title: 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.
authors.affiliation: Buffalo, New York.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cain
mesh_terms: D000368:Aged; D009202:Cardiomyopathies / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D016009:Chi-Square Distribution; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004452:Echocardiography; D004809:Ephedrine / Q000031:analogs & derivatives; D005260:Female; D006321:Heart / Q000294:innervation*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D055414:Myocardial Perfusion Imaging; D017682:Myocardial Stunning / Q000000981:diagnostic imaging* / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000503:physiopathology; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D014022:Tissue Survival; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D016277:Ventricular Function, Left
chemical_list: D019275:Radiopharmaceuticals; C065363:3-hydroxyephedrine; D004809:Ephedrine