Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy.
OBJECTIVE
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).
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.
James A
JA
Fallavollita
Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York.
Brendan M
BM
Heavey
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.
Andrew J
AJ
Luisi
Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York.
Suzanne M
SM
Michalek
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.
Sunil
S
Baldwa
Department of Biostatistics, University at Buffalo, Buffalo, New York.
Terry L
TL
Mashtare
Department of Biostatistics, University at Buffalo, Buffalo, New York.
Alan D
AD
Hutson
Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Robert A
RA
Dekemp
Department of Nuclear Medicine, University at Buffalo, Buffalo, New York.
Michael S
MS
Haka
Department of Nuclear Medicine, University at Buffalo, Buffalo, New York.
Munawwar
M
Sajjad
Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; Department of Medicine, University at Buffalo, Buffalo, New York.
Thomas R
TR
Cimato
Department of Medicine, University at Buffalo, Buffalo, New York.
Anne B
AB
Curtis
Department of Medicine, University at Buffalo, Buffalo, New York; Department of Biomedical Engineering, University at Buffalo, Buffalo, New York.
Michael E
ME
Cain
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.
John M
JM
Canty
D000368:Aged; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D017202:Myocardial Ischemia / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D049268:Positron-Emission Tomography; D011322:Primary Prevention / Q000379:methods*; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D013562:Sympathectomy / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D016277:Ventricular Function, Left
(11)C-HED; (11)C-meta-hydroxyephedrine; (123)I-meta-iodobenzylguanidine; (18)F-2-deoxyglucose; (18)FDG; B-type natriuretic peptide; BNP; ICD; LV; LVEF; MIBG; MRI; PET; SCA; VF; VT; implantable cardiac defibrillator; left ventricle; left ventricular ejection fraction; magnetic resonance imaging; myocardial viability; positron emission tomography; sudden cardiac arrest; sympathetic denervation; ventricular fibrillation; ventricular tachycardia