Pulmonary Vascular and Right Ventricular Reserve in Patients With Normalized Resting Hemodynamics After Pulmonary Endarterectomy

Abstract

BackgroundPatients with normalized mean pulmonary artery pressure (mPAP) after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) do not always regain normal exercise capacity. We evaluated right ventricular function, its interaction with both pulsatile and resistive afterload, and the effect of sildenafil during exercise in these patients.Methods and ResultsFourteen healthy controls, 15 CTEPH patients, and 7 patients with normalized resting mPAP (≤25 mm Hg) post‐PEA underwent cardiopulmonary exercise testing, followed by cardiac magnetic resonance imaging with simultaneous invasive mPAP measurement during incremental supine cycling exercise. Peak oxygen consumption and peak heart rate were significantly reduced in post‐PEA and CTEPH patients compared to controls. The mPAP–cardiac output slope was steeper in post‐PEA patients than in controls and similar to CTEPH. Relative to controls, resting right ventricular ejection fraction was reduced in CTEPH, but not in post‐PEA patients. In contrast, peak exercise right ventricular ejection fraction was reduced both in post‐PEA and CTEPH patients. Exercise led to reduction of pulmonary arterial compliance in all groups. Nevertheless, resting pulmonary arterial compliance values in CTEPH and post‐PEA patients were even lower than those in controls at peak exercise. In post‐PEA patients, sildenafil did not affect resting hemodynamics nor right ventricular function, but decreased the mPAP/cardiac output slope and increased peak exercise right ventricular ejection fraction.ConclusionsExercise intolerance in post‐PEA patients is explained by abnormal pulmonary vascular reserve and chronotropic incompetence. The mPAP/cardiac output slope and pulmonary arterial compliance are sensitive measures demonstrating abnormal resistive and pulsatile pulmonary vascular function in post‐PEA patients. These abnormalities are partially attenuated with sildenafil.

Exercise-induced pulmonary hypertension: at last!

“…These results confirm previous reports that a steep mPAP−CO relationship, starting at the upper limit of normal, is associated with a decreased exercise capacity [15,18,[20][21][22][23]. This is presumably related to an afterload limitation of right ventricular flow output, but may require confirmation with exercise measurements of function, cardiac output and oxygen extraction.…”

“…Further steps are needed to identify causal pulmonary vascular disease, diastolic heart failure, or both [10]. In the meantime, exercise-induced pulmonary hypertension, however measured, has been shown to be of diagnostic and/or prognostic relevance in mitral valve disease [11], aortic stenosis [12], heart failure [13], systemic sclerosis [14][15][16], chronic obstructive pulmonary disease [17] and symptomatic patients after pulmonary endarterectomy [18].…”

Exercise pulmonary haemodynamics: a test in search of purpose

“…Relying on TPR we cannot differentiate precapillary from post-capillary abnormalities. We have limited previous data to suggest that exercise elevation of pulmonary pressure in disease populations is associated with progression to PH [7,8] or worse outcomes [9][10][11]. The "disease" population consisted of those with standard risk factors for pulmonary arterial hypertension (PAH), those with chronic thromboembolic disease, those with Sickle cell disease and those with risk factors for left heart disease.…”

Right ventricular and pulmonary vascular reserve in asymptomatic BMPR2 mutation carriers

“…This is at least partly to the technical challenges in assessing the RV during exercise. In a manner akin to pressure-volume analysis, we used a hybrid technique combining invasive PAP and CMR-derived volume measurements to determine the ratio of resting to peak exercise RV ESPVR to detect sub-clinical RV dysfunction (10). Using this approach, we demonstrate that RV functional reserve is not different in BMPR2 mutation carriers compared to controls, even in those subjects with an abnormal pulmonary vascular response to exercise and/or hypoxia.…”

“…We developed a methodology which combines invasive PAP measures with gold-standard cardiac magnetic resonance (CMR) quantification of RV function and Q during exercise and have used this technique to identify sub-clinical pulmonary vascular dysfunction and RV dysfunction (9,10). Thus, this technique is ideally suited to assess our hypothesis that abnormal pulmonary vascular and RV function would be demonstrable during exercise in asymptomatic subjects with a known BMPR2 mutation.…”