Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension

Abstract

Objective Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterization with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Methods Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterization and Doppler echocardiography at rest and during incremental exercise, and cardiac magnetic resonance imaging (MRI) at rest. Measurements at rest included basic hemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z0), characteristic impedance (ZC, a measure of proximal PA stiffness) and proximal and distal PA compliance (CPA). Results In PAH patients, the proximal PAs were significantly stiffer at maximum exercise (ZC = 2.31 ± 0.38 vs. 1.33 ± 0.15 mmHg min/ml/m2 at rest; p=0.003) and PA compliance was decreased (CPA = 0.88 ± 0.10 vs. 1.32 ± 0.17 mL/mmHg/m2 at rest; p=0.0002). Z0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (1.00 ± 0.07 at vs. 0.67 ± 0.05 s; p<10−6). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited CPA reduction at maximum exercise. Conclusions In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor hemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated.

Pathophysiology of exercise intolerance in pulmonary arterial hypertension

“…The relationship between ventricular contractility and afterload is referred to as ‘ventriculoarterial coupling’ . In PAH, RV contractility is increased, but uncoupling occurs when the increase in contractility is inadequate to meet the demands of high afterload . This is manifested as attenuated RV contractile reserve during dobutamine stress .…”

“…10 In PAH, RV contractility is increased, but uncoupling occurs when the increase in contractility is inadequate to meet the demands of high afterload. 37,38 This is manifested as attenuated RV contractile reserve during dobutamine stress. 7 The gold standard for assessing ventriculoarterial coupling is via analysis of pressure-volume loops, obtained invasively.…”

“…70 Recent elegant work has demonstrated that, whilst reduced pulmonary vascular compliance and increased stiffness are important, the interaction between the vasculature and the ventricle is probably more important than either factor in isolation (see ventriculoarterial coupling described above). 37…”

Heartbeat:Blood urea nitrogen to creatinine ratio predicts outcome in acute heart failure

“…In an elegant and detailed study of 26 subjects with PAH, Bellofiore and colleagues2 measured proximal and distal pulmonary artery stiffness, pulmonary impedance and other measures of ventricular-vascular coupling at rest and with exercise. Compared to normal subjects, PAH patients had increased pulmonary arterial stiffness at rest and a further increase in stiffness with exercise, despite no change in pulmonary vascular resistance (the more conventional measure).…”

Stressing the right ventricular-pulmonary vascular unit: beyond pulmonary vascular resistance

“…In their Heart manuscript, Bellofiore et al 3 improve our mechanistic understanding of RV-pulmonary vascular uncoupling during exercise in patients with PAH. As elegantly depicted in figure 1 of their study, the authors used a comprehensive method combining echocardiographic PA flow measurements with simultaneous PA pressure measurements via a high-fidelity micromanometer-tipped catheter to investigate the effects of exercise on the different components of RV afterload.…”