cardiovascular-agents and Cardiomyopathies

Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-β), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on which research has been currently focusing.. This review initially discusses those drugs used in clinical practice for their anti-fibrotic properties and later examines emerging pathway-specific agents in preclinical and clinical development [phase I and II-concluded or ongoing trials]. We performed a PubMed, Embase and Google Scholar research including original articles, systematic reviews, ongoing and completed trials using combinations of keywords such as 'myocardial fibrosis', 'reverse remodeling', 'RAAs', 'therapy'.. A variety of preclinical evidences suggest that new drugs and molecules are potentially useful to target cardiac fibrosis and improve left ventricular function, reduce infarct size and scars, delay incident heart failure and cardiac dysfunction in animal models. However, there are very few clinical trials investigating the effect of such drugs in this setting, as well as a lack of new engineered molecules for specific targets.

Topics: Animals; Biomarkers; Cardiomyopathies; Cardiovascular Agents; Fibrosis; Humans; Molecular Targeted Therapy; Myocytes, Cardiac; Signal Transduction; Treatment Outcome

Cardiomyopathies represent an important cause of heart failure, often affecting young individuals, and have important implications for relatives. Genetic testing for cardiomyopathies is an established care pathway in contemporary cardiology practice. The primary cardiomyopathies where genetic testing is indicated are hypertrophic, dilated, arrhythmogenic, and restrictive cardiomyopathies, with left ventricular noncompaction as a variant phenotype. Early identification and initiation of therapies in patients with inherited cardiomyopathies allow for targeting asymptomatic and presymptomatic patients in stages A and B of the American College of Cardiology/American Heart Association classification of heart failure. The current approach for genetic testing uses gene panel-based testing with the ability to extend to whole-exome and whole-genome sequencing in rare instances. The central components of genetic testing include defining the genetic basis of the diagnosis, providing prognostic information, and the ability to screen and risk-stratify relatives. Genetic testing for cardiomyopathies should be coordinated by a multidisciplinary team including adult and pediatric cardiologists, genetic counsellors, and geneticists, with access to expertise in cardiac imaging and electrophysiology. A pragmatic approach for addressing genetic variants of uncertain significance is important. In this review, we highlight the indications for genetic testing in the various cardiomyopathies, the value of early diagnosis and treatment, family screening, and the care process involved in genetic counselling and testing.

Topics: Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Ethnicity; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Heart Failure; Humans; Patient Education as Topic; Phenotype; Prognosis; Risk Assessment

The use of implantable cardioverter-defibrillators (ICDs) significantly reduces the risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Current guidelines, which are based on seminal clinical trials published nearly 2 decades ago, recommend that patients be on optimal medical therapy for HF for a minimum of 3 months before referral for prophylactic ICD. This waiting period allows for left ventricular reverse remodelling and improvement in HF symptoms, which may render primary prevention ICD implantation unnecessary. However, medical therapy for HFrEF has significantly evolved since the publication of these landmark trials. Given the plethora of medical therapy options now available for HFrEF, it is appropriate to reassess the duration of this waiting period. In the present review, we examine the landmark randomised trials in primary prevention of sudden cardiac death in patients with HFrEF, summarise the novel medical therapies (sacubitril-valsartan, sodium-glucose cotransporter 2 inhibitors, ivabradine, vericiguat, and omecamtiv mecarbil) that have emerged since the publication of those trials, discuss the optimal timing of ICD referral, and review subtypes of nonischemic cardiomyopathy where timing of ICD insertion is guided by alternative criteria. With the steps now needed to optimise medical therapy for HFrEF, in terms of both classes of drugs and doses of each agent, it can easily take up to 6 months to achieve optimisation. Following that, waiting periods of 3 months for ischemic cardiomyopathy and 6 months for nonischemic cardiomyopathy may be required to allow adequate reverse remodelling before reevaluating for ICD implantation.

Topics: Cardiomyopathies; Cardiovascular Agents; Clinical Trials as Topic; Contraindications, Procedure; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Failure; Humans; Primary Prevention; Referral and Consultation; Stroke Volume

Transthyretin (ATTR) amyloidosis is a multisystem disease caused by organ deposition of amyloid fibrils derived from the misfolded transthyretin (TTR) protein. The purpose of this article is to provide an overview of current treatment regimens and summarize important considerations for each agent. A literature search was performed with the PubMed database for articles published through October 2020. Search criteria included therapies available on the market and investigational therapies used for ATTR amyloidosis treatment. Both prospective clinical trials and retrospective studies have been included in this review. Available therapies discussed in this review article are tafamidis, diflunisal, patisiran, and inotersen. Tafamidis is FDA approved for treatment of wild-type ATTR (ATTRwt) and hereditary ATTR (ATTRv) cardiomyopathy, and patisiran and inotersen are FDA approved for ATTRv polyneuropathy. Diflunisal does not have an FDA-labeled indication for amyloidosis but has been studied in ATTRv polyneuropathy and ATTRwt cardiomyopathy. Investigational therapies include a TTR stabilizer, AG10; 2 antifibril agents, PRX004 and doxycycline/tauroursodeoxycholic acid; and 2 gene silencers, vutrisiran and AKCEA-TTR-LRx; and clinical trials are ongoing. ATTR amyloidosis treatment selection is based on subtype and presence of cardiac or neurological manifestations. Additional considerations such as side effects, monitoring, and administration are outlined in this review.

Topics: Amyloid Neuropathies, Familial; Animals; Benzoxazoles; Cardiomyopathies; Cardiovascular Agents; Diflunisal; Genetic Predisposition to Disease; Humans; Mutation; Oligonucleotides; Phenotype; Prealbumin; RNA, Small Interfering; Treatment Outcome

The transthyretin (TTR) amyloidoses result from misfolding of the protein leading to fibril formation and aggregation as amyloid deposits in predominantly the cardiovascular and nervous systems. Cardiac involvement can manifest as heart failure, arrhythmias, and valvular disease. Neurologic involvement can cause sensorimotor polyneuropathies, mononeuropathies, and dysautonomia. Previously, treatment has focused on management of these symptoms and disease sequelae, with a high rate of mortality due to the absence of disease-modifying therapies. In this article, we review novel treatments focusing on 3 mechanistic pathways: (1) silencing of the TTR gene to suppress production, (2) stabilizing of TTR tetramers to prevent misfolding, or (3) disrupting of existing TTR amyloid fibrils to promote reabsorption.

Topics: Amyloid; Amyloid Neuropathies, Familial; Animals; Cardiomyopathies; Cardiovascular Agents; Gene Silencing; Genetic Predisposition to Disease; Genetic Therapy; Humans; Mutation; Myocytes, Cardiac; Phenotype; Prealbumin; Protein Stability

Peripartum cardiomyopathy is a form of systolic heart failure affecting young women toward the end of pregnancy or in the months following delivery. Incidence is higher in African-American women and in women with older maternal age, hypertensive disorders of pregnancy, and multiple gestation pregnancies. Symptoms of heart failure mimic those of normal pregnancy, often resulting in a delay in diagnosis and preventable complications. Echocardiography showing decreased myocardial function is essential for the diagnosis. Medical management is similar to heart failure with reduced ejection fraction of other etiologies, but adjustments during pregnancy are necessary to ensure fetal safety. Variable outcomes include complete recovery, persistent heart failure, arrhythmias, thromboembolic events, and death. Subsequent pregnancy confers substantial risk of relapse and even death if there is incomplete myocardial recovery. Additional research about the etiology, optimal therapy including the use of bromocriptine, long-term outcomes, and duration of treatment after recovery are needed.

Topics: Cardiomyopathies; Cardiovascular Agents; Female; Humans; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Review Literature as Topic

Background The emergence of specific therapies for transthyretin cardiac amyloidosis (CA) warrants the need for a systematic review of the literature. Methods and Results A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was performed on MEDLINE, PubMed, and Embase databases on November 29, 2019. Studies were selected based on the following predefined eligibility criteria: English-language randomized controlled trials (RCTs), non-RCTs, or observational studies, which included adult patients with variant/wild-type transthyretin-CA, assessed specific therapies for transthyretin-CA, and reported cardiovascular outcomes. Relevant data were extracted to a predefined template. Quality assessment was based on National Institute for Health and Care Excellence recommendations (RCTs) or a checklist by Downs and Black (non-RCTs). From 1203 records, 24 publications were selected, describing 4 RCTs (6 publications) and 16 non-RCTs (18 publications). Tafamidis was shown to significantly improve all-cause mortality and cardiovascular hospitalizations and reduce worsening in 6-minute walk test, Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in variant/wild-type transthyretin-CA. Patisiran showed promising results in a subgroup analysis of patients with variant transthyretin-CA, which have to be confirmed in RCTs. Inotersen showed conflicting results on cardiac imaging parameters. The one study on AG10 had only a 1-month duration and cardiovascular end points were exploratory and limited to cardiac biomarkers. Limited evidence from noncomparative single-arm small non-RCTs existed for diflunisal, epigallocatechin-3-gallate (green tea extract), and doxycycline+tauroursodeoxycholic acid/ursodeoxycholic acid. Conclusions This systematic review of the literature supports the use of tafamidis in wild-type and variant transthyretin-CA. Novel therapeutic targets including transthyretin gene silencers are currently under investigation.

Topics: Amyloid Neuropathies, Familial; Benzoxazoles; Cardiomyopathies; Cardiovascular Agents; Genetic Therapy; Humans

Cardiac sarcoidosis usually occurs in the context of systemic disease; however, isolated cardiac involvement can occur in up to 25% of cases and tends to be clinically silent. When symptoms are present, they are often nonspecific and occasionally fatal, representing a diagnostic challenge. A high index of clinical suspicion and the integration of appropriate imaging, laboratory, and pathologic findings is always required. Treatment aims to control the systemic inflammatory condition while preventing further cardiac damage. However, even with adequate diagnosis and treatment strategies, prognosis remains poor. We describe the case of a patient who presented with cardiac symptoms, whose initial examination was unrevealing. Diagnosis was made retrospectively based on later systemic manifestations that revealed characteristic sarcoidosis findings.

Topics: Cardiomyopathies; Cardiovascular Agents; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Losartan; Methotrexate; Metoprolol; Middle Aged; Prednisone; Sarcoidosis

Our understanding of the complexity of cardiovascular disease pathophysiology remains very incomplete and has hampered cardiovascular drug development over recent decades. The prevalence of cardiovascular diseases and their increasing global burden call for novel strategies to address disease biology and drug discovery. Areas covered: This review describes the recent history of cardiovascular drug discovery using in vivo phenotype-based screening in zebrafish. The rationale for the use of this model is highlighted and the initial efforts in the fields of disease modeling and high-throughput screening are illustrated. Finally, the advantages and limitations of in vivo zebrafish screening are discussed, highlighting newer approaches, such as genome editing technologies, to accelerate our understanding of disease biology and the development of precise disease models. Expert opinion: Full understanding and faithful modeling of specific cardiovascular disease is a rate-limiting step for cardiovascular drug discovery. The resurgence of in vivo phenotype screening together with the advancement of systems biology approaches allows for the identification of lead compounds which show efficacy on integrative disease biology in the absence of validated targets. This strategy bypasses current gaps in knowledge of disease biology and paves the way for successful drug discovery and downstream molecular target identification.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Cardiovascular Diseases; Disease Models, Animal; Drug Discovery; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Humans; Systems Biology; Zebrafish

Heritable cardiomyopathies are a class of heart diseases caused by variations in a number of genetic loci. Genetic variants on one allele lead to either a degraded protein, which causes a haploinsufficiency of that protein, or a nonfunctioning protein that subverts the molecular system within which the protein works. Over years, both of these mechanisms eventually lead to diseased heart tissue and symptoms of a failing heart. Most cardiomyopathy treatments repurpose heart failure drugs to manage these symptoms and avoid adverse outcomes. There are few therapies that correct the underlying pathogenic genetic or molecular mechanism. This review will reflect on this unmet clinical need in genetic cardiomyopathies and consider a variety of therapies that address the mechanism of disease rather than patient symptoms. These therapies are genetic, targeting a defective gene or transcript, or ameliorating a genetic insufficiency. However, there are also a number of small molecules under exploration that modulate downstream faulty protein products affected in cardiomyopathies.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Genetic Predisposition to Disease; Genetic Therapy; Humans; Molecular Targeted Therapy; Phenotype; Prognosis; Risk Factors

Currently, the percentage of non-specific myocardial lesions of non-inflammatory genesis has significantly increased in the structure of cardiovascular diseases in children and adolescents. Cardiomyopathies are a cluster of myocardial diseases that have become more of interest by cardiologists, morphologists, geneticists, and cardiac surgeons. Cardiomyopathies in children are regarded as a severe pathology characterized by a progressive course, resistance to therapy, and result in an unfavourable prognosis. The current article presents data from international publications dedicated to cardiomyopathy diagnostics in children. This article deals with terminology issues in compliance with international disease classification, primary diagnostic criteria of non-coronary myocardium pathology, and modern methods of diagnostics and pharmacotherapy.

Topics: Age of Onset; Animals; Cardiology; Cardiomyopathies; Cardiovascular Agents; Energy Metabolism; Humans; Metabolic Diseases; Myocardium; Pediatrics; Predictive Value of Tests; Risk Factors; Terminology as Topic; Treatment Outcome

Cardiovascular diseases are major complications in pregnancy worldwide and the number of patients who develop cardiac problems during pregnancy is increasing. Pregnancy-associated hypertensive complications such as pre-eclampsia (PE) or peripartum cardiomyopathy (PPCM) are potentially life-threatening heart diseases emerging during pregnancy, under delivery or in the first postpartal months in previously healthy women. Both disease entities display substantial morbidity and mortality in the acute phase. Long-term effects are just beginning to be evaluated. Pathophysiologies are not clear but may to some degree overlap with regard to angiogenic imbalance and endothelial damage. Genetics, lifestyle, and comorbidities are important modulators of PE and PPCM. The present review summarizes the current knowledge on epidemiology and pathophysiology, provides information on diagnostic and prognostic biomarkers and highlights promising novel therapeutic approaches for PE and PPCM.

Topics: Biomarkers; Cardiomyopathies; Cardiovascular Agents; Female; Humans; Hypertension; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular

The number of cancer survivors is exponentially increasing worldwide, due to both advances in cancer detection and treatment strategies, as well as the aging and growth of the population. This decrease in cancer mortality has brought forth a concurrent increase of non-ischemic (toxic) dilated cardiomyopathy in the survivor population, also known as cancer therapeutics-induced cardiomyopathy (CTIC). The optimal pharmacological management for this condition is still elusive, and hence, the focus of this work.. Our review of the literature did not identify any prospective randomized clinical trial of CTIC in adult cancer survivors, neither published nor in progress. However, available data seem to suggest that, when managed with standard guideline-derived medical therapy, the outcomes of CTIC are comparable to that of idiopathic dilated cardiomyopathy (IDC). Nonetheless, the evidence behind this strategy is inadequate. Until new information becomes available, pharmacological management of CTIC must parallel that of IDC. However, implementation of such may be hindered by other cancer therapeutics-induced comorbidities and conditioned by the particular effects of heart failure pharmacotherapy on cancer outcomes. This work succinctly reviews these three areas, in the context of adult cancer survivors.

Topics: Adult; Cancer Survivors; Cardiomyopathies; Cardiovascular Agents; Comorbidity; Global Health; Heart Failure; Humans; Neoplasms

Cardiovascular disease remains the leading cause of death among women globally, majority of which are due to ischemic heart disease. Despite the recent advances in the overall management of CVD, there are unique challenges in the diagnosis and management of women as well as poorer outcomes.. Women with ischemic cardiomyopathy experience significant morbidity and mortality. Differences in underlying pathology, delays in presentation, diagnosis, and treatment as well as the under-representation of women in clinical trials contribute to these poor outcomes. In this review, we discuss the nuances of gender-specific differences in the burden, clinical presentation, and outcomes of ischemic cardiomyopathy in women, in addition to discussion of areas needing further research.

Topics: Cardiac Rehabilitation; Cardiac Resynchronization Therapy; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Female; Healthcare Disparities; Heart-Assist Devices; Humans; Male; Myocardial Ischemia; Risk Factors; Sex Factors; Ventricular Remodeling

The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further.. To assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM, using measures of change in cardiac function over six months.. On 16 October 2017 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase, and on 12 December 2017, we searched two clinical trials registries. We also searched conference proceedings and bibliographies.. We considered only randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials for inclusion. In the Discussion, we reviewed open studies, longitudinal observational studies and individual case reports but only discussed studies that adequately described the diagnosis, intervention, pretreatment, and post-treatment states and in which follow-up lasted for at least six months.. Two authors independently reviewed the titles and abstracts identified from the search and performed data extraction. All three authors assessed risk of bias independently, compared results, and decided which trials met the inclusion criteria. They assessed the certainty of evidence using GRADE criteria.. We included five studies (N = 205) in the review; four studies included participants with DMD only, and one study included participants with DMD or BMD. All studied different interventions, and meta-analysis was not possible. We found no studies for XLDCM. None of the trials reported cardiac function as improved or stable cardiac versus deteriorated.The randomised first part of a two-part study of perindopril (N = 28) versus placebo (N = 27) in boys with DMD with normal heart function at baseline showed no difference in the number of participants with a left ventricular ejection fraction (LVEF%) of less than 45% after three years of therapy (n = 1 in each group; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.07 to 15.77). This result is uncertain because of study limitations, indirectness and imprecision. In a non-randomised follow-up study, after 10 years, more participants who had received placebo from the beginning had reduced LVEF% (less than 45%). Adverse event rates were similar between the placebo and treatment groups (low-certainty evidence).A study comparing treatment with lisinopril versus losartan in 23 boys newly diagnosed with Duchenne cardiomyopathy showed that after 12 months, both were equally effective in preserving or improving LVEF% (lisinopril 54.6% (standard deviation (SD) 5.19), losartan 55.2% (SD 7.19); mean difference (MD) -0.60% CI -6.67 to 5.47: N = 16). The certainty of evidence was very low because of very serious imprecision and study limitations (risk of bias). Two participants in the losartan group were withdrawn due to adverse events: one participant developed an allergic reaction, and a second exceeded the safety standard with a fall in ejection fraction greater than 10%. Authors reported no other adverse events related to the medication (N = 22; very low-certainty evidence).A study comparing idebenone versus placebo in 21 boys with DMD showed little or no difference in mean change in cardiac function between the two groups from baseline to 12 months; for fractional shortening the mean change was 1.4% (SD 4.1) in the idebenone group and 1.6% (SD 2.6) in the placebo group (MD -0.20%, 95% CI -3.07 to 2.67, N = 21), and for ejection fraction the mean change was -1.9% (SD 9.8) in the idebenone group and 0.4% (SD 5.5) in the placebo group (MD -2.30%, 95% CI -9.18 to 4.58, N = 21). The certainty of evidence was very low because of study limitations and very serious imprecision. Reported adverse events were similar between. Based on the available evidence from RCTs, early treatment with ACE inhibitors or ARBs may be comparably beneficial for people with a dystrophinopathy; however, the certainty of evidence is very low. Very low-certainty evidence indicates that adding eplerenone might give additional benefit when early cardiomyopathy is detected. No clinically meaningful effect was seen for growth hormone or idebenone, although the certainty of the evidence is also very low.

Topics: Adolescent; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiovascular Agents; Child; Disease Progression; Eplerenone; Human Growth Hormone; Humans; Lisinopril; Losartan; Male; Muscular Dystrophy, Duchenne; Non-Randomized Controlled Trials as Topic; Perindopril; Placebos; Randomized Controlled Trials as Topic; Stroke Volume; Ubiquinone; Young Adult

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy that causes systolic heart failure (HF) in previously healthy young women. Despite latest remarkable achievement, unifying pathophysiologic mechanism is not well established. Considering close temporal relationship to pregnancy, the recent prolactin theory is promising. Abnormal short form of 16-kDa prolactin may be produced in the oxidative stress milieu, show anti-angiogenic effect and damage cardiovascular structure in late pregnancy. Future study is needed to determine whether abnormal prolactin system is useful as a biomarker for diagnosis and therapy of PPCM. Diagnosis is made based on the finding of left ventricular systolic dysfunction after excluding other causes of HF. A multidisciplinary team approach is essential for acute HF, antepartum, labor and postpartum care. Recovery from left ventricular dysfunction is critical for prognosis. As PPCM can recur and cause serious clinical events, subsequent pregnancy is not recommended. This review focuses on the practical management of PPCM.

Topics: Cardiomyopathies; Cardiovascular Agents; Counseling; Diagnosis, Differential; Female; Humans; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis

Quantifying myocardial fibrosis (MF) with myocardial extracellular volume measures acquired during cardiovascular magnetic resonance promises to transform clinical care by advancing pathophysiologic understanding and fostering novel therapeutics. Extracellular volume quantifies MF by measuring the extracellular compartment depicted by the myocardial uptake of contrast relative to plasma. MF is a key domain of dysfunctional but viable myocardium among others (eg, microvascular dysfunction and cardiomyocyte/mitochondrial dysfunction). Although anatomically distinct, these domains may functionally interact. MF represents pathological remodeling in the heart associated with cardiac dysfunction and adverse outcomes likely mediated by interactions with the microvasculature and the cardiomyocyte. Reversal of MF improves key measures of cardiac dysfunction, so reversal of MF represents a likely mechanism for improved outcomes. Instead of characterizing the myocardium as homogenous tissue and using important yet still generic descriptors, such as thickness (hypertrophy) and function (diastolic or systolic), which lack mechanistic specificity, paradigms of cardiac disease have evolved to conceptualize myocardial disease and patient vulnerability based on the extent of disease involving its various compartments. Specifying myocardial compartmental involvement may then implicate cellular/molecular disease pathways for treatment and targeted pharmaceutical development and above all highlight the role of the cardiac-specific pathology in heart failure among myriad other changes in the heart and beyond. The cardiology community now requires phase 2 and 3 clinical trials to examine strategies for the regression/prevention of MF and eventually biomarkers to identify MF without reliance on cardiovascular magnetic resonance. It seems likely that efficacious antifibrotic therapy will improve outcomes, but definitive data are needed.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Contrast Media; Fibrosis; Heart Failure; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Myocardium; Predictive Value of Tests; Prognosis; Ventricular Remodeling

Cardiomyopathy is found in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies, which are linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects are not limited to DMD but are also present in mild BMD. The hereditary cardiomyopathic hamster of the UM-X7.1 strain is a particular experimental model of heart failure (HF) leading to early death in muscular dystrophy (dystrophin deficiency and sarcoglycan mutation) and heart disease (δ-sarcoglycan deficiency and dystrophin mutation) in human DMD. Using this model, our previous work showed a defect in intracellular sodium homeostasis before the appearance of any apparent biochemical and histological defects. This was attributed to the continual presence of the fetal slow sodium channel, which was also found to be active in human DMD. Due to muscular intracellular acidosis, the intracellular sodium overload in DMD and BMD was also due to sodium influx through the sodium-hydrogen exchanger NHE-1. Lifetime treatment with an NHE-1 inhibitor prevented intracellular Na

Topics: Animals; Calcium; Cardiomyopathies; Cardiovascular Agents; Disease Models, Animal; Heart Failure; Humans; Hydrogen-Ion Concentration; Ion Channels; Muscular Dystrophy, Duchenne; Myocardium; Signal Transduction; Sodium; Sodium-Hydrogen Exchanger 1

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.

Topics: Bromocriptine; Cardiomyopathies; Cardiovascular Agents; Disease Susceptibility; Female; Heart Failure; Heart Transplantation; Hormones; Humans; Hypertension; Incidence; Infant, Newborn; Lactation; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy, Multiple; Puerperal Disorders

Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.

Topics: Action Potentials; Animals; Cardiomyopathies; Cardiovascular Agents; Heart Conduction System; Heart Ventricles; Hemodynamics; Humans; Liver Cirrhosis; Liver Transplantation; Myocardium; Prognosis; Risk Assessment; Risk Factors; Ventricular Function

Glycogen synthase kinase-3 (GSK-3) is one of the few signaling molecules that regulate a truly astonishing number of critical intracellular signaling pathways. It has been implicated in several diseases including heart failure, bipolar disorder, diabetes mellitus, Alzheimer disease, aging, inflammation, and cancer. Furthermore, a recent clinical trial has validated the feasibility of targeting GSK-3 with small molecule inhibitors for human diseases. In the current review, we will focus on its expanding role in the heart, concentrating primarily on recent studies that have used cardiomyocyte- and fibroblast-specific conditional gene deletion in mouse models. We will highlight the role of the GSK-3 isoforms in various pathological conditions including myocardial aging, ischemic injury, myocardial fibrosis, and cardiomyocyte proliferation. We will discuss our recent findings that deletion of GSK-3α specifically in cardiomyocytes attenuates ventricular remodeling and cardiac dysfunction after myocardial infarction by limiting scar expansion and promoting cardiomyocyte proliferation. The recent emergence of GSK-3β as a regulator of myocardial fibrosis will also be discussed. We will review our recent findings that specific deletion of GSK-3β in cardiac fibroblasts leads to fibrogenesis, left ventricular dysfunction, and excessive scarring in the ischemic heart. Finally, we will examine the underlying mechanisms that drive the aberrant myocardial fibrosis in the models in which GSK-3β is specifically deleted in cardiac fibroblasts. We will summarize these recent results and offer explanations, whenever possible, and hypotheses when not. For these studies we will rely heavily on our models and those of others to reconcile some of the apparent inconsistencies in the literature.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Drug Delivery Systems; Enzyme Inhibitors; Glycogen Synthase Kinase 3; Humans

To date, no compounds or interventions exist that treat or prevent sarcomeric cardiomyopathies. Established therapies currently improve the outcome, but novel therapies may be able to more fundamentally affect the disease process and course. Investigations of the pathomechanisms are generating molecular insights that can be useful for the design of novel specific drugs suitable for clinical use. As perturbations in the heart are stage-specific, proper timing of drug treatment is essential to prevent initiation and progression of cardiac disease in mutation carrier individuals. In this review, we emphasize potential novel therapies which may prevent, delay, or even reverse hypertrophic cardiomyopathy caused by sarcomeric gene mutations. These include corrections of genetic defects, altered sarcomere function, perturbations in intracellular ion homeostasis, and impaired myocardial energetics.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Energy Metabolism; Genetic Markers; Genetic Predisposition to Disease; Genetic Therapy; Humans; Molecular Targeted Therapy; Mutation; Phenotype; Sarcomeres; Signal Transduction

In striated muscle, the protein troponin complex turns contraction on and off in a calcium-dependent manner. The calcium-sensing component of the complex is troponin C, which is expressed from the TNNC1 gene in both cardiac muscle and slow-twitch skeletal muscle (identical transcript in both tissues) and the TNNC2 gene in fast-twitch skeletal muscle. Cardiac troponin C (cTnC) is made up of two globular EF-hand domains connected by a flexible linker. The structural C-domain (cCTnC) contains two high affinity calcium-binding sites that are always occupied by Ca(2+) or Mg(2+) under physiologic conditions, stabilizing an open conformation that remains anchored to the rest of the troponin complex. In contrast, the regulatory N-domain (cNTnC) contains a single low affinity site that is largely unoccupied at resting calcium concentrations. During muscle activation, calcium binding to cNTnC favors an open conformation that binds to the switch region of troponin I, removing adjacent inhibitory regions of troponin I from actin and allowing muscle contraction to proceed. Regulation of the calcium binding affinity of cNTnC is physiologically important, because it directly impacts the calcium sensitivity of muscle contraction. Calcium sensitivity can be modified by drugs that stabilize the open form of cNTnC, post-translational modifications like phosphorylation of troponin I, or downstream thin filament protein interactions that impact the availability of the troponin I switch region. Recently, mutations in cTnC have been associated with hypertrophic or dilated cardiomyopathy. A detailed understanding of how calcium sensitivity is regulated through the troponin complex is necessary for explaining how mutations perturb its function to promote cardiomyopathy and how post-translational modifications in the thin filament affect heart function and heart failure. Troponin modulating drugs are being developed for the treatment of cardiomyopathies and heart failure.

Topics: Amino Acid Sequence; Animals; Cardiomyopathies; Cardiovascular Agents; Heart Failure; Humans; Models, Molecular; Molecular Sequence Data; Myocardium; Protein Binding; Protein Conformation; Protein Processing, Post-Translational; Troponin C

Peripartum cardiomyopathy is a form of heart failure occurring at the end of pregnancy or early in the postpartum period. Women may recover, have persistent cardiac dysfunction or suffer complications and death. Women who are African-American, older, hypertensive or have multiple gestation pregnancies have increased risk. Diagnosis and treatment may be delayed due to similarities between symptoms of normal pregnancy and heart failure. Echocardiography is essential for the diagnosis, and B-type natriuretic peptide can be helpful. Treatment for systolic heart failure must be adjusted during pregnancy, and anticoagulation may be indicated. Even after recovery, subsequent pregnancy confers substantial risk of worsening heart failure. Further investigations into the etiology, duration of treatment and risks for relapse are needed.

Topics: Age Factors; Black or African American; Breast Feeding; Cardiomyopathies; Cardiovascular Agents; Echocardiography; Female; Humans; Hypertension; Multiple Birth Offspring; Natriuretic Peptide, Brain; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Risk Factors; United States

Iron overload cardiomyopathy is the major cause of death in transfusion-dependent thalassemia (TDT) patients. Growing evidence demonstrates that combined iron chelators, or the combination of an iron chelator with antioxidant(s) are effective in diminishing myocardial iron deposition and attenuating cardiac dysfunction. This review comprehensively summarizes basic and clinical reports on the therapeutic efficacy of combined iron chelators, or the combination of an iron chelator with antioxidant(s) on the heart. Promising benefits of these treatments in preventing cardiac dysfunction due to iron overload could provide extensive insight into future therapeutic strategies for better treatment and prevention of cardiomyopathy in TDT patients.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Forecasting; Humans; Iron Chelating Agents; Iron Overload

The natural progression of cardiomyopathy in cats can lead to congestive heart failure. This review enumerates commonly and uncommonly used medications that can be used for the long-term treatment of cats that have positively responded to initial management of acute heart failure. The advantages, drawbacks, and authors' preferred approach are presented for each medication.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Cat Diseases; Cats

Treatment of cardiac disease in patients with dystrophinopathies substantially improves outcomes. In this Review, we summarize and discuss findings from the past 20 years and future perspectives for therapeutic options to treat cardiovascular disease in these patients. Their cardiac disease can be subclinical or symptomatic. Presymptomatic treatment with angiotensin-converting-enzyme inhibitors, angiotensin-II-receptor blockers, β-blockers, or mineralocorticoid-receptor antagonists is a well-established method to delay the clinical manifestations of cardiac disease. Treatment of patients with dystrophinopathy and symptomatic cardiac disease, such as heart failure or arrhythmia, follows well-established guidelines for the general treatment of cardiac disease. These treatments improve outcomes, particularly when supported by noncardiovascular measures in the advanced stages of cardiac involvement. Patients with dystrophinopathies and cardiac disease can also benefit from optimal management of scoliosis, noninvasive positive pressure ventilation, and from pain therapy. Molecular therapies for treating cardiac diseases in patients with dystrophinopathies are experimental, but promising.

Topics: Cardiomyopathies; Cardiovascular Agents; Dystrophin; Humans

An overview of pericarditis, cardiomyopathy, and acute myocarditis is presented. Clinical presentation, causes, physical signs, laboratory testing, and various imaging procedures are discussed. Established pharmacologic and mechanical therapies are reviewed. Short-term and long-term prognoses, when relevant, are discussed.

Topics: Acute Disease; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Cardiac Resynchronization Therapy; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Echocardiography; Electrocardiography; Humans; Myocarditis; Pericardial Effusion; Pericarditis

A metamorphosis in the etiology of valvular heart disease (VHD) has occurred over the last 6 decades. In this review, the factors contributing to this metamorphosis, the common causes of VHD today, the relationship of valvular calcification to atherosclerosis and the interrelationship of VHD with other systems/organs are presented.

Topics: Calcinosis; Cardiomyopathies; Cardiovascular Agents; Disease Susceptibility; Endocarditis; Female; Heart Neoplasms; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Iatrogenic Disease; Male; Pedigree; Renal Insufficiency, Chronic

Ischemic heart disease is a significant cause of morbidity and mortality in Western society. Although interventions, such as thrombolysis and percutaneous coronary intervention, have proven efficacious in ischemia and reperfusion injury, the underlying pathological process of ischemic heart disease, 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 ischemia and reperfusion injury and cardiomyopathy. However, despite promising mitochondria-targeted drugs emerging from the laboratory, very few have successfully completed clinical trials. As such, the mitochondrion is a potential untapped target for new ischemic heart disease and cardiomyopathy 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 ischemic heart disease and cardiomyopathy therapy and outlines emerging drug targets in this field.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Disease Models, Animal; Humans; Mitochondria, Heart; Myocardial Ischemia; Treatment Outcome

The ability to make informed benefit-risk assessments for potentially cardiotoxic new compounds is of considerable interest and importance at the public health, drug development, and individual patient levels. Cardiac imaging approaches in the evaluation of drug-induced myocardial dysfunction will likely play an increasing role. However, the optimal choice of myocardial imaging modality and the recommended frequency of monitoring are undefined. These decisions are complicated by the array of imaging techniques, which have varying sensitivities, specificities, availabilities, local expertise, safety, and costs, and by the variable time-course of tissue damage, functional myocardial depression, or recovery of function. This White Paper summarizes scientific discussions of members of the Cardiac Safety Research Consortium on the main factors to consider when selecting nonclinical and clinical cardiac function imaging techniques in drug development. We focus on 3 commonly used imaging modalities in the evaluation of cardiac function: echocardiography, magnetic resonance imaging, and radionuclide (nuclear) imaging and highlight areas for future research.

Topics: Cardiac Imaging Techniques; Cardiomyopathies; Cardiovascular Agents; Echocardiography; Humans; Magnetic Resonance Imaging; Radionuclide Angiography; Risk Assessment

About 50% of patients with sepsis show myocardial involvement characterized by biventricular enlargement, reduced contractility and diastolic dysfunction. This increases the risk of death and leads to an extremely poor prognosis in the case of severe sepsis or septic shock, with full recovery of cardiac function seen in survivors at 7-10 days. The pathogenesis of myocardial dysfunction has long been investigated and, although it is still not fully understood, seems not to be due to reduced coronary flow, but to circulating substances released by pathogens (e.g. endotoxins) and host immuno-inflammatory responses (e.g. cytokines and mechanisms related to nitric oxide). First-line therapy is causal and consists of antibiotics plus the surgical excision of the infectious focus; in the presence of severe sepsis or septic shock, it is also necessary to promptly start circulatory and multiorgan support treatment. This review describes current knowledge concerning the instrumental and clinical characteristics, pathophysiology, prognosis and therapy of myocardial dysfunction during sepsis, and briefly considers possible future therapeutic perspectives.

Topics: Anti-Bacterial Agents; Biomarkers; Cardiomyopathies; Cardiovascular Agents; Combined Modality Therapy; Complement C5a; Counterpulsation; Cytokines; Endothelins; Endotoxins; Humans; Immunotherapy; Mitochondria, Heart; Myocardial Contraction; Nitric Oxide; Prognosis; Sepsis; Toll-Like Receptor 4

Concealed undiagnosed congenital anomalies of coronary arteries (CACA) can cause sudden death of young men. Isolated CACA are detected at 0.6-1.8% of coronary angiographies. Classification of CACA (2002) includes anomalous origin of coronary artery from pulmonary artery, anomalous origin of coronary artery from the aorta, congenital atresia of the left main coronary artery, coronary arteriovenous fistula, coronary artery with myocardial bridge, coronary artery aneurism, coronary artery stenosis. In most cases coronary artery anomalies for long time remain asymptomatic. Clinical picture of anomalous origin of coronary artery from pulmonary artery is often erroneously related to cardiomyopathy or myocarditis because of signs of heart failure. Modern methods of visualization are used for diagnosis of CACA: echocardiography (transthoracic and transesophageal), computer angiotomography (electron beam tomography, multispiral computer tomography), magnetic resonance angiography, thallium stress scintigraphy, single photon positron emission tomography, dobutamine stress echocardiography, endovascular ultrasound study. Coronary angiography is the gold standard for diagnosis of congenital anomalies of coronary arteries. Drug therapy, transluminal balloon angioplasty with stenting or surgical revascularization are indicated to patients with overt clinical picture.

Topics: Adult; Angioplasty, Balloon, Coronary; Asymptomatic Diseases; Cardiomyopathies; Cardiovascular Agents; Coronary Angiography; Coronary Vessel Anomalies; Death, Sudden, Cardiac; Diagnosis, Differential; Echocardiography; Heart Failure; Humans; Magnetic Resonance Angiography; Male; Myocarditis; Tomography, Spiral Computed; Young Adult

Topics: Biomarkers; Cardiac Pacing, Artificial; Cardiomyopathies; Cardiovascular Agents; Heart Failure; Heart-Assist Devices; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney

Apoptosis plays an important role in pathogenesis of primary and secondary cardiomyopathies. It is proposed that antiapoptotic interventions may constitute an effective strategy for these diseases. Some of the antiapoptotic interventions are "old wine in a new bottle" measures already included in the conventional pharmacotherapy. As specific antiapoptotic treatment, caspase inhibitors and anti-TNF-alpha antibody are in early phases of clinical trials in non-cardiac diseases or being contemplated for clinical studies. Non-pharmacotherapies such as cardiac resynchronization and left ventricular assist device also exert cardioprotection partly by antiapoptotic mechanisms. In the field of regenerative medicine, myocardial transplantation of bone marrow-derived stem cells has been performed. Although it is controversial whether it is a true regenerative medicine or the cytokine therapy, antiapoptotic effect of transplanted cells may also have a role in cardioprotection. Moreover, apoptosis may develop despite efforts for cardioprotection in some severe situations of heart failure. Cardiac repair and regeneration by cardiac stem cells may compensate a loss of cardiomyocytes avoiding a deleterious situation. Therefore, protection and/or potentiation of such effects by cardiac stem cells appear to be promising therapeutic strategy in the future. In this review, we discuss about the antiapoptotic interventions for cardiomyopathies in the "real world" and the future of clinical cardiology.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Calcium Channel Blockers; Cardiomyopathies; Cardiovascular Agents; Exercise Therapy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunologic Factors; Myocytes, Cardiac; Prognosis; Stem Cell Transplantation

Cirrhotic cardiomyopathy is a recently identified pathological condition defined as "a chronic cardiac dysfunction in patients with cirrhosis characterized by blunted contractile responsiveness to stress and/or altered diastolic relaxation with electrophysiological abnormalities, in the absence of known cardiac disease". Overall there seems to be a link between the progression of liver function impairment, the development of portal hypertension and the degree of hyperdynamic circulation, the hallmark of the deranged cardiovascular function in advanced liver diseases. Although mechanical factors contribute to much of the increased resistance within the liver in portal hypertension, there is clearly a vasculogenic component to the development, perpetuation and progression of this syndrome as well. The vascular component of portal hypertension includes an increase in splanchnic blood flow, as well as an increase in intrahepatic vascular resistance. Dysregulation of the nitric oxide system appears to play a key role in both these processes with a paradoxical reduction of intrahepatic availability despite increased disposal in the splanchnic and other vascular districts with adverse effects on cardiac function and structure. Nevertheless, other putative mediators of cardiac damage in cirrhosis have been proposed and their role in the pathogenesis of cirrhotic cardiomyopathy investigated. This review involves a discussion of data achieved on pathogenesis and clinical features of cirrhotic cardiomyopathy but mainly focuses on considerations on potential therapeutic targets, in the light of the evidence that this mainly subclinical condition merges to clinical relevance when challenged with those therapeutic interventions and procedures currently employed to treat the major complications of cirrhosis that might produce a negative impact on the cardiovascular system.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Fibrosis; Humans

Heart failure secondary to ischemic heart disease, hypertension, and myocardial infarction is a common cause of death in developed countries. Although pharmacological therapies are very effective, poor prognosis and shorter life expectancy of heart disease patients clearly indicate the need for alternative interventions to complement the present therapies. Since the progression of heart disease is associated with the loss of myocardial cells, the concept of donor cell transplantation into host myocardium is emerging as an attractive strategy to repopulate the damaged tissue. To this end, a number of donor cell types have been tested for their ability to increase the systolic function of diseased hearts in both experimental and clinical settings. Although initial clinical trials with bone marrow stem cells are encouraging, long-term consequences of such interventions are yet to be rigorously examined. While additional laboratory studies are required to address several issues in this field, there is also a clear need for further characterization of drug interactions with donor cells in these interventions. Here, we provide a brief summary of current pharmacological and cell-based therapies for heart disease. Further, we discuss the potential of various donor cell types in myocardial repair, mechanisms underlying functional improvement in cell-based therapies, as well as potential interactions between pharmacological and cell-based therapies.

Topics: Adult Stem Cells; Animals; Cardiomyopathies; Cardiovascular Agents; Cell Differentiation; Cell Transplantation; Embryonic Stem Cells; Humans; Myocytes, Cardiac; Regenerative Medicine; Stem Cell Transplantation; Treatment Outcome

The phospholipases associated with the cardiac sarcolemmal (SL) membrane hydrolyze specific membrane phospholipids to generate important lipid signaling molecules, which are known to influence normal cardiac function. However, impairment of the phospholipases and their related signaling events may be contributory factors in altering cardiac function of the diseased myocardium. The identification of the changes in such signaling systems as well as understanding the contribution of phospholipid-signaling pathways to the pathophysiology of heart disease are rapidly emerging areas of research in this field. In this paper, I provide an overview of the role of phospholipid-mediated signal transduction processes in cardiac hypertrophy and congestive heart failure, diabetic cardiomyopathy, as well as in ischemia-reperfusion. From the cumulative evidence presented, it is suggested that phospholipid-mediated signal transduction processes could serve as novel targets for the treatment of the different types of heart disease.

Topics: Animals; Cardiomegaly; Cardiomyopathies; Cardiovascular Agents; Diabetes Complications; Enzyme Inhibitors; Heart Diseases; Heart Failure; Humans; Myocardial Reperfusion Injury; Myocardium; Phospholipases; Phospholipids; Sarcolemma; Signal Transduction

The use of anthracyclines in the treatment of acute lymphoblastic leukemia is limited by associated cardiotoxic effects, which can result in cardiomyopathy and congestive heart failure, and may be irreversible. Anthracycline-induced cardiotoxicity in long-term survivors of childhood cancer is characterized by reduced left ventricular wall thickness and mass, which is indicative of decreased cardiac muscle and depressed left ventricular contractility which is indicative of unhealthy heart muscle. Risk factors for anthracycline-induced cardiotoxicity include high cumulative anthracycline doses, high anthracycline dose intensity, and radiotherapy. Radiotherapy in patients with cancer treated with anthracyclines can exacerbate anthracycline-induced cardiac tissue damage. Several studies have shown that cardiomyopathy disease progression can be delayed in adults by using angiotensin-converting enzyme inhibitors such as enalapril. Studies in long-term survivors of pediatric cancer showed that enalapril has significant benefits in preventing cardiac functional deterioration on a short-term basis, but this is not sustained. Anthracycline-associated cardiotoxic effects can be combatted by preventing cardiac injury during chemotherapy administration. There is evidence that dexrazoxane significantly reduces the cardiotoxicity associated with anthracyclines such as daunorubicin, doxorubicin, and epirubicin in adult patients with a wide range of tumor types. A study of the efficacy of dexrazoxane in reducing doxorubicin-induced cardiotoxicity in children and adolescents with high-risk acute lymphoblastic leukemia, showed that significantly fewer dexrazoxane-treated patients (21%) had elevated serum cardiac troponin (a biomarker of acute myocardial injury) levels than patients treated with chemotherapy alone (50%; P <.001). Dexrazoxane was also shown to have no effect on the event-free survival rate at 2.5 years, emphasizing that it does not detrimentally affect the efficacy of anthracycline therapy.

Topics: Adolescent; Adult; Anthracyclines; Antineoplastic Agents; Cardiomyopathies; Cardiovascular Agents; Child; Disease Progression; Heart; Heart Failure; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Razoxane; Risk Factors; Survivors

Cardiac amyloidosis is a well-known but clinically rare cause of heart failure that has historically been associated with a poor prognosis. Cardiac amyloidosis involves fibril formation from one of several underlying conditions, and the course of illness and prognosis varies among these conditions. Evolving treatment strategies for patients with primary systemic amyloidosis have given this subset of cardiac amyloidosis patients a cause for hope. The identification and appropriate referral of patients in whom this condition is suspected will help to improve the likelihood of successful therapy and long-term survival.

Topics: Amyloidosis; Cardiomyopathies; Cardiovascular Agents; Clinical Trials as Topic; Heart Failure; Humans; Prognosis

The nthracycline antibiotics are among the most widely used and effective anticancer drugs. The therapeutic efficacy of this class of drugs is limited by cumulative cardiac toxicity. Dexrazoxane is the only clinically approved cardioprotective agent used in anthracycline-containing anticancer therapy. Its cardioprotective action allows the use of a much higher cumulative dose of anthracyclines and improvement in the effectiveness of treatment. Anthracyclines form complexes with iron ions, which are very active in the production of reactive oxygen species responsible for the lipid peroxidation of mitochondrial and endoplasmatic reticulum membranes. This process seems to be the major cause of anthracycline-induced cardiotoxicity. Dexrazoxane exerts its protective effects by rapid and complete binding of ferric and ferrous ions, even by displacing the metal ions from complexes with anthracyclines. Besides its cardioprotective effect, dexrazoxane also exhibits anticancer properties. Like other derivatives of bisdioxopiperazine, dexrazoxane is a catalytic inhibitor of eukaryotic DNA topoisomerase II, the key enzyme controlling DNA topology and contributing to the replication and transcription processes. Dexrazoxane is able to lock topoisomerase II at the stage of the enzyme reaction cycle where the enzyme forms a closed clamp around the DNA. This phenomenon seems to be the main reason for the generation of DNA double-strand breaks by dexrazoxane as well as its cytotoxicity against quickly proliferating cancer cells. Other effects of its topoisomerase II catalytic inhibition is the induction of cell differentiation and apoptosis. Dexrazoxane may be used not only as a cardioprotective agent, but also as a modulator of action of some anticancer drugs by enhancing their selectivity or by delaying the development of multidrug resistance.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Chelating Agents; Neoplasms; Razoxane

Topics: Cardiac Pacing, Artificial; Cardiomyopathies; Cardiovascular Agents; Coronary Angiography; Echocardiography; Heart Transplantation; Humans; Magnetic Resonance Imaging; Myocardial Ischemia; Patient Selection; Positron-Emission Tomography; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity

Anthracyclines play a major role in chemotherapeutic regimens for a variety of childhood cancers, but produce dose-related cardiotoxicity. Dexrazoxane, a chelating agent that binds iron intracellularly, has been cautiously included in anthracycline-based regimens. Our understanding of anthracycline and dexrazoxane pharmacokinetics in children is very limited. In addition, the administration schedule used for adults (bolus dexrazoxane prior to bolus anthracycline) may not be the best to attain both short- and long-term cardioprotection. Dexrazoxane could diminish the anti-tumor activity of and/or increase toxicities from anthracyclines. Pediatric oncologists must be assured this intervention does not diminish the success in curing children with cancer.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Humans; Neoplasms; Razoxane

Topics: Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Humans; Myocardial Ischemia; Risk Assessment; Ventricular Fibrillation

To provide a review of the cardiac and obstetrical literature regarding the development of peripartum cardiomyopathy and, in particular, to examine risk factors, incidence, diagnosis, prognosis, and evidence-based treatment modalities.. An extensive review of the current literature.. Peripartum cardiomyopathy is a cardiomyopathy of unknown cause that occurs in pregnant females, most commonly in the early postpartum period. It shares many clinical characteristics with idiopathic dilated cardiomyopathy but occurs at a younger age and is associated with a better prognosis. Diagnosis is based upon the clinical presentation of congestive heart failure and objective evidence of left ventricular systolic dysfunction. Conventional pharmacologic therapy for congestive heart failure, such as diuretics, digoxin, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and beta-adrenergic blockers, are routinely used and are quite effective. For those patients who remain refractory to conventional pharmacologic therapy, cardiac transplantation and mechanical circulatory support are viable options.. Mortality rates in peripartum cardiomyopathy have decreased, and this is most likely related to advances over the past 5 yrs in medical therapy for heart failure. Aggressive use of implantable defibrillators has significantly reduced the risk of sudden death in these patients. For >50% of peripartum cardiomyopathy patients, left ventricular function normalizes with pharmacologic therapy. However, subsequent pregnancies almost always are associated with recurrence of left ventricular systolic dysfunction.

Topics: Cardiomyopathies; Cardiovascular Agents; Critical Care; Defibrillators, Implantable; Female; Heart Failure; Humans; Pregnancy; Pregnancy Complications, Cardiovascular

Doxorubicin is a chemotherapeutic agent successfully used in the treatment of a wide range of cancers. However, with cumulative doses, doxorubicin also is known to have cardiotoxic effects, including cardiomyopathy and heart failure. Research is targeted at maximizing the antitumor effects of doxorubicin while attenuating the potential cardiotoxicity. Concurrent therapies under study are combinations of doxorubicin with drugs such as probucol, carvedilol (Coreg, GlaxoSmithKline, Research Triangle Park, NC), dexrazoxane (Zinecard, Pfizer, New York, NY), and antioxidant nutrients. As patient advocates, nurses must be aware of current research, treatment options, and evidence-based patient resources and be diligent in assessing and educating patients before, during, and after treatment with doxorubicin.

Topics: Antibiotics, Antineoplastic; Antihypertensive Agents; Antioxidants; Cardiomyopathies; Cardiovascular Agents; Doxorubicin; Drug Combinations; Drug Monitoring; Drug Therapy, Combination; Humans; Iron Chelating Agents; Nurse's Role; Nursing Assessment; Oncology Nursing; Patient Education as Topic; Risk Factors

Although the features of diabetic cardiomyopathy, atherosclerosis, and nephropathy have been clinically characterized, the pathogenesis and the mechanisms underlying the abnormalities in the diabetic heart and kidney are not fully understood. During the past several years, in an attempt to discover interventions for diabetes-related complications, researchers have refocused their attention from the hemodynamic aspects of the disease to the biochemical interactions of glucose and proteins. Diabetes is a disorder of chronic hyperglycemia, and glucose participates in diabetic complications such as atherosclerosis, cardiac dysfunction, and nephropathy. Chronic hyperglycemia accelerates the reaction between glucose and proteins and leads to the formation of advanced glycation end products (AGE), which form irreversible cross-links with many macromolecules such as collagen. In diabetes, these AGE accumulate in tissues at an accelerated rate. The development of the novel compound dimethyl-3-phenacylthiazolium chloride (alagebrium chloride), which chemically breaks AGE cross-links, led to several preclinical animal studies that showed an attenuation or reversal of disease processes of the heart and kidney. In diabetes, AGE not only structurally stiffen structural collagen backbones but also act as agonists to AGE receptors (RAGE) on various cell types, which stimulate the release of profibrotic growth factors, promote collagen deposition, increase inflammation, and ultimately lead to tissue fibrosis. In the heart, large vessels, and kidney, these reactions produce diastolic dysfunction, atherosclerosis, and renal fibrosis. Administration of the cross-link breaker alagebrium chloride in these diabetic animals attenuates these pathologic phenomena, restoring functionality to the heart, vasculature, and kidney.

Topics: Animals; Atherosclerosis; Blood Glucose; Cardiomyopathies; Cardiovascular Agents; Diabetic Angiopathies; Diabetic Nephropathies; Fibrosis; Glycation End Products, Advanced; Humans; Myocardium; Thiazoles

Peripartum cardiomyopathy is a rare and life-threatening disease of unknown etiology. This diagnosis should be limited to previously healthy women who present with congestive heart failure (CHF) and decreased left ventricular systolic function in the last month of pregnancy or within 5 months after delivery. The diagnosis is not made in the presence of other causes of cardiac dysfunction. Patients who fail to demonstrate improvement within 2 weeks after the onset of symptoms should be evaluated for myocarditis. The type and duration of heart failure treatment is determined by the patient's heart performance at rest and with exertion. Those with normal left ventricular function at rest and with exercise or dobutamine have a good prognosis, and their medical therapy can be tapered off or discontinued over a period of 6-12 months. Patients with normal ventricular function at rest, but abnormal response to exercise should be treated for long periods of time with angiotensin converting enzyme (ACE) inhibitors or beta-blockers. Patients who continue to have depressed LV function have a poor prognosis and require treatment with appropriate medications for the rest of their lives. Pharmacological treatment includes ACE inhibitors, beta-blocking agents, diuretics, digoxin, and anticoagulation. Angiotensin converting enzyme inhibitors are used only after delivery because of their teratogenic effects. Patients who fail to recover may require inotropic therapy, intra-aortic balloon pump and left ventricular assist device as needed. Cardiac transplantation should be considered for patients who fail therapy.

Topics: Adult; Cardiomyopathies; Cardiovascular Agents; Female; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis

A cardiac localization is one of the most severe manifestations of sarcoidosis and may cause sudden death (ventricular tachycardia or atrial ventricular block III) or restrictive cardiomyopathy. Lesions are most frequently observed in the interventricular septum and the free left wall. Granulomatous infiltation can provoke nonspecific clinical, electric and echocardiographic signs, which, associated with regressive dipyridamol uptake on tomoscintigraphy, are suggestive of cardiac sarcoidosis. The diagnosis of cardiac sarcoidosis is based on the presence of systemic sarcoidosis, histological evidence of granuloma and the lack of another cause of cardiomyopathy. Corticosteroid therapy is indicated, associated with specific cardiologic treatments.

Topics: Anti-Inflammatory Agents; Biopsy; Cardiomyopathies; Cardiomyopathy, Restrictive; Cardiovascular Agents; Death, Sudden, Cardiac; Dipyridamole; Echocardiography; Electrocardiography; Heart Block; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Sarcoidosis; Steroids; Tachycardia, Ventricular; Vasodilator Agents

Topics: Alcoholism; Animals; Cardiomyopathies; Cardiovascular Agents; Diagnosis, Differential; Free Radicals; Humans; Muscle Proteins; Prognosis; Temperance

Diastolic dysfunction is the underlying problem in one third of patients with heart failure, but it is still not well understood. Carefully excluding other causes of heart failure and recognizing indicators of diastolic dysfunction on invasive and noninvasive tests are important in establishing the diagnosis and in guiding therapy. Left ventricular relaxation and stiffness and left atrial function are the most important factors acting together to maintain adequate cardiac output under normal filling pressure. Echocardiography is the most important tool for the diagnosis of diastolic heart dysfunction. It is portable, safe, and excludes other causes of heart failure, such as valvular disease. Diuretics can be used to reduce volume overload, but caution is advised, as aggressive diuresis decreases stroke volume more in diastolic dysfunction than in systolic dysfunction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiac Output; Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Diastole; Diuretics; Echocardiography; Electrocardiography; Heart Failure; Humans; Ventricular Dysfunction, Left

Pheochromocytoma in pregnancy is very rare but it is associated with very high maternal and fetal mortality. Therefore, it is important to include pheochromocytoma in the differential diagnosis of hypertension associated with pregnancy. It is difficult to make a diagnosis of pheochromocytoma in pregnancy before delivery. The characteristic symptoms of pheochromocytoma could be initiated during delivery because the process of delivery, general anesthesia, fetal movement, induce acute surge of catecholamine release, which could also induce cardiomyopathy. Early diagnosis and intensive care can affect the prognosis of cardiomyopathy induced by pheochromocytoma. Proper management with alpha-blockade, beta-blockade and angiotension converting enzyme inhibitor could acutely reverse the course of cardiomyopathy.

Topics: Adrenal Gland Neoplasms; Adult; Cardiomyopathies; Cardiovascular Agents; Disease-Free Survival; Echocardiography; Electrocardiography; Female; Humans; Pheochromocytoma; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Tomography, X-Ray Computed

The chronic cardiotoxic effects of anthracyclines were initially detected in clinical trials with daunorubicin and doxorubicin. The clinical importance of anthracycline-induced chronic cardiotoxicity has led to the development of several animal models of this syndrome. Animal species examined in detail as models of this cardiac toxicity include the rabbit, the normotensive and spontaneously hypertensive rat, the mouse, the pig, and the dog. The advantages and disadvantages of these animal models differ according to species: small animals can be used for comparative investigations of anthracycline analogues and/or protectors, which may be available only in limited amounts, while large animals can be used for studies in which evaluation of cardiac function are to be made. Among the various animals examined, the spontaneously hypertensive rat and the beagle dog are considered the most suitable small and large animal models, respectively, because of the reproducibility of the lesions induced by anthracyclines in the two species. A variety of pharmacologic agents has been tested for cardioprotective activity. The most successful of these agents are those that function as antioxidants, because they either scavenge reactive oxygen species or prevent their formation. The most clinically useful of these agents is ICRF-187 (dexrazoxane), which has been found to be cardioprotective in all animal models.

Topics: Animals; Anthracyclines; Antineoplastic Agents; Cardiomyopathies; Cardiovascular Agents; Disease Models, Animal; Dogs; Heart; Mice; Rabbits; Rats; Razoxane; Swine

Doxorubicin (DOX) plus paclitaxel is an active combination for patients with metastatic breast cancer, producing objective response in approximately 50% to 90% of patients. The drugs may be combined using different doses and schedules. When 60 mg/m2 of DOX is given by intravenous bolus followed 15 to 30 minutes later by 200 mg/m2 of paclitaxel (given as a 3-hour infusion), approximately 20% of patients will have a substantial decrease in their left ventricular ejection fraction below normal after four cycles of therapy (or a cumulative DOX dose of 240 mg/m2). Approximately 4% will have symptoms of congestive heart failure. After eight cycles of therapy, or a cumulative DOX dose of 480 mg/m2, approximately 50% of patients will have a decrease in left ventricular ejection fraction below normal and 20% of patients will develop clinical evidence of congestive heart failure. This is a higher than expected incidence of congestive heart failure when compared with retrospectively derived historical data. Paclitaxel increases the area under the curve of DOX by approximately 30% when given before or after DOX, providing an explanation for this phenomenon. Several strategies seem to be associated with a reduced incidence of cardiac toxicity, including the use of dexrazoxane with the combination, restricting the cumulative DOX dose to < or = 360 mg/m2, increasing the interval between administration of the drugs, and use of other taxanes (eg, docetaxel) or other less cardiotoxic anthracyclines (eg, epirubicin or liposomal DOX). Most of these strategies were evaluated in noncomparative phase I/II trials, and further study will be required to determine the role of anthracycline-taxane combinations in the management of patients with operable and advanced breast cancer, and to determine a combination that has the most favorable therapeutic index.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Cardiomyopathies; Cardiovascular Agents; Clinical Trials as Topic; Doxorubicin; Drug Administration Schedule; Humans; Paclitaxel; Razoxane

Anthracyclines are one of the most active classes of antineoplastic compounds. The limiting toxicity of this class of drugs is a cumulative, dose-related diffuse cardiomyopathy, which occurs in up to 20% of patients with a cumulative doxorubicin dose of 450 to 500 mg/m2. Higher incidences of cardiac toxicity have more recently been reported when doxorubicin was combined with other agents such as paclitaxel. Methods to reduce or prevent this toxicity have been a major area of investigation. The use of anthracycline analogs has had limited success. Available data using anthracyclines incorporated into liposomes suggest that cardiac toxicity is significantly reduced. Dexrazoxane, a bisdioxopiperazine that chelates intracellular iron and prevents free radical formation in cardiac muscle, has been demonstrated to be cardioprotective in patients receiving anthracyclines. This article reviews the data regarding the mechanism of anthracycline-induced cardiac toxicity, diagnostic procedures, and methods of reducing this toxicity.

Topics: Adult; Animals; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cardiomyopathies; Cardiovascular Agents; Chelating Agents; Child; Clinical Trials as Topic; Diagnostic Imaging; Humans; Liposomes; Razoxane

Primary care physicians have an important role in timely diagnosis and appropriate treatment of gravid patients with cardiac disorders. Health of the mother and child can be optimized with thorough understanding of the pathophysiology of cardiac disorders during pregnancy, especially those with potentially serious effects, such as peripartum cardiomyopathy and acute myocardial infarction. Mitral stenosis often manifests for the first time during pregnancy. Mitral valve prolapse is usually benign but in some cases necessitates antibiotic prophylaxis for delivery. Pregnancy in women with prosthetic cardiac valves may expose mother and child to risks that can be minimized with appropriate safeguards.

Topics: Cardiomyopathies; Cardiovascular Agents; Contraindications; Female; Heart Diseases; Humans; Mitral Valve Stenosis; Myocardial Ischemia; Pregnancy; Pregnancy Complications, Cardiovascular

A review is presented of the various types of cardiotoxicity associated with the clinical use of doxorubicin, a highly effective antineoplastic agent of the anthracycline family. Acute toxicity is related to rapid intravenous administration of the drug and is manifested by vasodilatation, hypotension and cardiac arrhythmias. Subacute toxicity is very uncommon. It develops early in the course of therapy and is characterized by myocarditis and pericarditis. Chronic toxicity is the most common form of doxorubicin-induced cardiac toxicity. It is manifested by chronic dilated cardiomyopathy, which develops late in the course of therapy or shortly after its termination. Morphologic changes are characteristic and consist of myofibrillar loss and cytoplasmic vacuolization (which is due to dilatation of the sarcoplasmic reticulum) of the myocytes. The damaging effects of reactive oxygen species, generated by the interaction of doxorubicin with iron, play a critically important role in the pathogenesis of the chronic cardiotoxicity. Other factors related to this toxicity include inhibition of DNA topoisomerase II, stimulation of certain immune responses and a diversity of other biochemical effects on various cellular organelles. Doxorubicin induces apoptosis in a variety of cell types, but not in cardiac myocytes. The chronic cardiotoxicity of doxorubicin is significantly attenuated by chelation of iron by ICRF-187 (dexrazoxane). A greatly delayed type of doxorubicin cardiotoxicity has been recently found to occur in survivors of childhood cancers who were treated with doxorubicin without any immediate adverse effects, but develop chronic cardiomyopathy at periods of time ranging up to 15 years later. The pathogenesis of this type of toxicity remains to be determined.

Topics: Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Doxorubicin; Humans

The dose-limiting toxicity of the widely used anticancer agent, doxorubicin, is a destructive, irreversible and progressive cardiomyopathy. Prevention of this cardiotoxicity without reduction of antitumour efficacy or the production of new toxicities has therefore been a long-time therapeutic goal. It has now been largely achieved by prior administration of dexrazoxane (DXRz; Cardioxane in Europe; Zinecard in North America; ICRF 187). Six randomized, controlled clinical trials in breast and lung cancer and in soft tissue sarcomas of children have shown a 90% reduction in doxorubicin-induced cardiotoxicity. The results of all these trials lead to the conclusion that DXRz permits: (1) cardiotoxic doses of doxorubicin to be given without cardiotoxicity; (2) patients with increased cardiac risk factors to be treated with full doses of dioxorubicin; (3) second-line treatment with other cardiotoxic drugs.

Topics: Adult; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Doxorubicin; Female; Humans; Male; Neoplasms; Razoxane; Treatment Outcome

The incidence and prevalence of congestive heart failure increase exponentially with advancing age. Congestive heart failure in the elderly is characterized by a multifactorial etiology, a high proportion of accompanying degenerative changes of the cardiovascular system and age-specific problems regarding diagnosis and treatment. The treatment strategy is the same as in younger patients, but the higher incidence of adverse effects and complications demands special awareness. The majority of decompensations leading to hospitalization are precipitated by insufficient compliance in life style change and drug intake.

Topics: Adult; Aged; Aging; Arrhythmias, Cardiac; Arteriosclerosis; Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Heart Failure; Humans; Hypertension; Incidence; Middle Aged; Prevalence

Fifteen patients (8 men, 7 women) with right ventricular dysplasia (RVS) from the greater Zürich area are described. Two thirds of these patients were younger than 30 years at first manifestation. 12 presented with ventricular tachycardia of left bundle branch block type. Other forms of arrhythmia (supraventricular tachycardia, sinus node dysfunction) or condition disturbances were documented in 9 subjects. 6 patients had additional symptoms of congestive heart failure; in 3 of them this was the only symptom. 12-lead ECG at rest showed precordial T-negativity (1 pacemaker ECG not interpretable) in 14/15 subjects. Signal averaged ECG revealed late potentials as well as spectral turbulence in the Y or Z leads. Echocardiography yielded typical local abnormalities in the whole study cohort and all but 2 patients showed decreased right ventricular ejection fraction and right heart dilatation. Moreover, left ventricular ejection fraction was concomitantly impaired in 6 subjects. 4 of these 6 individuals suffered from further impairment of left ventricular function within a time period of 19 to 47 months. Recurrent ventricular tachycardia was documented in 11 patients. 2 subjects underwent heart transplantation because of severe progressive right heart failure. One subject died shortly after diagnosis and autopsy confirmed nearly total absence of right ventricular myocardium. This extreme form of right ventricular dysplasia corresponds to Uhl's anomaly. Thus, recurrent ventricular arrhythmias, in particular ventricular tachycardia of left bundle branch block type, together with precordial T-negativity without signs of ischemic heart disease, is highly suggestive of RVD. Echocardiography allows reliable diagnosis. Concomitant left ventricular involvement is frequent. Considering that the etiology and pathogenesis of this disease are unknown, the term right ventricular cardiomyopathy, rather than right ventricular dysplasia, seems more accurate.

Topics: Adult; Aged; Biopsy; Cardiomyopathies; Cardiovascular Agents; Female; Heart Function Tests; Heart Ventricles; Humans; Male; Middle Aged; Myocardium

Treatment of patients with heart failure due to major ventricular systolic dysfunction should aim not only at symptomatic but also at prognostic improvement. If correction of the underlying problem is not possible, treatment should slow down the progression of cardiac failure and eliminate triggers for sudden cardiac death due to electromechanical dissociation or arrhythmias. In every patient with chronic congestive heart failure screening for myocardial ischemia and complete revascularization is mandatory, if possible. In patients with coronary artery disease and diminished systolic function, beta-blockade may improve prognosis by reducing ischemic events and sudden cardiac death. The incidence of life-threatening arrhythmias in patients with heart failure may be reduced by eliminating facilitating factors like electrolyte disturbances, altered autonomic tone and raised intracardiac pressure rather than by antiarrhythmic medical treatment itself. One of the most important prognostic aspects in treatment is the interference with the development of the cardiomyopathy of overload, uniformly observed in chronic congestive heart failure. Modification of mechanical and neuroendocrine stimuli may postpone myocardial hypertrophy and interstitial hyperplasia as a consequence of altered gene expression. Early treatment with ACE inhibitors and in certain patients with betablockers are the most promising strategies to delay the progression of the disease. In contrast, positive inotropic drugs, including digitalis and phosphodiesterase inhibitors, do not improve prognosis. Calcium antagonists should also be used with restriction, as Verapamil and Diltiazem, but also Nifedipine may adversely affect the outcome in congestive heart failure patients.

Topics: Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Heart Failure; Humans; Myocardial Revascularization; Prognosis

Fifty years ago it was observed that a sudden restoration of antegrade flow in the ischemic myocardium can lead to a paradoxical deterioration of cardiac function. The implications of this observation were only fully understood during the last decade when, thanks to the improvement of angiographic methods and the development of thrombolytic agents, reperfusion could be demonstrated in humans. At present, it is generally accepted that reperfusion phenomena play an important role in ischemic heart disease and probably the reperfusion damage, which may occur as a consequence of thrombolytic therapy, reduces the finally observed effect of these agents. During the last few years, many agents have been studied for their potential to reduce reperfusion damage. Several groups of these agents and their mechanism of action are discussed in this report. Special attention is paid to the possible effects of angiotensin converting enzyme inhibitors in this situation, as this group of agents combine several interesting characteristics of other groups, among which are their effects on norepinephrine levels, prostaglandin synthesis, and free radicals.

Topics: Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Humans; Myocardial Reperfusion Injury

The landmark STICH trial found that surgical revascularization compared to medical therapy alone improved survival in patients with heart failure (HF) of ischaemic aetiology and an ejection fraction (EF) ≤ 35%. However, the interaction between the burden of medical co-morbidities and the benefit from surgical revascularization has not been previously described in patients with ischaemic cardiomyopathy.. The STICH trial (ClinicalTrials.gov Identifier: NCT00023595) enrolled patients ≥ 18 years of age with coronary artery disease amenable to coronary artery bypass grafting (CABG) and an EF ≤ 35%. Eligible participants were randomly assigned 1:1 to receive medical therapy (MED) (n = 602) or MED/CABG (n = 610). A modified Charlson co-morbidity index (CCI) based on the availability of data and study definitions was calculated by summing the weighted points for all co-morbid conditions. Patients were divided into mild/moderate (CCI 1-4) and severe (CCI ≥ 5) co-morbidity. Cox proportional hazards models were used to evaluate the association between CCI and outcomes and the interaction between severity of co-morbidity and treatment effect. The study population included 349 patients (29%) with a mild/moderate CCI score and 863 patients (71%) with a severe CCI score. Patients with a severe CCI score had greater functional limitations based on 6-min walk test and impairments in health-related quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire. A total of 161 patients (Kaplan-Meier rate = 50%) with a mild/moderate CCI score and 579 patients (Kaplan-Meier rate = 69%) with a severe CCI score died over a median follow-up of 9.8 years. After adjusting for baseline confounders, patients with a severe CCI score were at higher risk for all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.19-1.74; P < 0.001). There was no interaction between CCI score and treatment effect on survival (P = 0.756).. More than 70% of patients had a severe burden of medical co-morbidities at baseline, which was independently associated with increased risk of death. There was not a differential benefit of surgical revascularization with respect to survival based on severity of co-morbidity.

Topics: Cardiomyopathies; Cardiovascular Agents; Comorbidity; Coronary Artery Bypass; Coronary Artery Disease; Cost of Illness; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Quality of Life; Severity of Illness Index; Stroke Volume; Survival Analysis; Walk Test

Levosimendan is a promising new inodilator agent but its effectiveness in peripartum cardiomyopathy (PPCM) has not been tested in a clinical trial. The authors sought to evaluate the effect of levosimendan therapy and to determine the predictors of clinical outcome in patients with PPCM.. The authors prospectively randomized 24 consecutive women with PPCM. Twelve patients (control group) were randomized to conventional heart failure therapy and 12 patients (levosimendan group) were randomized to levosimendan in addition to the conventional therapy. Mean follow-up period was 20.9 ± 9 months (ranged 12-38 months). The two groups did not differ in baseline demographic and echocardiographic characteristics. Eleven patients (45.8%) recovered completely (6 in control group and 5 in levosimendan group, p > 0.05), 6 died (25%) (3 in control group and 3 in levosimendan group), and 7 (29.1%) were left with persistent left ventricular dysfunction (PLVD) (3 in control group and 4 in levosimendan group, p > 0.05). There were significant differences in baseline characteristics between deceased patients and survivors including left ventricular end-diastolic diameter (7.1 ± 0.6 vs. 6.4 ± 0.5 cm, p = 0.031), left ventricular end-systolic diameter (LVESD) (6.4 ± 0.8 vs. 5.5 ± 0.6 cm, p = 0.027), left ventricular ejection fraction (LVEF) (19.7 vs. 27.4%, p = 0.025), and left atrial diameter (4.9 ± 0.3 vs. 4.3 ± 0.4 cm, p = 0.011).. Addition of levosimendan to conventional therapy did not improve outcome in patients with PPCM. In patients with PLVD or patients who died, LVEF, LVESD and left atrial diameter were worse than those with complete resolution.

Topics: Adult; Cardiomyopathies; Cardiovascular Agents; Drug Therapy, Combination; Echocardiography; Female; Heart Ventricles; Humans; Hydrazones; Peripartum Period; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Cardiovascular; Pyridazines; Simendan; Treatment Outcome; Vasodilator Agents; Ventricular Function, Left; Young Adult

This study attempted to assess the incidence and outcome of anthracycline cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood solid tumors. The dexrazoxane group included 47 patients and the control group of historical cohort included 42. Dexrazoxane was given in the 10:1 ratio to doxorubicin. Fractional shortening and systolic and diastolic left ventricular diameters were used to assess the cardiac function. The median follow-ups were 54 months in the dexrazoxane group and 86 months in the control group. The mean cumulative doses of doxorubicin were 280.8+/-83.4 mg/m(2) in the dexrazoxane group and 266.1+/-75.0 mg/m(2) in the control group. The dexrazoxane group experienced significantly fewer cardiac events (27.7% vs. 52.4%) and less severe congestive heart failure (6.4% vs. 14.3%) than the control group. Thirteen cardiotoxicities including one cardiac death and 2 congestive heart failures occurred in the dexrazoxane group, and 22 cardiotoxicities including 2 cardiac deaths and 4 congestive heart failures, in the control group. Five year cardiac event free survival rates were 69.2% in the dexrazoxane group and 45.8% in the control group (P=0.04). Dexrazoxane reduces the incidence and severity of early and late anthracycline cardiotoxicity in childhood solid tumors.

Topics: Adolescent; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Cohort Studies; Disease-Free Survival; Doxorubicin; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Infant; Male; Neoplasms; Razoxane; Ventricular Function, Left

Doxorubicin chemotherapy is associated with cardiomyopathy. Dexrazoxane reduces cardiac damage during treatment with doxorubicin in children with acute lymphoblastic leukaemia (ALL). We aimed to establish the long-term effect of dexrazoxane on the subclinical state of cardiac health in survivors of childhood high-risk ALL 5 years after completion of doxorubicin treatment.. Between January, 1996, and September, 2000, children with high-risk ALL were enrolled from nine centres in the USA, Canada, and Puerto Rico. Patients were assigned by block randomisation to receive ten doses of 30 mg/m² doxorubicin alone or the same dose of doxorubicin preceded by 300 mg/m² dexrazoxane. Treatment assignment was obtained through a telephone call to a centralised registrar to conceal allocation. Investigators were masked to treatment assignment but treating physicians and patients were not; however, investigators, physicians, and patients were masked to study serum cardiac troponin-T concentrations and echocardiographic measurements. The primary endpoints were late left ventricular structure and function abnormalities as assessed by echocardiography; analyses were done including all patients with data available after treatment completion. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00165087.. 100 children were assigned to doxorubicin (66 analysed) and 105 to doxorubicin plus dexrazoxane (68 analysed). 5 years after the completion of doxorubicin chemotherapy, mean left ventricular fractional shortening and end-systolic dimension Z scores were significantly worse than normal for children who received doxorubicin alone (left ventricular fractional shortening: -0·82, 95% CI -1·31 to -0·33; end-systolic dimension: 0·57, 0·21-0·93) but not for those who also received dexrazoxane (-0·41, -0·88 to 0·06; 0·15, -0·20 to 0·51). The protective effect of dexrazoxane, relative to doxorubicin alone, on left ventricular wall thickness (difference between groups: 0·47, 0·46-0·48) and thickness-to-dimension ratio (0·66, 0·64-0·68) were the only statistically significant characteristics at 5 years. Subgroup analysis showed dexrazoxane protection (p=0·04) for left ventricular fractional shortening at 5 years in girls (1·17, 0·24-2·11), but not in boys (-0·10, -0·87 to 0·68). Similarly, subgroup analysis showed dexrazoxane protection (p=0·046) for the left ventricular thickness-to-dimension ratio at 5 years in girls (1·15, 0·44-1·85), but not in boys (0·19, -0·42 to 0·81). With a median follow-up for recurrence and death of 8·7 years (range 1·3-12·1), event-free survival was 77% (95% CI 67-84) for children in the doxorubicin-alone group, and 76% (67-84) for children in the doxorubicin plus dexrazoxane group (p=0·99).. Dexrazoxane provides long-term cardioprotection without compromising oncological efficacy in doxorubicin-treated children with high-risk ALL. Dexrazoxane exerts greater long-term cardioprotective effects in girls than in boys.. US National Institutes of Health, Children's Cardiomyopathy Foundation, University of Miami Women's Cancer Association, Lance Armstrong Foundation, Roche Diagnostics, Pfizer, and Novartis.

Topics: Adolescent; Antibiotics, Antineoplastic; Biomarkers; Canada; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Disease-Free Survival; Doxorubicin; Female; Humans; Kaplan-Meier Estimate; Male; Myocardial Contraction; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Puerto Rico; Razoxane; Risk Assessment; Risk Factors; Survivors; Time Factors; Treatment Outcome; Troponin T; Ultrasonography; United States; Ventricular Function, Left; Young Adult

The authors conducted a retrospective study to determine whether dexrazoxane (ICRF-187) would reduce late anthracycline-induced cardiotoxicity in patients treated in childhood for hematological malignancy.. The authors examined 108 patients (63 male, 45 female) 5-29 years old, (median 15 years). All patients were in long-term remission of their malignancy. The cardioprotection was given to 68 patients (39 male, 29 female), and standard treatment was used in 40 patients (24 male, 16 female). Dexrazoxane (cardioxane, Chiron Company, The Netherlands) was given in 20:1 ratio to anthracycline. The follow-up time was 2-20 years (mean 7 years). The control group consisted of 41 volunteers (22 males, 19 females) 4-31 years old (median 18 years). The cardiotoxicity has been defined as the presence of heart failure or the decline of shortening fraction below 30% or ejection fraction (EF) below 55%. The end-systolic wall stress (ESS), myocardial performance index (MPI; Tei index), and parameters of left ventricular diastolic filling were also assessed.. The anthracycline cardiomyopathy with the presence of heart failure was diagnosed in only one patient treated with a standard regimen. The pathological decline of fractional shortening was present in three (5%) and six (15%) patients with and without cardioprotection given, respectively. Similarly, none of the patients with cardioprotection revealed a pathological value of EF, while four (10%) patients without cardioprotection showed an EF decrease. Finally, ESS and isovolumic relaxation time were pathologically increased in the group without cardioprotection in comparison to the controls and to the group with cardioprotection. However, the MPI was significantly increased in both groups of patients.. Dexrazoxane reduces the risk of late clinical and subclinical cardiotoxicity and does not affect the response rates to chemotherapy and overall survival during the median follow-up period of 7 years (follow-up period 2-20 years).

Topics: Adolescent; Adult; Anthracyclines; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Echocardiography; Female; Follow-Up Studies; Heart Failure; Hematologic Neoplasms; Humans; Male; Razoxane; Retrospective Studies; Stroke Volume; Survival Analysis; Treatment Outcome

Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage.. To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter)--the primary end point--or extremely elevated (>0.025 ng per milliliter).. Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test).. Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

Topics: Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Chelating Agents; Child; Disease-Free Survival; Doxorubicin; Echocardiography; Female; Heart; Humans; Logistic Models; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Razoxane; Troponin T; Ventricular Function, Left

Doxorubicin is one of the most effective anticancer drug, but its usefulness is limited by the risk of developing cardiomyopathy, cardiac dysfunction and ventricular arrhythmias. Dexrazoxane is used to protect against doxorubicin cardiotoxicity. It is uncertain whether the dexrazoxane-mediated cardioprotective effect will be reflected in electrophysiological properties of the heart. The aim of the present study was to evaluate the occurrence of frequency-domain signal-averaged electrocardiographic (SAECG) abnormalities of the QRS complex and the initial ST segment in patients treated with and without dexrazoxane. Thirty children and young adults 2 months - 15 years after completion of doxorubicin-containing therapy for Hodgkin's disease were evaluated with SAECG. Patients from group I (n = 13) received combined therapy with doxorubicin and dexrazoxane (DOX/DZX), patients from group II (n = 17) received doxorubicin without dexrazoxane (DOX). Using fast Fourier transformation within the QRS complex and the initial ST segment, area ratio (AR) values 40-100/0-40 Hz were calculated. Significant differences in these frequency parameters in the QRS complex between DOX/DZX group and DOX group (19.45+/-12.72 vs 46.18+/-43.06; p = 0.03) might indicate protective effect of dexrazoxane on electrophysiological myocardial properties.

Topics: Adolescent; Antineoplastic Agents; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Combined Modality Therapy; Doxorubicin; Electrocardiography; Female; Fourier Analysis; Hodgkin Disease; Humans; Infant; Male; Razoxane

Twenty females with disseminated breast cancer received courses of polychemotherapy with 21-day intervals. The regimen comprised adriamycin (ADM), cyclophosphamide and 5-fluorouracil in the dose 50, 500 mg/m2, respectively. 30 minutes prior to the treatment the patients were given the cardioprotector cardioxan (1000 mg/m2). Cardiological control (ECG, EF according to echo-CG and radionuclide ventriculography, PP/EP M1/M2, T1/T2 according to echo-polycardiography and Doppler cardiography) was performed before the treatment and at ADM total dose 200-300 mg/m2 followed by measurements at each dose increase by 100 mg/m2. The findings showed no evidence of ADM-related cardiac damage up to ADM dose 900-1000 mg/m2 in the case of cardioxan protection, though there was a tendency to M1/M2 increase which needs further studies as it suggests worsening of left ventricular diastolic contractility.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiomyopathies; Cardiovascular Agents; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Heart; Humans; Middle Aged; Myocardial Contraction; Razoxane; Time Factors

Topics: Acute Disease; Bisoprolol; Cardiomegaly; Cardiomyopathies; Cardiovascular Agents; Echocardiography; Genetic Testing; Heart Failure; Humans; Loeys-Dietz Syndrome; Losartan; Male; Middle Aged; Mutation; Pulmonary Edema; Receptor, Transforming Growth Factor-beta Type I; Spironolactone; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Gene Deletion; Gene Expression Regulation; Lipopolysaccharides; Male; Mice; Myocytes, Cardiac; Norepinephrine; Rats; Rats, Sprague-Dawley; Toll-Like Receptor 4

To evaluate the impact of autoantibodies against the M2-muscarinic receptor (anti-M2-R) on the clinical outcomes of patients receiving the standard treatment for peripartum cardiomyopathy (PPCM).. A total of 107 PPCM patients who received standard heart failure (HF) treatment between January 1998 and June 2020 were enrolled in this study. According to anti-M2-R reactivity, they were classified into negative (n = 59) and positive (n = 48) groups, denoted as the anti-M2-R (-) and anti-M2-R (+) groups. Echocardiography, 6-min walk distance, serum digoxin concentration (SDC), and routine laboratory tests were performed regularly for 2 years. The all-cause mortality, cardiovascular mortality, and rehospitalisation rate for HF were compared between the two groups.. A total of 103 patients were included in the final data analysis, with 46 in the anti-M2-R (+) group and 57 in the anti-M2-R (-) group. Heart rate was lower in the anti-M2-R (+) group than in the anti-M2-R (-) group at the baseline (102.7 ± 6.1 bpm vs. 96.0 ± 6.4 bpm, p < 0.001). The initial SDC was higher in the anti-M2-R (+) group than in the anti-M2-R (-) group with the same dosage of digoxin (1.25 ± 0.45 vs. 0.78 ± 0.24 ng/mL, p < 0.001). The dosages of metoprolol and digoxin were higher in the anti-M2-R (-) patients than in the anti-M2-R (+) patients (38.8 ± 4.6 mg b.i.d. vs. 27.8 ± 5.3 mg b.i.d., p < 0.0001, respectively, for metoprolol; 0.12 ± 0.02 mg/day vs. 0.08 ± 0.04 mg/day, p < 0.0001, respectively, for digoxin). Furthermore, there was a greater improvement in cardiac function in the anti-M2-R (-) patients than in the anti-M2-R (+) patients. Multivariate analysis identified negativity for anti-M2-R as the independent predictor for the improvement of cardiac function. Rehospitalisation for HF was lower in the anti-M2-R (-) group, but all-cause mortality and cardiovascular mortality were the same.. There were no differences in all-cause mortality or cardiovascular mortality between the two groups. Rehospitalisation rate for HF decreased in the anti-M2-R (-) group. This difference may be related to the regulation of the autonomic nervous system by anti-M2-R.

Topics: Adult; Autoantibodies; Autoimmunity; Autonomic Nervous System; Cardiomyopathies; Cardiovascular Agents; Female; Heart; Humans; Patient Readmission; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prospective Studies; Puerperal Disorders; Receptor, Muscarinic M2; Recovery of Function; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Ventricular Function, Left

After enhancing the survivorship of cancers, the impact of cardiovascular diseases on mortality is increasing among cancer patients. However, anticancer therapies pose a higher cardiovascular risk to patients. As prevention against cancer therapy-induced cardiomyopathy has yet to be explored, the preventive ability of concomitant cardiovascular medications against incident heart failure was assessed.. A retrospective, population-based study was run using anonymized integration of healthcare databases. All the Hungarian patients diagnosed with breast or colorectal carcinoma and undergoing chemotherapy or biological therapy were analysed. Participants were not treated with any anticancer therapy nor suffered from heart failure/dilated cardiomyopathy during the preceding observational period (≥6.5 years). The heart failure endpoint was established by I50 International Classification of Diseases codes upon discharge from hospital or issuance of an autopsy report.. Among the 9575 patients who were enrolled, the cumulative incidence of heart failure over 4 years was 6.9%. The time until the first heart failure event in the propensity score-matched treated and untreated groups was compared using Cox proportional-hazards models. A significant association between lower heart failure risk and concomitant statin therapy was observed (hazard ratio: 0.748, P = 0.038); the preventive ability was more pronounced in the anthracycline/capecitabine/platinum-treated subgroup (hazard ratio: 0.660, P = 0.032). For angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy, a significantly lower heart failure risk was also observed (hazard ratio: 0.809, P = 0.032). Among beta blockers, nebivolol administered to anthracycline/capecitabine-treated patients was associated with a nonsignificant trend to lower heart failure risk (hazard ratio: 0.584, P = 0.069).. Only concomitant statin and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapies were associated with significantly lower risk of anticancer therapy-related heart failure.

Topics: Antineoplastic Agents; Cardiomyopathies; Cardiotoxicity; Cardiovascular Agents; Databases, Factual; Female; Heart Failure; Humans; Hungary; Incidence; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Protective Factors; Retrospective Studies; Risk Adjustment

Heart failure metrics specific to the pediatric population are required to successfully implement quality improvement initiatives in children with heart failure. Medication use at the time of discharge following admission for decompensated heart failure has been identified as a potential quality metric in this population. This study aimed to report medication use at discharge in the current era for children admitted with acute decompensated heart failure. All patients < 21 years of age with an index admission (1/1/2011-12/31/2019) for acute heart failure and a coexisting diagnosis of cardiomyopathy were identified from the Pediatric Health Information System. Medication use patterns were described and compared across age groups and centers. A total of 2288 patients were identified for inclusion. An angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker (ACEi/ARB) was prescribed in 1479 (64.6%), beta blocker in 1132 (49.5%), and mineralocorticoid receptor antagonist (MRA) in 864 (37.8%) patients at discharge. The use of ACEi/ARB at discharge has decreased over time (64.6% vs. 69.6%, p = 0.001) and the use of beta blockers has increased (49.5% vs. 36.8%, p < 0.001) compared to a historical cohort (2001-2010). There is considerable variability in medication use across centers with an overall increase in beta blocker and decrease in ACEi/ARB use over time. Collaborative efforts are needed to standardize care and define quality metrics to identify best practices in the management of pediatric heart failure.

Topics: Adolescent; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benchmarking; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Female; Heart Failure; Hospitalization; Humans; Male; Mineralocorticoid Receptor Antagonists; Patient Discharge; Practice Patterns, Physicians'; Quality of Life; Young Adult

Restrictive cardiomyopathy (RCM) is a common myocardial disease in cats, characterized by diastolic dysfunction and atrial enlargement without myocardial hypertrophy. Especially, endomyocardial form of RCM, one of the subtypes in RCM, is characterized by endocardial fibrosis, endocardial scar bridging the interventricular septum and left ventricular (LV) free wall, and deformation and distortion of the LV. However, it is unclear how the myocardial dysfunction and the endocardial scar contribute to the pathophysiology of RCM disease progression.. A 3 years and 2 months old, intact male, Domestic shorthaired cat was presented for consultation of cardiac murmur. At the first visit (day 0), the notable abnormal finding was echocardiography-derived chordae tendineae-like structure bridging the interventricular septum and the LV free wall, resulting high-speed blood flow in the left ventricle. Electrocardiography, thoracic radiography and noninvasive blood pressure measurements were normal. No left atrial enlargement was observed, and LV inflow velocity showed an abnormal relaxation pattern. Although there was no abnormality in tissue Doppler imaging-derived myocardial velocity, two-dimensional speckle tracking echocardiography (2D-STE) revealed a decrease in the LV longitudinal strain and an increase in endocardial to epicardial ratio of the LV circumferential strain on day 0. On day 468, obvious left atrium enlargement and smoke like echo in the left atrium were observed. The LV inflow velocity was fused, and the tissue Doppler imaging-derived early-diastolic myocardial velocity of the septal mitral annulus decreased. Regarding 2D-STE, LV circumferential strain was further decreased, and right ventricular strain was additionally decreased. Although the general condition was good, we made a clinical diagnosis of endomyocardial RCM based on the above findings. On day 503, the cat showed the radiographic evidence of pulmonary edema and congestive heart failure signs.. Cats with abnormal LV structure and associated myocardial dysfunction like this case needs careful observation. Additionally, 2D-STE indices may be useful for early detection of myocardial dysfunction in feline RCM.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Cat Diseases; Cats; Endomyocardial Fibrosis; Heart Failure; Male

Myocardial fibrosis is a hallmark of cardiac remodeling and functionally involved in heart failure development, a leading cause of deaths worldwide. Clinically, no therapeutic strategy is available that specifically attenuates maladaptive responses of cardiac fibroblasts, the effector cells of fibrosis in the heart. Therefore, our aim was to develop novel antifibrotic therapeutics based on naturally derived substance library screens for the treatment of cardiac fibrosis.. Antifibrotic drug candidates were identified by functional screening of 480 chemically diverse natural compounds in primary human cardiac fibroblasts, subsequent validation, and mechanistic in vitro and in vivo studies. Hits were analyzed for dose-dependent inhibition of proliferation of human cardiac fibroblasts, modulation of apoptosis, and extracellular matrix expression. In vitro findings were confirmed in vivo with an angiotensin II-mediated murine model of cardiac fibrosis in both preventive and therapeutic settings, as well as in the Dahl salt-sensitive rat model. To investigate the mechanism underlying the antifibrotic potential of the lead compounds, treatment-dependent changes in the noncoding RNAome in primary human cardiac fibroblasts were analyzed by RNA deep sequencing.. High-throughput natural compound library screening identified 15 substances with antiproliferative effects in human cardiac fibroblasts. Using multiple in vitro fibrosis assays and stringent selection algorithms, we identified the steroid bufalin (from Chinese toad venom) and the alkaloid lycorine (from. We identified the molecules bufalin and lycorine as drug candidates for therapeutic applications in cardiac fibrosis and diastolic dysfunction.

Topics: Amaryllidaceae Alkaloids; Animals; Apoptosis; Bufanolides; Cardiomyopathies; Cardiovascular Agents; Cell Proliferation; Cells, Cultured; Diastole; Disease Models, Animal; Extracellular Matrix; Fibroblasts; Fibrosis; High-Throughput Screening Assays; Humans; Hypertension; Male; Mice, Inbred C57BL; MicroRNAs; Myocardium; Phenanthridines; Rats, Inbred Dahl; Selenoprotein P; Ventricular Function, Left

Muscular dystrophies are a heterogeneous group of disorders that commonly involve cardiac and skeletal muscle. Comprehensive guidelines for the management of cardiac failure and arrhythmias are available. However, the studies from which their recommendations are derived did not include any patients with muscular dystrophy. Some medications (eg, betablockers) may have significant side effects in this cohort. In some situations the use of agents with unique mechanisms of action such as ivabradine (a 'funny' channel inhibitor) may be more appropriate. Use of ivabradine has not previously been reported in limb girdle muscular dystrophy (LGMD). We describe the course of a patient with LGMD type 2I, cardiomyopathy and inappropriate sinus tachycardia treated with ivabradine. As advances in respiratory support have improved the outcomes of patients with muscular dystrophy; the prognostic significance of cardiac disease has increased. Ivabradine is tolerated and may reduce symptoms, morbidity and mortality in this cohort.

Topics: Anti-Arrhythmia Agents; Cardiomyopathies; Cardiovascular Agents; Diagnosis, Differential; Female; Humans; Ivabradine; Metoprolol; Muscular Dystrophies, Limb-Girdle; Tachycardia, Sinus; Young Adult

Topics: Action Potentials; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Female; Heart Rate; Humans; Immunosuppressive Agents; Middle Aged; Tachycardia, Supraventricular; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Obesity-induced cardiomyopathy involves chronic and sustained inflammation. The toll-like receptor 4 (TLR4) signaling pathway can associate innate immunity with obesity. Myeloid differentiation primary response 88 (MyD88), an indispensable downstream adaptor molecule of TLR4, has been reported to mediate obesity complications. However, whether inhibition of MyD88 can mitigate obesity-induced heart injury remains unclear. LM8, a new MyD88 inhibitor, exhibits prominent anti-inflammatory activity in lipopolysaccharide-treated macrophages. In this study, the protective effects of LM8 on a high-fat diet (HFD)-induced heart injury were assessed in a mouse model of obesity. As suggested from the achieved results, LM8 treatment alleviated HFD-induced pathological and functional damages of the heart in mice. Meantime, the treatment of mice with LM8 could significantly inhibit myocardial hypertrophy, fibrosis, inflammatory cytokines expression, and inflammatory cell infiltration induced by HFD. Besides, LM8 administration inhibited the formation of MyD88/TLR4 complex, phosphorylation of ERK, and activation of nuclear factor-κB induced by HFD. According to the achieved results, MyD88 inhibitor LM8 ameliorated obesity-induced heart injury by inhibiting MyD88-ERK/nuclear factor-κB dependent cardiac inflammatory pathways. Furthermore, targeting MyD88 might be a candidate of a therapeutic method to treat obesity-induced heart injury.

Topics: Animals; Cardiomegaly; Cardiomyopathies; Cardiovascular Agents; Cells, Cultured; Cytokines; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Fibrosis; Male; Mice, Inbred C57BL; Myeloid Differentiation Factor 88; Myocarditis; Myocytes, Cardiac; NF-kappa B; Obesity; Signal Transduction; Toll-Like Receptor 4

One out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients.. We present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient's severe AS conservatively.. In the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient' prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.

Topics: Aged, 80 and over; Amyloid Neuropathies, Familial; Aortic Valve Stenosis; Cardiomyopathies; Cardiovascular Agents; Conservative Treatment; Humans; Male; Severity of Illness Index; Treatment Outcome

Ivabradine selectively inhibits the If current, reducing the heart rate and protecting against myocardial ischemia/reperfusion injury. We investigated the effects of ivabradine on post-resuscitation myocardial function in a porcine model of cardiopulmonary resuscitation.. Ventricular fibrillation was induced and untreated for 8 min while defibrillation was attempted after 6 min of cardiopulmonary resuscitation in anesthetized domestic swine. Then the animals were randomized into ivabradine and placebo groups (n = 5 each). Ivabradine and saline were administered at the same volume 5 min after Return of Spontaneous Circulation, followed by continuous intravenous infusion at 0.5 mg/kg for 480 min. Hemodynamic parameters were continuously recorded. Myocardial function was assessed by echocardiography at baseline and at 60, 120, 240, 480 min and 24 h after resuscitation. The serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured by commercial enzyme-linked immunosorbent assay kits. Animals were killed 24 h after resuscitation, and all myocardial tissue was removed for histopathological analysis. The heart rate was significantly reduced from 1 h after resuscitation in the ivabradine group (all P < 0.05). The post-resuscitation mitral E/A and E/e' velocity ratios and left ventricular ejection fraction were significantly better in the ivabradine than placebo group (P < 0.05). The serum levels of myocardial injury biomarkers (NT-proBNP, cTnI) and the myocardial biopsy scores were significantly lower in the ivabradine than placebo group (P < 0.05). Neurological deficit scores were lower in the IVA group at PR 24 h (P < 0.05).. Ivabradine improved post-resuscitation myocardial dysfunction, myocardial injury, and post-resuscitation cerebral function, and also slowed the heart rate in this porcine model.

Topics: Animals; Cardiomyopathies; Cardiopulmonary Resuscitation; Cardiovascular Agents; Disease Models, Animal; Heart Arrest; Ivabradine; Male; Stroke Volume; Swine; Ventricular Function, Left

Peripartum cardiomyopathy (PPCM) establishes late in pregnancy or in the first postpartum months. Many patients recover well within the first year, but long-term outcome studies on morbidity and mortality are rare. Here, we present 5-year follow-up data of a German PPCM cohort.. Five-year follow-up data were available for 66 PPCM patients (mean age 34 ± 5 years) with a mean left ventricular ejection fraction (LVEF) of 26 ± 9% at diagnosis. Ninety-eight percent initially received standard heart failure therapy (beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and/or mineralocorticoid receptor antagonists), and 86% were additionally treated with dopamine D2 receptor agonists (mainly bromocriptine) and anticoagulation. After 1 year, mean LVEF had improved to 50 ± 11% (n = 48) and further increased to 54 ± 7% at 5-year follow-up with 72% of patients having achieved full cardiac recovery (LVEF >50%). At 5-year follow-up, only three patients (5%) displayed no recovery, of whom one had died. However, 20% had arterial hypertension and 17% arrhythmias, including paroxysmal supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation. Moreover, 70% were still on at least one heart failure drug. Subsequent pregnancy occurred in 16 patients with two abortions and 14 uneventful pregnancies. Mean LVEF was 55 ± 7% at 5-year follow-up in these patients.. Our PPCM collective treated with standard therapy for heart failure, dopamine D2 receptor agonists, and anticoagulation displays a high and stable long-term recovery rate with low mortality at 5-year follow-up. However, long-term use of cardiovascular medication, persisting or de novo hypertension and arrhythmias were frequent.

Topics: Adult; Cardiomyopathies; Cardiovascular Agents; Comorbidity; Female; Follow-Up Studies; Germany; Humans; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Prospective Studies; Recovery of Function; Stroke Volume; Time Factors; Ventricular Function, Left

End-stage dilated cardiomyopathy (DCM) is the leading cause of morbidity and mortality in patients with Duchenne Muscular Dystrophy (DMD). No studies are available on the effect of ivabradine on long-term outcomes in end-stage DMD/DCM.. We prospectively enrolled a cohort of end-stage DMD/DCM patients with LV ejection fraction <40%, on chronic HF treatment with an ACE inhibitor referred consecutively from 2012 to 2017 to Bambino Gesù Children's Hospital. In each patient, before starting HRR strategy and after 1 year, we collected medical records comprehensive of clinical, demographic and imaging parameters, BNP levels, neurological and respiratory assessment.. Twenty male patients with DMD/DCM with a mean age of 15.0 ± 3.5 (13-19 IQR) years were enrolled and divided into 2 groups according to ivabradine therapy. This group showed a higher incidence of MACEs compared to others in treatment with ivabradine (87.5% vs 12.5%, p = 0.025). At Kaplan Meier survival analysis curves, the rate free from MACEs was higher in patients treated with ivabradine (log rank p = 0.017). At multivariate Cox regression analysis, ivabradine therapy was an independent predictor of freedom from MACEs (H.R. 0.078, 95% CI 0.007-0.877, p = 0.039).. HRR strategy, whether achieved by beta blockers alone or in combination with ivabradine, seemed to be effective in reducing the incidence of acute adverse events, reaching optimal target heart rate and improving left ventricular function in DMD/DCM patients.

Topics: Adolescent; Adult; Cardiomyopathies; Cardiovascular Agents; Cohort Studies; Follow-Up Studies; Heart Rate; Humans; Ivabradine; Magnetic Resonance Imaging, Cine; Male; Muscular Dystrophy, Duchenne; Pilot Projects; Prospective Studies; Young Adult

We investigated the influence of the extent of viability using low dose dobutamine wall motion score index (WMS) on the survival benefit of surgical revascularization (CABG) versus medical therapy. In the STICH trial, viability assessment was not helpful in determining the benefit of CABG. However, the extent of viable myocardium with contractile function was not assessed in the trial. Dobutamine echocardiography was performed in 250 patients with ischemic left ventricular dysfunction (125-medically treated, 125-CABG). The mean ejection fraction (EF) was 32% in both groups. WMS during low dose dobutamine infusion was used to classify patients into groups with extensive (WMS < 2.00), intermediate (WMS 2.00-2.49), and limited (WMS ≥ 2.50) viability. Survival free of cardiac death was assessed at 2 years and for the complete duration of follow-up. There were 44 (35.2%) and 67 (53.6%) cardiac deaths in the revascularized and medically treated patients respectively (follow-up of 5.7 ± 5.8 years). Revascularized and medically treated patients with extensive viability had similar 2-year survival (p = 0.567) but revascularized patients had improved long-term survival (p = 0.0001). In those with intermediate viability, revascularization improved both 2 year (p = 0.014) and long-term survival (p = 0.0001). In patients with limited viability, 2-year survival was worse in revascularized patients (p = 0.04) and long-term survival was similar (p = 0 .25) in revascularized and medically treated groups. Patients with extensive and intermediate amounts of viability have improved survival with CABG but those with limited viability have poorer short-term outcome and no long-term benefit.

Topics: Aged; Cardiomyopathies; Cardiotonic Agents; Cardiovascular Agents; Clinical Decision-Making; Coronary Artery Bypass; Dobutamine; Echocardiography, Stress; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Patient Selection; Predictive Value of Tests; Recovery of Function; Retrospective Studies; Risk Factors; Stroke Volume; Time Factors; Tissue Survival; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Asymptomatic Diseases; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiovascular Agents; Child, Preschool; Defibrillators, Implantable; Desmoplakins; Electric Countershock; Female; Genetic Predisposition to Disease; Hair Diseases; Heredity; Heterozygote; Humans; Keratoderma, Palmoplantar; Mutation; Pedigree; Phenotype; Treatment Outcome

Successful resuscitation from cardiac arrest results in a post-cardiac arrest syndrome, which can evolve in the days to weeks after return of sustained circulation. The components of post-cardiac arrest syndrome are brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathophysiology. Pediatric post-cardiac arrest care focuses on anticipating, identifying, and treating this complex physiology to improve survival and neurological outcomes. This scientific statement on post-cardiac arrest care is the result of a consensus process that included pediatric and adult emergency medicine, critical care, cardiac critical care, cardiology, neurology, and nursing specialists who analyzed the past 20 years of pediatric cardiac arrest, adult cardiac arrest, and pediatric critical illness peer-reviewed published literature. The statement summarizes the epidemiology, pathophysiology, management, and prognostication after return of sustained circulation after cardiac arrest, and it provides consensus on the current evidence supporting elements of pediatric post-cardiac arrest care.

Topics: Acute Kidney Injury; Adrenal Insufficiency; Anticonvulsants; Brain Damage, Chronic; Cardiomyopathies; Cardiopulmonary Resuscitation; Cardiovascular Agents; Child; Combined Modality Therapy; Fluid Therapy; Glucose Metabolism Disorders; Heart Arrest; Humans; Hypnotics and Sedatives; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infections; Inflammation; Monitoring, Physiologic; Multiple Organ Failure; Neuromuscular Blocking Agents; Oxygen Inhalation Therapy; Prognosis; Reperfusion Injury; Respiratory Therapy; Time Factors

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Angiotensin-Converting Enzyme Inhibitors; Benzoxazoles; Cardiomyopathies; Cardiovascular Agents; Clinical Trials as Topic; Diuretics; Female; Humans; Male; Rare Diseases

Peripartum cardiomyopathy (PPCM) is a left ventricular systolic dysfunction failure emerges during the antepartum or puerperal period, and can result in maternal death. Reported incidences are increasing and differing globally. Echocardiography is the cornerstone for the diagnosis. The immediate goals in acute management are the stabilization of the hemodynamic state, providing symptomatic relief, and ensuring fetal wellbeing. Emergency physicians should be aware of PPCM at the differential diagnosis of dyspnea in pregnancy related emergencies and play role in early diagnosis.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Anticoagulants; Cardiomyopathies; Cardiovascular Agents; Chest Pain; Drug Therapy, Combination; Dyspnea; Echocardiography; Emergency Service, Hospital; Female; Hemodynamics; Humans; Metoprolol; Puerperal Disorders; Radiography; Ventricular Dysfunction, Left

Junctional ectopic tachycardia (JET) is a rare form of arrhythmia that is most commonly seen during infancy. JET is continuous and incessant, characterized by persistently high heart rates that may result in impaired cardiac function and tachycardia-induced cardiomyopathy. Despite the availability of multiple antiarrhythmic treatments, including flecainide and amiodarone, management of JET is generally very difficult. Catheter ablation has a high risk of atrioventricular block and it may require the placement of a pacemaker. Ivabradine, also known as a cardiac pacemaker cell inhibitor, is a new-generation antiarrhythmic used to treat sinus tachycardia and angina pectoris in adult patients. In this article, we present three cases of subjects with infantile congenital JET who were admitted to our clinic with a tachycardia-induced cardiomyopathy. The age of the subjects ranged from 52 days to 10 months. Although the cases of tachycardia could not be controlled by multiple antiarrhythmics, including a combination of amiodarone and flecainide combined with either propranolol or digoxin, they were rapidly converted into sinus rhythm with an ivabradine treatment of 0.1-0.2 mg/kg/day. No cardiac or other side effects were observed during ivabradine treatment, and left ventricular functions and rhythms improved within 24 hours. These three cases therefore provide hope that ivabradine may be a suitable standard initial treatment for congenital JET. However, additional research is needed to confirm the validity of these results in other circumstances.

Topics: Cardiomyopathies; Cardiovascular Agents; Electrocardiography; Female; Humans; Infant; Ivabradine; Male; Tachycardia, Ectopic Junctional

Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM.. In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter. In PPCM patients diagnosed in the first postpartum week, serum Relaxin-2 levels were lower compared to healthy postpartum stage-matched controls. In PPCM patients diagnosed later (0.5-10 months postpartum) Relaxin-2 levels were in the range of non-pregnant controls and not different from healthy postpartum stage-matched controls. In mice, serum Relaxin-1 (functional equivalent of human Relaxin-2) was increased late in pregnancy and rapidly cleared in the first postpartum week. In mice with PPCM due to a cardiomyocyte-specific knockout of STAT3 (CKO) neither low nor high dose of recombinant Relaxin-2 (serelaxin, sRlx-LD: 30 µg/kg/day; sRlx-HD: 300 µg/kg/day) affected cardiac fibrosis, inflammation and heart failure but sRlx-HD increased capillary/cardiomyocyte ratio. sRlx-HD significantly increased heart/body weight ratio and cardiomyocyte cross-sectional area in postpartum CKO and wild-type mice without changing the foetal gene expression program (ANP or β-MHC). sRlx-HD augmented plasma Prolactin levels in both genotypes, which induced cardiac activation of STAT5. In vitro analyses showed that Prolactin induces cardiomyocyte hypertrophy via activation of STAT5.. Although Relaxin-2 levels seemed lower in PPCM patients diagnosed early postpartum, we observed a high pregnancy-related variance of serum Relaxin-2 levels peripartum making it unsuitable as a biomarker for this condition. Supplementation with sRlx may contribute to angiogenesis and compensatory hypertrophy in the diseased heart, but the effects are not sufficient to prevent heart failure in an experimental PPCM model.

Topics: Adult; Animals; Biomarkers; Cardiomegaly; Cardiomyopathies; Cardiovascular Agents; Case-Control Studies; Disease Models, Animal; Female; Heart Failure; Humans; Mice, Knockout; Myocytes, Cardiac; Postpartum Period; Pregnancy; Prolactin; Rats; Recombinant Proteins; Registries; Relaxin; Signal Transduction; STAT3 Transcription Factor; STAT5 Transcription Factor; Stroke Volume; Ventricular Function, Left

The burden of heart failure has long plagued the productive years of the population, with therapeutic advances in the timely treatment of ischemic heart disease decreasing its associated mortality. Angiotensin-converting enzyme inhibitors and β-blockers have impacted heart failure therapeutics in a revolutionary way. The importance of blockade of the renin-angiotensin system and adrenergic stimulation are fully accepted concepts that apply in young and old, symptomatic and asymptomatic, borderline low and very low Ejection Fraction (EF), left ventricular failure and biventricular failure. Despite several interventions, both pharmaceutical and device based for the treatment of ensuing heart failure, the incidence is increasing in large proportions. Newer molecules like sacubitril show more promise. Despite these novel therapies, several patients relentlessly progress to a stage of advanced heart failure. The use of left-ventricular-assist devices has variable clinical benefit, with some patients progressing to heart transplantation.

Topics: Cardiac Surgical Procedures; Cardiomyopathies; Cardiovascular Agents; Disease Progression; Heart Failure; Heart-Assist Devices; Hemodynamics; Humans; Models, Cardiovascular; Myocardial Ischemia; Recovery of Function; Renin-Angiotensin System; Risk Factors; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Cardiac disease in SSc can manifest in various ways and is associated with a poor prognosis. There is little evidence on how best to detect and manage cardiac disease in SSc. Our objective was to produce an expert consensus best practice pathway for the management of cardiac disease in SSc.. The UK Systemic Sclerosis Study Group set up several working groups to develop a number of consensus best practice pathways for the management of SSc-specific complications, including cardiac disease. A multidisciplinary task force was convened. The guidelines were partly informed by a comprehensive literature review.. A best practice pathway for cardiac disease (with a focus on primary cardiac disease) in SSc is presented, including approaches for early detection and standard pharmacological and device therapies. Due to the benefits, shared care and a multidisciplinary approach are recommended. A future research agenda has been formulated in response to the relative lack of understanding of the natural history of primary cardiac disease that was highlighted by the initiative.. The physician should be alert to the possibility of cardiac disease in SSc; it is best managed within a multidisciplinary team including both rheumatologists and cardiologists. This pathway provides a reference for all physicians managing patients with SSc.

Topics: Arrhythmias, Cardiac; Biomarkers; Cardiomyopathies; Cardiovascular Agents; Electrocardiography; Evidence-Based Medicine; Heart Failure; Humans; Magnetic Resonance Angiography; Medical History Taking; Monitoring, Ambulatory; Patient Care Team; Pericarditis; Physical Examination; Risk Factors; Scleroderma, Systemic

The purpose of this study is to describe disease presentation, co-morbidities, diagnosis and initial therapeutic management of patients with peripartum cardiomyopathy (PPCM) living in countries belonging to the European Society of Cardiology (ESC) vs. non-ESC countries.. Out of 500 patients with PPCM entered by 31 March 2016, we report on data of the first 411 patients with completed case record forms (from 43 countries) entered into this ongoing registry. There were marked differences in socio-demographic parameters such as Human Development Index, GINI index on inequality, and Health Expenditure in PPCM patients from ESC vs. non-ESC countries (P < 0.001 each). Ethnicity was Caucasian (34%), Black African (25.8%), Asian (21.8%), and Middle Eastern backgrounds (16.4%). Despite the huge disparities in socio-demographic factors and ethnic backgrounds, baseline characteristics are remarkably similar. Drug therapy initiated post-partum included ACE inhibitors/ARBs and mineralocorticoid receptor antagonists with identical frequencies in ESC vs. non-ESC countries. However, in non-ESC countries, there was significantly less use of beta-blockers (70.3% vs. 91.9%) and ivabradine (1.4% vs. 17.1%), but more use of diuretics (91.3% vs. 68.8%), digoxin (37.0% vs. 18.0%), and bromocriptine (32.6% vs. 7.1%) (P < 0.001). More patients in non-ESC vs. ESC countries continued to have symptomatic heart failure after 1 month (92.3% vs. 81.3%, P < 0.001). Venous thrombo-embolic events, arterial embolizations, and cerebrovascular accidents were documented in 28 of 411 patients (6.8%). Neonatal death rate was 3.1%.. PPCM occurs in women from different ethnic backgrounds globally. Despite marked differences in socio-economic background, mode of presentation was largely similar. Embolic events and persistent heart failure were common within 1 month post-diagnosis and required intensive, multidisciplinary management.

Topics: Adult; Cardiomyopathies; Cardiovascular Agents; Comorbidity; Demography; Disease Management; Ethnicity; Europe; Female; Health Expenditures; Heart Failure; Humans; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Registries; Socioeconomic Factors

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction-LVEF <40 %) with heart failure symptoms ≤ 6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm(2) and/or >7 T-lymphocytes/mm(2) in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm(2) and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm(2) (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = -0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = -0.33; p = 0.038 and R = -0.45; p = 0.003) and with the change in LVEDV (R = -0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment

Topics: Adult; Biomarkers; Biopsy; Cardiomyopathies; Cardiovascular Agents; Chemotaxis, Leukocyte; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Recovery of Function; Risk Factors; Stroke Volume; T-Lymphocytes; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Anticancer drug treatment, particularly with anthracyclines, is frequently associated with cardiotoxicity, an effect exacerbated by trastuzumab. Several compounds are in use clinically to attenuate the cardiac-damaging effects of chemotherapy drugs, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, the anti-diabetic drug metformin, and dexrazoxane. However, there is concern that the cardiac-preserving mechanisms of these drugs may also limit the anticancer efficacy of the chemotherapeutic agents.. Herein two breast cancer cell lines, SKBr3 and BT474, overexpressing human epithelial receptor 2 (HER2), the target of the humanised antibody trastuzumab, were treated with a range of concentrations (20-2000 nM) of doxorubicin with and without trastuzumab in the presence of clinically relevant doses of the ACE inhibitor enalapril, the beta-blocker carvedilol, metformin or dexrazoxane, and cell survival determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.. None of the drugs reduced the anticancer effect of doxorubicin or trastuzumab (nor of the two drugs combined). Using Chou and Talalay's combination index, dexrazoxane and doxorubicin were found to act synergistically on the SKBr3 cells. (18)F-Fluoro-2-deoxy-D-glucose ((18)F-FDG) incorporation was reduced by treatment of SKBr3 cells with doxorubicin and this was shown to be due to reduced phosphorylation of (18)F-FDG in doxorubicin-treated cells. Treatment of SKBr3 cells with doxorubicin and dexrazoxane further reduced (18)F-FDG incorporation, indicating that the synergy in the cytotoxicity of these two drugs was reflected in their combined effect on (18)F-FDG incorporation.. Commonly administered cardioprotective drugs do not interfere with anticancer activity of doxorubicin or tratsuzumab. Further studies to establish the effect of cardioprotective drugs on anticancer drug efficacy would be beneficial.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carbazoles; Cardiomyopathies; Cardiotonic Agents; Cardiovascular Agents; Carvedilol; Cell Line, Tumor; Cell Survival; Dexrazoxane; Dose-Response Relationship, Drug; Doxorubicin; Drug Interactions; Enalapril; Female; Fluorodeoxyglucose F18; Humans; Metformin; Propanolamines; Radionuclide Imaging; Radiopharmaceuticals; Receptor, ErbB-2; Trastuzumab

Elevated resting heart rate has been linked to poor outcomes in patients with chronic systolic heart failure. Blockade of funny current channel with ivabradine reduces heart rate without inotropic effects. Ivabradine was recently approved by US Food and Drug Administration for patients with stable, symptomatic chronic heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35 %, who are in sinus rhythm with resting heart rate (HR) ≥ 70 bpm and either are on maximally tolerated doses of beta-blockers, or have a contraindication to beta-blockers. This article will review and evaluate the data supporting the use of ivabradine in patients with HF and explore its mechanisms and physiologic effects.

Topics: Arrhythmias, Cardiac; Benzazepines; Cardiomyopathies; Cardiovascular Agents; Clinical Studies as Topic; Heart Failure; Heart Rate; Heart Transplantation; Humans; Ivabradine; Shock, Cardiogenic; Ultrasonography

Topics: Animals; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiovascular Agents; Claudin-5; Disease Progression; Double-Blind Method; Drug Evaluation, Preclinical; Dystrophin; Gene Expression Regulation; Genetic Therapy; Heart Failure; Humans; Mice; Mice, Inbred mdx; Mineralocorticoid Receptor Antagonists; Muscular Dystrophy, Animal; Muscular Dystrophy, Duchenne; Randomized Controlled Trials as Topic; Translational Research, Biomedical; Utrophin

Topics: Aged; Cardiomyopathies; Cardiovascular Agents; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Mortality; Myocardial Ischemia; Retrospective Studies

Topics: American Heart Association; Cardiomyopathies; Cardiovascular Agents; Humans; Myocardial Ischemia; Randomized Controlled Trials as Topic; Stents; United States

Prospective data on the safety and efficacy of the wearable cardioverter defibrillator (WCD) in a real-world setting are lacking. The Prospective Registry of Patients Using the Wearable Defibrillator (WEARIT-II) Registry was designed to provide real-world data on the WCD as a strategy during a period of risk stratification.. The WEARIT-II Registry enrolled 2000 patients with ischemic (n=805, 40%), or nonischemic cardiomyopathy (n=927, 46%), or congenital/inherited heart disease (n=268) prescribed WCD between August 2011 and February 2014. Clinical data, arrhythmia events, implantable cardioverter defibrillator implantation, and improvement in ejection fraction were captured. The median age was 62 years; the median ejection fraction was 25%. The median WCD wear time was 90 days, with median daily use of 22.5 hours. There was a total of 120 sustained ventricular tachyarrhythmias in 41 patients, of whom 54% received appropriate WCD shock. Only 10 patients (0.5%) received inappropriate WCD therapy. The rate of sustained ventricular tachyarrhythmias by 3 months was 3% among patients with ischemic cardiomyopathy and congenital/inherited heart disease, and 1% among nonischemic patients (P=0.02). At the end of WCD use, 840 patients (42%) were implanted with an implantable cardioverter defibrillator. The most frequent reason not to implant an implantable cardioverter defibrillator following WCD use was improvement in ejection fraction.. The WEARIT-II Registry demonstrates a high rate of sustained ventricular tachyarrhythmias at 3 months in at-risk patients who are not eligible for an implantable cardioverter defibrillator, and suggests that the WCD can be safely used to protect patients during this period of risk assessment.

Topics: Aged; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators; Defibrillators, Implantable; Electric Countershock; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Male; Middle Aged; Myocardial Ischemia; Patient Compliance; Prescriptions; Prospective Studies; Registries; Stroke Volume

Topics: Adrenal Cortex Hormones; Biopsy; Cardiomyopathies; Cardiovascular Agents; Catheter Ablation; Combined Modality Therapy; Cyclophosphamide; Defibrillators, Implantable; Electrocardiography; Heart Septum; Humans; Hypertrophy, Right Ventricular; Lymph Nodes; Magnetic Resonance Imaging; Male; Middle Aged; Sarcoidosis; Sarcoidosis, Pulmonary; Syncope; Tachycardia, Ventricular; Ultrasonography

The cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy.. Twenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control.. At 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05).. The combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure.

Topics: Animals; Anterior Wall Myocardial Infarction; Biomarkers; Cardiomyopathies; Cardiovascular Agents; Chemistry, Pharmaceutical; Combined Modality Therapy; Coronary Circulation; Delayed-Action Preparations; Disease Models, Animal; Dogs; Fibrosis; Heart Ventricles; Heart-Assist Devices; Natriuretic Peptide, Brain; Peptide Fragments; Prostaglandins I; Prosthesis Design; Pyridines; Recovery of Function; Time Factors; Ventricular Function, Left; Ventricular Remodeling

Peripartum cardiomyopathy is a life-threatening cardiac condition affecting pregnant women either late in pregnancy or early in the post-partum period. The latest studies show a dramatic improvement in the mortality rates of women affected with this disorder, which has been correlated with advances in medical therapy for heart failure. However, patients continue to die of this condition. The following case report describes a typical patient with peripartum cardiomyopathy diagnosed on clinical grounds, along with echocardiogram findings of severe systolic dysfunction and global hypokinesis consistent with dilated cardiomyopathy. Emergency cesarean delivery had to be performed for fetal distress. There was significant improvement of the patient's condition with standard pharmacological management for heart failure at the time of discharge. However, five weeks after discharge, fatal cardiac arrest occurred. It is hoped that this article will raise awareness about this rare but potentially fatal condition and promote understanding of its main clinical features, diagnostic criteria, and conventional pharmacological management.

Topics: Adult; Cardiomyopathies; Cardiovascular Agents; Cesarean Section; Death, Sudden, Cardiac; Emergency Treatment; Fatal Outcome; Female; Humans; Peripartum Period

Inherited heart conditions are the most common cause of sudden cardiac death in those under the age of 35 and the leading cause of non-traumatic death in young athletes. Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease affecting 1 in 500 of the population. Some patients may exhibit severe left ventricular hypertrophy, others may show nothing more than an abnormal ECG. Left ventricular hypertrophy most commonly manifests in the second decade of life. Sudden death is rare and usually affects patients in the first three decades whereas older patients present with heart failure, atrial fibrillation and stroke. Arrhythmogenic right ventricular cardiomyopathy is a rare, autosomal dominant heart muscle disorder which affects between 1 in 1,000 and 1 in 5,000 of the population. Dilated cardiomyopathy (DCM) is characterised by a dilated left ventricle with impaired function that cannot be explained by ischaemic heart disease, hypertension or valvular heart disease. At least 25% of cases of DCM are familial. DCM may be associated with multisystem conditions such as muscular dystrophy. Chemotherapy and certain other drugs, alcohol abuse and myocarditis may also lead to a dilated and poorly contracting left ventricle. In many cases the first manifestation of an inherited cardiomyopathy can be a sudden cardiac arrest. Other presentations include chest pain or breathlessness during exertion, palpitations and syncope. In many of the cardiomyopathies, the diagnosis can be made with a standard ECG and echocardiogram. However if the diagnosis is not certain or the cardiologist wishes to look at the heart structure in greater detail, a cardiac MRI may be performed.

Topics: Adult; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Death, Sudden, Cardiac; Desmoplakins; Disease Management; Echocardiography; Electric Countershock; Electrocardiography; Female; Heart Rate; Humans; Magnetic Resonance Imaging; Male; Mutation; Myocardium; Syncope

: Caveolin-1-deficient (cav1) mice display a severely diseased cardiac phenotype with systolic and diastolic heart failure. Accumulating evidence supports a causative role of uncoupled endothelial nitric oxide synthase in the development of these abnormalities. Interestingly, a similar molecular mechanism was proposed for anthracycline-induced cardiomyopathy. Currently, dexrazoxane is approved for the prevention of anthracycline-induced cardiomyopathy. Given the molecular similarities between the anthracycline-induced cardiomyopathy and the cardiomyopathy in cav1 mice, we questioned whether dexrazoxane may also prevent the evolution of the cardiac pathologies in cav1 mice. We evaluated dexrazoxane treatment for 6 weeks in cav1 mice and wild-type controls. This study provides the first evidence for a reduced reactive oxygen species formation in the vessels of dexrazoxane-treated cav1 mice. This reduced oxidative stress resulted in a markedly reduced rate of apoptosis, which finally was translated into a significantly improved heart function in dexrazoxane-treated cav1 mice. These hemodynamic improvements were accompanied by significantly lowered proatrial natriuretic peptide levels. Notably, these protective properties of dexrazoxane were not evident in wild-type animals. Taken together, these novel findings indicate that dexrazoxane significantly reduces vascular reactive oxygen species formation cav1. Because this is paralleled by an improved cardiac performance in cav1 mice, our data suggest dexrazoxane as a novel therapeutic strategy in this specific cardiomyopathy.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Cardiomyopathies; Cardiovascular Agents; Caveolin 1; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase; Phenotype; Razoxane; Reactive Oxygen Species; Treatment Outcome; Ventricular Function, Left

Topics: Acute Disease; Aged; Cardiac Surgical Procedures; Cardiomyopathies; Cardiovascular Agents; Chronic Disease; Echocardiography, Doppler, Color; Female; Fluid Therapy; Humans; Middle Aged; Recovery of Function; Severity of Illness Index; Stroke Volume; Treatment Outcome; Tricuspid Valve Insufficiency; Ventricular Function, Left

Left ventricle ejection fraction (LVEF) ≤ 30-35% is widely accepted as a cut-off for primary prevention with an implantable cardiac defibrillator (ICD) in patients with both ischaemic and non-ischaemic cardiomyopathy supposedly on optimal medical therapy. This study reports evolutions of LVEF and treatments of patients implanted in our institution with an ICD for primary prevention of sudden death, after 2 years of follow-up.. Among 84 patients with LVEF under 35% implanted between 2005 and 2007, 28 (33%) had improved their LVEF >35% after the 2 years of follow-up. During this period, even if Beta-blockers (98%) and renin-angiotensin system (RAS) blockers (95%) were already initially prescribed, treatments were significantly optimized with improvement of maximal doses of beta-blockers and RAS blockers at 2 year follow-up compared with initial prescription (62 vs. 37% and 68 vs. 45%, respectively). In patients with improved LVEF, a trend toward a better treatment optimization and revascularization procedures (in the sub-group of ischaemic patients) were observed compared with non-improved LVEF patients.. In our study of patients with prophylactic ICD, one-third of them have improved their LVEF after a 2 year follow-up. Despite an optimal medical therapy at the time of implantation, we were able to further improve the maximal treatment doses after implantation. This study highlights the issue of what should be considered as 'optimal' therapy and the possibility of improvement of LVEF related to a real optimized treatment before implantation.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathies; Cardiovascular Agents; Chi-Square Distribution; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Female; France; Humans; Male; Middle Aged; Primary Prevention; Recovery of Function; Retrospective Studies; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Doxorubicin, an anthracycline antibiotic commonly used as a chemotherapeutic agent for breast cancer, is well known to cause cardiotoxicity. We report the case of an active, otherwise healthy 57-year-old breast cancer survivor who, 17 years after chemotherapy, presented with symptoms of overt heart failure. She had no cardiac risk factors, and neither laboratory nor imaging findings suggested myocarditis or dilated cardiomyopathy. Echocardiographic findings and differential diagnosis led us to attribute her condition to late doxorubicin-induced cardiomyopathy. By virtue of tapered medical therapy, her left ventricular ejection fraction improved from 0.20 to 0.55 in 8 months, and she was asymptomatic after 1 year. The reversibility of left ventricular dysfunction in our patient and the very late appearance of cardiotoxicity secondary to doxorubicin therapy raise questions about the pathogenesis and prevalence of late doxorubicin-induced cardiomyopathy and how to improve outcomes in patients who present with related symptoms of heart failure.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cardiomyopathies; Cardiovascular Agents; Chemotherapy, Adjuvant; Doxorubicin; Electrocardiography; Female; Heart Failure; Humans; Magnetic Resonance Imaging; Mastectomy, Segmental; Middle Aged; Recovery of Function; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Erythropoietin exerts cardioprotective effects. The present study aimed to investigate the therapeutic effects of erythropoietin on cirrhotic cardiomyopathy.. Rats were divided into 5 groups: sham control; sham+ erythropoietin; bile duct ligation; bile duct ligation+erythropoietin; bile duct ligation+erythropoietin+anti-tumour necrosis factor alpha (TNFα) antibody and were studied 4 wk after surgery. Erythropoietin was administrated for 10 days before the study date. TNFα, erythropoietin receptor-1 expression and oxidative stress-related parameters were measured. In separate groups, isolated cardiomyocytes were subjected to contractile and relaxation studies. Cardiomyocyte cell line was used to test the direct effect of erythropoietin on nuclear factor (erythroid-derived 2)-like 2(Nrf2).. Erythropoietin receptor-1, TNFα and oxidative modified proteins were significantly increased (p<0.01), and the antioxidant regulator Nrf2 transcription decreased in cirrhotic hearts (p<0.01). Erythropoietin reversed these parameters. Maximal cardiac contractile and relaxation velocity was significantly decreased in cirrhotic cardiomyocytes. Erythropoietin significantly reversed these inhibitions. Anti-TNFα antibody significantly decreased cardiac TNFα content but did not further increase contractility.. TNFα and oxidative stress are involved in cardiac dysfunction in the cirrhotic heart. Erythropoietin significantly decreased TNFα and oxidative stress and reversed the impaired cardiac function.

Topics: Animals; Biomarkers; Blotting, Western; Cardiomyopathies; Cardiovascular Agents; Erythropoietin; Heart; Liver Cirrhosis, Experimental; Male; Myocardium; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Reverse Transcriptase Polymerase Chain Reaction; Treatment Outcome; Tumor Necrosis Factor-alpha

Topics: Aortic Aneurysm; Aortic Dissection; Cardiomyopathies; Cardiovascular Agents; Cooperative Behavior; Female; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Hypertension, Pulmonary; Infant, Newborn; Interdisciplinary Communication; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Diagnosis; Risk Assessment; Venous Thromboembolism

Cardiomyopathy refers to nonspecific myocardial dysfunction that may be due to a variety of causes. Viral illnesses have long been known to cause cardiomyopathy, and the list of viral causes is extensive. Influenza infection is a rare cause of myocarditis. Recent reports, however, indicate that influenza A (H1N1) can cause acute myocarditis and cardiomyopathy in adults and fulminant myocarditis in children as seen during the 2009 global outbreak of the H1N1 influenza virus. The following presents a case series of adult patients with acute reversible cardiomyopathy associated with influenza A (H1N1) infection (see Table 1 for patient characteristics).

Topics: Acute Disease; Aged; Antiviral Agents; Cardiomyopathies; Cardiovascular Agents; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Middle Aged; Myocarditis; Recovery of Function; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left

Noncompaction myocardium (NCM) is a genetic heterogeneous primary cardiomyopathy which affects both children and adults and can be either isolated or combined with other congenital heart disorders. It has common pathogenesis of symptoms but is distinguished by pronounced clinical polymorphism. We have observed 25 adult patients (15 men, 10 women aged from 20 to 62 years, mean age 42.9+/-13.3 years) with NCM syndrome. Heart failure have been found in 96% of patients (functional class [FC] I in 7, II - in 6, III in 7, and IV - in 4 patients). Ninety two percent of patients have ventricular extrasystoles, 32% - atrial fibrillation, 28% - FC I-III angina. Mean end diastolic left ventricular dimension is 6.5+/-0.8cm, ejection fraction 29.7+/-13.0%, mean pulmonary artery pressure - 42.6+/-13.5 mm Hg. Intracardiac thrombosis have been found in 24% of patients. In 7 patients morphological study of myocardium has been performed. NCM syndrome was diagnosed at initial investigation just in 1 case. We distinguished the following clinical masks (variants of diagnosis) of NCM: 1) clinically not manifest, is revealed at accidental examination (4%); 2) exists under mask of "idiopathic" rhythm disturbances (8%); 3) has a mask of ischemic heart disease; 4) is revealed in patients with acute or subacute myocarditis (12%); 5) has a mask of dilated cardiomyopathy (52%); 6) NCM in patients with other primary cardiomyopathies (hypertrophic, restrictive, genetic myopathy, arrhythmogenic right ventricular dysplasia). Combination of NCM with congenital heart defects has been found in 20% of patients. In 56% of cases myocarditis was diagnosed (it was viral in no less than 44%). Only in 32% of patients it is possible to consider presence of isolated NCM syndrome. This paper contains discussion of problems of diagnostics (including morphological) and treatment in the presented group of patients, significance of myocarditis for development of decompensation, role of NCM in patients with other primary cardiomyopathies, possibility of compensatory (secondary) character of NCM in severe systolic dysfunction.

Topics: Adult; Arrhythmias, Cardiac; Biopsy; Cardiomyopathies; Cardiovascular Agents; Diagnosis, Differential; Disease Management; Electrocardiography; Female; Heart Defects, Congenital; Heart Failure; Heart Function Tests; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocarditis; Myocardium; Prognosis; Syndrome; Tomography, Spiral Computed; Treatment Outcome

Patients with ischemic heart disease and depressed left ventricular (LV) ejection fraction (LVEF) develop varying degrees of LV remodeling after cardiac surgical revascularization. Fifty-three patients with stable ischemic heart disease and impaired LV function (LVEF 34.9 ± 4%) were prospectively followed up for 24 months. Thirty-seven patients underwent coronary artery bypass grafting (CABG), 16 patients were treated conservatively. Cardiac magnetic resonance imaging (MRI) and SPECT were performed at baseline and after 12 and 24 months of follow-up. The patients were divided into responders and non-responders depending on the degree of LVEF improvement at 24 months follow-up (>5%-responders). MRI with ≤5 segments with DE/wall thickness ratio (DEWTR) ≥50% predicted LV reverse remodeling with a sensitivity of 86% and a specificity of 75% (AUC 0.81). An MRI finding of ≤2 segments with the DEWTR ≥75% had a corresponding sensitivity of 71% and specificity of 67% (AUC 0.75) while fixed perfusion defect on SPECT <16.5% of LV predicted reverse remodeling with a sensitivity of 64% and a specificity of 69% (AUC 0.64). A preoperative number of segments with the DE/wall thickness ratio of ≥50 and ≥75% obtained by MRI, was found to be a better predictor of left ventricular reverse remodeling than fixed perfusion defect by SPECT. No other MRI or SPECT parameter predicted LVEF improvement at 24 months after CABG.

Topics: Aged; Aged, 80 and over; Cardiomyopathies; Cardiovascular Agents; Coronary Angiography; Coronary Artery Bypass; Czech Republic; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Prospective Studies; Recovery of Function; Stroke Volume; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

Topics: Biopsy; Cardiac Resynchronization Therapy; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Fatal Outcome; Female; Heart Failure; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Middle Aged; Multiple Organ Failure; Treatment Outcome

Spontaneous coronary artery dissection (SCAD) is a rare cause of chest pain and cardiomyopathy. This phenomenon usually occurs during the peripartum period. SCAD associated with exercise and heavy weight lifting is even rarer and has been reported in less than 10 cases in the literature. We describe a case of SCAD associated with heavy weight lifting and exercise in a 29-year-old male who presented with exertional chest pain. The patient subsequently underwent a cardiac catheterization that showed a left ventricular ejection fraction of 40% and a dissection in the left anterior descending (LAD) coronary artery after the first diagonal/septal branch with extension to the distal LAD that wrapped around the apex. He was effectively managed with the combination of medical therapy followed by a few days later with stenting. In summary, diagnosis and treatment of this rare phenomenon is a challenge, but early diagnosis and appropriate management can lead to a successful outcome.

Topics: Adult; Angina Pectoris; Angioplasty, Balloon, Coronary; Aortic Dissection; Cardiac Catheterization; Cardiomyopathies; Cardiovascular Agents; Coronary Aneurysm; Electrocardiography; Humans; Male; Myocardial Ischemia; Stents; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Weight Lifting

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.. Three month old female mdx mice were exposed to the β(1) 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.. 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.. This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice.

Topics: Adrenergic beta-Agonists; Analysis of Variance; Animals; Aortic Valve; Blood Pressure; Body Weight; Cardiomyopathies; Cardiovascular Agents; Collagen; Disease Models, Animal; Drug Administration Schedule; Dystrophin; Female; Fibrosis; Heart Rate; Injections, Intraperitoneal; Isoproterenol; Mice; Mice, Inbred mdx; Muscle Strength; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Myocardial Contraction; Myocardium; Poloxamer; Stroke Volume; Time Factors; Ventricular Function, Left; Ventricular Pressure

Elevated catecholamine levels are a well-recognized cause of various types of cardiomyopathy. Causes of catecholamine elevation include tumors, toxins, drugs, emotional stress, and sepsis. Milnacipran is a dual and equipotent inhibitor of norepinephrine and serotonin uptake. It is frequently prescribed as therapy for fibromyalgia, and the drug has a good safety profile. Herein, we report the case of a 42-year-old woman with undefined connective-tissue disease and fibromyalgia who developed a severe and reversible cardiomyopathy while taking recommended doses of milnacipran. The cardiomyopathy was associated with a hyperadrenergic state manifested by tachycardia, hypertension, and elevated plasma catecholamine levels. The discontinuation of milnacipran and the initiation of anti-failure therapy resulted in complete resolution of the cardiomyopathy in 6 months. To our knowledge, this is the first report of milnacipran as a possible cause of catecholamine-induced cardiomyopathy.

Topics: Adrenergic Uptake Inhibitors; Adult; Cardiomyopathies; Cardiovascular Agents; Catecholamines; Coronary Angiography; Cyclopropanes; Female; Humans; Hypertension; Magnetic Resonance Imaging; Milnacipran; Selective Serotonin Reuptake Inhibitors; Tachycardia; Time Factors; Treatment Outcome; Up-Regulation

We previously showed that omega-3 polyunsaturated fatty acids (PUFAs) reduce vulnerability to atrial fibrillation (AF). The mechanisms underlying this effect are unknown.. The purpose of this study was to use a genome-wide approach to identify gene expression profiles involved in a new model of AF vulnerability and to determine whether they were altered by PUFA therapy.. Thirty-six dogs were randomized evenly into three groups. Two groups were paced using simultaneous atrioventricular pacing (SAVP) at 220 bpm for 14 days to induce atrial enlargement, fibrosis, and susceptibility to AF. One group was supplemented with oral PUFAs (850 mg/day) for 21 days, commencing 7 days before the start of pacing (SAVP-PUFAs). The second group received no PUFAs (SAVP-No PUFAs). The remaining dogs were unpaced, unsupplemented controls (CTRL). Atrial tissue was sampled at the end of the protocol. Gene expression was analyzed in four dogs randomly selected from each group (n = 12) via microarray. Results were confirmed with quantitative real-time polymerase chain reaction (RT-PCR) and histology on all 36 dogs.. Microarray or quantitative RT-PCR results showed that SAVP-No PUFAs dogs had significantly increased mRNA levels of protein kinase B (Akt), epidermal growth factor (EGF), JAM3, myosin heavy chain alpha (MHCalpha), and CD99 and significantly decreased levels of Smad6 compared with CTRL dogs. Quantitative RT-PCR showed that PUFA supplementation was associated with significant down-regulation of Akt, EGF, JAM3, MHCalpha, and CD99 levels compared with SAVP-No PUFAs dogs.. The effect of PUFAs on these fibrosis, hypertrophy, and inflammation related genes suggests that, in this model, PUFA-mediated prevention of AF may be due to attenuation of adverse remodeling at the genetic level in response to mechanical stress.

Topics: Animals; Atrial Fibrillation; Atrial Function; Cardiomyopathies; Cardiovascular Agents; Disease Models, Animal; Dogs; Fatty Acids, Omega-3; Fibrosis; Gene Expression; Heart Atria; Hypertrophy; Stress, Mechanical

The matrix metalloproteinases (MMPs) play a key role during cardiac remodeling. The aim of the study was to investigate the changes in collagenous proteins and MMPs in the model of non-ischemic, anthracycline-induced chronic cardiomyopathy in rabbits using both biochemical and histological approaches. The study was carried out in three groups of Chinchilla male rabbits: 1) daunorubicin (3 mg/kg, once weekly for 10 weeks), 2) control (saline in the same schedule), 3) daunorubicin with the cardioprotectant dexrazoxane (60 mg/kg, before each daunorubicin). Morphological changes in the myocardium of daunorubicin-treated animals were characterized by focal myocardial interstitial fibrosis of different intensity. The subsequent proliferation of the fibrotic tissue was marked by an increased content of both collagen types I and III, which resulted in their typical coexpression in the majority of bundles of fibers forming either smaller or larger scars. Biochemical analysis showed a significantly increased concentration of hydroxyproline, mainly in the pepsin-insoluble fraction of collagenous proteins, in the daunorubicin-treated group (1.42+/-0.12 mg/g) as compared with the control (1.03+/-0.04 mg/g) and dexrazoxane (1.07+/-0.07 mg/g) groups. Dexrazoxane co-administration remarkably reduced the cardiotoxic effects of daunorubicin to the extent comparable with the controls in all evaluated parameters. Using zymography, it was possible to detect only a gelatinolytic band corresponding to MMP-2 (MMP-9 activity was not detectable). However, no significant changes in MMP-2 activity were determined between individual groups. Immunohistochemical analysis revealed increased MMP-2 expression in both cardiomyocytes and fibroblasts. Thus, this study has revealed specific alterations in the collagen network in chronic anthracycline cardiotoxicity in relationship to the expression and activity of major MMPs.

Topics: Animals; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Chronic Disease; Collagen; Daunorubicin; Disease Models, Animal; Drug Interactions; Fibrosis; Hydroxyproline; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myocardium; Rabbits; Razoxane; Ventricular Remodeling

Topics: Cardiomyopathies; Cardiovascular Agents; Echocardiography, Three-Dimensional; Humans

We investigated whether P144, a synthetic peptide from transforming growth factor-beta(1) (TGF-beta(1)) type III receptor betaglycan, exhibits cardiac antifibrotic properties.. The study was carried out in one group of 10-week-old normotensive Wistar-Kyoto rats treated with vehicle (V-WKY), one group of 10-week-old spontaneously hypertensive rats treated with vehicle (V-SHR), and one group of 10-week-old SHR treated with P144 (P144-SHR) for 12 weeks. Two more groups of 10-week-old untreated WKY and SHR were used to assess baseline values of the parameters tested. In addition, the effects of P144 on rat cardiac fibroblasts stimulated with TGF-beta(1) were also studied. Compared with V-WKY, V-SHR exhibited significant increases in the myocardial expression of phosphorylated Smad2, 38 and 42 kDa connective tissue growth factor (CTGF) isoforms, procollagen alpha1 (I) mRNA, and collagen type I protein, as well as in the expression of lysyl oxidase (LOX) mRNA and protein, collagen cross-linking and deposition. P144 administration was associated with significant reduction in all these parameters in P144-SHR. TGF-beta(1)-stimulated fibroblasts exhibited significant increases in phosphorylated Smad2, 38 and 42 kDa CTGF proteins, and procollagen alpha(1) (I) mRNA compared with control fibroblasts. No significant differences were found in these parameters between fibroblasts incubated with TGF-beta(1) and P144 and control fibroblasts.. These results show that P144 inhibits TGF-beta(1)-dependent signalling pathway and collagen type I synthesis in cardiac fibroblasts. These effects may be involved in the ability of this peptide to prevent myocardial fibrosis in SHR.

Topics: Animals; Blood Pressure; Cardiomyopathies; Cardiovascular Agents; Cell Line; Collagen Type I; Collagen Type I, alpha 1 Chain; Connective Tissue Growth Factor; Disease Models, Animal; Fibroblasts; Fibrosis; Hypertension; Injections, Intraperitoneal; Male; Myocardium; Peptide Fragments; Protein-Lysine 6-Oxidase; Proteoglycans; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Transforming Growth Factor beta; RNA, Messenger; Signal Transduction; Smad2 Protein; Transforming Growth Factor beta1

Methylphenidate is a potent central nervous system stimulant that exerts its effects by increasing synaptic levels of dopamine and norepinephrine. It has become key to treating attention deficit-hyperactivity disorder (ADHD) in children and adolescents. As the use of stimulant medications has ballooned in the past decade, so too has awareness of the cardiovascular complications of these drugs. Effects on heart rate and blood pressure as well as tachyarrhythmias have been well described. However, acute cardiomyopathy and pericarditis secondary to methylphenidate use has been rarely reported. We report the case of a 17-year-old male who developed chest pain, elevated cardiac biomarkers, and acute left ventricular dysfunction following a single dose of methylphenidate. The risk of cardiomyopathy in the setting of methylphenidate treatment should prompt further study on the safety of this drug, and lead to ways of identifying those at risk of developing these complications.

Topics: Acute Disease; Adolescent; Angina Pectoris; Attention Deficit Disorder with Hyperactivity; Cardiomyopathies; Cardiovascular Agents; Central Nervous System Stimulants; Drug Therapy, Combination; Electrocardiography; Humans; Male; Methylphenidate; Pericarditis; Ventricular Dysfunction, Left

The aim of this study was to report a series of patients with stress cardiomyopathy precipitated by the intravenous administration of catecholamines and beta-receptor agonists.. Stress cardiomyopathy is a syndrome of transient cardiac dysfunction precipitated by intense emotional or physical stress. Excessive sympathetic stimulation is believed to be central to the pathogenesis of this disorder, but a causal link has not been convincingly demonstrated.. We observed 9 cases of stress cardiomyopathy precipitated immediately by the intravenous administration of epinephrine (n = 6) or dobutamine (n = 3). Patients were evaluated with coronary angiography and with serial echocardiography, electrocardiography, and cardiac enzymes.. The median age was 44 years (interquartile range [IQR]: 30 to 48 years), and 7 (78%) were woman. Troponin-I was mildly elevated (median 4.07 ng/ml, IQR: 0.47 to 5.63 ng/ml), but none of the patients undergoing angiography had obstructive coronary disease. All patients developed corrected QT interval (QTc interval) prolongation (median QTc interval 504 ms, IQR: 477 to 568 ms) within 24 h of receiving drug. All 3 previously described variants of left ventricular "ballooning" (apical, midventricular, and basal) were observed. The median ejection fraction on admission was 35% (IQR: 35% to 40%). During follow-up (median 7 days, IQR: 4 to 13 days) there was recovery of left ventricular systolic function in all patients (median ejection fraction 55%, IQR: 40% to 60%, p < 0.001 vs. admission).. Exposure to catecholamines and beta-receptor agonists used routinely during procedures and diagnostic tests can precipitate all the features of stress cardiomyopathy, including cardiac isoenzyme elevation, QTc interval prolongation, and rapidly reversible cardiac dysfunction. These observations strongly implicate excessive sympathetic stimulation as central to the pathogenesis of this unique syndrome.

Topics: Adrenergic beta-Agonists; Adult; Cardiomyopathies; Cardiovascular Agents; Catecholamines; Dobutamine; Epinephrine; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Ventricular Dysfunction, Left

A 5-year-old English Bulldog was presented for acute onset of syncope and fatigue caused by sustained ventricular tachycardia with left bundle block morphology and inferior axis. This arrhythmia had the electrocardiographic features of a ventricular tachycardia arising from the right ventricular outflow tract (RVOT), as described in an experimental canine model and in people. Since a RVOT aneurysm was identified by echocardiography, a segmental form of arrhythmogenic right ventricular cardiomyopathy (ARVC) was suspected. Gross examination of the heart confirmed the bulging of the RVOT and histological examination of the ventricular myocardium revealed segmental involvement of the RVOT with transmural fibro-fatty degeneration. To the authors' knowledge, this is the first reported case of AVRC in an English Bulldog and the first example of segmental AVRC described in the dog.

Topics: Animals; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Dog Diseases; Dogs; Fatal Outcome; Female; Ventricular Dysfunction, Right

Severe and extensive coronary artery disease is the underlying cause of stress-induced wall motion abnormalities (SWMA) with low-dose (10 microg/kg/min) dobutamine suggesting that these abnormalities may identify those with poor outcome.. We assessed the prognostic value of low-dose SWMA in medically treated patients with ischemic cardiomyopathy.. Low- and peak-dose dobutamine echocardiography was performed in 235 patients with ischemic cardiomyopathy (ejection fraction 31% +/- 8%) who were treated with medical therapy. The survival of patients with low-dose SWMA (n = 33) was compared with the survival of patients without ischemia (n = 85) and those with peak-dose SWMA (n = 117).. There were 123 cardiac deaths (52%) during follow-up of 4.1 +/- 3.3 years. Multivariate predictors of cardiac death were age (p = 0.002, hazard ratio [HR]: 1.03), diabetes (p = 0.028, HR: 1.54), New York Heart Association (NYHA) class III, IV heart failure (p = 0.001, HR: 1.94), the presence of peak dose SWMA (p < 0.001, HR: 2.59), and low-dose SWMA (p = 0.005, HR: 2.28). Survival of patients without ischemia was significantly better than those with peak-dose SWMA (p < 0.0001) and those with low-dose SWMA (p = 0.001). The survival of patients with low-dose SWMA was the same as those with peak-dose SWMA (p = 0.89).. Low-dose SWMA is an independent predictor of cardiac mortality in medically treated patients with ischemic cardiomyopathy. Patients with low-dose SWMA are at equivalent risk to those with peak-dose SWMA.

Topics: Aged; Cardiomyopathies; Cardiovascular Agents; Dobutamine; Echocardiography, Stress; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), +/- dP/dt(max) and t-dP/d(max)t, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and +/- dP/dt(max), increased LVEDP, and prolonged t-dP/dt(max) than normal rats; (2) LVSP and +/- dP/dt(max) in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t-dP/dt(max) were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

Topics: Animals; Blood Pressure; Cardiomyopathies; Cardiovascular Agents; Connectin; Cytoskeleton; Diabetes Mellitus, Experimental; Female; Gene Expression; Gynostemma; Heart; Male; Muscle Proteins; Myocardium; Phytotherapy; Plant Extracts; Protein Kinases; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger

We present an unusual case of cardiomyopathy in a two month old male infant with a grade-I systolic murmur. Echocardiographic examination disclosed left ventricular (LV), dysplasia with saw-tooth like inwards myocardial projections extending from the lateral walls towards the LV cavity. There was mild LV systolic dysfunction with apical hypokinesia. Cardiovascular magnetic resonance demonstrated in detail these cross bridging muscular projections originating from the inferior interventricular septum and lateral LV wall, along with areas of hypokinesis at the LV septum and apex in a noncoronary distribution, without any late gadolinium enhancement. We have termed this condition saw-tooth cardiomyopathy because of the very characteristic appearance.

Topics: Cardiomyopathies; Cardiovascular Agents; Heart Failure; Heart Murmurs; Humans; Infant; Magnetic Resonance Imaging; Male; Myocardium; Ventricular Dysfunction, Left; Ventricular Septum

To study fractional composition of red cell membrane (RCM) lipids in patients with severe iron-deficiency anemia (IDA) complicated by myocardiodystrophy prior to treatment and after 1-month combined treatment with sorbifer and mildronate.. Fatty acid composition of RCM lipids was studied in 12 patients with severe chronic posthemorrhagic IDA complicated by myocardiodystrophy and in 15 healthy subjects. Extraction of lipids from blood red cells and methylation of fatty acids were performed according to K.M. Sinyak et al. (1976). Relative content of fatty acids was determined at chromatography.. The study detected increased content of saturated fatty acids, especially palmitic and decreased content of unsaturated fatty acids especially fraction of omega6-polyunsaturated fatty acids: arachidonic and gamma-linolenic.. Sorbifer in combination with mildronate improved fatty acid composition of blood red cells in patients with iron-deficiency anemia.

Topics: Anemia, Iron-Deficiency; Cardiomyopathies; Cardiovascular Agents; Drug Therapy, Combination; Erythrocytes; Fatty Acids; Follow-Up Studies; Humans; Methylhydrazines; Middle Aged; Treatment Outcome; Vitamin E; Vitamins

This report describes the prompt resolution of an apical left ventricular (LV)-thrombus complicating transient apical ballooning in a 74-year-old woman. The patient was admitted to our emergency department with acute chest pain and ST-elevation on the electrocardiogram. Coronary angiography showed normal coronary arteries and LV-angiography demonstrated the presence of apical ballooning akinesis associated with basal hypercontraction. Echocardiography and MRI studies confirmed the presence of LV-apex akinesis and detected an apical thrombus. Follow-up echocardiography on day 12 before discharge of the patient, revealed a marked improvement of regional contractility of the LV-apex and surprisingly the complete resolution of the LV-apical thrombus. The patient was diagnosed with takotsubo cardiomyopathy.

Topics: Aged; Angina Pectoris; Anticoagulants; Cardiomyopathies; Cardiovascular Agents; Female; Heart Diseases; Humans; Remission Induction; Thrombosis; Ventricular Dysfunction, Left

During the past 18 years, sildenafil has evolved from a potential anti-angina drug to an on-demand treatment for erectile dysfunction and more recently to a new orally active treatment for pulmonary hypertension. Recent studies suggest that the drug has powerful cardioprotective effect against ischemia/reperfusion injury, doxorubicin-induced cardiomyopathy and anti-hypertensive effect induced by chronic inhibition of nitric oxide synthase in animals. Based on several recent basic and clinical studies, it is clear that sildenafil and other clinically approved type-5 phosphodiesterase-5 inhibitors including vardenafil and tadalafil will eventually be developed for several cardiovascular indications including essential hypertension, endothelial dysfunction, ischemia/reperfusion injury, myocardial infarction, ventricular remodeling and heart failure.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Antihypertensive Agents; Carbolines; Cardiomyopathies; Cardiovascular Agents; Cyclic Nucleotide Phosphodiesterases, Type 5; Disease Models, Animal; Doxorubicin; Endothelium, Vascular; Enzyme Inhibitors; Erectile Dysfunction; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary; Imidazoles; Male; Myocardial Infarction; Myocardial Reperfusion Injury; NG-Nitroarginine Methyl Ester; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents; Ventricular Remodeling

Takotsubo cardiomyopathy is an acute cardiac syndrome characterized by transient LV regional wall motion abnormalities (with peculiar apical ballooning appearance), chest pain or dyspnea, ST-segment elevation and minor elevations of cardiac enzyme levels. A 68-year-old woman was admitted to the Emergency Department because of sudden onset chest pain occurred while transferring her daughter, who had earlier suffered a major seizure, to the hospital. The EKG showed sinus tachycardia with ST-segment elevation in leads V2-V3 and ST-segment depression in leads V5-V6, she was, thus, referred for emergency coronary angiography. A pre-procedural transthoracic echocardiogram revealed regional systolic dysfunction of the LV walls with hypokinesis of the mid-apical segments and hyperkinesis of the basal segments. Coronary angiography showed patent epicardial coronary arteries; LV angiography demonstrated the characteristic morphology of apical ballooning with hyperkinesis of the basal segments and hypokinesis of the mid-apical segments. The post-procedural course was uneventful; on day 5 after admission the echocardiogram revealed full recovery of apical and mid-ventricular regional wall-motion abnormalities.. Takotsubo cardiomyopathy is a relatively rare, unique entity that has only recently been widely appreciated. Acute stress has been indicated as a common trigger for the transient LV apical ballooning syndrome, especially in postmenopausal women. The present report is a typical example of stress-induced takotsubo cardiomyopathy in a Caucasian Italian postmenopausal woman.

Topics: Aged; Cardiomyopathies; Cardiovascular Agents; Coronary Angiography; Echocardiography; Electrocardiography; Female; Humans; Ventricular Dysfunction, Left

Doxorubicin causes a chronic cardiomyopathy in which reactive oxygen species (ROS) accumulate over time and are associated with genetic and functional lesions of mitochondria. Dexrazoxane is a cardioprotective iron chelator that interferes with ROS production. We aim to analyze the effects of dexrazoxane on mitochondria in the prevention of doxorubicin-induced chronic myocardial lesions.. Wistar rats (11 weeks of age) were injected with intravenous doxorubicin (0.8 mg kg(-1) weekly for 7 weeks) with or without simultaneous dexrazoxane (8 mg kg(-1)). Animals were killed at 48 weeks. Cardiomyopathy was scored clinically and histologically and cardiac mitochondria were analyzed.. Compared to control rats receiving saline, rats treated with doxorubicin alone developed a clinical, macroscopic, histological and ultrastructural cardiomyopathy with low cytochrome c-oxidase (COX) activity (26% of controls). The expression of the mtDNA-encoded COX II subunit was reduced (64% of controls). Myocardia exhibited a high production of ROS (malondialdehyde 338% and superoxide 787% of controls). Mitochondria were depleted of mitochondrial DNA (mtDNA copy number 46% of controls) and contained elevated levels of mtDNA deletions. Dexrazoxane co-administration prevented all these effects of doxorubicin on mitochondria, except that hearts co-exposed to doxorubicin and dexrazoxane had a slightly lower mtDNA content (81% of controls) and mtDNA deletions at low frequency.. Dexrazoxane prevented doxorubicin induced late-onset cardiomyopathy and also protected the cardiac mitochondria from acquired ultrastructural, genetic and functional damage.

Topics: Animals; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; DNA, Mitochondrial; Doxorubicin; Electron Transport Complex IV; Energy Metabolism; Gene Expression; Male; Malondialdehyde; Mitochondria, Heart; Oxidative Phosphorylation; Rats; Rats, Wistar; Razoxane; Reactive Oxygen Species; Superoxides

Topics: Angioplasty, Balloon, Coronary; Cardiomyopathies; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Bypass; Humans; Myocardial Ischemia; Paclitaxel; Patient Selection; Prosthesis Design; Radiography; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

We compared the outcome of drug eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction with the outcome of a similar group of patients undergoing coronary artery by-pass grafting (CABG).. Revascularization provides long-term benefits in patients with severe LV dysfunction. However the modality to achieve it is still unsettled in this high risk group of patients.. Two-hundred-twenty patients (20% women) with severe LV dysfunction (LV Ejection Fraction

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiomyopathies; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Bypass; Female; Follow-Up Studies; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Prosthesis Design; Research Design; Retrospective Studies; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; United States; Ventricular Dysfunction, Left

Chronic heart failure (CHF) in patients with diabetes mellitus (DM) is a condition that is frequent and has a poor prognosis. Diabetes mellitus is an independent risk factor for CHF and vice versa. CHF is found in 10-15% of the patients with DM compared to 3% in individuals without DM. Apart from CHD and hypertension, hyperglycaemia and insulin resistance are directly linked to the development of diastolic dysfunction and to CHF. According to the stepwise diagnostic procedure recommended by the ESC in its guidelines from 2005, if heart failure is suspected, the disease should first be diagnosed by ECG, X-ray, or testing for natriuretic peptide and followed by echocardiography when test results are abnormal. Treatment of CHF in patients with diabetes mellitus is the same as that for nondiabetic patients and includes the use of ACEIs, ARBSs (as an alternative to or in combination with ACEIs), BBs, diuretics (in particular loop diuretics), aldosterone inhibitors and digitalis. Most importantly, meticulous glucose control is a must in patients with diabetes mellitus and CHF to improve prognosis. Contraindications for antidiabetic drugs such as glitazones for CHF-NYHA classes I-IV and metformin for NYHA classes III-IV need to be considered in patients with CHF and diabetes mellitus.

Topics: Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Diabetes Complications; Diabetic Angiopathies; Heart Failure; Humans; Hypoglycemic Agents; Prognosis; Risk Factors

Doxorubicin is one of the most active drugs in oncology, with cardiotoxicity as a serious side effect of its application. The aim of this study was to investigate dexrazoxane and amifostine impact on the evolution of myocardial changes induced by doxorubicin. BalbC female mice were treated with doxorubicin only (10 mg/kg, single intravenous push), or with dexrazoxane (200 mg/kg, intraperitoneal [ip]) or amifostine (200 mg/kg, ip) 60 mins or 30 mins prior to treatment with doxorubicin, respectively. Blood sampling for determination of conventional serum-marker activity was performed 48 hrs later. The grade of histopathology changes was evaluated by light microscopy 1.5 and 3 months after treatments using the Billingham scoring method. Control groups consisted of nontreated mice. After doxorubicin-only treatment, the grade of heart tissue damage was found to increase in the period between 1.5 and 3 months. A similar but less intense progression was also detected in amifostine-pretreated animals, with significant difference among median Billingham scores between the two time points. The pretreatment with dexrazoxane suspended expansion of tissue lesions in time. Changes in serum enzyme activity revealed two correlations: the greater reduction in alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) leakage is associated with a lower percentage of damaged tissue, and the creatine kinase to alpha-HBDH percent of difference ratio being greater than one is correlated with limited spreading of pathological lesions. Our results indicate that the development of doxorubicin-induced heart failure is based on a slow and persistent expansion of pathological process even long after the completion of the treatment. Dexrazoxane has proved to be successful and superior over amifostine against such an evolution of doxorubicin cardiomyopathy.

Topics: Amifostine; Animals; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Creatine Kinase; Doxorubicin; Female; Hydroxybutyrate Dehydrogenase; Mice; Mice, Inbred BALB C; Myocardium; Radiation-Protective Agents; Razoxane; Time Factors

Efforts to improve severely impaired myocardial function include transplantation of autologous hematopoietic side population (SP) stem cells. The transmembrane ABC-type (ATP binding cassette) half-transporter ABCG2 (BCRP) serves as a marker protein for SP cell selection. We have recently shown that other ABC transport proteins such as ABCB1 and ABCC5 are differentially expressed in normal and diseased human heart. Here we investigated localization and individual ABCG2 expression in 15 ventricular (including 10 cardiomyopathic) and 51 auricular heart tissue samples using immunohistochemistry, confocal laser scanning fluorescence microscopy, and real-time RT-PCR. Individual genotypes were assigned using PCR-restriction fragment length polymorphism (RFLP) analysis and subsequently correlated to ABCG2 mRNA levels. ABCG2 was localized in endothelial cells of capillaries and arterioles of all samples. Ventricular samples from cardiomyopathic hearts exhibited significantly increased levels of ABCG2 mRNA (ABCG2/18S rRNA: 1.08 +/- 0.30 x 10(-7); p=0.028 (dilative cardiomyopathy) and 1.16 +/- 0.46 x 10(-7); p=0.009 (ischemic cardiomyopathy) compared with 0.44 +/- 0.26 x 10(-7) in nonfailing hearts). The individual haplotypes were not associated with altered mRNA expression. ABCG2 is variably expressed in endothelial cells of human heart, where it may function as a protective barrier against cardiotoxic drugs such as anthracyclines or mitoxantrone. ABCG2 expression is induced in dilative and ischemic cardiomyopathies.

Topics: Aged; Aged, 80 and over; Arterioles; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Capillaries; Cardiomyopathies; Cardiovascular Agents; Endothelial Cells; Endothelium, Vascular; Female; Genotype; Humans; Immunoblotting; Immunohistochemistry; Male; Microscopy, Confocal; Middle Aged; Myocardium; Neoplasm Proteins; Polymorphism, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stem Cells

Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes.. In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 microg/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone.. These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.

Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Blood Cell Count; Cardiomyopathies; Cardiovascular Agents; Cells, Cultured; Doxorubicin; Drug Evaluation, Preclinical; Heart Rate; Male; Mice; Mice, Inbred BALB C; Myoblasts; Myocytes, Cardiac; Proto-Oncogene Proteins c-akt; Rats; Razoxane; Reactive Oxygen Species; Single-Blind Method; Thrombopoietin; Ultrasonography

We examined the efficacy of drug-eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction and compared the outcome with a similar group of patients undergoing bare metal stent (BMS) implantation.. Patients with severe LV dysfunction are a high risk group. DES may improve the long term outcomes compared with BMS.. One hundred and ninety one patients (23% women) with severe LV dysfunction (LV ejection fraction < or =35%) underwent coronary stent implantation between May 2002 and May 2005 and were available for follow-up. One hundred and twenty eight patients received DES (Sirolimus in 72 and Paclitaxel in 54) and 63 patients had BMS. Patients with acute S-T elevation myocardial infarction (STEMI) were excluded. The primary endpoint was cardiovascular mortality. A composite endpoint of major adverse cardiac events (MACE) including cardiovascular mortality, myocardial infarction (MI), and target vessel revascularization (TVR) was the secondary endpoint.. Mean follow-up was 420 +/- 271 days. No differences were noted in age (69 +/- 10 years vs. 70 +/- 10 years, P = NS), number of vessel disease (2.3 +/- 0.7 vs. 2.2 +/- 0.8, P = NS), history of congestive heart failure (47% vs. 46%, P = NS), MI (60% vs. 61%, P = NS), or number of treated vessels (1.3 +/- 0.5 vs. 1.3 +/- 0.6, P = NS) for the DES and BMS group, respectively. Diabetes was more common among DES patients (45% vs. 25%, P = 0.01). The left ventricular ejection fraction (LVEF) was similar between the two groups (28% +/- 6% vs. 26% +/- 8%, P = NS for the DES and BMS, respectively). During the follow-up, there were a total of 25 deaths of which two were cancer related (2 in DES group). There were 23 cardiac deaths, 8/126 (6%) which occurred in the DES group and 15/63 (24%) in the BMS group (P = 0.05 by log-rank test). MACE rate was 10% for the DES group and 41% for the BMS group (P = 0.003). NYHA class improved in both groups (from 2.5 +/- 0.8 to 1.7 +/- 0.8 in DES and from 2 +/- 0.8 to 1.4 +/- 0.7 in the BMS, P = NS).. Compared with bare-metal stents, DES implantation reduces mortality and MACE in high risk patients with severe left ventricular dysfunction.

Topics: Aged; Aged, 80 and over; Blood Vessel Prosthesis Implantation; Cardiomyopathies; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Paclitaxel; Prosthesis Design; Research Design; Severity of Illness Index; Sirolimus; Stents; Stroke Volume; Survival Rate; Treatment Outcome; United States; Ventricular Dysfunction, Left

Background A 49-year-old woman presented at hospital, 8 days after giving birth to twins, with signs and symptoms of congestive heart failure. She had no history of heart disease, exposure to cardiotoxic agents or family history of heart muscle disease. Investigations Physical examination and laboratory blood tests, electrocardiography, transthoracic echocardiography. Diagnosis Peripartum cardiomyopathy. Management Standard heart failure therapy including beta-blockers, angiotensin-converting-enzyme inhibitors, diuretics and systemic anticoagulation.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiomyopathies; Cardiovascular Agents; Diuretics; Female; Humans; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Treatment Outcome

Topics: Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antineoplastic Agents; Cardiomyopathies; Cardiovascular Agents; Dose-Response Relationship, Drug; Heart; Humans; Predictive Value of Tests; Razoxane; Risk Factors; Stroke Volume

Peripartum cardiomyopathy (PPCM) is a condition that affects women during the reproductive years in the late pregnancy period and/or early postpartum period. Although it is associated with several risk factors and various hypotheses exist of its etiology the cause of this disorder is still unknown. Standard therapy for PPCM is the same as for heart failure. Studies examining new therapeutic approaches are adding to the armamentarium available to physicians treating patients with PPCM. Despite all the current knowledge the mortality rates associated with PPCM remain relatively high. This article is a review of the current knowledge of etiology, diagnosis, treatment and prognosis of PPCM and attempts to present areas of need of further research.

Topics: Cardiomyopathies; Cardiovascular Agents; Female; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors

After left ventricular-assist device (LVAD) support, a proportion of patients recover sufficient ventricular function to enable explantation of the device. The exact molecular mechanisms involved in myocardial recovery remain unknown. Cytoskeletal proteins are essential for the structure and function of the cardiac myocyte and might play a major role.. A total of 15 patients with nonischemic cardiomyopathy who required LVAD implantation were studied; 6 recovered sufficiently to allow explantation of the device compared with 9 who did not recover and required transplantation. LV myocardial samples were collected at implantation and explantation/transplantation. Affymetrix microarray analysis was performed on the paired samples and analyzed with reference to sarcomeric and nonsarcomeric cytoskeletal proteins. In the recovery group, of the nonsarcomeric proteins, lamin A/C increased 1.5-fold (P<0.05) and spectrin 1.6-fold (P<0.05) between the times of implantation and explantation. Integrins beta1, beta6, and alpha7 decreased 1.7-fold (P<0.05), 2.4-fold (P<0.05), and 1.5-fold (P<0.05), respectively, but integrins alpha5 and beta5 increased 2.3-fold (P<0.01) and 1.2-fold (P<0.01) at explantation. The following sarcomeric proteins changed in the recovered group only: beta-actin increased 1.4-fold (P<0.05); alpha-tropomyosin, 1.3-fold (P<0.05); alpha1-actinin, 1.8-fold (P<0.01); and alpha-filamin A, 1.6-fold (P<0.05). Both troponin T3 and alpha2-actinin decreased by 1.6-fold at the time of explantation (P<0.05). Vinculin decreased 1.7-fold (P=0.001) in the recovered group but increased by 1.7-fold (P<0.05) in the nonrecovered group. Vinculin protein levels decreased 4.1-fold in the recovered group.. Myocardial recovery was associated with a specific pattern of changes in sarcomeric, nonsarcomeric, and membrane-associated proteins, which could have important implications in understanding the mechanisms involved.

Topics: Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adult; Cardiomyopathies; Cardiovascular Agents; Clenbuterol; Combined Modality Therapy; Convalescence; Cytoskeletal Proteins; Device Removal; Female; Gene Expression Profiling; Heart Failure; Heart-Assist Devices; Hemodynamics; Humans; Integrins; Male; Middle Aged; Myocytes, Cardiac; Oligonucleotide Array Sequence Analysis; Postoperative Period; Reverse Transcriptase Polymerase Chain Reaction; Treatment Outcome

The prevalence of type 2 diabetes mellitus is rapidly increasing. Myocardial dysfunction may be a consequence of diabetic cardiomyopathy and it contributes to the poor prognosis of diabetic patients.. This study was designed to test whether tissue Doppler imaging might be a suitable tool for early detection of myocardial dysfunction in diabetic patients.. Forty-three diabetic patients and 33 non-diabetic controls, including age-matched subgroups without evidence of coronary artery disease (n=12), were recruited if they had normal LV-function by standard 2-D echocardiography and no clinical signs of heart failure. They were investigated with tissue Doppler imaging at rest and during pharmacological stress with dipyridamole and/or dobutamine. Myocardial function was calculated as the mean value from six basal myocardial segments for peak velocity at systole (Vs), early diastole (Ve) and atrial contraction (Va).. Compared to controls, diabetic patients had compromised Ve at rest (8.5 +/- 1.7 vs. 9.6 +/- 1.9 cm/sec, p < 0.02), as did the subgroups without coronary artery disease (9.3 +/- 1.7 vs. 10.7 +/- 1.5 cm/sec, p < 0.05). Dobutamine stress resulted in lower Vs (10.7 +/- 2.7 vs. 13.6 +/- 3.4 cm/sec, p < 0.05) and Ve (10.0 +/- 2.1 vs. 13.1 +/- 3.8 cm/sec, p < 0.05) in the diabetic patients, demonstrating an impaired increase of Vs, Vd and Va (p < 0.05, p < 0.0003 and p < 0.03, respectively). An inverse correlation was observed between Ve and age in both control and diabetic individuals. Thus, abnormal values were defined in relation to age.. Diastolic and systolic myocardial dysfunction in patients with type 2 diabetes may be identified by quantitative tissue Doppler imaging before the onset of clinical signs of heart failure and before the appearance of traditional echocardiographic indices of systolic myocardial dysfunction.

Topics: Age Factors; Aged; Cardiomyopathies; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diastole; Dipyridamole; Dobutamine; Echocardiography, Doppler, Pulsed; Echocardiography, Stress; Female; Humans; Male; Middle Aged; Myocardial Contraction; Systole

Topics: Anthracyclines; Cardiomyopathies; Cardiovascular Agents; Chelating Agents; Child; Heart; Humans; Predictive Value of Tests; Razoxane; Risk Factors; Troponin T

Topics: Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Disease-Free Survival; Doxorubicin; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Razoxane; Remission Induction

This retrospective study concerned 18 female and 23 male patients with cardiac sarcoidosis (CS). The average age at CS diagnosis was 38 years. CS was observed in white (73% of cases) and in black or Caribbean patients (27% of cases). All patients had extracardiac histologic proof of sarcoid tissue. In 63% of cases, the CS arose during the follow-up of systemic sarcoidosis. Systemic sarcoidosis was not specific except for a high frequency of neurosarcoidosis. Revealing cardiac signs were clinical in 63% of cases and electrical in 22%. In most patients these signs were associated with an abnormal echocardiography (77%) and/or a defect on thallium-201 or sestamibi imaging (75%). Thirty-nine patients received steroid therapy (initial dose mostly equal to 1 mg/kg per day), associated in 13 cases with another immunosuppressive treatment. In 26% of cases the immunosuppressive treatment was associated with a specific cardiac treatment. In the long-term follow-up (average follow-up, 58 mo), 87% of the cases showed an improvement, and 54% were cured from a clinical and laboratory point of view (electrocardiogram, 24-hour monitoring, echocardiography, radionuclide imaging). There was no sudden death. Two patients worsened, which can be explained in 1 case by very late treatment and in the other case by lack of treatment, except for a pacemaker. Our experience leads us to treat CS with corticosteroids as soon as possible and to use another immunosuppressive treatment where there is an insufficient therapeutic response or where there are contraindications to corticosteroids.

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Biopsy; Black People; Blood Cell Count; Blood Sedimentation; Cardiomyopathies; Cardiovascular Agents; Echocardiography; Electrocardiography; Female; Humans; Hypercalcemia; Immunosuppressive Agents; Male; Middle Aged; Peptidyl-Dipeptidase A; Retrospective Studies; Sarcoidosis; Treatment Outcome; White People

Topics: Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Chelating Agents; Child; Clinical Trials as Topic; Disease-Free Survival; Doxorubicin; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Razoxane; Troponin T

A 58-year-old man with a 64-month history of unclassified cardiomyopathy developed congestive heart failure (CHF) and had been dependent on long-term intravenous positive inotropes. Combined pimobendan and carvedilol administration resulted in marked symptomatic improvement from New York Heart Association functional class IV to I. Echocardiograms showed improvement of left ventricular (LV) ejection fraction from 15 to 48%, and LV end-diastolic diameter from 6.7 to 4.9 cm. This mode of therapy not only improved LV contractile function but also normalized LV volume, which was an unusual clinical course compared with the general course of advanced CHF.

Topics: Carbazoles; Cardiomyopathies; Cardiovascular Agents; Carvedilol; Heart Failure; Humans; Male; Middle Aged; Propanolamines; Pyridazines; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Humans; Razoxane

Peripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of unknown cause that occurs in the peripartum period in previously healthy women. In April 1997, the National Heart, Lung, and Blood Institute (NHLBI) and the Office of Rare Diseases of the National Institutes of Health (NIH) convened a Workshop on Peripartum Cardiomyopathy to foster a systematic review of information and to develop recommendations for research and education.. Fourteen workshop participants were selected by NHLBI staff and represented cardiovascular medicine, obstetrics, immunology, and pathology. A representative subgroup of 8 participants and NHLBI staff formed the writing group for this article and updated the literature on which the conclusions were based. The workshop was an open meeting, consistent with NIH policy.. Data presented at the workshop were augmented by a MEDLINE search for English-language articles published from 1966 to July 1999, using the terms peripartum cardiomyopathy, cardiomyopathy, and pregnancy. Articles on the epidemiology, pathogenesis, pathophysiology, diagnosis, treatment, and prognosis of PPCM were included. RECOMMENDATION PROCESS: After discussion of data presented, workshop participants agreed on a standardized definition of PPCM, a general clinical approach, and the need for a registry to provide an infrastructure for future research.. Peripartum cardiomyopathy is a rare lethal disease about which little is known. Diagnosis is confined to a narrow period and requires echocardiographic evidence of left ventricular systolic dysfunction. Symptomatic patients should receive standard therapy for heart failure, managed by a multidisciplinary team. If subsequent pregnancies occur, they should be managed in collaboration with a high-risk perinatal center. Systematic data collection is required to answer important questions about incidence, treatment, and prognosis.

Topics: Cardiomyopathies; Cardiovascular Agents; Congresses as Topic; Echocardiography; Female; Humans; Incidence; National Institutes of Health (U.S.); Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Third; Pregnancy, High-Risk; Prognosis; Puerperal Disorders; Risk Factors; United States; Ventricular Dysfunction, Left

Topics: Adult; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Diseases; Humans; Myocardial Infarction; Prognosis; Resuscitation; Risk Factors

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cardiomyopathies; Cardiovascular Agents; Doxorubicin; Humans; Razoxane

Topics: Cardiomyopathies; Cardiovascular Agents; Clinical Trials as Topic; Heart Failure; Humans; Risk Factors

Since calcium overload and increased in T-type calcium channel activity have been observed in the cardiomyopathic (CM) hamster, we hypothesized that mibefradil (Ro 40-5967), a new T- and L-type calcium channel blocker, may exert significant cardioprotection in the early phase of the disease. Young (30-day-old) CM hamsters of the UM-X7.1 subline were treated with mibefradil or verapamil for 4 to 6 weeks. Mibefradil doses were in the range of 0.5 to 8 mg/kg/day while verapamil was given at a dose of 5-10 mg/kg/day, both drugs being injected twice daily (s.c. and i.p. alternatively). At the end of the treatment period, myocardial and skeletal muscle (tongue) were harvested and processed for assessment of necrotic changes and calcification. In hearts from control CM hamsters, numerous necrotic and calcified foci were observed. These myocardial necrosis markers were not attenuated by mibefradil in the dose range studied whereas verapamil significantly reduced their severity. The dystrophic process in skeletal muscle (tongue) was not inhibited by mibefradil or verapamil. These results suggest that mechanisms other than inhibition of T- and L-type calcium channels are related to the cardioprotection observed in the presence of verapamil. A specific action on the sarcoplasmic reticulum (ryanodine-sensitive calcium channel) or the mitochondria may explain the efficacy of phenylalkylamines (verapamil) in this condition.

Topics: Animals; Biomarkers; Calcinosis; Calcium Channel Blockers; Cardiomyopathies; Cardiovascular Agents; Cricetinae; Female; Heart; Male; Mibefradil; Muscle, Skeletal; Myocardium; Necrosis; Time Factors; Tongue; Verapamil

Changes in cholinesterases activities in daunorubicin cardiomyopathy and in dexrazoxane (DRZX)-treated daunorubicin cardiomyopathy were investigated in rabbits. Acetyl- and butyrylcholinesterase (AChE and BuChE) were determined using Ellman's method. In the serum, a significant decrease of BuChE was observed in the daunorubicin group (9.05 at the beginning and 7.15 microcat/l at the end of the experiment). After DRZX, no significant changes were found and a significant increase in BuChE was observed in the control group (10.26-12.38 microcat/l). AChE activity in the left and right cardiac ventricles was not significantly different between the groups while in the septum there was a significantly lower AChE activity found in the daunorubicin group only. BuChE activity was significantly decreased in the left (15.64 ncat/g) and right (19.27 ncat/g) heart ventricles, in the septum and in the liver in the daunorubicin group. A significant decrease in serum total protein and albumin was demonstrated only in the daunorubicin group. Our results support the hypothesis about the influence of daunorubicin on protein (and enzyme) synthesis in the liver and heart. A protective effect of DRZX on cholinesterases activity was observed. The changes in cholinesterase activities may thus reflect their possible role in cardiomyopathy.

Topics: Acetylcholinesterase; Animals; Antibiotics, Antineoplastic; Body Weight; Butyrylcholinesterase; Cardiomyopathies; Cardiovascular Agents; Daunorubicin; Heart; Male; Myocardium; Rabbits; Razoxane; Ventricular Function, Left

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Chelating Agents; Humans; Randomized Controlled Trials as Topic; Razoxane

Treatment with anthracycline antibiotics may have a toxic effect on the myocardium. The report deals with the results of application of a cardioprotector--cardioxan--in 38 children, aged 2-13 years, with malignant tumors treated, among other drugs, with doxorubicin. These data were compared with those on 33 pediatric patients who had received anthracycline antibiotics until 1994. No cardioxan-related complications were recorded whenever the instructions on the use were followed. The results are inconclusive because of the short duration of the study and examination being still incomplete.

Topics: Adolescent; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Female; Humans; Male; Razoxane; Treatment Outcome

In laboratory animals, histology is most commonly used to study doxorubicin-induced cardiotoxicity. However, for monitoring during treatment, large numbers of animals are needed. Recently we developed a new method to measure ECG values in freely moving mice by telemetry. With this model we investigated the effect of chronic doxorubicin administration on the ECG of freely moving BALB/c mice and the efficacy of ICRF-187 as a protective agent. The ST interval significantly widened from 15.0 +/- 1.5 to 56.8 +/- 11.8 ms in week 10 (7 weekly doses of 4 mg/kg doxorubicin given i.v. plus 3 weeks of observation). The ECG of the control animals did not change during the entire study. After sacrifice the hearts of doxorubicin-treated animals were enlarged and the atria were hypertrophic. As this schedule exerted more toxicity than needed to investigate protective agents, the protection of ICRF-187 was determined using a dose schedule with lower general toxicity (6 weekly doses of 4 mg/kg doxorubicin given i.v. plus 2 weeks of observation). On this schedule, the animals' hearts appeared normal after sacrifice and ICRF-187 (50 mg/kg given i.p. 1 h before doxorubicin) provided almost full protection. These data were confirmed by histology. The results indicate that this new model is very sensitive and enables monitoring of the development of cardiotoxicity with time. These findings result in a model that allows the testing of protectors against doxorubicin-induced cardiotoxicity as demonstrated by the protection provided by ICRF-187.

Topics: Analysis of Variance; Animals; Antineoplastic Agents, Alkylating; Behavior, Animal; Body Weight; Cardiomyopathies; Cardiovascular Agents; Doxorubicin; Drug Interactions; Electrocardiography; Heart; Heart Atria; Heart Rate; Injections, Intraperitoneal; Injections, Intravenous; Male; Mice; Mice, Inbred BALB C; Razoxane; Telemetry

Previous studies have demonstrated that pharmacologic stress thallium-201 (201Tl) myocardial scintigraphy is a useful tool to evaluate preoperative cardiac risk.. The purpose of this study was to assess the utility of adenosine stress dual-isotope [rest 201Tl/stress technetium-99m (99mTc) sestamibi] myocardial single-photon emission computed tomography (SPECT) in predicting the risk of perioperative cardiac events (unstable angina, myocardial infarction, cardiac death) in patients undergoing major noncardiac surgery.. We evaluated 43 consecutive patients (20 men, 23 women, mean age 64 years, range 30-83 years) within 8 weeks prior to major noncardiac surgery requiring general anesthesia. SPECT imaging was performed with 111 MBq (3 mCi) 201Tl at rest and 925 MBq (25 mCi)99mTc sestamibi during adenosine stress.. Of the 43 patients, 15 (35%) had stress-induced ischemia and 28 (65%) did not. Perioperative cardiac events occurred in 4 (27%) of the 15 patients with stress-induced ischemia (2 unstable angina, 2 nonfatal myocardial infarctions) and in none of the 28 patients without inducible ischemia (p = 0.02).. Adenosine stress dual-isotope myocardial SPECT is useful in determining the preoperative cardiac risk of patients undergoing major noncardiac surgery.

Topics: Adenosine; Adult; Aged; Aged, 80 and over; Cardiomyopathies; Cardiovascular Agents; Exercise Test; Female; Follow-Up Studies; Heart; Hemodynamics; Humans; Male; Middle Aged; Preoperative Care; Retrospective Studies; Risk Assessment; Risk Factors; Technetium Tc 99m Sestamibi; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

The occurrence of apoptosis in heart, kidney and small intestine was investigated in spontaneously hypertensive rats (SHR) treated with doxorubicin (1 mg/kg/week for 6, 9 and 12 weeks) with and without pretreatment with the iron chelator ICRF-187 [(+)1.2-bis(3.5-dioxopiperazinyl-l-yl)propane] (25 mg/kg, i.p., given 30 min before doxorubicin). Animals receiving either ICRF-187 alone or saline were used as controls. Cells undergoing apoptosis were identified ultrastructurally and by staining using the nick-end labeling method. The results obtained by counting cells with positive nick-end labeling showed that, when given in cumulative doses of 9 and 12 (but not 6) mg/kg, doxorubicin induced significant toxicity in the heart, kidneys and intestine in association with apoptosis in epithelial cells of the intestinal mucosa and renal tubules but not in cardiac myocytes. At these doses nick end labeling in the heart was confined to occasional endothelial cells, interstitial dendritic cells and macrophages. The frequency of doxorubicin-induced apoptosis in renal and intestinal epithelial cells was decreased by pretreatment of the SHR with ICRF-187. Our data support the concept that the chronic cardiomyopathy induced by doxorubicin is not mediated by apoptosis of the cardiac myocytes.

Topics: Animals; Apoptosis; Cardiomyopathies; Cardiovascular Agents; Dose-Response Relationship, Drug; Doxorubicin; Heart; Hypertension; Immunohistochemistry; Intestines; Iron Chelating Agents; Kidney; Kidney Diseases; Male; Microscopy, Electron; Myocardium; Rats; Rats, Inbred SHR; Razoxane

To prove the protective effects of trivalent chromium (Cr3+) on myocardial damage, its ultrastructure and electro-physiological changes were observed in different groups of rats with intraperitoneal injection of normal saline, Cr3+ and selenium, and injection of adriamycin (ADR) by their tail vein. Results of ultrastructural observations showed nuclear margin of myocardial cells was obscure, cytoplasm became coarse and sparse, mitochondria vacuolar, myocardiofibril loose, broken and lytic in the group treated with ADR, myocardiopathic changes reduced and myocardial filaments arranged in good order in that with Cr3+ and selenium. QRS complex, Q-T interval, APD50 and APD90 in electrocardiograph (ECG) prolonged in the group with ADR and selenium, and no changes were observed in that with Cr3+. It suggests Cr3+ and selenium have apparently protective effects on rat's myocardium, and Cr3+ also can reverse the changes in ECG caused by ADR, which is of importance in prevention and treatment of cardiovascular diseases.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Chromium; Doxorubicin; Male; Myocardium; Rats; Rats, Wistar; Selenium

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiomyopathies; Cardiovascular Agents; Cyclophosphamide; Doxorubicin; Drug Evaluation; Drug Interactions; Female; Fluorouracil; Heart; Humans; Middle Aged; Razoxane; Remission Induction

Topics: Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Humans

The platelets from 74 patients with acute myocardial infarction or with unstable angina showed decreased prostaglandin E1/I2 receptor activity when compared with that of 56 normal volunteers by using [3H]prostaglandin E1 as a probe. In normals, Scatchard analyses showed the presence of one high-affinity-low-capacity (Kd1 = 9.0 +/- 1.2 nM [mean +/- SD]; n1 = 120 +/- 30 sites/cell) and one low-affinity-high-capacity (Kd2 = 1.1 +/- 0.5 microM; n2 = 1,460 +/- 250 sites/cell) prostaglandin E1/I2 receptor population in platelets. In contrast (p less than 0.01), platelets from patients showed decreased ligand binding (n1 = 40 +/- 20 sites/cell; n2 = 800 +/- 210 sites/cell) with little change in the affinity of the receptors (Kd1 = 7.50 +/- 1.6 nM; Kd2 = 0.68 +/- 0.24 microM). On the other hand, the platelets from the patients with dilated cardiomyopathy (n = 7) who were hospitalized for acute chest pain but had normal coronary arteries did not show any impairment of the receptor activity. The plasma prostacyclin level of the patients with acute ischemic heart disease was similar to that of normal volunteers; this finding indicated that the defective receptor function was not related to the prostaglandin receptors occupancy in vivo. The impaired receptor activity was temporary in nature. The follow-up studies showed that the prostaglandin receptor activity of the patients' platelets improved to "normal" levels within 2-8 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Angina, Unstable; Blood Platelets; Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Cyclic AMP; Epoprostenol; Female; Humans; Male; Middle Aged; Prostaglandins E; Receptors, Epoprostenol; Receptors, Prostaglandin; Receptors, Prostaglandin E; Reference Values

The development of new inotropic or vasodilator agents, with different spectra of action makes possible a physiological approach to the treatment of acute cardiac failure. The choice depends on the functional disturbances measured and is then adapted to the response obtained. In the most serious cases, where pharmacological treatment proves insufficient, there need be no hesitation in using invasive methods which were formerly reserved for the treatment of cardiogenic shock. Systematic application of therapeutic formulae gives way to rational selection of the agent best adapted to the particular conditions brought about by a specified cardiopathy in a given patient.

Topics: Acute Disease; Assisted Circulation; Cardiomyopathies; Cardiovascular Agents; Heart Failure; Hemodynamics; Humans; Myocardial Infarction; Pulmonary Heart Disease