Biomarkers of cardiac function and outcome in univentricular congenital heart disease

Figures & data

Table 1 Biomarkers for outcome and heart failure in univentricular physiology

Biomarker (AHA level of evidence)	Study	Patients (n)	Age (years)	Design/population	Key results
Demographic, anatomic, and hemodynamic (AHA level B)	Rogers (2012)^Citation15	771	Mean 2.3 (Range 0.9–38.4)	Retrospective/TCPS patients	Presence of AVVR associated with early death or TCPS takedown within 30 days HLHS, younger age at TCPS, no fenestration associated with hospital stay >14 days, pleural effusion >14 days Preoperative PA pressure ≥15 mmHg associated with prolonged pleural effusions, prolonged hospital stay, death
	D’Udekem (2007)^Citation7	305	Mean 4.4 (IQR 3–7)	Retrospective/TCPS patients	• Elevated preoperative PA pressure, presence of AVVR independently associated with in-hospital mortality
	Hirsch (2008)^Citation11	636	Mean 2 (IQR 1.7–2.5)	Retrospective/TCPS patients	Longer aortic cross-clamp time associated with lower long-term survival Pleural effusions >2 weeks associated with decreased short- and long-term survival
	Kim (2008)^Citation14	200	Mean 3.4 (Range 1.3–35.7)	Retrospective/TCPS patients	High preoperative PA pressure associated with mortality Heterotaxy syndromes, age at TCPS were associated with postoperative arrhythmias
	Khairy (2008)^Citation12	261	Mean 7.9 (IQR 4.4–14.8)	Retrospective/TCPS patients	• PLE, single RV morphology, high preoperative RA pressure associated with heart failure
	Ohuchi (2011)^Citation6	405	Mean±SEM 4.9±5.2	Retrospective/TCPS patients	Heterotaxy, AVVR associated with early mortality Type of TCPS associated with late mortality Low EF, AVVR, TAPVR in setting of extracardiac conduit associated with mortality
	Gaynor (2002)^Citation8	332	Mean 1.8 (Range 0.9–3 1.7)	Retrospective/TCPS patients	Common AV valve, high preoperative PA pressure associated with early death HLHS associated with prolonged pleural effusions
	Anderson (2008)^Citation34	546	Mean±SEM 3.4±2.1	Cross sectional/TCPS patients	Single RV morphology associated with poor ventricular function, AVVR Older age at TCPS associated with worse AVVR, arrhythmias
Cardiopulmonary exercise testing (AHA level B)	Diller (2010)^Citation16	321	Mean±SEM 20.9±8.6	Retrospective/TCPS patients	HRR, pVO2, percent predicted pVO2, VE/VCO2 slope associated with hospitalization HRR associated with death/transplantation
	Giardini (2008)^Citation18	50	Mean±SEM 15.4±6.3	Retrospective/TCPS, atriopulmonary, or AV connection patients	• Single RV morphology and non-TCPS palliation associated with increased rate of pVO2 decline over time
	Madan (2010)^Citation19	50	NYHAI/2 – Mean±SEM 15.5±5.5 NYHA3/4 – Mean±SEM 18.9+6.8	Retrospective/TCPS patients	• Higher mean/peak CircP and pVO2 associated with lower NYHA class
Natriuretic peptides (AHA level B)	Auerbach (2010)^Citation35	138	Mean 3.4 (IQR 1.1–11.0)	Post hoc analysis of Pediatric Carvedilol Study/Heart failure patients	• Higher median BNP associated with poor outcomes, however, not affected by age, diagnosis, sex, single ventricle morphology
	Shah (2009)^Citation24	29	Mean 2 (Range 0.3–6.7)	Cross sectional/univentricular patients	• BNP cut-point with sensitivity and specificity for diagnosing heart failure was lower in univentricular patients versus adults/children with structurally normal hearts
	Lowenthal (2012)^Citation20	71	Single RV – Mean 1.3 (Range 0.2–6.7) Single LV-Mean 3.7 (Range 0.3–6.5) Indeterminate ventricle-Mean 5 (Range 4.7–5.5)	Cross sectional/univentricular patients	• BNP cut-point >45 pg/mL predicted heart failure in univentricular patients across different stages of surgical palliation, and independent of single ventricle morphology

Note: AHA level B refers to limited populations evaluated, with data derived from a single randomized trial, or non-randomized studies.¹

Abbreviations: AHA, American Heart Association; AV, atrioventricular; AVVR, atrioventricular valve regurgitation; BNP, B-type natriuretic peptide; CircP, peak circulatory power; EF, ejection fraction; HLHS, hypoplastic left heart syndrome; HRR, heart rate reserve; IQR, interquartile range; LV, left ventricle; NYHA, New York Heart Association; PA, pulmonary artery; PLE, protein-losing enteropathy; pVO₂, peak oxygen consumption; RA, right atrium; RV, right ventricle; SEM, standard error of the mean; TAPVR, total anomalous pulmonary venous return; TCPS, total cavopulmonary shunt; VE/VCO2, minute ventilation-carbon dioxide production.

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