NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy

Familial isolated hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disorder characterized by abnormal thickening (hypertrophy) of the left ventricle, typically the interventricular septum, in the absence of other cardiac or systemic conditions that could explain the degree of hypertrophy. It is one of the most common inherited cardiovascular diseases and is classified as non-rare in Europe. The condition primarily affects the cardiovascular system, leading to impaired relaxation (diastolic dysfunction) of the heart, left ventricular outflow tract obstruction in some patients, and disorganization of heart muscle cells (myocyte disarray) and fibrosis at the tissue level. Key symptoms include exertional dyspnea (shortness of breath during physical activity), chest pain, palpitations, syncope (fainting) or presyncope, and exercise intolerance. In some cases, the first manifestation may be sudden cardiac death, particularly in young athletes. Many individuals, however, remain asymptomatic for years and are diagnosed incidentally or through family screening. The clinical course is highly variable, even within the same family, ranging from a benign lifelong course to progressive heart failure or life-threatening arrhythmias. Familial isolated HCM is most commonly caused by pathogenic variants in genes encoding sarcomeric proteins, including MYH7 (beta-myosin heavy chain), MYBPC3 (myosin-binding protein C), TNNT2 (cardiac troponin T), TNNI3 (cardiac troponin I), TPM1 (alpha-tropomyosin), ACTC1 (cardiac actin), MYL2, and MYL3. Treatment is aimed at symptom management and prevention of complications. Beta-blockers and calcium channel blockers (such as verapamil) are first-line therapies for symptomatic patients. Septal reduction therapy (surgical myectomy or alcohol septal ablation) may be offered for patients with significant outflow tract obstruction refractory to medical therapy. Implantable cardioverter-defibrillators (ICDs) are recommended for patients at high risk of sudden cardiac death. More recently, cardiac myosin inhibitors such as mavacamten have been approved as targeted therapies that directly address the underlying pathophysiology of hypercontractility. Genetic counseling and cascade family screening are essential components of management.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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