James A Fallavollita1, Brendan M Heavey2, Andrew J Luisi3, Suzanne M Michalek2, Sunil Baldwa1, Terry L Mashtare4, Alan D Hutson4, Robert A Dekemp5, Michael S Haka6, Munawwar Sajjad6, Thomas R Cimato7, Anne B Curtis8, Michael E Cain9, John M Canty10. 1. VA Western New York Health Care System, Buffalo, New York; Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; Department of Medicine, University at Buffalo, Buffalo, New York. 2. Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York. 3. Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; Department of Medicine, University at Buffalo, Buffalo, New York; Department of Nuclear Medicine, University at Buffalo, Buffalo, New York. 4. Department of Biostatistics, University at Buffalo, Buffalo, New York. 5. Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. 6. Department of Nuclear Medicine, University at Buffalo, Buffalo, New York. 7. Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; Department of Medicine, University at Buffalo, Buffalo, New York. 8. Department of Medicine, University at Buffalo, Buffalo, New York. 9. Department of Medicine, University at Buffalo, Buffalo, New York; Department of Biomedical Engineering, University at Buffalo, Buffalo, New York. 10. VA Western New York Health Care System, Buffalo, New York; Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; Department of Medicine, University at Buffalo, Buffalo, New York; Department of Biomedical Engineering, University at Buffalo, Buffalo, New York; Department of Physiology and Biophysics, University at Buffalo, Buffalo, New York. Electronic address: canty@buffalo.edu.
Abstract
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-stimulated (18)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 using (11)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).
RCT Entities:
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-stimulated (18)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 using (11)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).
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