In patients who have asymptomatic or minimally symptomatic mitral valve regurgitation as a result of flail mitral leaflets, early surgery yields markedly better survival, lower risk of heart failure, and equivalent rates of atrial fibrillation, compared with watchful waiting, according to a report published online August 13 in JAMA.

Overall long-term mortality is approximately 40% lower and HF risk is approximately 60% lower for early surgery than for watchful waiting. Moreover, these benefits persist for up to 20 years and are seen across every important subgroup of patients, said Dr. Rakesh M. Suri of the Mayo Clinic, Rochester, Minn., and his associates.

These are the findings of a series of analyses of data from an international registry of consecutive patients diagnosed in routine clinical practice – the largest study in the world of the comparative effectiveness of early surgery vs. watchful waiting in patients without traditional indications for immediate surgery. The study results "emanate from institutions that together provide a very high rate of mitral valve repair (more than 90%) with low operative mortality, emphasizing that such results might also be achieved in routine practice at many advanced repair centers," the investigators noted.

Despite the safety and efficacy of current surgical correction of flail mitral leaflets, clinicians disagree as to the best approach for patients who have no or minimal HF symptoms, a left ventricular ejection fraction of 60% or more, and a left ventricular end-systolic diameter of 40 mm or more. Those who support watchful waiting consider the consequences of uncorrected mitral regurgitation to be benign, especially when weighed against the potential morbidity and mortality of early surgical intervention. In particular, North American guidelines favor early surgery while European guidelines favor watchful waiting.

The Mitral Regurgitation International Database (MIDA) – a registry of patients at two tertiary care centers in France, two in Italy, one in Belgium, and one in the United States – provided an ideal study population to compare the two approaches. For their study, Dr. Suri and his associates examined data for 1,021 of these patients who had been diagnosed in 1980-2004 and followed for up to 25 years (mean follow-up, 10.3 years).

This study included only patients who had no ischemic mitral regurgitation and no significant concomitant aortic valve disease, congenital heart disease, mitral stenosis, or previous valve surgery.

A total of 446 of these patients underwent early surgery (within 30 days of diagnosis) and 575 had watchful waiting at the discretion of their treating physicians. Importantly, 339 (59%) of the watchful-waiting group eventually were advised by their cardiologists to undergo valve repair, at a median of 1.65 years after diagnosis.

Overall, there were 319 deaths during follow-up.

The primary end points of this study were all-cause mortality at 5, 10, and 20 years.

In the initial, unadjusted analysis, survival was 95%, 86%, and 63%, respectively, with early surgery. In contrast, survival was significantly lower with watchful waiting, at 84% at 5 years, 69% at 10 years, and 41% at 20 years, the researchers said (JAMA 2013; 310:609-16 [doi:10.1001/jama.2013.8643]).

The large survival benefit with early surgery was confirmed in a multivariable analysis that adjusted for patient age, sex, comorbidities, and the presence of subtle symptoms.

To account for differences between the two study groups in the propensity to undergo surgery, the investigators performed an analysis of the data in a set of 648 patients who were matched for age, comorbidities, and other factors. This analysis also showed a similar and distinct survival advantage with early surgery. Several subgroup analyses also confirmed the results.

Secondary end points were the incidence of heart failure and the onset of new atrial fibrillation during follow-up.

A total of 167 patients had at least one episode of HF. The rates were 7% with early surgery and 23% with watchful waiting at 10 years, and 10% vs. 35% at 20 years, showing a clear advantage for early surgery.

This strong advantage persisted in further analyses of the propensity-matched patients and in all other subgroups examined, at all time points examined.

New-onset AF developed in 227 patients overall. The rate was slightly higher in the early-surgery group during the immediate postoperative period but decreased thereafter and was equivalent between the two study groups at 5, 10, and 20 years.

"Long-term, the results are coherent by all methods used (direct comparison, adjusted comparison, propensity score matching, inverse probability weighing) that early surgical correction of mitral valve regurgitation was associated with a significant survival benefit (total mortality decrement of approximately 40%) and diminished HF risk (reduction of approximately 60%)," Dr. Suri and his associates wrote.

Dr. Suri reported ties to Edwards Lifesciences, Sorin Group, St. Jude Medical, and Abbott. His associates reported ties to Edwards Lifesciences, Valtech, and Abbott Vascular.

Early surgery vs. watchful waiting for flail mitral leaflets