Plasma Biomarkers for Prediction of Sudden Cardiac Death

Abstract

Sudden cardiac death (SCD) accounts for most cardiovascular deaths in the United States, claiming an estimated 300 000 lives per year.1 Despite intense efforts to develop resuscitation techniques, survival rates are still low, at ≈5%.2 This has led to a renewed focus in this field directed toward optimizing risk prediction to identify the candidate that would qualify for prophylactic or preventive interventions.3 At present, the clinical risk stratification is largely limited to the use of left ventricular ejection fraction (LVEF) for identifying primary prophylaxis candidates, but specificity of this predictor is modest.4 Moreover, the absolute numbers of these high-risk patients in the general population are low. Instead, the highest prevalence of SCD is likely observed among previously asymptomatic individuals, even though it is well-known that coronary artery disease (CAD) is present in most SCD cases.5 This underscores the need for the development of risk stratification models that can be applied to the general population where the largest health benefit is likely to be realized. The underpinnings of SCD are complex, and it is reasonable to believe that the risk stratification instrument of the future is likely to involve other components beyond clinical risk markers. Novel genomic variants show promise but are still in early phases of development as risk stratification targets. However, the “unbiased” approaches made possible through genomewide association studies have led to the recent identification of specific genetic variants that could predict SCD.6,7 This has reignited the interest in plasma biomarkers as a means for risk stratification. This article will review the emerging evidence and role of plasma biomarkers in predicting SCD in the general population and suggest a blueprint for future studies of potential utility. ### Uniform Definition of SCD Given the complexity and dynamic nature of the condition, there has been some variability …