INTRODUCTION — Management of patients with chronic primary mitral regurgitation (MR) requires an understanding of the pathophysiology and natural history of the disease (table 1) and the efficacy and timing of treatment, particularly mitral valve repair and replacement. While our knowledge of these areas is incomplete, a rational plan for management based upon the available evidence is presented here [1,2].
Primary MR is caused by a primary abnormality of one or more components of the valve apparatus (leaflets, chordae tendineae, papillary muscles, annulus) in contrast to secondary MR, which is caused by another cardiac disease (such as coronary heart disease or a cardiomyopathy) (table 2). Identification of the cause and type (primary or secondary) of MR is required for appropriate management of MR as well as any associated conditions.
The pathophysiology, natural history, diagnosis, and evaluation of chronic MR, and the management of chronic secondary MR are presented elsewhere. (See "Pathophysiology and natural history of chronic mitral regurgitation" and "Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet" and "Clinical manifestations and diagnosis of chronic mitral regurgitation" and "Management and prognosis of chronic secondary mitral regurgitation".)
STAGING — Staging of primary MR is based upon symptoms, valve anatomy, valve hemodynamics (severity of MR), and hemodynamic consequences of MR as reflected by left atrial size, left ventricular (LV) size and function, and pulmonary artery pressure (table 3) [1]:
●In stage A, patients are at risk of MR (or have mild MR). There are mild mitral valve abnormalities (mild mitral valve prolapse or mild valve thickening and leaflet restriction) with no or mild MR (small central jet <20 percent of left atrium on color Doppler with vena contracta <0.3 cm). The left atrial and LV sizes are normal and there are no symptoms.
●In stage B, patients have progressed to moderate MR with substantial valve abnormalities (severe mitral valve prolapse with normal coaptation, rheumatic valve changes with leaflet restriction and loss of central coaptation, or evidence of prior infective endocarditis).
•Progressive MR is identified by the following criteria: a central jet filling 20 to 40 percent of the area of the left atrium or late systolic eccentric MR, vena contracta of 0.3 to <0.7 cm, regurgitant volume <60 mL, regurgitant fraction <50 percent, and effective regurgitant orifice is <0.40 cm2. The angiographic grade is 1 to 2+.
•There is mild left atrial enlargement, little or no LV enlargement, normal pulmonary pressure, and no symptoms.
●In stage C, patients have asymptomatic severe MR. There are severe valve abnormalities (severe mitral valve prolapse with loss of coaptation or flail leaflet, rheumatic valve changes with leaflet restriction and loss of central coaptation, evidence of prior infective endocarditis, or thickening of leaflets with radiation heart disease).
•Severe MR is identified by presence of at least some of the following criteria: a central jet of MR >40 percent of the left atrium or holosystolic eccentric MR. Vena contracta is ≥0.7 cm, the regurgitant volume is ≥60 mL, the regurgitant fraction is ≥50 percent, and the effective regurgitant orifice is ≥0.40 cm2. The angiographic grade is 3 to 4+.
•There is moderate or severe left atrial enlargement, LV enlargement, and pulmonary hypertension is present at rest or with exercise.
•There are two subgroups in stage C:
-Patients with C1 disease have LV ejection fraction (LVEF) >60 percent and LV end-systolic dimension <40 mm. Such patients are said to have chronic compensated MR [3].
-Patients with C2 disease have LVEF ≤60 percent and LV end-systolic dimension ≥40 mm. Patients with C2 disease are exhibiting a transition to Stage D [3].
●In stage D, patients have symptomatic severe MR with severe valve abnormalities (as described above).
•Severe MR is identified as above.
•Moderate or severe left atrial enlargement, LV enlargement, and pulmonary hypertension are present.
•Symptoms include decreased exercise tolerance and exertional dyspnea or a history of overt heart failure.
MONITORING
Clinical and echocardiographic follow-up — Following initial evaluation and staging, serial monitoring (and re-staging) is warranted in patients with chronic MR. The goals of monitoring are to assess changes in clinical status by history and physical examination and to identify changes in severity of MR and left ventricular (LV) function which can occur in the absence of symptoms.
We agree with the following recommendations for clinical and transthoracic echocardiographic (TTE) monitoring in asymptomatic patients with chronic MR in the 2020 American College of Cardiology/American Heart Association guidelines [1].
●Follow-up of all patients with valve disease includes at least annual history and physical examination.
●Serial TTE is performed to assess the severity of valve disease, LV size, LV ejection fraction (LVEF), and LV end-systolic dimension. The frequency of recommended follow-up varies with the severity of MR:
•Patients with mild MR and no evidence of LV enlargement, LV dysfunction, or pulmonary hypertension should undergo echocardiography every three to five years.
•Patients with moderate MR should undergo echocardiography every one to two years.
•Patients with severe MR should be seen every 6 to 12 months (or sooner if symptoms occur). Repeat TTE should be obtained at these visits. The six-month interval is preferred if stability has not been documented, there is evidence of progression, or measurements are approaching values used in an indication for mitral valve surgery.
In addition, TTE should be performed in patients with MR with a change in symptoms (eg, dyspnea or reduced exercise tolerance) or signs, or new onset of atrial fibrillation [1].
Additional testing if needed
Transesophageal echocardiography — Transesophageal echocardiography (TEE) is not indicated for follow-up of most patients. TEE is indicated when noninvasive imaging fails to determine the severity or cause of MR [1]. TEE also has a role in preoperative and intraoperative evaluation for mitral valve surgery to determine valve anatomy and help guide repair.
Exercise testing — Exercise testing is not required for monitoring of most patients with chronic primary MR but may be helpful in certain settings [1]:
●Exercise stress testing may add objective evidence about symptoms and a change in exercise tolerance; it may be particularly useful if a good history of exercise capacity is difficult to obtain.
●For patients with symptoms that are greater than expected for the degree of MR at rest or borderline echocardiographic findings [4], exercise echocardiography including measurement of MR severity and pulmonary artery pressure during exercise may be helpful. Results of exercise echocardiography may have prognostic value in asymptomatic patients with moderate or severe chronic primary MR [5-7].
Cardiovascular magnetic resonance imaging — Cardiovascular magnetic resonance imaging is not generally indicated for monitoring of MR but is indicated when echocardiography is not adequate to assess MR severity or left and right ventricular volumes and function [1]. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Regurgitant valve disease'.)
Coronary angiography prior to valve surgery — Many patients requiring surgery for chronic primary MR (which should be distinguished from ischemic MR) also have significant coronary artery disease. Obstructive coronary lesions are generally revascularized at the time of mitral valve surgery, since concurrent bypass surgery typically adds little morbidity or mortality to the procedure. Assuming that the patient is not hemodynamically unstable, coronary angiography is recommended prior to mitral valve surgery in patients who have coronary disease or are at risk for coronary disease [1]. (See "Surgical procedures for severe chronic mitral regurgitation", section on 'Evaluation for coronary disease'.)
Other — A role for monitoring of other prognostic markers, such as brain natriuretic peptide, has not been established. Studies suggest that serum brain natriuretic peptide (BNP) may have prognostic value in patients with chronic primary MR [8]. As an example, a report evaluated 124 patients with chronic MR, 94 with mitral valve prolapse; almost all patients were asymptomatic or had only a mild limitation in physical activity and the mean LVEF was 69 percent [9]. Serum BNP values ≥31 pg/mL predicted lower five-year survival (72 versus 96 percent). BNP was independently predictive of mortality with adjustment for age, sex, functional class, MR severity, and LVEF. Thus, BNP level reflected the clinical consequences of MR rather than the severity of MR. Similarly, a study of 135 asymptomatic patients with moderate to severe primary MR and preserved LVEF found that BNP was an independent predictor of cardiac events [10]. Observational studies have also suggested that patients with MR with elevated BNP or NT-proBNP levels may face increased risk of adverse outcomes following mitral valve surgery [11,12].
GENERAL MANAGEMENT — There is a limited role for medical management in patients with chronic primary MR, since valve intervention is required to address the primary process. The approach to management presented here is in general agreement with 2020 American College of Cardiology/American Heart Association (ACC/AHA) valve guidelines and 2021 European Society of Cardiology valve guidelines [1,2].
Pharmacologic therapy for heart failure and hypertension
Indications — Medical therapy has a limited role in the treatment of primary MR since it does not address the primary process.
●Given lack of evidence of efficacy, we do not use vasodilators to treat normotensive asymptomatic patients with chronic primary MR (stages B and C1) and normal systolic LV function [1].
●Patients with chronic primary MR and concomitant hypertension should receive standard antihypertensive therapy to reduce the morbidity and mortality associated with hypertension; such therapy may also reduce the tendency to develop worsening MR [1]. (See "Overview of hypertension in adults", section on 'Treatment'.)
●Symptomatic patients with chronic primary MR (stage D) and left ventricular ejection fraction (LVEF) <60 percent who are awaiting valve surgery or who are not candidates for valve surgery are treated with standard guideline-based medical therapy for heart failure with reduced ejection fraction (including angiotensin converting enzyme [ACE] inhibitor [or angiotensin II receptor blocker or angiotensin receptor-neprilysin inhibitor], beta blocker, diuretics, and possibly also mineralocorticoid receptor antagonist) [1]. (See "Overview of the management of heart failure with reduced ejection fraction in adults".)
Evidence — The recommendation for medical therapy for symptomatic MR with LVEF <60 percent is largely based on evidence in patients with heart failure with reduced ejection fraction [1]. Scant evidence is available on heart failure therapy such as ACE inhibitors, beta blockers, and aldosterone antagonists in patients with MR. Small randomized trials evaluating ACE inhibitors in asymptomatic patients with chronic primary MR found little or no evidence of benefit as measured by LV size [13,14].
Limited evidence on beta blocker therapy in patients with MR suggests a possible benefit. A preliminary trial randomly assigned 38 asymptomatic adults with moderate to severe MR to placebo or beta-1 blockade (with extended release metoprolol) for two years [15]. LVEF and LV early diastolic filling rate improved with beta blocker therapy. A retrospective study of 895 patients with severe MR and normal LVEF found that beta blocker use was associated with a significantly decreased risk of mortality [16] but this finding is not sufficient to establish the efficacy of beta blocker therapy.
Vasodilators are not indicated for use in normotensive asymptomatic patients with chronic primary MR and normal systolic function [1,2]. There are no published studies that support the hypothesis that vasodilator therapy is beneficial in asymptomatic normotensive patients with chronic primary MR [17].
Endocarditis prophylaxis — In accordance with the 2007 AHA guidelines on infective endocarditis and the 2014 AHA/ACC valvular heart disease guidelines [1,18], antibiotic prophylaxis is not recommended when patients with mitral valve disease (in the absence of prosthetic valve replacement or history of infective endocarditis) undergo dental or other invasive procedures that produce significant bacteremia with organisms associated with endocarditis. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
Secondary prevention of rheumatic fever — For patients with rheumatic heart disease, long-term prophylaxis against rheumatic fever is recommended according to standard guidelines. (See "Acute rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)'.)
Exercise — Exercise has a variable effect on the regurgitant fraction in patients with chronic MR [19]. The reduction in systemic vascular resistance may result in no change or a mild reduction in the regurgitant fraction. On the other hand, an elevation in blood pressure or heart rate can lead to an increase in regurgitant volume and pulmonary capillary pressure.
We agree with the following recommendations for athletes with MR modified from the 2015 AHA/ACC scientific statement for competitive athletes with valvular heart disease [19] (figure 1):
●Athletes with MR should be evaluated annually by physical examination, echocardiography, and exercise stress testing to determine whether sport participation can continue.
•Exercise testing to at least the level of activity achieved in competition and training is useful to confirm asymptomatic status in patients with MR.
•Estimation of pulmonary artery systolic pressure during exercise by Doppler echocardiography can be helpful, particularly in athletes with significant MR. This evaluation is used to determine whether sport participation can continue.
●Athletes in sinus rhythm with mild to moderate MR, normal LV function, and normal pulmonary artery pressure can participate in all competitive sports.
●It is reasonable for athletes with moderate MR in sinus rhythm with normal LV systolic function at rest and mild LV enlargement (compatible with that resulting solely from athletic training; LV end-diastolic dimension [LVEDD] <60 mm or <35.3 mm/m2 in men or <40 mm/m2 in women) to participate in all competitive sports.
●Athletes with asymptomatic severe MR in sinus rhythm with normal LV systolic function at rest and mild LV enlargement (compatible with that resulting solely from athletic training; LVEDD <60 mm or <35.3 mm/m2 in men or <40 mm/m2 in women [stage C1]) can participate in low-intensity and some moderate-intensity sports (classes IA, IIA, and IB).
●Athletes with MR and definite LV enlargement (LVEDD ≥65 mm or ≥35.3 mm/m2 in men or ≥40 mm/m2 in women) pulmonary hypertension, or any degree of LV systolic dysfunction at rest (LVEF <60 percent or LV end-systolic dimension >40 mm) should not participate in any competitive sports, with the possible exception of low-intensity class IA sports.
●Athletes with a history of atrial fibrillation who are receiving long-term anticoagulation should not engage in sports involving risk of bodily contact (table 4).
Exercise following mitral valve replacement or repair is discussed separately. (See "Overview of the management of patients with prosthetic heart valves", section on 'Exercise recommendations'.)
MITRAL VALVE INTERVENTION
Approach to mitral valve intervention — Mitral valve intervention (primarily surgery) is required to address the primary process in patients with severe chronic primary MR. The approach to management presented here is in general agreement with 2020 American College of Cardiology/American Heart Association (ACC/AHA) valvular heart disease guidelines and the 2021 European Society of Cardiology (ESC) valve guidelines [1,2]. The decision to proceed with mitral valve intervention depends upon the stage (including presence of symptoms, left ventricular ejection fraction [LVEF], left ventricular end-systolic dimension [LVESD]) and in some clinical settings also depends upon the likelihood of successful and durable mitral valve repair:
•For some patients who are surgical candidates, a decision to proceed with mitral valve surgery is made independent of the type of mitral valve surgery (repair or replacement) that will be performed. This includes patients with the following characteristics:
-Symptomatic patients with chronic severe primary MR (stage D) with LVEF >30 percent.
-Asymptomatic patients with chronic severe primary MR and LVEF 30 to 60 percent and/or LVESD ≥40 mm (stage C2).
-Asymptomatic patients with chronic severe primary MR with LVEF >60 percent and LVESD <40 mm if there is a progressive increase in LV size or decrease in LVEF on serial imaging studies.
For patients with the above indications for surgery, the next step is determining which procedure should be performed (mitral valve replacement or repair). Among patients who undergo mitral valve replacement, a choice is made between prosthetic valve types (bioprosthetic versus mechanical). (See 'Choice of procedure' below and 'Choice of valve' below and "Surgical procedures for severe chronic mitral regurgitation".)
•For other patients who are surgical candidates, a decision to proceed with mitral valve surgery is made contingent upon the likelihood of successful and durable mitral valve repair without residual MR. This includes patients with the following characteristics:
-Asymptomatic patients with chronic severe primary MR with LVEF >60 percent and LVESD <40 mm (stage C1) with likelihood of successful and durable mitral valve repair without residual MR is >95 percent and expected operative mortality <1 percent.
•For asymptomatic patients who are undergoing cardiac surgery for other indications, concomitant mitral valve repair is recommended for patients with severe chronic primary MR.
●Choice of procedure
•For patients with severe primary MR with an indication for intervention with expected successful and durable repair, we suggest surgical mitral valve repair rather than valve replacement . The decision on whether to attempt mitral valve repair is based upon the specific valve lesion and the surgeon’s experience. (See 'Surgical mitral valve repair versus replacement' below.)
A surgical mitral valve repair procedure involves repair of the valve, assessment of the success of the repair, and if the repair is deemed inadequate, conversion to mitral valve replacement. (See 'Surgical mitral valve repair versus replacement' below.)
•For patients with high or prohibitive surgical risk because of severe comorbidities who are severely symptomatic (New York Heart Association class III to IV) despite optimal guideline-directed medical therapy with chronic severe primary MR (stage D) and who have a life expectancy of at least one year and favorable anatomy for transcatheter repair, we suggest transcatheter edge-to-edge mitral valve repair . The efficacy and safety of this procedure is discussed separately. (See "Transcatheter mitral valve repair".)
Intervention versus watchful waiting
Indications for mitral valve intervention — Determining the need for intervention in patients with chronic primary MR is based upon the severity of MR, the presence or absence of symptoms, LVESD and LVEF, the feasibility of valve repair, the presence of atrial fibrillation, the presence of pulmonary hypertension at rest or with exercise, whether other cardiac surgery is required, and the preference and expectations of the patient.
Some consideration of body size should be included in any estimation of LV dimension, since smaller women are less likely to reach the above criteria, which were largely established in men. However, simply normalizing for body surface area can lead to misleading conclusions, especially in patients who are overweight. In general, somewhat lower values should be used in very small patients and somewhat higher values in very large patients.
The following indications for mitral valve intervention are modified from those in the 2020 ACC/AHA valve guideline [1]:
For symptomatic patients — Patients with chronic primary severe MR who develop symptoms (eg, dyspnea or fatigue) are candidates for corrective mitral surgery, even if the symptoms improve with medical therapy or the LV appears to be compensated [1,2]. If there is uncertainty about the presence or absence of symptoms, exercise testing may provide objective information that may not be available from the medical history alone.
●For symptomatic patients with chronic severe primary MR (stage D) with LVEF >30 percent, we recommend mitral valve surgery. Surgery should be performed as soon as symptoms develop. (See 'Symptoms' below.)
●For symptomatic patients with chronic severe primary MR and LVEF ≤30 percent, with high likelihood of successful mitral repair, we suggest mitral valve repair. (See 'Severely impaired left ventricular function' below.)
●For symptomatic patients with chronic severe primary MR and LVEF ≤30 percent, with mitral valve not amenable to repair, we suggest not performing mitral valve surgery. (See 'Severely impaired left ventricular function' below.)
For asymptomatic patients — Waiting for the patient to experience dyspnea or exercise intolerance may allow time for the development of irreversible depression of LV function. For this reason, it is important to monitor LV size and function in patients with asymptomatic MR. In the absence of symptoms, management decisions and the indications for surgery rest largely upon the echocardiographic assessment of LV size and function as well as careful confirmation of the severity of MR. Some degree of LV and left atrial enlargement are to be expected in severe chronic MR; thus, chamber enlargement alone is generally not an indication for surgery in patients with severe chronic MR.
●For asymptomatic patients with chronic severe primary MR and an LVEF of 30 to 60 percent and/or an LVESD ≥40 mm (stage C2), we recommend mitral valve surgery. (See 'Reduced left ventricular function' below.)
Patients with chronic severe primary MR with an LVEF ≤30 percent would be expected to be symptomatic as discussed above. (See 'For symptomatic patients' above.)
●For asymptomatic patients with chronic severe primary MR undergoing cardiac surgery for other indications, we recommend concomitant mitral valve repair. (See 'Concomitant cardiac surgery' below.)
●For patients with chronic moderate primary MR undergoing cardiac surgery for other indications, we suggest concomitant mitral valve repair. (See 'Concomitant cardiac surgery' below.)
●For asymptomatic patients with chronic severe nonrheumatic primary MR (stage C1) and normal LV function (LVEF >60 percent and LVESD <40 mm) in whom there is a high likelihood of a successful and durable repair and who have new onset of atrial fibrillation or resting pulmonary hypertension (pulmonary artery systolic arterial pressure >50 mmHg), we suggest surgical mitral valve repair. (See 'Atrial fibrillation' below.)
In this setting, atrial fibrillation can be considered "new onset" if the onset is prospectively documented or if atrial fibrillation is present when the diagnosis of severe MR is first made.
●For asymptomatic patients with severe MR (stage C1) and normal LV function (LVEF >60 percent and LVESD <40 mm) who are deemed excellent candidates (with likelihood of repair without residual MR >95 percent and expected mortality rate of <1 percent) by the surgical team at a heart valve center of excellence, we suggest mitral valve repair. (See 'Impact of timing of surgery' below and "Surgical procedures for severe chronic mitral regurgitation", section on 'Valve repair versus valve replacement'.)
●For asymptomatic patients with severe MR (stage C1) and normal LV function (LVEF >60 percent and LVESD <40 mm) with progressive increase in LV size or decrease in LVEF on serial imaging studies, we suggest mitral valve repair.
Proposed indications — In addition to the above indications, some experts have suggested that the effective regurgitant orifice (ERO) and functional capacity may identify asymptomatic patients with isolated severe chronic MR who would benefit from surgery before they develop LV systolic dysfunction, atrial fibrillation, and/or pulmonary hypertension [20,21]. (See 'Effective regurgitant orifice' below and 'Functional capacity' below.)
Indications for watchful waiting — Watchful waiting is appropriate for asymptomatic patients with chronic severe MR with normal LV systolic function (with LVEF ≥60 percent and LVESD <40 mm) who lack criteria for intervention. Such patients should undergo physical examination and echocardiography every 6 to 12 months or any time symptoms occur [1]. The six-month interval is preferred if stability has not been documented, there is evidence of progression, or measurements are close to the echocardiographic cutoff values. (See 'Monitoring' above.)
A decision about watchful waiting must consider patient preference, the presence of other risk factors (new atrial fibrillation or pulmonary hypertension), and whether mitral valve repair, the preferred approach, can be performed. Surgery may be offered earlier in patients with borderline values in patients in whom access to such monitoring is limited. An occasional patient with a borderline LVEF or a technically limited study will require radionuclide, contrast angiography, or cardiovascular magnetic resonance imaging to assess LV function and regurgitant fraction. Exercise stress testing may add objective evidence about symptoms and a change in exercise tolerance; it may be particularly useful if a good history of exercise capacity is difficult to obtain. Measurement of MR severity and pulmonary artery pressure during exercise may also be helpful. (See "Tests to evaluate left ventricular systolic function" and 'Exercise testing' above.)
Careful monitoring is required for timely and accurate identification of an indication for mitral valve intervention:
●Because there is variability in measurement of LVEF and end-systolic size, any observed interval change should be reconfirmed with another study at a shorter time interval to determine if there is consistent, reproducible change in LV size or systolic function that would warrant intervention per the guidelines above.
●Because there is considerable variability in the accuracy of quantitation of regurgitation severity, some patients classified as having moderate MR may have hemodynamically severe disease. By contrast, others thought to have severe MR may have only moderate MR. This issue is not directly addressed in the major society guidelines. If symptoms are present, alternate causes for symptoms should be sought and the regurgitant fraction should be quantified using methods such as cardiac magnetic resonance imaging. If no other cause is evident, we favor watchful waiting in patients with mild symptoms (NYHA functional class II) (table 5) and moderate MR who have preserved LV function (LVEF >60 percent and LVESD <40 mm) and no other risk factors, such as early pulmonary hypertension.
●By contrast, some patients who appear to have severe MR (eg, by color Doppler evidence alone) may have only moderate MR. If the LV and/or left atrium are not enlarged, the diagnosis of severe MR should be questioned and quantitative regurgitant volume and regurgitant fraction data should be obtained.
Evidence on timing of intervention
Overview of evidence — Recommendations for mitral valve surgery in patients with chronic primary MR are based upon observational data, including comparisons of natural history data to outcomes when surgery is performed in response to symptoms and other indications. For patients 50 years or older with chronic primary MR treated medically, the estimated annual mortality rate is approximately 3 percent for moderate MR and 6 percent for severe MR [22]. Patients with severe chronic primary MR have annual cardiac event rates of approximately 10 to 12 percent (including an approximately 9 percent risk of heart failure and 5 percent risk of atrial fibrillation). Predictors of adverse outcomes include symptoms, depressed LVEF, increased LVESD, older age, pulmonary hypertension, atrial fibrillation, left atrial dilation, as well as greater effective regurgitant orifice area [1,2,22]. Among medically treated patients with severe chronic primary MR, the risk of sudden death ranges from approximately 1 percent per year in asymptomatic patients with normal LVEF to 8 percent per year in patients with class III or IV symptoms and flail mitral leaflet with severe MR [22]. (See "Arrhythmic complications of mitral valve prolapse", section on 'Sudden cardiac death'.)
Early mortality after mitral valve surgery varies from approximately 1 percent for patients less than 65 years old, 2 percent for patients 65 to 75 years old, and 4 to 5 percent for patients greater than 75 years old [22]. Patients with severe chronic primary MR and no or mild symptoms who undergo mitral valve surgery have life expectancy similar to that in the age- and sex-matched general population [22-24]. Mitral valve surgery for flail leaflet with severe MR is associated with a reduced incidence of sudden death [25]. (See "Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet", section on 'Mitral regurgitation' and "Surgical procedures for severe chronic mitral regurgitation" and "Arrhythmic complications of mitral valve prolapse", section on 'Sudden cardiac death'.)
Impact of timing of surgery — Observational data suggest that patients with severe chronic primary MR have better outcomes when surgery is performed soon after an indication for surgery develops. Patients with severe MR with an LVEF ≤60 percent or LVESD ≥40 mm have already developed systolic dysfunction [26-29]. One study of patients with severe MR undergoing mitral valve repair found that a preoperative LVEF ≥64 percent with LVESD <37 mm predicted low risk of postoperative LV dysfunction (9 percent) compared with preoperative LVEF <64 percent or LVESD ≥37 mm (21 percent), and preoperative LVEF <64 percent with LVESD ≥37 mm (33 percent) [27].
A retrospective study of 481 patients with severe primary degenerative MR with at least one 1998 ACC/AHA guideline indication for mitral valve surgery (similar to 2020 ACC/AHA guideline indications) compared outcomes with early surgery (performed within two months of presentation with an indication for surgery) to outcomes with late surgery (performed >2 months after presentation with an indication for surgery) [30]. Most of the patients were symptomatic (95 percent in the early surgery group and 87 percent in the late surgery group). In a multivariable model, early surgery was associated with a lower hazard for death compared with late surgery (hazard ratio [HR] 0.54, 95% CI 0.30-0.97).
Observational data suggest that patients with severe chronic primary MR have better outcomes when surgery is performed early (ie, when there is a high probability of mitral valve repair and no other indications) than after the development of symptoms, LV systolic dysfunction, pulmonary hypertension, or atrial fibrillation, though these data are subject to limitations [20,21,26,31-33].
A systematic review and meta-analysis included five observational studies that compared early surgery with watchful waiting [34]; three of the five studies that included propensity-matched watchful waiting and early surgery groups were included in pooled analysis (with mean follow-up of 7.5 to 10.3 years) [21,32,33]:
●Among patients without symptoms or LV systolic dysfunction, long-term mortality was significantly lower with an early surgery approach for the three pooled studies (HR 0.38, 95% CI 0.21-0.71). In a further subgroup of these patients without atrial fibrillation or pulmonary hypertension, some survival benefit of early surgery persisted (risk ratio [RR] 0.85, 95% CI 0.75-0.98).
●All five studies reported operative mortality rates ≤1 percent (aggregate mortality rates of 0.7 percent for both early surgery and watchful waiting cohorts).
●For the three pooled studies, early surgery was associated with a significantly higher rate of mitral valve repair versus replacement (RR 1.10, 95% CI 1.02-1.18).
Similar results were reported in a single-center study of 1512 patients with primary MR who underwent mitral valve surgery [26]; this study partially overlapped two studies included in the above systematic review. Long-term survival was lower in patients who underwent surgery for class I triggers (heart failure symptoms, LVEF <60 percent, or end-systolic diameter ≥40 mm) and for class II triggers based upon complications (atrial fibrillation or pulmonary hypertension), compared with those with a class II trigger based upon the combination of severe MR and high probability of valve repair (15-year survival rates of 42 and 53 versus 70 percent).
A limitation of studies included in the systematic review is that mitral valve surgery was not performed in all patients in the watchful waiting group who developed indications for surgery and when performed, the timeliness of surgery was not specified. Since the meta-analysis was based upon observational data, residual confounding cannot be excluded. In addition, the early surgery approach is applicable only to centers with similarly high rates of successful mitral valve repair and low rates of operative mortality.
Recommendations for watchful waiting are presented above. (See 'Indications for watchful waiting' above.)
Additional evidence according to clinical setting
Symptoms — Observational data suggest that mitral valve surgery (repair or replacement) alleviates symptoms in patients with symptomatic, chronic, primary, severe MR and reduces mortality in the subset with mild symptoms [20,23,24]. In patients with mild symptoms and chronic, primary, severe MR, surgery appears to restore life expectancy to expected levels while excess mortality risk remains in patients with moderate or severe symptoms. Delaying surgery until moderate to severe symptoms occurs is associated with increased perioperative and long-term mortality. The magnitude of this effect was illustrated in the following studies:
●A retrospective study compared outcomes after surgery in 199 patients with functional class I/II symptoms with those for 279 patients in class III/IV (table 5) [23]. Compared with those in class I/II, patients in class III/IV had a significantly higher surgical mortality (5.4 versus 0.5 percent) and a significantly lower 10-year survival (48 versus 76 percent). These differences were independent of all baseline characteristics, including LVEF (figure 2) and concomitant coronary artery bypass grafting (figure 3), and were seen in patients undergoing valve replacement or repair, although the outcomes were better with valve repair (figure 4). These observations illustrate the importance of careful monitoring to detect patients before such an advanced state is reached. (See 'Monitoring' above.)
●Similar results were observed in a later study of 4586 patients undergoing mitral valve surgery (93 percent repair) for primary MR [35]. Hospital mortality increased with progressive increases in NYHA functional class (0.29, 0.20, 0.67, and 5.1 percent for classes I to IV, respectively). Higher NYHA class was associated with reduced LV function, left atrial enlargement, development of atrial fibrillation and tricuspid regurgitation.
Reduced left ventricular function — The importance of surgical repair before there is a significant impairment in LV function was illustrated in a report of 409 patients who underwent surgery for isolated organic MR [36]. Ten-year survival was 72, 53, and 32 percent in patients with a preoperative LVEF of ≥60 percent, 50 to 59 percent, and less than 50 percent, respectively.
As noted above, among patients with primary MR with flail leaflet, the presence of reduced LV function (along with severity of symptoms) is a risk factor for sudden death and surgical correction is associated with significant reduced risk of sudden death [25].
Serial echocardiographic studies have shown that preoperative LVESD ≥40 to 45 mm or a low-normal or depressed LVEF is predictive of persistent postoperative LV enlargement and systolic dysfunction (table 1) [1,2,27,36-40].
Severely impaired left ventricular function — A separate issue is surgery in patients with severe chronic primary MR and severe LV dysfunction (LVEF <30 percent and/or LVESD >55 mm) in whom surgery may improve symptoms but may not alter long-term mortality rates or need for LV assist device support or transplantation. Such patients with primary mitral valve disease generally exhibit irreversible depression of ventricular contractility due to long-standing LV volume overload. LV systolic function does not improve after mitral valve surgery. Data are lacking to guide surgical management in this population, but guideline-based medical therapy is indicated. For patients with severe MR with LVEF <30 percent who have a high likelihood of durable repair and low comorbidity, some experts consider the potential benefit of mitral valve surgery with attempted repair to be greater than the risk. (See 'Pharmacologic therapy for heart failure and hypertension' above.)
Atrial fibrillation — Chronic MR is often complicated by the development of atrial fibrillation. If the ventricle is compensated and the heart rate is not excessive, the patient with atrial fibrillation merely notices palpitation. There is little or no disability in these cases except for an increased risk of stroke or other sign of systemic embolization. These patients are candidates for direct current cardioversion and antiarrhythmic drug therapy to maintain sinus rhythm. (See "Atrial fibrillation: Cardioversion" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".)
Preoperative variables that are associated with the persistence of AF after surgery are a prolonged duration of the arrhythmia (exceeding one year) and moderate to severe left atrial enlargement [41-43]. When the preoperative left atrial size exceeds 50 mm (by echocardiography), fewer than one-half of the patients return to normal sinus rhythm after surgery; in contrast, when left atrial dimension is normal, 85 percent of patients return to normal sinus rhythm [42].
These data and anecdotal clinical experience support the concept that, if postoperative atrial fibrillation and its complications are to be minimized, corrective surgery should be considered within months of the development of atrial fibrillation or before substantial left atrial enlargement is present. The 2020 ACC/AHA guidelines concluded that the weight of evidence was in favor of the efficacy of mitral valve surgery in asymptomatic patients with severe chronic MR and normal LV function who have new onset AF [1]. The 2021 ESC guidelines included a similar statement [2].
Pulmonary hypertension — Since pulmonary hypertension is associated with increased risk of adverse outcomes after valve surgery [44,45] and is likely to worsen without mitral valve intervention, the development of pulmonary hypertension is suggested as an indication to proceed with mitral valve repair.
Concomitant cardiac surgery — The rationale for performing concomitant mitral valve surgery (repair or replacement) in patients with chronic severe primary MR undergoing cardiac surgery for other indications is that mitral valve surgery is likely to be required eventually and the risk of a single operation is less than the risk of two operations. Early and late survival rates are higher after mitral valve repair with aortic valve replacement than following double valve replacement [46].
Effective regurgitant orifice — The predictive value of a large ERO was suggested by a prospective observational study of 465 patients with isolated primary MR (80 percent mitral valve prolapse), a normal LVEF (mean 70 percent), absence of pulmonary hypertension, and, in all but 9 percent, absence of atrial fibrillation [20]. An ERO ≥40 mm2, which was present in 43 percent of cases, was associated with a larger regurgitant volume (101 versus 29 mL/beat with an ERO <20 mm2) and was a powerful predictor of an adverse outcome, including all-cause mortality, cardiac events, and undergoing cardiac surgery.
Similarly, a prospective observational study of 447 asymptomatic patients with severe MR and normal LV function found that ERO, baseline grade of pulmonary hypertension, and age were independent predictors for development of an indication for MV surgery or heart failure [21].
A major limitation to the use of ERO is that quantitation of ERO is technically difficult and should only be performed in an experienced echocardiography laboratory [47]. Another key issue is that ERO does not account for the duration of regurgitation (mid-late systolic versus holosystolic), which likely explains why regurgitant volume rather than ERO predicted outcomes in one large series [48]. Eccentric MR jets are also more difficult to assess using echocardiographic measures. These issues are discussed in more detail separately. (See "Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet", section on 'Clinical outcome'.)
An additional issue complicating quantification of MR is that the severity of MR varies with hemodynamic conditions (loading conditions and inotropic state) [49]. The dynamic nature of MR explains variations in the degree of MR with general anesthesia and in some patients presenting with acute pulmonary edema [49].
Left atrial size — The prognostic significance of left atrial (LA) volume indexed to body surface area (LA index) was suggested by a prospective observational study of 492 patients with isolated primary MR (81 percent mitral valve prolapse) in sinus rhythm at baseline [50]. Five-year survival with medical management was 80 percent. LA index was an independent predictor of mortality and of cardiac events in patients receiving medical management. Patients with LA index ≥60 mL/m2 had lower five-year survival (53 percent) than those with LA index of 40 to 59 mL/m2 (84 percent) and those with LA index <40 mL/m2 (90 percent). LA index remained a significant predictor of mortality and cardiac events after adjustment by ERO.
In this cohort, mitral surgery was associated with decreased mortality (HR 0.46, 95% CI, 0.26-0.84) and cardiac events (HR 0.38, 95% CI 0.23 to 0.62). Postoperative outcomes were not significantly different in patients with LA index ≥60 mL/m2 as compared with those with LA index <60 mL/m2 (five-year mortality 9.1 versus 8.7 percent and cardiovascular events 20 versus 16.8 percent).
These findings suggest that LA index may be a useful parameter for risk stratification of patients with MR, although this study did not evaluate whether it provides predictive value beyond current monitored parameters such as pulmonary artery systolic pressure.
Functional capacity — The potential value of quantitative assessment of functional capacity (FC) using cardiopulmonary exercise testing (CPET) with determination of gas exchange was assessed in 134 asymptomatic patients with MR (57 percent severe) who underwent CPET and echocardiographic quantitation of MR (including the ERO), as well as measurement of LV systolic and diastolic function [51]. At three years, clinical events and the combined endpoint of clinical events and surgery were significantly more common in the 25 percent of patients with markedly reduced FC. This is not surprising since decreased exercise intolerance is often the first symptom of severe MR and, as described above, patients with more severe symptoms have worse outcomes. (See 'Symptoms' above.)
CHOICE OF PROCEDURE — Among patients with an indication for mitral valve intervention, a choice is made between mitral valve repair and valve replacement. The choice of procedure depends largely upon the mitral valve anatomy and available technical expertise to repair the valve. (See "Surgical procedures for severe chronic mitral regurgitation", section on 'Valve repair versus valve replacement'.)
In most patients, mitral valve repair at experienced surgical centers is the preferred approach because of both functional and survival benefits compared with valve replacement (figure 4). For patients with severely symptomatic chronic primary MR, prohibitive surgical risk due to comorbidities, and reasonable life expectancy, transcatheter mitral valve repair is an option if anatomy is favorable.
Surgical mitral valve repair versus replacement — For patients with chronic primary MR, when mitral valve repair is feasible, it is generally preferred to mitral valve replacement based upon the following considerations [1]:
●Observational studies suggest that mitral valve repair is associated with a lower operative mortality rate than mitral valve replacement. (See "Surgical procedures for severe chronic mitral regurgitation", section on 'Valve repair versus valve replacement'.)
●LV systolic function is better preserved with mitral valve repair than with standard mitral valve replacement. However, mitral valve replacement with chordal sparing preserves LV systolic function with results comparable to mitral valve repair. (See "Surgical procedures for severe chronic mitral regurgitation", section on 'Chordal preservation'.)
●Mitral valve repair avoids complications of prosthetic heart valves, including risks of thromboembolism and need for anticoagulation (particularly with mechanical valves) and risk of structural valve failure (particularly with bioprosthetic valves). (See "Diagnosis of mechanical prosthetic valve thrombosis or obstruction".)
However, the likelihood of successful and durable mitral valve repair depends upon mitral valve anatomy and surgical expertise. While successful posterior leaflet repair is generally expected, successful repair rates are more variable with anterior or bileaflet repair [1]. Successful mitral valve repair has generally to be considered less likely in patients with rheumatic mitral disease than in patients with degenerative disease [1], although some have reported comparable results [52]. These considerations are reflected in the following recommendations (see "Surgical procedures for severe chronic mitral regurgitation", section on 'Valve repair versus valve replacement'):
●When surgical treatment is indicated for patients with chronic severe primary MR limited to the posterior leaflet, mitral valve repair is recommended in preference to mitral valve replacement. (See "Surgical procedures for severe chronic mitral regurgitation", section on 'Valve repair versus valve replacement'.)
●When surgical treatment is indicated for patients with chronic severe primary MR involving the anterior leaflet or both leaflets in whom a successful and durable repair can be accomplished, mitral valve repair is recommended in preference to mitral valve replacement.
●When surgical treatment is indicated for patients with rheumatic mitral valve disease, mitral valve replacement is frequently required. Mitral valve repair should be limited to patients with disease amenable to durable repair or when the risk of attempting long-term anticoagulation for a mechanical mitral valve is deemed to outweigh the risk of unsuccessful valve repair.
In settings in which mitral valve repair is recommended, mitral valve surgery involves mitral valve repair, assessment of the success of the repair, and if the repair is deemed inadequate, conversion to mitral valve replacement.
Transcatheter mitral valve repair — For severely symptomatic patients (New York Heart Association class III to IV) despite optimal guideline-directed medical therapy with chronic severe primary MR (stage D) who have a reasonable life expectancy and favorable anatomy for transcatheter repair and have a prohibitive surgical risk because of severe comorbidities, we suggest percutaneous mitral valve repair. The efficacy and safety of this procedure is discussed separately. (See "Transcatheter mitral valve repair".)
Choice of valve — When mitral valve replacement is required, a choice is made between a mechanical or bioprosthetic valve. Mechanical valves have the disadvantage of requiring lifelong warfarin therapy, while bioprosthetic valves have the disadvantage of limited durability due to valve degeneration, particularly in patients under age 65. When valve replacement is necessary, choice of a bioprosthetic or mechanical valve is made by considering factors including valve durability, need for life-long anticoagulation with mechanical valves, and impact on overall mortality (table 6). (See "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement" and "Diagnosis of mechanical prosthetic valve thrombosis or obstruction".)
MANAGEMENT OF CONCURRENT CONDITIONS — Patients requiring mitral valve intervention frequently have concurrent conditions that may be addressed at the time of mitral valve surgery. These include coronary artery disease, significant tricuspid regurgitation, and management of atrial fibrillation. These issues are discussed separately. (See "Surgical procedures for severe chronic mitral regurgitation" and "Atrial fibrillation: Surgical ablation".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Mitral regurgitation (The Basics)")
●Beyond the Basics topic (see "Patient education: Mitral regurgitation (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Staging – Staging of primary mitral regurgitation (MR) is based upon symptoms, valve anatomy, valve hemodynamics (severity of MR), and hemodynamic consequences of MR as reflected by left atrial size, left ventricular (LV) size and function, and pulmonary artery pressure (table 3). (See 'Staging' above.)
●Monitoring – The frequency of transthoracic echocardiographic monitoring in patients with MR varies with the severity of MR and the clinical evaluation. (See 'Monitoring' above.)
●Indications for intervention
•For symptomatic patients – For symptomatic patients with chronic severe primary MR (stage D), we recommend mitral valve intervention (Grade 1B). The intervention (surgery or transcatheter) should be performed as soon as symptoms develop. (See 'For symptomatic patients' above and 'Overview of evidence' above and 'Symptoms' above.)
•For asymptomatic patients:
-Concomitant with other cardiac surgery – For asymptomatic patients with chronic severe primary MR undergoing cardiac surgery for other indications, we recommend concomitant mitral valve surgery (Grade 1B). (See 'Concomitant cardiac surgery' above.)
-Reduced left ventricular function – For asymptomatic patients with chronic severe primary MR and an LVEF ≤60 percent and/or an LVESD ≥40 mm (stage C2), we recommend mitral valve surgery (Grade 1B). (See 'For asymptomatic patients' above and 'Reduced left ventricular function' above.)
-Excellent candidates for mitral valve repair – For asymptomatic patients with severe MR and preserved LV function (LVEF >60 percent and LVESD <40 mm) who are deemed excellent candidates (with likelihood of surgical repair without residual MR >95 percent and expected mortality rate of <1 percent), we suggest surgical mitral valve repair (Grade 2B). (See 'Impact of timing of surgery' above and 'For asymptomatic patients' above and "Surgical procedures for severe chronic mitral regurgitation", section on 'Valve repair versus valve replacement'.)
-Progressive LV changes – For asymptomatic patients with severe MR (stage C1) and preserved LV function (LVEF >60 percent and LVESD <40 mm) with progressive increase in LV size or decrease in LVEF on at least three serial imaging studies, we suggest mitral valve repair (Grade 2C).
●Choice of procedure
•Surgical repair versus replacement – For patients with severe primary MR with an indication for intervention with expected successful and durable repair, we suggest surgical mitral valve repair rather than valve replacement (Grade 2C). The decision on whether to attempt mitral valve repair is based upon the specific valve lesion and the surgeon’s experience. (See 'Surgical mitral valve repair versus replacement' above.)
A surgical mitral valve repair procedure involves repair of the valve, assessment of the success of the repair, and if the repair is deemed inadequate, conversion to mitral valve replacement. (See 'Surgical mitral valve repair versus replacement' above.)
•High or prohibitive surgical risk – For patients with high or prohibitive surgical risk because of severe comorbidities who are severely symptomatic (New York Heart Association class III to IV) despite optimal guideline-directed medical therapy with chronic severe primary MR (stage D) and who have a life expectancy of at least one year and favorable anatomy for transcatheter repair, we suggest transcatheter edge-to-edge mitral valve repair (Grade 2C). The efficacy and safety of this procedure is discussed separately. (See "Transcatheter mitral valve repair".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William H Gaasch, MD (deceased), who contributed to an earlier version of this topic review.
