Low Ventricular Stiffness Is Associated With Suboptimal Outcomes in Patients With a Single Right Ventricle After the Fontan Operation: A Novel Phenotype

Abstract

Background: Despite a rigorous screening process, including cardiac catheterization, a subset of patients with a single right ventricle (SRV) demonstrates suboptimal short-term outcomes after the Fontan operation. The goal of this study was to perform a comprehensive assessment of diastolic function in pre-Fontan patients with an SRV using invasive reference-standard measures and determine their associations with post-Fontan outcomes.

Methods and results: Children aged 2 to 6 years with SRV physiology undergoing pre-Fontan heart catheterization were recruited prospectively. Patients were divided into those who had an optimal or suboptimal outcome. A suboptimal outcome was defined as length of stay ≥14 days or heart transplant/cardiac death in first year after Fontan. Patients underwent pressure-volume loop analysis using reference-standard methods. The measure of ventricular stiffness, β, was obtained via preload reduction. Cardiac magnetic resonance imaging for extracellular volume and serum draws for matrix metalloproteinase activity were performed. Of 19 patients with an SRV, 9 (47%) had a suboptimal outcome. Mean age was 4.2±0.7 years. Patients with suboptimal outcomes had lower ventricular stiffness (0.021 [0.009-0.049] versus 0.090 [0.031-0.118] mL^-1; P=0.02), lower extracellular volume (25% [28%-32%] versus 31% [28%-33%]; P=0.02), and lower matrix metalloproteinase-2 (90 [79-104] versus 108 [79-128] ng/mL; P=0.01) compared with patients with optimal outcomes. The only invasive measure that had an association with suboptimal outcome was β (P=0.038).

Conclusions: Patients with an SRV with suboptimal outcome after the Fontan operation had lower ventricular stiffness and evidence of maladaptive extracellular matrix metabolism compared with patients with optimal outcome. This appears to be a novel phenotype that may have important clinical implications and requires further study.

Keywords: Fontan; diastolic function; pressure–volume relation; single ventricle.

Figure 1. A 4 French microconductance catheter is placed antegrade through the inferior vena cava in the single right ventricle apex.

Sensors outside of the ventricle are excluded from analysis.

Figure 2. Pressure–volume loop obtained in a patient with a single right ventricle (A) and a control patient (B) during preload reduction with a low‐pressure balloon inflated in the superior vena cava at the bidirectional Glenn anastomosis site.

The red line represents the end‐systolic pressure–volume relationship. The blue line represents the end‐diastolic pressure volume relationship. The rightward exponential slope of the end‐diastolic pressure volume relationship represents β, the ventricular stiffness constant.

Figure 3. T1 mapping of an SRV patient from the mid short‐axis image.

Precontrast (A) and postcontrast (B) native T1 images are shown. Epicardial (green tracing), endocardial (red tracing), and blood pool (yellow tracing) borders are shown and are used to calculate T1 values shown on the right. These values and the patient's hematocrit are used to calculate the extracellular volume (ECV) map (C) and ECV value shown on the right. The model fit values are shown to the right.

Figure 4. Differences in ventricular stiffness (β) derived from pressure–volume loop analysis between the control (n=15), optimal outcome (n=10), and suboptimal outcome (n=9) groups.

P values represent differences between groups after Kruskal–Wallis analysis with multiple comparisons using Bonferroni correction.

Figure 5. Differences in extracellular volume derived from cardiac magnetic resonance imaging between optimal outcome (n=10), and suboptimal outcome (n=9) groups.

P values represent differences between groups after Mann–Whitney U tests.

Figure 6. Differences in serum matrix metalloproteinase 2 (MMP‐2) between the control (n=15), optimal outcome (n=10), and suboptimal outcome (n=9) groups.

P values represent differences between groups after Kruskal–Wallis analysis with multiple comparisons using Bonferroni correction.