Background: Pulmonary vascular resistance (PVR) and compliance are comparable in proximal and distal chronic thromboembolic pulmonary hypertension (CTEPH). However, proximal CTEPH is associated with inferior right ventricular (RV) adaptation. Early wave reflection in proximal CTEPH may be responsible for altered RV function. The aims of the study are 1) investigate whether reflected pressure returns sooner in proximal than in distal CTEPH, and 2) elucidate whether timing of reflected pressure is related to RV dimensions, ejection fraction (RVEF), hypertrophy and wall stress. Methods: Right heart catheterization and cardiac MRI were performed in 17 patients with proximal and 17 patients with distal CTEPH. In addition to determination of PVR, compliance and characteristic impedance, wave separation analysis was performed to determine the magnitude and timing of the peak reflected pressure (as % of systole). Findings were related to RV dimensions and time-resolved RV wall stress. Results: Proximal CTEPH was characterized by higher RV volumes, mass and wall stress, and lower RVEF. While PVR, compliance and characteristic impedance were similar, proximal CTEPH was related to an earlier return of reflected pressure than distal CTEPH (proximal 53±8% vs. distal 63±15%, P<0.05). The magnitude of the reflected pressure waves did not differ. RV volumes, RVEF, RV mass and wall stress were all related to the timing of peak reflected pressure. Conclusions: Poor RV function in patients with proximal CTEPH is related to an early return of reflected pressure wave. PVR, compliance and characteristic impedance do not explain differences in RV function between proximal and distal CTEPH.

In 2015, more than 800 papers were published in the field of pulmonary hypertension. A Clinical Year in Review article cannot possibly incorporate all this work and needs to be selective. The recently published European guidelines for the diagnosis and treatment of pulmonary hypertension contain an inclusive summary of all published clinical studies conducted until very recently. Here, we provide an overview of papers published after the finalisation of the guideline. In addition, we summarise recent advances in pulmonary vasculature science. The selection we made from the enormous amount of published work undoubtedly reflects our personal views and may not include all papers with a significant impact in the near or more distant future. The focus of this paper is on the diagnosis of pulmonary arterial hypertension, understanding the success of combination therapy on the right ventricle and scientific breakthroughs. @ERSpublicationsThe review summarises advances in pulmonary hypertension since the publication of the recent ESC/ERS guidelines http://ow.ly/WUwoeThe global picture of pulmonary arterial hypertension Table 1 summarises the recent classification of pulmonary hypertension [1,2]. Based on data from the large European and North American registries, the most common types of pulmonary arterial hypertension (PAH) are idiopathic PAH and PAH associated with connective tissue disease. Less is known of the epidemiology of PAH in other parts of the world. Using the data from a large reference centre in Brazil, ALVES et al. [3] showed that schistosomiasis is among the top three of causes of PAH in that country. These global epidemiological data emphasise the importance of accounting for such differences in future clinical trials. Pulmonary veno-occlusive diseaseAn important change from the previous classification is that significant progress has been made in the field of pulmonary veno-occlusive disease (PVOD). Several causes of PVOD have been identified in recent years, including genetics, drugs and radiation therapy. The finding of the EIF2AK4 (eukaryotic translation initiation factor 2α kinase 4) mutation in familial PVOD and pulmonary capillary haemangiomatosis (PCH) might boost further research [4,5]. By the discovery of this gene, it is possible to confirm the diagnosis of PVOD or PCH by demonstrating the presence of the mutation instead of a histological diagnosis [5]. Of interest is the recent study by PERROS et al. [6] showing not only that mitomycin is a risk factor for the development of PVOD, but also that mitomycin induces pulmonary vascular disease in rats that resembles the pathological features of PVOD. This finding not only offers a representative animal model to study the disease but also sheds new light on the possible role of alkylating chemotherapy on the development of pulmonary hypertension [7]. New associations between drugs and disease were not only made in PVOD; in PAH, a possible relationship between a drug and the disease also was found. A recent

Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. A larger volume at a given pressure generates more wall tension. Return of reflected waves early after the onset of contraction, when RV volume is larger, may augment RV load. We aimed to elucidate: (1) the distribution of arrival times of peak reflected waves in treatment-naïve PAH patients; (2) the relationship between time of arrival of reflected waves and RV morphology; and (3) the effect of PAH treatment on the arrival time of reflected waves. Wave separation analysis was conducted in 68 treatment-naïve PAH patients. In the treatment-naïve condition, 54% of patients had mid-systolic return of reflected waves (defined as 34-66% of systole). Despite similar pulmonary vascular resistance (PVR), patients with mid-systolic return had more pronounced RV hypertrophy compared to those with late-systolic or diastolic return (RV mass/body surface area; mid-systolic return 54.6 ± 12.6 g m -2 , late-systolic return 44.4 ± 10.1 g m -2 , diastolic return 42.8 ± 13.1 g m -2 ). Out of 68 patients, 43 patients were further examined after initial treatment. At follow-up, the stiffness of the proximal arteries, given as characteristic impedance, decreased from 0.12 to 0.08 mmHg s mL -1 . Wave speed was attenuated from 13.3 to 9.1 m s -1 , and the return of reflected waves was delayed from 64% to 71% of systole. In conclusion, reflected waves arrive at variable times in PAH. Early return of reflected waves was associated with more RV hypertrophy. PAH treatment not only decreased PVR, but also delayed the timing of reflected waves.