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Published on: November 2, 2020
Current and emerging perspectives on pathophysiology, diagnosis, and management of hypertrophic cardiomyopathy
Ilias K Gartzonikas1, Katerina K Naka2, Aris Anastasakis3
1Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece; Unit of Inherited and Rare Cardiovascular Diseases, Onassis Cardiac Surgery Center, Athens, Greece.
Insights
Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease. While current therapies manage symptoms and prevent sudden death, new treatments are emerging for disease modification and prevention.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, often linked to mutations in sarcomeric protein genes like MYBPC3 and MYH7.
- HCM diagnosis requires excluding secondary causes of left ventricular hypertrophy, such as hypertension and aortic stenosis.
- The condition presents with diverse clinical manifestations, frequently including diastolic dysfunction and ventricular arrhythmias.
Purpose of the Study:
- To provide an overview of hypertrophic cardiomyopathy, encompassing its genetic basis, diagnosis, clinical features, and current therapeutic strategies.
- To highlight the evolving landscape of HCM management, including novel targeted therapies and updated recommendations for sport participation.
- To identify unmet needs in HCM treatment, focusing on heart failure and atrial fibrillation as leading causes of morbidity and mortality.
Main Methods:
- Review of current literature on hypertrophic cardiomyopathy genetics, pathophysiology, clinical presentation, and treatment modalities.
- Analysis of the impact of existing therapies on HCM mortality and morbidity.
- Identification of emerging therapeutic targets and future research directions.
Main Results:
- Genetic mutations are identified in 34-60% of HCM cases, with MYBPC3 and MYH7 being the most common.
- Current therapies have reduced HCM mortality to under 1% annually but have shifted focus to heart failure and atrial fibrillation.
- A targeted therapy for left ventricular outflow tract obstruction (LVOTO) using allosteric cardiac myosin inhibitors has been developed.
Conclusions:
- Despite therapeutic advancements, heart failure and atrial fibrillation remain significant challenges in HCM management.
- Novel treatments aimed at disease prevention and modification are anticipated with a deeper understanding of HCM's genetic and molecular underpinnings.
- A more liberal approach to sport participation in HCM patients is now recommended following careful evaluation and shared decision-making.
Abstract:
Hypertrophic cardiomyopathy (HCM) is the most common genetically inherited cardiomyopathy with an autosomal dominant inheritance pattern. A disease-causing gene is found between 34% and >60% of the times and the two most frequently mutated genes, which encode sarcomeric proteins, are MYBPC3 and MYH7. HCM is a diagnosis of exclusion since secondary causes of left ventricular hypertrophy should first be ruled out. These include hypertension, aortic stenosis, infiltrative disease, metabolic and endocrine disorders, mitochondrial cardiomyopathies, neuromuscular disorders, malformation syndromes and some chronic drug use. The disease is characterized by great heterogeneity of its clinical manifestations, however diastolic dysfunction and increased ventricular arrhythmogenesis are commonly seen. Current HCM therapies focus on symptom management and prevention of sudden cardiac death. Symptom management includes the use of pharmacological agents, elimination of medication promoting outflow track obstruction, control of comorbid conditions and invasive procedures, whereas in the prevention of sudden cardiac death, implantable cardiac defibrillators and antiarrhythmic drugs are used. A targeted therapy for LVOTO represented by allosteric cardiac myosin inhibitors has been developed. In terms of sport participation, a more liberal approach is recently recommended, after careful evaluation and common-shared decision. The application of the current therapies has lowered HCM mortality rates to <1.0%/year, however it appears to have shifted focus to heart failure and atrial fibrillation, as the predominant causes of disease-related morbidity and mortality and, therefore, unmet treatment need. With improved understanding of the genetic and molecular basis of HCM, the present decade will witness novel treatments for disease prevention and modification.
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