Renin–angiotensin–aldosterone system genotype and serum BNP in a contemporary cohort of adults late after Fontan palliation. (15th October 2015)

• Record Type: Journal Article
• Authors: Burchill, Luke J.; Redington, Andrew N.; Silversides, Candice K.; Ross, Heather J.; Jimenez-Juan, Laura; Mital, Seema; Oechslin, Erwin N.; Dragulescu, Andreea; Slorach, Cameron; Mertens, Luc; Wald, Rachel M.
• Is Part Of: International journal of cardiology. Volume 197(2015)
• Page Start: 209
• Page End: 215
• Publication Date: 2015-10-15
• Subjects: ACE angiotensin converting enzyme -- BNP B-type natriuretic peptide -- CMR cardiac magnetic resonance -- CPET cardiopulmonary exercise test -- DBP diastolic blood pressure -- EDV end-diastolic volume -- ESV end-systolic volume -- HF heart failure -- IVRT isovolumic relaxation time -- LV left ventricle -- LVH left ventricular hypertrophy -- NYHA New York Heart Association -- RA right atrium -- RAAS renin–angiotensin–aldosterone system -- RER respiratory exchange ratio -- SBP systolic blood pressure -- TCPC total cavopulmonary connection; Angiotensin-converting enzyme -- Congenital heart disease -- Clinical genetics -- Fontan -- Heart failure -- Hypertrophy; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2015.06.018
• Languages: English
• ISSNs: 0167-5273

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.