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Hypertrophic cardiomyopathy in 2013: Current speculations and future perspectives.

ABSTRACT: Hypertrophic cardiomyopathy (HCM), the most variable cardiac disease in terms of phenotypic presentation and clinical outcome, represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance. To date, more than 1400 mutations of myofilament proteins associated with the disease have been identified, most of them "private" ones. This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations. Additionally, topics pertaining to patients' everyday lives, such as sudden cardiac death (SCD) risk stratification and prevention, along with disease prognosis, are grossly related to the genetic variation of HCM. This review incorporates contemporary research findings and addresses major aspects of HCM, including preclinical diagnosis, genetic analysis, left ventricular outflow tract obstruction and SCD. More specifically, the spectrum of genetic analysis, the selection of the best method for obstruction alleviation and the need for a unique and accurate factor for SCD risk stratification are only some of the controversial HCM issues discussed. Additionally, future perspectives concerning HCM and myocardial ischemia, as well as atrial fibrillation, are discussed. Rather than enumerating clinical studies and guidelines, challenging problems concerning the disease are critically appraised by this review, highlighting current speculations and recommending future directions.

SUBMITTER: Efthimiadis GK

PROVIDER: S-EPMC3935059 | biostudies-other | 2014 Feb

REPOSITORIES: biostudies-other

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Hypertrophic cardiomyopathy in 2013: Current speculations and future perspectives.

Efthimiadis Georgios K GK Pagourelias Efstathios D ED Gossios Thomas T Zegkos Thomas T

World journal of cardiology 20140201 2

Hypertrophic cardiomyopathy (HCM), the most variable cardiac disease in terms of phenotypic presentation and clinical outcome, represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance. To date, more than 1400 mutations of myofilament proteins associated with the disease have been identified, most of them "private" ones. This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype cor ...[more]

PMID: 24575171

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Project description:Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and defined by unexplained isolated progressive myocardial hypertrophy, systolic and diastolic ventricular dysfunction, arrhythmias, sudden cardiac death and histopathologic changes, such as myocyte disarray and myocardial fibrosis. Mutations in genes encoding for proteins of the contractile apparatus of the cardiomyocyte, such as ?-myosin heavy chain and myosin binding protein C, have been identified as cause of the disease. Disease is caused by altered biophysical properties of the cardiomyocyte, disturbed calcium handling, and abnormal cellular metabolism. Mutations in sarcomere genes can also activate other signaling pathways via transcriptional activation and can influence non-cardiac cells, such as fibroblasts. Additional environmental, genetic and epigenetic factors result in heterogeneous disease expression. The clinical course of the disease varies greatly with some patients presenting during childhood while others remain asymptomatic until late in life. Patients can present with either heart failure symptoms or the first symptom can be sudden death due to malignant ventricular arrhythmias. The morphological and pathological heterogeneity results in prognosis uncertainty and makes patient management challenging. Current standard therapeutic measures include the prevention of sudden death by prohibition of competitive sport participation and the implantation of cardioverter-defibrillators if indicated, as well as symptomatic heart failure therapies or cardiac transplantation. There exists no causal therapy for this monogenic autosomal-dominant inherited disorder, so that the focus of current management is on early identification of asymptomatic patients at risk through molecular diagnostic and clinical cascade screening of family members, optimal sudden death risk stratification, and timely initiation of preventative therapies to avoid disease progression to the irreversible adverse myocardial remodeling stage. Genetic diagnosis allowing identification of asymptomatic affected patients prior to clinical disease onset, new imaging technologies, and the establishment of international guidelines have optimized treatment and sudden death risk stratification lowering mortality dramatically within the last decade. However, a thorough understanding of underlying disease pathogenesis, regular clinical follow-up, family counseling, and preventative treatment is required to minimize morbidity and mortality of affected patients. This review summarizes current knowledge about molecular genetics and pathogenesis of HCM secondary to mutations in the sarcomere and provides an overview about current evidence and guidelines in clinical patient management. The overview will focus on clinical staging based on disease mechanism allowing timely initiation of preventative measures. An outlook about so far experimental treatments and potential for future therapies will be provided.

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Hypertrophic cardiomyopathy in 2013: Current speculations and future perspectives.

Publications

Hypertrophic cardiomyopathy in 2013: Current speculations and future perspectives.

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