Alcoholic Cardiomyopathy

Alcoholic cardiomyopathy is a dilated cardiomyopathy with reduced ejection fraction caused by prolonged heavy alcohol use after other causes have been excluded. It usually follows about 80 g of ethanol daily (10 units or more, each unit being 8 g of ethanol) for at least 5 years, commonly 10 to 15 years. Women develop it at lower cumulative intake.

It accounts for roughly 20 to 35% of non-ischaemic dilated cardiomyopathy. It is most frequent in men aged 30 to 55 years. Individual susceptibility differs, and truncating variants in the titin gene (TTN) and other cardiomyopathy genes increase risk.

Atrial fibrillation (including binge related "holiday heart"), ventricular arrhythmia, thromboembolism and sudden death complicate it. In sub-Saharan Africa, home brewed and illicit spirits have unpredictable ethanol content, and methanol adulteration can cause acute poisoning, so intake is hard to quantify.

Pathophysiology. Ethanol and acetaldehyde injure myocytes directly through oxidative stress, mitochondrial dysfunction, impaired calcium handling and contractile protein synthesis. Thiamine and other nutritional deficiencies, cobalt in some adulterated beverages, hypertension, and genetic predisposition add to the damage.

Early changes are diastolic dysfunction, then ventricular dilatation and falling ejection fraction. The injury is reversible in a large share of patients who stop drinking, with recovery over months.

• Exertional dyspnoea, orthopnoea, fatigue, oedema, palpitations, syncope. Some patients are asymptomatic when found.
• Atrial fibrillation or flutter, ventricular ectopy and tachycardia. Embolic stroke.
• Signs of heart failure: displaced apex, third heart sound, functional mitral regurgitation, raised venous pressure.
• Signs of heavy drinking: spider naevi, palmar erythema, hepatomegaly, parotid enlargement, tremor, peripheral neuropathy and cerebellar signs.
• Cardiac beriberi from thiamine deficiency: high output failure with warm peripheries, wide pulse pressure and lactic acidosis.

Red flags.

• Acute decompensated heart failure or cardiogenic shock
• Syncope or ventricular arrhythmia
• Rapid atrial fibrillation
• Confusion, ataxia or ophthalmoplegia (Wernicke encephalopathy)
• Features of alcohol withdrawal (tremor, sweating, agitation, hallucinations, seizures)
• Lactic acidosis in a heavy drinker
• Ejection fraction under 35%

• Alcohol history. Quantify intake in grams or units and duration. Use a validated questionnaire. Add collateral history.
• Biomarkers of use. Gamma glutamyl transferase, mean corpuscular volume, carbohydrate deficient transferrin, AST to ALT ratio over 2, and urine or hair ethyl glucuronide.
• Echocardiography. Dilated left ventricle, ejection fraction usually under 45%, global hypokinesia, functional mitral regurgitation, thrombus.
• ECG and ambulatory ECG. Atrial fibrillation, ventricular ectopy, conduction disease.
• Natriuretic peptide, troponin, thyroid function, ferritin and transferrin saturation, HIV, hepatitis B and C serology, liver function, creatinine, electrolytes (potassium, magnesium, phosphate), blood thiamine.
• Coronary evaluation by CT or invasive angiography when risk factors or chest pain are present. Cardiac MRI for fibrosis and exclusion of myocarditis or infiltrative disease.
• Genetic testing in younger patients, those with a family history, or recovery that does not occur with abstinence.
• Diagnosis is by exclusion. Recovery of ejection fraction with abstinence supports it.

Differential diagnosis.

• Idiopathic and familial dilated cardiomyopathy (TTN, LMNA)
• Ischaemic cardiomyopathy
• Viral and autoimmune myocarditis
• Thiamine deficiency (cardiac beriberi) unrelated to alcohol
• Tachycardia induced cardiomyopathy
• Haemochromatosis and other infiltrative disease
• Cobalt, anthracycline and other toxic cardiomyopathy
• Hypertensive heart disease and thyroid disease
• HIV-associated cardiomyopathy
• Peripartum cardiomyopathy
• Cirrhotic cardiomyopathy

Abstinence is the main treatment. Complete abstinence (not reduced drinking) gives the best recovery. Many patients improve ejection fraction by 10 points or more within 3 to 6 months. Continued heavy drinking carries a poor prognosis. Offer structured support (brief intervention, counselling, mutual support groups).

• Alcohol withdrawal. Assess severity with a validated score. Use chlordiazepoxide 20 to 30 mg orally four times daily on day 1, reduced by about 20% each day over 5 to 7 days. Withhold a dose for sedation or respiratory rate under 12/min. Use 10 mg doses in older adults and liver impairment, or lorazepam 1 mg orally every 6 hours in severe liver impairment. Treat in hospital with a history of seizures, delirium tremens or heavy dependence.
• Thiamine 200 to 300 mg orally once daily in all heavy drinkers. When Wernicke encephalopathy or cardiac beriberi is possible, give 500 mg intravenously over 30 minutes three times daily for 2 to 3 days, then 250 mg intravenously or intramuscularly once daily for 3 to 5 days, before any glucose containing fluid. Replace magnesium (magnesium sulphate 2 g intravenously over 20 minutes, repeated as needed to a serum level of 1.0 mmol/L or more, reduced at creatinine clearance under 30 mL/min), potassium and phosphate. Give folic acid 5 mg orally once daily.
• Relapse prevention. Acamprosate 666 mg orally three times daily (age 18 to 65 years, weight over 60 kg; 666 mg in the morning and 333 mg at midday and at night under 60 kg), for up to 12 months. Reduce to 333 mg three times daily at creatinine clearance 30 to 50 mL/min and avoid under 30 mL/min. Or naltrexone 50 mg orally once daily (25 mg for the first 1 to 3 days), with liver enzymes at baseline and monthly for 3 months. Contraindicated with opioid use and in acute hepatitis or liver failure. Avoid disulfiram in heart disease.
• Heart failure with reduced ejection fraction. Full tolerated therapy:
  • Sacubitril/valsartan 49/51 mg orally twice daily, doubled at 2 to 4 weeks to the target 97/103 mg twice daily (maximum 194/206 mg daily). Start 24/26 mg twice daily if not on an ACE inhibitor or angiotensin receptor blocker, on low doses, with eGFR under 30 mL/min/1.73 m2, or with moderate liver impairment. Stop any ACE inhibitor 36 hours before. Contraindicated with previous angio oedema, severe liver impairment and pregnancy. Check potassium and creatinine 1 to 2 weeks after each change.
  • Bisoprolol 1.25 mg orally once daily, increased every 1 to 4 weeks to the target 10 mg once daily, maximum 10 mg daily in heart failure. Contraindicated in cardiogenic shock, second degree or third degree AV block without a pacemaker, sick sinus syndrome and severe asthma.
  • Spironolactone 25 mg orally once daily (12.5 mg at eGFR 30 to 49 mL/min/1.73 m2), up to 50 mg daily. Check potassium and creatinine at 1 week and 4 weeks, then every 3 months. Withhold at potassium over 5.5 mmol/L and avoid at eGFR under 30 mL/min/1.73 m2.
  • Dapagliflozin 10 mg orally once daily, long term. Start at eGFR 25 mL/min/1.73 m2 or more. Withhold during acute illness with poor oral intake. Contraindicated in type 1 diabetes.
  • Furosemide 40 mg orally once daily in the morning, increased to 80 to 120 mg daily as needed (higher doses in renal impairment under specialist care). Monitor sodium, potassium and creatinine.
• Atrial fibrillation. Rate control with bisoprolol 1.25 mg orally once daily, increased every 1 to 4 weeks to the target 10 mg once daily. Cardioversion after 3 weeks of anticoagulation or exclusion of atrial thrombus by transoesophageal echocardiography. Anticoagulation by stroke risk, continuing at least 4 weeks after cardioversion: apixaban 5 mg orally twice daily, reduced to 2.5 mg twice daily when at least two of age 80 years or over, weight 60 kg or under and serum creatinine 133 micromol/L or over are present. Also 2.5 mg twice daily at creatinine clearance 15 to 29 mL/min, and avoided under 15 mL/min. Maximum 10 mg daily. Long term. Avoid apixaban in Child-Pugh class C cirrhosis and use with caution in class B. Warfarin with INR 2.0 to 3.0 is the alternative.
• Device therapy. Delay a primary prevention defibrillator until after 3 to 6 months of abstinence and full therapy, and implant when ejection fraction remains 35% or less. Implant earlier for survivors of cardiac arrest or sustained ventricular tachycardia. Use a wearable defibrillator as a bridge. Resynchronisation for left bundle branch block with QRS of 150 ms or more after the same period.
• Advanced disease. Mechanical support or transplantation requires documented abstinence, usually 6 months or more, with addiction service involvement.

Special groups.

• Women: lower threshold for harm, so counsel earlier.
• Pregnancy: complete abstinence. Stop sacubitril/valsartan, spironolactone and dapagliflozin before conception.
• Liver disease: reduce chlordiazepoxide and avoid nephrotoxic combinations. Treat hepatic and cardiac disease together.

Monitoring. Echocardiography at 3 and 6 months of abstinence, then yearly. Natriuretic peptide with symptoms. Alcohol biomarkers and addiction service review at each visit. Liver enzymes, creatinine, potassium and magnesium after each titration. Ambulatory ECG yearly.

Referral and escalation. Refer to cardiology and an addiction service. Urgent for decompensated heart failure, ventricular arrhythmia, severe withdrawal, or suspected Wernicke encephalopathy.