Target heart failure populations for newer therapies

The scarcity of donor hearts has created a large population of heart failure patients who are unlikely to undergo transplantation. Newer surgical therapies that might sustain such patients at home previously have been applied in critical situations in which early outcome is jeopardized by multiorgan failure. The optimal population for studies of extended support would be ambulatory patients with low operative risk but high risk of later unfavorable outcome.

Baseline clinical, echocardiographic, and hemodynamic data were collected prospectively between 1988 and 1993 in 500 patients who were discharged on tailored medical therapy after evaluation for transplantation. Specific criteria were examined to identify high risk of death or need for urgent transplantation during the next 2 years. In 265 patients with ejection fraction < or = 25% and initial New York Heart Association class IV symptoms, survival at 2 years was 55% (without urgent transplantation, 45%). Lower cardiac index or higher filling pressures at the time of referral did not confer higher risk, which was predicted by persistence of higher pressures after therapy. Serum sodium below 133 was associated with 34% 2-year survival without urgent transplantation, and ventricular dimension > 80 mm with a rate of 25%. Patients with initial peak oxygen consumption > 10 mL/kg per minute had a 2-year event-free rate of 72% compared with 48% for those with < 10 mL/kg per minute and 32% for those unable to exercise at referral. Demonstration of a 30% decrease in mortality with a controlled trial of new therapy in patients with ejection fraction < or = 25% would require 600 patients with class III symptoms or almost 300 patients with class IV symptoms unless another criterion were added.

Ambulatory populations with high predicted event rates can be identified at initial evaluation, when hemodynamic criteria may be less useful than ventricular dimension, serum sodium, and ability to exercise. The use of outcome data from previous eras may lead to overestimation of benefits from newer therapies and underestimation of the sample size required in a prospective trials.