7th March 2024

Hypertrophic Cardiomyopathy

Pathology

HCM is defined as myocardial hypertrophy in the absence of abnormal loading conditions (such as hypertension or valvular disease like aortic stenosis), which would otherwise precipitate a compensatory myocardial thickening. 

HCM is one of the most common of the cardiomyopathies, and left ventricular hypertrophy without abnormal loading conditions is seen in approximately 0.2% of the population – though not all of these will experience signs and symptoms of cardiac disease. 

The symptoms experienced in HCM are typically caused by cellular disarray, leading to disorganised left ventricular architecture and increased myocardial thickening. This can lead to left ventricular diastolic dysfunction due to impaired relaxation, abnormal intramural coronary arteries and dynamic obstruction of the left ventricular outflow tract (LVOT).

HCM is more commonly genetically inherited in an autosomal dominant manner, and almost all components of the sarcomere can be involved. Commonest include the beta myosin heavy chain, myosin binding protein C and troponins I and T. There are many other genetic conditions which can lead to an HCM including Fabry’s disease, Noonan’s syndrome and Friedreich’s Ataxia. Non-genetic causes include AL amyloid and obesity.

Signs and symptoms

The commonest presenting symptom in HCM is dyspnea, but it can also present with chest pain, palpitations and syncope.

Systolic function as measured by ejection fraction is typically preserved, though abnormalities of contractile function are often seen when assessing ventricular deformation parameters (LV global longitudinal strain and strain rate), while diastolic function is often impaired by the abnormalities of the hypertrophied musculature and failure of myocardial relaxation. Dyspnea thus occurs due to elevated intracardiac pressures as the myocardium fails to relax adequately to maintain low intrachamber pressures leading to raised pulmonary artery pressures.

Chest pain can occur due to the increased metabolic demands of the hypertrophied muscle. If the hypertrophy outstrips the vascular supply, then a supply/demand mismatch can lead to relative ischaemia despite normal epicardial coronary vessels.

Palpitations can occur due to arrhythmias generated in the hypertrophied muscle. Ventricular arrhythmias are not uncommon and are a cause for concern, with intervention with antiarrhythmics or device therapy commonly considered.

LVOT obstruction can occur due to hypertrophy of the septal myocardium. This interferes with the normal flow of blood through the LVOT and, ultimately, the aortic valve. If this is sufficiently diminished, then blood will not reach the aorta to perfuse the coronary arteries nor the carotid arteries to perfuse the brain. This can lead to chest pain in the former and syncope or presyncope in the latter. These are concerning symptoms in HCM and require urgent investigation, as unexplained syncope in the context of HCM is a significant risk marker for sudden cardiac death.

Classical examination findings include a forceful, non-displaced apical beat accompanied by a jerky (otherwise called bisferiens) pulse. The irregular pulse of atrial fibrillation is a common finding, seen in approximately 1/5 of patients.

On auscultation, if the outflow tract is obstructed one can hear a systolic murmur radiating to both mitral and aortic regions, with the volume increased on Valsalva and diminished on release. This occurs because in Valsalva there is less venous return due to the increased intrathoracic pressure. This leads to an underfilled left ventricle, allowing the septum to block off the outflow tract. Conversely, when Valsalva is released, increased blood flow helps to splint open the outflow tract, reducing the obstruction and thus reducing the murmur. An additional sound of an S4 can also be heard due to turbulent flow in a non-compliant ventricle.

In comparison, the opposite effect is seen in aortic stenosis, in which a reduction in flow due to Valsalva leads to a quieter murmur, while the increase in flow post Valsalva causes a louder murmur due to more turbulent flow through the stenotic valve.

Investigations

The ECG findings of HCM are normally relatively striking and most patients will have an abnormal ECG, though the findings on ECG do not correlate well with clinical outcome.

ECG can show:

• Voltage criteria for left ventricular hypertrophy (S wave in V1 + tallest R wave in V5-V6 >35mm)
• Left atrial enlargement (p mitrale (bifid p waves))
• Short PR intervals (accessory pathways are more common in patients with HCM)
• Atrial fibrillation and supraventricular tachycardias are common
• Giant T wave inversions seen in the precordial leads
• Narrow, “dagger-like” q waves in the inferior and lateral leads

Echocardiography is the most common confirmatory diagnostic test. This will typically show asymmetric septal hypertrophy with a ratio of septal wall to posterior wall thickness >1.4:1. The LV is typically non-dilated and systolic function is preserved as measured by left ventricular ejection fraction, though deformation parameters are often reduced. Systolic anterior motion of the anterior mitral leaflet can also be seen. A velocity gradient across the left ventricular outflow tract can be seen, and in the absence of this being found despite typical myocardial hypertrophy, echocardiography while performing Valsalva manoeuvre or an exercise test should be considered to assess for dynamic left ventricular outflow tract obstruction.

Cardiac MRI can provide similar information to echocardiography but with better tissue characterisation and may be better at identifying areas which are difficult to image on echo due to impaired echocardiographic windows. 

Treatment

The management of hypertrophic cardiomyopathy is very dependent upon the extent of the pathology and the consequent symptoms.

For patients with significant arrhythmias, these can be treated as normal, though in the context of atrial fibrillation, drugs such as flecainide are typically avoided.

For patients with left ventricular outflow tract (LVOT) gradients, beta blockers, or rate limiting calcium channel blockers are effective at reducing this by acting as negative inotropes which reduces the risk of outflow tract obstruction.

Mavacamten is a myosin-actin cross-bridge inhibitor, a novel agent which, at the time of writing, is not yet approved for use in HCM but appears to have a positive impact on LVOT gradient, NYHA functional class, dyspnoea scores and NT pro-BNP levels in symptomatic HCM patients.

Patients with symptoms due to outflow tract obstruction refractory to drug therapy can be considered for a surgical myomectomy or alcohol septal ablation to reduce the outflow tract gradient.

Online calculators exist to predict 5-year risk of sudden cardiac death. For patients with a 5-year risk of SCD <4%, an ICD is generally not indicated, in patients with a risk of 4 to less than 6%, an ICD may be considered and in patients with a 5-year risk ≥6%, an ICD should be considered.

First degree relatives of patients with HCM should be screened with echocardiography and ECG to look for the typical abnormalities as described above. The children of affected children should be screened routinely until the age of 20. If HCM is not discovered by this stage, then it is unlikely to occur in later life.

References

• https://patient.info/doctor/hypertrophic-cardiomyopathy-pro
• https://www.ahajournals.org/doi/10.1161/CIR.0000000000000937
• https://www.thelancet.com/article/S0140-6736(20)31792-X/fulltext
• 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).
• A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD).