HRS: Quantifying sympathetic denervation could provide new approach to identifying arrhythmic death
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| Short-axis representative PET images of two hypertrophic cardiomyopathy individuals, one with normal LVOTGs (5 and 12 mm Hg) and another with elevated gradients (97 and 135 mm Hg at rest and provocation, respectively). Source: J Nucl Med 2012;53(3):407-414. |
The researchers prospectively enrolled 204 coronary artery disease (CAD) patients who were candidates for implantable cardioverter-defibrillator (ICD) placement for the primary prevention of SCA in the PAREPET (Prediction of Arrhythmic Events with Positron Emission Tomography) study. Average age was 67 years with New York Heart Association functional class 2.1CHF and an ejection fraction (EF) of 27 percent. Cause specific mortality from SCA was defined using modified Hinkle-Thayer criteria or ICD discharge for ventricular flutter (or ventricular tachycardia less than 240 bpm).
The frequency of SCA is inversely related to left ventricular (LV) function yet many events occur in patients with an EF of less than 35 percent who are not currently candidates for ICD therapy, according to Fallavollita.
After baseline echocardiography and clinical evaluation, substrate remodeling was quantified using PET to image perfusion (13N-ammonia; NH3), the extent of sympathetic denervation (11C-meta-hydroxyephedrine; HED) and infarction (insulin-stimulated 18F-2-deoxyglucose; FDG).
Median follow-up was 4.2 years and cardiac mortality was 34 percent, of which half was from SCA (16 percent). As continuous variables, the volume (percentage LV) of denervated myocardium (where sympathetic nerves in the heart have died or become damaged due to inadequate blood flow) was a strong determinant of SCA. By multivariate analysis (including EF and BNP), denervated myocardium (less than 37.6 percent LV) remained an independent predictor of SCA (10.3 percent/year vs. 3.0 percent/year) whereas EF, infarct volume and hibernating myocardium were not.
Additional predictors by multivariate analysis included LV end-diastolic volume index, creatinine and no angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy.
“Quantifying the extent of sympathetic denervation could afford a new approach to selecting patients with relatively preserved systolic function who are at risk of arrhythmic death,” Fallavollita concluded. He acknowledged further study is needed.
Funding was provided by the National Institutes of Health.