Perspective:

CAD is the most common underlying substrate in patients with sudden death and the majority of those deaths occur in patients with LVEF >35%. Thus, most SAD events occur among patients without current guideline indications for implantable cardioverter-defibrillator (ICD) therapy. In order to address this intermediate-risk population with established CAD, but without severe LV dysfunction, the authors performed an analysis of a validated genome-wide polygenic score for coronary artery disease (GPS_CAD), which accounts for up to one-fourth of CAD heritability. The authors found that patients in the top GPS_CAD decile were at 77% increased risk for SAD after accounting for LVEF, clinical factors, and ECG parameters. There was no association between top GPS_CAD decile and non-SAD.

While prior studies have found that common variants associated with CAD are associated with elevations in SAD in the general population, the present study demonstrates a strong association between those variants and SAD in the presence of established CAD. By studying the intermediate-risk population where SAD rates are 10-fold higher than in the general population, the relative risk elevations are significant enough to warrant consideration of an ICD for primary prevention of SAD. These findings will require a future randomized study to assess the utility of polygenic risk models to identify patients in whom ICD therapy would be valuable.