Does Quantification of [(11)C]meta-hydroxyephedrine and [(13)N]ammonia Kinetics Improve Risk Stratification in Ischemic Cardiomyopathy

BACKGROUND: In ischemic cardiomyopathy patients, cardiac sympathetic nervous system dysfunction is a predictor of sudden cardiac arrest (SCA). This study compared abnormal innervation and perfusion measured by [(11)C]meta-hydroxyephedrine (HED) vs [(13)N]ammonia (NH(3)), conventional uptake vs parametric tracer analysis, and their SCA risk discrimination. METHODS: This is a sub-study analysis of the prospective PAREPET trial, which followed ischemic cardiomyopathy patients with reduced left ventricular ejection fraction (LVEF≤35%) for events of SCA. Using n=174 paired dynamic HED and NH(3) positron emission tomography (PET) scans, regional defect scores (%LV extent×severity) were calculated using HED and NH(3) uptake, as well as HED distribution volume and NH(3) myocardial blood flow by kinetic modelling. RESULTS: During 4.1 years follow-up, there were 27 SCA events. HED defects were larger than NH(3), especially in the lowest tertile of perfusion abnormality (p<0.001). Parametric defects were larger than their respective tracer uptake defects (p<0.001). SCA risk discrimination was not significantly improved with parametric or uptake mismatch (AUC=0.73 or 0.70) compared to HED uptake defect scores (AUC=0.67). CONCLUSION: Quantification of HED distribution volume and NH(3) myocardial blood flow produced larger defects than their respective measures of tracer uptake, but did not lead to improved SCA risk stratification vs. HED uptake alone.