Reproducible Quantification of Regional Sympathetic Denervation with [11C]meta-Hydroxyephedrine PET Imaging

Background Regional cardiac sympathetic denervation is predictive of sudden cardiac arrest in patients with ischemic cardiomyopathy. The reproducibility of denervation scores between automated software programs has not been evaluated. This study seeks to (1) compare the inter-rater reliability of regional denervation measurements using two analysis programs: FlowQuant(R) and Corridor4DM(R); (2) evaluate test-retest repeatability of regional denervation scores. Methods N = 190 dynamic [C-11]meta-hydroxyephedrine (HED) PET scans were reviewed from the PAREPET trial in ischemic cardiomyopathy patients with reduced left ventricular ejection fraction(LVEF <= 35%). N = 12 scans were excluded due to non-diagnostic quality. N = 178 scans were analyzed using FlowQuant and Corridor4DM software, each by two observers. Test-retest scans from N = 20 patients with stable heart failure were utilized for test-retest analysis. Denervation scores were defined as extent x severity of relative uptake defects in LV regions with < 75% of maximal uptake. Results were evaluated using intraclass correlation coefficient (ICC) and Bland-Altman coefficient of repeatability (RPC). Results Inter-observer, inter-software, and test-retest ICC values were excellent (ICC = 94% to 99%) and measurement variability was small (RPC < 11%). Mean differences between observers ranged .2% to 1.1% for Corridor4DM (P = .28), FlowQuant (P < .001), and between software programs (P < .001). Kaplan-Meier analysis demonstrated HED scores from both programs were predictive of SCA. Conclusion Inter-rater reliability for both analysis programs was excellent and test-retest repeatability was consistent. The minimal difference in scores between FlowQuant and Corridor4DM supports their use in future trials.