To compare medical therapy with coronary bypass surgery and/or surgical ventricular restoration for patients with congestive heart failure and coronary heart disease.

Condition	Treatment or Intervention
Cardiovascular Diseases Coronary Disease Heart Failure Heart Failure, Congestive Heart Diseases	Procedure: Coronary Artery Bypass  Drug: Modern medical management  Procedure: Surgical Ventricular Restoration

Further Study Details: 

BACKGROUND: Congestive heart failure afflicts approximately five million Americans and is the leading cause of hospitalization in Americans over the age of 65. Most cases of congestive heart failure are due to coronary artery disease, but surprisingly little is known about the relative benefits of medical versus surgical therapy for patients with obstructive coronary disease and congestive heart failure. Randomized clinical trials of medical therapy versus bypass surgery for obstructive coronary disease were conducted in the 1970's and did not include the systematic use of aspirin, arterial conduits, or lipid-lowering medications. In addition, patients with ejection fractions below 35 percent were specifically excluded from the three large randomized clinical trials of medical therapy versus bypass surgery. While observational data from the 1970's and early 1980's suggest a survival advantage associated with bypass surgery in patients with low ejection fraction and congestive heart failure, biases favoring the referral the fittest of such patients for bypass surgery may have confounded these comparisons. In addition, medical therapy for congestive heart failure has improved dramatically over the past two decades. Thus, the choice of medical therapy versus bypass surgery for patients with congestive heart failure and obstructive coronary disease, is usually decided by guesswork. This trial is designed to provide a solid answer.

DESIGN NARRATIVE: The study is a randomized, multicenter clinical trial of medical therapy versus coronary bypass surgery for patients with congestive heart failure, left ventricular ejection fraction less than 35 percent, and obstructive coronary disease suitable for revascularization. In addition, patients with extensive anterior ischemia assigned to the surgical arm of the study will be further randomized to coronary artery bypass (CABG) surgery alone versus bypass surgery plus surgical ventricular restoration (SVR). The surgical ventricular reconstruction procedure decreases the circumference of the endocardial scar through an incision into normal epicardium. The surgical repair uses the subendocardial scar or a patch to absorb excess linear wall tension from adjacent myocardium. Preliminary evidence indicates that this surgical reduction in left ventricular volume and consequent decrease in wall stress enhances function in myocardial regions remote from the repair and reduces the tendency for continued gradual expansion of the akinetic zone. In order to confirm these observations, patients undergoing surgical ventricular reconstruction at the time of coronary bypass surgery will also undergo cardiac magnetic resonance ventriculograms at baseline, four months, and two years after surgery in order to define the effects of the procedure on left ventricular size and function and the relation of those effects to survival.

Over three years, 50 clinical sites will recruit 2,800 patients with heart failure, left ventricular ejection fraction <.35, and coronary artery disease 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 either medical or surgical therapy. All patients will be evaluated further for appropriateness of surgical ventricular reconstruction indicated by an end-systolic volume index (ESVI) >60 ml/m2 and akinesia >35% of the anterior LV wall. 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 eligible for medical or surgical therapy, the 1,600 not SVR eligible will be evenly randomized between medical therapy only and medical therapy with CABG. The remaining 600 patients also eligible for SVR will be randomized between three treatments of medical therapy only, or medical therapy + CABG, or medical therapy + CABG + SVR. Registries of clinical information will be maintained on eligible patients who decline trial entry. At four-month intervals for a minimum of three years, all randomized patients will be followed by a clinical visit and registry patients will be followed by telephone. Appropriate subgroups of randomized patients will have core laboratory studies repeated at specified follow-up intervals.

Measurement will be made of endogenous peptides associated with exacerbation of left ventricular dysfunction [e.g., norepinephrine, endothelin, tumor necrosis factor {TNF}, interleukin-6 {IL-6}, atrial natriuretic peptide {ANP} and brain natriuretic peptide {BNP}]. These measurements will be used for the (retrospective) identification of patients most likely to benefit from surgery and/or to determine the effect of surgery on peptide expression and the relationship of changes in peptide expression to long-term survival.

For the comparison of medical vs. surgical therapy, the primary endpoint is long term survival. For the comparison of CABG plus surgical ventricular reconstruction vs. CABG alone, the primary endpoint is long term survival free of cardiac hospitalization. Secondary endpoints include cost-effectiveness and quality of life for each treatment, exercise capacity, and treatment-specific prediction of primary endpoints by baseline measurements of myocardial ischemia and viability and by baseline and post treatment measurements of left ventricular size and function, neurohormonal and pro-inflammatory cytokine levels.

Genders Eligible for Study:  Both

Criteria

Enrollment Requirements Inclusion Criteria: · Symptomatic heart failure defined as NYHA Class II - IV (within 3 months of entry) · LV < 35% defined by CMR or gated SPECT studies · Coronary anatomy suitable for revascularization · Age > 18 and competent to give informed consent Exclusion Criteria: · Primary valvular heart disease clearly defined indicating the need for valve repair or replacement · Patients with concurrent cardiogenic shock or requiring inotropic or intra-aortic balloon support · PCI planned for CAD treatment · Acute myocardial infarction within 30 days · More than one prior cardiac operation · Non-cardiac illness with life expectancy < three years · Non-cardiac illness imposing substantial operative mortality. Patients eligible to enter the study will be further evaluated by the STICH team for SVR eligibility.

North Carolina
      Duke University Medical Center, Durham,  North Carolina,  27715,  United States; Recruiting

Study chairs or principal investigators

Robert Bonow,  Northwestern University   
Arthur Feldman,  University of Pittsburgh   
Robert Jones,  Duke University   
Kerry Lee,  Duke University   
Daniel Mark,  Duke University   
Jae Oh,  Mayo Clinic   
Gerald Pohost,  University of Alabama   

Study ID Numbers:  140
Record last reviewed:  March 2005
Last Updated:  March 3, 2005
Record first received:  September 11, 2001
ClinicalTrials.gov Identifier:  NCT00023595
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08