NOS1AP Variant rs7539120 is Associated with Appropriate Implantable Cardioverter Defibrillators (ICD) Shock
De Grandi A
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Implantable cardioverter defibrillators (ICD) are used to prevent Sudden Cardiac Death (SCD) in patients with heart failure, but currently only 30% of them experience an appropriate ICD activation during their life. Implantation guidelines need to be improved and the inclusion of genetic factors represents a possibility. Multiple independent studies have shown that variants in the NOS1AP region are associated with SCD and with QT length, a predictor of SCD. Recently,a functional variant located in a cardiac enhancer upstream NOS1AP, rs7539120, has been shown to modulate the QT interval through altered cellular electrophysiology in cardiomyocytes. We studied the association of rs7539120 with life-threatening arrhythmias, as identified by the appropriate ICD shock and/or anti-tachycardia pacing therapy. We analysed 286 patients affected by ischemic or non-ischemic hypokinetic cardiomyopathy, enrolled at the hospitals of Bolzano and Trento (Italy), who received an ICD for primary prevention of SCD. The cohort was followed-up for a median time of 3.04 years (IQR: 1.71-5.68) after implantation, during which 79 (28%) appropriate ICD activations occurred. We analysed the data using multiple Cox regression models adjusted for age, gender and hospital. In the 128 non-ischemic cardiomyopathy patients, rs7539120 was associated with ICD appropriate shock (HR=2.58, 95% CI: 1.30-5.11, p=0.006),while we did not find any evidence of an effect in the 158 ischemic patients (HR=1.03, 95% CI: 0.62-1.73, p=0.904). Our findings are consistent with the hypothesis that a stronger genetic risk component underlies non-ischemic cardiomyopathy.