5th July 2026

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.