Apical Hypertrophic Cardiomyopathy

Apical hypertrophic cardiomyopathy is a variant of hypertrophic cardiomyopathy with hypertrophy predominantly in the LV apex (apical wall thickness 15 mm or more, or apical-to-basal ratio of 1.5 or more) and a spade shaped LV cavity.

It accounts for about 3 to 5% of hypertrophic cardiomyopathy in Western countries and up to 15 to 25% in East Asian populations. Sarcomere gene variants are found in a minority, mostly ACTC1, MYH7 and MYBPC3.

Sudden death risk is lower than in septal disease, but the mid-cavity obstruction, apical aneurysm, thrombus and atrial fibrillation complications are important.

Pathophysiology.

Apical hypertrophy reduces apical cavity size and distensibility, causing diastolic dysfunction and raised end diastolic pressure. Mid-cavity obliteration can generate a systolic gradient.

Microvascular dysfunction and fibrosis at the apex predispose to subendocardial ischaemia. Apical aneurysm forms from high apical wall stress with mid-cavity obstruction and scar, providing a substrate for ventricular tachycardia and thrombus.

Many patients are asymptomatic. Symptoms: chest pain (often atypical or ischaemic), dyspnoea, palpitations, syncope and embolic events. There may be a fourth heart sound with a displaced, sustained apical impulse. A murmur is often absent.

• ECG: giant negative T waves (10 mm or more) in V2 to V5 and high QRS voltage.
• Echocardiography with contrast to show apical hypertrophy, cavity obliteration, aneurysm or thrombus (apical views can be missed on routine imaging).
• Cardiac MRI: apical wall thickness, LGE, aneurysm, thrombus; the preferred test.
• Coronary angiography or CT coronary angiography to exclude coronary disease in patients with chest pain and T-wave inversion.
• Ambulatory ECG for non-sustained ventricular tachycardia and atrial fibrillation; genetic testing and cascade screening.

Differential diagnosis.

• Endomyocardial fibrosis (common in tropical Africa and relevant regionally) and eosinophilic endocardial disease.
• Ischaemic heart disease with apical ischaemia or Wellens pattern, and post-Takotsubo changes.
• Hypertensive heart disease, athlete's heart, LV non-compaction and apical thrombus.
• Cardiac amyloidosis and Fabry disease.

Symptoms.

• Metoprolol 25 to 50 mg orally twice daily (tartrate) or 50 to 200 mg once daily (succinate), long term; target resting heart rate 50 to 60 beats/min; maximum 400 mg daily (usual ceiling 200 mg); monitor heart rate and blood pressure; reduce in severe hepatic impairment.
• Verapamil modified release 120 to 240 mg orally once daily, titrated to a maximum of 480 mg daily, for angina or diastolic symptoms (avoid with systolic dysfunction or marked bradycardia); monitor PR interval, heart rate, blood pressure.
• Diuretics only for congestion (low dose; furosemide 20 to 40 mg orally daily, maximum individualised) because cavity obliteration makes the ventricle preload dependent.
• Mid-cavity obstruction: beta blocker or verapamil; refractory disease may need surgical myectomy, with transapical approach for apical disease. Mavacamten is licensed for LVOT obstruction only, and evidence in mid-cavity or apical disease is limited.

Apical aneurysm and thrombus.

• Anticoagulation for LV thrombus: warfarin to INR 2.0 to 3.0, or a direct oral anticoagulant (apixaban 5 mg twice daily, 2.5 mg if two of age 80 or over, weight 60 kg or under, creatinine 133 micromol/L or over; rivaroxaban 20 mg once daily with food, 15 mg if creatinine clearance 15 to 49 mL/min); minimum 3 months, repeat imaging, then continue if thrombus persists or aneurysm remains with high risk.
• Anticoagulation is considered for a large apical aneurysm without thrombus where bleeding risk is acceptable.
• ICD for ventricular tachycardia or fibrillation from the aneurysm margin, and often considered for aneurysm with extensive scar.

Atrial fibrillation. Anticoagulate regardless of CHA2DS2-VASc score (apixaban 5 mg twice daily, 2.5 mg twice daily if two of age 80 or over, weight 60 kg or under, creatinine 133 micromol/L or over; or rivaroxaban 20 mg once daily with food, 15 mg if creatinine clearance 15 to 49 mL/min), early rhythm control, and amiodarone 200 mg daily after loading (200 mg three times daily for 1 week, then twice daily for 1 week; thyroid and liver tests every 6 months).

Monitoring. Clinical review, ECG and echocardiography every 1 to 2 years, with contrast or MRI when the apex is poorly seen. MRI every 2 to 3 years with aneurysm. Ambulatory ECG yearly.

Referral and escalation. Refer all patients to a cardiomyopathy service. Urgent referral for aneurysm, thrombus, embolic stroke or limb ischaemia, ventricular arrhythmia, syncope, or ejection fraction under 50%.

Special groups.

• Pregnancy: continue metoprolol (avoid atenolol); anticoagulation with low molecular weight heparin if needed (DOACs and warfarin avoided in pregnancy).
• Relatives: first degree relative screening with ECG and echocardiography every 1 to 3 years.
• Region specific: endomyocardial fibrosis is a frequent mimic in tropical Africa and should be excluded on MRI.
• Kidney impairment: adjust DOAC doses by creatinine clearance.