Ischaemic Mitral Regurgitation

Ischaemic mitral regurgitation is regurgitation caused by coronary artery disease. It has a chronic form, from left ventricular remodelling after infarction, and an acute form, from papillary muscle rupture or ischaemic dysfunction, which is a surgical emergency.

Moderate or severe regurgitation occurs in about 10 to 20% of patients after myocardial infarction and doubles mortality. Papillary muscle rupture complicates about 0.05 to 0.3% of infarcts, usually 2 to 7 days after the event and usually after inferior infarction, since the posteromedial papillary muscle has a single blood supply.

The chronic form behaves like functional mitral regurgitation with ischaemia as the cause. Severity is graded as severe when the effective regurgitant orifice area is 40 mm2 or more (some use 30 mm2) and regurgitant volume 60 mL or more (some use 45 mL).

Pathophysiology.

In chronic disease, infarcted inferior or posterior wall displaces the posteromedial papillary muscle and tethers the posterior leaflet, giving asymmetric regurgitation with a posteriorly directed jet. Anterior or global remodelling tethers both leaflets symmetrically, with a central jet.

Annular dilatation, dyssynchrony and reduced closing force contribute. Reversible ischaemia can cause intermittent regurgitation and exercise induced pulmonary oedema.

In acute rupture, a complete or partial tear of a papillary muscle produces a flail leaflet and massive regurgitation into a normal sized left atrium. Pulmonary oedema and shock appear within hours, and the murmur may be soft because pressures equalise.

Chronic disease: exertional dyspnoea, orthopnoea, angina, fatigue and signs of heart failure; murmur is variable.

Acute rupture: abrupt pulmonary oedema, hypotension, tachycardia and shock days after a myocardial infarction, with a new systolic murmur (absent in up to half of patients).

• ECG: previous infarct pattern or ongoing ischaemia. Troponin if recent infarction.
• Echocardiography: wall motion abnormality, tethered leaflets (restricted posterior leaflet with a posteriorly directed jet), tenting height and area, annular size, regurgitant quantification. Rupture shows a flail leaflet with a mobile mass (the papillary head) prolapsing into the atrium; transoesophageal echocardiography is more sensitive and confirms it.
• Coronary angiography to define disease and plan revascularisation.
• Viability: cardiac MRI, dobutamine echocardiography or PET.
• Right heart catheterisation: large v waves in the wedge trace. A step up in oxygen saturation at right ventricular level points to ventricular septal rupture instead.

Differential diagnosis.

• Post-infarction ventricular septal rupture and free wall rupture.
• Functional regurgitation from non-ischaemic cardiomyopathy.
• Primary mitral valve disease, infective endocarditis and Takotsubo syndrome with obstruction.
• Acute pulmonary oedema without regurgitation.

Acute papillary muscle rupture (emergency).

• Admit to intensive care, with arterial line and continuous monitoring. Intra-aortic balloon counterpulsation to reduce afterload and increase forward flow.
• Afterload reduction while systolic blood pressure stays over 100 mmHg: glyceryl trinitrate 10 to 20 microgram/min intravenously, increased by 10 to 20 microgram/min every 5 to 10 minutes to a maximum of 200 microgram/min; or sodium nitroprusside 0.3 to 0.5 microgram/kg/min, increased every 5 minutes to a usual maximum of 5 microgram/kg/min (absolute maximum 10), for no longer than 24 to 48 hours, with lactate and thiocyanate monitoring and caution in renal or hepatic impairment.
• Furosemide 40 to 80 mg intravenously for oedema. Dobutamine 2.5 to 10 microgram/kg/min if output is low. Noradrenaline 0.05 to 0.5 microgram/kg/min if hypotensive.
• Ventilation with positive end expiratory pressure as needed. Extracorporeal membrane oxygenation as a bridge in refractory shock.
• Urgent surgery: mitral valve replacement (repair is seldom possible), with bypass grafting where needed. Do not delay surgery for stabilisation. Operative mortality is high. Transcatheter edge-to-edge repair is reported as a bridge or option in inoperable patients.

Chronic disease.

• Revascularise viable myocardium (bypass grafting for multivessel or left main disease, percutaneous intervention otherwise). Revascularisation alone improves moderate regurgitation in some patients, and does not address severe tethering.
• Heart failure therapy at maximal tolerated doses: sacubitril/valsartan 24/26 mg twice daily to 97/103 mg twice daily (or ramipril 2.5 to 10 mg daily); carvedilol 3.125 mg twice daily to 25 mg twice daily (50 mg twice daily over 85 kg) or bisoprolol 1.25 to 10 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 and 4 weeks); dapagliflozin 10 mg daily (eGFR 25 or over) or empagliflozin 10 mg daily (eGFR 20 or over); furosemide 40 to 160 mg daily for congestion. Check potassium and creatinine 1 to 2 weeks after changes.
• Secondary prevention after infarction: aspirin 75 to 100 mg daily; ticagrelor 90 mg twice daily (or prasugrel 10 mg daily, 5 mg when weight is under 60 kg or age is 75 or over; or clopidogrel 75 mg daily) for 12 months after an acute coronary syndrome, then single antiplatelet therapy; atorvastatin 40 to 80 mg daily (LDL cholesterol under 1.4 mmol/L); omeprazole 20 mg daily while on dual therapy.
• Cardiac resynchronisation for ejection fraction 35% or under with left bundle branch block and QRS 130 ms or more despite 3 months of optimal drug therapy; ICD for ejection fraction 35% or under despite 3 months of optimal therapy when expected survival exceeds 1 year.
• Severe regurgitation with coronary surgery: combined mitral surgery. Moderate regurgitation at the time of bypass: repair is reasonable for symptoms, but evidence for a survival benefit is lacking. Chordal sparing replacement is more durable than ring annuloplasty in advanced tethering or basal aneurysm.
• Transcatheter edge-to-edge repair for symptomatic severe regurgitation despite optimised therapy and revascularisation, when surgical risk is high.

Monitoring. Echocardiography 1 month after revascularisation, at 3 months, then every 6 to 12 months; NT-proBNP; renal function and electrolytes after each drug change; lipids at 4 to 12 weeks.

Referral and escalation. Papillary muscle rupture needs immediate transfer to a cardiac surgical centre. Refer chronic severe regurgitation to a heart team. Urgent referral for new heart failure or murmur after infarction.

Special groups.

• Older adults: favour transcatheter options; reduce nitroprusside rate and duration.
• Diabetes and chronic kidney disease: contrast minimisation, and avoid nitroprusside accumulation (thiocyanate) in renal impairment.
• Pregnancy: rare; care in a high risk cardio obstetric clinic; stop ACE inhibitors, sacubitril/valsartan, spironolactone and SGLT2 inhibitors.