Laboratory measures of exercise capacity and ventricular characteristics and function are weakly associated with functional health status after Fontan procedure

Abstract

Background: Patients after the Fontan procedure are at risk for suboptimal functional health status, and associations with laboratory measures are important for planning interventions and outcome measures for clinical trials.

Methods and results: Parents completed the generic Child Health Questionnaire for 511 Fontan Cross-Sectional Study patients 6 to 18 years of age (61% male). Associations of Child Health Questionnaire Physical and Psychosocial Functioning Summary Scores (FSS) with standardized measurements from prospective exercise testing, echocardiography, magnetic resonance imaging, and measurement of brain natriuretic peptide were determined by regression analyses. For exercise variables for maximal effort patients only, the final model showed that higher Physical FSS was associated only with higher maximum work rate, accounting for 9% of variation in Physical FSS. For echocardiography, lower Tei index (particularly for patients with extracardiac lateral tunnel connections), lower indexed end-systolic volume, and the absence of atrioventricular valve regurgitation for patients having Fontan procedure at age <2 years were associated with higher Physical FSS, accounting for 14% of variation in Physical FSS. For magnetic resonance imaging, ratio of lower mass to end-diastolic volume and midquartiles of indexed end-systolic volume (nonlinear) were associated with higher Physical FSS, accounting for 11% of variation. Lower brain natriuretic peptide was significantly but weakly associated with higher Physical FSS (1% of variation). Significant associations for Psychosocial FSS with laboratory measures were fewer and weaker than for Physical FSS.

Conclusions: In relatively healthy Fontan patients, laboratory measures account for a small proportion of the variation in functional health status and therefore may not be optimal surrogate end points for trials of therapeutic interventions.

Figure 1. Level of Participation of PHN Fontan Cross-Sectional Study Enrolled Subjects

BNP, brain natriuretic peptide; CHQ, Child Health Questionnaire; ECHO, echocardiography; MRI, magnetic resonance imaging; PHN, Pediatric Heart Network; vars, variables

Figure 2. Interaction of Subjective Grade of Atrioventricular Valvar Regurgitation from Echocardiography with Age at Fontan and the Association with Physical Functioning Summary Score

The detrimental impact of moderate or severe atrioventricular valve regurgitation appears to be limited to patients who had Fontan at <2 years of age. CHQ, Child Health Questionnaire; FSS, Functioning Summary Score; Mod-Sev, moderate to severe

Figure 3. Non-Linear Relationship Between MRI-Assessed End-Systolic Ventricular Volume Indexed to Body Surface Area (mL/m^1.3) and Physical Functioning Summary Score