Guideline sources The following summarized guidelines for the evaluation and management of mitral regurgitation are prepared by our editorial team based on guidelines from the European Society of Cardiology (ESC 2021), the American Heart Association (AHA/ACC 2021), the European Society of Cardiology (ESC/EACTS 2021), and the Society of Thoracic Surgeons (STS 2017). 1 2 3 4 5 5 6 7 Definition MR is a form of structural heart disease characterized by abnormal systolic flow of blood across the mitral valve, from the left ventricle to the left atrium. 5 Epidemiology Mechanisms of MR can broadly be classified into primary causes and secondary causes. Patients with primary MR are grouped according to the Carpentier classification (type 1 MR: normal leaflet size and motion; type 2 MR: excessive leaflet motion; type 3a MR: leaflet restriction in diastole; type 3b: leaflet restriction in systole). 6 h h i l https://web.pathway.md/diseases/recBu7iXQ5SAfC9UD 1/8 6/30/23, 1:04 AM Mitral regurgitation Pathway Pathophysiology The prevalence of MR in the United States is estimated at 1700 patients per 100,000 population. 5 Prognosis and risk of recurrence Significant MR is associated with an adjusted hazard ratio for mortality of 1.83 (95% CI 1.28 to 2.62, p < 0.001) as compared with matched controls. 7 Calculator Calculator Calculator Cardiac Anesthesia Risk Evaluati NYHA functional classification f Revised C Guidelines 1. Diagnostic investigations Transthoracic echocardiogram: obtain a TTE for baseline evaluation of LV size and function, RV function, LA size, pulmonary artery pressure, and the mechanism and severity of primary MR (stages A to D) in patients with known or suspected primary MR. B Show 3 more Transesophageal echocardiogram: Obtain a TEE to evaluate the severity of MR, mechanism of MR, and status of LV function (stages B to D) in patients with primary MR if TTE provides insufficient or discordant information. B Obtain a TEE to determine suitability for mitral valve intervention in patients with chronic secondary MR with severe symptoms (stage D) unresponsive to guideline-directed medical therapy and eligible for transcatheter mitral valve interventions. B Exercise stress testing: consider obtaining hemodynamic exercise testing using Doppler echocardiography or cardiopulmonary exercise testing in patients with primary MR (stages B and C) and symptoms likely attributable to MR. C Cardiac magnetic resonance imaging: obtain cardiac MRI is indicated to assess LV and RV volumes and function in patients with primary MR, as well as to help assess MR severity when there is a discrepancy between the findings on clinical assessment and echocardiography. B Cardiac biomarkers: consider obtaining serum biomarkers as an adjunct to guide the timing of intervention in asymptomatic patients with severe primary MR (stages B and C1). C 2. Diagnostic procedures https://web.pathway.md/diseases/recBu7iXQ5SAfC9UD 2/8 6/30/23, 1:04 AM Mitral regurgitation Pathway Cardiac catheterization: consider performing cardiac catheterization in patients with primary MR (stages B and C) and symptoms likely attributable to MR. C 3. Medical management Management of systolic dysfunction: Consider initiating guideline-directed medical therapy for systolic dysfunction in symptomatic or asymptomatic patients with severe primary MR and LV systolic dysfunction (stages C2 and D) if surgery is not possible or must be delayed. C Initiate standard guideline-directed medical therapy for HF, including ACEIs, ARBs, -blockers, aldosterone antagonists, and/or sacubitril/valsartan, and biventricular pacing, in patients with chronic severe secondary MR (stages C and D) and HF with reduced LVEF. A Vasodilator therapy: do not administer vasodilators in asymptomatic patients with primary MR and normal LV systolic function (stages B and C1) and normal BP. D 4. Perioperative care Intraoperative imaging: Obtain intraoperative TEE to establish the anatomic basis for primary MR (Stages C and D) and to guide repair in patients with severe primary MR undergoing mitral intervention. B Obtain intraprocedural TEE for guidance in patients with chronic secondary MR undergoing transcatheter mitral valve intervention. B 5. Surgical interventions Mitral valve repair, primary MR, symptomatic patients: As per AHA/ACC 2021 guidelines, perform mitral valve intervention in symptomatic patients with severe primary MR (stage D), irrespective of LV systolic function. B Show 4 more Landmark trials: MIDA In patients with mitral valve regurgitation due to flail mitral leaflets, early mitral surgery was superior to initial medical management with respect to survival at 10 years. Suri RM et al. JAMA. 2013 Aug 14. As per EACTS/ESC 2021 guidelines, perform mitral valve repair in patients with severe primary MR if the results are expected to be durable. B Show 2 more https://web.pathway.md/diseases/recBu7iXQ5SAfC9UD 3/8 6/30/23, 1:04 AM Mitral regurgitation Pathway Mitral valve repair, primary MR, asymptomatic patients: As per AHA/ACC 2021 guidelines, perform mitral valve surgery in asymptomatic patients with severe primary MR and LV systolic dysfunction (LVEF 60%, LV end-systolic diameter 40 mm) (stage C2). B Show 2 more As per EACTS/ESC 2021 guidelines, perform surgery in asymptomatic patients with LV dysfunction (LV end-systolic diameter 40 mm and/or LVEF 60%). B Show 2 more Mitral valve repair, secondary MR: As per ACC 2021 guidelines, consider performing mitral valve surgery in patients with chronic severe secondary MR from atrial annular dilation with preserved LV systolic function (LVEF 50%) and having severe persistent symptoms (New York Health Association class III or IV) despite therapy for HF and therapy for associated AF or other comorbidities (stage D). C Show 2 more As per ESC 2021 guidelines, perform valve surgery/intervention only in patients with severe secondary MR remaining symptomatic despite Guideline-directed medical therapy (including cardiac resynchronization therapy if indicated), decided by a structured collaborative heart team. B Show 3 more As per ESC 2021 guidelines: Consider performing percutaneous edge-to-edge mitral valve repair in carefully selected patients with secondary MR ineligible for surgery, not requiring coronary revascularization, being symptomatic despite optimal medical therapy, and fulfilling criteria for reducing HF hospitalizations. C Consider performing percutaneous edge-to-edge mitral valve repair to improve symptoms in carefully selected patients with secondary MR, ineligible for surgery and not requiring coronary revascularization, highly symptomatic despite optimal medical therapy, and not fulfilling criteria for reducing HF hospitalizations. C Landmark trials: COAPT In patients with HF and symptomatic moderate-to-severe or severe secondary MR despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral valve repair was superior to control with respect to all hospitalizations for HF within 24 months. Stone GW et al. N Engl J Med. 2018 Dec 13. 6. Specific circumstances Patients with coronary artery disease: https://web.pathway.md/diseases/recBu7iXQ5SAfC9UD 4/8 6/30/23, 1:04 AM Mitral regurgitation Pathway As per ACC 2021 guidelines: Consider performing chordal-sparing mitral valve replacement instead of downsized annuloplasty repair in patients with coronary artery disease and chronic severe secondary MR related to LV systolic dysfunction (LVEF < 50%) (stage D) undergoing mitral valve surgery because of severe symptoms (NYHA class III or IV) persisting despite guideline-directed medical therapy for HF. C Consider performing mitral valve surgery in patients with severe secondary MR (stages C and D) undergoing coronary artery bypass surgery for myocardial ischemia. C As per ESC 2021 guidelines: Perform valve surgery in patients in patients with concomitant coronary artery or other cardiac disease undergoing CABG or other cardiac surgery, respectively. B Consider performing PCI (and/or TAVI), possibly followed by transcatheter edge-to-edge repair (in case of persisting severe secondary MR) in symptomatic patients deemed not appropriate for surgery by the heart team based on their individual characteristics. C As per ESC 2021 guidelines, consider performing CABG and mitral valve surgery in patients with HF, severe secondary MR, and coronary artery disease requiring revascularization. C Patients with atrial fibrillation (surgical ablation): avoid performing surgical ablation for symptomatic AF by pulmonary vein ablation alone in patients with more than moderate MR. D Patients with atrial fibrillation (anticoagulation): initiate direct OACs over vitamin K antagonists for stroke prevention in patients with MR and AF eligible for oral anticoagulation. A Landmark trials: RIVER In patients with AF and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to time until death, major cardiovascular events, or major bleeding at 12 months. Helio P Guimar es et al. N Engl J Med. 2020 Nov 26. Patients undergoing non-cardiac surgery: obtain preoperative echocardiography in patients with clinically suspected moderate or greater degrees of valvular regurgitation undergoing non- cardiac surgery. B Show 2 more 7. Follow-up and surveillance Serial transthoracic echocardiogram: obtain TTEs every 6-12 months for surveillance of LV function (estimated by LVEF, LV end-diastolic diameter, and LV end-systolic diameter) and assessment of pulmonary artery pressure in asymptomatic patients with severe primary MR (stages B and C1). B https://web.pathway.md/diseases/recBu7iXQ5SAfC9UD 5/8 6/30/23, 1:04 AM Mitral regurgitation Pathway Clinical findings Symptoms Past medical history Chest pain Blunt cardiac injury Exercise intolerance Cardiomyopathy Fatigue Congenital heart disease Palpitations Coronary artery disease Shortness of breath HF Shortness of breath when lying down Infective endocarditis Mitral valve prolapse Shortness of breath with exertion Myocardial infarction Myocarditis Radiation therapy to the chest area Social history Rheumatic heart disease IV drug use Vital signs Vascular exam Hypotension Peripheral edema Signs of shock Lab findings Tachycardia blood B-type natriuretic peptide Cardiac exam serum NT-proB-type natriuretic peptide Accentuated P2 sound Displaced apical impulse Holosystolic murmur Imaging findings Late systolic murmur Cardiomegaly Systolic heart murmur LA enlargement Systolic thrill Mitral annular dilation Third heart sound Mitral valve thickening ECG findings Pulmonary edema LV end-diastolic diameter AF LV end-systolic diameter Cardiac arrhythmias LVEF Studies 2020 RIVER In patients with AF and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to time until death, major cardiovascular events, or major bleeding at 12 months. Helio P Guimar es et al. N Engl J Med. 2020 Nov 26. https://web.pathway.md/diseases/recBu7iXQ5SAfC9UD 6/8 6/30/23, 1:04 AM Mitral regurgitation Pathway 2018 Zochios In adult patients with pre-existing respiratory disease undergoing elective cardiac surgery, high-flow nasal oxygen was superior to standard oxygen therapy with respect to the total length of hospital stay. V Zochios et al. Anaesthesia. 2018 Dec. Show 4 more References 1. Theresa A McDonagh, Marco Metra, Marianna Adamo et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42 36 3599 3726. Open 2. Catherine M Otto, Rick A Nishimura, Robert O Bonow et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Thorac Cardiovasc Surg. 2021 Aug;162 2):e183-e353. Open 3. Alec Vahanian, Friedhelm Beyersdorf, Fabien Praz et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2021 Aug 28;ehab395. Open 4. Badhwar V, Rankin JS, Damiano RJ Jr et al. The Society of Thoracic Surgeons 2017 Clinical Practice Guidelines for the Surgical Treatment of Atrial Fibrillation. Ann Thorac Surg. 2017 Jan;103 1 329 341. Open 5. Nkomo VT, Gardin JM, Skelton TN et al. Burden of valvular heart diseases: a population-based study. Lancet. 2006 Sep 16;368 9540 1005 11. Open 6. El Sabbagh A, Reddy YNV, Nishimura RA. Mitral Valve Regurgitation in the Contemporary Era: Insights Into Diagnosis, Management, and Future Directions. JACC Cardiovasc Imaging. 2018 Apr;11 4 628 643. Open 7. Prakash R, Horsfall M, Markwick A et al. Prognostic impact of moderate or severe mitral regurgitation MR irrespective of concomitant comorbidities: a retrospective matched cohort study. BMJ Open. 2014 Jul 17;4 7):e004984. Open 8. 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Baumgartner H, Falk V, Bax JJ et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2017 Sep 21;38 36 2739 2791. Open https://web.pathway.md/diseases/recBu7iXQ5SAfC9UD 7/8 6/30/23, 1:04 AM Mitral regurgitation Pathway 12. Alec Vahanian, Friedhelm Beyersdorf, Fabien Praz et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease: Developed by the Task Force for the management of valvular heart disease of the European Society of Cardiology ESC and the European Association for Cardio-Thoracic Surgery EACTS . Eur Heart J. 2021;ehab395. Open https://web.pathway.md/diseases/recBu7iXQ5SAfC9UD 8/8