Pieles GE; University of Toronto, Toronto, Ontario, Canada. and other sites
Dorobantu DM; Caterini JE; Cifra B; Reyes J; Roldan Ramos S;
Hannon E; Williams CA; Humpl T; Mertens L; Wells GD; Friedberg MK

American Journal of Physiology – Heart & Circulatory Physiology.
327(4):H749-H764, 2024 Oct 01.

Despite exercise intolerance being predictive of outcomes in pulmonary
arterial hypertension (PAH), its underlying cardiac mechanisms are not
well described. The aim of the study was to explore the biventricular
response to exercise and its associations with cardiorespiratory fitness
in children with PAH. Participants underwent incremental cardiopulmonary
exercise testing and simultaneous exercise echocardiography on a recumbent
cycle ergometer. Linear mixed models were used to assess cardiac function
variance and associations between cardiac and metabolic parameters during
exercise. Eleven participants were included with a mean age of 13.4 +/-
2.9 yr old. Right ventricle (RV) systolic pressure (RVsp) increased from a
mean of 59 +/- 25 mmHg at rest to 130 +/- 40 mmHg at peak exercise (P <
0.001), whereas RV fractional area change (RV-FAC) and RV-free wall
longitudinal strain (RVFW-Sl) worsened (35.2 vs. 27%, P = 0.09 and -16.6
vs. -14.6%, P = 0.1, respectively). At low- and moderate-intensity
exercise, RVsp was positively associated with stroke volume and O2 pulse
(P < 0.1). At high-intensity exercise, RV-FAC, RVFW-Sl, and left
ventricular longitudinal strain were positively associated with oxygen
uptake and O2 pulse (P < 0.1), whereas stroke volume decreased toward peak
(P = 0.04). In children with PAH, the increase of pulmonary pressure alone
does not limit peak exercise, but rather the concomitant reduced RV
functional reserve, resulting in RV to pulmonary artery (RV-PA)
uncoupling, worsening of interventricular interaction and LV dysfunction.
A better mechanistic understanding of PAH exercise physiopathology can
inform stress testing and cardiac rehabilitation in this population. NEW &
NOTEWORTHY In children with pulmonary arterial hypertension, there is a
marked increase in pulmonary artery pressure during physical activity, but
this is not the underlying mechanism that limits exercise. Instead, right
ventricle-to-pulmonary artery uncoupling occurs at the transition from
moderate to high-intensity exercise and correlates with lower peak oxygen
uptake. This highlights the more complex underlying pathological responses
and the need for multiparametric assessment of cardiac function reserve in
these patients when feasible.