The influence of risk on the results of warm heart surgery: a substudy of a randomized trial

Objective — The Warm Heart Investigators Trial randomized isolated coronary bypass patients to cold or warm cardioplegia, and demonstrated that warm cardioplegia significantly reduced the prevalence of low output syndrome and myocardial infarction (as defined by CKMB enzyme release). This study was designed prospectively as a subanalysis of the original trial, to determine the effect of warm heart surgery on high risk patients, who were anticipated to derive the major benefit from warm cardioplegia.

Methods — The prespecified endpoint for this study was a composite outcome of morbidity and mortality (death and/or low output syndrome and/or enzymatic myocardial infarction). Only patients with complete data for all outcomes were included, totalling 1374 patients (692 warm cardioplegia, 682 cold cardioplegia) who were randomized in the Warm Heart Investigators Trial. High medium and low risk patients were identified by a multivariate model of predicted risk for the study outcome.

Results — Analysis of the independent and interactive influence of cardioplegia technique and predicted risk demonstrated that warm cardioplegia significantly reduced the overall prevalence of morbidity and mortality (warm: 15.9 versus cold: 25.2%, P < 0.01). However, no significant differences in warm-cold effects were detected among risk terciles. Cardioplegia technique had a similar differential influence on mortality and morbidity in low risk patients (warm: 7.3, cold: 17.4%) as it did in high risk patients (warm: 31.1, cold: 39.9%).

Conclusions — Although our analysis confirms the overall benefits of warm cardioplegia, our unanticipated finding in high risk subjects may be explained by the fact that morbidity and mortality in that patient subgroup is caused not only by poor myocardial protection, but by other clinical and technical factors. Further studies are necessary to identify those patients who might benefit most from improved myocardial protection techniques.