Post Infarction Left Ventricular Remodelling

Post-infarction left ventricular remodelling is the progressive change in size, shape and function of the left ventricle after myocardial infarction. It is usually defined as an increase of 20% or more in left ventricular end diastolic volume, or 15% or more in end systolic volume, over 3 to 6 months. It leads to dilatation, systolic dysfunction, mitral regurgitation and heart failure.

A substantial minority of patients with a large infarct develop adverse remodelling, even after primary reperfusion. It is more frequent after anterior infarction and with late reperfusion.

Predictors are large infarct size (peak troponin, late gadolinium enhancement over 20% of the myocardium), microvascular obstruction, late presentation, transmural infarction, anterior location, diabetes, hypertension, persistently occluded infarct artery, and early ejection fraction under 40%.

Remodelling is the main substrate of late heart failure and ventricular arrhythmia after infarction.

Pathophysiology.

Early expansion (within days) thins and stretches the infarct zone. Late remodelling (weeks to months) involves dilatation of the non-infarcted myocardium from increased wall stress, hypertrophy, neurohormonal activation (sympathetic, renin-angiotensin-aldosterone), inflammation and fibrosis.

Changes in left ventricular shape from elliptical to spherical raise wall stress, dilate the mitral annulus and tether the leaflets, producing functional mitral regurgitation. A ventricular aneurysm forms where scar bulges outward.

Early reperfusion, ACE inhibition, beta blockade and mineralocorticoid antagonism reduce remodelling, which is why early initiation matters.

Often asymptomatic at first. Later, exertional dyspnoea, fatigue, orthopnoea, oedema, palpitations, syncope and ventricular arrhythmia. Examination: displaced apex beat, third heart sound, mitral regurgitation murmur, and signs of congestion. Persistent ST elevation suggests aneurysm.

• Echocardiography at 24 to 72 hours, 1 month, 3 months and 6 months: end diastolic and end systolic volumes (a rise of 20% and 15% respectively marks adverse remodelling), ejection fraction, sphericity, mitral regurgitation, thrombus, and aneurysm.
• Cardiac MRI: infarct size, transmurality, microvascular obstruction, intramyocardial haemorrhage, volumes and viability. The most accurate tool for prediction.
• NT-proBNP and troponin, ECG for persistent ST elevation and conduction, ambulatory ECG.
• Coronary angiography for residual ischaemia and graft or stent patency.

Differential diagnosis.

• Left ventricular aneurysm and pseudoaneurysm.
• Ischaemic mitral regurgitation and ventricular septal rupture.
• Dilated cardiomyopathy and myocarditis.
• Tachycardia induced cardiomyopathy and stress cardiomyopathy.

Early prevention (first 24 hours to 14 days).

• Reperfusion as early as possible, preferably primary intervention within 120 minutes of first medical contact.
• Ramipril 1.25 to 2.5 mg orally twice daily from the first 24 hours (titrate every 1 to 2 days to 5 mg twice daily); check blood pressure, potassium and creatinine at 1 to 2 weeks. Continue long term in anterior infarction, ejection fraction 40% or under, hypertension, diabetes or kidney disease. Use valsartan 20 to 40 mg twice daily, titrated to 160 mg twice daily, if an ACE inhibitor is not tolerated.
• Sacubitril/valsartan 24/26 mg twice daily titrated every 2 to 4 weeks to 97/103 mg twice daily (maximum), once stable, for ejection fraction 40% or under with heart failure; do not combine with an ACE inhibitor (36 hours washout); hold when systolic blood pressure is under 100 mmHg or potassium over 5.5 mmol/L.
• Metoprolol succinate 12.5 to 25 mg daily titrated to 200 mg daily, carvedilol 3.125 mg twice daily titrated to 25 mg twice daily, or bisoprolol 1.25 mg daily titrated to 10 mg daily, once the patient is stable and not in heart failure with congestion or hypotension; heart rate and blood pressure each visit.
• Eplerenone 25 mg daily from day 3 to 14 after infarction, increased to 50 mg after 4 weeks when ejection fraction is 40% or under with heart failure or diabetes, with potassium under 5.0 mmol/L and eGFR over 30 mL/min/1.73 m2; check potassium and creatinine at 1 week, 4 weeks and every 3 months.
• Dapagliflozin 10 mg daily (eGFR 25 or over) or empagliflozin 10 mg daily (eGFR 20 or over) for ejection fraction 40% or under or heart failure; monitor volume status and genital infection; stop 3 days before surgery.
• Aspirin 75 to 100 mg daily, ticagrelor 90 mg twice daily (or clopidogrel 75 mg daily) for 12 months, atorvastatin 40 to 80 mg daily for LDL cholesterol under 1.4 mmol/L, pantoprazole 40 mg daily while on dual antiplatelet therapy.
• Avoid NSAIDs and high dose corticosteroids early after infarction because they promote expansion and rupture.

Established remodelling and heart failure.

• Diuretics: furosemide 20 to 80 mg orally daily, titrated to dry weight, with electrolytes and creatinine within 1 week of changes.
• Hydralazine 25 mg three times daily titrated to 75 mg three times daily with isosorbide dinitrate 20 mg three times daily titrated to 40 mg three times daily when renin angiotensin drugs are not tolerated.
• Cardiac resynchronisation for ejection fraction 35% or under, left bundle branch block and QRS 130 ms or more (strongest at 150 ms or more).
• Implantable defibrillator for primary prevention when ejection fraction is 35% or under at least 40 days after infarction and at least 3 months after optimised therapy, with expected survival over 1 year. A wearable defibrillator may bridge the interval in selected high risk patients.
• Anticoagulation for left ventricular thrombus: warfarin to INR 2.0 to 3.0, or apixaban 5 mg twice daily (2.5 mg when two of age 80 or over, weight 60 kg or under, creatinine 133 micromol/L or over) for 3 to 6 months with repeat imaging.

Mechanical and surgical options.

• Revascularisation of viable myocardium with residual ischaemia.
• Mitral valve intervention (transcatheter edge-to-edge repair or surgery) for severe functional mitral regurgitation despite optimised therapy.
• Aneurysmectomy or ventricular reconstruction in selected patients with large aneurysm, refractory failure or recurrent ventricular tachycardia, though a survival benefit is not shown.
• Ventricular assist device or transplantation for refractory disease.

Monitoring. Echocardiography at 1, 3 and 6 months, then yearly; NT-proBNP; potassium and creatinine at 1 to 2 weeks after each renin angiotensin or mineralocorticoid antagonist change and then every 3 to 6 months; lipids at 4 to 12 weeks; ambulatory ECG at 1 month and with symptoms.

Referral and escalation. Refer to a heart failure service when ejection fraction stays at 40% or under at 3 months or volumes increase. Urgent referral for ventricular arrhythmia, syncope, shock, severe mitral regurgitation or new thrombus.

Special groups.

• Pregnancy: ACE inhibitors, sacubitril/valsartan, eplerenone and SGLT2 inhibitors are stopped before conception; use metoprolol, hydralazine and nitrates, with specialist care.
• Older adults: lower starting doses with slower titration and attention to orthostatic hypotension.
• Kidney impairment: start sacubitril/valsartan at 24/26 mg when eGFR is under 30, and avoid eplerenone at eGFR under 30.
• Region specific: late presentation is common where primary intervention is unavailable, so early heart failure therapy matters even more.