SERCA2a gene therapy for the prevention of sudden cardiac death: a future theranostic for heart failure?

Sudden cardiac death (SCD) is a common cause of mortality, with an annual incidence in the United States ranging from 180 000 to 450 000 cases annually.1 Given the frequency and gravity of SCD, there has been considerable effort directed toward decreasing the burden of SCD.2 Most of these efforts have focused on those at highest risk for SCD: (1) patients with heart failure (HF), specifically those with reduced ejection fraction (HFrEF); and (2) patients who have suffered a myocardial infarction and have reduced EF.2 However, although these groups of patients have the highest rate of SCD, the absolute number of SCDs in patients with overt left ventricular (LV) systolic dysfunction pales in comparison with the number of SCDs that occur in the general population.3 Many SCD events in the general population likely occur in asymptomatic individuals who have cardiac structural or functional abnormalities, otherwise known as Stage B (subclinical) HF. For example, previous studies have found that structural heart disease (eg, increased LV mass4) without overt LV systolic dysfunction or HF is associated with increased risk of SCD.