Regional Myocardial Sympathetic Denervation Predicts the Risk of Sudden Cardiac Arrest in Ischemic Cardiomyopathy

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 (11C-meta-hydroxyephedrine [11C-HED]), perfusion (13N-ammonia) and viability (insulin-stimulated 18F-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 11C-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)

Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel on Renal Sympathetic Denervation

“…The PAREPET (prediction of arrhythmic events with positron emission tomography) study tested the hypothesis that a paucity of cardiac muscle sympathetic uptake, measured using carbon 11-meta-hydroxyephedrine, was associated with sudden cardiac events in patients with underlying ischemic cardiomyopathy (54). The use of this or similar PET agents to label neurotransmitters in the periphery, kidney, or other sites is a potential area of research into the effect of RDN on the kidney.…”

Myocardial Scar Delineation Using Diffusion Tensor Magnetic Resonance Tractography

“…A variety of imaging modalities and approaches have been used to assess myocardial injury, infiltration, and viability, most notably late gadolinium enhancement (LGE),1, 2, 3, 5, 6, 7 and positron emission tomography 10, 11, 12. LGE has emerged as a leading technique for tissue characterization of the myocardium; however, several issues complicate its use.…”

European perspective: Comparing the AHA/ACC and ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

“…Echo-, magnetic resonance (CMR)-or gated-SPECT-based analysis of contractile patterns have been introduced and explored with regards to their benefit for identification of candidates for CRT. 9 Imaging of sympathetic innervation with MIBG 10 or PET, 11 or imaging of the gray zone using contrast-enhanced CMR, 12 have been introduced to identify subjects at elevated risk of ventricular arrhythmia. For some of those techniques, larger registries have been created years before the 2015 update of the ESC guidelines.…”