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Increasing Benefit From Revascularization Is Associated With Increasing Amounts of Myocardial Hibernation

A Substudy of the PARR-2 Trial

Gianni D'Egidio, HBSc, MD^_*, Graham Nichol, MD, MPH, Kathryn A. Williams, MS^_*, Ann Guo, MEng^_*, Linda Garrard, BScN^_*, Robert deKemp, PhD^_*, Terrence D. Ruddy, MD^_*, Jean DaSilva, PhD^_*, Dennis Humen, MD, Karen Y. Gulenchyn, MD, Michael Freeman, MD^||, Normand Racine, MD^¶, Francois Benard, MD^#, Paul Hendry, MD^_*, Rob S.B. Beanlands, MD^_*,_* for the PARR-2 Investigators

^_* National Cardiac PET Centre, Divisions of Cardiology and Cardiac Surgery, Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
University of Washington–Harborview Center for Prehospital Emergency Care, Seattle, Washington
Division of Cardiology, London Health Sciences Center, London, Ontario, Canada
ES Garnett Memorial PET Center, Department of Nuclear Medicine, Hamilton Health Sciences, Hamilton, Ontario, Canada
^|| Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
^¶ Division of Cardiology, Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada
^# Division of Nuclear Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada

^_* Reprint requests and correspondence: Dr. Rob S. B. Beanlands, National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada (Email: rbeanlands{at}ottawaheart.ca).

Objectives: We sought to determine: 1) whether F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters identify high-risk patients who gain benefit from revascularization; 2) whether there is a cut point for such benefit; and 3) predictors of outcome in patients with severe left ventricular (LV) dysfunction due to coronary artery disease.

Background: Patients with ischemic LV dysfunction might benefit from revascularization but not without risk. The FDG PET imaging can detect viable myocardium that recovers after revascularization. In the PARR-2 (PET and Recovery Following Revascularization-2) trial, FDG PET imaging showed a nonsignificant trend for improved outcome compared with standard care. Understanding the predictors of outcome from this prospective trial should help better identify patients at risk and which patients most benefit from revascularization.

Methods: This post hoc analysis included 182 patients with left ventricular ejection fraction (LVEF) <35% and coronary artery disease, being considered for revascularization work-up, and randomized to the PET arm of PARR-2. The primary outcome was a composite of cardiac death, myocardial infarction, or cardiac repeat hospital stay at 1 year.

Results: There is an interaction between PET mismatch and protocol revascularization such that higher mismatch, when combined with revascularization, yields fewer primary outcome events (p = 0.02). On the basis of adjusted Cox modeling, with reduced mismatch (<7%), the risk is not significantly different with or without revascularization. As mismatch increases above this mark, risk is reduced with revascularization. Increasing creatinine (for a 10-µmol/l increase: hazard ratio: 1.03, 95% confidence interval: 1.01 to 1.06, p = 0.010) is also associated with increased risk, whereas decreasing LVEF (for a 2% decrease: hazard ratio: 1.08, 95% confidence interval: 0.99 to 1.18, p = 0.087) trends toward an association with increased risk.

Conclusions: In this post hoc analysis, patients with ischemic cardiomyopathy with larger amounts of mismatch have improved outcome with revascularization. Renal function was also an independent predictor of outcome. The FDG PET seems to define high-risk patients that gain benefit from revascularization. (PET and Recovery Following Revascularization [PARR 2]; NCT00385242 [ClinicalTrials.gov] )

Key Words: fluorodeoxyglucose • heart failure • ischemic heart disease • viability

Abbreviations and Acronyms   CKD = chronic kidney disease   FDG = F-18-fluorodeoxyglucose   ICD = implantable cardioverter-defibrillator   LV = left ventricle/ventricular   EF = ejection fraction   MI = myocardial infarction   PET = positron emission tomography   RNA = radionuclide angiogram

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