Primary MR disease stages

As with aortic stenosis, the concept of disease stages can be applied to patients with chronic primary MR to better aid the clinician in timing of operation (table 1). Stages A and B include patients at risk and asymptomatic patients with less than severe valve regurgitation. Stage C encompasses patients who meet criteria for ‘severe MR’ but remain asymptomatic. The new definition of ‘severe’ MR is based on integration of multiple parameters, including valve anatomy, regurgitant severity, LV size and systolic function and other consequences of chronic volume overload, such as pulmonary hypertension and atrial fibrillation. An effective orifice area of 0.4 cm² or greater was defined as severe MR because natural history studies have demonstrated poor clinical outcomes in patients with this degree of valve regurgitation.

Asymptomatic patients with severe MR are divided into two groups based on LV systolic function: stage C-1 indicates normal LV systolic function, whereas patients in stage C-2 have evidence of early LV systolic dysfunction. Evaluation of LV systolic function is challenging in patients with MR due to altered LV loading conditions, which means that significant contractile dysfunction may occur with apparently normal LV systolic performance. Numerous studies of outcomes after mitral valve surgery for severe MR have demonstrated poorer clinical outcomes and a postoperative depression in EF in patients with a preoperative EF ≤60% or end-systolic dimension (ESD) ≥40 mm. Therefore, these breakpoints were used to define LV systolic dysfunction and as indicators for intervention in the new guidelines. Stage D encompasses all patients with severe MR and symptoms due to valve regurgitation. As in previous guidelines, severe symptomatic MR is an indication for surgical intervention.

Intervention for primary MR

The threshold for valve surgery for patients with primary MR continues to be lowered to prevent the adverse consequences of long-standing volume overload (table 2). In asymptomatic patients, decisions on timing of intervention is made primarily on the basis of (1) LV size and function and (2) quantitative evaluation of the severity of MR. Thus, accurate measurements of the status of the LV, as well as the degree of MR, are essential for clinical decision making. These guidelines emphasise the need to assure quality control for a comprehensive imaging and Doppler echocardiogram performed by experienced laboratories with the competence to obtain not only conventional data but also the ability to perform accurate and reproducible quantitative measurements of MR severity, including the use of proximal isovelocity surface area measurements for calculation of effective orifice area, regurgitant fraction and regurgitant volume. There continues to be a need for invasive haemodynamic studies in the subset of patients in whom the clinical evaluation is discordant with the non-invasive evaluation. As with the echocardiogram, a haemodynamic invasive evaluation, including right heart catheterisation and left ventriculography, should be performed by experienced operators when this information is needed for clinical decision making.

The long-standing volume overload of MR causes gradual LV dilatation with eventual LV systolic dysfunction. LV systolic dysfunction may occur in the absence of symptoms but may also be present when conventional measurements of LV systolic performance are still ‘within normal limits’. Surgical mitral valve repair for primary MR has a low operative mortality and excellent long-term outcomes. Thus, earlier intervention is recommended for surgical valve repair for primary MR based on two criteria: (1) the presence of severe MR and (2) a high probability of a successful durable repair with low operative mortality. Unfortunately, although the rates of mitral valve repair have been increasing across all cardiac centres, many patients with a repairable valve continue to receive a mitral valve prosthesis for primary MR. Although most competent cardiovascular surgeons can perform a successful repair with an isolated posterior leaflet abnormality, the presence of bileaflet or severe anterior leaflet abnormalities requires a more complex surgical approach. Thus, achieving a successful durable repair may require sending patients to ‘valve centres of excellence’, in which there is a team of experienced cardiologists, imaging specialists and cardiovascular surgeons who have expertise in the area of mitral valve disease. In these centres of excellence, successful mitral valve repair is associated with better outcomes compared with mitral valve replacement. In addition, particularly in patients with a partial flail leaflet, early mitral valve repair is associated with better long-term outcomes than ‘watchful waiting’.3

Secondary MR

An important concept in these new guidelines is the differentiation of patients with primary MR (regurgitation due to an abnormality of the mitral valve leaflet) from secondary MR (regurgitation due to altered LV geometry as a consequence of ischaemic disease or dilated cardiomyopathy). Primary and secondary MR are two separate diseases with differences in aetiology, classification and treatment (table 3).

In patients with secondary MR, the LV is abnormal, not the mitral valve. Conventional measurements of LV size and function cannot be applied to patients with secondary MR because LV dysfunction is decreased due to a primary abnormality of the LV myocardium with progressive volume overload being exacerbated by superimposed MR. In these patients, adverse remodelling of the LV is likely to progress despite interventions on the mitral valve. In addition, it has been shown that a poor prognosis is associated with a smaller effective orifice area (0.2 cm²) in patients with secondary, as compared with primary, MR. A recent randomised trial compared the outcome of patients with severe ischaemic MR undergoing mitral valve repair versus mitral valve replacement.4 The 1-year mortality rate was high and similar in both groups (approximately 15%). At least moderately severe MR recurred in over 30% in the mitral valve repair group, indicating that a successful durable repair for secondary MR is much more difficult to achieve than with primary MR. Taken together, the published evidence on outcomes and treatment effects for secondary MR led to the recommendation that surgical intervention should be considered only if the patient continues to be severely symptomatic despite optimal guideline-directed medical therapy for coronary disease and heart failure, including biventricular pacing if indicated.

Transcatheter repair of severe MR now may be considered in patients with severe primary MR, but only in those patients who are at high or prohibitive risk for operation. Data are still pending to determine the ultimate role of transcatheter repair for patients with secondary MR with randomised prospective trials currently in progress.

Comparison with ESC guidelines

The ACC/AHA guidelines and the ESC/EACTS Guidelines on Valvular Heart Disease now are largely concordant with respect to the recommendations for intervention for MR5 (Table 3). Minor differences include (1) a lower cut-off of LV ESD for the definition of LV systolic dysfunction (ESD 40 mm vs 45 mm) for recommending valve repair in the asymptomatic patient, (2) a greater emphasis on the necessity of accomplishing a durable repair if atrial fibrillation or resting pulmonary hypertension are considered in the decision to operate and (3) a lower class recommendation for mitral surgery for patients with EF <30%. However, both documents clearly indicate that a paradigm shift is occurring in the timing of intervention for patients with chronic MR. The combination of improved imaging for evaluation of valve anatomy and measurement of regurgitant severity, a better understanding of the natural history of chronic MR, improved outcomes with surgical valve repair and new transcatheter therapies all have led to recommendations that continue to move the timing of intervention earlier in the disease course with the goal of preventing irreversible LV dysfunction, arrhythmias and pulmonary hypertension due to long-standing LV volume overload.