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Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle. Circulation 2011 May 31;123(21):2353-62

Date

05/18/2011

Pubmed ID

21576655

Pubmed Central ID

PMC3137902

DOI

10.1161/CIRCULATIONAHA.110.004341

Abstract

BACKGROUND: We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle.

METHODS AND RESULTS: Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with renin-angiotensin-aldosterone system upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate, and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high risk), and those with <2 homozygous risk genotypes (low risk) at 2 time points: before the superior cavopulmonary connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: Thirty-eight were high risk, and 116 were low risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and estimated glomerular filtration rate increased after SCPC in the low-risk (P<0.05), but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline, and height remained lower in the high-risk group at 14 months, especially in those receiving enalapril (P<0.05).

CONCLUSIONS: Renin-angiotensin-aldosterone system-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. Renin-angiotensin-aldosterone system genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume-unloading surgery. Follow-up is warranted to assess long-term impact.

CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00113087.

Author List

Mital S, Chung WK, Colan SD, Sleeper LA, Manlhiot C, Arrington CB, Cnota JF, Graham EM, Mitchell ME, Goldmuntz E, Li JS, Levine JC, Lee TM, Margossian R, Hsu DT, Pediatric Heart Network Investigators

Authors

Dudley Woodrow Benson MD Clinical Professor in the Pediatrics department at Medical College of Wisconsin
Peter C. Frommelt MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aldosterone
Angiotensins
Cohort Studies
Double-Blind Method
Female
Genotype
Growth Disorders
Heart Ventricles
Humans
Infant
Infant, Newborn
Kidney Function Tests
Male
Peptidyl-Dipeptidase A
Polymorphism, Genetic
Renin
Renin-Angiotensin System
Up-Regulation
Ventricular Function
Ventricular Remodeling
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75