Fewer endpoint events at two years when mitral and tricuspid repair combined

For adults with mitral valve regurgitation that requires surgical repair who also have a moderate leak of the tricuspid valve, a twofer approach to surgery may yield the best outcome, according to James S. Gammie, MD, of the division of cardiac surgery at Johns Hopkins School of Medicine, and co-investigators for the Cardiothoracic Surgical Trials Network (CTSN).

Gammie reported findings from a study of 401 patients who underwent mitral valve repair with or without concurrent repair of the tricuspid valve as a late-breaking science presentation at the American Heart Association’s 2021 virtual meeting.

The trial findings were simultaneously published in The New England Journal of Medicine.

“While there is general agreement that a severely leaky tricuspid valve should be fixed when a surgeon is operating on the mitral valve, there is considerable uncertainty as to whether to fix the tricuspid valve when the leakage is only moderate or less,” Gammie said in a prepared statement. “Repairing the tricuspid valve may confer benefit by preventing the development of significant leakage over time, which can cause damage to the heart. There are also potential disadvantages. The operation will take longer, which could increase complications and risk, and tricuspid valve repair increases the risk of patients needing a permanent pacemaker. Contemporary practice patterns are quite varied and reflect this uncertainty.”

The study, which was conducted at 39 centers in the U.S., Canada, and Germany from 2016 to 2018, recruited 401 patients with severe mitral valve regurgitation and mild or moderate tricuspid regurgitation. Just over half of the patients (n= 203) had only mitral valve repair, and 198 had mitral valve repair plus tricuspid annuloplasty (TA). Most of the patients were men (75%), average age 67, and almost all (91%) were White. “The primary 2-year end point was a composite of reoperation for tricuspid regurgitation, progression of tricuspid regurgitation by two grades from baseline or the presence of severe tricuspid regurgitation, or death.”

“Patients who underwent mitral-valve surgery plus TA had fewer primary-end-point events than those who underwent mitral-valve surgery alone (3.9% versus 10.2%) (relative risk, 0.37; 95% confidence interval [CI], 0.16-0.86; P=0.02). Two-year mortality was 3.2% in the surgery-plus-TA group and 4.5% in the surgery-alone group (relative risk, 0.69; 95% CI, 0.25-1.88). The 2-year prevalence of progression of tricuspid regurgitation was lower in the surgery-plus-TA group than in the surgery-alone group (0.6% versus 6.1%; relative risk, 0.09; 95% CI, 0.01-0.69). The frequencies of major adverse cardiac and cerebrovascular events, functional status, and quality of life were similar in the two groups at 2 years, although the incidence of permanent pacemaker implantation was higher in the surgery-plus-TA group than in the surgery-alone group (14.1% versus 2.5%; rate ratio, 5.75; 95% CI, 2.27-14.60),” Gammie and colleagues wrote.

The addition of tricuspid valve repair to the mitral valve surgery did prolong the amount of time patients spent on the heart-lung machine by 34 minutes.

In an editorial published with the study, Joanna Chikwe, MD, of the department of cardiac surgery at the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles, and Mario Gaudino, MD, of the department of cardiothoracic surgery at Weill Cornell Medicine in New York, applauded the trial findings as “timely and welcome.”

Chikwe and Gaudino noted that the difference in the primary end point “was driven by progression to severe tricuspid regurgitation, which occurred less often in patients who underwent TA (0.6% versus 5.6%). However, more permanent pacemakers were implanted after TA (14.1% versus 2.5%). Essentially, concomitant TA during mitral surgery in 20 patients prevented severe tricuspid regurgitation in about 1 patient, at the price of permanent pacemaker implantation in approximately 2 patients over 2 years. The planned 5-year follow-up may better delineate the clinical effect of severe tricuspid regurgitation after isolated mitral surgery, as compared with pacemaker placement after concomitant TA.”

About one in four patients who had only mitral valve repair had moderate or severe tricuspid regurgitation at two years, but at the same time, “we observed similar incidences of NYHA class III or IV heart failure (2.8% in the surgery-alone group and 1.1% in the surgery-plus-TA group), as compared with incidences of 33.5% and 26.9%, respectively, at baseline. Overall summary scores for quality of life on the KCCQ, the SF-12 physical and mental health scores, and scores on the EQ-5D and 6-minute walk test were also similar in the two groups. Notably, the 2-year KCCQ scores showed average increases from baseline in both groups that were indicative of clinical improvement that was ’large to very large.’ Readmission rates, including for cardiovascular and heart-failure events, were also similar in the two groups,” Gammie and colleagues wrote.

The trial had a number of limitations, including a failure to meet targets for recruiting a diverse population, as well as a composite primary endpoint that included both clinical and echocardographic outcomes. Finally, “measuring the primary end point at 24 months may not fully capture the clinical effect of progression of tricuspid regurgitation or permanent pacemaker implantation over time.”

Gammie noted that follow-up through five years is ongoing.

Gammie and colleagues acknowledged that although the trial was “not powered to analyze the primary end point according to the severity of tricuspid regurgitation at baseline, in a post hoc analysis, we found that the progression of tricuspid regurgitation occurred almost exclusively in patients with moderate tricuspid regurgitation at baseline and not in those with less-than-moderate regurgitation with annular dilatation. This observation calls into question reliance on the measurement of the tricuspid annular diameter to inform surgical decision making in patients with less-than-moderate tricuspid regurgitation—a question that can be answered only with additional research over a longer time period.”

  1. In a multicenter randomized trial among patients who had severe mitral-valve regurgitation and mild to moderate tricuspid valve regurgitation, combining mitral valve repair with tricuspid annuloplasty improved outcomes.

  2. Note that difference in primary endpoint was driven by progression to severe tricuspid regurgitation, which occurred less often in patients who underwent TA (0.6% versus 5.6%).

Peggy Peck, Editor-in-Chief, BreakingMED™

Supported by a cooperative agreement with the National Heart, Lung, and Blood Institute and a grant from the German Center for Cardiovascular Research.

Gammie disclosed a consultant agreement with and stock ownership in Edwards Lifesciences.

Chikwe served as Co-PI / Study Director of NCT 05051033 (a NHLBI sponsored CTSN trial of surgical versus transcatheter repair of primary MR) I collaborate with several of the study authors.

Gaudino reported grants from NIH/NHLBI outside the submitted work.

Cat ID: 232

Topic ID: 74,232,730,232,914,192,925,492,231