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Polygenic score predicts sudden death in CAD

Dr Roopinder Sandu, Smidt Heart Institute, CA, USA
Journal of the American College of Cardiology
In patients with coronary artery disease (CAD) without severe left ventricular dysfunction from the prospective cohort study named PRE-DETERMINE (NCT01114269), a validated genome-wide polygenic risk score was predictive of sudden cardiac death (SCD) [1]. The polygenic score may possibly improve the risk stratification for patients with CAD who are not eligible for implantable cardioverter-defibrillators (ICDs) according to the current guidelines.

According to Dr Roopinder Sandu (Smidt Heart Institute, CA, USA) and co-investigators, the options for predicting SCD in patients with CAD and an ejection fraction above 35% are limited, notwithstanding that SCD frequently occurs in this population. Therefore, the research team analysed genome-wide genotyping of 4,698 patients who were enrolled in the PRE-DETERMINE study to develop a genome-wide polygenic score for patients with CAD. The primary endpoint was sudden arrhythmic death.

The results showed that patients in the top decile of the polygenic score for CAD had a higher absolute (8% vs 4%; P=0.005) and proportional (29% vs 16%; P=0.0003) risk for sudden arrhythmic death than patients in any other decile. The effect was driven by SCD events (HR 1.77; 95% CI 1.23-2.54; P=0.002) but not by non-sudden arrhythmic death events (HR 1.00; 95% CI 0.8-1.25; P=0.98). These findings were consistent across left ventricular ejection fractions, ECG parameters, and clinical factors. According to the authors, the polygenic risk score for CAD is promising as a screening tool, but it needs to be established whether it predicts recurrent ischaemia or ventricular fibrillation. If it actually predicts ventricular fibrillation, the tool could help inform clinicians whether or not patients would benefit from an ICD. A randomised controlled trial is needed to solve this issue.

  1. Sandhu RK, et al. J Am Coll Cardiol. 2022;80(9):873-883

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