Impaired Cardiac Reserve and Abnormal Vascular Load Limit Exercise Capacity in Chronic Thromboembolic Disease.

This study was a comprehensive evaluation of cardiopulmonary function in patients with chronic thromboembolic (pulmonary vascular) disease (CTED) during exercise. Exertional dyspnea is frequent following pulmonary embolism, but only a minority of patients eventually develops chronic thromboembolic pulmonary hypertension (CTEPH). Better understanding of the factors that limit exercise capacity in patients with persistent pulmonary artery obstruction could help to further define the entity of CTED. Fifty-two subjects (13 healthy control subjects, 14 CTED patients, and 25 CTEPH patients) underwent cardiopulmonary exercise testing and exercise cardiac magnetic resonance with simultaneous invasive pressure registration. Pulmonary vascular function and right ventricular contractile reserve were assessed through combined invasive pressure measurements and magnetic resonance imaging volume measures. Exercise capacity was reduced by 29% and 57% in patients with CTED and CTEPH respectively, compared with control subjects. Both CTED (3.48 [interquartile range: 2.24 to 4.36] mm Hg × l-1 × min-1) and CTEPH patients (8.85 [interquartile range: 7.18 to 10.4] mm Hg × l-1 × min-1) had abnormal total pulmonary vascular resistance. Right ventricular contractile reserve was reduced in CTED patients compared with control subjects (2.23 ± 0.55 vs. 3.72 ± 0.94), but was still higher than that in CTEPH patients (1.34 ± 0.24; p < 0.001). As opposed to patients with CTEPH in whom right ventricular ejection fraction declined with exercise, right ventricular ejection fraction still increased in patients with CTED, albeit to a lesser extent than in healthy control subjects (interaction p < 0.001), which illustrated the distinct patterns of ventricular-arterial coupling. CTED represents an intermediate clinical phenotype. Exercise imaging unmasks cardiovascular dysfunction not evident at rest and identifies hemodynamically significant disease that results from reduced contractile reserve or increased vascular load.

Claeys M ，Claessen G ，La Gerche A ，Petit T ，Belge C ，Meyns B ，Bogaert J ，Willems R ，Claus P ，Delcroix M ... -  《-》

Pulmonary vascular and right ventricular reserve in patients with normalized resting hemodynamics after pulmonary endarterectomy.

Patients 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. Fourteen 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. Exercise 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.

Claessen G ，La Gerche A ，Dymarkowski S ，Claus P ，Delcroix M ，Heidbuchel H ... -  《Journal of the American Heart Association》

Right ventricular dysfunction in chronic thromboembolic obstruction of the pulmonary artery: a pressure-volume study using the conductance catheter.

McCabe C ，White PA ，Hoole SP ，Axell RG ，Priest AN ，Gopalan D ，Taboada D ，MacKenzie Ross R ，Morrell NW ，Shapiro LM ，Pepke-Zaba J ... -  《-》

Inefficient exercise gas exchange identifies pulmonary hypertension in chronic thromboembolic obstruction following pulmonary embolism.

Persistent obstruction in the pulmonary artery following acute pulmonary embolism (PE) can give rise to both chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease without PH (CTED). We hypothesised that cardiopulmonary exercise testing (CPET) may be able to differentiate patients with CTEPH and CTED following unresolved PE which may help guide patient assessment. Fifteen patients with CTEPH and 15 with CTED all diagnosed after PE underwent CT pulmonary angiography, CPET and resting right heart catheterisation. Exercise variables were compared between patients with CTEPH, CTED and 10 sedentary controls and analysed as predictors of a CTEPH diagnosis. Proximal thrombotic burden in CTEPH and CTED was quantified using CT criteria. Physiological dead space (Vd/Vt) (34.5±11.4 vs 50.8±6.6 %, p<0.001) and alveolar-arterial oxygen gradient (29±16 vs 46±12mmHg, p <0.001) at peak exercise strongly differentiated CTED and CTEPH groups respectively. Resting ventilatory efficiency also differed from control subjects. In both univariate and multivariate analyses, peak exercise Vd/Vt predicted a diagnosis of CTEPH (ROC AUC>0.88, 0.67 - 0.97) despite a similar degree of proximal thrombotic obstruction to the CTED group (67.5, 55 - 70% and 72.5, 60 - 80% respectively, p=0.08). Gas exchange at peak exercise differentiates CTED and CTEPH after PE that can present with no apparent relation to the degree of proximal thrombotic burden. A potential role for CPET exists in guiding further clinical investigations in this setting.

McCabe C ，Deboeck G ，Harvey I ，Ross RM ，Gopalan D ，Screaton N ，Pepke-Zaba J ... -  《-》

Accuracy of Echocardiography to Evaluate Pulmonary Vascular and RV Function During Exercise.

The authors have compared exercise echocardiography and exercise cardiac magnetic resonance imaging with simultaneous invasive pressure registration (ExCMRip) for the assessment of pulmonary vascular and right ventricular (RV) function. Exercise echocardiography may enable early diagnosis of pulmonary vascular disease, but its accuracy is untested. Exercise imaging was performed in 61 subjects (19 athletes, 9 healthy nonathletes, 8 healthy BMPR2 [bone morphogenetic protein receptor type II] mutation carriers, 5 patients with new or worsening dyspnea after acute pulmonary embolism, and 20 patients with chronic thromboembolic pulmonary hypertension). Echocardiographic variables included mean pulmonary artery pressure (mPAP) and systolic pulmonary artery pressure (sPAP), cardiac output (CO), RV fractional area change, tricuspid annular systolic excursion, and RV end-systolic pressure-area ratio as a surrogate measure of RV contractile reserve. ExCMRip provided measurements of CO, RV ejection fraction, mPAP, sPAP, and RV end-systolic pressure-volume ratio at rest and during exercise. Abnormal pulmonary vascular reserve was defined as mPAP/CO slope >3 mm Hg/l/min by ExCMRip. Echocardiographic determination of mPAP/CO was possible in 53 of 61 subjects (87%). mPAP/CO by echocardiography was higher than that obtained by ExCMRip (+0.9 mm Hg/l/min; 95% limits of agreement, -3.6 to 5.4), but enabled accurate identification of patients with abnormal pulmonary vascular reserve (area under the receiver-operating characteristic curve, 0.88 [95% confidence interval (CI): 0.77 to 1.00; p < 0.0001]). Simplified relationships between sPAP and exercise intensity had similar accuracy in identifying subjects with pulmonary vascular disease (area under the receiver-operating characteristic curve, 0.95 [95% CI: 0.88 to 1.01]; p < 0.0001). RV fractional area change by echocardiography correlated strongly with RV ejection fraction by ExCMRip, whereas a moderate correlation was found between tricuspid annular systolic excursion and RV ejection fraction. A moderate correlation was found between ratios of peak exercise to resting RV end-systolic pressure-area ratio and RV end-systolic pressure-volume ratio (r = 0.64; p < 0.0001). Echocardiographic estimates of RV and pulmonary vascular function are feasible during exercise and identify pathology with reasonable accuracy. They represent valid screening tools for the identification of pulmonary vascular disease in routine clinical practice.

Claessen G ，La Gerche A ，Voigt JU ，Dymarkowski S ，Schnell F ，Petit T ，Willems R ，Claus P ，Delcroix M ，Heidbuchel H ... -  《-》