Renin-angiotensin-aldosterone system genotype and serum BNP in a contemporary cohort of adults late after Fontan palliation

Luke J. Burchill, Andrew N. Redington, Candice K. Silversides, Heather J. Ross, Laura Jimenez-Juan, Seema Mital, Erwin N. Oechslin, Andreea Dragulescu, Cameron Slorach, Luc Mertens, Rachel M. Wald

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    Abstract

    Abstract Background Adults with single ventricle physiology palliated with a Fontan circulation experience high mortality due to circulatory failure. Renin-angiotensin-aldosterone system (RAAS) genotype contributes to adverse cardiovascular outcomes in acquired heart failure. This study evaluated associations between RAAS genotype, ventricular mass and function in a contemporary cohort of adults with a Fontan circulation. Methods This single-center prospective study included adults (n = 106) seen after the Fontan operation (mean age 27 ± 9 years). Patients were genotyped for 5 pro-hypertrophic RAAS gene polymorphisms. Serum BNP, ventricular mass and function, and clinical events were compared between those with ≥ 2 homozygous risk genotypes ("high-risk", n = 31) versus those with ≤ 1 homozygous risk genotypes ("low risk", n = 75). Results "High-risk" genotype was associated with diastolic dysfunction and higher serum BNP levels. There was no association between RAAS genotype and either ventricular mass or systolic function. During a mean follow-up duration of 9.5 ± 7.6 years, late Fontan failure occurred in 20% (n = 21) of patients, including 7 deaths. Serum BNP emerged as an independent predictor of late Fontan failure (HR 1.11 [CI 1.01-1.23] for each 50 unit increase in BNP, p = 0.04) and death alone (HR 1.25 [CI 1.07-1.47] for each 50 unit increase in BNP, p = 0.006). RAAS genotype was not associated with adverse clinical events. Conclusions Fontan failure is common among adults with single ventricle physiology. RAAS genotype is not associated with increased ventricular mass but does appear to influence diastolic function late after the Fontan operation. Elevated BNP is an independent predictor of Fontan failure and mortality in adulthood.

    Original languageEnglish (US)
    Article number20674
    Pages (from-to)209-215
    Number of pages7
    JournalInternational Journal of Cardiology
    Volume197
    DOIs
    StatePublished - Aug 5 2015

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    Keywords

    • Angiotensin-converting enzyme
    • Clinical genetics
    • Congenital heart disease
    • Fontan
    • Heart failure
    • Hypertrophy

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this

    Burchill, L. J., Redington, A. N., Silversides, C. K., Ross, H. J., Jimenez-Juan, L., Mital, S., Oechslin, E. N., Dragulescu, A., Slorach, C., Mertens, L., & Wald, R. M. (2015). Renin-angiotensin-aldosterone system genotype and serum BNP in a contemporary cohort of adults late after Fontan palliation. International Journal of Cardiology, 197, 209-215. [20674]. https://doi.org/10.1016/j.ijcard.2015.06.018