Microvascular Disease in Chronic Thromboembolic Pulmonary Hypertension: Hemodynamic Phenotyping and Histomorphometric Assessment

International audienceBackground: Pulmonary endarterectomy (PEA) is the gold standard treatment for patients with operable chronic thromboembolic pulmonary hypertension (CTEPH). However, persistent pulmonary hypertension (PH) after PEA remains a major determinant of poor prognosis. A concomitant small-vessel arteriopathy in addition to major pulmonary artery obstruction has been suggested to play an important role in the development of persistent PH and survival after PEA. One of the greatest unmet needs in the current preoperative evaluation is to assess the presence and severity of small-vessel arteriopathy. Using the pulmonary artery occlusion technique, we sought to assess the presence and degree of smallvessel disease in CTEPH patients undergoing PEA in order to predict postoperative outcome before surgery. Methods: Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure (P c' ), we partitioned pulmonary vascular resistance in larger arterial (Rup, upstream resistance) and small arterial plus venous components (Rds, downstream resistance) in 90 patients prior to PEA. For validation, lung wedge biopsies were taken from non-obstructed and obstructed lung territories during PEA in 49 cases. Biopsy sites were chosen according to the pulmonary angiogram still frames that were mounted in the operating room. All vessels per specimen were measured, in each patient. Percent media (%MT) (arteries) and intima thickness (%IT) (arteries, veins, and indeterminate vessels) were calculated relative to external vessel diameter. Results: Decreased Rup was an independent predictor of persistent PH (OR per 10%: 0.40 [0.23-0.69]; p=0.001) and survival (HR per 10%: 0.03 [0.00-0.33]; p=0.004). Arterial %MT and %IT of non-obstructed lung territories and venous %IT of obstructed lung territories were significantly increased in patients with persistent PH and non-survivors. Rup correlated inversely with %MT (r=-0.72, p<0.001) and %IT (r=-0.62, p<0.001) of arteries from nonobstructed lung territories and with %IT (r=-0.44, p=0.024) of veins from obstructed lung territories. Receiver operating characteristic analysis disclosed that Rup <66% predicted persistent PH after PEA, while Rup <60% identified patients with poor prognosis after PEA. Conclusions: Pulmonary artery occlusion waveform analysis with estimation of Rup seems to be a valuable technique for assessing the degree of small-vessel disease and postoperative outcome after PEA in CTEPH