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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 -
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 -
Journal of the American Heart... Mar 2020
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Journal of the American College of... Nov 2019The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic... (Observational Study)
Observational Study
BACKGROUND
The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries.
OBJECTIVES
The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data.
METHODS
Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis.
RESULTS
A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation-positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion.
CONCLUSIONS
The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers.
Topics: Adult; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Echocardiography; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; National Heart, Lung, and Blood Institute (U.S.); Registries; United States
PubMed: 31699273
DOI: 10.1016/j.jacc.2019.08.1057