[Risk Stratification in Patients with Pulmonary Arterial Hypertension under Treatment - Results of Four German Centers]. / Risikoänderung bei Patienten mit Pulmonaler Arterieller Hypertonie unter medikamentöser Therapie ­ Ergebnisse aus vier deutschen Zentren.

Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). According to the current European guidelines the expected 1-year risk of mortality for PAH patients can be categorized as low, intermediate, or high, based on clinical, non-invasive and hemodynamic data.Data from 131 patients with incident PAH (age 64 ±â€Š14) and frequent comorbidities (in 66.4 %) treated between 2016 and 2018 at 4 German PH centers were analyzed. At baseline, most patients were classified as intermediate risk (76 %), 13.8 % as high risk and only 9.9 % as low risk.During follow-up while on treatment after 12 ±â€Š3 months (range 9-16 months) 64.9 % were still classified as intermediate risk (76 %), 14.4 % as high risk and 20.7 % as low risk.Survival at 12 and 24 months was 96 % and 82 % in the intermediate risk group, while only 89 % and 51 % of the high risk patients were alive at these time points. In contrast, all patients in the low risk category were alive at 24 months.Despite the availability of various treatment options for patients with PAH even in specialized centers only a minority of patients can be stabilized in the low risk group associated with a good outcome.

[Invasive Cardiopulmonary Exercise Testing: A Review]. / Übersicht über die Entwicklung der invasiven Spiroergometrie (iCPET).

Right heart catheterization (RHC) is the internationally standardized reference method for measuring pulmonary hemodynamics under resting conditions. In recent years, increasing efforts have been made to establish the reliable assessment of exercise hemodynamics as well, in order to obtain additional diagnostic and prognostic data. Furthermore, cardiopulmonary exercise testing (CPET), as the most comprehensive non-invasive exercise test, is increasingly performed in combination with RHC providing detailed pathophysiological insights into the exercise response, so-called invasive cardiopulmonary exercise testing (iCPET).In this review, the accumulated experience with iCPET is presented and methodological details are discussed. This complex examination is especially helpful in differentiating the underlying causes of unexplained dyspnea. In particular, early forms of cardiac or pulmonary vascular dysfunction can be detected by integrated analysis of hemodynamic as well as ventilatory and gas exchange data. It is expected that with increasing validation of iCPET parameters, a more reliable differentiation of normal from pathological stress reactions will be possible.

Monotherapy in patients with pulmonary arterial hypertension at four German PH centres.

BACKGROUND: Although combination therapy is the gold standard for patients with pulmonary arterial hypertension (PAH), some of these patients are still being treated with monotherapy. METHODS: We conducted a retrospective analysis at four German PH centres to describe the prevalence and characteristics of patients receiving monotherapy. RESULTS: We identified 131 incident PAH patients, with a mean age of 64 ± 13.8 years and a varying prevalence of comorbidities, cardiovascular risk factors and targeted therapy. As in other studies, the extent of prescribed PAH therapy varied with age and coexisting diseases, and younger, so-called "typical" PAH patients were more commonly treated early with combination therapy (48% at 4-8 months). In contrast, patients with multiple comorbidities or cardiovascular risk factors were more often treated with monotherapy (69% at 4-8 months). Survival at 12 months was not significantly associated with the number of PAH drugs used (single, dual, triple therapy) and was not different between "atypical" and "typical" PAH patients (89% vs. 85%). CONCLUSION: Although "atypical" PAH patients with comorbidities or a more advanced age are less aggressively treated with respect to combination therapy, the outcome of monotherapy in these patients appears to be comparable to that of dual or triple therapy in "typical" PAH patients.

Risk assessment in medically treated chronic thromboembolic pulmonary hypertension patients.

Abbreviated versions of the risk stratification strategy of the European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines have been recently validated in patients with pulmonary arterial hypertension. We aimed to investigate their prognostic value in medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients from the COMPERA registry, which collects six variables of interest (World Health Organization Functional Class, 6-min walk distance, brain natriuretic peptide, right atrial pressure, cardiac index and mixed venous oxygen saturation).We included patients with at least one follow-up visit, no pulmonary endarterectomy and at least three of the six variables available, and classified the patients into low-, intermediate- and high-risk groups. As a secondary analysis, the number of noninvasive low-risk criteria was counted. The association between risk assessment and survival was evaluated.Data from inclusion and follow-up (median 7 months) visits were available for 561 and 231 patients, respectively. Baseline 1- and 5-year survival estimates were significantly different (p<0.0001) in the baseline low-risk (98.6% and 88.3%, respectively), intermediate-risk (94.9% and 61.8%, respectively) and high-risk (75.5% and 32.9%, respectively) cohorts. Follow-up data were even more discriminative, with 100%, 92% and 69% 1-year survival, respectively. The number of low-risk noninvasive criteria was also associated with survival.These analyses suggest that the ESC/ERS risk assessment may be applicable in patients with medically treated CTEPH.

Right Heart Catheterization During Exercise in Patients with COPD-An Overview of Clinical Results and Methodological Aspects.

While right heart catheterization (RHC) at rest is the gold standard to assess pulmonary hemodynamics in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH), the invasive measurement of exercise hemodynamics is less well established in this group. Since exercise hemodynamics are increasingly recognized as important clinical information in patients with PH, our goal was to review the literature in this field to provide a basis for clinical use, further studies, and future recommendations. We identified 69 studies (published since 1968) reporting RHC data in 2819 patients with COPD, of whom 2561 underwent exercise testing. Few studies simultaneously measured gas exchange during exercise. Overall, these studies showed large variations in the patient populations and research questions studied and the methods and definitions employed. Despite these limitations, the data consistently demonstrated the presence of precapillary PH at rest in up to 38% of patients with COPD. With exercise, a relevant proportion of patients developed an abnormal hemodynamic response, depending on the definition used. Furthermore, some studies assessed right ventricular function during exercise and showed a blunted increase in right ventricular ejection fraction. Drug effects and the impact of interventional procedures were also studied. Again, due to large variations in the patients studied and the methods used, firm conclusions are difficult to derive. Despite the limitations of this dataset, several recommendations with respect to technical aspects (body position, exercise protocol, and data acquisition) can be inferred for this challenging patient population and may be helpful for further studies or recommendations.

Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA).

BACKGROUND: For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH). METHODS AND RESULTS: We analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year survival (P=0.006) in patients on anticoagulation compared with patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant (P=0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio, 0.79; 95% confidence interval, 0.66-0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH. CONCLUSIONS: The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01347216.

Expert consensus for performing right heart catheterisation for suspected pulmonary arterial hypertension in systemic sclerosis: a Delphi consensus study with cluster analysis.

OBJECTIVE: To establish an expert consensus on which criteria are the most appropriate in clinical practice to refer patients with systemic sclerosis (SSc) for right heart catheterisation (RHC) when pulmonary hypertension (PH) is suspected. METHODS: A three stage internet based Delphi consensus exercise involving worldwide PH experts was designed. In the first stage, a comprehensive list of domains and items combining evidence based indications and expert opinions were obtained. In the second and third stages, experts were asked to rate each item selected in the list. After each of stages 2 and 3, the number of items and criteria were reduced according to a cluster analysis. RESULTS: A literature search and the opinions of 47 experts participating in Delphi stage 1 provided a list of seven domains containing 142 criteria. After stages 2 and 3, these domains and tools were reduced to three domains containing eight tools: clinical (progressive dyspnoea over the past 3 months, unexplained dyspnoea, worsening of WHO dyspnoea functional class, any finding on physical examination suggestive of elevated right heart pressures and any sign of right heart failure), echocardiography (systolic pulmonary artery pressure >45 mm Hg and right ventricle dilation) and pulmonary function tests (diffusion lung capacity for carbon monoxide <50% without pulmonary fibrosis). CONCLUSIONS: Among experts in pulmonary arterial hypertension-SSc, a core set of criteria for clinical practice to refer SSc patients for RHC has been defined by Delphi consensus methods. Although these indications are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present tools in further studies.

Economic evaluation of exercise training in patients with pulmonary hypertension.

PURPOSE: Exercise training as an add-on to medical therapy has been shown to improve exercise capacity, quality of life, and possibly prognosis in patients with pulmonary hypertension (PH). The purpose of this study was to analyze the impact of exercise training on healthcare costs in PH. METHODS: Estimated healthcare costs have been compared between patients with severe PH under optimized medical therapy only (control group) versus patients who received exercise training as an add-on to medical therapy (training group). Cost-analysis included a cost-estimation model of costs for baseline and follow-up visits and all PH-related healthcare events that occurred within the follow-up period. Time to clinical worsening and survival were assessed by clinical records, phone, and/or control visits. RESULTS: At baseline, the training (n = 58) and control group (n = 48) did not differ in age, gender, WHO-functional class, 6-min walking distance, hemodynamic parameters, or PH-targeted medication. During a follow-up of 24 ± 12 months, the training group had significantly better survival rates at 1 and 3 years and less worsening events (death, lung transplantation, hospitalization due to PH, new PAH-targeted medication) than the control group (15 vs. 25 events, p < 0.05), which also led to lower estimated healthcare costs of 657 within a period of 2 years. CONCLUSIONS: This is the first study to investigate the cost-effectiveness of exercise training in PH. Due to less worsening events within 2 years, healthcare costs were lower in patients performing exercise training as add-on to medical therapy than in patients with medical treatment only. Further prospective, randomized studies are needed to confirm these findings.

Pulmonary Embolism: An Update Based on the Revised AWMF-S2k Guideline.

Pulmonary embolism (PE) is the third most common acute cardiovascular disease. The risk of PE increases with age and mortality is high. Patients are stratified into hemodynamically stable versus unstable patients, as this has important implications for diagnosis and therapy. Since clinical signs and symptoms of acute PE are nonspecific, the clinical likelihood of PE is estimated to guide diagnostic pathways. D-dimer testing is performed in hemodynamically stable patients with low or intermediate probability of PE and the visualization of thromboembolism and its sequelae is commonly achieved with computed tomography pulmonary angiography (CTPA), supplemented by ultrasound techniques. With confirmed PE, another risk stratification estimates disease severity and defines intensity and setting of the ensuing treatment. The therapeutic spectrum ranges from outpatient treatment with initial oral anticoagulation to thrombolytic or interventional treatment in the intensive care unit or catheterization laboratory. In single cases, even acute surgical thrombectomy is attempted.

Unsupervised clustering of venous thromboembolism patients by clinical features at presentation identifies novel endotypes that improve prognostic stratification.

BACKGROUND: Individuals with acute venous thromboembolism (VTE) constitute a heterogeneous group of patients with diverse clinical characteristics and outcome. OBJECTIVES: To identify endotypes of individuals with acute VTE based on clinical characteristics at presentation through unsupervised cluster analysis and to evaluate their molecular proteomic profile and clinical outcome. METHODS: Data from 591 individuals from the Genotyping and Molecular phenotyping of Venous thromboembolism (GMP-VTE) project were explored. Hierarchical clustering was applied to 58 variables to define VTE endotypes. Clinical characteristics, three-year incidence of thromboembolic events or death, and acute-phase plasma proteomics were assessed. RESULTS: Four endotypes were identified, exhibiting different patterns of clinical characteristics and clinical course. Endotype 1 (n = 300), comprising older individuals with comorbidities, had the highest incidence of thromboembolic events or death (HR [95 % CI]: 3.76 [1.96-7.19]), followed by endotype 4 (n = 127) (HR [95 % CI]: 2.55 [1.26-5.16]), characterised by men with history of VTE and provoking risk factors, and endotype 3 (n = 57) (HR [95 % CI]: 1.57 [0.63-3.87]), composed of young women with provoking risk factors, vs. reference endotype 2 (n = 107). The reference endotype was constituted by individuals diagnosed with PE without comorbidities, who had the lowest incidence of the investigated endpoint. Differentially expressed proteins associated with the endotypes were related to distinct biological processes, supporting differences in molecular pathophysiology. The endotypes had superior prognostic ability compared to existing risk stratifications such as provoked vs unprovoked VTE and D-dimer levels. CONCLUSION: Four endotypes of VTE were identified by unsupervised phenotype-based clustering that diverge in clinical outcome and plasmatic protein signature. This approach might support the future development of individualized treatment in VTE.

Strategies for optimizing intravenous prostacyclin-analog therapy in patients with pulmonary arterial hypertension.

INTRODUCTION: Intravenous prostacyclin-analogs (PCA, e.g. epoprostenol, treprostinil, iloprost) have become an essential part in the therapy of patients with pulmonary hypertension (PH), mainly pulmonary arterial hypertension (PAH). They show considerable differences in pharmacology. A combination therapy including intravenous drugs is regarded as the 'gold standard' in most of PAH patients. AREAS COVERED: This review discusses and summarizes the studies and concepts on which this therapy is based. To date, intravenous prostacyclin-analogs are mainly administered when standard therapy fails to improve patients to low-risk status. However, preliminary data from uncontrolled studies suggest that an 'upfront triple' therapy including intravenous or subcutaneous prostacyclin-analogs could be preferable in selected patients. EXPERT OPINION: Various IV PCA have been evaluated in the treatment of patients with PAH. Today, combination therapy is the 'gold standard' for the majority of patients. Intravenous PCA is recommended from functional class III onwards. Timing of its initiation is still a point of discussion. An escalation of therapy to IV or SC PCA is always necessary if a low-risk status cannot be achieved with other targeted therapies. Preliminary data suggest that selected patients could benefit from an 'upfront triple' therapy. Controlled studies on which such recommendation could be based are lacking.

Comparison between thermodilution and Fick methods for resting and exercise-induced cardiac output measurement in patients with chronic dyspnea.

Studies comparing thermodilution (TD) and the direct Fick method (dFM) for cardiac output (CO) measurement are rare. We compared CO measurements between TD (2-5 cold water injections), the dFM, and indirect Fick method (iFM) at rest and during exercise, and assessed the effect of averaging different numbers of TD measurements during exercise. This retrospective study included 300 patients (52.3% women, mean age 66 ± 11 years) having pulmonary hypertension (76.0%) or unexplained dyspnea. Invasive hemodynamic and gas exchange parameters were measured at rest (supine; n = 300) and during unloaded cycling (semi-supine; n = 275) and 25-W exercise (semi-supine; n = 240). All three methods showed significant differences in CO measurement (ΔCO) at rest (p ≤ 0.001; ΔCO > 1 L/min: 45.0% [iFM vs. dFM], 42.0% [iFM vs. TD], and 45.7% [TD vs. dFM]). ΔCO (TD vs. dFM) was significant during unloaded cycling (p < 0.001; ΔCO > 1 L/min: 56.6%) but not during 25-W exercise (p = 0.137; ΔCO > 1 L/min: 52.8%). ΔCO (TD vs. dFM) during 25-W exercise was significant when using one or two (p ≤ 0.01) but not three (p = 0.06) TD measurements. Mean ΔCO (TD [≥3 measurements] vs. dFM) was -0.43 ± 1.98 and -0.06 ± 2.29 L/min during unloaded and 25-W exercise, respectively. Thus, TD and dFM CO measurements are comparable during 25-W exercise (averaging ≥3 TD measurements), but not during unloaded cycling or at rest. Individual ΔCOs vary substantially and require critical interpretation to avoid CO misclassification.

Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis.

Animal experiments and early phase human trials suggest that inhibition of factor XIa (FXIa) safely prevents venous thromboembolism (VTE), and specific murine models of sepsis have shown potential efficacy in alleviating cytokine storm. These latter findings support the role of FXI beyond coagulation. Here, we combine targeted proteomics, machine learning and bioinformatics, to discover associations between FXI activity (FXI:C) and the plasma protein profile of patients with VTE. FXI:C was measured with a modified activated partial prothrombin time (APTT) clotting time assay. Proximity extension assay-based protein profiling was performed on plasma collected from subjects from the Genotyping and Molecular Phenotyping of Venous Thromboembolism (GMP-VTE) Project, collected during an acute VTE event (n = 549) and 12-months after (n = 187). Among 444 proteins investigated, N = 21 and N = 66 were associated with FXI:C during the acute VTE event and at 12 months follow-up, respectively. Seven proteins were identified as FXI:C-associated at both time points. These FXI-related proteins were enriched in immune pathways related to causes of thrombo-inflammation, extracellular matrix interaction, lipid metabolism, and apoptosis. The results of this study offer important new avenues for future research into the multiple properties of FXI, which are of high clinical interest given the current development of FXI inhibitors.

Peripheral endothelial dysfunction is associated with gas exchange inefficiency in smokers.

AIMS: To assess the cross-sectional association between exercise capacity, gas exchange efficiency and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in a large-scale population-based survey. METHODS: The study population was comprised of 1416 volunteers 25 to 85 years old. Oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2) and ventilatory efficiency (VE vs. VCO2 slope and VE/VCO2@AT) were assessed on a breath-by-breath basis during incremental symptom-limited cardiopulmonary exercise. FMD and NMD measurements at rest were performed using standardised ultrasound techniques. RESULTS: Multivariable logistic regression analyses revealed a significant association between FMD and ventilatory efficiency in current smokers but not in ex-smokers or non-smokers. There was no association between FMD and VO2@AT or peak VO2. In current smokers, for each one millimetre decrement in FMD, VE/VCO2@AT improved by -3.6 (95% CI -6.8, -0.4) in the overall population [VE vs. VCO2 slope -3.9 (-7.1, -0.6)]. These results remained robust after adjusting for all major influencing factors. Neither exercise capacity nor ventilatory efficiency was significantly associated with NMD. CONCLUSION: In current smokers, FMD is significantly associated with ventilatory efficiency. This result may be interpreted as a potential clinical link between smoking and early pulmonary vasculopathy due to smoking.

Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension.

BACKGROUND: Even though specific agents for the treatment of patients with pulmonary hypertension (PH) are available, in PH patients, physical capacity and quality of life (QoL) are often restricted and survival is reduced. OBJECTIVES: This study prospectively investigated the long-term effects of respiratory and exercise training in patients with severe chronic PH regarding safety, time to clinical worsening and survival. METHODS: Fifty-eight consecutive patients with severe PH on stable disease-targeted medication received exercise and respiratory training in hospital for 3 weeks and continued at home. They were prospectively followed for 24 ± 12 months. Primary endpoints were time to clinical worsening and survival. Adverse events and changes in the 6-min walking test, QoL, WHO functional class and gas exchange were secondary endpoints and were evaluated at baseline and at weeks 3 and 15. RESULTS: All patients tolerated the exercise training well without severe adverse events. In week 15, 6-min walking test results were significantly improved compared to baseline (by 84 ± 49 m, p < 0.001), as well as QoL scores, WHO functional class (from 2.9 ± 0.5 to 2.6 ± 0.6, p < 0.01), peak oxygen consumption (from 12.5 ± 3.0 to 14.6 ± 3.9 ml/min/kg, p < 0.001), heart rate at rest (from 75 ± 12 to 61 ± 18 beats/min, p < 0.001) and maximal workload (from 65 ± 21 to 80 ± 25 W, p < 0.001). Survival at 1 and 2 years was 100 and 95%, respectively. Fifteen events occurred during the follow-up. CONCLUSION: This study indicates that exercise and respiratory training as add-on to medical treatment may improve exercise capacity and QoL, and that they have a good long-term safety in the described setting.

Intravenous prostacyclin-analogue therapy in pulmonary arterial hypertension - A review of the past, present and future.

Therapy with intravenous prostacyclin analogues in patients with pulmonary arterial hypertension (PAH) has been established for decades and is an integral component of the current guidelines for the treatment of pulmonary hypertension. Initially, these drugs were infused by external pump systems via tunnelled right atrial catheters with the need for cooling and frequent exchange of drug reservoirs. Associated complications included, among others, catheter-related infections. More recently, fully implantable pump systems have been developed with drug reservoirs that are filled transcutaneously, allowing intervals between refills of several weeks. This technique results in a low rate of infections. Epoprostenol, iloprost and treprostinil have all been used intravenously in PAH, but titration, dosing and dose escalation in long-term therapy are not standardized. Intravenous prostacyclin analogues are still under-used, despite available data suggesting that early and broad application of these therapies as part of risk-oriented, guideline-directed combination therapy for patients with PAH may lead to a survival benefit. This review provides a detailed overview of the drugs, infusion systems and dosing strategies used for intravenous therapy in patients with PAH.

Validation of the 6 min walk test according to the OMERACT filter: a systematic literature review by the EPOSS-OMERACT group.

OBJECTIVE: To assess the validity of the 6 min walk test (6MWT) in pulmonary arterial hypertension secondary to systemic sclerosis (PAH-SSc) according to the OMERACT filter. METHODS: A systematic literature search was conducted from 1966 through June 2009. The assessment of validation of the 6MWT was based on the OMERACT filter criteria with the domains 'truth', 'discrimination' and 'feasibility'. RESULTS: From the 57 articles identified, 9 (16%) were analysed. The 6MWT had face validity as it has been accepted by the registration agencies as a surrogate of PAH-SSc. It was sensitive to change in response to therapy, with effect sizes ranging from 0.30 to 1.37 with a parallel variation of haemodynamic parameters measured by right heart catheterisation. Feasibility was also validated. Content validity was not confirmed as this test was not specific for PAH-SSc. There was some evidence that 6MWT might meet criterion/construct validity, reproducibility and sensitivity to change over time, but insufficient data were provided to fully validate these components. CONCLUSIONS: Current evidence suggests partial validation of the 6MWT in PAH-SSc according to the OMERACT filter. Further dedicated studies are needed to validate completely the 6MWT in PAH-SSc, taking into account the comorbidities interfering with the 6MWT.

Interactions between rheumatologists and cardio-/pulmonologists in the assessment and use of outcome measures in pulmonary arterial hypertension related to systemic sclerosis.

OBJECTIVES: Pulmonary arterial hypertension in patients with systemic sclerosis is a disease involving multiple organ systems. We investigated the differences in perceptions of how to measure PAH-SSc among cardiologists, pulmonologists and rheumatologists. We also examined how a Delphi exercise can improve agreement among these subspecialties. METHODS: The outcome measures derived from the recent Delphi survey were used for a detailed analysis of the contribution of the various specialties contributing to it. We compared rheumatologists and cardiologist/pulmonologists with regards to preferences and ratings of various endpoints and the actual use of tools to measure these outcomes. We also examined the effects of the Delphi process among these groups. RESULTS: We could show that the different expert groups each tended to contribute differently to the development of the core set of measures and that interactions in the Delphi process resulted in convergence of rankings. Despite agreement on the high importance of the domains in the Delphi, the use of tools within those domains was sometimes divergent and dependent on specialty. CONCLUSIONS: Based on these results, use of differing tools in the diagnosis and treatment of PAH-SSc can be anticipated. Further, the convergence of results provides evidence, for the first time, for the ability of various approaches in these disciplines to reach harmonious endpoints of care for PAHSSc patients. A collaborative, interdisciplinary approach is advantageous for PAH-SSc patients.

Exercise and fluid challenge during right heart catheterisation for evaluation of dyspnoea.

This prospective study compared exercise test and intravenous fluid challenge in a single right heart catheter procedure to detect latent diastolic heart failure in patients with echocardiographic heart failure with preserved ejection function. We included 49 patients (73% female) with heart failure with preserved ejection function and pulmonary artery wedge pressure ≤15 mmHg. A subgroup of 26 patients had precapillary pulmonary hypertension. Invasive haemodynamic and gas exchange parameters were measured at rest, 45° upright position, during exercise, after complete haemodynamic and respiratory recovery in lying position, and after rapid infusion of 500 mL isotonic solution. Most haemodynamic parameters increased at both exercise and intravenous fluid challenge, with the higher increase at exercise. Pulmonary vascular resistance decreased by -0.21 wood units at exercise and -0.56 wood units at intravenous fluid challenge (p = 0.3); 20% (10 of 49) of patients had an increase in pulmonary artery wedge pressure above the upper limit of 20 mmHg at exercise, and 20% above the respective limit of 18 mmHg after intravenous fluid challenge. However, only three patients exceeded the upper limit of pulmonary artery wedge pressure in both tests, i.e. seven patients only at exercise and seven other patients only after intravenous fluid challenge. In the subgroup of pulmonary hypertension patients, only two patients exceeded pulmonary artery wedge pressure limits in both tests, further five patients at exercise and four patients after intravenous fluid challenge. A sequential protocol in the same patient showed a significantly higher increase in haemodynamic parameters at exercise compared to intravenous fluid challenge. Both methods can unmask diastolic dysfunction at right heart catheter procedure, but in different patient groups.