Effects of therapeutic beta blockade on myocardial function and cardiac remodelling in congenital cardiac disease.
BACKGROUND
Cardiac remodelling is now recognised as an important aspect of cardiovascular disease progression and is, therefore, emerging as a therapeutic target in cardiac failure due to different etiologies. Little is known about the influence of different therapies for cardiac failure on the remodelling seen in infants with congenital cardiac disease.


METHODS
During follow-up of a prospective and randomized trial, we investigated therapeutic effects on neurohormonal activation, ventricular function, and myocardial gene expression. We compared the data from 8 infants with severe congestive heart failure due to left-to-right shunts, who received digoxin and diuretics alone, to 9 infants who received additional treatment with propranolol.


RESULTS
In these infants, beta-adrenergic blockade significantly reduced highly elevated levels of renin, from 284 +/- 319 microU/ml compared to 1061 +/- 769 microU/ml. Systolic ventricular function was normal in both groups, but diastolic ventricular function was improved in those receiving propranolol, indicated by significantly lower left atrial pressures, lower end-diastolic pressures, and less pronounced ventricular hypertrophy, the latter estimated by lower ratios of myocardial wall to ventricular cavity areas on average of 42%. Further hemodynamic parameters showed no significant differences between the groups, except for the lower heart rate in infants treated with propranolol. In those treated with digoxin and diuretics, there was a significant downregulation of beta2-receptor and angiotensin-2 receptor genes, and up-regulation of endothelin A receptor and connective tissue growth factor genes, that were partially prevented by additional treatment with propranolol.


CONCLUSIONS
Beta-blockade is a new therapeutic approach for congestive heart failure in infants with congenital cardiac disease, producing with significant benefits on neurohormonal activation, diastolic ventricular function, and cardiac remodelling.
Buchhorn
Reiner
R
Department of Pediatric Cardiology, Georg-August-University, Göttingen, Germany. rbuchho@gwdg.de
Hulpke-Wette
Martin
M
Ruschewski
Wolfgang
W
Ross
Robert D
RD
Fielitz
Jens
J
Pregla
Reinhard
R
Hetzer
Roland
R
Regitz-Zagrosek
Vera
V
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D004077:Digoxin / Q000008:administration & dosage*; D004232:Diuretics / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications* / Q000175:diagnosis; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D011336:Probability; D011379:Prognosis; D011433:Propranolol / Q000008:administration & dosage*; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D004232:Diuretics; D004077:Digoxin; D011433:Propranolol