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》

Long-term changes of exercise hemodynamics and physical capacity in chronic thromboembolic pulmonary hypertension after pulmonary thromboendarterectomy.

A substantial number of chronic thromboembolic pulmonary hypertension (CTEPH) patients experience dyspnea on exertion and limited exercise capacity despite surgically successful pulmonary endarterectomy (PEA). We sought to prospectively evaluate resting and peak exercise hemodynamics before, 3 and 12 months after PEA in consecutive CTEPH-patients and correlate it to physical functional capacity. Twenty consecutive CTEPH-patients were examined. Twelve months after PEA, 75% of patients with severely increased pre-PEA mean pulmonary arterial pressure (mPAP) at rest had normal or mildly increased mPAP. However, mPAP reduction was less pronounced during exercise where only 45% had normal or mildly increased mPAP at 12 months. Hemodynamic changes during exercise were tested using the pressure-flow relationship (i.e. mPAP/cardiac output (CO) slope). The average mPAP/CO slope was 7.5 ± 4.2 mm Hg/L/min preoperatively and 3.9 ± 3.0 mm Hg/L/min at 12 months (p < .005). CO reserve (CO increase from rest to peak exercise) was increased (5.7 ± 2.9 L/min) 12 months after PEA compared with pre-PEA (2.5 ± 1.8 L/min), p < .0001. However, 12 months after PEA, the CO reserve was only 49% of that of healthy controls, p < .0001. Changes in cardiac output (∆CO), calculated as the difference between CO before PEA and 12 months later, were significantly correlated with six-minute-walk-test and peak oxygen uptake (VO2), both at rest and peak exercise. Invasive exercise hemodynamic examination in CTEPH-patients demonstrates that after otherwise successful PEA surgery, >50% of patients have a significant increase in exercise mPAP, and the CO reserve remains compromised 12 months after PEA. Improvement in physical capacity is correlated with ∆CO.

Waziri F ，Mellemkjær S ，Clemmensen TS ，Hjortdal VE ，Ilkjær LB ，Nielsen SL ，Poulsen SH ... -  《-》

Right ventricular adaptation to pulmonary pressure load in patients with chronic thromboembolic pulmonary hypertension before and after successful pulmonary endarterectomy--a cardiovascular magnetic resonance study.

Rolf A ，Rixe J ，Kim WK ，Börgel J ，Möllmann H ，Nef HM ，Liebetrau C ，Kramm T ，Guth S ，Krombach GA ，Mayer E ，Hamm CW ... -  《-》

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 Hemodynamic Response to Exercise in Chronic Thromboembolic Pulmonary Hypertension before and after Pulmonary Endarterectomy.

Richter MJ ，Sommer N ，Gall H ，Voswinckel R ，Seeger W ，Mayer E ，Wiedenroth CB ，Rieth A ，Grimminger F ，Guth S ，Ghofrani HA ... -  《-》