Serial cardiac biomarker assessment in adults with congenital heart disease hospitalized for decompensated heart failure☆

Abstract

Background: Biomarkers are increasingly part of assessing and managing heart failure (HF) in adults with congenital heart disease (CHD).

Objectives: To understand the response of cardiac biomarkers with therapy for acute decompensated heart failure (ADHF) and the relationship to prognosis after discharge in adults with CHD.

Design: A prospective, observational cohort study with serial blood biomarker measurements.

Settings: Single-center study in the inpatient setting with outpatient follow-up.

Participants: Adults (≥18 years old) with CHD admitted with ADHF between August 1, 2019, and March 1, 2020.

Exposure: We measured body mass, Kansas City Cardiomyopathy Questionnaire (KCCQ-12) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) at enrollment, discharge, and 1st clinic follow-up visit; soluble suppression of tumorigenicity 2 (sST2) was measured at the first two time points.

Measures: Univariate regression assessed the association between changes in weight, biomarkers, and changes in KCCQ-12 scores, between enrollment and discharge (Δ _{Hospitalization} ) and between discharge and 1st clinical follow-up visit (Δ _{Post-discharge} ). Wilcoxon rank-sum tests assessed the association between change in biomarkers, KCCQ-12 scores, and the composite outcome of cardiovascular death or rehospitalization for ADHF.

Results: A total of 26 patients were enrolled. The median age was 51.9 years [IQR: 38.8, 61.2], 13 (54.2%) were women, and median hospital stay was 6.5 days [IQR: 4.0, 15.0] with an associated weight loss of 2.8 kg [IQR -5.1, -1.7]. All three cardiac biomarkers decreased during hospitalization with diuresis while KCCQ-12 scores improved; a greater decrease in sST2 was associated with an improved KCCQ-12 symptom frequency (SF) subdomain score (p = 0.012), but otherwise, there was no significant relationship between biomarkers and KCCQ-12 change. Change in hsCRP and NT-proBNP after discharge was not associated with the composite outcome (n = 8, vs. n = 16 who did not experience the outcome; Δ _{Post-discharge} hsCRP +5.1 vs. -1.0 mg/l, p = 0.061; NT-proBNP +785.0 vs. +130.0 pg/ml, p = 0.220).

Conclusions: Serial biomarker measurements respond to acute diuresis in adults with CHD hospitalized for ADHF. These results should motivate further research into the use of biomarkers to inform HF therapy in adults with CHD.

Keywords: Acute decompensated heart failure; Adult congenital heart disease; Biomarkers; High sensitivity C-Reactive protein; N-terminal pro-B-Type natriuretic peptide; Soluble suppression of tumorigenicity 2; The patient-reported outcomes.

Fig. 1

Study Timeline. Flow chart clarifies study timeline and data collection. Adults with CHD admitted for ADHF were enrolled in the study. Blood collections were done at three-time points (enrollment, discharge, and 1st clinic follow-up visit), and multiple variables were measured. Abbreviations: ADHF ​= ​acute decompensated heart failure; CHD ​= ​congenital heart disease, hsCRP ​= ​high-sensitivity C-reactive protein; KCCQ-12 ​= ​Kansas City Cardiomyopathy Questionnaire; NT-proBNP ​= ​N-terminal B-type natriuretic peptide; sST2 ​= ​soluble human suppression of tumorigenicity 2 glycoprotein, Δ _{Hospitalization} ​= ​discharge value-enrollment value; Δ _{Post discharge} ​= ​1st clinic follow up visit value-discharge value.

Fig. 2

Boxplots of KCCQ-12, Biomarkers, and Weight at the Three Time Points.The change in median weight from enrollment to discharge to the first clinic follow-up visit (A). The change in median KCCQ-12 overall summary score from enrollment to discharge to the 1st clinic follow-up visit (B). The change in median NT-proBNP (C), sST2 (D), and hsCRP (E) from enrollment to discharge to the 1st clinic follow-up visit. [KCCQ-12 subdomains panels are available as online supplement]. Abbreviation: hsCRP ​= ​high sensitivity C-reactive protein; KCCQ-12 ​= ​Kansas City Cardiomyopathy Questionnaire; NT-proBNP ​= ​N-terminal B-type natriuretic peptide; sST2 ​= ​soluble human suppression of tumorigenicity 2 glycoprotein.