5th July 2026

Hypertrophic cardiomyopathy

• Genetic, autosomal dominant 
• Prevalence: HCM is estimated to affect about 1 in 500 people worldwide. It is the most genetically inherited cardiac disease and the most common cardiomyopathy.
• Age: It can occur at any age, but is most commonly diagnosed in people in adulthood.
• Gender: HCM affects men and women equally, although some studies suggest a slightly higher prevalence in men.

Hypertrophic cardiomyopathy (HCM) is defined by the presence of left ventricular hypertrophy (maximum left ventricular end diastolic wall thickness ≥15 mm on echocardiography) not explained exclusively by other cardiac, systemic or metabolic conditions that may mimic the degree of hypertrophy observed in a given patient. 

HCM is the most common inherited cardiac disease. It is primarily inherited in an autosomal dominant pattern. Mutations in genes encoding proteins of the cardiac sarcomere are the most common causes. The most common gene includes MYH7 (encoding the beta-myosin heavy chain), and other common genes include MYBPC3 (encoding cardiac myosin-binding protein C), TNNT2 (encoding cardiac troponin T), TNNI3 (encoding cardiac troponin I) and TPM1 (encoding alpha-tropomyosin). Non-sarcomeric genes are less common in causing HCM. The impaired sarcomeric function is responsible for inefficient contraction. In response, the myocardium hypertrophies to compensate. 

It is estimated that the prevalence of HCM in the general adult population worldwide is 1:500. Although the most common mode of genetic inheritance is autosomal dominant, it does not follow sex predilection. Furthermore, penetrance is incomplete and age-related. This implies that not every individual carrying a pathogenic variant will exhibit the disease; meanwhile, there is a great variability in age of onset and disease severity amongst symptomatic individuals. 

Pathophysiology

The following mechanisms make up the pathophysiology of HCM: left ventricular outflow tract obstruction (LVOTO), mitral regurgitation, diastolic dysfunction, myocardial ischaemia and arrhythmia. 

Left ventricular outflow tract obstruction 

Left ventricular outflow tract obstruction (LVOTO), either present at rest or provoked during exertion, is demonstrated in approximately two-thirds of individuals with HCM. It is sensitive to ventricular preload, afterload and contractility; and can vary with volume status, level of activity, heart rate, blood pressure and medications. A peak LVOT gradient of greater than 30 mmHg is associated with an increased risk of death and progression to congestive heart failure. 

The pattern of hypertrophy in the left ventricle influences the likelihood of obstruction, the commonest being asymmetric left ventricular hypertrophy, where the basal interventricular septum is typically affected. Increase in septal wall thickness reduces the LVOT diameter and results in abnormal movement of the mitral valve leaflets. Systolic anterior motion (SAM) of the anterior mitral valve leaflets is frequently seen in HCM, the mechanism of which can be explained by the Venturi effect of the rapid flow within the narrowed LVOT, leading to the displacement of the distal anterior mitral valve leaflet towards the septum, resulting in subaortic obstruction. Premature aortic valve closure is also implicated in LVOTO due to abnormal valve apparatus with leaflet slack.

Mitral regurgitation

Mitral regurgitation (MR) occurs secondarily due to SAM or primarily from structural abnormalities of the mitral valve, which can enhance symptom burden. MR caused by SAM is a consequence of compromised leaflet coaptation, and the resulting jet is mid-to-late systolic in timing and posterior or lateral in orientation. Common structural abnormalities of the mitral valve can include excessive leaflet length, anomalous papillary muscle insertion, and anteriorly displaced papillary muscles.

Diastolic dysfunction and autonomic dysfunction

This occurs due to delayed inactivation from abnormal intracellular calcium reuptake, reduced LV compliance due to hypertrophy and fibrosis, and altered ventricular load. LV hypertrophy and stiffness impair compliance, which leads to restricted diastolic filling and decreased stroke volume. Exercise capacity is limited as a result. 

Patients with HCM may also experience autonomic dysfunction, with blunted heart rate recovery and inappropriate vasodilatation. Approximately 25% of patients have an abnormal blood pressure (BP) response to exercise, i.e. systolic BP fails to increase by ≥20 mmHg or demonstrates a paradoxical reduction of >20 mmHg from the peak value. 

Myocardial ischaemia

Several factors contribute to the development of myocardial ischaemia in patients with HCM. Myocardial hypertrophy, microvascular dysfunction with impaired coronary flow reserve, and medial hypertrophy and reduced density of the intramural arterioles are frequently observed in patients with HCM. These are potentiated by LVOTO and hyperdynamic systolic function. LV aneurysm is a negative consequence of apical myocardial ischaemia, which leads to an increased risk of heart failure and ventricular arrhythmias.  

Arrhythmia

Ventricular arrhythmias can be exacerbated by myocardial ischaemia resulting from compromised coronary flow reserve and LVOTO. Non-sustained ventricular tachycardia (NSVT) in particular occurs in approximately 23% of patients. Patients with HCM are also susceptible to developing atrial fibrillation (AF) owing to diastolic dysfunction and LV flow obstruction. Raised filling pressures, MR and LVOTO are features of HCM which result in adverse LA remodelling and dilatation, thus increasing the likelihood of developing AF. Atrial fibrosis caused by microvascular dysfunction and atrial ischaemia is also a substrate for AF.  AF not only increases the risk of thromboembolism, but it also has deleterious effects on cardiac function and overall mortality. 

Diagnosis

History and physical examination 

• Patients may describe chest pain, dyspnoea, palpitations, and/or syncope, in relation to exercise or dehydration.
•  A three-generation family history is important to identify family members with HCM or who have experienced a sudden, unexpected death. 
• Physical examination may reveal a jerky carotid pulse, and a harsh ejection systolic murmur is heard loudest at the left sternal edge in patients with associated LVOTO. The intensity of the murmur increases with manoeuvres that reduce preload, such as the Valsalva manoeuvre and standing from the squatting position. By contrast, those without LVOTO may have a normal physical examination.
•  Clinical signs: 
  • systolic ejection murmur may be noted with a crescendo-decrescendo pattern at the apex, during the Valsalva manoeuvre or when standing from a squatting position
  • left sternal border pansystolic murmur of mitral regurgitation at the apex
  • S4 gallop may be noted or a jugular venous pulse with a prominent ‘a’ wave

Investigations

Genetic Testing

• Genetic testing: where wall thickness of ≥15mm in one or more left ventricular myocardial segments is present, unexplained by loading conditions, in a patient whose age of onset is less than 60. Otherwise, unexplained increased LV wall thickness of ≥13mm in one or more LV myocardial segments in those patients with a first-degree relative with unequivocal disease (ideally with LV hypertrophy of ≥15 mm).

• Genetic testing may not be appropriate for adults with wall thickness ≥15 mm not solely explained by loading conditions, especially if clinical and imaging features (e.g., asymmetric hypertrophy, specific wall thickness ratios) provide a clear diagnosis. It also may not be appropriate in cases with characteristic apical hypertrophy that does not meet the full criteria for apical HCM (apical hypertrophic cardiomyopathy diagnostic wall thickness cut-off of ≥15mm, with spade‐like configuration and apical obliteration).

Management

General Management 

• Avoid dehydration, excessive alcohol consumption and exposure to drastic weather conditions (humidity, heat). 
• Weight loss and regular low- to moderate-intensity exercise are advisable in all individuals with cardiomyopathy. 
• High-intensity exercise and competitive sports are not recommended in high-risk individuals and in individuals with LVOTO and exercise-induced ventricular arrhythmia. 
• Cardiopulmonary exercise testing should be performed every 2-3 years in stable patients, or sooner in those with progressive symptoms.

Medical Management 

• Beta-blockers or non-dihydropyridine calcium channel blockers are first-line therapies to improve diastolic filling and reduce outflow tract gradient. 
• Disopyramide, a class Ia antiarrhythmic agent, can be added in HCM patients with refractory LVOTO symptoms. 
• Mavacamten, a novel cardiac myosin ATPase inhibitor, has also demonstrated an improvement in LVOT gradient and exercise performance in patients with LVOTO in a recent phase III, double-blind, placebo-controlled trial. 
• HCM patients with LV systolic dysfunction should be started on guideline-directed medical therapy for HF. 
  • It is recommended that diuretics are started cautiously in patients with LVOTO to avoid exacerbating symptoms. 
• Amiodarone can be used to suppress atrial and ventricular arrhythmias in HCM patients refractory to beta-blockers. 
• All HCM patients with atrial fibrillation must be started on oral anticoagulants irrespective of CHA2DS2-VA to reduce thromboembolic risk.

Surgical Management 

• Device therapy
  • Implantable cardiac defibrillator (ICD) is recommended in HCM patients who have survived a cardiac arrest due to a ventricular arrhythmia, or who have sustained VT resulting in haemodynamic compromise. 
  • The HCM Risk-SCD calculator should be utilised as a tool to risk-stratify HCM patients over the age of 16 years for sudden cardiac death (SCD) at 5 years. It encompasses family history of SCD, NSVT, age, history of unexplained syncope, LVOT gradient, LV wall thickness and LA diameter.  
  • Primary prevention ICD is indicated in patients with a risk score ≥6% with life expectancy over one year and should be considered on an individual basis if 4-6%. 
  • Cardiac resynchronisation therapy (CRT) can be assessed in individuals with persistent LV dysfunction with left bundle branch block and QRS interval ≥130ms.
• Surgery
  • Surgical myomectomy ought to be considered in patients with obstructive symptoms refractory to medical therapy and is performed in combination with mitral valve repair. 
  • Alcohol septal ablation is an alternative to surgical myomectomy to reduce LVOT gradient. 
  • Cardiac transplantation is only considered in eligible patients with NYHA class III-IV symptoms or ventricular arrhythmias refractory to medical and device therapy.

Complications

• Arrhythmias and SCD
  • HCM is associated with an increased risk of ventricular arrhythmias, which can lead to syncope, cardiac arrest, or sudden cardiac death, particularly in young individuals, athletes, or those with a family history of SCD. 
  • Following septal myectomy, likely due to atrial remodelling and changes in haemodynamics following the reduction of LVOT obstruction, atrial fibrillation can be a common complication.
• Heart Failure
  • Severe left ventricular hypertrophy, diastolic dysfunction, and outflow tract obstruction can lead to heart failure symptoms.
• Mitral Valve Abnormalities
  • Mitral valve abnormalities, including mitral regurgitation and systolic anterior motion of the mitral valve, can contribute to heart failure symptoms and increase the risk of arrhythmias.
• Endocarditis
  • HCM is associated with structural abnormalities such as hypertrophied myocardium and altered blood flow dynamics, particularly in the left ventricular outflow tract. These structural changes create areas of turbulence and endothelial injury, which can facilitate bacterial colonisation and increase the risk of endocarditis. 
  • Endocarditis in HCM can lead to severe complications such as worsening heart failure, arrhythmias, systemic embolisation (e.g., stroke), and even death.