Mitral valve (MV) repair is now the treatment of choice for surgical correction of primary (degenerative) mitral regurgitation (MR). The improvements in repair surgery, and its increasingly widespread use instead of valve replacement, have made surgical intervention earlier in the course of MR a more realistic prospect. Nevertheless, the timing of surgery in MR in asymptomatic patients remains controversial.
Mitral valve repair vs replacement
The benefits of MV repair over replacement are undeniable. Compared with valve replacement, repair provides lower peri-operative morbidity and mortality, better post-operative left ventricular (LV) function, the avoidance of life-long anticoagulation (in the absence of concomitant atrial fibrillation (AF)) and lower risk of infective endocarditis or need for repeat surgery.
The complexity of surgery varies according to the underlying pathology: isolated prolapse of the posterior leaflet is generally amenable to simple quadrangular resection, whereas anterior or bileaflet disease requires more sophisticated techniques. Specialist training is therefore required, though with further development of surgical expertise in more centres the trend towards increased repair surgery will continue. Cardiologists should be aware of which lesions are repairable and, in the best interests of their patients, should ensure referral to an appropriate surgeon.
Why timing of surgery is complex – the pathophysiology of MR
The decision of when to proceed to surgery in MR depends primarily on the effects of volume overload on left ventricular (LV) function and on the patient’s symptoms. With chronic MR, the LV initially undergoes a period of adaptive remodeling to accommodate the increased volume load. During this time, MV surgery has the potential to restore normal LV function and survival. However, at a poorly-defined and unpredictable point, the LV begins to decompensate. Surgery beyond this point can lead to irreversible post-operative LV dysfunction. Whilst the onset of symptoms is a clear indication for surgery, the timing of surgery in asymptomatic patients presents several difficulties:
(1) There may be a long symptom-free period
(2) LV dysfunction may often precede the onset of symptoms due to adaptation of the LV and left atrium (LA)
(3) There is no simple non-invasive load-independent measure of LV contractility. Measures such as ejection fraction (EF) are load-dependent and the increased preload may enhance EF despite a subtle decrease in contractility. By the time EF is low, there may already have been irreversible damage.
Of course, other factors must be taken into account in deciding upon surgical intervention (in addition to symptoms and LV function):
(1) Patient’s wishes, surgical risk and comorbidities (particularly the requirement for CABG at the time of MV surgery)
(2) Surgical expertise and valve anatomy (repair of the posterior leaflet has a higher success rate than of the anterior leaflet or where both leaflets are involved)
(3) Pulmonary artery pressure
(4) The presence of AF
When to proceed to surgery in asymptomatic patients – updated American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) guidelines
The ACC/AHA guidelines were updated in 2006 [1] and recommend surgery in asymptomatic patients with chronic severe MR when the EF is <60% and/or the end-systolic dimension (ESD) is ≥40mm. The ESC guidelines from 2007 [2] differ in recommending an ESD of >45mm.
Furthermore, the ACC/AHA guidelines suggest that “MV repair is recommended over MV replacement in the majority of patients with severe chronic MR who require surgery, and patients should be referred to surgical centers experienced in MV repair.”
However, in those patients with severe primary MR who are asymptomatic, but who do not yet meet the above echocardiographic criteria, the timing of surgery remains a difficult issue. There is conflicting evidence for and against early surgery, but importantly there has been no randomised controlled trial to compare early surgery with a more conservative approach.
In favour of early surgery
In 1997, Ling et al. reviewed 221 patients with flail leaflets diagnosed on echocardiography between 1980 and 1989 [3]. 63 of these patients had early surgery (within one month of diagnosis) whilst the other 158 were initially treated conservatively (80 of these 158 later had surgery). The early surgery group was significantly younger, more symptomatic and had a greater frequency of AF than the conservative group. The EF was not significantly different between the two groups.
In this study, early surgery was associated with an improved survival rate, a lower incidence of cardiovascular death, congestive heart failure and new AF. The authors concluded that “early surgery is a reasonable treatment option to be considered in low-risk candidates with repairable valves and severe MR.”
Further support for early surgery was provided by a study of 456 patients by Enriquez-Sarano et al. in 2005 [4]. These patients were asymptomatic and the severity of MR was quantified using regurgitant volume and effective regurgitant orifice (ERO). They showed that those with an ERO>40mm2 had a reduced 5 year survival. 230 patients eventually underwent mitral surgery (of whom 209 had valve repair) and this was independently associated with improved survival.
Based on these studies, the 2006 ACC/AHA guidelines suggest that “MV repair is reasonable in experienced surgical centers for asymptomatic patients with chronic severe MR with preserved LV function (EF>60% and ESD< 40mm) in whom the likelihood of successful repair without residual MR is greater than 90%.” The strength of their recommendation is IIa (weight of evidence/opinion is in favour of usefulness/efficacy).
The ESC guidelines are less favourable about early surgery in “asymptomatic patients with preserved LV function, high likelihood of durable repair, and low risk for surgery”, suggesting that “usefulness/efficacy is less well established by evidence/opinion” (Class IIb recommendation).
In favour of "watchful waiting"
A study by Rosenhek et al. in 2006 assessed the outcome of "watchful waiting" in 132 asymptomatic patients with severe degenerative MR. Patients were followed-up over 5 years with serial clinical and echocardiographic assessment. Patients were referred for surgery when they became symptomatic, or developed LV enlargement/dysfunction (EF<60% and/or ESD>45mm [previous ACC/AHA guidelines from 1998]), pulmonary hypertension or recurrent AF. 38 patients met the criteria for surgery during the follow-up period. They showed that overall survival was not significantly different from expected survival and that the most common indication for surgery was symptomatic deterioration rather than LV enlargement/dysfunction. The authors therefore suggested that there is no need for early surgery in most patients and that adherence to the previous ACC/AHA guidelines (combined with careful follow-up) is associated with good outcome.
The additional concern about early intervention with valve repair is the potential for failure and consequent need for a prosthetic valve. This would expose a patient, who did not previously require a prosthesis, to the significant risks of valve replacement. Committing a patient to the lifelong risks of anticoagulation, thromboembolic stroke and prosthetic valve endocarditis is clearly a significant consideration and the potential for failure must form part of the discussion before attempted valve repair.
Future prospects
Percutaneous MV repair is an exciting and rapidly developing area. Although the feasibility of valve repair in the elderly has been confirmed in one recent series, [6] many patients in this group have other significant comorbidities that preclude open heart surgery. Techniques for percutaneous annuloplasty and leaflet repair are being developed, and, whilst still in their infancy, early human studies have been encouraging with reduction in MR in a significant number of patients at 6 months [7]. Ongoing trials will assess long-term safety and durability and guide suitable patient selection.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
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