Impact of denervated myocardium on improving risk stratification for sudden cardiac death

Abstract

Between 184,000 and 462,000 Americans die suddenly each year. Fifty percent to 70% of these deaths are due to ventricular tachycardia/fibrillation (VT/VF). We tested whether hibernating myocardium or myocardial sympathetic denervation identifies patients at high-risk for developing VT/VF independently of ejection fraction (EF). Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion ((13)N-ammonia), and viability (insulin-stimulated (18)F-2-deoxyglucose [(18)FDG]) in patients with ischemic cardiomyopathy (EF < 35%) eligible for a primary prevention implantable cardioverter defibrillator (ICD). The primary end-point was sudden cardiac arrest (SCA) defined as arrhythmic death or ICD discharge for VT/VF > 240 bpm. Volumes of total denervated (P = .001) and viable denervated myocardium ((11)C-HED-(18)FDG mismatch, P = .03) predicted SCA, whereas hibernating and infarcted myocardium did not. Multivariate analysis identified four independent predictors of SCA: denervated myocardium > 37.6% of left ventricule (LV), LV end-diastolic volume > 98 mL/m(2), creatinine level > 1.49 mg/dL, and no angiotensin- inhibition therapy. Denervated myocardium had a hazard ratio of 3.5 for SCA (10.3%/year vs. 3.0%/year, p=0.001). Absence of all four factors predicted low risk (44% of cohort; SCA <1%/y) whereas two or more factors identified subjects at high-risk (20% of cohort; SCA 12%/y). Denervated myocardium quantified using PET strongly predicts risk of SCA, and is independent of EF, infarct volume, and other clinical variables.

Trial registration: ClinicalTrials.gov NCT01400334.