Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. HCM is caused by mutations in the cardiac sarcomere with a phenotypic expression affecting 1 in 500 people worldwide. It’s the leading cause of sudden death in children. This disease is defined by the finding of left ventricular hypertrophy in its classical form — asymmetrical LVH affecting the septum with hypertrophy greater than 15 mm.

Differential diagnosis

First, exclude other identifiable etiologies, such as uncontrolled hypertension, renal failure aortic valve stenosis, subvalvular aortic stenosis, or infiltrate diseases such as amyloidosis. The exclusion criteria of the differential for an observable ‘thick wall’ syndrome can be extended to include renal failure, glycogen storage diseases, Anderson-Fabry disease, and Freidreich’s ataxia. A positive mutation in ½ alleles is only present in 36% of patients presenting with HCM. This finding may indicate the involvement of environmental factors, or it could be that other unidentified mutations are at work in the remaining 64% of cases.

Assessment of HCM

Echocardiography remains the gold standard for diagnosis, and requires the presence of LVH in any concentric or asymmetric patterning, with or without septal involvement. Ventricle flow obstruction is present in only 60% of patients and isn’t diagnostic. Septal morphology is a reliable marker for the severity of HCM as well as genetic involvement. Diffuse septal involvement causing a reverse curve of the septum is seen in about 80% of established genetically-linked HCMs, and most often presents in younger patients. In this instance, genetic testing, while not readily available in Canada, may become one way to screen. First-degree relatives may need to be subsequently screened for sarcomeric mutations. Currently, among asymptomatic relatives, echocardiology is recommended every 18 months in youth and every 5 years in those aged over 20 to look for the development of hypertrophy.

In contrast, senile HCM, presenting in patients often in the 5th and 6th decade of life, is often characterized by an isolated basal septal bulge in the sigmoid region. This finding only presents in 8% of genetically-linked cases. In these cases, it’s hard to determine how much hypertension (vs genetic factors) is contributing to the hypertrophy. The risk of sudden death is believed to be much lower.

You can clearly see a spectrum of disease. Diffuse hypertrophy of the ventricular septum and the anterior lateral free wall occurs in 70% of cases followed by basal septum hypertrophy in 10-15% of cases, and concentric hypertrophy in approximately 5%. More recently, an apical variant was first described in Japan; it’s seen in less than 5% of cases. Lateral wall hypertrophy is seen in 1-2%. Clearly the echo study is needed to identify patients at risk and help guide and monitor therapies. Diastolic flow velocities in patients presenting with HCM are typically lower than in healthy controls and may reinforce your diagnosis and assessment.

Management of HCM

It’s important to keep in mind that close to 100% of patients will have some degree of symptomatic diastolic dysfunction or impaired relaxation. Moreover, about two-thirds of patients will have dynamic outflow tract obstruction. This abnormal systolic anterior motion of the mitral valve causes appreciable mitral regurgitation, increased myocardial oxygen demand, decreased profusion pressures, and subsequent ischemia, which will manifest in your patient as typical angina-like pain. These cardiac shortfalls also contribute to dypsnea and effort-related syncope or presyncope, known collectively as the classic triad of symptoms. The increased filling pressures and previously mentioned pathophysiologies may also result in atrial or ventricular arrhythmias, which are the most direct cause of HCM-related sudden death.

The goal of medical therapy in HCM isn’t relief of the obstruction but relief of reported symptoms. Verapamil, β-blockers, type IA anti-arrhythmic agents and amiodarone have all been used to manage patients with HCM, especially those deemed at high risk for sudden death. Risk factors for sudden death associated with HCM include the severity of septal involvement, inversely correlated age, arrhythmias, significant physical activity such as competitive athletics, or prior family history of sudden death. ICDs or intra-cardiac defibrillators have been used in increasing numbers in these patients and have been shown to significantly reduce the risk of HCM-related sudden death.

It’s vital when diagnosing and managing people with HCM to approach them on a case-by-case basis. Those with two or three risk factors have a sudden cardiac death rate of 4.7% per year. Stratifying risk, severity, and progression should be made by ECHO, with special attention paid to morphology of the septum and systolic anterior motion of the heart. But successful medical therapy in HCM should be marked by reduction of reported symptoms, not of observable dysfunction. Given all the variations of hypertrophic cardiomyopathic disease, not just patients but also family members should be referred to specialized centres.