BAG3 protein in advanced-stage heart failure.

We thank Dr. Weir for the insightful comments in regard to our recent report (1). We wholeheartedly agree with the assertion that biomarkers may play a role in prediction of risk of sudden cardiac death in combination with electrical and structural assessments of the heart. It would be expected that inclusion of specifics of the surface electrocardiogram such as QT variability and novel imaging modalities such as late gadolinium enhancement on cardiac magnetic resonance could potentially add both accuracy and precision to the prediction of sudden cardiac death. However, such detailed phenotyping was not performed in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) study. Furthermore, patients with chronic heart failure have an increased risk of death from a variety of causes other than sudden cardiac death, and extremely accurate predictors of one mode of death might not be clinically feasible in the setting of these competing risks. Risk of sudden cardiac death is also not static, and frequent detailed assessments of cardiac structure and electrocardiography may not be practical in the clinical setting. With these unanswered questions in mind, there is an unmet need to compare various predictors of sudden cardiac death to assess their comparative prognostic and cost effectiveness.