The Surgical Treatment for Ischemic Heart Failure (ST1CH) multicenter international randomized trial addresses two specific primary hypotheses in patients with clinical heart failure (HF) and left ventricular (LV) dysfunction who have coronary artery disease (CAD) amenable to surgical revascularization: 1) Coronary artery bypass grafting (CABG) with intensive medical therapy (MED) improves long-term survival compared to intensive medical therapy alone; 2) In patients with regional LV dysfunction, surgical ventricular restoration (SVR) to a more normal LV size and shape improves survival free of subsequent hospitalization in comparison to CABG alone. Important secondary endpoints reflecting morbidity, cost, and quality of life will be assessed. Core laboratories for cardiac magnetic resonance (CMR), echocardiography (ECHO), neurohormonal/cytokine/genetic (NCG), and radionuclide (RN) studies will ensure consistent testing practices and standardization of data necessary to identify eligiblepatients and address specific questions related to the primary hypotheses. Over three years, 50 clinical sites will recruit 2,800 consenting patients with HF, LV ejection fraction (EF) < .35, and CAD amenable to CABG. These patients first will be characterized by angina intensity or presence of left main coronary stenosis as appropriate for only surgical therapy or both medical and surgical therapy. AH patients will be evaluated further for appropriateness of SVR indicated by an end-systolic volume index (ESVI) > 60 ml/m2 and dysfunction in a single LV region. The 600 patients estimated to be eligible for SVR but ineligible for randomization to medical therapy will be evenly randomized to CABG with or without SVR. Of the 2,200 consenting patients eligiblefor medical or surgical therapy, the 1,600 not SVR eligiblewill be evenly randomized between MED only and MED with CABG. The remaining600 patients also eligible for SVR will be evenly randomized between three treatments of MED only, or MED + CABG, or MED + CABG + SVR. Registries of clinical information will be maintained on patients who are eligible but decline trial entry. AHrandomized and some registry patients will be followed by a clinic visit at four-month intervals for a minimum of three years. Appropriate subgroups of randomized patients will have core laboratory studies repeated at specified follow-up intervals. The neurohormone/cytokine/genetic core will test three hypothesis: 1) pre-operative levels of neurohormones, natriuretic peptides, and pro-inflammatory cytokines will be useful in predicting that group of patients who will most likely benefit from either surgical revascularization and/or surgical revascularization with SVR; 2) salutary changes post-operatively in neurohormonal/cytokine/natriuretic peptide activation will predict long term outcomes in patients undergoing either surgical revascularization and/or revascularization with SVR and will provide the physiologic rationale for these changes; and 3) patients having a favorable genotype (eg.Low expression of ACE gene or high levels of adenosine) will be most likely to achieve long-term benefit from either CABG or CABG with SVR.
