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Journal of the American College of... Feb 2022Hypertrophic cardiomyopathy (HCM) is a relatively common often inherited global heart disease, with complex phenotypic and genetic expression and natural history,...
Hypertrophic cardiomyopathy (HCM) is a relatively common often inherited global heart disease, with complex phenotypic and genetic expression and natural history, affecting both genders and many races and cultures. Prevalence is 1:200-1:500, largely based on the disease phenotype with imaging, inferring that 750,000 Americans may be affected by HCM. However, cross-sectional data show that only a fraction are clinically diagnosed, suggesting under-recognition, with most clinicians exposed to small segments of the broad disease spectrum. Highly effective HCM management strategies have emerged, altering clinical course and substantially lowering mortality and morbidity rates. These advances underscore the importance of reliable HCM diagnosis with echocardiography and cardiac magnetic resonance. Family screening with noninvasive imaging will identify relatives with the HCM phenotype, while genetic analysis recognizes preclinical sarcomere gene carriers without left ventricular hypertrophy, but with the potential to transmit disease. Comprehensive initial patient evaluations are important for reliable diagnosis, accurate portrayal of HCM and family history, risk stratification, and distinguishing obstructive versus nonobstructive forms.
Topics: Cardiac Imaging Techniques; Cardiomyopathy, Hypertrophic; Humans
PubMed: 35086660
DOI: 10.1016/j.jacc.2021.12.002 -
Biomolecules Dec 2019Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac muscle disorder with a diverse natural history, characterized by unexplained left ventricular... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac muscle disorder with a diverse natural history, characterized by unexplained left ventricular hypertrophy (LVH), with histopathological hallmarks including myocyte enlargement, myocyte disarray and myocardial fibrosis. Although these features can cause significant cardiac symptoms, many young individuals with HCM are asymptomatic or mildly symptomatic. Sudden cardiac death (SCD) may occur as the initial clinical manifestation. Over the past few decades, HCM has been considered a disease of sarcomere, and typically as an autosomal dominant disease with variable expressivity and incomplete penetrance. Important insights into the genetic landscape of HCM have enhanced our understanding of the molecular pathogenesis, empowered gene-based diagnostic testing to identify at-risk individuals, and offered potential targets for the development of therapeutic agents. This article reviews the current knowledge on the clinical genetics and management of HCM.
Topics: Adrenergic beta-Antagonists; Cardiomyopathy, Hypertrophic; Humans
PubMed: 31888115
DOI: 10.3390/biom9120878 -
European Journal of Heart Failure Feb 2020Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder most often caused by sarcomeric mutations resulting in left ventricular hypertrophy, fibrosis,... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder most often caused by sarcomeric mutations resulting in left ventricular hypertrophy, fibrosis, hypercontractility, and reduced compliance. It is the most common inherited monogenic cardiac condition, affecting 0.2% of the population. Whereas currently available therapies for HCM have been effective in reducing morbidity, there remain important unmet needs in the treatment of both the obstructive and non-obstructive phenotypes. Novel pharmacotherapies directly target the molecular underpinnings of HCM, while innovative procedural techniques may soon offer minimally-invasive alternatives to current septal reduction therapy. With the advent of embryonic gene editing, there now exists the potential to correct underlying genetic mutations that may result in disease. This article details the recent developments in the treatment of HCM including pharmacotherapy, septal reduction procedures, mitral valve manipulation, and gene-based therapies.
Topics: Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Heart Failure; Humans; Mitral Valve; Treatment Outcome
PubMed: 31919938
DOI: 10.1002/ejhf.1715 -
Journal of the American College of... Feb 2022Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly...
Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly treatable condition with effective options that alter natural history along specific personalized adverse pathways at all ages. HCM patients with disease-related complications benefit from: matured risk stratification in which major markers reliably select patients for prophylactic defibrillators and prevention of arrhythmic sudden death; low risk to high benefit surgical myectomy (with percutaneous alcohol ablation a selective alternative) that reverses progressive heart failure caused by outflow obstruction; anticoagulation prophylaxis that prevents atrial fibrillation-related embolic stroke and ablation techniques that decrease the frequency of paroxysmal episodes; and occasionally, heart transplant for end-stage nonobstructive patients. Those innovations have substantially improved outcomes by significantly reducing morbidity and HCM-related mortality to 0.5%/y. Palliative pharmacological strategies with currently available negative inotropic drugs can control symptoms over the short-term in some patients, but generally do not alter long-term clinical course. Notably, a substantial proportion of HCM patients (largely those identified without outflow obstruction) experience a stable/benign course without major interventions. The expert panel has critically appraised all available data and presented management insights and recommendations with concise principles for clinical decision-making.
Topics: Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Humans
PubMed: 35086661
DOI: 10.1016/j.jacc.2021.11.021 -
International Journal of Molecular... Jan 2023The intention of this Special Issue is to highlight novel approaches and new paradigms for understanding the pathogenesis of hypertrophic cardiomyopathy (HCM) [...].
The intention of this Special Issue is to highlight novel approaches and new paradigms for understanding the pathogenesis of hypertrophic cardiomyopathy (HCM) [...].
Topics: Humans; Cardiomyopathy, Hypertrophic
PubMed: 36768840
DOI: 10.3390/ijms24032522 -
Journal of the American Heart... Dec 2022Hypertrophic cardiomyopathy is the most common genetic heart disease. Biomarkers, molecules measurable in the blood, could inform the clinician by aiding in diagnosis,... (Review)
Review
Hypertrophic cardiomyopathy is the most common genetic heart disease. Biomarkers, molecules measurable in the blood, could inform the clinician by aiding in diagnosis, directing treatment, and predicting outcomes. We present an updated review of circulating biomarkers in hypertrophic cardiomyopathy representing key pathologic processes including wall stretch, myocardial necrosis, fibrosis, inflammation, hypertrophy, and endothelial dysfunction, in addition to their clinical significance.
Topics: Humans; Cardiomyopathy, Hypertrophic; Biomarkers
PubMed: 36382968
DOI: 10.1161/JAHA.122.027618 -
Journal of Feline Medicine and Surgery Nov 2021Hypertrophic cardiomyopathy (HCM) is the most common form of feline cardiomyopathy observed clinically and may affect up to approximately 15% of the domestic cat...
PRACTICAL RELEVANCE
Hypertrophic cardiomyopathy (HCM) is the most common form of feline cardiomyopathy observed clinically and may affect up to approximately 15% of the domestic cat population, primarily as a subclinical disease. Fortunately, severe HCM, leading to heart failure or arterial thromboembolism (ATE), only occurs in a small proportion of these cats.
PATIENT GROUP
Domestic cats of any age from 3 months upward, of either sex and of any breed, can be affected. A higher prevalence in male and domestic shorthair cats has been reported.
DIAGNOSTICS
Subclinical feline HCM may or may not produce a heart murmur or gallop sound. Substantial left atrial enlargement can often be identified radiographically in cats with severe HCM. Biomarkers should not be relied on solely to diagnose the disease. While severe feline HCM can usually be diagnosed via echocardiography alone, feline HCM with mild to moderate left ventricular (LV) wall thickening is a diagnosis of exclusion, which means there is no definitive test for HCM in these cats and so other disorders that can cause mild to moderate LV wall thickening (eg, hyperthyroidism, systemic hypertension, acromegaly, dehydration) need to be ruled out.
KEY FINDINGS
While a genetic cause of HCM has been identified in two breeds and is suspected in another, for most cats the cause is unknown. Systolic anterior motion of the mitral valve (SAM) is the most common cause of dynamic left ventricular outflow tract obstruction (DLVOTO) and, in turn, the most common cause of a heart murmur with feline HCM. While severe DLVOTO is probably clinically significant and so should be treated, lesser degrees probably are not. Furthermore, since SAM can likely be induced in most cats with HCM, the distinction between HCM without obstruction and HCM with obstruction (HOCM) is of limited importance in cats. Diastolic dysfunction, and its consequences of abnormally increased atrial pressure leading to signs of heart failure, and sluggish atrial blood flow leading to ATE, is the primary abnormality that causes clinical signs and death in affected cats. Treatment (eg, loop diuretics) is aimed at controlling heart failure. Preventive treatment (eg, antithrombotic drugs) is aimed at reducing the risk of complications (eg, ATE).
CONCLUSIONS
Most cats with HCM show no overt clinical signs and live a normal or near-normal life despite this disease. However, a substantial minority of cats develop overt clinical signs referable to heart failure or ATE that require treatment. For most cats with clinical signs caused by HCM, the long-term prognosis is poor to grave despite therapy.
AREAS OF UNCERTAINTY
Genetic mutations (variants) that cause HCM have been identified in a few breeds, but, despite valiant efforts, the cause of HCM in the vast majority of cats remains unknown. No treatment currently exists that reverses or even slows the cardiomyopathic process in HCM, again despite valiant efforts. The search goes on.
Topics: Animals; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Echocardiography; Heart Ventricles; Male; Systole
PubMed: 34693811
DOI: 10.1177/1098612X211020162 -
Journal of the American College of... Mar 2015Hypertrophic cardiomyopathy (HCM) is an important genetic heart muscle disease for which prevalence in the general population has not been completely resolved. For the... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is an important genetic heart muscle disease for which prevalence in the general population has not been completely resolved. For the past 20 years, most data have supported the occurrence of HCM at about 1 in 500. However, the authors have interrogated a number of relevant advances in cardiovascular medicine, including widespread fee-for-service genetic testing, population genetic studies, and contemporary diagnostic imaging, as well as a greater index of suspicion and recognition for both the clinically expressed disease and the gene-positive-phenotype-negative subset (at risk for developing the disease). Accounting for the potential impact of these initiatives on disease occurrence, the authors have revisited the prevalence of HCM in the general population. They suggest that HCM is more common than previously estimated, which may enhance its recognition in the practicing cardiovascular community, allowing more timely diagnosis and the implementation of appropriate treatment options for many patients.
Topics: Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Echocardiography, Doppler; Female; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging, Cine; Male; Phenotype; Prevalence; Prognosis; Risk Assessment; Severity of Illness Index; Survival Analysis
PubMed: 25814232
DOI: 10.1016/j.jacc.2015.01.019 -
Heart Failure Clinics Jan 2022RASopathies are multisystemic disorders caused by germline mutations in genes linked to the RAS/mitogen-activated protein kinase pathway. Diagnosis of RASopathy can be... (Review)
Review
RASopathies are multisystemic disorders caused by germline mutations in genes linked to the RAS/mitogen-activated protein kinase pathway. Diagnosis of RASopathy can be triggered by clinical clues ("red flags") which may direct the clinician toward a specific gene test. Compared with sarcomeric hypertrophic cardiomyopathy, hypertrophic cardiomyopathy in RASopathies (R-HCM) is associated with higher prevalence of congestive heart failure and shows increased prevalence and severity of left ventricular outflow tract obstruction. Biventricular involvement and the association with congenital heart disease, mainly pulmonary stenosis, have been commonly described in R-HCM. The aim of this review is to assess the prevalence and unique features of R-HCM and to define the available therapeutic options.
Topics: Cardiomyopathy, Hypertrophic; Genetic Testing; Heart Defects, Congenital; Humans; Noonan Syndrome; Prognosis
PubMed: 34776080
DOI: 10.1016/j.hfc.2021.07.004 -
Clinical Medicine (London, England) Jan 2019
Review
Topics: Cardiomyopathy, Hypertrophic; Heart; Humans; Myocardium
PubMed: 30651247
DOI: 10.7861/clinmedicine.19-1-61