Association of Albuminuria With Major Adverse Outcomes in Adults With Congenital Heart Disease: Results From the Boston Adult Congenital Heart Biobank

Abstract

Importance: Albuminuria is associated with adverse outcomes in diverse groups of patients, but the importance of albuminuria in the emerging population of increasingly complex adults with congenital heart disease (ACHD) remains unknown.

Objective: To assess the prevalence, risk factors, and prognostic implications of albuminuria in ACHD.

Design, setting, and participants: This prospective study assessed a cohort of ambulatory patients aged 18 years and older who were examined at an ACHD referral center and enrolled in the Boston ACHD Biobank between May 17, 2012, to August 5, 2016. Albuminuria was defined as an urine albumin-to-creatinine (ACR) ratio of 30 mg/g or more.

Main outcomes and measures: Death or nonelective cardiovascular hospitalization, defined as overnight admission for heart failure, arrhythmia, thromboembolic events, cerebral hemorrhage, and/or disease-specific events.

Results: We measured the ACR of 612 adult patients with CHD (mean [SD] age, 38.6 [13.4] years; 308 [50.3%] women). Albuminuria was present in 106 people (17.3%) and was associated with older age (patients with ACR <30 mg/g: mean [SD]: 37.5 [13.2] years; vs patients with ACR ≥30 mg/g: 43.8 [13.1] years; P < .001), presence of diabetes mellitus (ACR <30 mg/g: 13 of 506 [2.6%]; vs ≥30 mg/g: 11 of 106 [10.4%]; P < .001), lower estimated glomerular filtration rate (ACR <30 mg/g: median [interquartile range (IQR)]: 103.3 [90.0-116.4] mL/min/1.73 m2; ACR ≥30 mg/g: 99.1 [78.8-108.7] mL/min/1.73 m2; P = .002), and cyanosis (ACR <30 mg/g: 23 of 506 [5.1%]; vs ACR ≥30 mg/g: 21 of 106 [22.6%]; P < .001). After a mean (SD) follow-up time of 270 (288) days, 17 patients (2.5%) died, while 68 (11.1%) either died or experienced overnight inpatient admission. Albuminuria predicted outcome, with 30 of 106 patients with albuminuria (28.3%) affected vs 38 of 506 patients without albuminuria (7.5%; hazard ratio [HR], 3.0; 95% CI, 1.9-4.9; P < .001). Albuminuria was also associated with increased mortality (11 of 106 [10.4%]; vs 6 of 506 [1.2%] in patients with and without albuminuria, respectively; HR, 6.4; 95% CI, 2.4-17.3; P < .001). Albuminuria was associated with the outcomes only in patients with a biventricular circulation (HR, 4.5; 95% CI, 2.5-8.0) and not those with single-ventricle circulation (HR, 1.0; 95% CI, 0.4-2.8; P = 0.01 compared with biventricular circulation group). Among 133 patients (21.7%) in NYHA functional class 2, albuminuria was strongly associated with death or nonelective hospitalization.

Conclusions and relevance: Albuminuria is common and is associated with increased risk for adverse outcome in patients with ACHD with biventricular circulation. Albuminuria appears especially useful in stratifying risk in patients categorized as NYHA functional class 2.

Figure 1.. Prevalence of Albuminuria in Adults by Type of Congenital Heart Disease

Frequency of albuminuria (defined as an albumin-to-creatinine ratio ≥30 mg/g) according to underlying congenital heart disease diagnosis. The solid line represents the approximate general population prevalence (6.5%). Subgroups included 18 patients with Eisenmenger syndrome/complex cyanotic, 18 with a simple shunt with clinical sequelae, 86 with single ventricle Fontan circulation, 60 with TGA with systemic RV, 16 with AVSD, 16 with Ebstein anomaly, 126 with tetralogy of Fallot, 20 with TGA with systemic left ventricle, 141 with left ventricular obstructive lesions, 71 with a simple shunt with no sequelae, and 40 with miscellaneous other disorders. AVSD indicates atrioventricular septal defect; LV, left ventricle; RV, right ventricle; TGA, transposition of the great arteries.

Figure 2.. Survival Time Free From Death or Nonelective Cardiovascular Hospitalization, Categorized by Degree of Albuminuria

Kaplan-Meier survival plots for adults with congenital heart disease classified by degree of albuminuria: normal or mildly increased (ACR <30 mg/g; n = 506; vs moderately increased (ACR ≥30-300 mg/g; n = 90; P < .001 compared with normal/mild albuminuria); vs severely increased, (ACR >300 mg/g; n = 16; P < .001 in comparison to moderately increased albuminuria). ACR indicates albumin-to-creatinine ratio.

Figure 3.. Survival Time Free from Death or Nonelective Cardiovascular Hospitalization, Stratified by Type of Circulation

A, Kaplan-Meier survival plot for adult congenital heart disease patients by albuminuria status, for patients with biventricular circulation; an ACR level of 30 mg/g or greater was a significant predictor of the combined outcome (hazard ratio, 4.5; 95% CI, 2.5-8.0; P < .001 by log-rank test). B, For patients with single-ventricle Fontan circulation, an ACR level of 30 mg/g or greater was not a significant predictor of the combined outcome (hazard ratio, 1.0; 95% CI, 0.4-2.8; P = .95 by log-rank test). ACR indicates albumin-to-creatinine ratio.