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)
Many survivors of sudden cardiac death (SCD) have normal global ventricular function and severe coronary artery disease but no evidence of symptomatic ischemia or infarction before the development of lethal ventricular arrhythmias, and the trigger for ventricular tachycardia (VT)/ventricular fibrillation (VF) remains unclear. We sought to identify the role of spontaneous ischemia and temporal hemodynamic factors preceding SCD using continuous telemetry of left ventricular (LV) pressure and the ECG for periods up to 5 mo in swine (n = 37) with hibernating myocardium who experience spontaneous VT/VF in the absence of heart failure or infarction. Hemodynamics and ST deviation at the time of VT/VF were compared with survivors with hibernating myocardium as well as sham controls. All episodes of VT/VF occurred during sympathetic activation and were initiated by single premature ventricular contractions, and the VT degenerated into VF in ∼ 30 s. ECG evidence of ischemia was infrequent and no different from those that survived. Baseline hemodynamics were no different among groups, but LV end-diastolic pressure during sympathetic activation was higher at the time of SCD (37 ± 4 vs. 26 ± 4 mmHg, P < 0.05) and the ECG demonstrated QT shortening (155 ± 4 vs. 173 ± 5 ms, P < 0.05). The week before SCD, both parameters were no different from survivors. These data indicate that there are no differences in the degree of sympathetic activation or hemodynamic stress when VT/VF develops in swine with hibernating myocardium. The transiently elevated LV end-diastolic pressure and QT shortening preceding VT/VF raises the possibility that electrocardiographically silent subendocardial ischemia and/or mechanoelectrical feedback serve as a trigger for the development of SCD in chronic ischemic heart disease.
Background:
Viable dysfunctional myocardium can be classified as chronically stunned (normal resting perfusion) or hibernating (reduced resting flow). While
13
N-ammonia (NH
3
) retention (late uptake) is typically used to estimate perfusion, the frequency and extent of hibernating myocardium (HM) may differ when quantification of dynamically-acquired absolute myocardial blood flow (MBF) is performed.
Methods:
Patients with stable ischemic cardiomyopathy (n = 25, EF 32 ± 2%, NYHA Class 2.1 ± 0.7) who were candidates for an ICD for the primary prevention of sudden death underwent imaging with NH
3
and insulin-clamp
18
F-2-deoxyglucose (FDG). Segmental perfusion (17 segment LV model, % peak segment) was assessed by both retention (20 minute summed image) and absolute MBF using a 3-compartment model (ml/min/g). Normal segments were defined as perfusion ≤ 80% peak segment. Segments with <50% peak segment FDG uptake were defined as scar. The remaining segments were considered HM if FDG/perfusion ratio was ≥ 1.2.
Results:
Of the 425 total segments, only 15 (3.5%) were considered HM when NH
3
retention was used to assess perfusion. In contrast, the number of HM segments increased markedly with quantification of absolute MBF (159 or 37%, p<0.001 vs. retention), with a commensurate reduction in the number of normally-perfused segments.
Conclusions:
The estimation of perfusion with NH
3
retention significantly overestimates MBF (Figure
) and hence underestimates the frequency and extent of HM. While the differentiation of chronically stunned from HM may not influence the decision for revascularization, the distinction may be important if HM is an independent risk factor for sudden death.
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