Strategies to attenuate pathological remodeling in heart failure.

PURPOSE OF REVIEW: The incidence of heart failure is increasing due to an aging population and improved management of diseases that are precursors to ventricular dysfunction. The success of therapeutic advances has created a challenge for the next generation of investigational heart failure treatments because the mortality rate has decreased to such a degree that larger trials will be needed to demonstrate mortality advantage. Prior work has linked favorable changes in ventricular geometry to improved survival, suggesting that remodeling may be a suitable surrogate endpoint.

RECENT FINDINGS: In addition to the established benefits of neurohormonal blockade, new mechanical and electrical therapies are proving beneficial in heart failure. Passive cardiac support devices and cardiac resynchronization therapy have been recently demonstrated to induce reverse remodeling of the left ventricle and may improve outcomes, including quality of life, functional status, and mortality.

SUMMARY: Ventricular remodeling is strongly correlated with improvement in other heart failure outcomes. Early phase trials of novel therapeutics should carefully examine remodeling to obtain an efficacy signal. Larger clinical investigations should include remodeling metrics as endpoints and consider their use in a composite primary endpoint to reduce trial size.