Severe Mitral Regurgitation: A Primer for Clinicians

Abstracts & Commentary

By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque. Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis.

Synopsis: Asymptomatic patients with severe degenerative mitral regurgitation can be safely followed up until either symptoms occur or currently recommended cutoff values for LV size, LV function, or pulmonary hypertension are reached.

Sources: Rosenhek R, et al. Outcome of Watchful Waiting in Asymptomatic Severe Mitral Regurgitation. Circulation. 2006;113:2238-2244; Griffin BP. Timing of Surgical Intervention in Chronic Mitral Regurgitation: Is Vigilance Enough? Circulation. 2006;113:2169-2172.

Severe mitral regurgitation (MR) has long fascinated cardiovascular physicians. Issues as to left ventricular (LV) responses to volume overload, the role of the left atrium in modulating the degree of symptoms (if any), and the functions of the complex mitral valve apparatus have been discussed in the literature for decades. The most common cause of MR is myxomatous or degenerative, often with a flail mitral leaflet contributing to the degree of MR. Individuals with mitral valve prolapse physiology may have a disproportionate amount of blood flow into the left atrium during the second half of systole, as the LV gets smaller and the chordal apparatus cannot maintain leaflet coaptation. The Mayo Clinic group has made significant contributions about when to intervene in severe MR, how to treat asymptomatic MR, and whether it is better to repair the valve rather than replace it.

This report from the Medical University of Vienna is a significant contribution to the question of timing of intervention in severe MR. Rosenhek and colleagues utilized a number of parameters that should influence the decision for mitral valve surgery, even in asymptomatic patients. In the absence of such features, a policy of watchful waiting is appropriate and safe. Rosenhek et al emphasize that the markers for favoring surgery are compatible with current surgical guidelines in MR patients with mild symptoms or who are asymptomatic. These include impaired left ventricular systolic dysfunction, pulmonary hypertension, or atrial fibrillation. Left ventricular enlargement and ejection fraction (EF) are also parameters demanding close scrutiny.

Rosenhek et al studied a group of 132 asymptomatic patients with severe degenerative mitral regurgitation (flail leaflet or valve prolapse) for 5 years on average. All patients underwent serial clinical and echo examinations. Surgical referral occurred when one or more markers of poor prognosis (see above) were present. The mean age of the study group was 55 ± 15 years, with the usual male preponderance (49 females, 73 males). Patients were referred for surgery when clinical or echo criteria were met. Rosenhek et al emphasized their adherence to current practice guidelines; criteria for non-intervention included normal LV function, asymptomatic status, ejection fraction > 60, systolic LV diameter < 45 mm, and systolic pulmonary artery pressure < 50 mm Hg.

In addition, patients had to be in sinus rhythm. A variety of sophisticated echo parameters were employed in "an integrated approach that included valve morphology, LV volume load, proximal regurgitant jet width, proximal flow convergence, and pulmonary venous flow pattern." Patients underwent repeated echocardiography every 12 months, or every 3-6 months for those first entering into the cohort or thought to be unstable. Referral to surgery took place with the onset of symptoms, even mild, or if patients developed one or more of the parameters previously listed. The Kaplan-Meier method was used to assess overall and event-free survival; the cohort was compared to the age and gender-specific annual mortality rates in the Austrian population. Patients with flail leaflets were analyzed separately, but there were no differences in the outcomes. Median follow-up was approximately 69 months. There were 8 deaths overall, resulting in overall survival of 99% at 2 years, 96% at 4 years, and 91% at 8 years. Survival was comparable to that expected in the general population.

During the study period, 38 patients developed one or more criteria leading to surgery. These included atrial fibrillation, pulmonary hypertension, and LV dysfunction, but were relatively rare. Survival, free of any indication for surgery, was 92% at 2 years, 78% at 4 years, 65% at 6 years, and 55% at 8 years. Of the 38 patients who developed criteria for surgical intervention, 24 underwent mitral valve surgery. Survival, free of indications for surgery in flail and prolapse patients, was similar, although flail patients did require a greater number of surgical interventions. Surgery in the majority was mitral valve repair. There was no surgical mortality. All patients had good functional status; 23 asymptomatic and 12 with mild symptoms only.

Rosenhek et al conclude that their study is the first "to provide prospective outcome data on a specific treatment strategy." Their results were excellent in the individuals who received careful follow-up, with strict criteria for referral to surgery. Only 24% of the asymptomatic individuals had surgical indications. "Thus, development of symptoms appears to be the most frequent indication for surgery and precedes LV impairment in the majority of patients." The 91% overall survival at 8 years was similar to expected survival in the Austrian population. "These data, therefore, strongly support adherence to current practice guidelines instead of consideration of surgery in any asymptomatic patient with severe MR."

Rosenhek et al discuss a number of previous reports, emphasizing the Mayo Clinic publications, including a recent report that suggested that all asymptomatic patients with normal LV function, severe MR, and an effective regurgitant orifice area (ERO) > 40 mm2 had a cardiac mortality of 36% at 5 years and a cardiac event rate, including death, of 62%. The Viennese group believes that closer follow-up and referral to surgery using recommended criteria would obviate such poor outcomes. The authors emphasize the optimal choice of mitral valve repair over replacement, and stress that surgery is indicated when LV dysfunction and/or dilatation occur, even without symptoms. Patients with an EF of > 60% and no-to-mild symptoms have the best reported outcomes.

The American and European practice guidelines support surgery in asymptomatic patients when LV EF is < 60, ESD > 45, SPAP > 50, or when recurrent atrial fibrillation occurs. "The results of the present studies support adherence to current recommendations instead of consideration of elective surgery in all patients with severe MR." The final conclusion is that patients with severe MR should not be sent for prophylactic surgery if they are asymptomatic and have none of the findings that should trigger consideration of mitral valve repair or replacement. Finally, they stress the need for careful follow-up with serial echo examination performed by experienced individuals.

In an accompanying editorial by Dr. Griffin of the Cleveland Clinic, the pathophysiology of severe MR is reviewed, and mechanisms for abnormal contractile dysfunction are discussed. Griffin emphasizes the positive effects of beta blockade in animal models of severe MR, suggesting that catecholamine excess is a player in the development of intrinsic myocardial dysfunction. He also emphasizes that LV size, particularly end-systolic, is predictive of outcomes that are related to intrinsic LV contractility. Thus, patients can have normal ejection fraction and severe MR but still have normal LV contractile function. As with the Vienna group, Griffin emphasizes the preferred procedure of MV repair over prosthetic valve replacement; he points out that valve repair "is still not universally preformed in situations in which it is generally feasible." He also observes that surgeons have variable experience with this operation. He suggests that the high morbidity and mortality in the report of the Mayo Clinic cohort of 476 patients with chronic MR may be due in part to the fact that many of the patients did not have expert cardiology care. He also believes that surgical intervention should be entertained only when patients meet specific criteria. The Cleveland Clinic group has been using stress echo to help differentiate individuals who are candidates for watchful waiting. These include those with a reduction in end-systolic volume at peak exercise and an improvement in ejection fraction. Griffin stresses that the guidelines work well in patients who are closely followed by interested, expert physicians, and that it may be appropriate to intervene in selected patients. He concludes, "the price of maintaining normal left ventricular function and therefore survival in chronic asymptomatic MR is vigilance."

Commentary

Severe MR therapies have interested cardiologists for years, and remain somewhat unresolved. The Vienna paper and the editorial by Griffin emphasize that there are subtle differences between those who advocate surgery for all (eg, the Mayo Clinic) and those who advocate a more selective approach consonant with published guidelines. Actually, the differences between the 2 strategies are very minor, reflecting incremental alterations in left ventricular size and function that may be difficult to track on routine echoes every 6-18 months. The echocardiographic expertise at the Mayo and Cleveland clinics is certainly of very high quality, and it may be that such laboratories are better able to fine tune decisions about left ventricular contractility, as well as left ventricular and left atrium size.

Certainly, the degree of mitral regurgitation is critical in decision making; there are a number of techniques available. Those used by the Mayo Clinic may or may not be applicable to most echo labs. It may be difficult for clinicians to make a wrong decision in severe MR, particularly with an experienced surgeon who is willing and committed to doing mitral valve repair. Thus, intervention in asymptomatic patients has an excellent prognosis, both short and long term. By the same token, the approach of the Vienna group (withholding surgery unless one of the several markers of poor outcome are reached) works very well indeed, with remarkably low mortality both early and late. Mild symptoms would appear to favor early surgery, but it remains unclear what to do with patients with little impairment who do not meet any of the adverse parameters. The Mayo clinic would operate, the Cleveland clinic would not. What is certain is that this individual will ultimately be coming to mitral valve surgery done on a timely basis, and the procedure should be a repair rather than a replacement.