Left Ventricular Noncompaction

Cardiomyopathy defined by a thick, two layered left ventricular myocardium with prominent trabeculations and deep intertrabecular recesses communicating with the ventricular cavity, and a thin compacted layer. It may be isolated or coexist with congenital heart disease, neuromuscular disease or other cardiomyopathy.

• Prevalence is uncertain: about 0.05 to 0.3% of adults referred for echocardiography. The diagnosis is debated because hypertrabeculation also occurs in healthy people, athletes, pregnancy, sickle cell disease and people of African ancestry, and many people with these features never develop disease. Imaging criteria alone are not sufficient without clinical context.
• Genetics: sarcomere genes (MYH7, MYBPC3, TNNT2), usually autosomal dominant; X-linked forms (TAZ gene, Barth syndrome with neutropenia, skeletal myopathy and 3-methylglutaconic aciduria); association with neuromuscular disease and chromosomal syndromes.
• Phenotypes: asymptomatic, dilated with heart failure, hypertrophic, arrhythmic, thromboembolic, or mixed. Outcome depends on ventricular function and symptoms; a reduced ejection fraction, heart failure, arrhythmia and late gadolinium enhancement predict events.

• Asymptomatic in many; dyspnoea, fatigue, palpitations, syncope, stroke or other embolic events (about 5 to 25% in symptomatic cohorts), and sudden cardiac death.
• Signs: signs of heart failure when present; otherwise normal. Look for neuromuscular weakness, dysmorphic features or family history.
• Differential diagnosis: dilated cardiomyopathy with prominent trabeculation, hypertrophic cardiomyopathy (apical form), apical thrombus, endomyocardial fibrosis, hypereosinophilic syndrome, Fabry disease, left ventricular false tendons, normal variant in athletes and pregnancy.
• Complications: heart failure, atrial and ventricular arrhythmias, conduction disease, left ventricular thrombus with stroke or systemic embolism, and sudden cardiac death.

• ECG: left ventricular hypertrophy, repolarisation changes, bundle branch block, pre-excitation, prolonged QT. Holter monitoring for arrhythmia.
• Echocardiography: multiple (3 or more) prominent trabeculations apical to the papillary muscles, deep recesses with colour Doppler flow, and a ratio of non-compacted to compacted layer greater than 2:1 at end systole.
• Cardiac MRI: non-compacted to compacted ratio greater than 2.3 in end diastole, trabeculated left ventricular mass greater than 20% of total mass, and late gadolinium enhancement (fibrosis, which carries a worse prognosis).
• Genetic testing and screening of first degree relatives; creatine kinase, lactate, urine organic acids, neutrophil count (Barth syndrome) and neuromuscular examination when indicated.
• Exclude other causes of hypertrabeculation. Isolated imaging features without symptoms, family history, reduced function or arrhythmia do not justify treatment.

• Asymptomatic with normal ejection fraction, normal ECG and no family history: no drug treatment, no restriction beyond avoiding extreme endurance training, and surveillance.
• Heart failure with reduced ejection fraction:
  • Ramipril 1.25 to 2.5 mg daily titrated to 10 mg, or sacubitril/valsartan 24/26 mg twice daily titrated to 97/103 mg twice daily (not together with an ACE inhibitor).
  • Bisoprolol 1.25 mg daily titrated to 10 mg daily.
  • Spironolactone 12.5 to 25 mg daily, up to 50 mg, if potassium is less than 5.0 mmol/L and eGFR is greater than 30.
  • Dapagliflozin 10 mg daily or empagliflozin 10 mg daily.
  • Furosemide 20 to 80 mg daily for congestion.
• Anticoagulation:
  • Warfarin to INR 2.0 to 3.0 (or apixaban 5 mg twice daily, 2.5 mg twice daily if two of age 80 or more, weight 60 kg or less, creatinine 133 micromol/L or more) for atrial fibrillation, prior embolic event or intracardiac thrombus.
  • For sinus rhythm with ejection fraction less than 40%, consider anticoagulation or aspirin 75 mg daily; evidence is limited.
• Arrhythmia: beta blocker first; amiodarone 400 mg daily for 2 to 4 weeks then 200 mg daily for ventricular or atrial arrhythmia; catheter ablation for symptomatic arrhythmia or pre-excitation.
• Devices: implantable defibrillator for cardiac arrest or sustained ventricular tachycardia, syncope with significant dysfunction, or ejection fraction 35% or less after 3 months of optimal therapy; cardiac resynchronisation for left bundle branch block with QRS 130 ms or more and ejection fraction 35% or less.
• Heart transplantation for end stage failure.
• Exercise: avoid competitive sport if ejection fraction is reduced, arrhythmia is present or there are symptoms; light to moderate activity is acceptable otherwise.
• Family screening: ECG and echocardiography (or cardiac MRI) of first degree relatives every 1 to 3 years, yearly in children, with genetic testing for the family variant.
• Special groups:
  • Children: poorer outcome in infancy; give heart failure therapy at weight based doses; check neutrophils and metabolic markers for Barth syndrome.
  • Pregnancy: assess before conception; avoid pregnancy if ejection fraction is less than 30%; stop ACE inhibitors, sacubitril/valsartan, spironolactone and SGLT2 inhibitors; continue metoprolol; use enoxaparin 1 mg/kg twice daily if anticoagulation is needed.
  • Elderly: start drugs at low doses; monitor renal function and potassium.
• Red flags: syncope, stroke or transient ischaemic attack, sustained ventricular tachycardia, worsening heart failure, falling ejection fraction.
• Follow up: every 6 to 12 months with ECG, Holter and echocardiography; cardiac MRI at diagnosis and for change in status.