Regional Myocardial Sympathetic Denervation Predicts the Risk of Sudden Cardiac Arrest in Ischemic Cardiomyopathy

• Published in: Journal of the American College of Cardiology Vol. 63; no. 2; pp. 141 - 149
• Main Authors: Fallavollita, James A., MD, Heavey, Brendan M., MPH, Luisi, Andrew J., MD, Michalek, Suzanne M., MS, Baldwa, Sunil, MBBS, Mashtare, Terry L., PhD, Hutson, Alan D., PhD, deKemp, Robert A., PhD, Haka, Michael S., PhD, Sajjad, Munawwar, PhD, Cimato, Thomas R., MD, Curtis, Anne B., MD, Cain, Michael E., MD, Canty, John M., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 21.01.2014; Elsevier; Elsevier Limited
• Subjects: 11C-meta-hydroxyephedrine; Aged; Biological and medical sciences; Cardiac arrest; Cardiology; Cardiology. Vascular system; Cardiomyopathy; Cardiovascular; Cardiovascular disease; Confidence intervals; Death, Sudden, Cardiac - epidemiology; Death, Sudden, Cardiac - etiology; Death, Sudden, Cardiac - prevention & control; Female; Follow-Up Studies; Heart; Heart attacks; Heart failure; Hospice care; Humans; Incidence; Internal Medicine; Ischemia; Male; Medical imaging; Medical sciences; Mortality; Myocardial Ischemia - mortality; Myocardial Ischemia - physiopathology; Myocardial Ischemia - surgery; myocardial viability; Myocarditis. Cardiomyopathies; Positron-Emission Tomography; Primary Prevention - methods; Prospective Studies; Retention; sudden cardiac arrest; Survival Rate - trends; Sympathectomy - methods; sympathetic denervation; Time Factors; Treatment Outcome; United States - epidemiology; Ventricular Function, Left; United States; magnetic resonance imaging; BNP; left ventricle; MIBG; MRI; LVEF; 11C-HED; LV; left ventricular ejection fraction; 18FDG; myocardial viability; 18F-2-deoxyglucose; sudden cardiac arrest; ventricular fibrillation; sympathetic denervation; ICD; 11C-meta-hydroxyephedrine; SCA; VF; B-type natriuretic peptide; 123I-meta-iodobenzylguanidine; ventricular tachycardia; implantable cardiac defibrillator; positron emission tomography; PET; VT; Cardiocirculatory arrest; Cardiomyopathy; Acute; Prediction; Cardiovascular disease; Risk; Sudden; Regional; Myocardial disease; Ischemia; Heart disease; Risk factor; Myocardium; Circulatory system; Cardiology; Predictive factor; Denervation; FDG; C-HED; C-meta-hydroxyephedrine; I-meta-iodobenzylguanidine; F-2-deoxyglucose
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2013.07.096

Objectives The PAREPET (Prediction of ARrhythmic Events with Positron Emission Tomography) study sought to test the hypothesis that quantifying inhomogeneity in myocardial sympathetic innervation could identify patients at highest risk for sudden cardiac arrest (SCA). Background Left ventricular ejection fraction (LVEF) is the only parameter identifying patients at risk of SCA who benefit from an implantable cardiac defibrillator (ICD). Methods We prospectively enrolled 204 subjects with ischemic cardiomyopathy (LVEF ≤35%) eligible for primary prevention ICDs. 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-stimulated18 F-2-deoxyglucose). The primary endpoint was SCA defined as arrhythmic death or ICD discharge for ventricular fibrillation or ventricular tachycardia >240 beats/min. Results After 4.1 years follow-up, cause-specific SCA was 16.2%. Infarct volume (22 ± 7% vs. 19 ± 9% of left ventricle [LV]) and LVEF (24 ± 8% vs. 28 ± 9%) were not predictors of SCA. In contrast, patients developing SCA had greater amounts of sympathetic denervation (33 ± 10% vs. 26 ± 11% of LV; p = 0.001) reflecting viable, denervated myocardium. The lower tertiles of sympathetic denervation had SCA rates of 1.2%/year and 2.2%/year, whereas the highest tertile had a rate of 6.7%/year. Multivariate predictors of SCA were PET sympathetic denervation, left ventricular end-diastolic volume index, creatinine, and no angiotensin inhibition. With optimized cut-points, the absence of all 4 risk factors identified low risk (44% of cohort; SCA <1%/year); whereas ≥2 factors identified high risk (20% of cohort; SCA ∼12%/year). Conclusions In ischemic cardiomyopathy, sympathetic denervation assessed using11 C-HED PET predicts cause-specific mortality from SCA independently of LVEF and infarct volume. This may provide an improved approach for the identification of patients most likely to benefit from an ICD. (Prediction of ARrhythmic Events With Positron Emission Tomography [PAREPET]; NCT01400334 )