Does quantification of [¹¹C]meta-hydroxyephedrine and [¹³N]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 [¹¹C]meta-hydroxyephedrine (HED) vs [¹³N]ammonia (NH₃), 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 NH₃ positron emission tomography (PET) scans, regional defect scores (%LV extent × severity) were calculated using HED and NH₃ uptake, as well as HED distribution volume and NH₃ myocardial blood flow by kinetic modeling. Results: During 4.1 years follow-up, there were 27 SCA events. HED defects were larger than NH₃, especially in the lowest tertile of perfusion abnormality (P <.001). Parametric defects were larger than their respective tracer uptake defects (P <.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 NH₃ 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.