Search

BackgroundIn this study, we investigated the impact of the new haemodynamic definition of pulmonary arterial hypertension (PAH) as proposed by the 6th PH World Symposium on phenotypes and survival in patients with systemic sclerosis (SSc).MethodsIn SSc patients who were prospectively and consecutively screened for PAH including right heart catheterisation in Heidelberg or Zurich, haemodynamic and clinical variables have been reassessed according to the new PAH definition. Patients have been followed for 3.7±3.7 (median 3.4) years; Kaplan-Meier survival analysis was performed. Patients with significant lung or left heart disease were excluded from comparative analyses.ResultsThe final dataset included 284 SSc patients, 146 patients (49.2%) had mean pulmonary arterial pressure (mPAP) ≤20 mm Hg, 19.3% had mPAP 21–24 mm Hg and 29.4% had mPAP ≥25 mm Hg. In the group of mildly elevated mPAP, only four patients (1.4% of the whole SSc cohort) had pulmonary vascular resistance (PVR) values ≥3 Wood Units (WU) and could be reclassified as manifest SSc-APAH. Twenty-eight (9.8%) patients with mPAP of 21–24 mm Hg and PVR ≥2 WU already presented with early pulmonary vascular disease with decreased 6 min walking distance (6MWD) (pConclusionThe data of this study show that a PVR threshold ≥3 WU is too high to enable an early diagnosis of PAH. A PVR threshold ≥2 WU was already associated with pulmonary vascular disease, significantly reduced survival and would be more appropriate in SSc patients with mild PAH.

Background Iron deficiency affects up to 50% of patients with pulmonary arterial hypertension (PAH) but iron markers such as ferritin and serum iron are confounded by several non-disease related factors like acute inflammation and diet. The aim of this study was to identify a new marker for iron deficiency and clinical outcome in PAH patients. Methods In this single-center, retrospective study we assessed indicators of iron status and clinical parameters specifying the time to clinical worsening (TTCW) and survival in PAH patients at time of initial diagnosis and at 1-year follow-up using univariable and multivariable analysis. Results In total, 150 patients were included with an invasively confirmed PAH and complete data on iron metabolism. The proportion of hypochromic erythrocytes > 2% at initial diagnosis was identified as an independent predictor for a shorter TTCW (p = 0.0001) and worse survival (p = 0.002) at initial diagnosis as well as worse survival (p = 0.016) at 1-year follow-up. Only a subset of these patients (64%) suffered from iron deficiency. Low ferritin or low serum iron neither correlated with TTCW nor survival. Severe hemoglobin deficiency at baseline was significantly associated with a shorter TTCW (p = 0.001). Conclusions The presence of hypochromic erythrocytes > 2% was a strong and independent predictor of mortality and shorter TTCW in this cohort of PAH patients. Thus, it can serve as a valuable indicator of iron homeostasis and prognosis even in patients without iron deficiency or anemia. Further studies are needed to confirm the results and to investigate therapeutic implications.

Objective This prospective study was undertaken to evaluate right ventricular function and pulmonary arterial compliance (PAC; ratio of stroke volume to pulse pressure) at rest and during exercise in patients with systemic sclerosis (SSc) with normal mean pulmonary artery pressure (PAP), patients with SSc with mildly elevated mean PAP, and patients with SSc with manifest pulmonary hypertension (PH). Methods Patients with SSc (n = 112) underwent clinical assessment and right-sided heart catheterization at rest and during exercise and were divided into 3 groups according to their resting mean PAP values: normal mean PAP (≤20 mm Hg), mildly elevated mean PAP (21-24 mm Hg), and PH (mean PAP ≥25 mm Hg). Results were compared between groups by analysis of variance followed by post hoc Student's t-test. Results Compared to patients with normal mean PAP, patients with mildly elevated mean PAP had a lower 6-minute walking distance (P = 0.008), lower cardiac index (P = 0.027) and higher pulmonary vascular resistance (P = 0.0002) during exercise, and lower PAC at rest (P = 0.016) and different stages of exercise (P = 0.033 for 25W and P = 0.024 for 75W). Conclusion The results of this study suggest that impaired 6-minute walking distance in SSc patients with mildly elevated mean PAP might be caused by reduced PAC during exercise and reduced right ventricular output reserve, presumably due to impaired coupling between the right ventricle and the pulmonary vasculature. These findings provide further evidence of the clinical relevance of mildly elevated mean PAP in patients with SSc.

To assess the diagnostic accuracy of automated 3D volumetry of central pulmonary arteries using computed tomography pulmonary angiography (CTPA) for suspected pulmonary hypertension alone and in combination with echocardiography.This retrospective diagnostic accuracy study included 70 patients (mean age 66.7, 48 female) assessed for pulmonary hypertension by CTPA and transthoracic echocardiography with estimation of the pulmonary arterial systolic pressure (PASP). Gold standard right heart catheterisation with measurement of the invasive mean pulmonary arterial pressure (invasive mPAP) served as the reference. Volumes of the main, right and left pulmonary arteries (MPA, RPA and LPA) were computed using automated 3D segmentation. For comparison, axial dimensions were manually measured. A linear regression model was established for prediction of mPAP (predicted mPAP).MPA, RPA and LPA volumes were significantly increased in patients with vs. without pulmonary hypertension (all p 0.001). Of all measures, MPA volume demonstrated the strongest correlation with invasive mPAP (r = 0.76, p 0.001). Predicted mPAP using MPA volume and echocardiographic PASP as covariates showed excellent correlation with invasive mPAP (r = 0.89, p 0.001). Area under the curves for predicting pulmonary hypertension were 0.94 for predicted mPAP, compared to 0.90 for MPA volume and 0.92 for echocardiographic PASP alone. A predicted mPAP 25.8 mmHg identified pulmonary hypertension with sensitivity, specificity, positive and negative predictive values of 86%, 93%, 95% and 81%, respectively.Automated 3D volumetry of central pulmonary arteries based on CTPA may be used in conjunction with echocardiographic pressure estimates to noninvasively predict mPAP and pulmonary hypertension as confirmed by gold standard right heart catheterisation with higher diagnostic accuracy than either test alone.• This diagnostic accuracy study derived a regression model for noninvasive prediction of invasively measured mean pulmonary arterial pressure as assessed by gold standard right heart catheterisation. • This regression model using automated 3D volumetry of the central pulmonary arteries based on CT pulmonary angiography in conjunction with the echocardiographic pressure estimate predicted pulmonary arterial pressure and the presence of pulmonary hypertension with good diagnostic accuracy. • The combination of automated 3D volumetry and echocardiographic pressure estimate in the regression model provided superior diagnostic accuracy compared to each parameter alone.

Background: Pulmonary arterial compliance (PAC) is a prognostic parameter in pulmonary arterial hypertension (PAH) reflecting the elasticity of the pulmonary vessels. Objectives: The objective of this post hoc analysis of a prospective randomized controlled trial (RCT) was to assess the effect of exercise training on PAC and stroke volume (SV) in patients with PAH and persistent/inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Method: From the previous RCT, 43 out of 87 patients with severe PAH (n = 29) and CTEPH (n = 14) had complete haemodynamic examinations at baseline and after 15 weeks by right heart catheterization and were analysed (53% female, 79% World Health Organization functional class III/IV, 58% combination therapy, 42% on supplemental oxygen therapy, training group n = 24, and control group n = 19). Medication remained unchanged for all patients. Results: Low-dose exercise training at 4–7 days/week significantly improved PAC (training group 0.33 ± 0.65 mL/mm Hg vs. control group −0.06 ± 1.10 mL/mm Hg; mean difference 0.39 mL/mm Hg, 95% confidence interval [CI] 0.15–0.94 mL/mm Hg; p = 0.004) and SV (training group 9.9 ± 13.4 mL/min vs. control group −4.2 ± 11.0 mL/min; mean difference 14.2 mL, 95% CI 6.5–21.8 mL; p < 0.001) in the training versus control group. Furthermore, exercise training significantly improved cardiac output and pulmonary vascular resistance at rest, peak oxygen consumption, and oxygen pulse. Conclusions: Our findings suggest that supervised exercise training may improve right ventricular function and PAC at the same time. Further prospective studies are needed to evaluate these findings.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors Eli Lilly and Company; Pfizer; Bayer; GlaxoSmithKline; Merck; Actelion Pharmaceuticals; Meso Scale Diagnostics; United Therapeutics Corporation; Novartis Pharma; Merck Sharp and Dohme; GlaxoSmithKline Australia; Deutsche Forschungsgemeinschaft; Grupo Ferrer Internacional, S.A The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG.

Background The objective of this study was to analyze prognostic factors and risk stratification in patients with pulmonary arterial hypertension (PAH) and comorbidities. Methods Patients with invasively diagnosed PAH were included in the analysis. Comorbidities were clinically diagnosed as proposed in the 6th World Symposium of pulmonary hypertension. Uni- and multivariate analysis were employed for identification of factors predicting survival and time to first clinical worsening (TTCW). Risk stratification was based on parameters from ESC/ERS-guidelines 2015. Results In total 142 patients were enrolled in the study, 90 of them were diagnosed as PAH without and 52 with comorbidities. All patients received targeted PAH therapy and were followed for 3.3 ± 2.4 years. In PAH patients without comorbidities survival and TTCW were significantly associated with reduced 6-min walking distance (6MWD), elevated N-terminal pro brain natriuretic peptide (NT-proBNP), WHO-functional class (WHO-FC) and right atrial (RA) area. In the multivariate analysis, 6MWD was an independent predictor for survival (p = 0.002) and WHO-FC for TTCW (p = 0.001). In patients with PAH and comorbidities these parameters had no significant association with survival and TTCW. Average risk score was significantly associated with survival (p = 0.001) and TTCW (p = 0.013) in PAH but not in PAH with comorbidities (both p > 0.05; figure 1). Conclusion Risk stratification based on ESC/ERS-guidelines could only be confirmed in patients without comorbidities, but not in patients with PAH and comorbidities. The data of this study suggest, that a different risk stratification needs to be applied to PAH patients with comorbidities. Further studies are needed to confirm these results. Trial registration Not applicable, retrospective registry.

In their correspondence Iudici et al 1 highlight three important aspects which are to consider in the interpretation of survival data when introducing new thresholds of an early stage of disease.2 They point out, that lead-time bias, length-time bias as well as increasing numbers of patients have to be considered for the new haemodynamic definition of pulmonary arterial hypertension (PAH). In studies investigating the effect of systematic PAH screening programmes on survival in patients with systemic sclerosis, part of the effect of an increased survival may be attributed to lead-time bias and length-time bias.3 4 We agree with Iudici et al that lead-time bias is an important aspect when introducing a new definition of a disease, which includes patients at a less severe stage. This becomes especially important for screening programmes, as survival of screened patients who are diagnosed at early disease stages may implicitly be better compared with patients with a more severe disease. In our study we analysed the frequency of PAH in patients with systemic sclerosis when applying the new PAH definition according to the suggestion from the World Symposium on pulmonary hypertension in Nice 2018. According to a large meta-analysis of haemodynamic data of healthy people, a pulmonary vascular resistance (PVR) >2 Wood Units (WU) …

Background Patients with systemic sclerosis (SSc) are at high risk of developing concomitant pulmonary hypertension (PH) which has a crucial impact on the patients' symptoms, quality of life and prognosis. Purpose The aim of this study was to analyse the impact of the new hemodynamic definition of precapillary PH as proposed at the 2018 World Symposium on PH in Nice in patients with SSc. Although recent data suggest that PVR >2 WU could be considered as abnormal in the new definition a conservative cut-off value of PVR ≥3 WU has been used. Methods SSc-patients were screened for PH using clinical assessments as WHO-functional class, 6 minute walking distance and right heart catheterisation. Patients were divided into hemodynamic subgroups according to their mean pulmonary arterial pressure (mPAP) values with mPAP ≤20 mmHg, 21–24 mmHg and ≥25 mmHg. These subgroups were further divided according to their pulmonary vascular resistance (PVR) with PVR Results One-hundred-twenty-two patients (79% female, age 57.6±12.7 years, 6MWD 439.5±98.1 meters, 70% diffuse cutaneous SSc, 30% limited cutaneous SSc, 53% WHO-FC II, 25% WHO-FC III) who were prospectively screened for PH were included in the analysis (Figure 1). Among them 26 had a symptomatic manifest PH using the cut-off value of mPAP ≥25 mmHg. Only half of this group presented with PVR ≥3 WU, the others had PVR Overview of systemic sclerosis patients Conclusions The new definition of precapillary pulmonary hypertension may on the one hand allow detecting an additional 10% of PH patients with mild elevated mPAP. On the other hand, eight of 13 patients (62%), who met the former definition of pulmonary arterial hypertension, would be classified as “normal” due to a lack of increase in PVR according to the new definition. The data of this study suggest that for SSc-patients the cut-off value of mPAP >20 mmHg is useful, but the criteria of PVR ≥3 WU may be too strict. Further studies with larger sample sizes will be needed to better characterise these hemodynamic subgroups and to define the extent of pulmonary vascular disease and treatability.

Background: Prostacyclins (PCs) are used as targeted treatment for pulmonary arterial hypertension (PAH). Data regarding safety and long-term outcomes of s.c. and/or i.v. treprostinil (T) administered via s.c. Corno and the implantable LENUS Pro pump in patients with PAH are lacking. Methods: Thirty-seven PAH patients (20 females, 51±15 y.o., mean pulmonary arterial pressure 62.3±14.4 mmHg, cardiac index 2.4±0.7 L/min/m2, 6 WHO functional class II, 26 III, 5 IV) on triple targeted PAH medication (ERA, PDE5 inhibitors and treprostinil s.c.) were clinically assessed every 3 months. Survival rate was analysed using Kaplan Mayer estimation. Results: Patients showed a significant improvement of 6-minute walking distance after 3 (p=0.021), 6 (p=0.033) and 12 months (p=0.042) of s.c. treprostinil treatment. Furthermore, tricuspid annular plane systolic excursion, right atrial and right ventricular area improved after 3 and 6 months s.c. treatment (all p Conclusion: Subcutaneous T as add-on to double combination treatment significantly improved right heart size and function in this patient cohort. In most patients T could be continued i.v. by implanted Lenus Pro pump with a good overall-survival.

Background: Patients with systemic sclerosis (SSc) are at high risk of developing pulmonary hypertension (PH) which crucially affects patients’ symptoms, quality of life and prognosis. The aim of this study was to analyse the impact of the new hemodynamic definition of precapillary PH as proposed at the 2018 World Symposium on PH in SSc-patients. Methods: SSc-patients were screened for PH using clinical assessments as WHO-functional class, 6 minute walking distance (6MWD) and right heart catheterisation. Patients were divided into hemodynamic subgroups according to their mean pulmonary arterial pressure (mPAP) values with mPAP ≤20mmHg, 21-24mmHg and ≥25mmHg and their pulmonary vascular resistance (PVR) with PVR Results: The analysis included 158 patients (81% female, age 57±13years, 6MWD 438±101meters, 76% WHO-FC II or III) who were prospectively screened for PH. Among them, 40 had a manifest PH with an mPAP ≥25mmHg. Half of them presented with PVR ≥3WU. Thirteen presented with PH due to left heart disease. Out of 30 patients with mPAP 21-24mmHg, 4 (13%) met the new definition criteria of PH. Out of 88 patients with mPAP Conclusions: The new definition of precapillary PH may allow detecting an additional ~10% of PH patients with mPAP 21-24mmHg. On the other hand, 11/27 patients (40.7%), would be classified as “normal” due to PVR 20mmHg presented as useful, while the criterium of PVR ≥3WU seemed too strict. Further studies will be needed to characterise thee hemodynamic subgroups and to define the extent of pulmonary vascular disease and treatability.

Objective The objective of this randomized, placebo-controlled, double-blind, parallel group, trial was to assess the effect of ambrisentan on mean pulmonary arterial pressure (mPAP) in patients with systemic sclerosis (SSc) and mildly elevated pulmonary hypertension (PH). Methods Thirty-eight SSc patients with mildly elevated mPAP at rest between 21 and 24 mmHg and/or > 30 mmHg during low-dose exercise were randomly assigned to treatment with either ambrisentan 5–10 mg/day or placebo. Right heart catheterization and further clinical parameters were assessed at baseline and after 6 months. The primary endpoint was the difference of mPAP change at rest between groups. Results After 6 months, the two groups did not differ in the primary endpoint (ambrisentan mPAP − 1 ± 6.4 mmHg vs. placebo − 0.73 ± 3.59 mmHg at rest, p = 0.884). However, three patients from the placebo group but none of the ambrisentan group progressed to SSc-associated pulmonary arterial hypertension. Furthermore, ambrisentan treatment showed significant improvements in the secondary endpoints cardiac index (CI) and pulmonary vascular resistance (PVR) at rest (CI 0.36 ± 0.66 l/min/m2 vs. − 0.31 ± 0.71 l/min/m2, p = 0.010; PVR − 0.70 ± 0.78 WU vs. 0.01 ± 0.71 WU, p = 0.012) and during exercise (CI 0.7 ± 0.81 l/min/m2 vs. − 0.45 ± 1.36 l/min/m2, p = 0.015; PVR − 0.84 ± 0.48 WU vs. − 0.0032 ± 0.34 WU, p Conclusion This is the first randomized, double-blind, placebo-controlled study testing the effect of ambrisentan in patients with mildly elevated mPAP and/or exercise PH. The primary endpoint change in mPAP did only tendentially improve in the ambrisentan group, but the significant improvement of other hemodynamic parameters points to a possible benefit of ambrisentan and will be helpful to design future trials. Trial registration www.ClinicalTrials.gov, unique identifier NCT: NCT02290613, registered 14th of November 2014.

Background The objective of this study was to assess, whether right atrial (RA) and ventricular (RV) size is related to RV pump function at rest and during exercise in patients with pulmonary arterial hypertension (PAH). Methods We included 54 patients with invasively diagnosed PAH that had been stable on targeted medication. All patients underwent clinical assessments including right heart catheterization and echocardiography at rest and during exercise. RV output reserve was defined as increase of cardiac index (CI) from rest to peak exercise (∆CIexercise). Patients were classified according to the median of RA and RV-area. RV pump function and further clinical parameters were compared between groups by student’s t-test. Uni- and multivariate Pearson correlation analyses were performed. Results Patients with larger RA and/or RV-areas (above a median of 16 and 20cm2, respectively) showed significantly lower ∆CIexercise , higher mean pulmonary arterial pressure, pulmonary vascular resistance at rest and NT-proBNP levels. Furthermore, patients with higher RV-areas presented with a significantly lower RV stroke volume and pulmonary arterial compliance at peak exercise than patients with smaller RV-size. RV area was identified as the only independent predictor of RV output reserve. Conclusion RV and RA areas represent valuable and easily accessible indicators of RV pump function at rest and during exercise. Cardiac output reserve should be considered as an important clinical parameter. Prospective studies are needed for further evaluation.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the management of decompensated right heart failure, intensive care management and perioperative management in patients with pulmonary hypertension. This article summarizes the results and recommendations of the working group on decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension.

Background: Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTPEH). The objective of this study was to evaluate right heart size and function assessed by echocardiography during long term treatment with riociguat. Methods: Patients who started riociguat treatment (1.0–2.5 mg tid) within the trials phase II, PATENT, PATENTplus, EAS, CHEST and continued treatment for 3–12 months were included in this study. Echocardiography was analysed off-line at baseline, after 3, 6 and 12 months by investigators who were blinded to clinical data. Last and baseline observation carried forward method (LOCF, BOCF) were performed as sensitivity analysis. Results: Seventy-one patients (45% PAH, 55% CTEPH; 53.5% female; 60 ± 13 years, mean pulmonary arterial pressure 46 ± 10 mmHg, mean PVR 700 ± 282dynes·sec·cm-5) were included. After 6 months, RA and RV area, RV thickness tricuspid regurgitation velocity showed a significant reduction. After 12 months, patients receiving riociguat therapy showed a significant reduction in right atrial (− 2.6 ± 4.4 cm2, 95% CI -3.84, − 1.33; p

Background: Right ventricular(RV) dimensions and function play a pivotal role in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Riociguat is the first drug that has been approved for the treatment of both PAH and CTEPH. Sparse data are currently available about the effects of riociguat on right heart size and function. Methods: Seventy-one patients who were enrolled in the riociguat trials (CHEST, PATENT, EAS) by German centres (54% PAH, 46% CTEPH, 54% female, 83% treatment-naive, 60±13 years, mean pulmonary arterial pressure 46±10 mmHg) and received echocardiographic assessments were retrospectively included. Measurements of all echocardiographic parameters were performed off-line by a single investigator and merged with clinical data from the riociguat studies. Changes of echocardiographic data were analyzed from baseline to 3, 6 and 12 months by student’s t-test for paired samples. Results: Riociguat therapy was associated with significant reduction in right atrial area (-2.6±4.4cm²; p Conclusion: Riociguat is able to reduce right heart size and improve its function within 12 months of treatment.

Background In patients with systemic sclerosis (SSc) borderline mean pulmonary arterial pressures (mPAP; 21–24 mmHg at rest) are a frequent finding and could represent an intermediate stage between normal pulmonary pressures and manifest pulmonary hypertension (PH).1. Objectives The objective of this prospective study was to compare right ventricular function and pulmonary arterial compliance (PAC) at rest and during exercise between systemic sclerosis (SSc)-patients with normal and borderline mean pulmonary artery pressures, respectively. Methods SSc-patients (n=112) underwent clinical assessment. including right heart catheterization at rest and during exercise and were divided in three groups according to their resting mPAP values: normal mPAP (≤20 mmHg), borderline mPAP (21–24 mmHg) and manifest pulmonary hypertension (PH, mPAP ≥25 mmHg). Results were compared between groups by ANOVA followed by post-hoc student’s t-test. Results SSc Patients with borderline PAP showed significantly lower cardiac index (CI) increase during exercise and higher PVR values than SSc patients with normal PAP at rest. Six-Minute-walking distance (6MWD) and PAC (stroke volume/(systolicPAP-diastolicPAP) were significantly lower in the borderline PAP group compared to patients with normal PAP. Conclusions The results of this study suggest that impaired 6MWD in SSc-patients with borderline PAP (and normal RV function at rest) might be caused by reduced RV contractile reserve (reduced RV output) and reduced PAC during exercise rather than by elevated pressures in the borderline range alone. These findings give further evidence for borderline PAP being an early stage of pulmonary vascular disease. Reference [1] Visovatti SH, Distler O, Coghlan JG, Denton CP, Grunig E, Bonderman D, Muller-Ladner U, Pope JE, Vonk MC, Seibold JR, Torres-Martin JV, Doelberg M, Chadha-Boreham H, Rosenberg DM, McLaughlin VV, Khanna D. Borderline pulmonary arterial pressure in systemic sclerosis patients: a post-hoc analysis of the DETECT study. Arthritis Res Ther. 2014Dec 10;16(6):493. Acknowledgements Special thanks to the patients that participated in this research. Disclosure of Interest None declared

Background: Right ventricular (RV) dysfunction is a major prognostic predictor in pulmonary arterial hypertension (PAH). Objectives: The objective of this study was to assess the prognostic impact of a newly developed index merging haemodynamic parameters into 1 variable. Methods: We retrospectively assessed 2 cohorts of 248 patients (164 from Hamburg and 84 from Heidelberg) with invasively diagnosed PAH. During a median follow-up time of 3.6 years (3.1 and 4.0 years for Hamburg and Heidelberg, respectively), the composite endpoint of all-cause mortality and lung transplantation occurred in 57 patients (53 and 4 patients for Hamburg and Heidelberg, respectively). The RV index was developed in the Hamburg cohort and validated in the Heidelberg cohort: (right atrial pressure × pulmonary vascular resistance)/mixed venous oxygen saturation. Results: Patients with a high RV index had a higher incidence of the combined endpoint in Kaplan-Meier analyses in the Hamburg and Heidelberg cohort (p = 0.017 and p = 0.034, respectively). The calculated RV index cut-off value was 91 and identified patients with a worse outcome in the Hamburg cohort and showed a trend in the Heidelberg cohort (p < 0.001 and p = 0.089, respectively). The RV index in Cox regression hazard models was an independent predictor of outcomes after adjustment for sex and age in both cohorts (Hamburg: hazard ratio [HR] 1.26 [95% CI 1.08, 1.47], p = 0.0027; Heidelberg: HR 2.27 [95% CI 1.46, 3.51], p < 0.001). A nomogram based on these results allowed risk stratification. Conclusion: Merging 3 haemodynamic variables into 1 variable, the RV index increased the prognostic power up to an independent risk factor. The RV index is easy to calculate and allows the construction of a nomogram for an individualized risk assessment.

In June 2016, members of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) met for a Consensus Conference in Cologne, Germany. Aim of this Conference was to compile consensus based practice recommendations based on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. This article summarizes the results and updated recommendations 2018 of the working group on decompensated right heart failure (RHF), intensive care and perioperative management in patients with pulmonary hypertension. The RHF section comprises definition and pathophysiology, diagnosis and monitoring, identification of triggering factors and supportive therapy of RHF, volume management as well as PAH targeting therapy, therapy with inotropic, inodilator and vasopressor drugs, extracorporeal support and transplantation. The second part of this article summarizes preoperative management, perioperative monitoring and choice of anesthesia.

Background: Despite optimized medical therapy, severe idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease with a poor outcome. Autoantibodies have been detected in IPAH that can contribute to worsening of the disease. Objectives: The objective of this prospective, open-label, single-arm, multicenter trial was to evaluate the safety and efficacy of immunoadsorption (IA) as an add-on to optimized medical treatment for patients with IPAH. Methods: A total of 10 IPAH patients received IA over 5 days. Their clinical parameters, including hemodynamics measured by right heart catheter, were assessed at baseline and after 3 and 6 months. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included the change in 6-min walking distance, quality of life, safety, and plasma levels of IgG and autoantibodies. Results: The evaluation of the 10 IPAH patients (75% female; 51 ± 12 years; 166 ± 10 cm; WHO functional class III; 53% on combination therapy) revealed that IA was a safe procedure that efficiently removed IgG and autoantibodies from the circulation. After 3 months, the mean PVR improved significantly by 13.2% (p = 0.03) and the cardiac index improved by 13.1%, but no significant changes were found in 6-min walking distance. The quality of life physical functioning subscale score significantly improved after 6 months. The serious adverse events in 3 patients were possibly related to IA and included pneumonia, temporary disturbance in attention, and thrombocytopenia. Conclusions: IA as an add-on to targeted medical treatment for IPAH is a safe procedure with beneficial effects on hemodynamics, especially in patients with high levels of autoantibodies. Larger-scale controlled studies are needed to assess its efficacy in IPAH and to identify responders.

Background: Despite optimized medical therapy, severe idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease with a poor outcome. Autoantibodies have been detected in IPAH that can contribute to worsening of the disease. Objectives: The objective of this prospective, open-label, single-arm, multicenter trial was to evaluate the safety and efficacy of immunoadsorption (IA) as an add-on to optimized medical treatment for patients with IPAH. Methods: A total of 10 IPAH patients received IA over 5 days. Their clinical parameters, including hemodynamics measured by right heart catheter, were assessed at baseline and after 3 and 6 months. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included the change in 6-min walking distance, quality of life, safety, and plasma levels of IgG and autoantibodies. Results: The evaluation of the 10 IPAH patients (75% female; 51 ± 12 years; 166 ± 10 cm; WHO functional class III; 53% on combination therapy) revealed that IA was a safe procedure that efficiently removed IgG and autoantibodies from the circulation. After 3 months, the mean PVR improved significantly by 13.2% (p = 0.03) and the cardiac index improved by 13.1%, but no significant changes were found in 6-min walking distance. The quality of life physical functioning subscale score significantly improved after 6 months. The serious adverse events in 3 patients were possibly related to IA and included pneumonia, temporary disturbance in attention, and thrombocytopenia. Conclusions: IA as an add-on to targeted medical treatment for IPAH is a safe procedure with beneficial effects on hemodynamics, especially in patients with high levels of autoantibodies. Larger-scale controlled studies are needed to assess its efficacy in IPAH and to identify responders.

Background and Objectives: Patients with connective tissue disease (CTD) often develop borderline pulmonary hypertension (BPH) which is considered as an intermediate stage between normal pulmonary pressure and manifest pulmonary hypertension (PH). The aim of this study was to compare pulmonary vascular response at rest and during exercise in CTD-patients with normal mean pulmonary arterial pressure (mPAP) at rest and with BPH. Methods: Patients with confirmed CTD (n=112) underwent right heart catheterization (RHC) at rest and during exercise and were divided in three groups according to their resting mPAP values: normal mPAP (normals mPAP ≤ 20 mmHg), BPH (mPAP: 21-24 mmHg), manifest PH (mPAP ≥ 25 mmHg). Values were compared between groups by ANCOVA analysis of differences using the baseline variable as covariate. Results: Patients with BPH showed significantly lower right ventricular contractile reserve than CTD-patients with normal mPAP as shown by the reduced cardiac output increase during exercise measured by right heart catheterization (Δ CO: 4,36 ± 2,74 l/min vs 5,92 ± 2,8, p: 0.0002) (Figure 1). Conclusion: CTD-patients with borderline mPAP values at rest showed significantly more often an abnormal pulmonary hemodynamic response to exercise. These finding suggest that right ventricular dysfunction can occur at an early stage in patients at risk for pulmonary hypertension.

Ziel der praoperativen Lungenfunktionsanalyse und kardiologischen Funktionsdiagnostik ist es, Patienten mit einem erhohten Komplikationsrisiko zu identifizieren und uber Behandlungsmoglichkeiten und Risiken bestmoglich aufzuklaren, sodass eine fundierte Therapieentscheidung getroffen werden kann. Die Identifikation von Patienten mit erhohtem periinterventionellen Risiko durch die praoperative physiologische Diagnostik bildet auch die Grundlage fur weitere Entwicklungen und Verbesserungen von Interventionen und Interventionstechniken, um das Komplikationsrisiko insgesamt reduzieren zu konnen. Die Erhebung einer ausfuhrlichen Anamnese, eine eingehende korperliche Untersuchung sowie die Diagnostik mittels EKG und Spirometrie konnen erste Hinweise fur das Vorliegen relevanter Komorbiditaten liefern. Bei elektiven Eingriffen muss praoperativ eine differenzierte Bewertung der Komorbiditaten erfolgen, da die Assoziation von zunehmendem Alter und operativer Letalitat nicht auf das Alter allein, sondern auf das Spektrum an Komorbiditaten zuruckzufuhren ist. Die hier aufgefuhrte Diagnostik richtet sich nach den in Deutschland gultigen S3-Leitlinen der Deutschen Gesellschaft fur Pneumologie von 2010. Sowohl deutsche als auch internationale Leitlinien empfehlen zur Indikationsstellung vor lungenresezierenden Eingriffen die interdisziplinare Falldiskussion, bei der Thoraxchirurgen, Onkologen, Radioonkologen und Pneumologen gemeinsam entscheiden. Patienten im fortgeschrittenen Lebensalter sollten immer praoperativ erweitert kardiopulmonal untersucht werden.

Introduction: Aim of this study was to compare plasma concentrations in PAH patients according to different combination treatments and to identify combinations that cause relevant interactions. Methods: PAH patients receiving a stable combination treatment with Endothelin-Receptor-Antagonists (ERA) and Phosphodiesterase-type-5 inhibitors (PDE-5I) for ≥1 month were routinely assessed, including demographics, clinical status, and plasma drug concentrations. Plasma concentrations were normalised for dose and time from last medication intake and presented as multiples of the expected mean (MOM) of the respective monotherapies with values 1 higher values than the expected mean. Results: 125 patients (67% female, 34% idiopathic, 57% ≥WHO FC III, mean pulmonary arterial pressure 47±15mmHg) were included in the study. Results for mean and standard deviation of plasma concentrations were Bosentan (BOS)-Sildenafil (SIL) 0.44±0.42 (n=39), BOS-Tadalafil (TAD) 0.89±0.53 (n=7), Ambrisentan (AMB)-SIL 1.3±0.97 (n=19), AMB-TAD 1.67±0.63 (n=21), Macitentan (MAC)-SIL 1.16±0.87 (n=33) and MAC-TAD 1.59±0.99 (n=6). SIL plasma concentrations were significantly lower when co-administered with BOS than with AMB or MAC (both p Conclusions: The study results suggest that specific combinations of PAH-specific therapies lead to decreased PDE-5I plasma concentrations. The lowest levels were detected in the combination of BOS-SIL treatment. Further, larger scaled investigations are needed to analyse the association with clinical data.

Aims: This prospective randomized controlled study investigates the effects of exercise training on peak VO 2 /kg, hemodynamics and further clinically relevant parameters in pulmonary hypertension (PH) patients. Methods: Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thromboembolic PH (54% female, 56±15years, 84% WHO functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO 2 /kg. Secondary endpoints included changes in hemodynamics. For missing data, multiple imputation and responder analyses were performed. Results: Study results showed a significant improvement of peak VO 2 /kg in the training group (difference baseline to 15 weeks: training +3.1±2.7 equals +24.3% vs. control -0.2±2.3mL/min/kg equals +0.9%, p Conclusions: Low-dose exercise training at 4-7days/week significantly improved peak VO 2 /kg, hemodynamics and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicenter trials are necessary to confirm these results.

Background: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation. Objectives: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management. Methods: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study. Results: Thirty-nine patients with idiopathic or heritable pulmonary arterial hypertension on stable treatment with oral pulmonary arterial hypertension-approved drugs (90% on dual combination therapy) were included. Patients achieved a median treprostinil dosage of 35.7 ng/kg/min after 16 weeks. A good overall safety profile was demonstrated with 3 patients (8%) withdrawing due to infusion site pain, which occurred in 97% of patients. After 16 weeks, median 6-min walking distance, cardiac index, pulmonary vascular resistance, and tricuspid annular plane systolic excursion improved. Conclusions: Rapid up-titration of subcutaneous treprostinil was well tolerated, achieving a clinically effective dose associated with improvement of exercise capacity and haemodynamics after 16 weeks. A rapid dose titration regimen and proactive infusion site pain management may improve the handling of this therapy and contribute to better treatment outcome.

Aims The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients. Methods and results Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO2/kg. Secondary endpoints included changes in haemodynamics. For missing data, multiple imputation and responder analyses were performed. The study results showed a significant improvement of peak VO2/kg in the training group (difference from baseline to 15 weeks: training +3.1 ± 2.7 mL/min/kg equals +24.3% vs. control −0.2 ± 2.3 mL/min/kg equals +0.9%, P < 0.001). Cardiac index (CI) at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life, and exercise capacity significantly improved by exercise training. Conclusion Low-dose exercise training at 4–7 days/week significantly improved peak VO2/kg, haemodynamics, and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicentre trials are necessary to confirm these results.

Introduction: In patients with systemic sclerosis (SSc), associated pulmonary arterial hypertension (SSc-APAH) is the leading cause of death. The objective of this prospective screening study was to analyse sensitivity and specificity of stress Doppler echocardiography (SDE) in detecting pulmonary hypertension (PH). Methods: Pulmonary artery pressures and further parameters of PH were assessed by echocardiography and right heart catheterisation (RHC) at rest and during exercise in patients with SSc. Investigators of RHC were blinded to the results of non-invasive measurements. Results: Of 76 patients with SSc (64 were female and mean age was 58±14 years), 22 (29 %) had manifest PH confirmed by RHC: four had concomitant left heart diseases, three had lung diseases, and 15 had SSc-APAH. Echocardiography at rest missed PH diagnosis in five of 22 patients with PH when a cutoff value for systolic pulmonary arterial pressure (PASP) was more than 40 mm Hg at rest. The sensitivity of echocardiography at rest was 72.7 % (95 % confidence interval (CI) 0.52–0.88), and specificity was 88.2 % (95 % CI 0.78–0.95). When a cutoff value for PASP was more than 45 mm Hg during low-dose exercise, SDE missed PH diagnosis in one of the 22 patients with PH and improved sensitivity to 95.2 % (95 % CI 0.81–1.0) but reduced specificity to 84.9 % (95 % CI 0.74–0.93). Reduction of specificity was partly due to concomitant left heart disease. Conclusions: The results of this prospective cross-sectional study using RHC as gold standard in all patients showed that SDE markedly improved sensitivity in detecting manifest PH to 95.2 % compared with 72.7 % using echocardiography at rest only. Thus, for PH screening in patients with SSc, echocardiography should be performed at rest and during exercise. Trial registration: ClinicalTrials.gov NCT01387035 . Registered 29 June 2011.

Most recently, a specialized and carefully monitored exercise training and rehabilitation program has been recommended as add-on to medical treatment in patients with pulmonary arterial hypertension (class I, level of evidence A). Three prospective randomized, controlled trials, 10 prospective uncontrolled trials, 2 retrospective studies and 2 case series in more than 470 patients with severe pulmonary hypertension (PH) and right heart failure reported beneficial effects of a specialized exercise training and rehabilitation program, i.e. significant improvement in symptoms, exercise capacity, cardiorespiratory function and quality of life, compared with untrained controls. All training studies reported an acceptable safety profile, and some uncontrolled studies showed excellent 1- and 2-year survival rates. However, most studies had a quite small sample size (ranging from 2 to 183 patients) and an uncontrolled design, and they were not designed to assess hemodynamic changes, time to clinical worsening and survival. Nevertheless, there is large evidence that exercise training programs should be performed by centers experienced in both PH patient care and rehabilitation. The best method and duration of the training, characteristics of supervision, and the mechanisms resulting in symptom improvement and increased functional capacity are unclear. In this review, we summarize data of molecular and clinical effects of exercise training in PH patients. Furthermore, we discuss safety data and the role of a self-care management of exercise training in these patients.

Background: Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTPEH). Objectives: Aim of this study was to evaluate the change of right heart size and function assessed by echocardiography during long-term treatment with riociguat. Methods: We assessed patients who started riociguat treatment within the trials PATENT, PATENTplus, EAS, CHEST and continued for 3-12 months. Echocardiography, 6-minute walking distance (6MWD) and further clinical parameters were analyzed at baseline, after 3, 6 and 12 months. Right heart catheterization was performed at baseline and after 3 months. For missing data we performed the last and baseline observation carried forward (LOCF, BOCF) method. Results: Thirty-nine patients (21 PAH, 18 CTEPH, 56.4% treatment-naive) were included. Mean right ventricular (RV) area significantly decreased after 3 (-2.1±3.9cm 2 , equals 7.4±15.3%, p 2 , equals 16.1±11.5%, p 2 , equals 22.1±14.2%, p 2 , equals 16.8±19.2%, p Conclusion: Treatment with riociguat significantly reduced right heart size and improved RV function in PAH and CTEPH. Further prospective studies are needed.

Background: The right ventricular (RV) area is important for diagnosis and follow-up in patients with various diseases, such as in pulmonary hypertension. Objectives: The aim of this study was to define the reference ranges of the end-diastolic RV area in healthy adults and to assess the determining factors. Methods: In the first part of the study 860 healthy subjects (37.6% female; mean age 28 ± 5.84; 395 endurance athletes, 255 strength athletes and 210 non-athletes) were prospectively assessed. In the second part we performed a pooled analysis of studies published between 1979 and 2014 describing the RV area in healthy subjects (n = 5,248). Statistical analysis included the calculation of reference ranges and the analysis of determining factors. Results: Mean end-diastolic RV areas in 860 healthy subjects were significantly larger in endurance athletes (25.1 ± 2.0 cm2) compared with strength athletes (22.9 ± 1.7 cm2) and non-athletes (16.7 ± 2.0 cm2, p < 0.001). In the synopsis of both data sets, mean end-diastolic RV area was significantly larger in European/American males (17 cm2) compared with females (14 cm2, p < 0.001) and in Asian males (16 cm2) compared with females (13 cm2, p < 0.001). The area increased with body surface area and older age. Conclusion: This is the largest data set to define RV size in healthy adults aged 50 years as well as in children are needed.

Background Whole-body magnetic resonance angiography (WB-MRA) has shown its potential for the non-invasive assessment of nearly the entire arterial vasculature within one examination. Since the presence of extra-cardiac atherosclerosis is associated with an increased risk of coronary events, our goal was to establish the relationship between WB-MRA findings, including a systemic atherosclerosis score index, and the presence of significant coronary artery disease (CAD). Methods WB-MRA was performed on a 1.5T scanner in 50 patients scheduled to undergo elective cardiac catheterization for suspected CAD. In each patient, 40 extra-cardiac vessel segments were evaluated and assigned scores according to their luminal narrowing. The atherosclerosis score index (ASI) was generated as the ratio of summed scores to analyzable segments. Results ASI was higher in patients with significant (> 50% stenosis) CAD (n = 27) vs. patients without CAD (n = 22; 1.56 vs. 1.28, p = 0.004). ASI correlated with PROCAM (R = 0.57, p < 0.001) and Framingham (R = 0.36, p = 0.01) risk scores as estimates of the 10-year risk of coronary events. A ROC derived ASI of > 1.54 predicted significant CAD with a sensitivity of 59%, specificity of 86% and a positive predictive value of 84%. Logistic regression revealed ASI > 1.54 as the strongest independent predictor for CAD with a 11-fold increase in likelihood to suffer from significant coronary disease. On the contrary, while 15/27 (55%) of patients with CAD exhibited at least one extra-cardiac stenosis > 50%, only 3/22 (14%) of those patients without CAD did (p = 0.003). The likelihood for an extra-cardiac stenosis when CAD is present differed between vascular territories and ranged from 15% for a carotid stenosis to 44% for a stenosis in the lower extremities. Conclusion This study provides important new evidence for the close association of extra-cardiac and coronary atherosclerosis. The novel findings that a WB-MRA derived systemic atherosclerosis score index is not only associated with established cardiovascular risk scores but is also predictive of significant CAD suggest its potential prognostic implications and underline the importance to screen for coronary disease in patients with extra-cardiac manifestations of atherosclerosis.