Obesity-related Cardiomyopathy

Obesity related cardiomyopathy is structural and functional myocardial disease attributable to excess adiposity after other causes have been excluded. It features eccentric or concentric left ventricular hypertrophy, diastolic dysfunction, left atrial enlargement and heart failure with preserved ejection fraction, with systolic dysfunction developing late.

Obesity (body mass index of 30 kg/m2 or more) is present in about 40 to 50% of patients with heart failure with preserved ejection fraction, and the risk of heart failure rises by about 5% for each 1 kg/m2 increase. Disease is most common with body mass index over 35 to 40 kg/m2 and long duration.

Associations include hypertension, type 2 diabetes, obstructive sleep apnoea, obesity hypoventilation, atrial fibrillation, chronic kidney disease, fatty liver disease and coronary disease.

Pathophysiology.

Raised circulating volume and cardiac output increase preload and cause eccentric hypertrophy. Hypertension, neurohormonal activation and aldosterone excess add concentric remodelling.

Epicardial and pericardial fat restrains the ventricles and promotes inflammation and fibrosis. Lipotoxicity, insulin resistance and mitochondrial dysfunction impair myocardial energetics.

Obesity reduces chest wall compliance and increases pulmonary hypertension through sleep disordered breathing and hypoxia. Together these produce high filling pressures with exertion and later right ventricular failure.

Exertional dyspnoea, fatigue, peripheral oedema, orthopnoea and exercise intolerance, often attributed to deconditioning. Signs are difficult to elicit: the jugular venous pressure and heart sounds are hard to assess, and an atrial fibrillation rhythm is common. Look for sleep apnoea, daytime somnolence and hypoventilation.

Diagnosis is by exclusion with positive supporting evidence of raised filling pressures.

• NT-proBNP is lower in obesity, so lower thresholds apply (about 40% lower); a normal value does not exclude heart failure.
• Echocardiography: LV hypertrophy, left atrial volume index over 34 mL/m2, E/e' over 14 (average), tricuspid regurgitation velocity over 2.8 m/s, and right ventricular dysfunction.
• Cardiac MRI where echocardiographic windows are poor, or to exclude infiltrative disease.
• Exercise or invasive haemodynamics where uncertain: pulmonary capillary wedge pressure of 15 mmHg or more at rest or 25 mmHg or more on exercise.
• Exclude coronary disease, valve disease, infiltrative disease and hypothyroidism. Overnight oximetry or sleep study, and spirometry or blood gas for hypoventilation.
• Glucose or HbA1c, lipids, liver tests, creatinine and eGFR, urine albumin to creatinine ratio.

Differential diagnosis.

• Hypertensive heart disease and ischaemic cardiomyopathy.
• Cardiac amyloidosis and hypertrophic cardiomyopathy.
• Obesity hypoventilation syndrome with cor pulmonale, and pulmonary arterial hypertension.
• Thyroid disease and sleep apnoea without cardiomyopathy.

Weight loss is the central treatment. A weight loss of 10 to 15% improves symptoms, filling pressures and remodelling.

• Semaglutide: 0.25 mg subcutaneously once weekly for 4 weeks, then 0.5 mg for 4 weeks, 1.0 mg for 4 weeks, 1.7 mg for 4 weeks, then 2.4 mg weekly (maximum 2.4 mg weekly) long term; improves symptoms, function and weight in heart failure with preserved ejection fraction and obesity. Monitor weight, heart rate, glucose, renal function with vomiting or diarrhoea, and gallbladder symptoms. Contraindicated with personal or family history of medullary thyroid carcinoma or MEN2; stop if pancreatitis; avoid in pregnancy (stop 2 months before conception); delayed gastric emptying is relevant before sedation or anaesthesia; reduce insulin or sulphonylurea doses to prevent hypoglycaemia; no renal adjustment.
• Tirzepatide: 2.5 mg subcutaneously once weekly for 4 weeks, then increase by 2.5 mg every 4 weeks as tolerated to 5, 7.5, 10, 12.5 and 15 mg weekly (maximum 15 mg weekly), long term; same cautions as semaglutide; oral contraceptive absorption is reduced for 4 weeks after starting and after each increase.
• Bariatric surgery for body mass index of 40 kg/m2 or more, or 35 kg/m2 or more with complications, particularly with refractory heart failure; it reduces heart failure and atrial fibrillation risk. Lifelong micronutrient supplementation including thiamine.
• Dietary energy restriction with a structured exercise programme (150 minutes of moderate activity weekly, with resistance training).

Heart failure therapy.

• SGLT2 inhibitor: dapagliflozin 10 mg orally once daily (eGFR 25 or over) or empagliflozin 10 mg once daily (eGFR 20 or over); long term; monitor eGFR at 2 to 4 weeks, volume status and genital infection; reduce diuretic if volume depleted; stop 3 days before major surgery or when fasting or acutely unwell.
• Loop diuretic: furosemide 20 to 80 mg orally daily (higher doses are often needed because of large volume load), or torsemide 10 to 40 mg daily; titrate to weight; electrolytes and creatinine at 1 to 2 weeks.
• Spironolactone 25 to 50 mg orally once daily (potassium under 5.0 mmol/L, eGFR over 30; check potassium and creatinine at 1 week and 4 weeks). Obesity related hyperaldosteronism makes this particularly useful.
• Control blood pressure (target under 130/80 mmHg) with ACE inhibitor or ARB (ramipril 2.5 to 10 mg daily; losartan 50 to 100 mg daily); if ejection fraction falls under 40%, start therapy for heart failure with reduced ejection fraction: sacubitril/valsartan 24/26 mg orally twice daily titrated to 97/103 mg twice daily (maximum), bisoprolol 1.25 mg daily titrated to 10 mg, spironolactone 25 to 50 mg daily (potassium under 5.0 mmol/L, eGFR over 30) and dapagliflozin 10 mg daily (eGFR 25 or over), with potassium and creatinine checked at 1 to 2 weeks.
• Atrial fibrillation: anticoagulate by 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); apixaban and rivaroxaban are acceptable in body mass index over 40 kg/m2 but data are limited. Weight loss reduces atrial fibrillation burden.
• Treat sleep apnoea and hypoventilation: continuous positive airway pressure, or non-invasive ventilation for hypoventilation.

Monitoring. Weight, blood pressure and symptoms at each visit; renal function and electrolytes every 3 to 6 months; echocardiography every 1 to 2 years; HbA1c yearly.

Referral and escalation. Refer to a weight management service, and to a heart failure service for symptoms or ejection fraction under 50%. Refer for bariatric assessment where criteria are met.

Special groups.

• Pregnancy: stop semaglutide and tirzepatide; stop SGLT2 inhibitors, spironolactone, ARNI and ACE inhibitors before conception.
• Older adults: guard against loss of lean mass during weight loss; maintain protein intake and resistance exercise.
• Kidney impairment: start dapagliflozin only at eGFR 25 mL/min/1.73 m2 or over and empagliflozin at eGFR 20 or over; incretin based drugs can be used with caution and with hydration advice.