cardiovascular-agents and Cardiomyopathy--Hypertrophic

Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM). There is limited data regarding the outcomes of AF catheter ablation in HCM patients. In this study, we aimed to synthesize all available evidence on the effectiveness of ablation of AF in patients with HCM compared to those without HCM.. We systematically reviewed bibliographic databases to identify studies published through February 2023. We included cohort studies with available quantitative information on rates of recurrent atrial arrhythmias, anti-arrhythmic drug (AAD) therapy, and repeat ablation procedures after initial AF ablation in patients with vs without HCM. Estimates were combined using random-effects meta-analysis models and reported as risk ratios (RR) and 95% confidence intervals (CI). Eight studies were included in quantitative synthesis (262 HCM and 642 non-HCM patients). During median follow-up 13-54 months across studies, AF recurrence rates ranged from 13.3% to 92.9% in HCM and 7.6% to 58.8% in non-HCM patients. The pooled RR for recurrent atrial arrhythmia after the first AF ablation in HCM patients compared to non-HCM controls was 1.498 (95% CI = 1.305-1.720; P < 0.001). During follow-up, HCM patients more often required AAD therapy (RR = 2.844; 95% CI = 1.713-4.856; P < 0.001) and repeat AF ablation (RR = 1.544; 95% CI = 1.070-2.228; P = 0.02). The pooled RR for recurrent atrial arrhythmias after the last AF ablation was higher in patients with HCM than those without HCM (RR = 1.607; 95% CI = 1.235-2.090; P < 0.001).. Compared to non-HCM patients, those with HCM had higher rates of recurrent atrial arrhythmias, AAD use, and need for repeat AF ablation after initial ablation of AF.

Topics: Ablation Techniques; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Catheter Ablation; Humans

Myocardial infarction (MI) in the absence of obstructive coronary artery disease (MINOCA) is prevalent in around 5% of acute myocardial infarction (AMI) presentations. MINOCA is a heterogeneous entity with many different etiologies. It is important for health care providers to familiarize themselves with the disease process, presentation, and possible underlying causes in order to guide appropriate management strategies. In this article, the authors review the contemporary definition, etiologies and assessment, and management for AMI patients with MINOCA.

Topics: Aortic Dissection; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Coronary Artery Disease; Coronary Circulation; Coronary Vasospasm; Coronary Vessels; Humans; Myocardial Infarction; Myocarditis; Platelet Aggregation Inhibitors; Risk Factors; Severity of Illness Index; Takotsubo Cardiomyopathy; Thromboembolism

Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease with a highly variable phenotypic expression, ranging from asymptomatic to drug refractory heart failure (HF) presentation. Pharmacological therapy is the first line of treatment, but options are currently limited to nonspecific medication like betablockers or calcium channel inhibitors, with frequent suboptimal results. While being the gold standard practice for the management of drug refractory HCM patients, septal reduction therapy (SRT) remains an invasive procedure with associated surgical risks and it requires the expertise of the operating centre, thus limiting its accessibility. It is therefore with high interest that researchers look for pharmacological alternatives that could provide higher rates of success. With new data gathering these past years as well as the development of a new drug class showing promising results, this review provides an up-to-date focused synthesis of existing medical treatment options and future directions for HCM pharmacological treatment.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Repositioning; Humans; Myosins; Sodium Channel Blockers; Spironolactone; Vasodilator Agents

Hypertrophic cardiomyopathy is an inherited cardiac disease and a major cause of heart failure and sudden death. Even though it was described more than 50 years ago, sarcomeric hypertrophic cardiomyopathy still lacks a disease-specific treatment. The drugs routinely used alleviate symptoms but do not prevent or revert the phenotype. With recent advances in the knowledge about the genetics and pathophysiology of hypertrophic cardiomyopathy, new genetic and pharmacological approaches have been recently discovered and studied that, by influencing different pathways involved in this disease, have the potential to function as disease-modifying therapies. These promising new pharmacological and genetic therapies will be the focus of this review.

Topics: Acetylcysteine; Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium; Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Diltiazem; Genetic Therapy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocytes, Cardiac; Sodium Channel Blockers

Mutations in sarcomere genes can cause both hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). However, the complex genotype-phenotype relationships in pathophysiology of cardiomyopathies by gene or mutation location are not fully understood. In addition, it is still unclear how mutations within same molecule result in different clinical phenotypes such as HCM and DCM. To clarify how the initial functional insult caused by a subtle change in one protein component of the sarcomere with a given mutation is critical for the development of proper effective treatments for cardiomyopathies. Fortunately, recent technological advances and the development of direct sarcomere modulators have provided a more detailed understanding of the molecular mechanisms that govern the effects of specific mutations. The direct inhibition of sarcomere contractility may be able to suppress the development and progression of HCM with hypercontractile mutations and improve clinical parameters in patients with HCM. On the other hand, direct activation of sarcomere contractility appears to exert unexpected beneficial effects such as reverse remodeling and lower heart rate without increasing adverse cardiovascular events in patients with systolic heart failure due to DCM. Direct sarcomere modulators that can positively influence the natural history of cardiomyopathies represent promising treatment options.

Topics: Animals; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Humans; Myocardial Contraction; Myosins; Sarcomeres

Hypertrophic cardiomyopathy is the most common inherited cardiovascular disease. It is characterized by increased ventricular wall thickness and is highly complex due to its heterogeneous clinical presentation, several phenotypes, large number of associated causal mutations and broad spectrum of complications. It is caused by mutations in sarcomeric proteins, which are identified in up to 60% of cases of the disease. Clinical manifestations of Hypertrophic Cardiomyopathy include shortness of breath, chest pain, palpitations and syncope, which are related to the onset of diastolic dysfunction, left ventricular outflow tract obstruction, ischemia, atrial fibrillation and abnormal vascular responses. It is associated with an increased risk of sudden cardiac death, heart failure and thromboembolic events. In this article, we discuss the diagnostic and therapeutic aspects of this disease.

Topics: Animals; Atrial Fibrillation; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Clinical Trials as Topic; Death, Sudden, Cardiac; Diagnostic Techniques, Cardiovascular; Drug Evaluation, Preclinical; Dyspnea; Genetic Association Studies; Heart; Heart Failure; Heart Septum; Heart Ventricles; Humans; Muscle Proteins; Pacemaker, Artificial; Penetrance; Risk Assessment; Sarcomeres; Syncope

There are several methods to measure cardiomyocyte and muscle contraction, but these require customized hardware, expensive apparatus, and advanced informatics or can only be used in single experimental models. Consequently, data and techniques have been difficult to reproduce across models and laboratories, analysis is time consuming, and only specialist researchers can quantify data.. Here, we describe and validate an automated, open-source software tool (MUSCLEMOTION) adaptable for use with standard laboratory and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes, and pharmacological responses.. MUSCLEMOTION allowed rapid and easy measurement of movement from high-speed movies in (1) 1-dimensional in vitro models, such as isolated adult and human pluripotent stem cell-derived cardiomyocytes; (2) 2-dimensional in vitro models, such as beating cardiomyocyte monolayers or small clusters of human pluripotent stem cell-derived cardiomyocytes; (3) 3-dimensional multicellular in vitro or in vivo contractile tissues, such as cardiac "organoids," engineered heart tissues, and zebrafish and human hearts. MUSCLEMOTION was effective under different recording conditions (bright-field microscopy with simultaneous patch-clamp recording, phase contrast microscopy, and traction force microscopy). Outcomes were virtually identical to the current gold standards for contraction measurement, such as optical flow, post deflection, edge-detection systems, or manual analyses. Finally, we used the algorithm to quantify contraction in in vitro and in vivo arrhythmia models and to measure pharmacological responses.. Using a single open-source method for processing video recordings, we obtained reliable pharmacological data and measures of cardiac disease phenotype in experimental cell, animal, and human models.

Topics: Algorithms; Animals; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Cell Differentiation; Cells, Cultured; GTP-Binding Protein beta Subunits; Humans; Long QT Syndrome; Male; Microscopy; Models, Cardiovascular; Myocardial Contraction; Myocytes, Cardiac; Patch-Clamp Techniques; Phenotype; Pluripotent Stem Cells; Rabbits; Software; Video Recording; Zebrafish; Zebrafish Proteins

Hypertrophic cardiomyopathy is the most common inherited heart disease. Although it was first described over 50 years ago, there has been little in the way of novel disease-specific therapeutic development for these patients. Current treatment practice largely aims at symptomatic control using old drugs made for other diseases and does little to modify the disease course. Septal reduction by surgical myectomy or percutaneous alcohol septal ablation are well-established treatments for pharmacologic-refractory left ventricular outflow tract obstruction in hypertrophic cardiomyopathy patients. In recent years, there has been a relative surge in the development of innovative therapeutics, which aim to target the complex molecular pathophysiology and resulting hemodynamics that underlie hypertrophic cardiomyopathy. Herein, we review the new and emerging therapeutics for hypertrophic cardiomyopathy, which include pharmacologic attenuation of sarcomeric calcium sensitivity, allosteric inhibition of cardiac myosin, myocardial metabolic modulation, and renin-angiotensin-aldosterone system inhibition, as well as structural intervention by percutaneous mitral valve plication and endocardial radiofrequency ablation of septal hypertrophy. In conclusion, while further development of these therapeutic strategies is ongoing, they each mark a significant and promising advancement in treatment for hypertrophic cardiomyopathy patients.

Topics: Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Humans; Treatment Outcome

Myocardial hypertrophic remodeling is a pathophysiological feature of several cardiac conditions and is the hallmark of hypertrophic cardiomyopathy (HCM), the most common monogenic inherited disease of the heart. In recent years, preclinical and clinical studies investigated the underlying molecular mechanisms and intracellular signaling pathways involved in pathologic cardiomyocyte hypertrophy and highlighted a number of possible molecular targets of therapy aimed at preventing its development. Early prevention of myocardial hypertrophic remodeling is particularly sought after in HCM, as current therapeutic strategies are unable to remove the primary cause of disease, i.e. the disease-causing gene mutation. Studies on transgenic animal models or human myocardial samples from patients with HCM identified intracellular calcium overload as a central mechanism driving pathological hypertrophy. In this review, we analyze recent preclinical and clinical studies on animal models and patients with HCM aimed at preventing or modifying hypertrophic myocardial remodeling. Mounting evidence shows that prevention of pathological hypertrophy is a feasible strategy in HCM and will enter the clinical practice in the near future. Considering the close mechanistic similarities between HCM and secondary hypertrophy, these studies are also relevant for the common forms of cardiac hypertrophy, such as hypertensive or valvular heart disease.

Topics: Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Evidence-Based Medicine; Feasibility Studies; Genetic Predisposition to Disease; Heart Valve Diseases; Humans; Hypertension; Myocardium; Myocytes, Cardiac; Risk Factors; Signal Transduction; Treatment Outcome; Ventricular Remodeling

To date, up to 65% of drugs used in neonates and infants are off-label or unlicensed, as they were implemented in clinical care without the usual regulatory phases of pharmacological drug development. Pharmacotherapy in this age group is still mainly based on the individual clinical expertise of specialized pediatricians. Pharmacological trials involving neonates are indeed more difficult to perform: appropriate dosing is hampered by the rapid physiological changes occurring at this stage of development, and the selection of proper end-points and biomarkers is complicated by the limited knowledge of the pathophysiology of the specific diseases of infancy. Moreover, there are many ethical challenges in planning and conducting drug studies in pediatric patients (especially in newborns and infants). In the current review, we address some challenges and discuss possible perspectives to stimulate scientific and clinical pharmacological research in neonates and infants. We hereby aim to illustrate the add on value of the regulatory framework for model-based neonatal medicinal development currently used in Europe and the United States. We provide several examples of successful recent pharmacological trials performed in neonates and infants. In these examples, success was ensured by the implementation of specific pharmacokinetic assessments, thanks to accurate drug dosing achieved with a combination of dose validation, population pharmacokinetics and mathematical models of drug clearance and distribution; moreover, age-specific pharmacodynamics was considered via appropriate evaluations of drug efficacy with end-points adapted to the peculiar pathophysiology of diseases in this age group. These "pharmacological" challenges add to the ethical challenges that are always present in planning and conducting clinical studies in neonates and infants and support the opinion that clinical research in pediatrics should be evaluated by ad hoc ethical committees with specific expertise.

Topics: Anti-Bacterial Agents; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Discovery; Humans; Infant; Infant, Newborn; Pediatrics; Pharmaceutical Research; Tachycardia, Supraventricular

Hypertrophic cardiomyopathy (HCM) is microscopically characterized by cardiomyocyte hypertrophy, myofibrillar disarray, and fibrosis. During the evolvement of the hypertrophic disease, myocardium suffers a heterogeneous remodeling which includes enhancement of extracellular matrix. The most commonly used pharmacological agents are β- blockers and verapamil, a calcium antagonist, which are the mainstay of therapy. Their proposed mechanisms of effect include improved ventricular relaxation, and increased diastolic filling time but its impact on HCM pathophysiology remains unclear. The results of genetic and pharmacological studies in animal models suggest that cardiac hypertrophy and fibrosis in HCM are potentially reversible. However, current pharmacological treatments of HCM in patients, while are effective for symptomatic improvement, have not been established to prevent, ameliorate, or reverse cardiac hypertrophy in patients. An effective treatment of HCM has to target the molecular mechanisms that are involved in the pathogenesis of the phenotype and novel pharmacological therapies are moving in that direction. In this review, we analyse potential beneficial effects of specific experimental pharmacological agents on decreasing myocardial hypertrophy, regression of fibrosis or improving myocardial metabolic efficiency.

Topics: Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Fibrosis; Humans; Myocardium; Myocytes, Cardiac; Ventricular Remodeling

The management of patients with hypertrophic cardiomyopathy (HCM) has evolved markedly over the past 20 years, particularly with the rising number of indications for implantable cardiac defibrillators (ICDs) and alcohol septal ablation (ASA). However, medical therapies targeted to improve quality of life are underused; when resting and/or exercise obstruction is present, an incremental and additive approach should be used based on a high dosage of beta-blockers, verapamil and/or disopyramide. Radiofrequency catheter ablation of atrial fibrillation or A-V node has been proposed in some instances. Treatment of syncope or presyncope due to an abnormal blood pressure response during exercise remains challenging. Only patients with obstruction who remain severely symptomatic despite maximal medical therapy should be considered for invasive procedures, including dual-chamber (DDD) pacing, ASA or surgery. The reported complication rates of ASA (essentially complete A-V block, incidence above 5-10%, with mortality rates ranging from 0-4%) and the benefits at medium-term follow-up appear comparable to those observed after myectomy, which, according to guidelines, should remain the primary treatment for most severely symptomatic drug-refractory young patients with obstruction. While the overall survival of patients with HCM is similar to that of the general population, detection of patients at high risk of sudden cardiac death remains challenging, particularly in the young, and indications for ICDs in high risk patients without prior cardiac arrest should be patient- and family-orientated.

Topics: Cardiac Pacing, Artificial; Cardiology; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Catheter Ablation; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Embolization, Therapeutic; Ethanol; Heart Transplantation; Humans; Mitral Valve; Patient Selection; Quality of Life; Risk Assessment; Treatment Outcome

Topics: Anti-Bacterial Agents; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Catheter Ablation; Death, Sudden, Cardiac; Endocarditis; Humans; Treatment Outcome; Ventricular Outflow Obstruction

The quintessential clinical diagnostic phenotype of human hypertrophic cardiomyopathy (HCM) is primary cardiac hypertrophy. Cardiac hypertrophy is also a major determinant of mortality and morbidity including the risk of sudden cardiac death (SCD) in patients with HCM. Reversal and attenuation of cardiac hypertrophy and its accompanying fibrosis is expected to improve morbidity as well as decrease the risk of SCD in patients with HCM.The conventionally used pharmacological agents in treatment of patients with HCM have not been shown to reverse or attenuate established cardiac hypertrophy and fibrosis. An effective treatment of HCM has to target the molecular mechanisms that are involved in the pathogenesis of the phenotype. Mechanistic studies suggest that cardiac hypertrophy in HCM is secondary to activation of various hypertrophic signaling molecules and, hence, is potentially reversible. The hypothesis is supported by the results of genetic and pharmacological interventions in animal models. The results have shown potential beneficial effects of angiotensin II receptor blocker losartan, mineralocorticoid receptor blocker spironolactone, 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors simvastatin and atorvastatin, and most recently, N-acetylcysteine (NAC) on reversal or prevention of hypertrophy and fibrosis in HCM. The most promising results have been obtained with NAC, which through multiple thiol-responsive mechanisms completely reversed established cardiac hypertrophy and fibrosis in three independent studies. Pilot studies with losartan and statins in humans have established the feasibility of such studies. The results in animal models have firmly established the reversibility of established cardiac hypertrophy and fibrosis in HCM and have set the stage for advancing the findings in the animal models to human patients with HCM through conducting large-scale efficacy studies.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Death, Sudden, Cardiac; Drugs, Investigational; Fibrosis; Genetic Predisposition to Disease; Humans; Myocardium; Phenotype; Treatment Outcome

Topics: Cardiac Pacing, Artificial; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Disease Management; Humans

Several systemic and cardiac diseases cause an impairment of left ventricular filling or of the ability to maintain cardiac output, without an increase in end-diastolic pressure. Prevalence of diastolic dysfunction has been found to be higher than systolic dysfunction in most studies. Many physiological conditions (age, sex and body weight), and pathological processes, such as cardiac or systemic diseases, can increase the incidence of diastolic dysfunction. Early diagnosis of left ventricular diastolic impairment has been demonstrated to have important therapeutic implications. Several invasive or non-invasive methods to investigate diastolic properties of the left ventricle have been described; a large number of studies compared different parameters of diastolic function in order to find the most accurate: this is of particular prognostic relevance since diastolic dysfunction may remain asymptomatic for a long period before resulting in overt heart failure. The purpose of this article is to provide an extensive review of the contemporary literature regarding diastolic function assessment and its role in daily practice.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Diabetes Complications; Diastole; Echocardiography; Humans; Hypertension; Myocardial Ischemia; Pericarditis; Renin-Angiotensin System; Ventricular Dysfunction, Left; Ventricular Function, Left

Hypertrophic cardiomyopathy (HCM) is a complex cardiac disease, relatively common among genetic disorders. The prevalence is about 1:500 in the general population. Obstructive type occurs in about 25% of the cases. The clinical course is heterogeneous due to the large variety of genetic-based phenotypes with different prognostic impact. Primary HCM is one of the most important causes of sudden death in young people and may be a medical problem in athletes with physiologic left ventricular hypertrophy. In the last decade, however, several studies reported normal longevity. Echocardiography has emerged as the most important noninvasive method to make diagnosis and provide classifications of the disease. In this commentary, some out of the most recent and sophisticated applications of this method in HCM are reported. The most common pathophysiologic aspects and a proposal of classification of the obstruction-causing mechanisms, like systolic anterior motion of the mitral valve, papillary hypertrophy and dislocation, chordal slack, mid-cavity obliteration, are described. Some recent studies on coronary blood flow velocity and coronary reserve, performed by sophisticated Doppler echocardiography, have demonstrated important pathophysiological insights on microcirculatory impairment in patients with HCM. At present, advanced echocardiography surely improves the clinical management of these patients, and contributes to optimize the therapeutic strategies. However, the most appropriate framework of tests to be performed in the majority of them still remains a challenging clinical matter.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Coronary Circulation; Echocardiography; Humans; Prognosis

Topics: Angioplasty, Balloon, Coronary; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Randomized Controlled Trials as Topic

Hypertrophic cardiomyopathy is one of the most common inherited cardiovascular diseases and is characterized by a heterogeneous appearance and natural history. Although previously thought to be a disease of the young, HCM is frequently diagnosed in patients over age 50. A careful history and physical examination and readily available non-invasive testing will diagnose most cases, but genetic testing can identify those not expressing the typical phenotype. Treatment of symptomatic patients is targeted toward improving LV diastolic function; for patients with the obstructive form HCM, treatment involves relieving outflow tract obstruction. Identification of those at risk for sudden death may require consideration of prophylactic defibrillator placement.

Topics: Aged; Algorithms; Auscultation; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Echocardiography; Electrocardiography; Humans; Middle Aged; Ventricular Outflow Obstruction

Hypertrophic cardiomyopathy (HCM) is a relatively common disease of the cardiac sarcomere with broad heterogeneity in terms of the disease-causing gene mutation, phenotypic expression, therapy and prognosis. Besides the standard drug treatment, there are several therapeutic options available for severe refractory symptomatic HCM with obstruction. Dual-chamber pacing and transcoronary ablation of septal hypertrophy (TASH) have recently emerged as alternatives to myectomy. However, myectomy remains the current gold standard of therapy for HCM until the promising initial follow-up data for TASH can be transferred into a long-term follow-up period, or prospective randomized comparative trials between these therapies are available. However, even now, TASH represents an important therapeutic alternative in patients with relevant co-morbidities and a high operative risk. Despite significant gradient reduction and amelioration of clinical symptoms, none of these treatment strategies has a proven influence on the natural history of HCM. Hence, regarding the long-term prognosis of the disease, risk stratification of sudden cardiac death using non-invasive risk assessment has become of paramount importance, while genotyping might become the determinant and stratifying marker in the near future. At present, according to secondary prevention, treatment with an implanted cardioverter-defibrillator +/- amiodarone therapy is mandatory, while according to primary prevention treatment should particularly depend on the individual risk profile.

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Septum; Humans; Minimally Invasive Surgical Procedures; Pacemaker, Artificial; Survival Rate; Ventricular Outflow Obstruction

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease characterized by unexplained left ventricular hypertrophy, typically involving the interventricular septum. Hypertrophy may be present in infants, but commonly develops during childhood and adolescence. Management of children with HCM aims to provide symptomatic relief and prevention of sudden death, which is the primary cause of death. Unfortunately, no randomized comparative trials to date have assessed different treatment options in HCM. Medical treatment with negative inotropic agents (beta-adrenoceptor antagonists [beta-blockers], verapamil) is the first therapeutic choice in all symptomatic patients. Beta-blockers also appear to have prognostic merit in children. Surgical myectomy is effective in reducing symptoms in children with left ventricular (LV) obstruction who are unresponsive to medical treatment, although a repeat operation may be needed in a substantial proportion of patients due to relapse of LV obstruction. The recently introduced percutaneous septal ablation can also be regarded as a feasible alternative in this cohort. Technical limitations of both invasive therapeutic options should be carefully considered, preferably in experienced centers. Results of recent randomized trials indicate that dual chamber pacing, once considered a therapeutic option for patients with HCM, should only be used as treatment for conduction abnormalities. Regular clinical risk stratification for sudden death is of vital importance for the prevention of sudden death in young patients. Familial history of sudden death at a young age, LV hypertrophy >3 cm, unexplained syncope, nonsustained ventricular tachycardia in Holter monitoring, and abnormal blood pressure response during exercise are currently considered clinical risk factors for sudden death. Each factor has a low positive predictive accuracy, but patients having two or more of these risk factors are deemed as high risk. Secondary prevention of sudden death in patients successfully resuscitated from cardiac arrest and/or sustained ventricular tachycardia warrants treatment with an implantable cardioverter defibrillator (ICD). Primary prevention of sudden death in patients considered to be at high risk should aim at the management of obvious arrhythmogenic mechanisms (paroxysmal atrial fibrillation, sustained monomorphic ventricular tachycardia, conduction system disease, accessory pathway, myocardial ischemia), and the prevention and/or

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiac Pacing, Artificial; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Catheter Ablation; Child; Death, Sudden, Cardiac; Endocarditis; Humans; Risk Factors

Chronic heart failure (CHF) is a life threatening disease with an enormous medical requirement. Approximately 15 million people worldwide suffer from CHF. The prevalence will inevitably increase due to the ageing population. Nevertheless, current treatment options based on angiotensin-converting enzyme inhibitors and beta-adrenergic receptor antagonists merely slow progression of the disease. Novel treatment concepts based on new therapeutic targets must have the capability to reverse the severity of this disease. This review, focusing on the emerging targets in the most promising therapeutic areas for the treatment of CHF, will be divided into two parts. In Part I, disease concepts such as altered calcium handling and ion channel activity, pathophysiological hypertrophy and inefficient cardiac metabolism are discussed. Validation status and potential therapeutic value for new targets in each research field is given by summarising the results of in vitro and in vivo studies.

Topics: Animals; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Calcium Channels; Calcium Signaling; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Energy Metabolism; Fatty Acids; Heart Failure; Humans; Ion Channels; MAP Kinase Signaling System; Mice; Muscle Proteins; PPAR alpha; Rats; Transcription Factors

Cardiomyopathies have either a primary (without associated anomalies) or a secondary origin. They are classified in three groups according to their anatomy and function: hypertrophic, dilated or restrictive. We review here the relevant diagnostic points of each type as well as their treatment. Restrictive cardiomyopathies, arrhythmogenic right ventricle, non compaction and Uhl's anomaly will not be dealt with in detail as they are very seldom in children.

Topics: Cardiac Surgical Procedures; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Child; Death, Sudden, Cardiac; Diagnosis, Differential; Electrocardiography; Genetic Predisposition to Disease; Humans; Hypertrophy, Left Ventricular; Incidence

Hypertrophic cardiomyopathy is characterized by left or right ventricular hypertrophy that is usually asymmetric and involves the interventricular septum. The condition has numerous genetic, anatomic, and clinical variations and continues to stimulate interest and investigation into causes and treatment options. New genetic forms of the disorder are being identified because of the rapid growth of molecular genetics. However, even with technological advances and a large database of information, risk stratification and treatment of hypertrophic cardiomyopathy remain difficult and controversial. Because of the high risk of sudden death, it is imperative that patients be advised against participation in competitive sports.

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Death, Sudden; Electrocardiography; Humans; Physical Examination; Risk Factors

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Humans

We report the case of a 63-year-old female patient with apical hypertrophic cardiomyopathy, diagnosed by the presence of localized apical hypertrophy in the echocardiogram and a typical "spade like" left ventricular angiographic image, but with unique electrocardiographic features, characterized by chronic ST segment elevation, and T wave inversion, in the anterolateral leads. These changes were initially interpreted as a manifestation of acute ischemic heart disease. Chronic ST segment elevation has been occasionally described in patients with hypertrophic cardiomyopathy complicated with apical necrosis and aneurysm formation, but not in uncomplicated cases of apical hypertrophic cardiomyopathy. Its knowledge by the physician could allow avoidance of problems of differential diagnosis with more frequent heart diseases, especially acute atherosclerotic ischaemic heart disease.

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Diagnosis, Differential; Diltiazem; Electrocardiography; Female; Humans; Middle Aged; Myocardial Infarction

Therapy of hypertrophic cardiomyopathy aspires to reduce symptoms, increase exercise tolerance, retard or prevent disease progression, and improve prognosis. Medical treatment with calcium antagonists and suppression of rhythm disturbances with amiodarone seem to be most effective. In patients who show no improvement, surgical treatment must be considered.

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Humans

Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder which frequently leads to symptoms such as dyspnea and exercise intolerance, often due to severe dynamic left ventricular outflow tract obstruction (LVOTO). Current guideline-recommended pharmacotherapies have variable therapeutic responses to relieve LVOTO. In recent phases 2 and 3, clinical trials for symptomatic obstructive HCM (oHCM), mavacamten, a small molecule inhibitor of β-cardiac myosin has been shown to improve symptoms, exercise capacity, health status, reduce LVOTO, along with having a beneficial impact on cardiac structure and function.. VALOR-HCM is designed as a multicenter (approximately 20 centers in United States) phase 3, double-blind, placebo-controlled, randomized study. The study population consists of approximately 100 patients (≥18 years old) with symptomatic oHCM who meet 2011 American College of Cardiology/American Heart Association and/or 2014 European Society of Cardiology HCM-guideline criteria and are eligible and willing to undergo septal reduction therapy (SRT). The study duration will be up to 138 weeks, including an initial 2-week screening period, followed by16 weeks of placebo-controlled treatment, 16 weeks of active blinded treatment, 96 weeks of long-term extension, and an 8-week posttreatment follow-up visit. The primary endpoint will be a composite of the decision to proceed with SRT prior to or at Week 16 or remain guideline eligible for SRT at Week 16. Secondary efficacy endpoints will include change (from baseline to Week 16 in the mavacamten group vs placebo) in postexercise LVOT gradient, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire clinical summary score, NT-proBNP, and cardiac troponin. Exploratory endpoints aim to characterize the effect of mavacamten on multiple aspects of oHCM pathophysiology.. In severely symptomatic drug-refractory oHCM patients meeting guideline criteria of eligibility for SRT, VALOR-HCM will primarily study if a 16-week course of mavacamten reduces or obviates the need for SRT using clinically driven endpoints.

Topics: Adult; Benzylamines; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Clinical Trials, Phase III as Topic; Double-Blind Method; Dyspnea; Eligibility Determination; Exercise Tolerance; Female; Humans; Male; Randomized Controlled Trials as Topic; Uracil; Ventricular Myosins

The presence and extent of left ventricular hypertrophy (LVH) is a major determinant of symptoms in patients with hypertrophic cardiomyopathy (HCM). There is increasing evidence to suggest that myocardial energetic impairment represents a central mechanism leading to LVH in HCM. There is currently a significant unmet need for disease-modifying therapy that regresses LVH in HCM patients. Perhexiline, a potent carnitine palmitoyl transferase-1 (CPT-1) inhibitor, improves myocardial energetics in HCM, and has the potential to reduce LVH in HCM.. The primary objective is to evaluate the effects of perhexiline treatment on the extent of LVH, in symptomatic HCM patients with at least moderate LVH.. RESOLVE-HCM is a prospective, multicenter double-blind placebo-controlled randomized trial enrolling symptomatic HCM patients with at least moderate LVH. Sixty patients will be randomized to receive either perhexiline or matching placebo. The primary endpoint is change in LVH, assessed utilizing cardiovascular magnetic resonance (CMR) imaging, after 12-months treatment with perhexiline.. RESOLVE-HCM will provide novel information on the utility of perhexiline in regression of LVH in symptomatic HCM patients. A positive result would lead to the design of a Phase 3 clinical trial addressing long-term effects of perhexiline on risk of heart failure and mortality in HCM patients.

Topics: Adult; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Double-Blind Method; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Perhexiline; Prospective Studies

Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by unexplained left ventricular (LV) hypertrophy associated with dynamic LV outflow tract obstruction. Current medical therapies are nonspecific and have limited efficacy in relieving symptoms. Mavacamten is a first-in-class targeted inhibitor of cardiac myosin, which has been shown to reduce LV outflow tract obstruction, improve exercise capacity, and relieve symptoms of oHCM in the PIONEER-HCM phase 2 study.. EXPLORER-HCM is a multicenter, phase 3, randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of mavacamten in treating symptomatic oHCM. Eligible adults with oHCM and New York Heart Association Functional Class II or III are randomized 1:1 to receive once-daily, oral mavacamten, or matching placebo for 30 weeks. The primary composite functional end point is clinical response at week 30 compared to baseline defined as either (1) an increase in peak oxygen consumption ≥1.5 mL/kg/min and reduction of at least one New York Heart Association class; or (2) an improvement of ≥3.0 mL/kg/min in peak oxygen consumption with no worsening of New York Heart Association class. Secondary end points include change in postexercise LV outflow tract gradient, New York Heart Association class, peak oxygen consumption, and patient-reported outcomes assessed by the Kansas City Cardiomyopathy Questionnaire and a novel HCM-specific instrument. Exploratory end points aim to characterize the effect of mavacamten on multiple aspects of oHCM pathophysiology.. EXPLORER-HCM is a phase 3 trial in oHCM testing a first-in-class, targeted strategy of myosin inhibition to improve symptom burden and exercise capacity through reducing LV outflow tract obstruction. Results of this trial will provide evidence to support the first disease-specific treatment for HCM. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03470545.

Topics: Benzylamines; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Clinical Trials, Phase III as Topic; Double-Blind Method; Exercise Tolerance; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Recovery of Function; Treatment Outcome; Uracil; Ventricular Function, Left

Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying biomechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM).. To characterize the effect of mavacamten on left ventricular outflow tract (LVOT) gradient.. Open-label, nonrandomized, phase 2 trial. (ClinicalTrials.gov: NCT02842242).. 5 academic centers.. 21 symptomatic patients with oHCM.. Patients in cohort A received mavacamten, 10 to 20 mg/d, without background medications. Those in cohort B received mavacamten, 2 to 5 mg/d, with β-blockers allowed.. The primary end point was change in postexercise LVOT gradient at 12 weeks. Secondary end points included changes in peak oxygen consumption (pVO2), resting and Valsalva LVOT gradients, left ventricular ejection fraction (LVEF), and numerical rating scale dyspnea score.. In cohort A, mavacamten reduced mean postexercise LVOT gradient from 103 mm Hg (SD, 50) at baseline to 19 mm Hg (SD, 13) at 12 weeks (mean change, -89.5 mm Hg [95% CI, -138.3 to -40.7 mm Hg]; P = 0.008). Resting LVEF was also reduced (mean change, -15% [CI, -23% to -6%]). Peak VO2 increased by a mean of 3.5 mL/kg/min (CI, 1.2 to 5.9 mL/kg/min). In cohort B, the mean postexercise LVOT gradient decreased from 86 mm Hg (SD, 43) to 64 mm Hg (SD, 26) (mean change, -25.0 mm Hg [CI, -47.1 to -3.0 mm Hg]; P = 0.020), and mean change in resting LVEF was -6% (CI, -10% to -1%). Peak VO2 increased by a mean of 1.7 mL/kg/min (SD, 2.3) (CI, 0.03 to 3.3 mL/kg/min). Dyspnea scores improved in both cohorts. Mavacamten was well tolerated, with mostly mild (80%), moderate (19%), and unrelated (79%) adverse events. The most common adverse events definitely or possibly related to mavacamten were decreased LVEF at higher plasma concentrations and atrial fibrillation.. Small size; open-label design.. Mavacamten can reduce LVOT obstruction and improve exercise capacity and symptoms in patients with oHCM.. MyoKardia.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Adult; Aged; Benzylamines; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Exercise Tolerance; Female; Humans; Male; Middle Aged; Oxygen Consumption; Prospective Studies; Stroke Volume; Uracil; Ventricular Function, Left; Young Adult

The impact of ethanol dose on the long-term outcome of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy was investigated.. Fifty-four patients (age 24-82 years; 65% women) undergoing ASA were randomized into 2 groups according to the dose of injected ethanol: Group A 1-2 ml, Group B >2 ml. Clinical and echocardiographic data were obtained at baseline and during follow-up. The volume of ethanol injected was 1.50+/-0.4 and 2.60+/-0.6 ml (p<0.001) with a subsequent peak of creatine kinase-MB of 2.25+/-1.00 and 2.62+/-1.57 microkat/L (p=0.02) in Groups A and B, respectively. The median follow-up was 39 (range 6-72) months after ASA, during which 1 patient died and 1 repeat procedure was necessary in both groups of patients. Both groups had a significant and similar improvement in outflow pressure gradient, dyspnea (New York Heart Association functional class) and angina pectoris (Canadian Cardiovascular Society class) (p<0.001). There was a significant decrease in the left ventricular ejection fraction (LVEF) in Group B (81+/-7 vs 75+/-7%; p=0.002), but not in Group A (80+/-7 vs 79+/-7%; p=0.67). Thinning of the basal septum was more pronounced in Group B than in Group A (9.3+/-5.7 vs 6.6+/-3.4 mm; p=0.04).. A lower dose of ethanol injected into the target septal branch reduces both the size of necrosis and subsequent thinning of the basal septum, and preserves LVEF during long-term follow-up. Moreover, the low dose (1-2 ml) is as safe and as hemodynamically efficacious as higher doses.

Topics: Adult; Aged; Cardiac Catheterization; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Ethanol; Female; Humans; Injections, Intralesional; Male; Middle Aged; Prospective Studies; Treatment Outcome

Topics: Action Potentials; Algorithms; Calcium; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Computer Simulation; Drug Evaluation, Preclinical; Electrocardiography; Humans; Myocytes, Cardiac; Risk Assessment; Sarcoplasmic Reticulum; Torsades de Pointes

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Heart Septum; Humans

Topics: Benzylamines; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Enzyme Inhibitors; Humans; Myocardial Contraction; Myocytes, Cardiac; Myosins; Randomized Controlled Trials as Topic; Recovery of Function; Treatment Outcome; Uracil; Ventricular Function, Left; Ventricular Outflow Obstruction; Ventricular Remodeling

Topics: Anti-Arrhythmia Agents; Antineoplastic Agents; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Drug Repositioning; Echocardiography; Gene Expression Regulation; Heart Valves; Heterozygote; Humans; Infant; MAP Kinase Kinase 1; Mutation; Natriuretic Peptide, Brain; Noonan Syndrome; Peptide Fragments; Propranolol; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; ras Proteins; Signal Transduction; Treatment Outcome

: A 55-year-old gentleman with hypertrophic obstructive cardiomyopathy and heart failure symptoms underwent cardiac catheterization, which confirmed a significant pressure drop (60 mmHg) across the left ventricular outflow tract, a double-peaked pulse (pulsus bisferiens) and an absent postextrasystolic potentiation (Brockenbrough-Braunwald-Morrow sign) in the left ventricular outflow tract and the aorta. He was treated with medical therapy optimization and intracardiac defibrillator implantation. Cardiac catheterization may provide characteristic clues not only to diagnose obstructive hypertrophic cardiomyopathy, but also to understand its pathophysiological correlates.

Topics: Arrhythmias, Cardiac; Cardiac Catheterization; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Defibrillators, Implantable; Echocardiography; Electric Countershock; Electrocardiography; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Predictive Value of Tests; Treatment Outcome; Ventricular Function, Left; Ventricular Outflow Obstruction; Ventricular Pressure

Topics: Aged; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Female; Humans; Male; Middle Aged; Midodrine; Recovery of Function; Treatment Outcome; Ventricular Function, Left

Topics: Aged; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Computed Tomography Angiography; Connectin; Coronary Angiography; DNA Mutational Analysis; Echocardiography; Electrocardiography; Epigenesis, Genetic; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging; Mutation; Phenotype; Risk Factors; Treatment Outcome; Twins, Monozygotic

The indications for a concomitant mitral valve (MV) procedure remain controversial for patients with hypertrophic obstructive cardiomyopathy (HOCM). According to previous studies, a concomitant MV surgery was required in 11-20% of inpatient operations. Thus, we aimed to study the outcomes of an extended Morrow procedure without a concomitant MV procedure for HOCM patients who had no intrinsic abnormalities of the MV apparatus. We retrospectively reviewed 232 consecutive HOCM patients who underwent extended Morrow procedures from January 2010 to October 2014. Only 10 (4.31%) patients with intrinsic MV diseases underwent concomitant MV procedures. Of the 232 patients, 230 had no to mild mitral regurgitation (MR) postoperatively. We separated the 232 patients into two groups according to preoperative MR degree. One group is mild MR, and the other is moderate or severe MR. The three-month, one-year, and three-year composite end-point event-free survival rates had no difference between two groups (p = 0.820). When we separated the patients to postoperative no or trace MR group and mild MR group, there was also no difference on survival rates (p = 0.830). In conclusion, concomitant mitral valve procedures are not necessary for HOCM patients with MR caused by systolic anterior motion, even moderate to severe extent.

Topics: Adult; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; China; Combined Modality Therapy; Disease-Free Survival; Female; Follow-Up Studies; Heart Septum; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Proportional Hazards Models; Retrospective Studies; Treatment Outcome; Ventricular Outflow Obstruction

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Female; Heart Failure; Humans; Pregnancy; Pregnancy Complications, Cardiovascular

Topics: Aged; Angina Pectoris; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Dyspnea; Female; Humans; Male; Middle Aged; Pilot Projects; Ranolazine

Topics: Ablation Techniques; Aged; Cardiac Resynchronization Therapy Devices; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Diagnosis, Differential; Disease Management; Echocardiography; Female; Heart Septum; Humans; Takotsubo Cardiomyopathy; Time; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Outflow Obstruction

Topics: Cardiac Pacing, Artificial; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Ethanol; Humans

Topics: Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Exercise Test; Genetic Predisposition to Disease; Genetic Testing; Heredity; Humans; Magnetic Resonance Imaging; Mutation; Pedigree; Phenotype; Predictive Value of Tests; Primary Prevention; Risk Assessment; Risk Factors; Risk Reduction Behavior; Ventricular Outflow Obstruction

Myocardial fibrosis plays a key role in the pathogenesis of cardiovascular diseases. The chronic pressure overload of the heart activates collagen that leads to its excessive accumulation, fibrosis and cardiac hypertrophy. Myocardial injury is often accompanied by liver damage. These two processes are closely linked. One of the links of this chain is the activation of the renin-angiotensin-aldosterone system (RAAS). There is impressive evidence base for drugs that block the RAAS, and thus break the vicious cycle of cardiovascular continuum. Fibrogenesis is nonspecific process and prospect of drug application affecting the activity of the RAAS may be useful for fibrosis prevention not only for the heart and liver, but also for other organs.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Clinical Trials as Topic; Collagen; Female; Fibrosis; Heart Function Tests; Humans; Liver Cirrhosis; Male; Middle Aged; Myocardium; Renin-Angiotensin System

Haemodynamic changes that occur during pregnancy are maximal between 28 and 34 weeks. In the pregnant woman with several associated diseases, such as hypertensive myocardiopathy and pre-gestational diabetes, these changes can lead to a difficult control of pulmonary hypertension and acute pulmonary oedema. We report the case of a pregnant woman with long term type 1 diabetes mellitus who suffered pre-eclampsia in a previous pregnancy, and since then developed hypertensive cardiomyopathy. She was admitted at 30 week gestation for metabolic and blood pressure control, and developed congestive cardiac failure after the administration of betamethasone for foetal lung maturity. A transthoracic echocardiogram showed a non-dilated hypertrophic left ventricle with good systolic function, restrictive diastolic dysfunction and moderate pulmonary arterial hypertension. When her general condition improved, we performed a caesarean section under regional anaesthesia to prevent the complications of pulmonary and systemic hypertension. We present the anaesthetic management and resolution of complications after oxytocin administration.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Betamethasone; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Cesarean Section, Repeat; Diabetes Mellitus, Type 1; Diastole; Female; Heart Failure; Humans; Hypertension, Pulmonary; Hypotension; Infant, Newborn; Intraoperative Complications; Norepinephrine; Oxytocin; Phenylephrine; Pre-Eclampsia; Preanesthetic Medication; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Supine Position

Hypertrophic cardiomyopathy is a complex and relatively common genetic cardiac disease and has been the subject of intensive scrutiny and investigation for over 40 years. The aim of this non-randomized cohort study was to compare subjective and objective outcomes in hypertrophic cardiomyopathy patients undergoing drug therapy, surgical myotomy-myectomy, dual-chamber pacing and alcohol septal ablation.. We examined 194 patients: 103 with non-obstructive hypertrophic cardiomyopathy and 91 with obstructive hypertrophic cardiomyopathy. All the patients with a non-obstructive form were on drug therapy. Ninety-one consecutive patients with drug-refractory obstructive hypertrophic cardiomyopathy were treated invasively. Dual-chamber pacemaker implantation was performed for 49 patients with previous positive temporary pacing test (Group 1). In 28 patients with massive left ventricle hypertrophy and obliteration of its cavities, extensive myotomy-myectomy was performed (Group 2). In 14 patients with midventricular obstruction and appropriate coronary anatomy, alcohol septal ablation was performed (Group 3).. The peak left ventricle outflow tract gradient was 84.1 ± 15.2 mmHg in Group 1, 113.3 ± 14.9 mmHg in Group 2 and 97.5 ± 8.9 mmHg in Group 3. Dual-chamber pacing in Group 1 with optimal atrio-ventricular delay (85-180 ms for atrium pacing and 45-120 ms for atrial sensing) leads to dramatic decreases in left ventricle outflow tract gradient to 17.6 ± 11.8 mmHg and degree of mitral regurgitation. After extensive myectomy in Group 2, we observed a reduction of left ventricle outflow tract gradient to 17.3 ± 10.2 mmHg. Septal alcohol ablation in Group 3 leads to a left ventricle outflow tract gradient decrease from 97.5 ± 8.9 to 25.3 ± 5.8 mmHg.. Surgical myectomy, dual-chamber pacing and alcohol septal ablation are equally effective in reducing obstruction in case of correct indications. Dual-chamber pacing is indicated in functional reversible states characterized by excitation delay. Alcohol septal ablation is preferable in cases with midventricular obstruction and appropriate coronary anatomy. Surgical methods are indicated in anatomical irreversible changes and remain the gold standard for obstructive hypertrophic cardiomyopathy treatment.

Topics: Ablation Techniques; Adolescent; Adult; Cardiac Pacing, Artificial; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Disease Progression; Ethanol; Female; Humans; Male; Middle Aged; Patient Selection; Recovery of Function; Retrospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Pressure; Young Adult

To evaluate the effects of the pacemaker funny current (I(f)) inhibitor ivabradine on heart rate (HR), left ventricular (LV) systolic and diastolic function, and left atrial performance in healthy cats and cats with hypertrophic cardiomyopathy (HCM).. 6 healthy cats and 6 cats with subclinical HCM.. Anesthetized cats underwent cardiac catheterization and were studied over a range of hemodynamic states induced by treatment with esmolol (200 to 400 μg/kg/min, IV), esmolol and dobutamine (5 μg/kg/min, IV), ivabradine (0.3 mg/kg, IV), and ivabradine and dobutamine. Left ventricular systolic and diastolic function, cardiac output, and left atrial function were studied via catheter-based methods and echocardiography.. Treatment with ivabradine resulted in a significant reduction of HR, rate-pressure product, and LV contractile function and a significant increase in LV end-diastolic pressure, LV end-diastolic wall stress, and LV relaxation time constant (tau) in cats with HCM. Concurrent administration of ivabradine and dobutamine resulted in a significant increase of LV contractility and lusitropy, with blunted chronotropic effects of the catecholamine. Left atrial performance was not significantly altered by ivabradine in cats with HCM. Regression analysis revealed an association between maximum rate of LV pressure rise and tau in cats with HCM.. Ivabradine had significant effects on several cardiovascular variables in anesthetized cats with HCM. Studies in awake cats with HCM are needed to clinically validate these findings.

Topics: Adrenergic beta-1 Receptor Agonists; Adrenergic beta-1 Receptor Antagonists; Animals; Benzazepines; Blood Pressure; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Cat Diseases; Cats; Dobutamine; Dose-Response Relationship, Drug; Heart Rate; Ivabradine; Propanolamines; Ventricular Function, Left

The management of patients with hypertrophic cardiomyopathy (HCM) and refractory symptoms due to massive hypertrophy and severe diastolic dysfunction represents a real challenge for the clinical cardiologist. Such patients often require novel therapeutic approaches, both invasive and pharmacological, involving multidisciplinary teamwork; however, the implementation of potentially viable treatment options is hindered by lack of disease-specific evidence. We report the case of a young woman with severe HCM and restrictive physiology, who underwent extensive myectomy via the transaortic and transapical approach, followed by biventricular pacing for cardiac resynchronization, with significant but incomplete symptomatic improvement. The subsequent introduction of ranolazine, based on promising preclinical data, has led to an excellent final result. An ongoing randomized clinical trial is currently testing the efficacy of ranolazine in symptomatic HCM.

Topics: Acetanilides; Adult; Cardiac Pacing, Artificial; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Restrictive; Cardiovascular Agents; Catheter Ablation; Enzyme Inhibitors; Female; Humans; Pacemaker, Artificial; Piperazines; Ranolazine; Severity of Illness Index; Treatment Outcome

To evaluate the long-term prognostic impact of baseline symptoms in a cohort of hypertrophic cardiomyopathy (HCM) patients.. We considered 84 HCM patients symptomatic at diagnosis: 26 (31%) with heart failure (group 1), 34 (40%) with syncope/palpitations (group 2) and 24 (29%) with chest pain (group 3). During a median follow-up of 102 (53-187) months, 25 (30%) patients died/underwent heart transplant (HTx), 14 of 26 (54%) in group 1, 10 of 34 (29%) in group 2 and one of 24 (4%) in group 3. At 12, 60 and 120 months, HTx-free survival rates were 100, 79 and 52% in group 1, vs. 100, 97 and 69% in group 2, vs. 96, 96 and 96% in group 3, respectively (P = 0.008). At multivariate analysis, heart failure [hazard ratio (HR) 2.59, confidence interval (CI) 95% 1.09-6.17, P = 0.032] and left atrium diameter (HR 1.83, CI 95% 1.16-2.89, P = 0.009) emerged as independent predictors of death/HTx, with incremental prognostic power with respect to echo Doppler variables of left ventricular systolic and diastolic dysfunction [area under the curve (AUC) of receiver operating characteristics (ROC) curves at 5 years: 0.90 vs. 0.78, respectively, P = 0.03].. Clinical presentation emerged as a relevant prognostic tool in HCM patients symptomatic at onset, as heart failure was associated with a particularly poor outcome. Heart failure and left atrium diameter at diagnosis showed incremental prognostic power compared with echo Doppler assessment of left ventricular systolic and diastolic dysfunction.

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Chest Pain; Chi-Square Distribution; Child; Child, Preschool; Disease-Free Survival; Echocardiography, Doppler; Female; Heart Atria; Heart Failure; Heart Transplantation; Humans; Infant; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Registries; Risk Factors; Syncope; Time Factors; Ventricular Function, Left; Young Adult

Topics: Acetanilides; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Restrictive; Cardiovascular Agents; Enzyme Inhibitors; Female; Humans; Piperazines

Topics: Angioplasty, Balloon, Coronary; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Echocardiography; Humans; Male; Middle Aged; Myocardial Bridging; Platelet Aggregation Inhibitors; Predictive Value of Tests; Treatment Outcome; Ultrasonography, Interventional

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Death, Sudden, Cardiac; Genetic Predisposition to Disease; Humans; Phenotype; Recovery of Function; Risk Factors; Treatment Outcome

An adult castrated male pet kinkajou (Potos flavus) presented with dyspnea due to congestive heart failure and was diagnosed with hypertrophic cardiomyopathy (HCM) and suspected pulmonary arterial hypertension. Diagnosis was based on history, clinical signs, clinical pathology, radiographs, abdominal ultrasonography, abdominal fluid analysis, electrocardiography, and echocardiogram. An undetermined hepatopathy also was found at presentation and resolved after metronidazole antimicrobial treatment. Cardiopulmonary medical treatment, including a loop diuretic, an angiotensin-converting enzyme inhibitor, a beta-adrenergic receptor blocker, and a bronchodilator provided improvement of the clinical signs. To the best of our knowledge, this is the first reported case of antemortem diagnosis and treatment of congestive heart failure and cardiomyopathy in a member of the family Procyonidae, suggesting that HCM should be considered as a differential diagnosis in kinkajous displaying clinical signs of dyspnea and exercise intolerance.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Infective Agents; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Diuretics; Furosemide; Heart Failure; Liver Diseases; Male; Metronidazole; Procyonidae

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Carnitine O-Palmitoyltransferase; Energy Metabolism; Exercise Tolerance; Humans; Myocardium; Perhexiline

Topics: Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Death, Sudden, Cardiac; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging

Topics: Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Continuous Positive Airway Pressure; Hemodynamics; Humans; Risk Factors; Sleep Apnea Syndromes; Sympathetic Nervous System; Treatment Failure; Ventricular Outflow Obstruction

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Humans; Iceland

Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) may create an ischemic substrate conducive to sudden death, but it remains unknown whether the extent of hypertrophy is associated with proportionally poorer perfusion reserve. Comparisons between magnitude of hypertrophy, impairment of perfusion reserve, and extent of fibrosis may offer new insights for future clinical risk stratification in HCM but require multiparametric imaging with high spatial and temporal resolution.. Degree of hypertrophy, myocardial blood flow at rest and during hyperemia (hMBF), and myocardial fibrosis were assessed with magnetic resonance imaging in 35 HCM patients (9 [26%] male/26 female) and 14 healthy controls (4 [29%] male/10 female), aged 18 to 78 years (mean+/-SD, 42+/-14 years) with the use of the American Heart Association left ventricular 16-segment model. Resting MBF was similar in HCM patients and controls. hMBF was lower in HCM patients (1.84+/-0.89 mL/min per gram) than in healthy controls (3.42+/-1.76 mL/min per gram, with a difference of -0.95+/-0.30 [SE] mL/min per gram; P<0.001) after adjustment for multiple variables, including end-diastolic segmental wall thickness (P<0.001). In HCM patients, hMBF decreased with increasing end-diastolic wall thickness (P<0.005) and preferentially in the endocardial layer. The frequency of endocardial hMBF falling below epicardial hMBF rose with wall thickness (P=0.045), as did the incidence of fibrosis (P<0.001).. In HCM the vasodilator response is reduced, particularly in the endocardium, and in proportion to the magnitude of hypertrophy. Microvascular dysfunction and subsequent ischemia may be important components of the risk attributable to HCM.

Topics: Adolescent; Adult; Aged; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Contrast Media; Coronary Circulation; Endocardium; Female; Fibrosis; Gadolinium DTPA; Humans; Hyperemia; Image Processing, Computer-Assisted; Magnetic Resonance Angiography; Male; Microcirculation; Middle Aged; Myocardial Ischemia; Myocardium; Rest; Risk; Vasodilation

To determine the range of survival rates of patients with hypertrophic cardiomyopathy (HCM) by comparing and contrasting the natural history of a cohort of patients seen between 1988 and 2002 with that of other published series.. 956 adult (> or = 16 years old) patients with HCM (572 men, mean (SD) age 42 (15) years, range 16-88) were evaluated by ECG, Holter, exercise testing, and echocardiography. Patient characteristics and survival data were compared with those in natural history studies from referral and non-referral centres published between 1960 and January 2003.. The duration of follow up was 69 (45) months. 120 (12.6%) patients died or underwent cardiac transplantation. Sudden cardiac death (n = 48) was the most common mode of death. The annual rate of sudden death or implantable cardioverter-defibrillator discharge was 1.02 (95% confidence interval (CI) 0.76 to 1.26). Annual rates for heart failure death or transplantation and stroke related death were 0.55% (95% CI 0.37% to 0.78%) and 0.07% (95% CI 0.02% to 0.19%), respectively. When studies published within the last 10 years of the study period were compared with earlier reports, the size of individual study cohorts was larger (309 (240.6) v 136.5 (98.8), p = 0.058) and the proportion with severe functional limitation NYHA class III/IV lower (12.4% v 24.8%, p < 0.0001), and fewer patients underwent septal myotomy-myectomy (5.2% v 18.7%, p < 0.0001). Published sudden death rates over the last 10 years were lower than previously published figures (median 1.0% (range 0.1-1.7) v 2.0% (0-3.5)).. Published survival rates in HCM cohorts have improved progressively over the past 40 years. In the modern era the prevalence of disease related complications is similar in all reporting centres.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiac Pacing, Artificial; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Cause of Death; Cohort Studies; Female; Follow-Up Studies; Heart Transplantation; Humans; London; Male; Middle Aged; Mortality; Survival Rate

A male infant with clinical features of Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy is reported. He manifested severe heart failure and failure to thrive. Administration of propranolol and cibenzoline improved ventricular outflow tract obstruction, leading to catch-up growth. Genetic analysis of the patient revealed a novel missense mutation in the PTPN11 gene.. This is the first description of a patient with a Gln510Glu mutation in the protein-tyrosine phosphatase, non-receptor type 11 gene. This specific mutation may be associated with a rapidly progressive hypertrophic cardiomyopathy.

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Chromosomes, Human, Pair 12; Drug Therapy, Combination; Glutamic Acid; Glutamine; Humans; Imidazoles; Infant; Intracellular Signaling Peptides and Proteins; Male; Mutation, Missense; Noonan Syndrome; Propranolol; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatases; Treatment Outcome

We have shown earlier that cardiomyocyte apoptosis continues at a high level late after myocardial infarction and contributes to adverse cardiac remodeling. Here we studied whether this process can be inhibited by the vasopeptidase inhibitor omapatrilat, a drug which causes simultaneous inhibition of both angiotensin converting enzyme and neutral endopeptidase. Our hypothesis was that omapatrilat-treated rats would have less cardiomyocyte apoptosis, and less adverse cardiac remodeling compared to rats treated with selective inhibitors of angiotensin converting enzyme, neutral endopeptidase or placebo. Myocardial infarction was produced by ligation of the left anterior descending coronary artery. Rats were randomized to receive omapatrilat, captopril, neutral endopeptidase inhibitor SQ-28603 or vehicle. Rats treated with omapatrilat and captopril had reduced cardiac BNP mRNA levels and less myocardial fibrosis by comparison with the vehicle-treated rats. However, omapatrilat was more effective than captopril in attenuating hypertrophy as measured by relative cardiac weight (3.0+/-0.2 vs. 3.8+/-0.2 mg/g, P<0.01) or by echocardiographically determined left ventricular mass (0.61+/-0.05 vs. 0.83+/-0.06 g, P<0.01). Myocardial apoptosis was elevated both in the infarction border zone (0.129+/-0.017%) and in the remote area (0.035+/-0.005%) still 4 weeks after myocardial infarction. Angiotensin converting enzyme inhibition proved to be important in the prevention of apoptosis since both omapatrilat and captopril reduced the number of apoptotic myocytes whereas selective neutral endopeptidase inhibitor SQ-28603 had no effect. In conclusion, myocardial apoptosis, remaining increased 4 weeks after myocardial infarction, was reduced by angiotensin converting enzyme inhibition. Vasopeptidase inhibition was more effective than selective angiotensin converting enzyme inhibition in preventing adverse cardiac remodeling after myocardial infarction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Blood Pressure; Body Weight; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Fibrosis; Male; Muscle Cells; Myocardial Infarction; Myocardium; Neprilysin; Organ Size; Pyridines; Rats; Rats, Wistar; Thiazepines; Ventricular Remodeling

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Septum; Humans; Minimally Invasive Surgical Procedures; Pacemaker, Artificial; Survival Rate; Ventricular Outflow Obstruction

Chest pain in patients with hypertrophic cardiomyopathy seems to be caused by relative myocardial ischemia due to the left ventricular outflow pressure gradient and myocardial hypertrophy. However, in 2 cases of hypertrophic cardiomyopathy chest pain was associated with coronary vasospasm. Thus, chest pain in these cases was decreased not by a beta-blocker but by isosorbide dinitrate and a calcium antagonist. Because beta-blockers are commonly used for hypertrophic obstructive cardiomyopathy and chest pain may be aggravated by beta-blockers in patients with coronary vasospasm, a combination of beta-blocker, isosorbide dinitrate and calcium antagonist was necessary for this hypertrophic cardiomyopathy with variant angina.

Topics: Adrenergic beta-Antagonists; Aged; Angina Pectoris, Variant; Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Coronary Vasospasm; Diltiazem; Drug Therapy, Combination; Electrocardiography; Humans; Isosorbide Dinitrate; Male; Middle Aged

Hypertrophic cardiomyopathy (HC) is characterized by impaired diastolic function, and left ventricular (LV) outflow tract obstruction in about one-fourth of patients. Verapamil improves diastolic properties, but may have dangerous adverse effects. This study investigates the effects of diltiazem on hemodynamics and LV function in 16 patients with HC who were studied with cardiac catheterization and simultaneous radionuclide angiography. Studies were performed during atrial pacing (15 beats above spontaneous rhythm) at baseline and during intravenous diltiazem administration (0.25 mg x kg(-1) over 2 minutes, and 0.014 mg x kg(-1) x min(-1). Diltiazem induced a systemic vasodilation (cardiac index: 3.4 +/- 1.0 to 4.0 +/- 1.0 L x min(-1) x m(-2), p = 0.003; aortic systolic pressure: 116 +/- 16 to 107 +/- 19 mm Hg, p = 0.007; systemic resistance index: 676 +/- 235 to 532 +/- 193 dynes x s x cm(-5) x m(-2), p = 0.006), not associated with changes in the LV outflow tract gradient. The end-systolic pressure/volume ratio decreased (30 +/- 42 to 21 +/- 29 mm Hg x ml(-1) x m(-2); p = 0.044). Pulmonary artery wedge pressure (11 +/- 5 to 15 +/- 6 mm Hg, p = 0.006), and peak filling rate increased (4.1 +/- 1.3 to 6.0 +/- 2.4 stroke counts x s(-1), p = 0.004). The time constant of isovolumetric relaxation tau decreased (74 +/- 40 to 59 +/- 38 ms, p = 0.045). The constant of LV chamber stiffness did not change. Thus, active diastolic function is improved by the acute administration of diltiazem by both direct action and changes in hemodynamics and loading conditions. LV outflow tract gradient does not increase despite systemic vasodilation. In some patients, however, a marked increase in obstruction and a potentially harmful elevation in pulmonary artery wedge pressure do occur. Passive diastolic function is not affected.

Topics: Adult; Blood Pressure; Calcium Channel Blockers; Cardiac Catheterization; Cardiac Output; Cardiac Pacing, Artificial; Cardiac Volume; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Diastole; Diltiazem; Female; Heart Atria; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged; Myocardial Contraction; Pulmonary Wedge Pressure; Radionuclide Angiography; Systole; Vascular Resistance; Vasodilator Agents; Ventricular Function, Left; Ventricular Outflow Obstruction