

    Lin, Chen-Huan; Chiu, Lian; Lee, Hsu-Tung; Chiang, Chun-Wei; Liu, Shih-Ping; Hsu, Yung-Hsiang; Lin, Shinn-Zong; Hsu, Chung Y; Hsieh, Chia-Hung; Shyu, Woei-Cherng

    2015-01-01

    Understanding stem cell homing, which is governed by environmental signals from the surrounding niche, is important for developing effective stem cell-based repair strategies. The molecular mechanism by which the brain under ischemic stress recruits bone marrow-derived cells (BMDCs) to the vascular niche remains poorly characterized. Here we report that hypoxia-inducible factor-1α (HIF-1α) activation upregulates pituitary adenylate cyclase-activating peptide 38 (PACAP38), which in turn activates PACAP type 1 receptor (PAC1) under hypoxia in vitro and cerebral ischemia in vivo. BMDCs homing to endothelial cells in the ischemic brain are mediated by HIF-1α activation of the PACAP38-PAC1 signaling cascade followed by upregulation of cellular prion protein and α6-integrin to enhance the ability of BMDCs to bind laminin in the vascular niche. Exogenous PACAP38 confers a similar effect in facilitating BMDCs homing into the ischemic brain, resulting in reduction of ischemic brain injury. These findings suggest a novel HIF-1α-activated PACAP38-PAC1 signaling process in initiating BMDCs homing into the ischemic brain for reducing brain injury and enhancing functional recovery after ischemic stroke. Stem Cells 2015;33:1153–1172 PMID:25523790

  7. A Metabolomic Study of Rats with Doxorubicin-Induced Cardiomyopathy and Shengmai Injection Treatment

    PubMed Central

    Chen, Yu; Tang, Yong; Zhang, Ya-Chen; Huang, Xiao-Hong; Xie, Yu-Quan; Xiang, Yin

    2015-01-01

    Doxorubicin-induced cardiomyopathy (DOX-CM) is a severe complication of doxorubicin (DOX) chemotherapy. Characterized by cumulative and irreversible myocardial damage, its pathogenesis has not been fully elucidated. Shengmai Injection (SMI), a Traditional Chinese Medicine, may alleviate myocardial injury and improve heart function in the setting of DOX-CM. As a result of its multi-component and multi-target nature and comprehensive regulation, the pharmacological mechanisms underlying SMI’s effects remain obscure. The emerging field of metabolomics provides a potential approach with which to explore the pathogenesis of DOX-CM and the benefits of SMI treatment. DOX-CM was induced in rats via intraperitoneal injections of DOX. Cardiac metabolic profiling was performed via gas chromatography/mass spectrometry and ultra-performance liquid chromatography/tandem mass spectrometry. A bioinformatics analysis was conducted via Ingenuity Pathway Analysis (IPA). Eight weeks following DOX treatment, significant cardiac remodeling, dysfunction and metabolic perturbations were observed in the rats with DOX-CM. The metabolic disturbances primarily involved lipids, amino acids, vitamins and energy metabolism, and may have been indicative of both an energy metabolism disorder and oxidative stress secondary to DOX chemotherapy. However, SMI improved cardiac structure and function, as well as the metabolism of the rats with DOX-CM. The metabolic alterations induced via SMI, including the promotion of glycogenolysis, glycolysis, amino acid utilization and antioxidation, suggested that SMI exerts cardioprotective effects by improving energy metabolism and attenuating oxidative stress. Moreover, the IPA revealed that important signaling molecules and enzymes interacted with the altered metabolites. These findings have provided us with new insights into the pathogenesis of DOX-CM and the effects of SMI, and suggest that the combination of metabolomic analysis and IPA may represent a

  8. Dietary nitrate supplementation protects against doxorubicin-induced cardiomyopathy by improving mitochondrial function

    PubMed Central

    Zhu, Shu-Guang; Kukreja, Rakesh C.; Das, Anindita; Chen, Qun; Lesnefsky, Edward J.; Xi, Lei

    2014-01-01

    Objectives We tested the hypothesis that chronic dietary nitrate supplementation protects against doxorubicin-induced cardiomyopathy through improving ventricular function and reducing mitochondrial respiratory chain damage. Background Doxorubicin is a powerful anthracycline antibiotic used to treat divergent human neoplasms. Its clinical use is limited due to severe cardiotoxic side-effects. Dietary nitrate/nitrite are essential nutrients for maintenance of the steady-state tissue levels of nitric oxide (NO) and may play a therapeutic role in diseases associated with NO insufficiency or dysregulation. Dietary nitrate/nitrite supplementation alleviates myocardial injury caused by ischemia-reperfusion and cardiac arrest-resuscitation. Methods Adult male CF-1 mice were given a single dose of doxorubicin (15 mg/kg, i.p.) and left ventricular contractile function was assessed 5 days later with both echocardiography and pressure-volume Millar catheter. Nitrate supplementation regimen (1 g/L NaNO3 in drinking water) was started 7 days before doxorubicin injection and continued thereafter. Cardiomyocyte necrosis/apoptosis, tissue lipid peroxidation, and plasma nitrate/nitrite levels were assessed. In addition, mitochondrial complex I activity, oxidative phosphorylation capacity, and H2O2 generation were determined in paralleled experiments. Results Doxorubicin caused impairment of ventricular contractility and cell death, which were significantly reduced by nitrate supplementation (P<0.05). These cardioprotective effects were associated with a significant decrease in tissue lipid peroxidation. Nitrate supplementation significantly preserved mitochondrial complex I activity, oxidative phosphorylation and attenuated H2O2 generation following doxorubicin treatment. Conclusions Chronic oral intake of inorganic nitrate attenuates doxorubicin-induced ventricular dysfunction, cell death, oxidative stress, and mitochondrial respiratory chain damage. Nitrate could be a promising

  9. Dietary nitrate supplementation protects against Doxorubicin-induced cardiomyopathy by improving mitochondrial function.

    PubMed

    Zhu, Shu-Guang; Kukreja, Rakesh C; Das, Anindita; Chen, Qun; Lesnefsky, Edward J; Xi, Lei

    2011-05-24

    The aim of this study was to test the hypothesis that long-term dietary nitrate supplementation protects against doxorubicin-induced cardiomyopathy by improving ventricular function and reducing mitochondrial respiratory chain damage. Doxorubicin is a powerful anthracycline antibiotic used to treat divergent human neoplasms. Its clinical use is limited because of severe cardiotoxic side effects. Dietary nitrate and nitrite are essential nutrients for maintenance of steady-state tissue levels of nitric oxide and may play a therapeutic role in diseases associated with nitric oxide insufficiency or dysregulation. Dietary nitrate and nitrite supplementation alleviates myocardial injury caused by ischemia-reperfusion and cardiac arrest-resuscitation. Adult male CF-1 mice were given a single dose of doxorubicin (15 mg/kg intraperitoneally), and left ventricular contractile function was assessed 5 days later using both echocardiography and pressure-volume Millar catheterization. A nitrate supplementation regimen (1 g/l sodium nitrate in drinking water) was started 7 days before doxorubicin injection and continued thereafter. Cardiomyocyte necrosis and apoptosis, tissue lipid peroxidation, and plasma nitrate and nitrite levels were assessed. In addition, mitochondrial complex I activity, oxidative phosphorylation capacity, and hydrogen peroxide generation were determined in parallel experiments. Doxorubicin caused impairment of ventricular contractility and cell death, which were significantly reduced by nitrate supplementation (p < 0.05). These cardioprotective effects were associated with a significant decrease in tissue lipid peroxidation. Nitrate supplementation significantly preserved mitochondrial complex I activity and oxidative phosphorylation and attenuated hydrogen peroxide generation after doxorubicin treatment. Long-term oral intake of inorganic nitrate attenuates doxorubicin-induced ventricular dysfunction, cell death, oxidative stress, and mitochondrial

  10. Role of cardiac MRI in nonischemic cardiomyopathies.

    PubMed

    Anand, Senthil; Janardhanan, Rajesh

    2016-01-01

    Cardiac magnetic resonance (CMR) with its higher spatial resolution is considered the gold standard for evaluating ventricular mass, volumes, and ejection fraction. CMR can be used for accurate diagnosis of several conditions, especially cardiomyopathies. The purpose of this article is to review the utility of CMR in the diagnosis and management of nonischemic cardiomyopathies. We have reviewed both common and rare types of nonischemic cardiomyopathies in detail and elaborated on the specific CMR findings in each. We believe that CMR is an invaluable tool, not only in differentiating nonischemic from ischemic cardiomyopathy, but also in aiding the accurate diagnosis and management of the subtype of nonischemic cardiomyopathy. CMR should routinely be integrated in the diagnostic workup of various cardiomyopathies. Published by Elsevier B.V.

  11. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies.

    PubMed

    Wang, Gang; McCain, Megan L; Yang, Luhan; He, Aibin; Pasqualini, Francesco Silvio; Agarwal, Ashutosh; Yuan, Hongyan; Jiang, Dawei; Zhang, Donghui; Zangi, Lior; Geva, Judith; Roberts, Amy E; Ma, Qing; Ding, Jian; Chen, Jinghai; Wang, Da-Zhi; Li, Kai; Wang, Jiwu; Wanders, Ronald J A; Kulik, Wim; Vaz, Frédéric M; Laflamme, Michael A; Murry, Charles E; Chien, Kenneth R; Kelley, Richard I; Church, George M; Parker, Kevin Kit; Pu, William T

    2014-06-01

    Study of monogenic mitochondrial cardiomyopathies may yield insights into mitochondrial roles in cardiac development and disease. Here, we combined patient-derived and genetically engineered induced pluripotent stem cells (iPSCs) with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene encoding tafazzin (TAZ). Using BTHS iPSC-derived cardiomyocytes (iPSC-CMs), we defined metabolic, structural and functional abnormalities associated with TAZ mutation. BTHS iPSC-CMs assembled sparse and irregular sarcomeres, and engineered BTHS 'heart-on-chip' tissues contracted weakly. Gene replacement and genome editing demonstrated that TAZ mutation is necessary and sufficient for these phenotypes. Sarcomere assembly and myocardial contraction abnormalities occurred in the context of normal whole-cell ATP levels. Excess levels of reactive oxygen species mechanistically linked TAZ mutation to impaired cardiomyocyte function. Our study provides new insights into the pathogenesis of Barth syndrome, suggests new treatment strategies and advances iPSC-based in vitro modeling of cardiomyopathy.

  12. Peripartum Cardiomyopathy.

    PubMed

    Arany, Zolt; Elkayam, Uri

    2016-04-05

    Peripartum cardiomyopathy is a potentially life-threatening pregnancy-associated disease that typically arises in the peripartum period and is marked by left ventricular dysfunction and heart failure. The disease is relatively uncommon, but its incidence is rising. Women often recover cardiac function, but long-lasting morbidity and mortality are not infrequent. Management of peripartum cardiomyopathy is largely limited to the same neurohormonal antagonists used in other forms of cardiomyopathy, and no proven disease-specific therapies exist yet. Research in the past decade has suggested that peripartum cardiomyopathy is caused by vascular dysfunction, triggered by late-gestational maternal hormones. Most recently, information has also indicated that many cases of peripartum cardiomyopathy have genetic underpinnings. We review here the known epidemiology, clinical presentation, and management of peripartum cardiomyopathy, as well as the current knowledge of the pathophysiology of the disease. © 2016 American Heart Association, Inc.

  13. Evaluation of the topoisomerase II-inactive bisdioxopiperazine ICRF-161 as a protectant against doxorubicin-induced cardiomyopathy.

    PubMed

    Martin, Elke; Thougaard, Annemette Vinding; Grauslund, Morten; Jensen, Peter B; Bjorkling, Fredrik; Hasinoff, Brian B; Tjørnelund, Jette; Sehested, Maxwell; Jensen, Lars H

    2009-01-08

    Anthracycline-induced cardiomyopathy is a major problem in anti-cancer therapy. The only approved agent for alleviating this serious dose limiting side effect is ICRF-187 (dexrazoxane). The current thinking is that the ring-opened hydrolysis product of this agent, ADR-925, which is formed inside cardiomyocytes, removes iron from its complexes with anthracyclines, hereby reducing the concentration of highly toxic iron-anthracycline complexes that damage cardiomyocytes by semiquinone redox recycling and the production of free radicals. However, the 2 carbon linker ICRF-187 is also is a catalytic inhibitor of topoisomerase II, resulting in the risk of additional myelosuppression in patients receiving ICRF-187 as a cardioprotectant in combination with doxorubicin. The development of a topoisomerase II-inactive iron chelating compound thus appeared attractive. In the present paper we evaluate the topoisomerase II-inactive 3 carbon linker bisdioxopiperazine analog ICRF-161 as a cardioprotectant. We demonstrate that this compound does chelate iron and protects against doxorubicin-induced LDH release from primary rat cardiomyocytes in vitro, similarly to ICRF-187. The compound does not target topoisomerase II in vitro or in cells, it is well tolerated and shows similar exposure to ICRF-187 in rodents, and it does not induce myelosuppression when given at high doses to mice as opposed to ICRF-187. However, when tested in a model of chronic anthracycline-induced cardiomyopathy in spontaneously hypertensive rats, ICRF-161 was not capable of protecting against the cardiotoxic effects of doxorubicin. Modulation of the activity of the beta isoform of the topoisomerase II enzyme by ICRF-187 has recently been proposed as the mechanism behind its cardioprotection. This concept is thus supported by the present study in that iron chelation alone does not appear to be sufficient for protection against anthracycline-induced cardiomyopathy.

  14. Oleuropein prevents doxorubicin-induced cardiomyopathy interfering with signaling molecules and cardiomyocyte metabolism.

    PubMed

    Andreadou, Ioanna; Mikros, Emmanuel; Ioannidis, Konstantinos; Sigala, Fragiska; Naka, Katerina; Kostidis, Sarantos; Farmakis, Dimitrios; Tenta, Roxane; Kavantzas, Nikolaos; Bibli, Sofia-Iris; Gikas, Evangelos; Skaltsounis, Leandros; Kremastinos, Dimitrios Th; Iliodromitis, Efstathios K

    2014-04-01

    Oleuropein, a natural phenolic compound, prevents acute doxorubicin (DXR)-induced cardiotoxicity but there is no evidence regarding its role in chronic DXR-induced cardiomyopathy (DXR-CM). In the present study, we investigated the role of oleuropein in DXR-CM by addressing cardiac geometry and function (transthoracic echocardiography), cardiac histopathology, nitro-oxidative stress (MDA, PCs, NT), inflammatory cytokines (IL-6, Big ET-1), NO homeostasis (iNOS and eNOS expressions), kinases involved in apoptosis and metabolism (Akt, AMPK) and myocardial metabonomics. Rats were randomly divided into 6 groups: Control, OLEU-1 and OLEU-2 [oleuropein at 1000 and 2000 mg/kg in total, respectively, intraperitoneally (i.p.) for 14 days], DXR (18 mg/kg, i.p. divided into 6 equal doses for 2 weeks), DXR-OLEU-1 and DXR-OLEU-2 (both oleuropein and DXR as previously described). Impaired left ventricular contractility and inflammatory and degenerative pathology lesions were encountered only in the DXR group. The DXR group also had higher MDA, PCs, NT, IL-6 and Big ET-1 levels, higher iNOS and lower eNOS, Akt and AMPK activation compared to controls and the oleuropein-treated groups. Metabonomics depicted significant metabolite alterations in the DXR group suggesting perturbed energy metabolism and protein biosynthesis. The effectiveness of DXR in inhibiting cell proliferation is not compromised when oleuropein is present. We documented an imbalance between iNOS and eNOS expressions and a disturbed protein biosynthesis and metabolism in DXR-CM; these newly recognized pathways in DXR cardiotoxicity may help identifying novel therapeutic targets. Activation of AMPK and suppression of iNOS by oleuropein seem to prevent the structural, functional and histopathological cardiac effects of chronic DXR toxicity. Copyright © 2014. Published by Elsevier Ltd.

  15. Embryonic stem cells improve cardiac function in Doxorubicin-induced cardiomyopathy mediated through multiple mechanisms.

    PubMed

    Singla, Dinender K; Ahmed, Aisha; Singla, Reetu; Yan, Binbin

    2012-01-01

    Doxorubicin (DOX) is an effective antineoplastic agent used for the treatment of a variety of cancers. Unfortunately, its use is limited as this drug induces cardiotoxicity and heart failure as a side effect. There is no report that describes whether transplanted embryonic stem (ES) cells or their conditioned medium (CM) in DOX-induced cardiomyopathy (DIC) can repair and regenerate myocardium. Therefore, we transplanted ES cells or CM in DIC to examine apoptosis, fibrosis, cytoplasmic vacuolization, and myofibrillar loss and their associated Akt and ERK pathway. Moreover, we also determined activation of endogenous c-kit(+ve) cardiac stem cells (CSCs), levels of HGF and IGF-1, growth factors required for c-kit cell activation, and their differentiation into cardiac myocytes, which also contributes in cardiac regeneration and improved heart function. We generated DIC in C57Bl/6 mice (cumulative dose of DOX 12 mg/kg body weight, IP), and animals were treated with ES cells, CM, or cell culture medium in controls. Two weeks post-DIC, ES cells or CM transplanted hearts showed a significant (p < 0.05) decrease in cardiac apoptotic nuclei and their regulation with Akt and ERK pathway. Cardiac fibrosis observed in the ES cell or CM groups was significantly less compared with DOX and cell culture medium groups (p < 0.05). Next, cytoplasmic vacuolization and myofibrillar loss was reduced (p < 0.05) following treatment with ES cells or CM. Moreover, our data also demonstrated increased levels of c-kit(+ve) CSCs in ES cells or CM hearts and differentiated cardiac myocytes from these CSCs, suggesting endogenous cardiac regeneration. Importantly, the levels of HFG and IGF-1 were significantly increased in ES cells or CM transplanted hearts. In conclusion, we reported that transplanted ES cells or CM in DIC hearts significantly decreases various adverse pathological mechanisms as well as enhances cardiac regeneration that effectively contributes to improved heart function.

  16. Doxorubicin Cardiomyopathy

    PubMed Central

    Chatterjee, Kanu; Zhang, Jianqing; Honbo, Norman; Karliner, Joel S.

    2010-01-01

    Established doxorubicin cardiomyopathy is a lethal disease. When congestive heart failure develops, mortality is approximately 50%. Extensive research has been done to understand the mechanism and pathophysiology of doxorubicin cardiomyopathy, and considerable knowledge and experience has been gained. Unfortunately, no effective treatment for established doxorubicin cardiomyopathy is presently available. Extensive research has been done and is being done to discover preventive treatments. However an effective and clinically applicable preventive treatment is yet to be discovered. PMID:20016174

  17. Takotsubo cardiomyopathy triggered by alcohol withdrawal.

    PubMed

    Alexandre, Joakim; Benouda, Leila; Champ-Rigot, Laure; Labombarda, Fabien

    2011-07-01

    Takotsubo cardiomyopathy is a reversible cardiomyopathy frequently precipitated by a sudden emotional or physical stress. The exact physiopathology is still debated and may involve catecholamine-induced myocardial stunning. Alcohol withdrawal is associated with an hyperadrenergic state and may be a period at risk of cardiac events. We report a 56-year-old man with Takotsubo cardiomyopathy triggered by alcohol withdrawal.

  18. EET intervention on Wnt1, NOV, and HO-1 signaling prevents obesity-induced cardiomyopathy in obese mice.

    PubMed

    Cao, Jian; Singh, Shailendra P; McClung, John A; Joseph, Gregory; Vanella, Luca; Barbagallo, Ignazio; Jiang, Houli; Falck, John R; Arad, Michael; Shapiro, Joseph I; Abraham, Nader G

    2017-08-01

    We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on vascular function; in addition to its antiapoptotic action, it increases insulin sensitivity and inhibits inflammation. To uncover the signaling mechanisms by which EET reduces cardiomyopathy, we hypothesized that EET infusion might ameliorate obesity-induced cardiomyopathy by improving heme oxygenase (HO)-1, Wnt1, thermogenic gene levels, and mitochondrial integrity in cardiac tissues and improved pericardial fat phenotype. EET reduced levels of fasting blood glucose and proinflammatory adipokines, including nephroblastoma overexpressed (NOV) signaling, while increasing echocardiographic fractional shortening and O2 consumption. Of interest, we also noted a marked improvement in mitochondrial integrity, thermogenic genes, and Wnt 1 and HO-1 signaling mechanisms. Knockout of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in EET-treated mice resulted in a reversal of these beneficial effects including a decrease in myocardial Wnt1 and HO-1 expression and an increase in NOV. To further elucidate the effects of EET on pericardial adipose tissues, we observed EET treatment increases in adiponectin, PGC-1α, phospho-AMP-activated protein kinase, insulin receptor phosphorylation, and thermogenic genes, resulting in a "browning" pericardial adipose phenotype under high-fat diets. Collectively, these experiments demonstrate that an EET agonist increased Wnt1 and HO-1 signaling while decreasing NOV pathways and the progression of cardiomyopathy. Furthermore, this report presents a portal into potential therapeutic approaches for the treatment of heart failure and metabolic syndrome.NEW & NOTEWORTHY The mechanism by which EET acts on obesity-induced cardiomyopathy is unknown. Here, we describe a previously unrecognized function of EET infusion that inhibits nephroblastoma overexpressed (NOV) levels and activates Wnt1, hence identifying NOV inhibition

  19. Remote ischemic preconditioning for prevention of contrast-induced acute kidney injury in diabetic patients.

    PubMed

    Savaj, Shokoufeh; Savoj, Javad; Jebraili, Ismail; Sezavar, Seyed Hashem

    2014-11-01

    There are some clinical trials showing that short-term ischemia in one organ can protect different organs against higher intensity and longer ischemic insult. We designed a study to assess whether remote ischemic preconditioning (RIPC) on one organ can decrease the rate of contrast-induced acute kidney injury (AKI) in diabetic patients who undergo coronary artery angiography (CAA). This randomized control trial included 96 diabetic patients who were candidates for CAA. Exclusion criteria were congestive heart failure and complications during CAA. All of the patients received 1000 mL of normal saline before CAA. The RIPC group underwent 3 cycles of 5-minute ischemia in their right arm. Serum creatinine was measured before and 24 hours after CAA. Contrast-induced AKI was reported in 5 cases in the control group and 1 case in the RIPC group (P = .13, odds ratio, 5.4). The differences in serum creatinine level before and after the procedure was significantly lower in RIPC group than that in the control group (P = .04, odds ratio, 0.08). Serum creatinine rise significantly correlated with contrast dose (P = .02) and a history of hypertension (P = .02) in both groups. Ischemic preconditioning had a protective effect on contrast-induced AKI in our study. Since this method is harmless and cost effective, further studies on patients with chronic kidney disease is required to evaluate addition of ischemic preconditioning to our clinical practice for prevention of contrast-induced AKI.

  20. Cerebral embolic stroke after disappearing takotsubo cardiomyopathy.

    PubMed

    Matsuzono, Kosuke; Ikeda, Yoshio; Deguchi, Shoko; Yamashita, Toru; Kurata, Tomoko; Deguchi, Kentaro; Abe, Koji

    2013-11-01

    Takotsubo cardiomyopathy can induce cerebral embolic stroke because of intracardiac thrombosis, but the timing of cardiogenic embolism relating to takotsubo cardiomyopathy has not been well described. We evaluated a 71-year-old woman with takotsubo cardiomyopathy, who developed cardiogenic cerebral embolism after recovery of cardiac wall motion. Nevertheless, we treated her with anticoagulation therapy. The present clinical observation suggests that attention should be paid to the timing when takotsubo cardiomyopathy resolves against risk of cardiogenic cerebral embolism.

  1. Decongestive effects of levosimendan in cardiogenic shock induced by postpartum cardiomyopathy.

    PubMed

    Labbene, I; Arrigo, M; Tavares, M; Hajjej, Z; Brandão, J L; Tolppanen, H; Feliot, E; Gayat, E; Ferjani, M; Mebazaa, A

    2017-02-01

    Catecholamines and/or levosimendan have been proposed for haemodynamic restoration during cardiogenic shock (CS). In CS induced by post-partum cardiomyopathy (PPCM), levosimendan might be particularly favourable. The aim of this study was to evaluate the haemodynamic and echocardiographic effects of levosimendan in patients with CS, in particular in patients with PPCM-induced CS. Twenty-eight patients with refractory CS were retrospectively included in the study. Among them, a cohort of 8 women with PPCM-induced CS was included. All patients were treated with levosimendan (loading dose followed by a continuous infusion for 24 h) and were invasively monitored, including a pulmonary artery catheter, for 48hours. Echocardiographic measurements were performed at baseline and during follow-up. Significant improvements in haemodynamic parameters were observed 48 h after starting levosimendan. The cardiac index increased (+1.2±0.6L/min, P<0.001) and filling pressures decreased (pulmonary artery occlusion pressure, PAOP: -11.2±4.3mmHg, P<0.001; right-atrial pressure, RAP: -6.1±4.9mmHg, P<0.001). The left ventricular ejection fraction was significantly higher at 48 h compared to baseline (38% [34-46%] versus 27% [22-30%], P<0.001). Despite similar characteristics at baseline, in the subgroup of patients with PPCM, more profound decongestive effects at 48hours were observed: PAOP (13±2 versus 17±4mmHg, P=0.007) and RAP (12±4 versus 17±4mmHg, P=0.006) were significantly lower in the PPCM subgroup compared to the non-PPCM subgroup. Haemodynamics and left-ventricular ejection fraction rapidly improved after treatment with levosimendan. In patients with PPCM-induced CS, a more profound reduction of congestion was observed. Copyright © 2016 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  2. Muscle ring finger-3 protects against diabetic cardiomyopathy induced by a high fat diet.

    PubMed

    Quintana, Megan T; He, Jun; Sullivan, Jenyth; Grevengoed, Trisha; Schisler, Jonathan; Han, Yipin; Hill, Joseph A; Yates, Cecelia C; Stansfield, William E; Mapanga, Rudo F; Essop, M Faadiel; Muehlbauer, Michael J; Newgard, Christopher B; Bain, James R; Willis, Monte S

    2015-07-28

    The pathogenesis of diabetic cardiomyopathy (DCM) involves the enhanced activation of peroxisome proliferator activating receptor (PPAR) transcription factors, including the most prominent isoform in the heart, PPARα. In cancer cells and adipocytes, post-translational modification of PPARs have been identified, including ligand-dependent degradation of PPARs by specific ubiquitin ligases. However, the regulation of PPARs in cardiomyocytes and heart have not previously been identified. We recently identified that muscle ring finger-1 (MuRF1) and MuRF2 differentially inhibit PPAR activities by mono-ubiquitination, leading to the hypothesis that MuRF3 may regulate PPAR activity in vivo to regulate DCM. MuRF3-/- mice were challenged with 26 weeks 60% high fat diet to induce insulin resistance and DCM. Conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1 activities were assayed. MuRF3-/- mice exhibited a premature systolic heart failure by 6 weeks high fat diet (vs. 12 weeks in MuRF3+/+). MuRF3-/- mice weighed significantly less than sibling-matched wildtype mice after 26 weeks HFD. These differences may be largely due to resistance to fat accumulation, as MRI analysis revealed MuRF3-/- mice had significantly less fat mass, but not lean body mass. In vitro ubiquitination assays identified MuRF3 mono-ubiquitinated PPARα and PPARγ1, but not PPARβ. These findings suggest that MuRF3 helps stabilize cardiac PPARα and PPARγ1 in vivo to support resistance to the development of DCM. MuRF3 also plays an unexpected role in regulating fat storage despite being found only in striated muscle.

  3. Antimony-induced cardiomyopathy in guinea-pig and protection by L-carnitine

    PubMed Central

    Alvarez, Marco; Malécot, Claire O; Gannier, François; Lignon, Jacques M

    2004-01-01

    Antimony (Sb) is the mainstay for the treatment of Leishmaniasis. It has serious, often lethal, cardiovascular side effects. The objective of this study was to examine the effects of Sb treatment upon the electrocardiogram (ECG), myocyte contractility (assessed by monitoring sarcomere length during field stimulation), whole-cell action potential (AP) and calcium current (ICa) of the guinea-pig and to evaluate L-carnitine as a cardioprotective agent. Guinea-pigs received daily injections of either saline, Sb(V), Sb(III), L-carnitine or L-carnitine with Sb(III). Eight lead ECGs were recorded under halothane anaesthesia every 4 days. At the end of each treatment regime, animals were killed and ventricular myocytes were enzymatically isolated. Treatment with Sb(V) for 26 days prolonged the QT interval of the ECG. Treatment with Sb(III) was lethal within 2 days for ∼50% of the animals. The survivors showed ECG alterations similar to those described in man: T wave flattening and/or inversion, depression of the ST segment, and elongation of RR and QT intervals. Their ventricular myocytes showed impaired contraction responses to changes in stimulus frequency, elongated AP and reduced ICa. Combined treatment with L-carnitine and Sb(III) delayed mortality. Prior treatment with L-carnitine followed by combined treatment with L-carnitine and Sb(III) reduced mortality to <10% over 12 days and these animals showed normal ECG. Their myocytes showed normal contractility and AP. It is concluded that L-carnitine has a preventive cardioprotective role against antimony-induced cardiomyopathy. The mechanism of action of L-carnitine may be to counter oxidative stress caused by Sb(III). PMID:15644865

  4. Antioxidant vitamins attenuate oxidative stress and cardiac dysfunction in tachycardia-induced cardiomyopathy.

    PubMed

    Shite, J; Qin, F; Mao, W; Kawai, H; Stevens, S Y; Liang, C

    2001-11-15

    We administered antioxidant vitamins to rabbits with pacing-induced cardiomyopathy to assess whether antioxidant therapy retards the progression of congestive heart failure (CHF). Although oxidative stress is increased in CHF, whether progression of heart failure could be prevented or reduced by antioxidants is not known. Rabbits with chronic cardiac pacing and sham operation were randomized to receive a combination of beta-carotene, ascorbic acid and alpha-tocopherol, alpha-tocopherol alone or placebo over eight weeks. Echocardiography was used to measure cardiac function weekly. Resting hemodynamics and in vivo myocardial beta-adrenergic responsiveness were studied at week 8. Animals were then sacrificed for measuring myocardial beta-receptor density, norepinephrine (NE) uptake-1 site density, sympathetic neuronal marker profiles, tissue-reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and oxidative damage of mitochondrial DNA (mtDNA). Rapid cardiac pacing increased myocardial oxidative stress as evidenced by reduced myocardial GSH/GSSG ratio and increased oxidized mtDNA and produced cardiac dysfunction, beta-adrenergic subsensitivity, beta-receptor downregulation, diminished sympathetic neurotransmitter profiles and reduced NE uptake-1 carrier density. A combination of antioxidant vitamins reduced the myocardial oxidative stress, attenuated cardiac dysfunction and prevented myocardial beta-receptor downregulation and sympathetic nerve terminal dysfunction. Administration of alpha-tocopherol alone produced similar effects, but the effects were less marked than those produced by the three vitamins together. Vitamins produced no effects in sham-operated animals. Antioxidant vitamins reduced tissue oxidative stress in CHF and attenuated the associated cardiac dysfunction, beta-receptor downregulation and sympathetic nerve terminal abnormalities. The findings suggest that antioxidant therapy may be efficacious in human CHF.

  5. Prevalence and risk factors of sepsis-induced cardiomyopathy: A retrospective cohort study.

    PubMed

    Sato, Ryota; Kuriyama, Akira; Takada, Tadaaki; Nasu, Michitaka; Luthe, Sarah Kyuragi

    2016-09-01

    The aim of the study is to evaluate the epidemiology and clinical features of sepsis-induced cardiomyopathy (SICM).A retrospective cohort study was conducted.A total of 210 adult patients with sepsis or septic shock admitted to a Japanese tertiary care hospital from January 1, 2013, to December 31, 2015, who underwent transthoracic echocardiography (TTE) on admission.The definition of SICM was ejection fraction (EF) < 50% and a ≥10% decrease compared to the baseline EF which recovered within 2 weeks, in sepsis or septic shock patients.Our primary outcome was the incidence rate of SICM. Our secondary outcomes were the in-hospital mortality rate and length of intensive care unit (ICU) stay according to the presence or absence of SICM. In total, 29 patients (13.8%) were diagnosed with SICM. The prevalence rate of SICM was significantly higher in male than in female (P = 0.02). Multivariate logistic regression analyses revealed that the incidence of SICM was associated with younger age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95-0.99), higher lactate level on admission (OR, 1.18; 95% CI, 1.05-1.32) and history of heart failure (HF) (OR, 3.77; 95% CI, 1.37-10.40). There were no significant differences in the in-hospital and 30-day mortality between patients with and without SICM (24.1% vs 12.7%, P = 0.15; 20.7% vs 12.1%, P = 0.23). Lengths of hospital and ICU stay were significantly longer in patients with SICM than in those without SICM (median, 43 vs 26 days, P = 0.04; 9 vs 5 days, P < 0.01).SICM developed in 13.8% of patients with sepsis and septic shock. A younger age, higher lactate levels on admission and history of HF were risk factors.

  6. Arginase inhibition augments nitric oxide production and facilitates left ventricular systolic function in doxorubicin‐induced cardiomyopathy in mice

    PubMed Central

    Toya, Takumi; Hakuno, Daihiko; Shiraishi, Yasunaga; Kujiraoka, Takehiko; Adachi, Takeshi

    2014-01-01

    Abstract A metabolizing enzyme arginase can decrease nitric oxide (NO) production by competing with NO synthase for arginine as a substrate, but its pathophysiological role in heart failure remains unknown. We aimed to investigate the effect of pharmacological inhibition of arginase on left ventricular function in doxorubicin‐induced cardiomyopathy in mice. Doxorubicin administration for 5 weeks significantly increased protein expression levels or activity of arginase in the lungs and liver, and caused moderate increase in arginase 2 expression in the aorta. In the lungs, accumulated interstitial cells strongly expressed both arginase 1 and arginase 2 by doxorubicin administration. Echocardiography revealed that administration of a potent, reversible arginase inhibitor N‐omega‐hydroxy‐nor‐l‐arginine completely reversed doxorubicin‐induced decrease in the ejection fraction, in parallel with expression levels of BNP mRNA, without affecting apoptosis, hypertrophy, fibrosis, or macrophage infiltration in the left ventricle. Arginase inhibition reversibly lowered systolic blood pressure, and importantly, it recovered doxorubicin‐induced decline in NO concentration in the serum, lungs, and aorta. Furthermore, arginase inhibition stimulated NO secretion from aortic endothelial cells and peritoneal macrophages in vitro. In conclusion, pharmacological inhibition of arginase augmented NO concentration in the serum, lungs, and aorta, promoted NO‐mediated decrease in afterload for left ventricle, and facilitated left ventricular systolic function in doxorubicin‐induced cardiomyopathy in mice. PMID:25263201

  7. Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart.

    PubMed

    Cai, Zheqing; Luo, Weibo; Zhan, Huiwang; Semenza, Gregg L

    2013-10-22

    Both preclinical and clinical studies suggest that brief cycles of ischemia and reperfusion in the arm or leg may protect the heart against injury following prolonged coronary artery occlusion and reperfusion, a phenomenon known as remote ischemic preconditioning. Recent studies in mice indicate that increased plasma interleukin-10 (IL-10) levels play an important role in remote ischemic preconditioning induced by clamping the femoral artery for 5 min followed by 5 min of reperfusion for a total of three cycles. In this study, we demonstrate that remote ischemic preconditioning increases plasma IL-10 levels and decreases myocardial infarct size in wild-type mice but not in littermates that are heterozygous for a knockout allele at the locus encoding hypoxia-inducible factor (HIF) 1α. Injection of a recombinant adenovirus encoding a constitutively active form of HIF-1α into mouse hind limb muscle was sufficient to increase plasma IL-10 levels and decrease myocardial infarct size. Exposure of C2C12 mouse myocytes to cyclic hypoxia and reoxygenation rapidly increased levels of IL-10 mRNA, which was blocked by administration of the HIF-1 inhibitor acriflavine or by expression of short hairpin RNA targeting HIF-1α or HIF-1β. Chromatin immunoprecipitation assays demonstrated that binding of HIF-1 to the Il10 gene was induced when myocytes were subjected to cyclic hypoxia and reoxygenation. Taken together, these data indicate that HIF-1 activates Il10 gene transcription and is required for remote ischemic preconditioning.

  8. The coxsackie-adenovirus receptor induces an inflammatory cardiomyopathy independent of viral infection.

    PubMed

    Yuen, Stella; Smith, Julie; Caruso, Laura; Balan, Marko; Opavsky, Mary Anne

    2011-05-01

    The coxsackie-adenovirus receptor (CAR) is a viral receptor for Group B coxsackieviruses (CVBs) and adenoviruses. CAR has been linked with the innate immune response to CVB myocarditis, and with activation of inflammatory cells in vitro. We hypothesized that CAR activates signals that promote inflammation in the myocardium independent of viral infection. To test this we conditionally overexpressed murine CAR in cardiomyocytes of adult binary transgenic mice under the control of a tetracycline-responsive (tet-off) α-myosin heavy chain (αMtTA) promoter (mCAR(+)/αMtTA(+) mice). An inflammatory cardiomyopathy developed in both lines generated (6-mCAR(+)/αMtTA(+) and 12-mCAR(+)/αMtTA(+)) following withdrawal of doxycycline. Cardiac CAR was upregulated at 4weeks of age in 6-mCAR(+)/αMtTA(+) mice and induced a mild inflammatory infiltrate (score 1.3 of 4.0±0.3) at 6weeks, with 95% of mice surviving to that time. In the second line, 12-mCAR(+)/αMtTA(+) mice, CAR was upregulated in the majority of mice by 3weeks of age, and by 5weeks of age more severe cardiac inflammation (score 2.8 of 4.0±0.4) developed with only 56% of mice surviving. The cardiac inflammatory infiltrate was primarily natural killer cells and macrophages in both mCAR(+)/αMtTA(+) lines. A proinflammatory cytokine response with increased cardiac interferon-γ, interleukin (IL)-12, IL-1β, tumor necrosis factor-α and IL-6 was detected by real-time RT-PCR. CAR has been linked to signaling via the inflammatory mitogen-activated protein kinase (MAPK) cascades; therefore, we evaluated the response of these pathways in hearts with upregulated CAR. Both stress-activated JNK and p38MAPK were activated in mCAR(+)/αMtTA(+) hearts prior to onset of inflammation and in isolated mCAR(+)/αMtTA(+) cardiomyocytes. In conclusion, we show for the first time that CAR upregulation in the adult mouse heart induces cardiac inflammation reminiscent of early viral myocarditis. CAR-induced stress-activated MAPK

  9. Potent Paracrine Effects of human induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells Attenuate Doxorubicin-induced Cardiomyopathy

    PubMed Central

    Zhang, Yuelin; Liang, Xiaoting; Liao, Songyan; Wang, Weixin; Wang, Junwen; Li, Xiang; Ding, Yue; Liang, Yingmin; Gao, Fei; Yang, Mo; Fu, Qingling; Xu, Aimin; Chai, Yuet-Hung; He, Jia; Tse, Hung-Fat; Lian, Qizhou

    2015-01-01

    Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can protect cardiomyocytes against anthracycline-induced cardiomyopathy (AIC) through paracrine effects. Nonetheless the paracrine effects of human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) on AIC are poorly understood. In vitro studies reveal that doxorubicin (Dox)-induced reactive oxidative stress (ROS) generation and cell apoptosis in neonatal rat cardiomyocytes (NRCMs) are significantly reduced when treated with conditioned medium harvested from BM-MSCs (BM-MSCs-CdM) or iPSC-MSCs (iPSC-MSCs-CdM). Compared with BM-MSCs-CdM, NRCMs treated with iPSC-MSCs-CdM exhibit significantly less ROS and cell apoptosis in a dose-dependent manner. Transplantation of BM-MSCs-CdM or iPSC-MSCs-CdM into mice with AIC remarkably attenuated left ventricular (LV) dysfunction and dilatation. Compared with BM-MSCs-CdM, iPSC-MSCs-CdM treatment showed better alleviation of heart failure, less cardiomyocyte apoptosis and fibrosis. Analysis of common and distinct cytokines revealed that macrophage migration inhibitory factor (MIF) and growth differentiation factor-15 (GDF-15) were uniquely overpresented in iPSC-MSC-CdM. Immunodepletion of MIF and GDF-15 in iPSC-MSCs-CdM dramatically decreased cardioprotection. Injection of GDF-15/MIF cytokines could partially reverse Dox-induced heart dysfunction. We suggest that the potent paracrine effects of iPSC-MSCs provide novel “cell-free” therapeutic cardioprotection against AIC, and that MIF and GDF-15 in iPSC-MSCs-CdM are critical for these enhanced cardioprotective effects. PMID:26057572

  10. Mitochondrial Cardiomyopathies.

    PubMed

    El-Hattab, Ayman W; Scaglia, Fernando

    2016-01-01

    Mitochondria are found in all nucleated human cells and perform various essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA), whereas more than 99% of them are encoded by nuclear DNA (nDNA). Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs for various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular non-compaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain complexes subunits and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs, ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia.

  11. INHERITED CARDIOMYOPATHIES

    PubMed Central

    Towbin, Jeffrey A.

    2015-01-01

    Cardiomyopathies, diseases of the heart muscle, are major causes of morbidity and mortality. A significant percentage of patients with cardiomyopathies have genetic-based, inheritable disease and, over the past two decades the genetic causes of these disorders have been increasingly discovered. The genes causing these disorders when they are mutated appear to encode proteins that frame a “final common pathway” for that specific disorder but the specifics of the phenotype, including age of onset, severity, and outcome is variable for reasons not yet understood. The “final common pathways” for the classified forms of cardiomyopathy include the sarcomere in the primarily diastolic dysfunction disorders hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM), the linkage of the sarcomere and sarcolemma in the systolic dysfunction disorder dilated cardiomyopathy (DCM), and the desmosome in arrhythmogenic cardiomyopathy (AVC). Left ventricular noncompaction cardiomyopathy (LVNC) is an overlap disorder and appears that any of these “final common pathways” can be involved depending on the specific form of LVNC. The genetics and mechanisms responsible for these clinical phenotypes will be described. PMID:25186923

  12. Peripartum cardiomyopathy.

    PubMed

    Sundin, Courtney Stanley

    2014-01-01

    Peripartum cardiomyopathy is a very rare, but serious life-threatening emergency. Early recognition of signs and symptoms, along with radiologic imaging and blood work, can facilitate timely diagnosis. Once peripartum cardiomyopathy is diagnosed, a multidisciplinary team can facilitate the delivery of quality care to promote optimal outcomes.

  13. Mitochondrial Cardiomyopathies

    PubMed Central

    El-Hattab, Ayman W.; Scaglia, Fernando

    2016-01-01

    Mitochondria are found in all nucleated human cells and perform various essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA), whereas more than 99% of them are encoded by nuclear DNA (nDNA). Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs for various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20–40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular non-compaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain complexes subunits and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs, ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia. PMID:27504452

  14. Reversible T-wave inversions and neurogenic myocardial stunning in a patient with recurrent stress-induced cardiomyopathy.

    PubMed

    Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Suyama, Jumpei; Toshida, Tsutomu; Kayano, Hiroyuki; Shinozuka, Akira; Gokan, Takehiko; Kobayashi, Youichi

    2014-05-01

    A 72-year-old female was diagnosed as a stress-induced cardiomyopathy from apical ballooning pattern of left ventricular dysfunction without coronary artery stenosis after the mental stress. ECG showed the transient T-wave inversions after the ST-segment elevations. By the mental stress after 1 year, she showed a transient dysfunction with similar ECG changes again. T-wave inversions recovered earlier, and cardiac sympathetic dysfunction showed a lighter response corresponding to the less severe dysfunction than those after the first onset. Wellens' ECG pattern was associated with the degree of neurogenic myocardial stunning with sympathetic hyperinnervation caused by mental stress.

  15. MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression

    PubMed Central

    Vanhoutte, Laetitia; Guilbaud, Céline; Martherus, Ruben; Bouzin, Caroline; Gallez, Bernard; Dessy, Chantal; Balligand, Jean-Luc; Moniotte, Stéphane; Feron, Olivier

    2017-01-01

    The cardiopathogenic role of autoantibodies (aabs) directed against β1-adrenoreceptors (β1-AR) is well established. In mouse models, they cause progressive dilated cardiomyopathy (DCM) whose characterization with echocardiography requires prolonged protocols with numerous animals, complicating the evaluation of new treatments. Here, we report on the characterization of β1-aabs-induced DCM in mice using 11.7T MRI. C57BL/6J mice (n = 10 per group) were immunized against the β1-AR and left ventricular (LV) systolic function was assessed at 10, 18 and 27 weeks. Increase in LV mass/tibial length ratio was detected as the first modification at 10 weeks together with dilation of cavities, thereby outperforming echocardiography. Significant impairment in diastolic index was also observed in immunized animals before the onset of systolic dysfunction. Morphometric and histological measurements confirmed these observations. The same protocol performed on β3-AR-overexpressing mice and wild-type littermates (n = 8–12 per group) showed that transgenic animals were protected with reduced LV/TL ratio compared to wild-type animals and maintenance of the diastolic index. This study demonstrates that MRI allows a precocious detection of the subtle myocardial dysfunction induced by β1-aabs and that β3-AR stimulation blunts the development of β1-aabs-induced DCM, thereby paving the way for the use of β3AR-stimulating drugs to treat this autoimmune cardiomyopathy. PMID:28276515

  16. Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning

    PubMed Central

    Fraessdorf, Jan; Hollmann, Markus W.; Hanschmann, Iris; Heinen, André; Weber, Nina C.; Preckel, Benedikt; Huhn, Ragnar

    2015-01-01

    Background Opioid receptors (OR) are involved in myocardial late preconditioning (LPC) induced by morphine and δ1-opioid receptor (δ1-OR) agonists. The role of OR in ischemic-induced LPC is unknown. We investigated whether 1) OR are involved in the trigger and/or mediation phase of LPC and 2) a time course effect on the expression of different opioid receptors and their endogenous ligands exists. Methods Male Wistar rats were randomly allocated to four groups (each group n = 8). Awake animals were ischemic preconditioned by a 5 minutes coronary occlusion. 24 hours later, anesthetized animals underwent 25 minutes coronary occlusion followed by 2 hours of reperfusion. The role of OR was investigated by treatment with intraperitoneal naloxone (Nal) 10 minutes prior to LPC (Nal-LPC; trigger phase) or 10 min prior to sustained ischemia (LPC-Nal; mediation phase). Results LPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001). Naloxone during trigger or mediation phase completely abolished LPC-induced cardioprotection (59±9% and 62±9%; P<0.001 vs. LPC). 8, 12 and 24 hours after the ischemic stimulus, expression of δ-OR in the heart was increased, whereas μ-opioid receptor (μ-OR) and κ-opioid receptor (κ-OR) were not. Plasma concentrations of β-endorphin and leu-enkephalin but not dynorphin were increased by LPC. Conclusion Ischemic LPC is triggererd and mediated by OR. Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC. PMID:26226627

  17. Effects of estradiol on ischemic factor-induced astrocyte swelling and AQP4 protein abundance.

    PubMed

    Rutkowsky, Jennifer M; Wallace, Breanna K; Wise, Phyllis M; O'Donnell, Martha E

    2011-07-01

    In the early hours of ischemic stroke, cerebral edema forms as Na, Cl, and water are secreted across the blood-brain barrier (BBB) and astrocytes swell. We have shown previously that ischemic factors, including hypoxia, aglycemia, and arginine vasopressin (AVP), stimulate BBB Na-K-Cl cotransporter (NKCC) and Na/H exchanger (NHE) activities and that inhibiting NKCC and/or NHE by intravenous bumetanide and/or HOE-642 reduces edema and infarct in a rat model of ischemic stroke. Estradiol also reduces edema and infarct in this model and abolishes ischemic factor stimulation of BBB NKCC and NHE. There is evidence that NKCC and NHE also participate in ischemia-induced swelling of astrocytes. However, little is known about estradiol effects on astrocyte cell volume. In this study, we evaluated the effects of AVP (100 nM), hypoxia (7.5% O(2)), aglycemia, hypoxia (2%)/aglycemia [oxygen glucose deprivation (OGD)], and estradiol (1-100 nM) on astrocyte cell volume using 3-O-methyl-d-[(3)H]glucose equilibration methods. We found that AVP, hypoxia, aglycemia, and OGD (30 min to 5 h) each significantly increased astrocyte cell volume, and that estradiol (30-180 min) abolished swelling induced by AVP or hypoxia, but not by aglycemia or OGD. Bumetanide and/or HOE-642 also abolished swelling induced by AVP but not aglycemia. Abundance of aquaporin-4, known to participate in ischemia-induced astrocyte swelling, was significantly reduced following 7-day but not 2- or 3-h estradiol exposures. Our findings suggest that hypoxia, aglycemia, and AVP each contribute to ischemia-induced astrocyte swelling, and that the edema-attenuating effects of estradiol include reduction of hypoxia- and AVP-induced astrocyte swelling and also reduction of aquaporin-4 abundance.

  18. Prothymosin-alpha preconditioning activates TLR4-TRIF signaling to induce protection of ischemic retina.

    PubMed

    Halder, Sebok Kumar; Matsunaga, Hayato; Ishii, Ken J; Ueda, Hiroshi

    2015-12-01

    Prothymosin-alpha protects the brain and retina from ischemic damage. Although prothymosin-alpha contributes to toll-like receptor (TLR4)-mediated immnunopotentiation against viral infection, the beneficial effects of prothymosin-alpha-TLR4 signaling in protecting against ischemia remain to be elucidated. In this study, intravitreal administration of prothymosin-alpha 48 h before induction of retinal ischemia prevented retinal cellular damage as evaluated by histology, and retinal functional deficits as evaluated by electroretinography. Prothymosin-alpha preconditioning completely prevented the ischemia-induced loss of ganglion cells with partial survival of bipolar and photoreceptor cells, but not amacrine cells, in immunohistochemistry experiments. Prothymosin-alpha treatment in the absence of ischemia caused mild activation, proliferation, and migration of retinal microglia, whereas the ischemia-induced microglial activation was inhibited by prothymosin-alpha preconditioning. All these preventive effects of prothymosin-alpha preconditioning were abolished in TLR4 knock-out mice and by pre-treatments with anti-TLR4 antibodies or minocycline, a microglial inhibitor. Prothymosin-alpha preconditioning inhibited the retinal ischemia-induced up-regulation of TLR4-related injury genes, and increased expression of TLR4-related protective genes. Furthermore, the prothymosin-alpha preconditioning-induced prevention of retinal ischemic damage was abolished in TIR-domain-containing adapter-inducing interferon-β knock-out mice, but not in myeloid differentiation primary response gene 88 knock-out mice. Taken together, the results of this study suggest that prothymosin-alpha preconditioning selectively drives TLR4-TIR-domain-containing adapter-inducing interferon-β signaling and microglia in the prevention of retinal ischemic damage. We propose the following mechanism for prothymosin-alpha (ProTα) preconditioning-induced retinal prevention against ischemia: Pro

  19. Ischemic conditioning-induced endogenous brain protection: Applications Pre-, Per- or Post-Stroke

    PubMed Central

    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H.

    2015-01-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre- or post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stoke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post- ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on those

  20. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

    PubMed

    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

  1. Alcohol-induced exacerbation of ischemic brain injury: role of NAD(P)H oxidase.

    PubMed

    Zhao, Honggang; Mayhan, William G; Arrick, Denise M; Xiong, Wanfen; Sun, Hong

    2010-11-01

     Chronic alcohol consumption increases ischemic stroke and exacerbates ischemic brain injury. We determined the role of NAD(P)H oxidase in exacerbated ischemic brain injury during chronic alcohol consumption.  Sprague Dawley rats were fed a liquid diet with or without alcohol (6.4% v/v) for 8 weeks. We measured the effect of apocynin on 2-hour middle cerebral artery occlusion (MCAO)/24-hour reperfusion-induced brain injury. In addition, superoxide production and expression of NAD(P)H oxidase subunit, gp91phox, in the peri-infarct area were assessed. Chronic alcohol consumption produced a larger infarct volume, worse neurological score, and higher superoxide production. Acute (5 mg/kg, ip, 30 minutes before MCAO) and chronic treatment with apocynin (7.5 mg/kg/d in the diet, 4 weeks prior to MCAO) reduced infarct volume, improved neurological outcome, and attenuated superoxide production in alcohol-fed rats. Expression of gp91phox at basal conditions and following ischemia/reperfusion was greater in alcohol-fed rats compared to non-alcohol-fed rats. In addition, neurons are partially responsible for upregulated gp91phox during alcohol consumption. Our findings suggest that NAD(P)H oxidase may play an important role in exacerbated ischemic brain injury during chronic alcohol consumption. Copyright © 2010 by the Research Society on Alcoholism.

  2. Hypoxia Induces Dilated Cardiomyopathy in the Chick Embryo: Mechanism, Intervention, and Long-Term Consequences

    PubMed Central

    Ahmad, Shakil; Crispi, Fatima; van Bilsen, Marc; Carmeliet, Peter; Staff, Anne Cathrine; Tjwa, Marc; Cetin, Irene; Gratacos, Eduard; Hernandez-Andrade, Edgar; Hofstra, Leo; Jacobs, Michael; Lamers, Wouter H.; Morano, Ingo; Safak, Erdal; Ahmed, Asif; le Noble, Ferdinand

    2009-01-01

    Background Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood. PMID:19357774

  3. Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy.

    PubMed

    Elkareh, Jihad; Periyasamy, Sankaridrug M; Shidyak, Amjad; Vetteth, Sandeep; Schroeder, Jeremy; Raju, Vanamala; Hariri, Imad M; El-Okdi, Nasser; Gupta, Shalini; Fedorova, Larisa; Liu, Jiang; Fedorova, Olga V; Kahaleh, M Bashar; Xie, Zijian; Malhotra, Deepak; Watson, Dennis K; Bagrov, Alexei Y; Shapiro, Joseph I

    2009-05-01

    The cardiotonic steroid marinobufagenin (MBG) has been implicated in the pathogenesis of experimental uremic cardiomyopathy, which is characterized by progressive cardiac fibrosis. We examined whether the transcription factor Friend leukemia integration-1 (Fli-1) might be involved in this process. Fli-1-knockdown mice demonstrated greater cardiac collagen-1 expression and fibrosis compared with wild-type mice; both developed increased cardiac collagen expression and fibrosis after 5/6 nephrectomy. There was a strong inverse relationship between the expressions of Fli-1 and procollagen in primary culture of rat cardiac and human dermal fibroblasts as well as a cell line derived from renal fibroblasts and MBG-induced decreases in nuclear Fli-1 as well as increases in procollagen-1 expression in these cells. Transfection of a Fli-1 expression vector prevented increased procollagen-1 expression from MBG. MBG exposure induced a rapid translocation of the delta-isoform of protein kinase C (PKCdelta) to the nucleus. This translocation was prevented by pharmacological inhibition of phospholipase C, and MBG-induced increases in procollagen-1 expression were prevented with a PKCdelta- but not a PKCalpha-specific inhibitor. Finally, immunoprecipitation studies strongly suggest that MBG induced phosphorylation of Fli-1. We feel these data support a causal relationship with MBG-induced translocation of PKCdelta, which results in phosphorylation of as well as decreases in nuclear Fli-1 expression, which, in turn, leads to increases in collagen production. Should these findings be confirmed, we speculate that this pathway may represent a therapeutic target for uremic cardiomyopathy as well as other conditions associated with excessive fibrosis.

  4. Takotsubo cardiomyopathy post liver transplantation.

    PubMed

    Vachiat, Ahmed; McCutcheon, Keir; Mahomed, Adam; Schleicher, Gunter; Brand, Liezl; Botha, Jean; Sussman, Martin; Manga, Pravin

    2016-10-23

    A patient with end-stage liver disease developed stress-induced Takotsubo cardiomyopathy post liver transplantation, with haemodynamic instability requiring a left ventricular assist device. We discuss the diagnosis and management of this condition.

  5. Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium.

    PubMed

    Tang, Yao Liang; Zhao, Qiang; Zhang, Y Clare; Cheng, Leilei; Liu, Mingya; Shi, Jianhui; Yang, Yin Zeng; Pan, Chuizhen; Ge, Junbo; Phillips, M Ian

    2004-01-15

    Neovascularization induced by vascular endothelial growth factor (VEGF) represents an appealing approach for treating ischemic heart disease. However, VEGF therapy has been associated with transient therapeutic effects and potential risk for hemangioma growth. Adult mesenchymal stem cells (MSCs) derived from bone marrow are a promising source for tissue regeneration and repair. In order to achieve a safe and persistent angiogenic effect, we have explored the potential of autologous MSCs transplantation to enhance angiogenesis and cardiac function of ischemic hearts. One week after myocardial infarction induced by occlusion of left anterior descending artery, autologous MSCs expanded in vitro was administrated intramyocardially into the infarct area of the same donor rats. By 2 months, MSCs implantation significantly elevated VEGF expression levels, accompanied by increased vascular density and regional blood flow in the infarct zone. The neovascularization resulted in a decreased apoptosis of hypertrophied myocytes and markedly improved the left ventricular contractility (ejection fraction: 79.9+/-7.6% vs. 37.2+/-6.9% in control animals). Therefore, mechanisms underlying MSCs improvement of cardiac functions may involve neovascularization induced by differentiation of MSCs to endothelial cells and para-secretion of growth factors, in addition to the apoptosis reduction and previously reported cardiomyocytes regeneration. Two months after cell transplantation, there are significant improvement of left ventricular function. Hence, autologous MSCs transplantation may represent a promising therapeutic strategy free of ethical concerns and immune rejection, for neovascularization in ischemic heart diseases.

  6. Pheochromocytoma-Induced Inverted Takotsubo-Like Cardiomyopathy Leading to Cardiogenic Shock Successfully Treated With Extracorporeal Membrane Oxygenation.

    PubMed

    Flam, Benjamin; Broomé, Michael; Frenckner, Björn; Bränström, Robert; Bell, Max

    2015-09-01

    Pheochromocytoma classically displays a variety of rather benign symptoms, such as headache, palpitations, and sweating, although severe cardiac manifestations have been described. We report a case of pheochromocytoma-induced inverted takotsubo-like cardiomyopathy leading to shock and cardiac arrest successfully treated with extracorporeal membrane oxygenation (ECMO) as a bridge to pharmacological therapy and curative adrenalectomy. A previously healthy 46-year-old woman presented to the emergency department with abdominal pain, dyspnea, nausea, and vomiting. Clinical evaluation revealed cardiorespiratory failure with hypoxia and severe metabolic acidosis. Computed tomography (CT) scan showed pulmonary edema and a left adrenal mass. Transthoracic echocardiography (TTE) displayed severe left ventricular dysfunction with inverted takotsubo contractile pattern. Despite mechanical ventilation and inotropic and vasopressor support, asystolic cardiac arrest ensued. The patient was resuscitated using manual chest compressions followed by venoarterial ECMO. Repeated TTEs demonstrated resolution of the cardiomyopathy within a few days. Laboratory results indicated transient renal and hepatic dysfunction, and CT scan of the brain displayed occipital infarctions. Biochemical testing and radionuclide scintigraphy confirmed a pheochromocytoma. Pharmacological adrenergic blockade was instituted prior to delayed adrenalectomy after which the diagnosis was histopathologically verified. The patient recovered after rehabilitation. We conclude that pheochromocytoma should be considered in patients presenting with unexplained cardiovascular compromise, especially if they display (inverted) takotsubo contractile pattern. Timely, adequate management might involve ECMO as a bridge to pharmacological therapy and curative surgery. © The Author(s) 2014.

  7. Microbubble-Mediated Sonothrombolysis Improves Outcome After Thrombotic Microembolism-Induced Acute Ischemic Stroke.

    PubMed

    Lu, Yongkang; Wang, Junfen; Huang, Ruizhu; Chen, Gangbin; Zhong, Lintao; Shen, Shuxin; Zhang, Chuanxi; Li, Xinzhong; Cao, Shiping; Liao, Wangjun; Liao, Yulin; Bin, Jianping

    2016-05-01

    Microthrombi originating from disintegrated clots or formed in situ may account for the poor clinical improvement of acute ischemic stroke after recanalization therapy. We attempted to determine whether microbubble-mediated sonothrombolysis could dissolve platelet-rich and erythrocyte-rich microthrombi, thereby reducing their brain injury-causing potential. Platelet- and erythrocyte-rich microthrombosis were induced by periadventitial application of 5% ferric chloride or thrombin to mesenteric microvessels in 75 Sprague-Dawley rats. Acute ischemic stroke was induced by intracarotid injection of platelet- or erythrocyte-rich microthrombi in another 50 rats. Rats were randomly divided into control (CON), ultrasound (US), ultrasound and microbubble (US+MB), recombinant tissue-type plasminogen activator (r-tPA), and US+MB+r-tPA groups. The post-treatment mesenteric microvessel recanalization rates, cerebral infarct volumes, and neurological scores were determined. The recanalization rates of platelet- and erythrocyte-rich microthrombi in mesenteric microvessels were higher (P<0.05), and the cerebral infarct volumes and neurological scores of rats with either microthrombi were lower in the US+MB group than in the CON group (P<0.01). The infarct volumes and neurological scores were greater in the r-tPA group than in the US+MB and US+MB+r-tPA groups after treatment of rats with platelet-rich microthrombi (P<0.05). In contrast, after treatment of rats with erythrocyte-rich microthrombi, the infarct volumes and neurological scores were similar in the r-tPA and US+MB groups, but smaller in the US+MB+r-tPA group (P<0.05). Microbubble-mediated sonothrombolysis improved the outcomes of microthrombi-induced acute ischemic stroke. Thus, this method may serve as an attractive adjunct to recanalization therapy for acute ischemic stroke. © 2016 American Heart Association, Inc.

  8. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    PubMed

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values < 0.05). For every reduction of 5% in left ventricular ejection fraction induced by mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  9. Beneficial effect of muscarinic-2 antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic-2 receptor.

    PubMed

    Matsui, S; Fu, M L; Hayase, M; Katsuda, S; Yamaguchi, N; Teraoka, K; Kurihara, T; Takekoshi, N

    2001-10-01

    We have previously shown that a peptide corresponding to the sequence of the second extracellular loop of the human muscarinic-2 (M2) receptor (M2-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we investigated the effect of M2-antagonist (otenzepad) on M2-peptide-induced cardiomyopathy in rabbits. New Zealand White rabbits were divided into four groups: 1) control group, saline injection; 2) M2-peptide group, M2-peptide injection; 3) M2-antagonist group, otenzepad (30 mg/day) orally and saline injection; and (4) M2-antagonist + M2-peptide group, otenzepad (30 mg/day) orally and M2-peptide injection. The study duration was 1 year. Saline or peptide was injected once a month. All rabbits in both the M2-peptide group and the M2-antagonist + M2-peptide group had high titers of anti-M2-autoantibodies in their sera. Rabbits in the M2-peptide group showed an increase in heart weight, wall thinning and dilatation of the right ventricle. On the contrary, rabbits in the M2-antagonist + M2-peptide group had normal heart weight and shape. All rabbits in the M2-peptide group showed multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells, while four rabbits in the M2-antagonist + M2-peptide group showed slight infiltration of inflammatory cells with normal myocardial cells and interstitium, and another three showed no histological changes in the hearts. In conclusion, M2-antagonist protects the myocardium from injury induced by autoimmune mechanism against M2-muscarinic receptor.

  10. NLRP3 inflammasome knockout mice are protected against ischemic but not cisplatin-induced acute kidney injury.

    PubMed

    Kim, Hyun-Jung; Lee, Dong Won; Ravichandran, Kameswaran; O Keys, Daniel; Akcay, Ali; Nguyen, Quocan; He, Zhibin; Jani, Alkesh; Ljubanovic, Danica; Edelstein, Charles L

    2013-09-01

    We have demonstrated that caspase-1 is a mediator of both cisplatin-induced acute kidney injury (AKI) and ischemic AKI. As caspase-1 is activated in the inflammasome, we investigated the inflammasome in cisplatin-induced and ischemic AKI. Mice were injected with cisplatin or subjected to bilateral renal pedicle clamping. Immunoblot analysis of whole kidney after cisplatin-induced AKI revealed: 1) an increase in apoptosis-associated Speck-like protein containing a caspase recruitment domain (ASC), the major protein that complexes with nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing proteins (NLRP) 1 or 3 to form the inflammasome; 2) an increase in caspase-1 activity, caspase-5, and NLRP1, components of the NLRP1 inflammasome; and 3) a trend toward increased NLRP3. To determine whether the NLRP3 inflammasome plays an injurious role in cisplatin-induced AKI, we studied NLRP knockout (NLRP3(-/-)) mice. In cisplatin-induced AKI, the blood urea nitrogen, serum creatinine, acute tubular necrosis score, and tubular apoptosis score were not significantly decreased in NALP3(-/-) mice compared with wild-type mice. We have previously demonstrated the injurious role of caspase-1 in ischemic AKI. NLRP3, but not ASC or NLRP1, is increased in ischemic AKI. NLRP3(-/-) mice with ischemic AKI had significantly lower blood urea nitrogen, serum creatinine, and acute tubular necrosis and apoptosis scores than the wild-type controls. The difference in protection against cisplatin-induced AKI compared with ischemic AKI in NLRP3(-/-) mice was not explained by the differences in proinflammatory cytokines interleukin (IL)-1β, IL-6, chemokine (C-X-C motif) ligand 1, or tumor necrosis factor α. NLRP3 inflammasome is a mediator of ischemic AKI but not cisplatin-induced AKI, and further investigation of the NLRP1 inflammasome in cisplatin-induced AKI should prove interesting.

  11. TRAINING-INDUCED VASCULAR ADAPTATIONS TO ISCHEMIC MUSCLE

    PubMed Central

    YANG, H.T.; PRIOR, B.M.; LLOYD, P.G.; TAYLOR, J.C.; LI, Z.; LAUGHLIN, M.H.; TERJUNG, R.L.

    2009-01-01

    Peripheral arterial insufficiency is a progressive degenerative disease associated with an increased morbidity and mortality. It decreases exercise tolerance and often presents with symptoms of intermittent claudication. Enhanced physical activity is one of the most effective means of improving the life of affected patients. While this occurs for a variety of reasons, vascular remodeling can be an important means for improved oxygen exchange and blood flow delivery. Relevant exercise-induced signals stimulate angiogenesis, within the active muscle (e.g. hypoxia), and arteriogenesis (enlargement of pre-existing vessels via increased shear stress) to increase oxygen exchange and blood flow capacity, respectively. Evidence from pre-clinical studies shows that the increase in collateral blood flow observed with exercise progresses over time of training, is accompanied by significant enlargement of isolated collateral vessels, and enhances the responses observed with angiogenic growth factors (e.g. VEGF, FGF-2). Thus, enhanced physical activity can be an effective means of enlarging the structure and function of the collateral circuit. Interestingly, disrupting normal NO production (via L-NAME) eliminates this increase in collateral blood flow induced by training, but does not disturb the increase in muscle capillarity within the active muscle. Similarly, inhibiting VEGF receptor kinase activity eliminates the increase in collateral-dependent blood flow, and lessens, but does not eliminate, angiogenesis within the calf muscle. These findings illustrate distinctions between the processes influencing angiogenesis and arteriogenesis. Further, sympathetic modulation of the collateral circuit does not eliminate the increase in collateral circuit conductance induced by exercise training. These findings indicate that structural enlargement of the collateral vessels is essential to realize the increase in collateral-dependent blood flow capacity caused by exercise training

  12. The influence of sulindac on diabetic cardiomyopathy: a non-invasive evaluation by Doppler echocardiography in streptozotocin-induced diabetic rats.

    PubMed

    Krishna, Kota M; Gopal, Gopisetty S; Chalam, Chitrapu R V; Madan, Kalagara; Kumar, Veeravalli K; Prakash, Gomedhikam J; Annapurna, Akula

    2005-08-01

    The aim of the present study was to investigate the cardioprotective activity of sulindac as an aldose reductase inhibitor in the development of cardiomyopathy by non-invasive techniques; M-mode and Doppler echocardiography. Diabetes was induced by streptozotocin (45 mg/kg, iv) in the Sprague-Dawley rats. Echocardiography, biochemical and histological studies were carried out in normal control, diabetic untreated, diabetic vehicle (sodium carboxy methyl cellulose, 1%, po) and sulindac (6 mg/kg and 20 mg/kg, po) treated animals at varying time intervals. In the diabetic untreated and vehicle treated rats at 12 weeks after induction of diabetes, there was a significant decrease in the E-wave, an increase in the A-wave and corresponding decrease in the E/A ratio was observed. Significant decrease in the Eat was found after 12 weeks (P < 0.05). Whereas systolic function variables; ejection fraction and fractional shortening were significantly decreased (P < 0.05) after 12 weeks compared to their baseline data. In the sulindac treated animals, there were no significant alterations in the systolic and diastolic parameters were found throughout the study period. Myocardial fructose levels were significantly increased in the diabetic untreated animals compared to normal control rats (P < 0.05), whereas these were significantly decreased in the sulindac (6 mg/kg and 20 mg/kg) treated animals (301.11+/-37.98, 214.11+/-25.31, vs. 914.88+/-56.01 nmol/g) compared to diabetic vehicle treated group (P < 0.05). Extensive focal ischemic myocyte degeneration was observed in the diabetic untreated and vehicle treated rats, whereas in the sulindac (6 mg/kg) treated rats, minimal necrosis was found, with no evidence of necrosis in sulindac (20 mg/kg) group. Our results show for the first time that sulindac has a cardioprotective activity as this agent prevented the development of left ventricular dysfunction in STZ-induced diabetic rats in the 12-week chronic study.

  13. Angiotensin II-induced dilated cardiomyopathy in Balb/c but not C57BL/6J mice.

    PubMed

    Peng, Hongmei; Yang, Xiao-Ping; Carretero, Oscar A; Nakagawa, Pablo; D'Ambrosio, Martin; Leung, Pablo; Xu, Jiang; Peterson, Edward L; González, Germán E; Harding, Pamela; Rhaleb, Nour-Eddine

    2011-08-01

    Balb/c mice, which are T-helper lymphocyte 2 (Th2) responders, are highly susceptible to infectious and non-infectious heart diseases, whereas C57BL/6 mice (Th1 responders) are not. Angiotensin II (Ang II) is not only a vasopressor but also a pro-inflammatory factor that leads to cardiac hypertrophy, fibrosis and dysfunction. We hypothesized that Ang II exacerbates cardiac damage in Balb/c but not in C57BL/6 mice even though both strains have a similar level of hypertension. Twelve-week-old male C57BL/6J and Balb/c mice received either vehicle or Ang II (1.4 mg kg(-1) day(-1), s.c. via osmotic minipump) for 8 weeks. At baseline, Balb/c mice exhibited the following: (1) a lower heart rate; (2) an enlarged left ventricular chamber; (3) a lower ejection fraction and shortening fraction; and (4) twice the left ventricular collagen deposition of age-matched C57BL/6J mice. Angiotensin II raised systolic blood pressure (to ∼150 mmHg) and induced cardiomyocyte hypertrophy in a similar manner in both strains. While C57BL/6J mice developed compensatory concentric hypertrophy and fibrosis in response to Ang II, Balb/c mice demonstrated severe left ventricular chamber dilatation, wall thinning and fibrosis, leading to congestive heart failure as evidenced by dramatically decreased ejection fraction and lung congestion (significant increase in lung weight), which are both characteristic of dilated cardiomyopathy. Our study suggests that the Th phenotype plays an active role in cardiac remodelling and function both in basal conditions and in hypertension. Angiotensin II-induced dilated cardiomyopathy in Balb/c mice is an ideal animal model for studying the impact of the adaptive immune system on cardiac remodelling and function and for testing strategies to prevent or treat hypertension-associated heart failure.

  14. Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms

    PubMed Central

    Gammella, Elena; Recalcati, Stefania; Rybinska, Ilona; Buratti, Paolo; Cairo, Gaetano

    2015-01-01

    The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies. PMID:25878762

  15. Furazolidone-induced cardiomyopathy in turkeys. Association with a relative alpha1-antitrypsin deficiency.

    PubMed

    Staley, N A; Noren, G R; Bandt, C M; Sharp, H L

    1978-06-01

    A naturally occurring cardiomyopathy (round heart disease) which is potentiated by inbreeding and a cardiomyopathy produced by furazolidone, a nitrofuran derivative, were studied for an associated alpha1-antitrypsin deficiency in two flocks of turkeys (one inbred for round heart disease and a commercial flock). At 4 weeks of age, the furazolidone-fed birds of both flocks demonstrated a marked increase in mortality and cardiac dilatation associated with disordered hepatic metabolism when compared with controls. Although PAS-positive, diastase-resistant globules were observed in the livers of both strains of turkeys fed furazolidone, these globules were present in lysosomes and not in the rough endoplasmic reticulum as in alpha1-antitrypsin deficiency. The control inbred birds with round heart disease did not demonstrate histologic or biochemical evidence of an alpha1-antitrypsin deficiency. It is proposed that furazolidone in the turkey produces primary hepatic damage that is reflected in lowered total serum proteins, including trypsin inhibitory capacity, and that the alterations produced by furazolidone are superimposed on round heart disease in the inbred flock.

  16. Furazolidone-induced cardiomyopathy in turkeys. Association with a relative alpha1-antitrypsin deficiency.

    PubMed Central

    Staley, N. A.; Noren, G. R.; Bandt, C. M.; Sharp, H. L.

    1978-01-01

    A naturally occurring cardiomyopathy (round heart disease) which is potentiated by inbreeding and a cardiomyopathy produced by furazolidone, a nitrofuran derivative, were studied for an associated alpha1-antitrypsin deficiency in two flocks of turkeys (one inbred for round heart disease and a commercial flock). At 4 weeks of age, the furazolidone-fed birds of both flocks demonstrated a marked increase in mortality and cardiac dilatation associated with disordered hepatic metabolism when compared with controls. Although PAS-positive, diastase-resistant globules were observed in the livers of both strains of turkeys fed furazolidone, these globules were present in lysosomes and not in the rough endoplasmic reticulum as in alpha1-antitrypsin deficiency. The control inbred birds with round heart disease did not demonstrate histologic or biochemical evidence of an alpha1-antitrypsin deficiency. It is proposed that furazolidone in the turkey produces primary hepatic damage that is reflected in lowered total serum proteins, including trypsin inhibitory capacity, and that the alterations produced by furazolidone are superimposed on round heart disease in the inbred flock. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:148846

  17. [Peripartum cardiomyopathy].

    PubMed

    Mouquet, Frédéric; Bouabdallaoui, Nadia

    2015-01-01

    The peripartum cardiomyopathy is a rare form of dilated cardiomyopathy resulting from alteration of angiogenesis toward the end of pregnancy. The diagnosis is based on the association of clinical heart failure and systolic dysfunction assessed by echocardiography or magnetic resonance imaging. Diagnoses to rule out are myocardial infarction, amniotic liquid embolism, myocarditis, inherited cardiomyopathy, and history of treatment by anthracycline. Risk factors are advance maternal age (>30), multiparity, twin pregnancy, African origin, obesity, preeclampsia, gestational hypertension, and prolonged tocolytic therapy. Treatment of acute phase is identical to usual treatment of acute systolic heart failure. After delivery, VKA treatment should be discussed in case of systolic function <25% because of higher risk of thrombus. A specific treatment by bromocriptine can be initiated on a case-by-case basis. Complete recovery of systolic function is observed in 50% of cases. The mortality risk is low. Subsequent pregnancy should be discouraged, especially if systolic function did not recover.

  18. Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts.

    PubMed

    Guaiquil, Victor H; Golde, David W; Beckles, Daniel L; Mascareno, Eduardo J; Siddiqui, M A Q

    2004-11-01

    Reactive oxygen species play a central role in myocardial ischemic injury and are a target for therapeutic intervention. Vitamin C is an essential antioxidant yet difficult to deliver in pharmacologic concentration to the myocardium. We found that adult rat cardiomyocytes accumulate vitamin C by transporting dehydroascorbic acid (DHA), the oxidized form of vitamin C, but do not transport ascorbic acid. Loading cells with vitamin C by DHA treatment resulted in resistance to hypoxia- and hypoxia/reoxygenation-induced cell death associated with the quenching of reactive oxygen species. When rats were injected with DHA before coronary occlusion, the ascorbic acid content in the heart was six to eight times higher than in untreated controls and myocardial infarction was reduced by 62%. DHA also provided significant protection when administered intravenously 2 h after coronary occlusion. In cardiomyocytes subjected to hypoxia/reoxygenation, DHA treatment resulted in decreased apoptosis associated with inhibition of Bax expression, caspase-3 activation, and cytochrome c translocation into the cytoplasm. DHA treatment also inhibited Jak2, STAT1, and STAT5 phosphorylation, and increased STAT3 phosphorylation, in hypoxic cardiomyocytes and ischemic myocardial tissue. Our findings suggest that DHA may be useful as a cardioprotectant in ischemic heart disease.

  19. Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain.

    PubMed

    Kawai, Hiromi; Yamashita, Toru; Ohta, Yasuyuki; Deguchi, Kentaro; Nagotani, Shoko; Zhang, Xuemei; Ikeda, Yoshio; Matsuura, Tohru; Abe, Koji

    2010-08-01

    Stroke is a major neurologic disorder. Induced pluripotent stem (iPS) cells can be produced from basically any part of patients, with high reproduction ability and pluripotency to differentiate into various types of cells, suggesting that iPS cells can provide a hopeful therapy for cell transplantation. However, transplantation of iPS cells into ischemic brain has not been reported. In this study, we showed that the iPS cells fate in a mouse model of transient middle cerebral artery occlusion (MCAO). Undifferentiated iPS cells (5 x 10(5)) were transplanted into ipsilateral striatum and cortex at 24 h after 30 mins of transient MCAO. Behavioral and histologic analyses were performed at 28 day after the cell transplantation. To our surprise, the transplanted iPS cells expanded and formed much larger tumors in mice postischemic brain than in sham-operated brain. The clinical recovery of the MCAO+iPS group was delayed as compared with the MCAO+PBS (phosphate-buffered saline) group. iPS cells formed tridermal teratoma, but could supply a great number of Dcx-positive neuroblasts and a few mature neurons in the ischemic lesion. iPS cells have a promising potential to provide neural cells after ischemic brain injury, if tumorigenesis is properly controlled.

  20. Exercise-induced ischemic preconditioning detected by sequential exercise stress tests: a meta-analysis.

    PubMed

    Lalonde, François; Poirier, Paul; Sylvestre, Marie-Pierre; Arvisais, Denis; Curnier, Daniel

    2015-01-01

    Exercise-induced ischemic preconditioning (IPC) can be assessed with the second exercise stress test during sequential testing. Exercise-induced IPC is defined as the time to 1 mm ST segment depression (STD), the rate-pressure product (RPP) at 1 mm STD, the maximal ST depression and the rate-pressure product at peak exercise. The purpose of this meta-analysis is to validate the parameters used to assess exercise-induced IPC in the scientific community. A literature search was performed using electronic database. The main key words were limited to human studies, which were (a) ischemic preconditioning, (b) warm-up phenomenon, and (c) exercise. Meta-analyses were performed on the study-specific mean difference between the clinical measures obtained in the two consecutive stress tests (second minus first test score). Random effect models were fitted with inverse variance weighting to provide greater weight to studies with larger sample size and more precise estimates. The search resulted in 309 articles of which 34 were included after revision (1053 patients). Results are: (a) time to 1 mm ST segment depression increased by 91 s (95% confidence interval (CI): 75-108), p < 0.001; (b) peak ST depression decreased by -0.38 mm (95% CI: -0.66 to -0.10), p < 0.01; and (c) rate-pressure product at 1 mm STD increased by 1.80 × 10(3)mmHg (95% CI: 1.0-2.0), p < 0.001. This is the first meta-analysis to set clinical parameters to assess the benefit of exercise-induced ischemic preconditioning in sequential stress testing. The results of this first meta-analysis on the sequential stress test confirm what is presented in the literature by independent studies on exercise-induced ischemic preconditioning. From now on, the results could be used in further research to set standardized parameters to assess the phenomenon. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Genistein inhibits hypoxia, ischemic-induced death, and apoptosis in PC12 cells.

    PubMed

    Wang, Yu-Xiang; Tian, Kun; He, Cong-Cong; Ma, Xue-Ling; Zhang, Feng; Wang, Hong-Gang; An, Di; Heng, Bin; Jiang, Yu-Gang; Liu, Yan-Qiang

    2017-03-01

    A hypoxia/ischemia neuronal model was established in PC12 cells using oxygen-glucose deprivation (OGD). OGD-induced neuronal death, apoptosis, glutamate receptor subunit GluR2 expression, and potassium channel currents were evaluated in the present study to determine the effects of genistein in mediating the neuronal death and apoptosis induced by hypoxia and ischemia, as well as its underlying mechanism. OGD exposure reduced the cell viability, increased apoptosis, decreased the GluR2 expression, and decreased the voltage-activated potassium currents. Genistein partially reversed the effects induced by OGD. Therefore, genistein may prevent hypoxia/ischemic-induced neuronal apoptosis that is mediated by alterations in GluR2 expression and voltage-activated potassium currents. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. How Exercise May Amend Metabolic Disturbances in Diabetic Cardiomyopathy

    PubMed Central

    Hafstad, Anne D.; Boardman, Neoma

    2015-01-01

    Abstract Significance: Over-nutrition and sedentary lifestyle has led to a worldwide increase in obesity, insulin resistance, and type 2 diabetes (T2D) associated with an increased risk of development of cardiovascular disorders. Diabetic cardiomyopathy, independent of hypertension or coronary disease, is induced by a range of systemic changes and may through multiple processes result in functional and structural cardiac derangements. The pathogenesis of this cardiomyopathy is complex and multifactorial, and it will eventually lead to reduced cardiac working capacity and increased susceptibility to ischemic injury. Recent Advances: Metabolic disturbances such as altered lipid handling and substrate utilization, decreased mechanical efficiency, mitochondrial dysfunction, disturbances in nonoxidative glucose pathways, and increased oxidative stress are hallmarks of diabetic cardiomyopathy. Interestingly, several of these disturbances are found to precede the development of cardiac dysfunction. Critical Issues: Exercise training is effective in the prevention and treatment of obesity and T2D. In addition to its beneficial influence on diabetes/obesity-related systemic changes, it may also amend many of the metabolic disturbances characterizing the diabetic myocardium. These changes are due to both indirect effects, exercise-mediated systemic changes, and direct effects originating from the high contractile activity of the heart during physical training. Future Directions: Revealing the molecular mechanisms behind the beneficial effects of exercise training is of considerable scientific value to generate evidence-based therapy and in the development of new treatment strategies. Antioxid. Redox Signal. 22, 1587–1605. PMID:25738326

  3. Acute hemodynamic effects of right ventricular pacing site and pacing mode in patients with congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.

    PubMed

    Gold, M R; Brockman, R; Peters, R W; Olsovsky, M R; Shorofsky, S R

    2000-05-01

    The hemodynamic effects of pacing in patients with congestive heart failure (CHF) remain controversial. Early studies reported that pacing from the right ventricular (RV) apex improved acute hemodynamic parameters in patients with left ventricular systolic dysfunction, but these findings were not confirmed in subsequent controlled studies. More recently, it has been proposed that pacing from the RV side of the ventricular septum improves hemodynamic function compared with intrinsic conduction or apical pacing. Either dual-chamber or ventricular pacing have been evaluated, again with inconsistent findings. To assess the effects of pacing site and mode on acute hemodynamic function, we evaluated 21 subjects with CHF and intrinsic conduction disease. Hemodynamics were compared in AAI, VVI, and DDD modes with pacing from the RV apex or high septum. The pacing rate was constant in each patient and the order of testing was randomized. In the absence of ventricular pacing (AAI mode), the mean systemic arterial pressure was 85 +/- 11 mm Hg, the right atrial pressure was 11 +/- 4 mm Hg, the pulmonary capillary wedge pressure was 18 +/- 8 mm Hg and the cardiac index was 2.4 +/- 0.7 L/min/m(2). Compared with AAI pacing, there were no improvements in any hemodynamic parameter with DDD pacing from either RV site. Hemodynamic function worsened with VVI pacing from both RV sites. Subgroup analyses of patients with dilated cardiomyopathy, with prolonged PR interval, or with significant mitral regurgitation also failed to demonstrate an improvement with pacing. We conclude that pacing mode but not RV pacing site affects acute hemodynamic function. Pacing in the DDD mode prevents the deleterious effects of VVI pacing in this patient population.

  4. A Three-Dimensional Regional Strain Computation Method with Displacement ENcoding with Stimulated Echoes (DENSE) in Non-Ischemic, Non-Valvular Dilated Cardiomyopathy Patients and Healthy Subjects Validated by Tagged MRI

    PubMed Central

    Kar, Julia; Knutsen, Andrew K.; Cupps, Brian P.; Zhong, Xiaodong; Pasque, Michael K.

    2015-01-01

    Purpose Fast cine displacement encoding with stimulated echoes (DENSE) MR has higher spatial resolution and enables rapid post-processing. Thus we compared the accuracy of regional strains computation by DENSE with tagged MR in healthy and non-ischemic, non-valvular dilated cardiomyopathy (DCM) subjects. Materials and Methods Validation of 3D regional strains computed with DENSE was conducted in reference to standard tagged MRI (TMRI) in healthy subjects and patients with DCM. Additional repeatability studies in healthy subjects were conducted to increase confidence in DENSE. A meshfree multiquadrics radial point interpolation method (RPIM) was used for computing Lagrange strains in sixteen left ventricular segments. Bland-Altman analysis and Student's t-tests were conducted to observe similarities in regional strains between sequences and in DENSE repeatability studies. Results Regional circumferential strains ranged from -0.21 ± 0.07 (Lateral-Apex) to -0.11 ± 0.05 (Posterorseptal-Base) in healthy subjects and -0.15 ± 0.04 (Anterior-Apex) to -0.02 ± 0.08 (Posterorseptal-Base) in DCM patients. Computed mean differences in regional circumferential strain from the DENSE-TMRI comparison study was 0.01 ± 0.03 (95% limits of agreement) in normal subjects, -0.01 ± 0.06 in DCM patients and 0.0 ± 0.02 in repeatability studies, with similar agreements in longitudinal and radial strains. Conclusion We found agreement between DENSE and tagged MR in patients and volunteers in terms of evaluation of regional strains. PMID:24753028

  5. Comparison of coronary artery bypass grafting versus medical therapy on long-term outcome in patients with ischemic cardiomyopathy (a 25-year experience from the Duke Cardiovascular Disease Databank).

    PubMed

    O'Connor, Christopher M; Velazquez, Eric J; Gardner, Laura H; Smith, Peter K; Newman, Mark F; Landolfo, Kevin P; Lee, Kerry L; Califf, Robert M; Jones, Robert H

    2002-07-15

    In this observational treatment comparison in a single center over 25 years, we sought to assess long-term outcomes of coronary artery bypass surgery (CABG) or medical therapy in patients with heart failure, coronary artery disease, and left ventricular systolic dysfunction. The benefit of CABG compared with medical therapy alone in these patients is a source of continuing clinical debate. This analysis considered all patients with New York Heart Association class II or greater symptoms, 1 or more epicardial coronary vessels with a > or = 75% stenosis, and a left ventricular ejection fraction <40% who underwent an initial cardiac catheterization at Duke University Medical Center from 1969 to 1994. Patients were classified into the medical therapy group (n = 1,052) or CABG group (n = 339) depending on which therapy they received within 30 days of catheterization. Cardiovascular event and mortality follow-up commenced on the day of CABG, or at catheterization plus 8 days (the mean time to CABG) for the medical therapy arm. A Cox proportional-hazards model was employed to adjust for differences in baseline characteristics. In the first 30 days from baseline, there was an interaction between treatment strategy and number of diseased vessels. Unadjusted, event-free, and adjusted survival strongly favored CABG over medical therapy after 30 days to >10 years regardless of the extent of coronary disease (p <0.001). Thus, regardless of the severity of coronary disease, heart failure symptoms, or ventricular dysfunction, CABG provides extended event-free and survival advantage over medical therapy alone in patients with an ischemic cardiomyopathy.

  6. Effect of the stop-flow technique on cardiac retention of c-kit positive human cardiac stem cells after intracoronary infusion in a porcine model of chronic ischemic cardiomyopathy.

    PubMed

    Keith, Matthew C L; Tokita, Yukichi; Tang, Xian-Liang; Ghafghazi, Shahab; Moore, Joseph B; Hong, Kyung U; Elmore, Julius B; Amraotkar, Alok R; Guo, Haixun; Ganzel, Brian L; Grubb, Kendra J; Flaherty, Michael P; Vajravelu, Bathri N; Wysoczynski, Marcin; Bolli, Roberto

    2015-09-01

    It is commonly thought that the optimal method for intracoronary administration of cells is to stop coronary flow during cell infusion, in order to prolong cell/vascular wall contact, enhance adhesion, and promote extravasation of cells into the interstitial space. However, occlusion of a coronary artery with a balloon involves serious risks of vascular damage and/or dissection, particularly in non-stented segments such as those commonly found in patients with heart failure. It remains unknown whether the use of the stop-flow technique results in improved donor cell retention. Acute myocardial infarction was produced in 14 pigs. One to two months later, pigs received 10 million indium-111 oxyquinoline (oxine)-labeled c-kit(pos) human cardiac stem cells (hCSCs) via intracoronary infusion with (n = 7) or without (n = 7) balloon inflation. Pigs received cyclosporine to prevent acute graft rejection. Animals were euthanized 24 h later and hearts harvested for radioactivity measurements. With the stop-flow technique, the retention of hCSCs at 24 h was 5.41 ± 0.80 % of the injected dose (n = 7), compared with 4.87 ± 0.62 % without coronary occlusion (n = 7), (P = 0.60). When cells are delivered intracoronarily in a clinically relevant porcine model of chronic ischemic cardiomyopathy, the use of the stop-flow technique does not result in greater myocardial cell retention at 24 h compared with non-occlusive infusion. These results have practical implications for the design of cell therapy trials. Our observations suggest that the increased risk of complications secondary to coronary manipulation and occlusion is not warranted.

  7. Cardiovascular Magnetic Resonance Imaging of Myocardial Infarction, Viability, and Cardiomyopathies

    PubMed Central

    West, Amy M.; Kramer, Christopher M.

    2010-01-01

    Cardiovascular magnetic resonance provides the opportunity for a truly comprehensive evaluation of patients with a history of MI, with regards to characterizing the extent of disease, impact on LV function and degree of viable myocardium. The use of contrast-enhanced CMR for first-pass perfusion and late gadolinium enhancement is a powerful technique for delineating areas of myocardial ischemia and infarction. Using a combination of T2-weighted and contrast-enhanced CMR images, information about the acuity of an infarct can be obtained. There is an extensive amount of literature using contrast-enhanced CMR to predict myocardial functional recovery with revascularization in patients with ischemic cardiomyopathies. In addition, CMR imaging in patients with cardiomyopathies can distinguish between ischemic and non-ischemic etiologies, with the ability to further characterize the underlying pathology for non-ischemic cardiomyopathies. PMID:20197150

  8. iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death.

    PubMed

    Notari, Mario; Hu, Ying; Sutendra, Gopinath; Dedeić, Zinaida; Lu, Min; Dupays, Laurent; Yavari, Arash; Carr, Carolyn A; Zhong, Shan; Opel, Aaisha; Tinker, Andrew; Clarke, Kieran; Watkins, Hugh; Ferguson, David J P; Kelsell, David P; de Noronha, Sofia; Sheppard, Mary N; Hollinshead, Mike; Mohun, Timothy J; Lu, Xin

    2015-03-03

    Desmosomes are anchoring junctions that exist in cells that endure physical stress such as cardiac myocytes. The importance of desmosomes in maintaining the homeostasis of the myocardium is underscored by frequent mutations of desmosome components found in human patients and animal models. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a phenotype caused by mutations in desmosomal components in ∼ 50% of patients, however, the causes in the remaining 50% of patients still remain unknown. A deficiency of inhibitor of apoptosis-stimulating protein of p53 (iASPP), an evolutionarily conserved inhibitor of p53, caused by spontaneous mutation recently has been associated with a lethal autosomal recessive cardiomyopathy in Poll Hereford calves and Wa3 mice. However, the molecular mechanisms that mediate this putative function of iASPP are completely unknown. Here, we show that iASPP is expressed at intercalated discs in human and mouse postmitotic cardiomyocytes. iASPP interacts with desmoplakin and desmin in cardiomyocytes to maintain the integrity of desmosomes and intermediate filament networks in vitro and in vivo. iASPP deficiency specifically induces right ventricular dilatation in mouse embryos at embryonic day 16.5. iASPP-deficient mice with exon 8 deletion (Ppp1r13l(Δ8/Δ8)) die of sudden cardiac death, displaying features of ARVC. Intercalated discs in cardiomyocytes from four of six human ARVC cases show reduced or loss of iASPP. ARVC-derived desmoplakin mutants DSP-1-V30M and DSP-1-S299R exhibit weaker binding to iASPP. These data demonstrate that by interacting with desmoplakin and desmin, iASPP is an important regulator of desmosomal function both in vitro and in vivo. This newly identified property of iASPP may provide new molecular insight into the pathogenesis of ARVC.

  9. iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death

    PubMed Central

    Notari, Mario; Hu, Ying; Sutendra, Gopinath; Dedeić, Zinaida; Lu, Min; Dupays, Laurent; Yavari, Arash; Carr, Carolyn A.; Zhong, Shan; Opel, Aaisha; Tinker, Andrew; Clarke, Kieran; Watkins, Hugh; Ferguson, David J. P.; Kelsell, David P.; de Noronha, Sofia; Sheppard, Mary N.; Hollinshead, Mike; Mohun, Timothy J.; Lu, Xin

    2015-01-01

    Desmosomes are anchoring junctions that exist in cells that endure physical stress such as cardiac myocytes. The importance of desmosomes in maintaining the homeostasis of the myocardium is underscored by frequent mutations of desmosome components found in human patients and animal models. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a phenotype caused by mutations in desmosomal components in ∼50% of patients, however, the causes in the remaining 50% of patients still remain unknown. A deficiency of inhibitor of apoptosis-stimulating protein of p53 (iASPP), an evolutionarily conserved inhibitor of p53, caused by spontaneous mutation recently has been associated with a lethal autosomal recessive cardiomyopathy in Poll Hereford calves and Wa3 mice. However, the molecular mechanisms that mediate this putative function of iASPP are completely unknown. Here, we show that iASPP is expressed at intercalated discs in human and mouse postmitotic cardiomyocytes. iASPP interacts with desmoplakin and desmin in cardiomyocytes to maintain the integrity of desmosomes and intermediate filament networks in vitro and in vivo. iASPP deficiency specifically induces right ventricular dilatation in mouse embryos at embryonic day 16.5. iASPP-deficient mice with exon 8 deletion (Ppp1r13lΔ8/Δ8) die of sudden cardiac death, displaying features of ARVC. Intercalated discs in cardiomyocytes from four of six human ARVC cases show reduced or loss of iASPP. ARVC-derived desmoplakin mutants DSP-1-V30M and DSP-1-S299R exhibit weaker binding to iASPP. These data demonstrate that by interacting with desmoplakin and desmin, iASPP is an important regulator of desmosomal function both in vitro and in vivo. This newly identified property of iASPP may provide new molecular insight into the pathogenesis of ARVC. PMID:25691752

  10. Bioinformatics method identifies potential biomarkers of dilated cardiomyopathy in a human induced pluripotent stem cell-derived cardiomyocyte model.

    PubMed

    Zhuang, Yu; Gong, Yu-Jia; Zhong, Bei-Fen; Zhou, Yi; Gong, Li

    2017-10-01

    Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy that account for the majority of heart failure cases. The present study aimed to reveal the underlying molecular mechanisms of DCM and provide potential biomarkers for detection of this condition. The public dataset of GSE35108 was downloaded, and 4 normal induced pluripotent stem cell (iPSC)-derived cardiomyocytes (N samples) and 4 DCM iPSC-derived cardiomyocytes (DCM samples) were utilized. Raw data were preprocessed, followed by identification of differentially expressed genes (DEGs) between N and DCM samples. Crucial functions and pathway enrichment analysis of DEGs were investigated, and protein-protein interaction (PPI) network analysis was conducted. Furthermore, a module network was extracted from the PPI network, followed by enrichment analysis. A set of 363 DEGs were identified, including 253 upregulated and 110 downregulated genes. Several biological processes (BPs), such as blood vessel development and vasculature development (FLT1 and MMP2), cell adhesion (CDH1, ITGB6, COL6A3, COL6A1 and LAMC2) and extracellular matrix (ECM)-receptor interaction pathway (CDH1, ITGB6, COL6A3, COL6A1 and LAMC2), were significantly enriched by these DEGs. Among them, MMP2, CDH1 and FLT1 were hub nodes in the PPI network, while COL6A3, COL6A1, LAMC2 and ITGB6 were highlighted in module 3 network. In addition, PENK and APLNR were two crucial nodes in module 2, which were linked to each other. In conclusion, several potential biomarkers for DCM were identified, such as MMP2, FLT1, CDH1, ITGB6, COL6A3, COL6A1, LAMC2, PENK and APLNR. These genes may serve significant roles in DCM via involvement of various BPs, such as blood vessel and vasculature development and cell adhesion, and the ECM-receptor interaction pathway.

  11. Large In-transient Left Ventricular Thrombus due to Anabolic Steroid-induced Cardiomyopathy

    PubMed Central

    Sabzi, Feridoun; Faraji, Reza

    2017-01-01

    The presence of small or moderate size thrombosis is not uncommon in left ventricle (LV) as results of basic co-moribund disease, but huge LV thrombosis that protrudes to aortic valve in the LV outflow tract (LVOT) tract is an exceptionally rare phenomenon. We report a 34-year-old bodybuilder athlete with cardiomyopathy and massive LV thrombosis. The thrombosis extended to LVOT and protruded through the aortic valve in systole and posed a high risk of systemic emboli. The patient underwent open heart surgery, and the clot was removed. The operation was complicated by low cardiac output syndrome that managed by intra-aortic balloon pump and high dose of inotropic drugs and hemodialysis. The patient died on the 15th day after surgery with multiorgan failures. PMID:28197053

  12. Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy.

    PubMed

    Lin, Bo; Li, Yang; Han, Lu; Kaplan, Aaron D; Ao, Ying; Kalra, Spandan; Bett, Glenna C L; Rasmusson, Randall L; Denning, Chris; Yang, Lei

    2015-05-01

    Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca(2+), mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca(2+) level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients.

  13. Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy

    PubMed Central

    Lin, Bo; Li, Yang; Han, Lu; Kaplan, Aaron D.; Ao, Ying; Kalra, Spandan; Bett, Glenna C. L.; Rasmusson, Randall L.; Denning, Chris; Yang, Lei

    2015-01-01

    ABSTRACT Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca2+, mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca2+ level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients. PMID:25791035

  14. Restrictive cardiomyopathies.

    PubMed

    Nihoyannopoulos, Petros; Dawson, David

    2009-12-01

    Restrictive cardiomyopathies constitute a heterogenous group of heart muscle conditions that all have, in common, the symptoms of heart failure. Diastolic dysfunction with preserved systolic function is often the only echocardiographic abnormality that may be noted, although systolic dysfunction may also be an integral part of some specific pathologies, particularly in the most advanced cases such as amyloid infiltration of the heart. By far, the majority of restrictive cardiomyopathies are secondary to a systemic disorder such as amyloidosis, sarcoidosis, scleroderma, haemochromatosis, eosinophilic heart disease, or as a result of radiation treatment. The much more rare diagnosis of idiopathic restrictive cardiomyopathy is supported only by the absence of specific pathology on either endomyocardial biopsies or at post-mortem. Restrictive cardiomyopathy is diagnosed based on medical history, physical examination, and tests: such as blood tests, electrocardiogram, chest X-ray, echocardiography, and magnetic resonance imaging. With its wide availability, echocardiography is probably the most important investigation to identify the left ventricular dysfunction and should be performed early and by groups that are familiar with the wide variety of aetiologies. Finally, on rare occasions, the differential diagnosis from constrictive pericarditis may be necessary.

  15. Cirrhotic cardiomyopathy.

    PubMed

    Ruiz-del-Árbol, Luis; Serradilla, Regina

    2015-11-07

    During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e' ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function.

  16. Differentiating cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy utilizing positron emission tomography

    SciTech Connect

    Mody, F.V.; Brunken, R.C.; Stevenson, L.W.; Nienaber, C.A.; Phelps, M.E.; Schelbert, H.R. )

    1991-02-01

    To determine if imaging of blood flow (using N-13 ammonia) and glucose metabolism (using F-18 2-deoxyglucose) with positron emission tomography can distinguish cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy, 21 patients with severe left ventricular dysfunction who were evaluated for cardiac transplantation were studied. The origin of left ventricular dysfunction had been previously determined by coronary angiography to be ischemic (11 patients) or nonischemic (10 patients). Images were visually analyzed by three observers on a graded scale in seven left ventricular segments and revealed fewer defects in dilated cardiomyopathy compared with ischemic cardiomyopathy for N-13 ammonia (2.7 +/- 1.6 versus 5 +/- 0.6; p less than 0.03) and F-18 deoxyglucose (2.8 +/- 2.1 versus 4.6 +/- 1.1; p less than 0.03). An index incorporating extent and severity of defects revealed more homogeneity with fewer and less severe defects in subjects with nonischemic than in those with ischemic cardiomyopathy as assessed by imaging of flow (2.8 +/- 1.8 versus 9.2 +/- 3; p less than 0.001) and metabolism (3.8 +/- 3.3 versus 8.5 +/- 3.6; p less than 0.005). Diagnostic accuracy for distinguishing the two subgroups by visual image analysis was 85%. Using previously published circumferential count profile criteria, patients with dilated cardiomyopathy had fewer ischemic segments (0.4 +/- 0.8 versus 2.5 +/- 2 per patient; p less than 0.01) and infarcted segments (0.1 +/- 0.3 versus 2.4 +/- 1.4 per patient; p less than 0.001) than did patients with cardiomyopathy of coronary artery disease. The sensitivity for differentiating the two clinical subgroups using circumferential profile analysis was 100% and the specificity 80%.

  17. Ischemic postconditioning may not influence early brain injury induced by focal cerebral ischemia/reperfusion in rats

    PubMed Central

    Kim, Yoo Kyung; Shin, Jin Woo; Joung, Kyoung Woon

    2010-01-01

    Background Experimental studies have shown that ischemic postconditioning can reduce neuronal injury in the setting of cerebral ischemia, but the mechanisms are not yet clearly elucidated. This study was conducted to determine whether ischemic postconditioning can alter expression of heat shock protein 70 and reduce acute phase neuronal injury in rats subjected to transient focal cerebral ischemia/reperfusion. Methods Focal cerebral ischemia was induced by intraluminal middle cerebral artery occlusion for 60 min in twenty male Sprague-Dawley rats (250-300 g). Rats were randomized into control group and an ischemic postconditioning group (10 rats per group). The animals of control group had no intervention either before or after MCA occlusion. Ischemic postconditioning was elicited by 3 cycles of 30 s reperfusion interspersed by 10 s ischemia immediately after onset of reperfusion. The infarct ratios, brain edema ratios and motor behavior deficits were analyzed 24 hrs after ischemic insult. Caspase-3 reactive cells and cells showing heat shock protein 70 activity were counted in the caudoputamen and frontoparietal cortex. Results Ischemic postconditiong did not reduce infarct size and brain edema ratios compared to control group. Neurologic scores were not significantly different between groups. The number of caspase-3 reactive cells in the ischemic postconditioning group was not significantly different than the value of the control group in the caudoputamen and frontoparietal cortex. The number of cells showing heat shock protein 70 activity was not significantly different than the control group, as well. Conclusions These results suggest that ischemic postconditioning may not influence the early brain damage induced by focal cerebral ischemia in rats. PMID:20498797

  18. Cytokines in myocarditis and cardiomyopathies.

    PubMed

    Matsumori, A

    1996-05-01

    Myocarditis is thought to be caused by various viruses, and accumulating evidence links viral myocarditis with the eventual development of dilated cardiomyopathy. Recently the importance of hepatitis C virus infection was noted in patients with dilated cardiomyopathy. Cytokines are increasingly recognized as an important factor in the pathogenesis and pathophysiology of myocarditis and cardiomyopathy. Elevated circulating cytokines have been reported in patients with heart failure, and various cytokines have been shown to depress myocardial contractility in vitro and in vivo. A number of recent studies showed that cytokines generated by activated immune cells cause an increase in NO (nitric oxide) via induction of NO synthase. Increased generation of NO may induce negative inotropism and myocardial damage. This review discusses the etiology and pathogenesis of myocarditis and cardiomyopathy from this point of view.

  19. Transformation of myocarditis and inflammatory cardiomyopathy to idiopathic dilated cardiomyopathy: facts and fiction.

    PubMed

    Figulla, Hans R

    2004-05-01

    There is broad evidence that enteroviruses and adenoviruses can induce an acute inflammation of the myocardium without cardiac dysfunction (i.e. myocarditis) or with cardiac dysfunction (i.e. inflammatory cardiomyopathy) that can transform to a virus-negative dilated cardiomyopathy. In the adult patient neither other viruses (parvo-B 19 virus, hepatitis C virus, cytomegalovirus) nor post-infection autoimmunity are likely to induce idiopathic dilated cardiomyopathy.

  20. What Is Cardiomyopathy?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Cardiomyopathy? Cardiomyopathy refers to diseases of the heart muscle. These ... many causes, signs and symptoms, and treatments. In cardiomyopathy, the heart muscle becomes enlarged, thick, or rigid. ...

  1. [The use of acetylsalicylic acid in patients with ischemic cardiomyopathy cared for in Spanish emergency services (results of the EVICURE Study). Evaluacion del Manejo de la cardiopatia isquemica en los Servicios de Urgencias Hospitalarios of the Sociedad Espanola de Medicina de Urgencias y Emergencias (SEMES)].

    PubMed

    Epelde, F; Garca-Castrillo Riesgo, L; Loma-Osorio, A; Verdier, J; Recuerda Martnez, E

    2000-10-14

    Acetyl salicylic acid is a drug with demonstrated effectiveness in ischemic cardiomyopathy. The objective of our study was to know the use of this drug in the emergency services of Spain. The EVICURE study analyzes the use of acetyl salicylic acid in 35 emergency services of Spanish hospitals. 2,168 patients were studied. Of the 473 patients with stable angina, 9.2% received acetyl salicylic acid before going to the hospital and 90,7% at the arrival to the hospital, of 1,067 with unstable angina 13% received acetyl salicylic acid before the arrival to the hospital and 56% at the arrival to the hospital. Of 600 patients affected of myocardial infarction only 17% received acetyl salicylic acid before the arrival to the hospital and 59.8% received this drug in the emergency room. The use of acetyl salicylic acid in patients affected of ischemic cardiopathy assisted in the emergency services of Spain is improperly low.

  2. [Takotsubo and surroundings. Step by step postpartum stress-induced cardiomyopathy shows its facet. A peculiar case of atypical takotasubo in the peripartum period].

    PubMed

    Russo, Marco; Sappa, Roberta; Gianfagna, Enrico; Salame, Kareem; Sinagra, Gianfranco; Proclemer, Alessandro

    2014-01-01

    Takotsubo syndrome is an acquired cardiomyopathy with transient and reversible left ventricular dysfunction that can mimic an acute coronary syndrome. It is characterized by ECG abnormalities, including minimal ST-segment elevation and T-wave changes, mild troponin elevation, typical left ventricular regional wall motion abnormalities (apical ballooning) and atypical forms (midventricular or reverse apical ballooning) without significant coronary artery stenosis. Its etiology and pathophysiology remain unclear. The sympathetic system seems to play a central role: its exaggerated response to emotional or physical stress triggers may induce microvascular dysfunction and catecholamine-induced cardiotoxicity due to cyclic AMP-mediated calcium overload. We report our experience highlighting the possible pathophysiological and clinical overlap of emotional-triggered catecholamine cardiotoxicity, arterial hypertension and physiological cardiovascular overload in pregnancy describing an atypical case of takotsubo cardiomyopathy with diffuse left ventricular hypokinesia at onset and subsequent evolution to apical ballooning.

  3. MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet.

    PubMed

    He, Jun; Quintana, Megan T; Sullivan, Jenyth; L Parry, Traci; J Grevengoed, Trisha; Schisler, Jonathan C; Hill, Joseph A; Yates, Cecelia C; Mapanga, Rudo F; Essop, M Faadiel; Stansfield, William E; Bain, James R; Newgard, Christopher B; Muehlbauer, Michael J; Han, Yipin; Clarke, Brian A; Willis, Monte S

    2015-08-05

    In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2-/- hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. MuRF2-/- mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2-/- hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2-/- hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2's regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However

  4. Caffeine does not attenuate experimentally induced ischemic pain in healthy subjects.

    PubMed

    Dellermalm, J; Segerdahl, M; Grass, S

    2009-11-01

    Caffeine is likely the most widely used psychoactive substance in the world. It is also an analgesic adjuvant and has individual analgesic properties. The latter effect has been attributed to adenosine receptor antagonism, but the site of action is unknown. The aim of this study was to investigate the analgesic properties of caffeine on experimentally induced ischemic pain and to attempt to elucidate whether the site of action is central or peripheral. Seventeen healthy subjects received intravenous (i.v.) regional and systemic infusions of caffeine at 10 mg/kg or placebo in a double-blind, crossover fashion to investigate the site of action for caffeine-induced analgesia. Subjects underwent a sub-maximum effort tourniquet test. Pain scores [visual analogue scale (VAS), 0-100] were assessed every minute up to a maximum of 45 min. The sum of pain scores (SPS, accumulation of VAS scores) was attenuated neither by systemic 2405 (+/-234) nor by i.v. regional caffeine 2427 (+/-190) as compared with placebo 2442 (+/-205), P=0.99 (mean+/-SEM). Time to maximal VAS score did not differ significantly between treatments, P=0.94. There was no correlation between caffeine concentration in plasma and time to maximal pain score, or between SPS and plasma concentration. Caffeine does not have an analgesic effect on ischemic pain, either by a peripheral or by a central site of action.

  5. Hypoxic-ischemic brain damage induces distant inflammatory lung injury in newborn piglets.

    PubMed

    Arruza, Luis; Pazos, M Ruth; Mohammed, Nagat; Escribano, Natalia; Lafuente, Hector; Santos, Martín; Alvarez-Díaz, Francisco J; Martínez-Orgado, Jose

    2016-03-01

    We aimed to investigate whether neonatal hypoxic-ischemic (HI) brain injury induces inflammatory lung damage. Thus, hypoxic (HYP, FiO2 10% for 30 min), ischemic (ISC, bilateral carotid flow interruption for 30 min), or HI event was performed in 1-2-d-old piglets. Dynamic compliance (Cdyn), oxygenation index (OI), and extravascular lung water (EVLW) were monitored for 6 h. Then, histologic damage was assessed in brain and lung (lung injury severity score). Total protein content (TPC) was determined in broncoalveolar lavage fluid (BALF), and IL-1β concentration was measured in lung and brain tissues and blood. Piglets without hypoxia or ischemia served as controls (SHM). HI-induced brain damage was associated with decreased Cdyn, increased OI and EVLW, and histologic lung damage (interstitial leukocyte infiltration, congestive hyperemia, and interstitial edema). BALF TPC was increased, suggesting inflammatory damage. In agreement, tissue IL-1β concentration increased in the brain and lung, in correspondence with increased IL-1β serum concentration. Neither HYP nor ISC alone led to brain or lung damage. HI brain damage in newborn piglets led to inflammatory lung damage, suggesting an additional mechanism accounting for the development of lung dysfunction after neonatal HI encephalopathy.

  6. Inflammation and metabolic cardiomyopathy.

    PubMed

    Nishida, Kazuhiko; Otsu, Kinya

    2017-03-15

    Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signalling pathways are directly triggered by nutrients. The pro-inflammatory mediators in adipocytes and macrophages infiltrating adipose tissue promote both local and systemic pro-inflammatory status. Metabolic cardiomyopathy is a chronic metabolic disease characterized by structural and functional alterations and interstitial fibrosis without coronary artery disease or hypertension. In the early stage of metabolic cardiomyopathy, metabolic disturbance is not accompanied by substantial changes in myocardial structure and cardiac function. However, metabolic disturbance induces subcellular low-grade inflammation in the heart, and in turn, subcellular component abnormalities, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and impaired calcium handling, leading to impaired myocardial relaxation. In the advanced stage, the vicious cycle of subcellular component abnormalities, inflammatory cell infiltration, and neurohumoral activation induces cardiomyocyte injury and death, and cardiac fibrosis, resulting in impairment of both diastolic and systolic functions. This review discusses some recent advances in understanding involvement of inflammation in metabolic cardiomyopathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  7. Shengmai Injection Improved Doxorubicin-Induced Cardiomyopathy by Alleviating Myocardial Endoplasmic Reticulum Stress and Caspase-12 Dependent Apoptosis

    PubMed Central

    Chen, Yu; Tang, Yong; Xiang, Yin; Xie, Yu-Quan; Huang, Xiao-Hong; Zhang, Ya-Chen

    2015-01-01

    Background. Apoptosis plays vital roles in the progression of doxorubicin-induced cardiomyopathy (DOX-CM). Endoplasmic reticulum stress (ER stress) could induce specific apoptosis by caspase-12 dependent pathway. Shengmai Injection (SMI), a famous Traditional Chinese Medicine, could alleviate the heart damage via inhibiting myocardial apoptosis. However, it is unknown whether SMI can alleviate ER stress and its specific apoptosis in the setting of DOX-CM. Objective. To explore the effects of SMI on heart function, myocardial ER stress, and apoptosis of DOX-CM rats. Methods. Rats with DOX-CM were treated by SMI. Heart function was assessed by echocardiography and brain natriuretic peptide. Myocardial apoptosis was detected by TUNEL assay. ER stress was assessed by detecting the expressions of GRP78 and caspase-12. Results. At the end of eight-week, compared to control, significant heart dysfunction happened in DOX group. The ratio of apoptotic cardiomyocytes and the expressions of GRP78 and caspase-12 increased significantly (P < 0.05). Compared to DOX group, the apoptotic ratio and the expressions of GRP78 and caspase-12 significantly decreased in DOX + SMI group (P < 0.05), accompanied with improved heart function. Conclusion. SMI could alleviate myocardial ER stress and caspase-12 dependent apoptosis, which subsequently helped to improve the heart function of rats with DOX-CM. PMID:25839043

  8. Cardiomyopathy induced by artificial cardiac pacing: myth or reality sustained by evidence?

    PubMed Central

    Ferrari, Andrés Di Leoni; Borges, Anibal Pires; Albuquerque, Luciano Cabral; Sussenbach, Carolina Pelzer; da Rosa, Priscila Raupp; Piantá, Ricardo Medeiros; Wiehe, Mario; Goldani, Marco Antônio

    2014-01-01

    Implantable cardiac pacing systems are a safe and effective treatment for symptomatic irreversible bradycardia. Under the proper indications, cardiac pacing might bring significant clinical benefit. Evidences from literature state that the action of the artificial pacing system, mainly when the ventricular lead is located at the apex of the right ventricle, produces negative effects to cardiac structure (remodeling, dilatation) and function (dissinchrony). Patients with previously compromised left ventricular function would benefit the least with conventional right ventricle apical pacing, and are exposed to the risk of developing higher incidence of morbidity and mortality for heart failure. However, after almost 6 decades of cardiac pacing, just a reduced portion of patients in general would develop these alterations. In this context, there are not completely clear some issues related to cardiac pacing and the development of this cardiomyopathy. Causality relationships among QRS widening with a left bundle branch block morphology, contractility alterations within the left ventricle, and certain substrates or clinical (previous systolic dysfunction, structural heart disease, time from implant) or electrical conditions (QRS duration, percentage of ventricular stimulation) are still subjecte of debate. This review analyses contemporary data regarding this new entity, and discusses alternatives of how to use cardiac pacing in this context, emphasizing cardiac resynchronization therapy. PMID:25372916

  9. Metabolic imaging of patients with cardiomyopathy

    SciTech Connect

    Geltman, E.M. )

    1991-09-01

    The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies.

  10. Ischemic Preconditioning Mediates Neuroprotection against Ischemia in Mouse Hippocampal CA1 Neurons by Inducing Autophagy.

    PubMed

    Gao, Chunlin; Cai, Ying; Zhang, Xuebin; Huang, Huiling; Wang, Jin; Wang, Yajing; Tong, Xiaoguang; Wang, Jinhuan; Wu, Jialing

    2015-01-01

    The hippocampal CA1 region is sensitive to hypoxic and ischemic injury but can be protected by ischemic preconditioning (IPC). However, the mechanism through which IPC protects hippocampal CA1 neurons is still under investigation. Additionally, the role of autophagy in determining the fate of hippocampal neurons is unclear. Here, we examined whether IPC induced autophagy to alleviate hippocampal CA1 neuronal death in vitro and in vivo with oxygen glucose deprivation (OGD) and bilateral carotid artery occlusion (BCCAO) models. Survival of hippocampal neurons increased from 51.5% ± 6.3% in the non-IPC group (55 min of OGD) to 77.3% ± 7.9% in the IPC group (15 min of OGD, followed by 55 min of OGD 24 h later). The number of hippocampal CA1 layer neurons increased from 182 ± 26 cells/mm2 in the non-IPC group (20 min of BCCAO) to 278 ± 55 cells/mm2 in the IPC group (1 min × 3 BCCAO, followed by 20 min of BCCAO 24 h later). Akt phosphorylation and microtubule-associated protein light chain 3 (LC3)-II/LC3-I expression were increased in the preconditioning group. Moreover, the protective effects of IPC were abolished only by inhibiting the activity of autophagy, but not by blocking the activation of Akt in vitro. Using in vivo experiments, we found that LC3 expression was upregulated, accompanied by an increase in neuronal survival in hippocampal CA1 neurons in the preconditioning group. The neuroprotective effects of IPC on hippocampal CA1 neurons were completely inhibited by treatment with 3-MA. In contrast, hippocampal CA3 neurons did not show changes in autophagic activity or beneficial effects of IPC. These data suggested that IPC may attenuate ischemic injury in hippocampal CA1 neurons through induction of Akt-independent autophagy.

  11. Ischemic Preconditioning Mediates Neuroprotection against Ischemia in Mouse Hippocampal CA1 Neurons by Inducing Autophagy

    PubMed Central

    Zhang, Xuebin; Huang, Huiling; Wang, Jin; Wang, Yajing; Tong, Xiaoguang; Wang, Jinhuan; Wu, Jialing

    2015-01-01

    The hippocampal CA1 region is sensitive to hypoxic and ischemic injury but can be protected by ischemic preconditioning (IPC). However, the mechanism through which IPC protects hippocampal CA1 neurons is still under investigation. Additionally, the role of autophagy in determining the fate of hippocampal neurons is unclear. Here, we examined whether IPC induced autophagy to alleviate hippocampal CA1 neuronal death in vitro and in vivo with oxygen glucose deprivation (OGD) and bilateral carotid artery occlusion (BCCAO) models. Survival of hippocampal neurons increased from 51.5% ± 6.3% in the non-IPC group (55 min of OGD) to 77.3% ± 7.9% in the IPC group (15 min of OGD, followed by 55 min of OGD 24 h later). The number of hippocampal CA1 layer neurons increased from 182 ± 26 cells/mm2 in the non-IPC group (20 min of BCCAO) to 278 ± 55 cells/mm2 in the IPC group (1 min × 3 BCCAO, followed by 20 min of BCCAO 24 h later). Akt phosphorylation and microtubule-associated protein light chain 3 (LC3)-II/LC3-I expression were increased in the preconditioning group. Moreover, the protective effects of IPC were abolished only by inhibiting the activity of autophagy, but not by blocking the activation of Akt in vitro. Using in vivo experiments, we found that LC3 expression was upregulated, accompanied by an increase in neuronal survival in hippocampal CA1 neurons in the preconditioning group. The neuroprotective effects of IPC on hippocampal CA1 neurons were completely inhibited by treatment with 3-MA. In contrast, hippocampal CA3 neurons did not show changes in autophagic activity or beneficial effects of IPC. These data suggested that IPC may attenuate ischemic injury in hippocampal CA1 neurons through induction of Akt-independent autophagy. PMID:26325184

  12. Induction of early biomarkers in a thrombus-induced sheep model of ischemic heart failure.

    PubMed

    Chandrakala, Aluganti N; Kwiatkowski, Pawel; Sai-Sudhakar, Chittoor B; Sun, Benjamin; Phillips, Angela; Parthasarathy, Sampath

    2013-01-01

    The levels of brain natriuretic peptide (BNP) and monocyte chemoattractant protein-1 (MCP-1) are known to be increased in the sera of subjects with heart failure. Existing models do not account for the biomass of thrombus that occurs in patients undergoing myocardial infarction. In this study, we compared the expressions of sheep-derived genes for BNP, MCP-1, and atrial natriuretic peptide in a new large-animal model of thrombus-induced heart failure. Thrombus of autologous platelets was injected directly into the left circumflex coronary arteries of sheep. Cardiac ischemic injury was evaluated by troponin I levels, and heart failure progression was monitored with the aid of echocardiogram-based evaluation. After outlined time intervals, the sheep were killed and their hearts excised for tissue sampling. Reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay (ELISA) tests were performed to establish gene and protein expressions. At 72 hours after embolization, myocardial BNP and MCP-1 expressions had increased significantly in the ischemic region, compared either with the nonischemic region or with tissue from healthy sheep. As heart failure progressed to 90 days after embolization, the expression of BNP in the ischemic region decreased, whereas its expression in the nonischemic region increased several fold. In contrast, MCP-1 gene expression showed no changes in either tissue after 90 days of embolization. Plasma levels of BNP, determined by Western blot and ELISA, also correlated with the gene-expression studies. Our results show regional changes in BNP and MCP-1, as well as differences in the expression of these 2 genes.

  13. Yogurt Containing the Probacteria Lactobacillus acidophilus Combined with Natural Antioxidants Mitigates Doxorubicin-Induced Cardiomyopathy in Rats.

    PubMed

    Abu-Elsaad, Nashwa M; Abd Elhameed, Ahmed G; El-Karef, Amr; Ibrahim, Tarek M

    2015-09-01

    Probiotics and antioxidants have a definite improving effect in cardiovascular diseases. This study aims at mitigating doxorubicin toxicity on cardiac function through consuming a functional food. Five groups of adult male Sprague-Dawley rats were used along 22 weeks. Group I received 30 g/kg/day food enriched with yogurt, green tea extract, and carrots (80, 0.84, and 100 g/kg diet, respectively) from the first week, group II received carvedilol 30 mg/kg/day orally from week 17, group III received both carvedilol and tested food, and groups IV and V were +ve and -ve control groups, respectively. In week 17, cardiomyopathy was induced by i.p. injection of 2.5 mg/kg doxorubicin every 48 h for 2 weeks. Histopathological and electrophysiological examinations and biochemical analysis were done. Lipid peroxidation, antioxidant effect, heart failure compensatory mediators, and proinflammatory cytokines were assessed. Tested food normalized time between the start of Q wave and the end of T wave on electrocardiogram (QT interval) and heart rate compared to the doxorubicin group (P<.05). It also improved hypertrophy indicated by a significant (P<.05) decrease in heart/body weight ratio, angiotensin-II (Ang-II), and atrial natriuretic peptide (ANP) serum levels. Histopathological examination of cardiac sections from the tested food group revealed less marked vacuolization and low perivascular fibrosis percentage (0.7803 ± 0.04). A significant (P<.001) decrease in serum creatine kinase-membrane bound, lactate dehydrogenase, triglycerides, cholesterol, low-density lipoprotein cholesterol, and tissue malondialdehyde (MDA) levels was observed in addition to an increase in serum Na(+)/K(+) ATP1A1 and cardiac reduced glutathione (GSH) levels. Tested food also lowered the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) serum levels significantly (P<.01). Probiotic food containing Lactobacillus acidophilus, green tea, and carrots can improve

  14. Arrhythmogenic Cardiomyopathy.

    PubMed

    Corrado, Domenico; Basso, Cristina; Judge, Daniel P

    2017-09-15

    Arrhythmogenic cardiomyopathy is an inherited heart muscle disorder, predisposing to sudden cardiac death, particularly in young patients and athletes. Pathological features include loss of myocytes and fibrofatty replacement of right ventricular myocardium; biventricular involvement is often observed. It is a cell-to-cell junction cardiomyopathy, typically caused by genetically determined abnormalities of cardiac desmosomes, which leads to detachment of myocytes and alteration of intracellular signal transduction. The diagnosis of arrhythmogenic cardiomyopathy does not rely on a single gold standard test but is achieved using a scoring system, which encompasses familial and genetic factors, ECG abnormalities, arrhythmias, and structural/functional ventricular alterations. The main goal of treatment is the prevention of sudden cardiac death. Implantable cardioverter defibrillator is the only proven lifesaving therapy; however, it is associated with significant morbidity because of device-related complications and inappropriate implantable cardioverter defibrillator interventions. Selection of patients who are the best candidates for implantable cardioverter defibrillator implantation is one of the most challenging issues in the clinical management. © 2017 American Heart Association, Inc.

  15. Protection from Doxorubicin-Induced Cardiomyopathy Using the Modified Anthracycline N-Benzyladriamycin-14-valerate (AD 198)

    PubMed Central

    Cai, Chun; Lothstein, Leonard; Morrison, R. Ray

    2010-01-01

    The anthracycline doxorubicin (Dox) is an effective antitumor agent. However, its use is limited because of its toxicity in the heart. N-Benzyladriamycin-14-valerate (AD 198) is a modified anthracycline with antitumor efficacy similar to that of Dox, but with significantly less cardiotoxicity and potentially cardioprotective elements. In the present study, we investigated the possibility of in vivo protective effects of low-dose AD 198 against Dox-induced cardiomyopathy. To do this, rats were divided into four groups: vehicle, Dox (20 mg/kg; single injection day 1), AD 198 (0.3 mg/kg per injection; injections on days 1, 2, and 3), or a combination treatment of Dox + AD 198. Seventy-two hours after beginning treatment, hearts from the Dox group had decreased phosphorylation of AMP kinase and troponin I and reduced poly(ADP-ribose) polymerase, β-tubulin, and serum albumin expression. Dox also increased the phosphorylation of phospholamban and expression of inducible nitric-oxide synthase in hearts. Each of these Dox-induced molecular changes was attenuated in the Dox + AD 198 group. In addition, excised hearts from rats treated with Dox had a 25% decrease in left ventricular developed pressure (LVDP) and a higher than normal increase in LVDP when perfused with a high extracellular Ca2+ solution. The Dox-induced decrease in baseline LVDP and hyper-responsiveness to [Ca2+] was not observed in hearts from the Dox + AD 198 group. Thus Dox, with well established and efficient antitumor protocols, in combination with low levels of AD 198, to counter anthracycline cardiotoxicity, may be a promising next step in chemotherapy. PMID:20668052

  16. Longitudinal MRI evaluation of neuroprotective effects of pharmacologically induced hypothermia in experimental ischemic stroke.

    PubMed

    Wang, Silun; Gu, Xiaohuan; Paudyal, Ramesh; Wei, Ling; Dix, Thomas A; Yu, Shan P; Zhang, Xiaodong

    2017-04-01

    Pharmacologically induced hypothermia (PIH) shows promising neuroprotective effects after stroke insult. However, the dynamic evolution of stroke infarct during the hypothermic therapy has not been understood very well. In the present study, MRI was utilized to longitudinally characterize the infarct evolution in a mouse model of ischemic stroke treated by PIH using the neurotensin agonist HPI201. Adult male C57BL/6 mice underwent permanent occlusion of the right middle cerebra artery (MCA). Each animal received a vehicle or HPI201 intraperitoneal injection. The temporal changes of stroke lesion were examined using T2-weighted imaging and diffusion-weighted imaging (DWI) in the acute phase (1-3h) and 24h post stroke. Significantly reduced infarct and edema volumes were observed in PIH treated stroke mice, in agreement with TTC staining findings. Also, the TUNEL staining results indicated apoptotic cells were widely distributed among the ischemic cortex in control group but limited in PIH treated mice. Dramatically reduced growth rate of infarction was seen in PIH treated stroke mice. These results demonstrate HPI201 has strong neuroprotection effects during acute stroke. In particular, MRI with the numerical modelling of temporal infarct evolution could provide a unique means to examine and predict the dynamic response of the PIH treatment on infarct evolution.

  17. Docosahexaenoic Acid Supplementation Does Not Improve Western Diet-Induced Cardiomyopathy in Rats

    PubMed Central

    Jeckel, Kimberly M.; Veeramachaneni, D. N. Rao; Chicco, Adam J.; Chapman, Phillip L.; Mulligan, Christopher M.; Hegarty, Jennifer R.; Pagliassotti, Michael J.; Ferguson, Lindsay A.; Bouma, Gerrit J.; Frye, Melinda A.

    2012-01-01

    Obesity increases risk for cardiomyopathy in the absence of hypertension, diabetes or ischemia. The fatty acid milieu, modulated by diet, may modify myocardial structure and function, lending partial explanation for the array of cardiomyopathic phenotypy. We sought to identify gross, cellular and ultrastructural myocardial changes associated with Western diet intake, and subsequent modification with docosahexaenoic acid (DHA) supplementation. Wistar and Sprague-Dawley (SD) rats received 1 of 3 diets: control (CON); Western (WES); Western + DHA (WES+DHA). After 12 weeks of treatment, echocardiography was performed and myocardial adiponectin, fatty acids, collagen, area occupied by lipid and myocytes, and ultrastructure were determined. Strain effects included higher serum adiponectin in Wistar rats, and differences in myocardial fatty acid composition. Diet effects were evident in that both WES and WES+DHA feeding were associated with similarly increased left ventricular (LV) diastolic cranial wall thickness (LVWcr/d) and decreased diastolic internal diameter (LVIDd), compared to CON. Unexpectedly, WES+DHA feeding was associated additionally with increased thickness of the LV cranial wall during systole (LVWcr/s) and the caudal wall during diastole (LVWca/d) compared to CON; this was observed concomitantly with increased serum and myocardial adiponectin. Diastolic dysfunction was present in WES+DHA rats compared to both WES and CON. Myocyte cross sectional area (CSA) was greater in WES compared to CON rats. In both fat-fed groups, transmission electron microscopy (TEM) revealed myofibril degeneration, disorganized mitochondrial cristae, lipid inclusions and vacuolation. In the absence of hypertension and whole body insulin resistance, WES+DHA intake was associated with more global LV thickening and with diastolic dysfunction, compared to WES feeding alone. Myocyte hypertrophy, possibly related to subcellular injury, is an early change that may contribute to gross

  18. A dilated cardiomyopathy mutation blunts adrenergic response and induces contractile dysfunction under chronic angiotensin II stress

    PubMed Central

    Wilkinson, Ross; Song, Weihua; Smoktunowicz, Natalia

    2015-01-01

    We investigated cardiac contractility in the ACTC E361G transgenic mouse model of dilated cardiomyopathy (DCM). No differences in cardiac dimensions or systolic function were observed in young mice, whereas young adult mice exhibited only mild diastolic abnormalities. Dobutamine had an inotropic and lusitropic effect on the mouse heart. In papillary muscle at 37°C, dobutamine increased relaxation rates [∼50% increase of peak rate of force decline normalized to force (dF/dtmin/F), 25% reduction of time to 90% relaxation (t90) in nontransgenic (NTG) mice], but in the ACTC E361G mouse, dF/dtmin/F was increased 20–30%, and t90 was only reduced 10% at 10 Hz. Pressure-volume measurements showed increases in maximum rate of pressure decline and decreases in time constant of left ventricular pressure decay in the ACTC E361G mouse that were 25–30% of the changes in the NTG mouse, consistent with blunting of the lusitropic response. The inotropic effect of dobutamine was also blunted in ACTC E361G mice, and the dobutamine-stimulated increase in cardiac output (CO) was reduced from 2,100 to 900 μl/min. Mice were treated with high doses of ANG II for 4 wk. The chronic stress treatment evoked systolic dysfunction in ACTC E361G mice but not in NTG. There was a significant reduction in rates of pressure increase and decrease, as well as reduced end-systolic pressure and increased volume. Ejection fraction and CO were reduced in the ACTC E361G mouse, indicating DCM. In vitro DCM-causing mutations uncouple the relationship between Ca2+ sensitivity and troponin I phosphorylation. We conclude that this leads to the observed, reduced response to β1 agonists and reduced cardiac reserve that predisposes the heart to DCM under conditions of chronic stress. PMID:26432839

  19. A dilated cardiomyopathy mutation blunts adrenergic response and induces contractile dysfunction under chronic angiotensin II stress.

    PubMed

    Wilkinson, Ross; Song, Weihua; Smoktunowicz, Natalia; Marston, Steven

    2015-12-01

    We investigated cardiac contractility in the ACTC E361G transgenic mouse model of dilated cardiomyopathy (DCM). No differences in cardiac dimensions or systolic function were observed in young mice, whereas young adult mice exhibited only mild diastolic abnormalities. Dobutamine had an inotropic and lusitropic effect on the mouse heart. In papillary muscle at 37°C, dobutamine increased relaxation rates [∼50% increase of peak rate of force decline normalized to force (dF/dtmin/F), 25% reduction of time to 90% relaxation (t90) in nontransgenic (NTG) mice], but in the ACTC E361G mouse, dF/dtmin/F was increased 20-30%, and t90 was only reduced 10% at 10 Hz. Pressure-volume measurements showed increases in maximum rate of pressure decline and decreases in time constant of left ventricular pressure decay in the ACTC E361G mouse that were 25-30% of the changes in the NTG mouse, consistent with blunting of the lusitropic response. The inotropic effect of dobutamine was also blunted in ACTC E361G mice, and the dobutamine-stimulated increase in cardiac output (CO) was reduced from 2,100 to 900 μl/min. Mice were treated with high doses of ANG II for 4 wk. The chronic stress treatment evoked systolic dysfunction in ACTC E361G mice but not in NTG. There was a significant reduction in rates of pressure increase and decrease, as well as reduced end-systolic pressure and increased volume. Ejection fraction and CO were reduced in the ACTC E361G mouse, indicating DCM. In vitro DCM-causing mutations uncouple the relationship between Ca(2+) sensitivity and troponin I phosphorylation. We conclude that this leads to the observed, reduced response to β1 agonists and reduced cardiac reserve that predisposes the heart to DCM under conditions of chronic stress.

  20. Blood glucose and tissue glycogen levels in turkey poults with spontaneous round heart disease and furazolidone-induced cardiomyopathy.

    PubMed

    Czarnecki, C M; Reneau, J K; Jankus, E F

    1975-01-01

    Furazolidone (FZ) at 700 ppm was added to feed mixtures fed turkey poults two weeks posthatching to induce acute experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. Four of the control poults developed spontaneous round heart disease. From EKG data and blood samples obtained at weekly intervals, poults were selected for sacrifice at 5 weeks of age. Tissue samples from the left myocardial wall, liver, and pectoralis major and tibialis anterior muscles were analyzed for glycogen by biochemical assay. Blood glucose was determined with the Technicon autoanalyzer. Deposition of glycogen increased significantly (p less than 0.05) in the myocardium of all affected poults and in the liver of all FZ-treated poults. Glycogen levels of the pectoralis major and tibialis anterior muscles were not affected by FZ, but a significant increase (p less than 0.05) was apparent in the pectoralis major muscle of spontaneous round heart poults. It was concluded that FZ influences glycogen metabolism, probably by enzyme inhibition, and that it tends to magnify effects seen in the spontaneous round heart syndrome. Glycogen infiltration of tissues such as the heart and white skeletal muscle suggests that the round heart syndrome may be a manifestation of the glycogen storage disease, idiopathic generalized glycogenosis. Lack of significant differences in the blood serum glucose levels of all poults indicates that these levels are not a reliable clinical parameter for monitoring development of the round heart syndrome.

  1. Unraveling the role of adenosine in remote ischemic preconditioning-induced cardioprotection.

    PubMed

    Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

    2016-06-15

    Remote ischemic preconditioning (RIPC) induced by alternate cycles of preconditioning ischemia and reperfusion protects the heart against sustained ischemia-reperfusion-induced injury. This technique has been translated to clinical levels in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention and heart valve surgery. Adenosine is a master regulator of energy metabolism and reduces myocardial ischemia-reperfusion-induced injury. Furthermore, adenosine is a critical trigger as well as a mediator in RIPC-induced cardioprotection and scientists have demonstrated the role of adenosine by showing an increase in its levels in the systemic circulation during RIPC delivery. Furthermore, the blockade of cardioprotective effects of RIPC in the presence of specific adenosine receptor blockers and transgenic animals with targeted ablation of A1 receptors has also demonstrated its critical role in RIPC. The studies have shown that adenosine may elicit cardioprotection via activation of neurogenic pathway. The present review describes the possible role and mechanism of adenosine in mediating RIPC-induced cardioprotection.

  2. Ramipril restores PPARβ/δ and PPARγ expressions and reduces cardiac NADPH oxidase but fails to restore cardiac function and accompanied myosin heavy chain ratio shift in severe anthracycline-induced cardiomyopathy in rat.

    PubMed

    Cernecka, Hana; Doka, Gabriel; Srankova, Jasna; Pivackova, Lenka; Malikova, Eva; Galkova, Kristina; Kyselovic, Jan; Krenek, Peter; Klimas, Jan

    2016-11-15

    We hypothesized that peroxisome proliferator-activated receptors (PPARs) might be involved in a complex protective action of ACE inhibitors (ACEi) in anthracyclines-induced cardiomyopathy. For purpose of study, we compared effects of ramipril on cardiac dysfunction, cardiac failure markers and PPAR isoforms in moderate and severe chronic daunorubicin-induced cardiomyopathy. Male Wistar rats were administered with a single intravenous injection of daunorubicin: 5mg/kg (moderate cardiomyopathy), or 15mg/kg (severe cardiomyopathy) or co-administered with daunorubicin and ramipril (1mg/kg/d, orally) or vehicle for 8 weeks. Left ventricular function was measured invasively under anesthesia. Cardiac mRNA levels of heart failure markers (ANP, Myh6, Myh7, Myh7b) and PPARs (alpha, beta/delta and gama) were measured by qRT-PCR. Protein expression of NADPH subunit (gp91phox) was measured by Western blot. Moderate cardiomyopathy exhibited only minor cardiac dysfunction what was corrected by ramipril. In severe cardiomyopathy, hemodynamic dysfunction remained unaltered upon ramipril although it decreased the significantly up-regulated cardiac ANP mRNA expression. Simultaneously, while high-dose daunorubicin significantly decreased PPARbeta/delta and PPARgama mRNA, ramipril normalized these abnormalities. Similarly, ramipril reduced altered levels of oxidative stress-related gp91phox. On the other hand, ramipril was unable to correct both the significantly decreased relative abundance of Myh6 and increased Myh7 mRNA levels, respectively. In conclusion, ramipril had a protective effect on cardiac function exclusively in moderate chronic daunorubicin-induced cardiomyopathy. Although it normalized abnormal PPARs expression and exerted also additional protective effects also in severe cardiomyopathy, it was insufficient to influence impaired cardiac function probably because of a shift in myosin heavy chain isoform content. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING

    EPA Science Inventory

    Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.

    Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic Preconditioning

    Craig...

  4. TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING

    EPA Science Inventory

    Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.

    Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic Preconditioning

    Craig...

  5. Impact of triggering event in outcomes of stress-induced (Takotsubo) cardiomyopathy.

    PubMed

    Yerasi, Charan; Koifman, Edward; Weissman, Gaby; Wang, Zuyue; Torguson, Rebecca; Gai, Jiaxiang; Lindsay, Joseph; Satler, Lowell F; Pichard, Augusto D; Waksman, Ron; Ben-Dor, Itsik

    2017-04-01

    Takotsubo syndrome is also known as stress cardiomyopathy because of the regularity with which it has been associated with physical or emotional stress. Such stress may well be a "trigger" of the syndrome. This analysis was undertaken to describe our experience with this disorder and in particular to examine the effects of the underlying trigger on outcomes. We conducted a retrospective review of the medical records of 345 consecutive patients treated at our institution from 2006 to 2014. All presented with acute cardiac symptoms, a characteristic left ventricular contraction pattern (typical, atypical), and no major obstructive coronary artery disease. Patients were grouped based on their triggering event: (a) medical illness; (b) post-operative period; (c) emotional distress; or (d) no identified trigger. Baseline demographic characteristics, death in hospital, length of stay in hospital, and cardiac complications were abstracted from the patients' medical records. The mean±SD age of the population was 72±12 years and 91% were women. No significant difference in baseline characteristics was noted between the groups except for a higher prevalence of African Americans in the group with a medical illness. ST elevation was noted in 13.3% of patients and the average peak troponin level was 5±12 ng/dl. An inotropic drug was required in 49 (14.2%) patients, an intra-aortic balloon pump in 37 (10.7%) patients, and mechanical ventilation in 54 (15.7%) patients; 43.5% required treatment in the intensive care unit. Overall, 12 (3.5%) patients died. In only two (16.7%) patients was a there a direct cardiac cause of death. In those patients in whom the cardiac manifestations seemed to be triggered by a medical illness, the death rate was 7.1% and this was significantly higher than in the other groups ( p=0.03). Medical illness (odds ratio=6.25, p=0.02) and ST elevation (odds ratio=5.71, p=0.04) were both significantly associated with death. Our study showed that different

  6. Risk of contrast-induced nephropathy in patients undergoing endovascular treatment of acute ischemic stroke.

    PubMed

    Sharma, Jitendra; Nanda, Ashish; Jung, Richard S; Mehta, Sonal; Pooria, Javad; Hsu, Daniel P

    2013-11-01

    We report the incidence and risk factors for contrast-induced nephropathy after the use of iodinated contrast for endovascular treatment of acute ischemic stroke. A retrospective chart review was performed in 194 consecutive patients who underwent endovascular treatment for acute ischemic stroke between January 2006 and January 2011. No patients were excluded from treatment for elevated creatinine (Cr). Each patient received approximately 150 ml intra-arterial non-ionic low-osmolar contrast agent (Optiray 320) during the endovascular procedure. Contrast-induced nephropathy (CIN) was defined according to the Acute Kidney Injury Network criteria as a relative increase of serum Cr 50% above the baseline or an absolute increase of 0.3 mg/dl at 48 h following the endovascular procedure. Of 194 patients (mean age 65 ± 14 years), 52% were women (n=100) and 25% (n=48) were diabetic. Baseline Cr levels for 191 patients ranged between 0.4 and 2.7 mg/dl. Three patients on chronic hemodialysis had baseline Cr levels ranging between 5.3 and 6.1 mg/dl. Cr was ≤ 1.5 mg/dl in 163 patients (84%) and ≥ 1.5 mg/dl in 31 (16%). Three of the 191 patients (1.5%) developed CIN as noted from Cr measurements between baseline and within 48 h. One patient who developed an elevated Cr level had a known history of chronic renal insufficiency (Cr > 1.5 mg/dl) and two had baseline Cr levels within the normal range. An additional CT angiogram was obtained in 44 patients, none of which developed CIN. Female gender and diabetes were not associated with a higher risk of developing CIN. The risk of developing CIN is low among patients with acute stroke who undergo emergency endovascular treatment. Treatment of acute stroke should be performed irrespective of Cr levels.

  7. IL-20 is regulated by hypoxia-inducible factor and up-regulated after experimental ischemic stroke.

    PubMed

    Chen, Wei-Yu; Chang, Ming-Shi

    2009-04-15

    IL-20, an IL-10 family member, is involved in various inflammatory diseases, such as psoriasis, rheumatoid arthritis, and atherosclerosis. We investigated whether hypoxia in vitro and an in vivo model of ischemic stroke would up-regulate IL-20 expression. In vitro, IL-20 expression increased in hypoxic HaCaT, HEK293 cells, chondrocytes, monocytes, and glioblastoma cells. Inhibition of hypoxia-inducible factor 1alpha inhibited CoCl(2)-induced IL-20 expression. We identified two putative hypoxia response elements in the human il20 gene promoter. Promoter activity assays showed that CoCl(2) mimicked hypoxia-activated luciferase reporter gene expression. In vivo, experimental ischemic stroke up-regulated IL-20 in the sera and brain tissue of rats. IL-20 stained positively in glia-like cells in peri-infarcted lesions, but not in contralateral tissue. Administration of IL-20 mAb ameliorated ischemia-induced brain infarction of rats after experimental ischemic stroke. In vitro, RT-PCR analysis showed that glioblastoma cells, GBM8901, expressed IL-20 and its receptor subunits IL-20R1, IL-20R2, and IL-22R1. IL-20 induced cell proliferation in GBM8901 cells by activating the JAK2/STAT3 and ERK1/2 pathways. IL-20 also induced production of IL-1beta, IL-8, and MCP-1 in GBM8901 cells. We conclude that IL-20 was responsive to hypoxia in vitro and in the ischemic stroke model and that up-regulation of IL-20 in the ischemic brain may contribute to brain injury.

  8. Ischemic preconditioning decreases intracellular zinc accumulation induced by oxygen-glucose deprivation in gerbil hippocampal CA1 neurons.

    PubMed

    Miyawaki, Takahiro; Yokota, Hidenori; Oguro, Keiji; Kato, Kengo; Shimazaki, Kuniko

    2004-05-27

    In normal gerbils, intracellular zinc ions ([Zn2+]i) and calcium ions ([Ca2+]i) accumulate in hippocampal CA1 neurons after global ischemia. We examined whether ischemic preconditioning modifies these changes in gerbil hippocampal slices. In normal slices, large increases in [Zn2+]i and [Ca2+]i were observed in the stratum radiatum of the CA1 area after oxygen-glucose deprivation. In preconditioned slices, there were significantly decreased peak levels of [Zn2+]i and [Ca2+]i in CA1. However, there were no differences in the peak levels of these ions in CA3 and dentate gyrus. These results suggest that modified [Zn2+]i and [Ca2+]i accumulation after an ischemic insult might be important for the mechanisms of ischemic tolerance induced by preconditioning.

  9. Burn-induced subepicardial injury in frog heart: a simple model mimicking ST segment changes in ischemic heart disease.

    PubMed

    Kazama, Itsuro

    2016-02-01

    To mimic ischemic heart disease in humans, several animal models have been created, mainly in rodents by surgically ligating their coronary arteries. In the present study, by simply inducing burn injuries on the bullfrog heart, we reproduced abnormal ST segment changes in the electrocardiogram (ECG), mimicking those observed in ischemic heart disease, such as acute myocardial infarction and angina pectoris. The "currents of injury" created by a voltage gradient between the intact and damaged areas of the myocardium, negatively deflected the ECG vector during the diastolic phase, making the ST segment appear elevated during the systolic phase. This frog model of heart injury would be suitable to explain the mechanisms of ST segment changes observed in ischemic heart disease.

  10. Cannabidiol reduces lung injury induced by hypoxic-ischemic brain damage in newborn piglets.

    PubMed

    Arruza, Luis; Pazos, Maria Ruth; Mohammed, Nagat; Escribano, Natalia; Lafuente, Hector; Santos, Martín; Alvarez-Díaz, Francisco J; Hind, William; Martínez-Orgado, Jose

    2017-07-01

    BackgroundBrain hypoxic-ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario.MethodsNewborn piglets received intravenous vehicle, CBD, or CBD+WAY100635 (5-HT1A receptor antagonist) after HI brain damage (carotid flow interruption and FiO2 0.10 for 30 min). Total lung compliance (TLC), oxygenation index (OI), and extravascular lung water content (EVLW) were monitored for 6 h. Histological damage, interleukin (IL)-1β concentration, and oxidative stress were assessed in brain and lung tissue. Total protein content was determined in bronchoalveolar lavage fluid (BALF).ResultsCBD prevented HI-induced deleterious effects on TLC and OI and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted the beneficial effects of CBD on histological damage, IL-1 concentration, and EVLW.ConclusionsCBD reduced brain HI-induced distant lung damage, with 5-HT1A receptor involvement in these effects. Whether the effects of CBD on the lungs were due to the anti-inflammatory effects on the brain or due to the direct effects on the lungs remains to be elucidated.

  11. Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats.

    PubMed

    Huang, Jingyang; Liu, Baoyi; Yang, Chenghui; Chen, Haili; Eunice, Dzivor; Yuan, Zhongrui

    2013-10-16

    Hyperglycemia adversely affects the outcome of ischemic stroke. Extracellular HMGB1 plays a role in aggravating brain damage in the postischemic brain. The aim of this study was to determine whether the extracellular HMGB1 is involved in the worsened ischemic damage during hyperglycemic stroke. Male Wistar rats underwent middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Acute hyperglycemia was induced by an injection of 50% dextrose. Rats received glycyrrhizin, a specific HMGB1 inhibitor, or vehicle. HMGB-1 in cerebrospinal fluid and in brain parenchyma was detected at 2 or 4 h post-reperfusion. Neurological deficits, infarct volume and cerebral edema were assessed 24 h post-MCAO the disruption of blood-brain barrier (BBB) and the expression of tight junction protein Occludin were measured at 4 h post-reperfusion. Hyperglycemia enhanced the early release of HMGB1 from ischemic brain tissue, which was accompanied by increased infarct volume, neurological deficit, cerebral edema and BBB disruption. Glycyrrhizin alleviated the aggravation of infarct volume, neurological deficit, cerebral edema and BBB disruption by decreasing the degradation of tight junction protein Occludin in the ischemic hemisphere of hyperglycemic rats. In conclusion, enhanced early extracellular release of HMGB1 might represent an important mechanism for worsened ischemic damage, particularly early BBB disruption, during hyperglycemic stroke. An HMGB1 inhibitor glycyrrhizin is a potential therapeutic option for hyperglycemic stroke.

  12. Primary Prevention of Sudden Death in Patients With Valvular Cardiomyopathy.

    PubMed

    Rodríguez-Mañero, Moisés; Barrio-López, María Teresa; Assi, Emad Abu; Expósito-García, Víctor; Bertomeu-González, Vicente; Sánchez-Gómez, Juan Miguel; González-Torres, Luis; García-Bolao, Ignacio; Gaztañaga, Larraitz; Cabanas-Grandío, Pilar; Iglesias-Bravo, José Antonio; Arce-León, Álvaro; la Huerta, Ana Andrés; Fernández-Armenta, Juan; Peinado, Rafael; Arias, Miguel Angel; Díaz-Infante, Ernesto

    2016-03-01

    Few data exist on the outcomes of valvular cardiomyopathy patients referred for defibrillator implantation for primary prevention. The aim of the present study was to describe the outcomes of this cardiomyopathy subgroup. This multicenter retrospective study included consecutive patients referred for defibrillator implantation to 15 Spanish centers in 2010 and 2011, and to 3 centers after 1 January 2008. Of 1174 patients, 73 (6.2%) had valvular cardiomyopathy. These patients had worse functional class, wider QRS, and a history of atrial fibrillation vs patients with ischemic (n=659; 56.1%) or dilated (n=442; 37.6%) cardiomyopathy. During a follow-up of 38.1 ± 21.3 months, 197 patients (16.7%) died, without significant differences among the groups (19.2% in the valvular cardiomyopathy group, 15.8% in the ischemic cardiomyopathy group, and 17.9% in the dilated cardiomyopathy group; P=.2); 136 died of cardiovascular causes (11.6%), without significant differences among the groups (12.3%, 10.5%, and 13.1%, respectively; P=.1). Although there were no differences in the proportion of appropriate defibrillator interventions (13.7%, 17.9%, and 18.8%; P=.4), there was a difference in inappropriate interventions (8.2%, 7.1%, and 12.0%, respectively; P=.03). All-cause and cardiovascular mortality in patients with valvular cardiomyopathy were similar to those in other patients referred for defibrillator implantation. They also had similar rates of appropriate interventions. These data suggest that defibrillator implantation in this patient group confers a similar benefit to that obtained by patients with ischemic or dilated cardiomyopathy. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  13. Beneficial effects of intramyocardial mesenchymal stem cells and VEGF165 plasmid injection in rats with furazolidone induced dilated cardiomyopathy.

    PubMed

    Yu, Qin; Fang, Weiyi; Zhu, Ning; Zheng, Xiaoqun; Na, Rongmei; Liu, Baiting; Meng, Lili; Li, Zhu; Li, Qianxiao; Li, Xiaofei

    2015-08-01

    To explore the impact of myocardial injection of mesenchymal stem cells (MSCs) and specific recombinant human VEGF165 (hVEGF165 ) plasmid on collagen remodelling in rats with furazolidone induced dilated cardiomyopathy (DCM). DCM was induced by furazolidone (0.3 mg/bodyweight (g)/day per gavage for 8 weeks). Rats were then divided into four groups: (i) PBS group (n = 18): rats received equal volume myocardial PBS injection; (ii) MSCs group (n = 17): 100 μl culture medium containing 10(5) MSCs were injected into four sites of left ventricular free wall (25 μl per site); (iii) GENE group (n = 18): pCMVen-MLC2v-EGFP-VEGF165 plasmid [5 × 10(9) pfu (0.2 ml)] were injected into four sites of left ventricular free wall (0.05 ml per site)] and (iv) MSCs+GENE group (n = 17): rats received both myocardial MSCs and pCMVen-MLC2v-EGFP-VEGF165 plasmid injections. After 4 weeks, cardiac function was evaluated by echocardiography. Myocardial mRNA expressions of type I, type III collagen and transforming growth factor (TGF)-β1 were detected by RT-PCR. The protein expression of hVEGF165 was determined by Western blot. Myocardial protein expression of hVEGF165 was demonstrated in GENE and MSCs+GENE groups. Cardiac function was improved in MSCs, GENE and MSCs+GENE groups. Collagen volume fraction was significantly reduced and myocardial TGF-β1 mRNA expression significantly down-regulated in both GENE and MSCs+GENE groups, collagen type I/III ratio reduction was more significant in MSCs+GENE group than in MSCs or GENE group. Myocardial MSCs and hVEGF165 plasmid injection improves cardiac function possibly through down-regulating myocardial TGF-β1 expression and reducing the type I/III collagen ratio in this DCM rat model.

  14. Metabolic cardiomyopathies

    PubMed Central

    Guertl, Barbara; Noehammer, Christa; Hoefler, Gerald

    2000-01-01

    The energy needed by cardiac muscle to maintain proper function is supplied by adenosine Ariphosphate primarily (ATP) production through breakdown of fatty acids. Metabolic cardiomyopathies can be caused by disturbances in metabolism, for example diabetes mellitus, hypertrophy and heart failure or alcoholic cardiomyopathy. Deficiency in enzymes of the mitochondrial β-oxidation show a varying degree of cardiac manifestation. Aberrations of mitochondrial DNA lead to a wide variety of cardiac disorders, without any obvious correlation between genotype and phenotype. A completely different pathogenetic model comprises cardiac manifestation of systemic metabolic diseases caused by deficiencies of various enzymes in a variety of metabolic pathways. Examples of these disorders are glycogen storage diseases (e.g. glycogenosis type II and III), lysosomal storage diseases (e.g. Niemann-Pick disease, Gaucher disease, I-cell disease, various types of mucopolysaccharidoses, GM1 gangliosidosis, galactosialidosis, carbohydrate–deficient glycoprotein syndromes and Sandhoff's disease). There are some systemic diseases which can also affect the heart, for example triosephosphate isomerase deficiency, hereditary haemochromatosis, CD 36 defect or propionic acidaemia. PMID:11298185

  15. A pilot study on transient ischemic stroke induced with endothelin-1 in the rhesus monkeys

    PubMed Central

    Dai, PeiMin; Huang, Hui; Zhang, Lin; He, Jing; Zhao, XuDong; Yang, FuHan; Zhao, Ning; Yang, JianZhen; Ge, LongJiao; Lin, Yu; Yu, HuaLin; Wang, JianHong

    2017-01-01

    Endothelin-1 (ET-1), a vasoconstrictor, has recently been used to induce focal ischemia in rodents and marmoset monkeys. The rhesus monkey, however, has numerous advantages to the rodent and marmoset that make it a superior and irreplaceable animal model for studying stroke in the brain. In the present study, after mapping the preferred hand representation in two healthy male monkeys with intracortical micro-stimulation, ET-1 was microinjected into the contralateral motor cortex (M1) to its preferred hand. The monkeys had been trained in three manual dexterity tasks before the microinjection and were tested for these tasks following the ET-1 injection. Brain Magnetic Resonance Imaging scans were performed 1, 7, 14 and 28 days post ischemia. It was found that ET-1 impaired the manual dexterity of the monkeys in the vertical slot and rotating Brinkman board tasks 3–8 days after the injection. Brain imaging found that severe edema was present 7 days after the focal ischemia. This data suggest that ET-1 can induce transient ischemic stroke in rhesus monkey and that ET-1 induced focal ischemia in non-human primates is a potential model to study the mechanism of stroke and brain repair after stroke. PMID:28358140

  16. Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase.

    PubMed

    Wang, Feng; Yin, Jianyong; Lu, Zeyuan; Zhang, Guangyuan; Li, Junhui; Xing, Tao; Zhuang, Shougang; Wang, Niansong

    2016-07-01

    Clinical trials shows that remote ischemic preconditioning (IPC) can protect against contrast induced nephropathy (CIN) in risky patients, however, the exact mechanism is unclear. In this study, we explored whether renalase, an amine oxidase that has been previously shown to mediate reno-protection by local IPC, would also mediate the same effect elicited by remote IPC in animal model. Limb IPC was performed for 24h followed by induction of CIN. Our results indicated that limb IPC prevented renal function decline, attenuated tubular damage and reduced oxidative stress and inflammation in the kidney. All those beneficial effects were abolished by silencing of renalase with siRNA. This suggests that similar to local IPC, renalase is also critically involved in limb IPC-elicited reno-protection. Mechanistic studies showed that limb IPC increased TNFα levels in the muscle and blood, and up-regulated renalase and phosphorylated IκBα expression in the kidney. Pretreatment with TNFα antagonist or NF-κB inhibitor, largely blocked renalase expression. Besides, TNFα preconditioning increased expression of renal renalase in vivo and in vitro, and attenuated H2O2 induced apoptosis in renal tubular cells. Collectively, our results suggest that limb IPC-induced reno-protection in CIN is dependent on increased renalase expression via activation of the TNFα/NF-κB pathway.

  17. A pilot study on transient ischemic stroke induced with endothelin-1 in the rhesus monkeys.

    PubMed

    Dai, PeiMin; Huang, Hui; Zhang, Lin; He, Jing; Zhao, XuDong; Yang, FuHan; Zhao, Ning; Yang, JianZhen; Ge, LongJiao; Lin, Yu; Yu, HuaLin; Wang, JianHong

    2017-03-30

    Endothelin-1 (ET-1), a vasoconstrictor, has recently been used to induce focal ischemia in rodents and marmoset monkeys. The rhesus monkey, however, has numerous advantages to the rodent and marmoset that make it a superior and irreplaceable animal model for studying stroke in the brain. In the present study, after mapping the preferred hand representation in two healthy male monkeys with intracortical micro-stimulation, ET-1 was microinjected into the contralateral motor cortex (M1) to its preferred hand. The monkeys had been trained in three manual dexterity tasks before the microinjection and were tested for these tasks following the ET-1 injection. Brain Magnetic Resonance Imaging scans were performed 1, 7, 14 and 28 days post ischemia. It was found that ET-1 impaired the manual dexterity of the monkeys in the vertical slot and rotating Brinkman board tasks 3-8 days after the injection. Brain imaging found that severe edema was present 7 days after the focal ischemia. This data suggest that ET-1 can induce transient ischemic stroke in rhesus monkey and that ET-1 induced focal ischemia in non-human primates is a potential model to study the mechanism of stroke and brain repair after stroke.

  18. Fatty acid nitroalkenes induce resistance to ischemic cardiac injury by modulating mitochondrial respiration at complex II

    PubMed Central

    Koenitzer, Jeffrey R.; Bonacci, Gustavo; Woodcock, Steven R.; Chen, Chen-Shan; Cantu-Medellin, Nadiezhda; Kelley, Eric E.; Schopfer, Francisco J.

    2015-01-01

    Nitro-fatty acids (NO2-FA) are metabolic and inflammatory-derived electrophiles that mediate pleiotropic signaling actions. It was hypothesized that NO2-FA would impact mitochondrial redox reactions to induce tissue-protective metabolic shifts in cells. Nitro-oleic acid (OA-NO2) reversibly inhibited complex II-linked respiration in isolated rat heart mitochondria in a pH-dependent manner and suppressed superoxide formation. Nitroalkylation of Fp subunit was determined by BME capture and the site of modification by OA-NO2 defined by mass spectrometric analysis. These effects translated into reduced basal and maximal respiration and favored glycolytic metabolism in H9C2 cardiomyoblasts as assessed by extracellular H+ and O2 flux analysis. The perfusion of NO2-FA induced acute cardioprotection in an isolated perfused heart ischemia/reperfusion (IR) model as evidenced by significantly higher rate-pressure products. Together these findings indicate that NO2-FA can promote cardioprotection by inducing a shift from respiration to glycolysis and suppressing reactive species formation in the post-ischemic interval. PMID:26722838

  19. Low-dose radiation prevents type 1 diabetes-induced cardiomyopathy via activation of AKT mediated anti-apoptotic and anti-oxidant effects.

    PubMed

    Zhang, Fangfang; Lin, Xiufei; Yu, Lechu; Li, Weihua; Qian, Dingliang; Cheng, Peng; He, Luqing; Yang, Hong; Zhang, Chi

    2016-07-01

    We investigated whether low-dose radiation (LDR) can prevent late-stage diabetic cardiomyopathy and whether this protection is because of the induction of anti-apoptotic and anti-oxidant pathways. Streptozotocin-induced diabetic C57BL/6J mice were treated with/without whole-body LDR (12.5, 25, or 50 mGy) every 2 days. Twelve weeks after onset of diabetes, cardiomyopathy was diagnosed characterized by significant cardiac dysfunction, hypertrophy and histopathological abnormalities associated with increased oxidative stress and apoptosis, which was prevented by LDR (25 or 50 mGy only). Low-dose radiation-induced cardiac protection also associated with P53 inactivation, enhanced Nrf2 function and improved Akt activation. Next, for the mechanistic study, mouse primary cardiomyocytes were treated with high glucose (33 mmol/l) for 24 hrs and during the last 15 hrs bovine serum albumin-conjugated palmitate (62.5 μmol/l) was added into the medium to mimic diabetes, and cells were treated with LDR (25 mGy) every 6 hrs during the whole process of HG/Pal treatment. Data show that blocking Akt/MDM2/P53 or Akt/Nrf2 pathways with small interfering RNA of akt, mdm2 and nrf2 not only prevented LDR-induced anti-apoptotic and anti-oxidant effects but also prevented LDR-induced suppression on cardiomyocyte hypertrophy and fibrosis against HG/Pal. Low-dose radiation prevented diabetic cardiomyopathy by improving cardiac function and hypertrophic remodelling attributed to Akt/MDM2/P53-mediated anti-apoptotic and Akt/Nrf2-mediated anti-oxidant pathways simultaneously. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. Arrhythmogenic cardiomyopathy.

    PubMed

    Pilichou, Kalliopi; Thiene, Gaetano; Bauce, Barbara; Rigato, Ilaria; Lazzarini, Elisabetta; Migliore, Federico; Perazzolo Marra, Martina; Rizzo, Stefania; Zorzi, Alessandro; Daliento, Luciano; Corrado, Domenico; Basso, Cristina

    2016-04-02

    Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias and pathologically by an acquired and progressive dystrophy of the ventricular myocardium with fibro-fatty replacement. Due to an estimated prevalence of 1:2000-1:5000, AC is listed among rare diseases. A familial background consistent with an autosomal-dominant trait of inheritance is present in most of AC patients; recessive variants have also been reported, either or not associated with palmoplantar keratoderma and woolly hair. AC-causing genes mostly encode major components of the cardiac desmosome and up to 50% of AC probands harbor mutations in one of them. Mutations in non-desmosomal genes have been also described in a minority of AC patients, predisposing to the same or an overlapping disease phenotype. Compound/digenic heterozygosity was identified in up to 25% of AC-causing desmosomal gene mutation carriers, in part explaining the phenotypic variability. Abnormal trafficking of intercellular proteins to the intercalated discs of cardiomyocytes and Wnt/beta catenin and Hippo signaling pathways have been implicated in disease pathogenesis.AC is a major cause of sudden death in the young and in athletes. The clinical picture may include a sub-clinical phase; an overt electrical disorder; and right ventricular or biventricular pump failure. Ventricular fibrillation can occur at any stage. Genotype-phenotype correlation studies led to identify biventricular and dominant left ventricular variants, thus supporting the use of the broader term AC.Since there is no "gold standard" to reach the diagnosis of AC, multiple categories of diagnostic information have been combined and the criteria recently updated, to improve diagnostic sensitivity while maintaining specificity. Among diagnostic tools, contrast enhanced cardiac magnetic resonance is playing a major role in detecting left dominant forms of AC, even preceding morpho

  1. Exogenous H2S facilitating ubiquitin aggregates clearance via autophagy attenuates type 2 diabetes-induced cardiomyopathy.

    PubMed

    Wu, Jichao; Tian, Zhiliang; Sun, Yu; Lu, Cuicui; Liu, Ning; Gao, Zhaopeng; Zhang, Linxue; Dong, Shiyun; Yang, Fan; Zhong, Xin; Xu, Changqing; Lu, Fanghao; Zhang, Weihua

    2017-08-10

    Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. Hydrogen sulphide (H2S), a newly found gaseous signalling molecule, has an important role in many regulatory functions. The purpose of this study is to investigate the effects of exogenous H2S on autophagy and its possible mechanism in DCM induced by type II diabetes (T2DCM). In this study, we found that sodium hydrosulphide (NaHS) attenuated the augment in left ventricular (LV) mass and increased LV volume, decreased reactive oxygen species (ROS) production and ameliorated H2S production in the hearts of db/db mice. NaHS facilitated autophagosome content degradation, reduced the expression of P62 (a known substrate of autophagy) and increased the expression of microtubule-associated protein 1 light chain 3 II. It also increased the expression of autophagy-related protein 7 (ATG7) and Beclin1 in db/db mouse hearts. NaHS increased the expression of Kelch-like ECH-associated protein 1 (Keap-1) and reduced the ubiquitylation level in the hearts of db/db mice. 1,4-Dithiothreitol, an inhibitor of disulphide bonds, increased the ubiquitylation level of Keap-1, suppressed the expression of Keap-1 and abolished the effects of NaHS on ubiquitin aggregate clearance and ROS production in H9C2 cells treated with high glucose and palmitate. Overall, we concluded that exogenous H2S promoted ubiquitin aggregate clearance via autophagy, which might exert its antioxidative effect in db/db mouse myocardia. Moreover, exogenous H2S increased Keap-1 expression by suppressing its ubiquitylation, which might have an important role in ubiquitin aggregate clearance via autophagy. Our findings provide new insight into the mechanisms responsible for the antioxidative effects of H2S in the context of T2DCM.

  2. Exogenous H2S facilitating ubiquitin aggregates clearance via autophagy attenuates type 2 diabetes-induced cardiomyopathy

    PubMed Central

    Wu, Jichao; Tian, Zhiliang; Sun, Yu; Lu, Cuicui; Liu, Ning; Gao, Zhaopeng; Zhang, Linxue; Dong, Shiyun; Yang, Fan; Zhong, Xin; Xu, Changqing; Lu, Fanghao; Zhang, Weihua

    2017-01-01

    Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. Hydrogen sulphide (H2S), a newly found gaseous signalling molecule, has an important role in many regulatory functions. The purpose of this study is to investigate the effects of exogenous H2S on autophagy and its possible mechanism in DCM induced by type II diabetes (T2DCM). In this study, we found that sodium hydrosulphide (NaHS) attenuated the augment in left ventricular (LV) mass and increased LV volume, decreased reactive oxygen species (ROS) production and ameliorated H2S production in the hearts of db/db mice. NaHS facilitated autophagosome content degradation, reduced the expression of P62 (a known substrate of autophagy) and increased the expression of microtubule-associated protein 1 light chain 3 II. It also increased the expression of autophagy-related protein 7 (ATG7) and Beclin1 in db/db mouse hearts. NaHS increased the expression of Kelch-like ECH-associated protein 1 (Keap-1) and reduced the ubiquitylation level in the hearts of db/db mice. 1,4-Dithiothreitol, an inhibitor of disulphide bonds, increased the ubiquitylation level of Keap-1, suppressed the expression of Keap-1 and abolished the effects of NaHS on ubiquitin aggregate clearance and ROS production in H9C2 cells treated with high glucose and palmitate. Overall, we concluded that exogenous H2S promoted ubiquitin aggregate clearance via autophagy, which might exert its antioxidative effect in db/db mouse myocardia. Moreover, exogenous H2S increased Keap-1 expression by suppressing its ubiquitylation, which might have an important role in ubiquitin aggregate clearance via autophagy. Our findings provide new insight into the mechanisms responsible for the antioxidative effects of H2S in the context of T2DCM. PMID:28796243

  3. Nefiracetam attenuates post-ischemic nonconvulsive seizures in rats and protects neuronal cell death induced by veratridine and glutamate.

    PubMed

    Lu, Xi-Chun May; Dave, Jitendra R; Chen, Zhiyong; Cao, Ying; Liao, Zhilin; Tortella, Frank C

    2013-06-13

    Stroke patients are at a high risk of developing post-ischemic seizures and cognitive impairment. Nefiracetam (NEF), a pyrrolidone derivative, has been shown to possess both anti-epileptic and cognitive-enhancing properties. In this study the anti-seizure effects of NEF were evaluated in a rat model of post-ischemic nonconvulsive seizures (NCSs). Its potential mechanisms were investigated in neuronal cell culture assays of neurotoxicity associated with ischemic brain injury and epileptogenesis. In the in vivo study, rats received 24h permanent middle cerebral artery occlusion. NEF was administered intravenously either at 15 min post-injury but prior to the first NCS event (30 mg/kg, pre-NCS treatment) or immediately after the first NCS occurred (30 or 60 mg/kg, post-NCS treatment). In the in vitro study, neuronal cell cultures were exposed to veratridine or glutamate and treated with NEF (1-500 nM). The NEF pre-NCS treatment significantly reduced the NCS frequency and duration, whereas the higher NEF dose (60 mg/kg) was required to achieve similar effects when given after NCS occurred. The NEF treatment also dose-dependently (5-500 nM) protected against neuronal cell death induced by veratridine as measured by MTT cell viability assay, but higher doses (250-500 nM) were required against glutamate toxicity. The anti-seizure property of NEF was demonstrated in a clinically relevant rat model of post-ischemic NCS. The preferential effects of NEF against in vitro veratridine toxicity suggest the involvement of its modulation of sodium channel malfunction. Future studies are warranted to study the mechanisms of NEF against ischemic brain injury and post-ischemic seizures. Published by Elsevier Inc.

  4. The Cardiomyopathy of Iron Deficiency

    PubMed Central

    Hegde, Nikita; Rich, Michael W.; Gayomali, Charina

    2006-01-01

    Iron-deficiency anemia can have deleterious effects on the heart. Herein, we describe the effects of iron deficiency on the heart as corroborated with electrocardiography, radiology, echocardiography, and cardiac catheterization. We review the pathophysiology, clinical features, and management of iron-deficiency–induced cardiomyopathy. PMID:17041692

  5. Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection

    PubMed Central

    2010-01-01

    Ischemic tolerance defines transient resistance to lethal ischemia gained by a prior sublethal noxious stimulus (i.e., preconditioning). This adaptive response is thought to be an evolutionarily conserved defense mechanism, observed in a wide variety of species. Preconditioning confers ischemic tolerance if not in all, in most organ systems, including the heart, kidney, liver, and small intestine. Since the first landmark experimental demonstration of ischemic tolerance in the gerbil brain in early 1990's, basic scientific knowledge on the mechanisms of cerebral ischemic tolerance increased substantially. Various noxious stimuli can precondition the brain, presumably through a common mechanism, genomic reprogramming. Ischemic tolerance occurs in two temporally distinct windows. Early tolerance can be achieved within minutes, but wanes also rapidly, within hours. Delayed tolerance develops in hours and lasts for days. The main mechanism involved in early tolerance is adaptation of membrane receptors, whereas gene activation with subsequent de novo protein synthesis dominates delayed tolerance. Ischemic preconditioning is associated with robust cerebroprotection in animals. In humans, transient ischemic attacks may be the clinical correlate of preconditioning leading to ischemic tolerance. Mimicking the mechanisms of this unique endogenous protection process is therefore a potential strategy for stroke prevention. Perhaps new remedies for stroke are very close, right in our cells. PMID:20298534

  6. Effect of remote ischemic preconditioning on platelet activation and reactivity induced by ablation for atrial fibrillation.

    PubMed

    Stazi, Alessandra; Scalone, Giancarla; Laurito, Marianna; Milo, Maria; Pelargonio, Gemma; Narducci, Maria Lucia; Parrinello, Rossella; Figliozzi, Stefano; Bencardino, Gianluigi; Perna, Francesco; Lanza, Gaetano A; Crea, Filippo

    2014-01-07

    Radiofrequency ablation of atrial fibrillation has been associated with some risk of thromboembolic events. Previous studies showed that preventive short episodes of forearm ischemia (remote ischemic preconditioning [IPC]) reduce exercise-induced platelet reactivity. In this study, we assessed whether remote IPC has any effect on platelet activation induced by radiofrequency ablation of atrial fibrillation. We randomized 19 patients (age, 54.7±11 years; 17 male) undergoing radiofrequency catheter ablation of paroxysmal atrial fibrillation to receive remote IPC or sham intermittent forearm ischemia (control subjects) before the procedure. Blood venous samples were collected before and after remote IPC/sham ischemia, at the end of the ablation procedure, and 24 hours later. Platelet activation and reactivity were assessed by flow cytometry by measuring monocyte-platelet aggregate formation, platelet CD41 in the monocyte-platelet aggregate gate, and platelet CD41 and CD62 in the platelet gate in the absence and presence of ADP stimulation. At baseline, there were no differences between groups in platelet variables. Radiofrequency ablation induced platelet activation in both groups, which persisted after 24 hours. However, compared with control subjects, remote IPC patients showed a lower increase in all platelet variables, including monocyte-platelet aggregate formation (P<0.0001), CD41 in the monocyte-platelet aggregate gate (P=0.002), and CD41 (P<0.0001) and CD62 (P=0.002) in the platelet gate. Compared with control subjects, remote IPC was also associated with a significantly lower ADP-induced increase in all platelet markers. Our data show that remote IPC before radiofrequency catheter ablation for paroxysmal atrial fibrillation significantly reduces the increased platelet activation and reactivity associated with the procedure.

  7. Multiscale technologies for treatment of ischemic cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Mahmoudi, Morteza; Yu, Mikyung; Serpooshan, Vahid; Wu, Joseph C.; Langer, Robert; Lee, Richard T.; Karp, Jeffrey M.; Farokhzad, Omid C.

    2017-09-01

    The adult mammalian heart possesses only limited capacity for innate regeneration and the response to severe injury is dominated by the formation of scar tissue. Current therapy to replace damaged cardiac tissue is limited to cardiac transplantation and thus many patients suffer progressive decay in the heart's pumping capacity to the point of heart failure. Nanostructured systems have the potential to revolutionize both preventive and therapeutic approaches for treating cardiovascular disease. Here, we outline recent advancements in nanotechnology that could be exploited to overcome the major obstacles in the prevention of and therapy for heart disease. We also discuss emerging trends in nanotechnology affecting the cardiovascular field that may offer new hope for patients suffering massive heart attacks.

  8. Effects of histidine and N-acetylcysteine on doxorubicin-induced cardiomyopathy in rats.

    PubMed

    Farshid, Amir Abbas; Tamaddonfard, Esmaeal; Simaee, Naeime; Mansouri, Sanam; Najafi, Sima; Asri-Rezaee, Siamak; Alavi, Hossein

    2014-06-01

    The amino acids histidine and n-acetylcysteine have many biological activities such as antioxidant effect. The present study investigated the effects of histidine and n-acetylcysteine on the heart lesions induced by doxorubicin (DOX) in rats. Forty-eight male Wistar rats were divided into two major groups treated intraperitoneally (i.p.) with normal saline and 4 mg/kg of DOX, respectively. Each group was further divided into four subgroups that were treated with separate and combined i.p. injections of histidine and n-acetylcysteine (NAC) at a same dose of 40 mg/kg. Electrocardiography (ECG) was recorded using lead II. The heart lesions were evaluated by light microscopy. Serum levels of creatine phosphokinase and lactate dehydrogenase and heart tissue malondialdehyde levels were measured. Histidine and especially NAC at a same dose of 40 mg/kg recovered ECG changes, improved heart lesions and prevented biochemical changes induced by DOX. Co-administration of histidine and NAC showed better responses when compared with them used alone. The results of the present study showed protective effects for histidine and NAC on the heart. Reduction in free radical-induced toxic effects may be involved in cardioprotective properties of histidine and NAC.

  9. Specific activation of CD4(-) CD8(-) double-negative T cells by Trypanosoma cruzi-derived glycolipids induces a proinflammatory profile associated with cardiomyopathy in Chagas patients.

    PubMed

    Passos, L S A; Magalhães, L M D; Soares, R P; Marques, A F; Nunes, M do C P; Gollob, K J; Dutra, W O

    2017-10-01

    Cardiomyopathy is the most severe outcome of Chagas disease, causing more than 12 000 deaths/year. Immune cells participate in cardiomyopathy development either by direct tissue d