LOS ANGELES — Repairing a mitral valve using an annuloplasty ring on top of CABG surgery is better than CABG alone for improving functional capacity in patients with moderate ischemic mitral regurgitation (MR), results of the Randomized Ischemic Mitral Evaluation (RIME) trial show [1]. The small trial was stopped early after an interim review showed a greater improvement at one year among patients treated with the combination surgery.
Dr KM John Chan (Imperial College London, UK) presented the RIME results here at the American Heart Association (AHA) 2012 Scientific Sessions. They were published online simultaneously in Circulation.
Functional ischemic mitral regurgitation arises from LV remodeling and dilatation, often secondary to MI: in functional MR, the mitral valve is anatomically normal, but the dilated ventricle disrupts normal valve competence. Annuloplasty rings, implanted surgically, are used to support the posterior mitral annulus and restore it to size, thereby improving coaptation of the valve leaflets. Imaging studies have shown an improvement in MR grade, but according to the authors, evidence showing that annuloplasty rings can lead to improved valve function and/or reverse remodeling is lacking.
Results From RIME
Chan and colleagues screened 172 patients referred for CABG with moderate functional MR; 73 were ultimately randomized to CABG only or CABG plus an annuloplasty ring. The Carpentier-McCarthy-Adams IMR ETlogix annuloplasty ring (Edwards Lifesciences) was "recommended" for use in the trial, but other complete rigid or semirigid rings were also "permissible" in the study. Ultimately, the recommended ring was used in 85% of patients, with the remainder treated with the Carpentier-Edwards Physio annuloplasty ring (Edwards Lifesciences).
At one year, peak oxygen consumption, a well-validated marker of functional capacity, was improved to a greater degree in patients who had undergone CABG plus mitral valve repair than among CABG-only patients.
Secondary end points, including LV end-systolic index, MR volume, and plasma BNP, also all favored the combination surgery group.
Importantly, however, operational, intubation, and hospital-stay duration were all longer in the group that also underwent annuloplasty implantation, and blood transfusions were significantly greater in this group.
Procedural and One-Year End Points
| End point |
CABG |
CABG + MVR |
p |
| Peak oxygen consumption (mL/kg/min)* |
0.8 |
3.3 |
<0.001 |
| LV end-systolic volume index (mL/m2) |
-4.4 |
-22.2 |
0.002 |
| MR volume (mL/beat) |
-9.2 |
-28.2 |
0.001 |
| Plasma BNP (pg/mL) |
-394.7 |
-557.4 |
0.003 |
| Operation duration (min) |
84 |
147 |
<0.001 |
| Intubation duration (h) |
17 |
28 |
0.004 |
| Hospital stay (d) |
9 |
15 |
0.05 |
| Blood transfusion (mL) |
153 |
900 |
0.016 |
*Primary end point
MVR=mitral valve repair
Survival at 30 days (3%) and one year (9%) were no different between groups.
"Longer follow-up is clearly necessary. This study was not designed and not powered to evaluate clinical events and survival; however, peak oxygen consumption is a recognized predictor of survival," Chan noted. "The impact of these benefits on longer-term clinical outcomes remains to be defined."
"There Are Not Clinical End Points"
Commenting on the results after Chan's presentation, Dr Michael Davidson (Brigham and Women's Hospital) quipped that he is "one of the few surgeons in the US who doesn't have an annuloplasty ring named after him."
RIME, he said, "clearly showed a meaningful impact on some objective criteria, whether it be LV dimension, BNP levels, or functional reserve. But these are not clinical end points."
Also, of note, by stopping the study early, the trialists "missed the opportunity to see if there are meaningful differences in safety."
For example, blood transfusions were significantly more common among patients who also received an annuloplasty ring. "Blood transfusion in cardiac surgery is an independent predictor of late mortality. So if it turns out that these patients are transfused more consistently, there may be more adverse events down the road."
Trial results, he added, likely were not specific to the type of recommended ring used in the bulk of trial patients but probably applied to all rigid, complete rings.
Small Study, Specific Patients
Speaking with heartwire , Dr Robert Bonow (Northwestern University, Chicago, IL) emphasized RIME's small size but said, "It provides helpful information in patients with this degree of severity of MR, who are undergoing CABG, that adding an additional procedure led to a better functional outcome and improvement in symptoms."
But of note, he said, these were only patients who had ejection fractions >30%, so that these results pertain only to these patients. "Many times we see patients with worse LV function, and remember, this is a disease of the ventricle, not a disease of the valve." What's not known is whether patients with more or less severe ejection fraction would also benefit from this procedure, Bonow said.
In RIME, patients were enrolled if they had moderate ischemic MR as defined as by the AHA/American College of Cardiology/American Society of Echocardiography guidelines. As Dr Subodh Verma (University of Toronto, ON) pointed out to heartwire , however, the study population ended up being "at the very low end of moderate in both effective regurgitant orifice and regurgitant volume.
"Hence, the benefits observed also seem to apply to the lower range of moderate mitral regurgitation, which is an important point."
Verma also pointed to a surprisingly high use of intra-aortic balloon pump, despite the fact that patients had relatively preserved ejection fractions.
Both Verma and Bonow made note of Surgical Interventions for Moderate Ischemic Mitral Regurgitation, a larger study currently under way, cosponsored by the National Institutes of Health and the Cardiothoracic Surgical Trials Network. "[This] may help outline whether these surrogate indices translate into real mortality benefits for patients," Verma said.
Annuloplasty Rings in the Spotlight
In recent years, annuloplasty rings have made headlines for reasons unrelated to their putative medical benefits. As reported by heartwire , annuloplasty rings attracted the attention of the FDA and US Senate in the wake of a heartwire series about what was then known as the "Myxo" ring. The ring was tested and marketed without following what the FDA later clarified was the appropriate path to market. In 2010, the Carpentier-McCarthy-Adams IMR ETlogix was one of a number of annuloplasty rings cited in an FDA letter following an inspection of the Edwards Lifesciences manufacturing plant in Irvine, CA. According to the FDA, adverse-event complaints relating to mitral annuloplasty rings were not appropriately reported to the agency. Annuloplasty rings have since been cited as one of the subclasses of devices at the heart of recent FDA efforts to overhaul its 510(k) and premarket-approval processes.
Dr Nalini Rajamannan (Sacred Heart Cardiology, Chicago, IL), who first raised concerns about how the Myxo annuloplasty ring reached the US market, also commented on the RIME study for heartwire . "These results are promising, but extended follow-up would be helpful to determine if these results hold up in the long term in this complex patient population. If there is continued improvement in the physiologic parameters at 16 to 24 months, then the short-term morbidity may be an acceptable approach for this very ill patient population."
Pointing out that two different types of annuloplasty rings were used in the study, Rajamannan suggested that "a subanalysis of how to determine the ring size; also, an explanation of any clinical-outcome differences between the two rings is necessary to guide the surgical approach for this patient population."
The RIME trial was funded by the UK's Department of Health and National Institute for Health Research (NIHR), the British Heart Foundation, and the British Medical Association (BMA). It was also supported by the NIHR Cardiovascular Biomedical Research Unit of the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London. Chan was funded on a grant from the NIHR and the BMA. Disclosures for the coauthors are listed in the paper. Davidson disclosed consulting for Edwards Lifesciences and Sorin.
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Cite this: RIME: Annuloplasty Rings Boost Functional Capacity in Moderate MR - Medscape - Nov 08, 2012.
