August 28th, 2013
Remote Ischemic Preconditioning for CABG: An Investigator’s Perspective
CardioExchange’s John Ryan interviews Gerd Heusch about his study group’s randomized trial, published in the Lancet, of remote ischemic preconditioning before coronary artery bypass graft surgery. (See CardioExchange’s news coverage here and a prior discussion of the trial here.)
Researchers randomized 329 patients with triple vessel CAD undergoing elective, isolated first-time CABG to receive remote ischemic preconditoning (rIPC; consisting of 3 cycles of inflation of a blood-pressure cuff for 5 minutes, followed by 5 minutes of reperfusion) or no preconditioning. In the first 72 hours after CABG, serum cardiac troponin I (cTnI) levels were 17% lower in the rIPC group than the control group (a significant difference). Clinical benefits were not evident at 30 days, but rIPC was associated with significantly lower rates of cardiac and all-cause mortality at 1 year. The rIPC group’s hazard ratio for 1-year all-cause mortality, compared with the control group, was 0.27 (95% CI, 0.08–0.98; P=0.046).
Ryan: Your study is impressive but small. Do we need validation before adopting this approach into routine practice?
Heusch: Indeed, our study was a single-center trial. In addition, the primary endpoint was troponin release, and the trial was not statistically powered for the secondary endpoints, including mortality, during follow-up. Validation with a multicenter trial that has mortality as a primary endpoint is needed before remote preconditioning is recommended for routine clinical practice.
Ryan: You enrolled participants for more than 4 years, and the intervention is innocuous. Why did it take so long to get 329 patients?
Heusch: We used very strict inclusion criteria to avoid all potential interference with the remote preconditioning phenomenon in our proof-of-principle study. Therefore, we selected the study participants from almost 3000 consecutive CABG patients.
Ryan: Can you explain why patients with diabetes were initially excluded, as well as the issue about cardioprotective signaling?
Heusch: Diabetes has been shown to interfere with cardioprotective signaling and to attenuate cardioprotection in several experimental studies. It is currently not clear whether diabetes interferes with the transfer of the protective signal from the ischemic/reperfused arm to the heart and/or with the activation of the molecular protection program in the heart. In our proof-of-principle study, we therefore wanted to avoid such interference and initially excluded patients with diabetes. Our ongoing studies now include patients with diabetes.
Ryan: The mortality benefit seems too good to be true — and difficult to link with the troponin difference. Also, many of the deaths seem unrelated. How do you interpret that finding?
Heusch: Indeed, the mortality benefit from remote preconditioning in our study is fairly large, almost out of proportion with the moderate level of cardioprotection suggested by the 17% reduction in troponin release. We explain this discrepancy by emphasizing the systemic nature of the remote preconditioning phenomenon, which appears to protect not only the heart but also the kidneys (we found also better postoperative kidney function) and other organs (there were no strokes with remote preconditioning, compared with one stroke among the controls).
Ryan: You note that some trials of this approach have not led to benefits. What precisely did you do that was effective that the others did not?
Heusch: One important confounder that we identified is the choice of anesthesia. The remote preconditioning phenomenon is operative with isoflurane anesthesia, but not with propofol. Most negative studies have used propofol in at least one of their protocols.
JOIN THE DISCUSSION
What’s your view on remote ischemic preconditioning for CABG, given the study author’s remarks about this randomized trial?