TOPLINE:

In adults with Fontan circulation, a higher pulmonary vascular resistance index (PVRI) during exercise and failure to reduce the PVRI were associated with a greater risk for death or heart transplantation, whereas the PVRI at rest was not associated with these outcomes. PVRI reduction was associated with better event-free survival over 2 years.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to evaluate whether the PVRI response to exercise predicted outcomes in adults with Fontan circulation.
• They included 88 adults with a prior Fontan procedure who underwent invasive supine-cycling exercise cardiac catheterization between January 2019 and July 2024.
• Researchers measured resting and peak-exercise hemodynamics during cardiac catheterization, and the PVRI was calculated. Patients were grouped according to whether the PVRI decreased with exercise or not.
• The primary outcome was a composite of all-cause death or heart transplantation over a mean follow-up of 2.2 years.
• The mean age of the patients at cardiac catheterization was 32.2 years, and 45.5% of the patients were women.

TAKEAWAY:

• A higher exercise PVRI was associated with a greater risk for death or transplantation (hazard ratio [HR], 2.15 per Wood Unit [WU]·m²; P = .007), whereas the resting PVRI showed no such association (P = .86).
• Less reduction in the PVRI was linked to a greater risk for the composite outcome (HR, 1.49 per WU·m²; P = .04). The 2-year event-free survival was greater in patients with a reduction in the PVRI than in those without (95% vs 67%; P < .001).
• Patients without PVRI reduction had a larger increase in mean pulmonary artery pressure compared with those with PVRI reduction (13.6 mm Hg vs 10.8 mm Hg; P = .03) and smaller increases in pulmonary blood flow (44.1% vs 71.1%; P = .02) during exercise.
• The combination of no PVRI reduction and elevated exercise pulmonary artery wedge pressure (> 20 mm Hg) was associated with the worst survival, whereas PVRI reduction with lower exercise pulmonary artery wedge pressure was linked to no events (log-rank P = .002).

IN PRACTICE:

“PVRI response with exercise, but not resting PVRI, is a predictor of adverse clinical outcomes in adults post-Fontan palliation. These findings suggest that exercise hemodynamic testing may offer valuable insights for risk stratification in this unique population, though prospective validation in external cohorts is warranted,” the researchers wrote.

“[This study] highlights the value of dynamic, stress-based assessment, with exercise PVRI emerging as a robust prognostic marker that links ventricular and pulmonary vascular reserve. This approach not only improves risk prediction but also opens the door to personalized, physiology-guided therapies aimed at prolonging transplantation-free survival in the Fontan population,” experts wrote in an accompanying editorial.

SOURCE:

This study was led by Jacob Y. Cao of the Mayo Clinic in Rochester, Minnesota, and Royal Prince Alfred Hospital in Sydney, Australia. It was published online on December 23, 2025, in the European Heart Journal.

LIMITATIONS:

The retrospective design and referral-based selection may have introduced selection bias and included more complex patients. The cohort was small, and the follow-up duration was short. The findings lacked external validation.

DISCLOSURES:

One author reported receiving grants from the National Heart, Lung, and Blood Institute. All others reported having no disclosures of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.