Surgery in severe mitral regurgitation: focus on patients with no symptoms or complications

Background

Mitral valve (MV) repair is optimal surgical treatment for severe degenerative mitral regurgitation (MR) (1). The ESC guidelines on valvular heart disease (2012) recommend MV repair in symptomatic severe degenerative MR and in cases of initial signs of left ventricular (LV) dilatation or dysfunction - end-systolic diameter ≥45 mm (2) or ≥40 mm (ACC/AHA 2006 guidelines) - (3) and/or ejection fraction <60% (class I).
Asymptomatic patients with preserved LV function, in presence of atrial fibrillation (AF) and/or pulmonary hypertension (PHT) (SPAP>50 mmHg at rest) (class IIa) as well as pulmonary induced hypertension with exercise (SPAP >60 mmHg) are indicated for MV repair as well (class IIa) (3). Left ventricular dysfunction/dilatation (4-5), PHT (6) and AF (7) are each a predictor of poor outcome under medical management and are triggers to prompt surgery without further delay, even if actual repair is unlikely. 
Patients who are asymptomatic and free from mitral regurgitation however, can be the object of either a "wait and see" (watchful waiting) approach or an "early repair" strategy according to the specific factors that we present in this review.

I - Deciding on valve repair

Asymptomatic patients with severe degenerative MR under the "wait and see" approach receive regular clinical and echocardiographic exams and are sent for surgery as soon as symptoms of LV dilatation/dysfunction, PHT or recurrent AF develop. Rosenhek and co-workers (8) demonstrated that close follow-up (every 3-12 months) in experienced hands with prompt surgical referral offer survival rates that are no significantly different than those yielded from early repair. Other groups nevertheless have challenged the safety of this approach (9-13). Montant demonstrated that the overall outcome of asymptomatic patients with severe degenerative MR is more favorable with an early surgery approach than regular and close (at least once a year) outpatient follow-ups for timely referral.
The rationale behind early repair in these instances is to treat severe MR before pathological changes have occurred thus preserving patients in a state of normal ventricular and atrial chambers, normal rhythm (i.e. no persistent or permanent disturbances) and good long-term valve function, the aim being to ultimately ensure a survival rate and quality of life identical to the matched population. Thus, mitral repair is performed in asymptomatic patients well before the development of symptoms, LV dysfunction, AF or PHT in many referral centers.
Early repair, nevertheless, is to be considered only if the surgical risk is very low and the likelihood of a successful valve repair is very high (greater than 90%) (2,3). Today's excellence centers in reconstructive mitral surgery are able to provide a repair rate above 95% (14-18), a hospital mortality below 1% (19-24) and very satisfactory long-term outcomes (11,20-23,25). In these centers, freedom from reoperation is >90% at 10 years (18,20-22,25,26) and >80 % at 20 years (21,25). Long-term survival and quality of life are rigorously identical to that of the matched general population (13,27). The vast majority of cardiac surgery units however uncommonly offer the possibility of mitral repair to patients with potentially reparable valves. In these units, these potential candidates for repair receive valve replacement instead. 

II - Early markers of initial MR decompensation 

Several silent pathological alterations may occur in patients with severe MR before the occurrence of the classic I or IIa indications for surgery. Even under medical management, the severity of MR itself (28), dilatation of the left atrium (volume index ≥ 60 ml/m²) (29), elevated BNP levels (30), reduced functional capacity (31) and exercise induced pulmonary hypertension (≥60 mm Hg) (32) are associated with significant risk.
Indeed, patients with a left atrial volume index ≥ 60 ml/m2 experience more cardiac events and higher mortality compared to the normal population or patients with MR and lower LA enlargement (29). Similarly, the occurrence of exercise pulmonary hypertension (≥60 mm Hg) is associated with an event-free survival rate of 35%±8% at 2 years compared with 75%±7% for patients without exercise pulmonary hypertension. Reduced functional capacity (<84% than expected) in patients with severe MR who are otherwise completely asymptomatic has also been shown to be associated with a higher rate of cardiac events or need for surgery. High brain natriuretic peptide (BNP) levels in asymptomatic patients with severe MR were shown to be associated with a significantly increased rate of congestive heart failure episodes, LV dysfunction and death (30-32). Those markers, therefore, may help in the risk stratification process of patients and should be considered triggers for earlier surgical valve repair. Interestingly, they do not seem to expose the patients to excess postoperative risk. This means that, as demonstrated for some of them, restoration of life expectancy can be obtained without increased postoperative mortality if surgery is promptly performed (33). 
The European guidelines recommend that early surgery be considered, if the surgical risk is low and the likelihood of a durable repair very high, in case of flail leaflet and LVESD ≥40 mm (IIa) and may be considered in presence of exercise induced SPAP > 60 mmHg and/or severe left atrial dilatation (volume index ≥60 ml/m2 BSA) (IIb). 

Conclusions 

In presence of low surgical risk and high probability of durable repair, early surgery may represent the preferred approach, particularly in advanced repair centers. This strategy can avoid leaving the patient with the irreversible consequences of the adverse changes in cardiac structure and function associated with the complications of MR. 
Furthermore, dilatation of the left atrium (volume index ≥ 60 ml/m²), elevated BNP levels, reduced functional capacity and exercise induced pulmonary hypertension (≥60 mm Hg) are markers that may help in the risk stratification process of patients and should be considered triggers for earlier surgical valve repair. 
Nevertheless, a watchful waiting approach should probably be preferred in case of high surgical risk (elderly patients with relevant comorbidities) and/or low probability of durable repair (complex valve lesions/insufficient surgical expertise). 
Until high-quality valve repair surgery becomes widespread, an early repair strategy cannot be generally adopted and should be limited to the relatively small number of referral centers with proven expertise in mitral repair surgery.