Experience with beta-blocker therapy in patients with advanced heart failure evaluated for HTx.
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).


CONCLUSIONS
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).
Berger
R
R
Department of Cardiology and Ludwig Boltzman Institute of Cardiovascular Research, University of Vienna, Vienna, Austria. RBerger@gmx.at
Strecker
K
K
Hülsmann
M
M
Frey
B
B
Pacher
R
R
Stanek
B
B
D000206:Actuarial Analysis; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D001262:Atenolol / Q000008:administration & dosage / Q000009:adverse effects; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D016027:Heart Transplantation; D006801:Humans; D011412:Propanolamines / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D001262:Atenolol; D004656:Enalapril