Background—: Chronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension. Methods and Results—: A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospectively included over a 24-month period. Estimated survival at 1, 2, and 3 years was 93% (95% confidence interval [CI], 90–95), 91% (95% CI, 87–93), and 89% (95% CI, 86–92) in operated patients (n=404), and only 88% (95% CI, 83–91), 79% (95% CI, 74–83), and 70% (95% CI, 64–76) in not-operated patients (n=275). In both operated and not-operated patients, pulmonary arterial hypertension–targeted therapy did not affect survival estimates significantly. Mortality was associated with New York Heart Association functional class IV (hazard ratio [HR], 4.16; 95% CI, 1.49–11.62; P =0.0065 and HR, 4.76; 95% CI, 1.76–12.88; P =0.0021), increased right atrial pressure (HR, 1.34; 95% CI, 0.95–1.90; P =0.0992 and HR, 1.50; 95% CI, 1.20–1.88; P =0.0004), and a history of cancer (HR, 3.02; 95% CI, 1.36–6.69; P =0.0065 and HR, 2.15; 95% CI, 1.18–3.94; P =0.0129) in operated and not-operated patients, respectively. Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension–targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients. Conclusions—: The long-term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients.

Chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary hypertension (IPAH) share a similar clinical presentation, and a differential diagnosis requires a thorough workup. Once CTEPH is confirmed, patients who can be safely operated have to be identified. We investigated risk factors associated with CTEPH and IPAH, and the criteria for the selection of operable CTEPH patients. This case-control study included 436 consecutive patients with CTEPH and 158 with IPAH in eight European centres, between 2006 and 2010. Conditions identified as risk factors for CTEPH included history of acute venous thromboembolism (p < 0.0001), large size of previous pulmonary embolism (p = 0.0040 in univariate analysis), blood groups non-O (p < 0.0001 in univariate analysis), and older age (p = 0.0198), whereas diabetes mellitus (p = 0.0006), female gender (p = 0.0197) and higher mean pulmonary artery pressure (p = 0.0103) were associated with increased likelihood for an IPAH diagnosis. Operability of CTEPH patients was associated with younger age (p = 0.0108), proximal lesions (p ≤ 0.0001), and pulmonary vascular resistance below 1200 dyn.s.cm^-5 (p = 0.0080). Non-operable CTEPH patients tended to be less differentiable from IPAH patients by risk factor analysis than operable patients. This study confirmed the association of CTEPH with history of acute venous thromboembolism and blood groups non-O, and identified diabetes mellitus and higher mean pulmonary artery pressure as factors suggesting an IPAH diagnosis. Non-operable CTEPH is more similar to IPAH than operable CTEPH regarding risk factors.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by pulmonary vasoconstriction, pulmonary arterial remodeling, abnormal angiogenesis and impaired right ventricular function. Despite progress in pharmacological therapy, there is still no cure for PAH. The peptide apelin and the G‐protein coupled apelin receptor (APLNR) are expressed in several tissues throughout the organism. Apelin is localized in vascular endothelial cells while the APLNR is localized in both endothelial and smooth muscle cells in vessels and in the heart. Apelin is regulated by hypoxia inducible factor‐1α and bone morphogenetic protein receptor‐2. Patients with PAH have lower levels of plasma‐apelin, and decreased apelin expression in pulmonary endothelial cells. Apelin has therefore been proposed as a potential biomarker for PAH. Furthermore, apelin plays a role in angiogenesis and regulates endothelial and smooth muscle cell apoptosis and proliferation complementary and opposite to vascular endothelial growth factor. In the systemic circulation, apelin modulates endothelial nitric oxide synthase (eNOS) expression, induces eNOS‐dependent vasodilatation, counteracts angiotensin‐II mediated vasoconstriction, and has positive inotropic and cardioprotective effects. Apelin attenuates vasoconstriction in isolated rat pulmonary arteries, and chronic treatment with apelin attenuates the development of pulmonary hypertension in animal models. The existing literature thus renders APLNR an interesting potential new therapeutic target for PH.

Background In contrast to systemic hypertension, the significance of arterial waves in pulmonary hypertension (PH) is not well understood. We hypothesized that arterial wave energy and wave reflection are augmented in PH and that wave behavior differs between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Methods and Results Right heart catheterization was performed using a pressure and Doppler flow sensor–tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery. Wave intensity analysis was subsequently applied to the acquired data. Ten control participants, 11 patients with PAH, and 10 patients with CTEPH were studied. Wave speed and wave power were significantly greater in PH patients compared with controls, indicating increased arterial stiffness and right ventricular work, respectively. The ratio of wave power to mean right ventricular power was lower in PAH patients than CTEPH patients and controls. Wave reflection index in PH patients (PAH: ≈25%; CTEPH: ≈30%) was significantly greater compared with controls (≈4%), indicating downstream vascular impedance mismatch. Although wave speed was significantly correlated to disease severity, wave reflection indexes of patients with mildly and severely elevated pulmonary pressures were similar. Conclusions Wave reflection in the pulmonary artery increased in PH and was unrelated to severity, suggesting that vascular impedance mismatch occurs early in the development of pulmonary vascular disease. The lower wave power fraction in PAH compared with CTEPH indicates differences in the intrinsic and/or extrinsic ventricular load between the 2 diseases.