Background: The aim of this study was to review our experience with beta-blocker therapy on top of high-dose angiotensin-converting enzyme inhibitors (ACE-I) in patients with advanced heart failure evaluated for heart transplantation, and to question the value of intended heart transplantation for patients receiving this therapy.
Methods: Three hundred eighteen patients (New York Heart Association (NYHA) function class III 34%, class IV 66%, average left ventricular ejection fraction (LVEF) 16%, and average cardiac index 2.2 l/min per m(2) at time of referral) were treated with digitalis, loop diuretics, maximally uptitrated ACE-I, beta-blockers (if tolerated), and intravenous support (if needed). After 3 months, patients were retrospectively stratified into those receiving beta-blockers plus ACE-I (Group A, n = 126), ACE-I (Group B, n = 135), and ACE-I plus intravenous support (Group C, n = 57). Endpoint 1 of the study was combined urgent heart transplantation, mechanical assist device implantation, and pretransplant death during a follow-up of 12 to 48 (mean 19 +/- 11) months. Endpoint 2 was posttransplant mortality up to 48 (mean 14 +/- 8) months.
Results: In the pretransplantation period the survival rate was 58% and the mortality rate was 20%. Between Groups A and B there was a significant difference in mortality (9% vs 27%, p = 0.001) due to a lower sudden-death rate in Group A (6% vs 17%, p < 0.01). While between Groups A and C all event rates of Endpoint 1 differed significantly, between Group C and Group B total mortality (30% vs 27%) was similar. However, in Group C urgent heart transplantation (HTx) was more often performed than in Group B (54% vs 11%, p < 0.0001). Seventy of 318 patients (22%) underwent heart transplantation (16% urgent, 6% elective). Posttransplant actuarial survival of the entire transplanted cohort (n = 70, 12 deaths) was significantly lower (log rank p < 0.01) than event-free survival in Group A (n = 126, 18 events), significantly higher (log rank p < 0. 0001) than event-free survival in Group C (n = 57, 34 events), and similar to that in Group B (n = 135, 52 events).
Conclusion: This experience suggests that it may be particularly useful to add a beta-blocker to ACE-I therapy in patients referred for heart transplantation. In patients who tolerate this treatment, heart transplantation does not seem to provide additional survival benefit in the short term (2 years).