Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer.
OBJECTIVE
A common late effect of doxorubicin therapy for childhood cancer is reduced left-ventricular (LV) wall thickness resulting in elevated LV afterload and depressed LV function. Many children are given angiotensin-converting enzyme inhibitors, which have been studied primarily in adults. We document the long-term effects of angiotensin-converting enzyme inhibitors in doxorubicin-treated survivors of childhood cancer.


METHODS
In this retrospective study, we reviewed records of 18 children who had regular echocardiographic examinations during enalapril therapy (mean age at cancer diagnosis, 8 years; mean time between completion of doxorubicin therapy and start of enalapril, 7 years; median follow-up since the start of enalapril, 10 years).


RESULTS
Over the first 6 years of enalapril therapy, there was progressive improvement toward normal values in LV dimension, afterload, fractional shortening, and mass, but all these parameters deteriorated between 6 and 10 years. LV wall thickness deteriorated throughout the study period, as did LV contractility and systolic blood pressure. Diastolic blood pressure fell slightly. By 6 years on enalapril, all six patients who had had congestive heart failure at the start of enalapril therapy had either died or undergone cardiac transplantation, compared with three of the 12 asymptomatic patients.


CONCLUSIONS
In doxorubicin-treated long-term survivors of childhood cancer, enalapril-induced improvement in LV structure and function is transient. The primary defect, which is LV wall thinning, continues to deteriorate, and thus the short-term improvement was mostly related to lowered diastolic blood pressure.
Lipshultz
Steven E
SE
Division of Pediatric Cardiology, University of Rochester Medical Center, NY 14642, USA. steve_lipshultz@urmc.rochester.edu
Lipsitz
Stuart R
SR
Sallan
Stephen E
SE
Simbre
Valeriano C
VC
Shaikh
Seema L
SL
Mone
Suzanne M
SM
Gelber
Richard D
RD
Colan
Steven D
SD
D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D003971:Diastole / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004452:Echocardiography; D004656:Enalapril / Q000627:therapeutic use*; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D012189:Retrospective Studies; D012306:Risk; D017741:Survivors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000903:Antibiotics, Antineoplastic; D000959:Antihypertensive Agents; D004656:Enalapril; D004317:Doxorubicin