Hibernating Myocardium

Hibernating myocardium is chronically reduced left ventricular contraction caused by a persistent reduction in coronary blood flow, which recovers partly or wholly after blood flow is restored. It is an adaptive down regulation of function that preserves viability.

It is found in a large proportion of patients with ischaemic cardiomyopathy and severe coronary disease. A substantial minority of dysfunctional segments in such patients show viability, and revascularisation can improve ejection fraction in those with enough viable myocardium.

Typical patients are those with chronic coronary disease, previous infarction with multivessel disease and heart failure. The concept is important because the dysfunction is potentially reversible, but the benefit of revascularisation depends on the extent of viable tissue, the anatomy and the surgical risk.

Pathophysiology.

A chronic reduction of resting flow, or repeated stunning, leads to adaptive reduction of contractile function to match flow. Cells show loss of contractile proteins, glycogen accumulation, and a foetal gene programme.

Prolonged hibernation causes structural change and fibrosis, so recovery becomes less likely the longer the interval before revascularisation. Hibernating segments can generate arrhythmia and carry risk of sudden death.

Viability is judged by contractile reserve, membrane integrity and metabolic activity.

Heart failure with exertional dyspnoea, fatigue and angina (although many patients have no angina), a previous infarct, and signs of left ventricular dilatation. Ventricular arrhythmia and sudden death can occur.

• Echocardiography: regional dysfunction and reduced ejection fraction. Low dose dobutamine (5 to 10 microgram/kg/min) shows improved thickening, and a biphasic response (improvement at low dose, worsening at high dose) predicts recovery. End diastolic wall thickness of 6 mm or more suggests viability.
• Cardiac MRI: late gadolinium enhancement involving under 50% of wall thickness suggests viability, and over 50% (transmural) predicts no recovery. End diastolic wall thickness under 5.5 mm suggests scar.
• Nuclear imaging: SPECT with tracer uptake over 50 to 60% of peak, and PET with fluorodeoxyglucose uptake in segments with reduced flow (mismatch) are the most sensitive tests for viability.
• Coronary angiography or CT angiography for anatomy and graftable targets. Surgical risk score, anatomical complexity score and frailty assessment.
• NT-proBNP, creatinine, ambulatory ECG.

Differential diagnosis.

• Stunned myocardium and scar.
• Dilated cardiomyopathy of non-ischaemic cause.
• Myocarditis, sarcoidosis and tachycardia induced cardiomyopathy.
• Microvascular dysfunction without epicardial disease.

Medical therapy for ischaemic cardiomyopathy.

• Sacubitril/valsartan 24/26 mg orally twice daily, doubled every 2 to 4 weeks to 97/103 mg twice daily (start at 24/26 mg when eGFR is under 30 mL/min/1.73 m2; hold when systolic blood pressure is under 100 mmHg or potassium over 5.5 mmol/L); potassium and creatinine at 1 to 2 weeks. Alternative: ramipril 2.5 mg daily titrated to 10 mg daily.
• Carvedilol 3.125 mg twice daily, doubled every 2 weeks to 25 mg twice daily (50 mg twice daily when weight is over 85 kg), or bisoprolol 1.25 mg daily titrated to 10 mg daily (reduce when eGFR is under 20 mL/min/1.73 m2 or in severe hepatic impairment), or metoprolol succinate 12.5 to 25 mg daily titrated to 200 mg daily.
• Spironolactone 25 to 50 mg daily or eplerenone 25 to 50 mg daily (potassium under 5.0 mmol/L, eGFR over 30; check at 1 week and 4 weeks).
• Dapagliflozin 10 mg daily (eGFR 25 or over) or empagliflozin 10 mg daily (eGFR 20 or over).
• Furosemide 20 to 80 mg daily for congestion, titrated to dry weight.
• Aspirin 75 to 100 mg daily, atorvastatin 40 to 80 mg daily, and anti-anginal therapy as needed.

Revascularisation.

• Consider when there is viable myocardium in dysfunctional segments with graftable targets, symptoms or angina, and acceptable operative risk. The benefit is greatest with ejection fraction of 35% or under, multivessel disease, left main disease or proximal left anterior descending disease.
• Bypass surgery is preferred in multivessel disease with reduced ejection fraction and in diabetes. Percutaneous intervention is chosen for suitable single vessel or two vessel disease or high surgical risk.
• Viability alone does not decide treatment, and non-viable myocardium is not an indication to withhold revascularisation when symptoms or ischaemia are present. Functional recovery after revascularisation is usually seen within 3 to 6 months.
• After bypass: aspirin 75 to 100 mg daily lifelong; after stenting: dual antiplatelet therapy as the indication requires.

Device therapy.

• Implantable defibrillator for primary prevention when ejection fraction is 35% or under after at least 3 months of optimised therapy and at least 90 days after revascularisation, with life expectancy over 1 year.
• Cardiac resynchronisation for ejection fraction 35% or under with left bundle branch block and QRS 130 ms or more (150 ms or more strongest).

Advanced disease. Ventricular assist device or transplantation for refractory heart failure after revascularisation options are exhausted.

Monitoring. Echocardiography at 3 and 6 months after revascularisation and yearly after, NT-proBNP, creatinine and potassium at each drug change, lipids at 4 to 12 weeks, ambulatory ECG yearly.

Referral and escalation. Refer all patients with ischaemic cardiomyopathy and suspected viability to a heart team. Urgent referral for refractory angina, ventricular arrhythmia, decompensated heart failure and syncope.

Special groups.

• Older adults and frailty: lower titration rates and consider percutaneous options.
• Kidney impairment: contrast sparing; adjust ARNI, spironolactone and SGLT2 inhibitor starting thresholds.
• Pregnancy: rare; stop renin angiotensin drugs, mineralocorticoid antagonists and SGLT2 inhibitors before conception.