RIME: Mitral Annuloplasty Plus CABG Improves Functional Capacity, Regurgitation

LOS ANGELES, CA—Compared with coronary artery bypass grafting (CABG) alone, bypass surgery with mitral valve annuloplasty improves functional capacity and symptoms at 1 year in patients with moderate functional mitral regurgitation (MR). Results of the RIME trial, stopped early for evidence of benefit, were presented November 7, 2012, at the American Heart Association Scientific Sessions.

The findings were published simultaneously online in Circulation.

For the Randomized Ischemic Mitral Evaluation (RIME) trial, K.M. John Chan, FRCS CTh, of Imperial College London (London, UK), and colleagues analyzed 73 patients with moderate functional ischemic MR referred for elective CABG. The patients were randomized to undergo adjunctive mitral valve annuloplasty or CABG alone at 7 European centers. The trial was halted after an interim analysis revealed significant benefit with the combined therapy in 59 evaluable patients. 

Patients in the combined therapy arm required longer procedure time and increased blood transfusions as well as longer hospital stay (table 1).

Table 1. Periprocedural Outcomes (Median)

At 1 year, the primary endpoint of improvement in functional capacity (peak oxygen consumption, or VO₂) was greater in the combined therapy group. Improvements in LV reverse remodeling, MR, and BNP levels were also apparent with CABG plus annuloplasty (table 2).

Table 2. Change in 1-Year Outcomes

In addition, MR classifications were improved with the combined therapy at 1 year, with 74% of annuloplasty patients showing no MR vs. 9% of patients who received CABG alone. Similar results were shown for mild MR (22% vs. 41% of patients receiving CABG alone), moderate MR (4% vs. 41%), and moderate/severe MR (0 vs. 3%; P < 0.001 for overall trend).

In addition, combined therapy showed improved symptoms at 1 year (P = 0.03 for overall trend):

• NYHA I (76% vs. 21% with CABG alone)
• NYHA II (20% vs. 64%)
• NYHA III (4% vs. 15%)

In terms of hard clinical endpoints, 30-day mortality was similar between the 2 groups, at 3% in each arm. One-year survival was also equivalent (91% with combined therapy vs. 95% with CABG alone; P = 0.66). The same was true for hospital admissions for heart failure (3% vs. 8%; P = 0.62).

Dr. Chan noted that the study was not designed or powered to evaluate clinical endpoints and survival, and that longer follow-up is necessary to confirm the 1-year results. Nevertheless, based on the improvements shown with combined therapy, “concomitant CABG plus mitral valve annuloplasty should be considered in patients with moderate functional ischemic MR,” he concluded.

Is MR Repair Worth It?

Commenting on the trial, Michael H. Davidson, MD, of the University of Chicago Pritzker School of Medicine (Chicago, IL), noted that “there is no question that MR reduces survival in the setting of coronary disease. There is, however, unclear benefit to reversing mitral regurgitation despite what we know about the adverse effects of having [MR].”

He observed that studies have repeatedly failed to show clinical benefit in terms of survival or functional class from adding ring annuloplasty to bypass alone. Still, “as far as the [RIME] trial results, they clearly showed meaningful impact on some objective criteria.”

A key problem, though, is that by stopping the trial early, the researchers were unable to look at potential long-term safety effects related to blood transfusion, Dr. Davidson noted.

“Blood transfusions in cardiac surgery are an independent predictor of late mortality,” he said. “By stopping the trial early, have we missed the opportunity to see if there are meaningful differences in safety? As surgeons, that’s what it comes down to for our clinical decision-making. For a patient with moderate MR and multivessel coronary disease, the decision we have to make is, is it worth the added risk of the operation to add a ring versus doing the bypass alone?”

Unanswered Questions

The RIME trial “tells us we can achieve meaningful benefit in terms of functional status. It does not tell us if we pay a price in safety,” Dr. Davidson said. “The study is simply too small for this, and this unfortunately remains an unanswered question.”

In an accompanying editorial, Patrick T. O’Gara, MD, of Brigham and Women’s Hospital (Boston, MA), agreed, noting that despite RIME and other trials, “firm conclusions regarding the efficacy and safety of [mitral valve repair] at time of CABG surgery in patients with moderate ischemic MR cannot be drawn.”

However, he noted that research should continue. In particular, Dr. O’Gara writes, “There is also growing interest in the use of percutaneous MitraClip (Abbott Vascular, Redwood City, CA) therapy in high surgical risk patients with severe functional MR, a treatment modality that will require rigorous longitudinal study.”

Study Details

For mitral valve annuloplasty, a complete rigid or semi-rigid annuloplasty ring was used, sized by measurement of the anterior mitral valve leaflet. The aim was coaptation of at least 8 mm between the anterior and posterior mitral valve leaflets with no more than trace MR.

 

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Sources:
1. Chan KMJ, Punjabi PP, Flather M, et al. Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation: Final results of the Randomized Ischemic Mitral Evaluation (RIME) trial. Circulation. 2012;Epub ahead of print.

2. O’Gara PT. Randomized trials in moderate ischemic mitral regurgitation. Many questions, limited answers. Circulation;Epub ahead of print.

 

Disclosures:

• The study was funded by the UK Department of Health, National Institute of Health Research (NIHR), the British Heart Foundation, British Medical Association, NIHR Biomedical Research Unit of the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.
• Dr. Chan reports no relevant conflicts of interest.
• Dr. Davidson reports serving as a consultant for Edwards Lifesciences and Sorin.
• Dr. O’Gara reports serving as the co-chair of the National Heart, Lung, and Blood Institute-sponsored Cardiothoracic Surgery Network Steering Committee.

 

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