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Circulation. 2011 May 31;123(21):2353-62. doi: 10.1161/CIRCULATIONAHA.110.004341. Epub 2011 May 16.

Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle.

Author information

  • 1Division of Pediatric Cardiology Hospital for Sick Children, Toronto, Ontario, Canada. seema.mital@sickkids.ca

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.

PMID:
21576655
[PubMed - indexed for MEDLINE]
PMCID:
PMC3137902
Free PMC Article

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