Evidence and unresolved questions in pulmonary hypertension: Insights from the 5th French Pulmonary Hypertension Network Meeting.

Pulmonary hypertension (PH) continues to present significant challenges to the medical community, both in terms of diagnosis and treatment. The advent of the updated 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines has introduced pivotal changes that reflect the rapidly advancing understanding of this complex disease. These changes include a revised definition of PH, updates to the classification system, and treatment algorithm. While these guidelines offer a critical framework for the management of PH, they have also sparked new discussions and questions. The 5th French Pulmonary Hypertension Network Meeting (Le Kremlin-Bicêtre, France, 2023), addressed these emergent questions and fostering a deeper understanding of the disease's multifaceted nature. These discussions were not limited to theoretical advancements but extended into the practical realms of patient management, highlighting the challenges and opportunities in applying the latest guidelines to clinical practice.

Bioreactance assessment of cardiac output lacks reliability for the follow-up of patients with pulmonary hypertension.

Cardiac output (CO) is one of the primary prognostic factors evaluated during the follow-up of patients treated for pulmonary hypertension (PH). It is recommended that it be measured using the thermodilution technique during right heart catheterization. The difficulty to perform iterative invasive measurements on the same individual led us to consider a non-invasive option. The aims of the present study were to assess the agreement between CO values obtained using bioreactance (Starling™ SV) and thermodilution, and to evaluate the ability of the bioreactance monitor to detect patients whose CO decreased by more than 15% during follow-up and, accordingly, its usefulness for patient monitoring. A prospective cohort study evaluating the performance of the Starling™ SV monitor was conducted in patients with clinically stable PH. Sixty patients referred for hemodynamic assessment were included. CO was measured using both the thermodilution technique and bioreactance during two follow-up visits. A total of 60 PH patients were included. All datasets were available at the baseline visit (V0) and 50 of them were usable during the follow-up visit (V1). Median [IQR] CO was 4.20 l/min [3.60-4.70] when assessed by bioreactance, and 5.30 l/min [4.57-6.20] by thermodilution (p<0.001). The Spearman correlation coefficient was 0.51 [0.36-0.64], and the average deviation on Bland-Altman plot was -1.25 l/min (95% CI [-1.48-1.01], p<0.001). The ability of the monitor to detect a variation in CO of more than 15% between two follow-up measurements, when such variation existed using thermodilution, was insufficient for clinical practice (AUC = 0.54, 95% CI [0.33-0.75]).

Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis.

Introduction: Asthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma. Objective: Our aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under "real-world" conditions. Methods: This was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0. Results: Twenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (p ≤ 0.01). At 12 months, 23% of patients were weaned off corticosteroids, while an increase or no change in dose was observed in 27% of patients. The median eosinophil count was significantly reduced from 365 cells/mm3 to 55 cells/mm3 at 6 months and 70 cells/mm3 at 12 months, respectively. No significant change was observed in FEV1. After 12 months of treatment, 14% of patients had had an average of 1 exacerbation of asthma, compared with 52% of patients before baseline. The tolerability profile was favorable. Conclusion: In this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function.

Risk stratification refinements with inclusion of haemodynamic variables at follow-up in patients with pulmonary arterial hypertension.

BACKGROUND AND AIMS: Haemodynamic variables are prognostic factors in pulmonary arterial hypertension (PAH). However, right heart catheterization (RHC) is not systematically recommended to assess the risk-status during follow-up. This study aimed to assess the added value of haemodynamic variables in prevalent patients to predict the risk of death or lung transplantation according to their risk status assessed by the non-invasive 4 strata model as recommended by the European guidelines. METHODS: We evaluated incident patients with PAH enrolled in the French PAH Registry between 2009 and 2020 who had a first follow-up RHC. Cox regression identified, in each follow-up risk status, haemodynamic variables significantly associated with transplant-free survival (TFS). Optimal thresholds were determined by time-dependent Receiver-Operating Characteristics. Several multivariable Cox regression models were performed to identify the haemodynamic variables improving the non-invasive risk stratification model. RESULTS: We analysed 1240 incident patients reassessed within a year by RHC. None of haemodynamic variable were significantly associated with TFS among low-risk (n=386) or high-risk (n=71) patients. Among patients at intermediate (-low, n=483, -high, n=300) risk at first follow-up, multivariable models including either stroke volume index (SVi) or mixed venous oxygen saturation (SvO2) were the best. The prognostic performance of refined 6 strata risk stratification model including the non-invasive 4 strata model and SVi>37 mL·m-2 and/or SvO2>65% for patients at intermediate-risk (Area Under the Curve 0.81, c-index 0.74), was better than that of 4 strata model (0.79, p=0.009; c-index 0.72). CONCLUSIONS: Cardiopulmonary haemodynamics may improve risk stratification at follow-up in patients at intermediate-risk.

Pulmonary function test results are correlated with 6-minute walk distance, distance-saturation product, and 6-minute walk work in patients with lymphangioleiomyomatosis.

BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare multicystic lung disease. Although a correlation between pulmonary function test (PFT) results and exercise capacity appears probable, it has not yet been demonstrated. The aim of this study was to assess whether PFT results correlate with 6-minute walk test (6MWT) results in patients with LAM. METHODS: We conducted a retrospective study of all patients with a diagnosis of LAM followed in a French reference centre over a 13-year period. PFT and 6MWT data were collected. Distance-saturation product (DSP) and 6-minute walk work (6MWORK) were calculated. RESULTS: A total of 62 patients were included. Their median forced expiratory volume in 1 s (FEV1) was 82.7 % predicted and their median forced vital capacity (FVC) was 96.7 % predicted. The median diffusing capacity of the lungs for carbon monoxide (DLCO) was 58.5 % predicted and was decreased in 79 % of the patients. The median 6-minute walk distance was 535 m, which was 90.9 % of the 602 m predicted distance. The median DSP was 497.4 m % and the median 6MWORK was 32,910 kg.m. The distance walked during the 6MWT was significantly correlated with FVC%predicted (R = 0.435), FEV1 %predicted (R = 0.303), TLC%predicted (R = 0.345), FRC%predicted (R = 0.262), RV/TLC ratio (R = -0.271), and DLCO%predicted (R = 0.279). DSP and 6MWORK were each significantly correlated with different PFT results. CONCLUSION: The present study shows that PFT results are potential predictors of the exercise capacity in patients with LAM. Additional studies are required to evaluate the interest of DSP and 6MWORK in LAM.

Interstitial lung disease-associated pulmonary hypertension - what the future holds.

PURPOSE OF REVIEW: Pulmonary hypertension associated with interstitial lung disease (ILD-PH) is associated with significant alteration of quality of life, exercise capacity, and survival. Over the past 2 years, there were changes in the guideline definition and classification of ILD-PH, and positive randomized controlled trials were published. RECENT FINDINGS: Pulmonary hypertension associated with chronic lung disease is now hemodynamically defined as a mean pulmonary artery pressure more than 20 mmHg, with pulmonary artery wedge pressure 15 mmHg or less, and pulmonary vascular resistance (PVR) at least 2 Wood units. Severe ILD-PH is defined by PVR more than 5 Wood units. In the INCREASE trial, patients receiving inhaled treprostinil had favorable significant changes in 6-min walk distance, NT-proBNP level, clinical worsening events, and forced vital capacity, which were maintained in the open label extension study. Promising results were obtained in a placebo-controlled pilot trial using escalated doses of inhaled nitric oxide. According to European guidelines, patients with ILD-PH should be referred to pulmonary hypertension centers, where inhaled treprostinil may be considered; phosphodiesterase type-5 inhibitors may also be considered in patients with severe ILD-PH. SUMMARY: Recent changes in the definitions and a new therapeutic option have an impact on the diagnosis and management of ILD-PH.

Changes in the management of chronic thromboembolic pulmonary hypertension over a 10-year period, in a French expert regional competence centre.

Over the last few years, the advent of balloon pulmonary angioplasty (BPA) had led to changes in the management of chronic thromboembolic pulmonary hypertension (CTEPH). We reviewed data from 98 CTEPH patients diagnosed during the last decade in a pulmonary hypertension (PH) expert centre. The management modalities of 2 periods (Period A: 2011-15 and Period B: 2016-20) were compared. Age (period A: 72 [58-80] years; period B: 69 [62-79] years), clinical (New York Heart Association (NYHA) functional class III-IV: 25/41, 61% vs 39/57, 68%), and hemodynamic assessments (pulmonary vascular resistance: 7.5 [6.2-8.7] WU vs 8.0 [6.0-10.2] WU) at baseline were not significantly different. Pulmonary endarterectomy was performed in less than one third of patients (12, 29.3% vs 15, 26.3%). For patients not eligible for surgery, medical therapy was mostly prescribed alone during period A (medical therapy alone, patients diagnosed in period A: 61% vs in period B: 17.5%) while it was associated with BPA during period B (medical therapy + BPA, 12% vs 61.4%). The 5-year survival rate was excellent for patients who underwent surgery (96.3%) or BPA (95.2%), but was only 42.1% for patients under oral medication only (p < 0.0001). Patients diagnosed with CTEPH who cannot be operated should undergo BPA. The survival rate after BPA is as good as after surgery and significantly better than that of oral medication only.

French recommendations for the diagnosis and management of lymphangioleiomyomatosis.

BACKGROUND: The present article is an English-language version of the French National Diagnostic and Care Protocol, a pragmatic tool to optimize and harmonize the diagnosis, care pathway, management and follow-up of lymphangioleiomyomatosis in France. METHODS: Practical recommendations were developed in accordance with the method for developing a National Diagnosis and Care Protocol for rare diseases of the Haute Autorité de Santé and following international guidelines and literature on lymphangioleiomyomatosis. It was developed by a multidisciplinary group, with the help of patient representatives and of RespiFIL, the rare disease network on respiratory diseases. RESULTS: Lymphangioleiomyomatosis is a rare lung disease characterised by a proliferation of smooth muscle cells that leads to the formation of multiple lung cysts. It occurs sporadically or as part of a genetic disease called tuberous sclerosis complex (TSC). The document addresses multiple aspects of the disease, to guide the clinicians regarding when to suspect a diagnosis of lymphangioleiomyomatosis, what to do in case of recurrent pneumothorax or angiomyolipomas, what investigations are needed to make the diagnosis of lymphangioleiomyomatosis, what the diagnostic criteria are for lymphangioleiomyomatosis, what the principles of management are, and how follow-up can be organised. Recommendations are made regarding the use of pharmaceutical specialties and treatment other than medications. CONCLUSION: These recommendations are intended to guide the diagnosis and practical management of pulmonary lymphangioleiomyomatosis.

Lung Dual-Energy CT Perfusion Blood Volume as a Marker of Severity in Chronic Thromboembolic Pulmonary Hypertension.

In chronic thromboembolic pulmonary hypertension (CTEPH), assessment of severity requires right heart catheterization (RHC) through cardiac index (CI). Previous studies have shown that dual-energy CT allows a quantitative assessment of the lung perfusion blood volume (PBV). Therefore, the objective was to evaluate the quantitative PBV as a marker of severity in CTEPH. In the present study, thirty-three patients with CTEPH (22 women, 68.2 ± 14.8 years) were included from May 2017 to September 2021. Mean quantitative PBV was 7.6% ± 3.1 and correlated with CI (r = 0.519, p = 0.002). Mean qualitative PBV was 41.1 ± 13.4 and did not correlate with CI. Quantitative PBV AUC values were 0.795 (95% CI: 0.637-0.953, p = 0.013) for a CI ≥ 2 L/min/m2 and 0.752 (95% CI: 0.575-0.929, p = 0.020) for a CI ≥ 2.5 L/min/m2. In conclusion, quantitative lung PBV outperformed qualitative PBV for its correlation with the cardiac index and may be used as a non-invasive marker of severity in CTPEH patients.

Nintedanib in idiopathic and secondary pleuroparenchymal fibroelastosis.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) has a variable disease course with dismal prognosis in the majority of patients with no validated drug therapy. This study is to evaluate the effect of nintedanib in patients with idiopathic and secondary PPFE. Patients admitted to a tertiary care center (2010-2019) were included into this retrospective analysis if they had a multidisciplinary diagnosis of PPFE, had been followed-up for 3 months or more, and had lung function tests and chest CTs available for review. Changes in pulmonary function tests were assessed using non-parametric tests and linear mixed effect model. Lung volumes were measured with lobar segmentation using chest CT. RESULTS: Out of 21 patients with PPFE, nine had received nintedanib, six had received another treatment and another six patients were monitored without drug therapy. Annual FVC (% of predicted) relative decline was - 13.6 ± 13.4%/year before nintedanib and - 1.6 ± 6.02%/year during nintedanib treatment (p = 0.014), whereas no significant change in FVC% relative decline was found in patients receiving another treatment (- 13.25 ± 34 before vs - 16.61 ± 36.2%/year during treatment; p = 0.343). Using linear mixed effect model, the slope in FVC was - 0.97%/month (95% CI: - 1.42; - 0.52) before treatment and - 0.50%/month (95% CI: - 0.88; 0.13) on nintedanib, with a difference between groups of + 0.47%/month (95% CI: 0.16; 0.78), p = 0.004. The decline in the upper lung volumes measured by CT was - 233 mL/year ± 387 mL/year before nintedanib and - 149 mL/year ± 173 mL/year on nintedanib (p = 0.327). Nintedanib tolerability was unremarkable. CONCLUSION: In patients with PPFE, nintedanib treatment might be associated with slower decline in lung function, paving the way for prospective, controlled studies.

Pulmonary hypertension in hereditary haemorrhagic telangiectasia is associated with multiple clinical conditions.

Multiple clinical conditions are combined with genetic mutations to contribute to the development of pulmonary vascular remodelling in hereditary haemorrhagic telangiectasia. A systematic aetiological evaluation is required for these patients. https://bit.ly/34V7HPy.

Hemodynamic Response to Treatment and Outcomes in Pulmonary Hypertension Associated With Interstitial Lung Disease Versus Pulmonary Arterial Hypertension in Systemic Sclerosis: Data From a Study Identifying Prognostic Factors in Pulmonary Hypertension Associated With Interstitial Lung Disease.

OBJECTIVE: Patients with systemic sclerosis and both pulmonary hypertension and interstitial lung disease (SSc-PH-ILD) generally carry a worse prognosis than patients with SSc and pulmonary arterial hypertension (SSc-PAH) without ILD. There is no evidence of the efficacy of PAH therapies in SSc-PH-ILD. We undertook this study to compare survival of and response to treatment in patients with SSc-PH-ILD and those with SSc-PAH. METHODS: We analyzed 128 patients (66 with SSc-PH-ILD and 62 with SSc-PAH) from 15 centers, in whom PH was diagnosed by right-sided heart catheterization; they were prospectively included in the PH registry. All patients received PAH-specific therapy. Computed tomography of the chest was used to confirm or exclude ILD. RESULTS: At baseline, patients with SSc-PH-ILD had less severe hemodynamic impairment than those with SSc-PAH (pulmonary vascular resistance 5.7 Wood units versus 8.7 Wood units; P = 0.0005) and lower diffusing capacity for carbon monoxide (median 25% [interquartile range (IQR) 18%, 35%] versus 40% [IQR 31%, 51%]; P = 0.0005). Additionally, patients with SSc-PH-ILD had increased mortality (8.1% at 1 year, 21.2% at 2 years, and 41.5% at 3 years) compared to those with SSc-PAH (4.1%, 8.7%, and 21.4%, respectively; P = 0.04). Upon treatment with PAH-targeted therapy, no improvement in the 6-minute walk distance was observed in either group. Improvement in the World Health Organization functional class was observed less frequently in patients with SSc-ILD-PH compared to those with SSc-PAH (13.6% versus 33.3%; P = 0.02). Hemodynamics improved similarly in both groups. CONCLUSION: ILD confers a worse prognosis to SSc-PH. Response to PAH-specific therapy is clinically poor in SSc-PH-ILD but was not found to be hemodynamically different from the response observed in SSc-PAH.

Impact of Lung Biopsy on Lung Function in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Video-assisted surgical lung biopsy (SLB) is performed in 10-30% of cases to establish the diagnosis of idiopathic pulmonary fibrosis (IPF). OBJECTIVES: The aim of the study was to analyze the impact of SLB on lung function in patients eventually diagnosed with IPF. METHODS: This is an observational, retrospective, monocentric study of all consecutive patients eventually diagnosed with IPF in multidisciplinary discussion who underwent SLB over 10 years in a specialized center. The primary end point was the variation in forced vital capacity (FVC) before and after the SLB. The secondary end points were the variations in forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO), and morbidity and mortality associated with the SLB. RESULTS: In 118 patients who underwent SLB and were diagnosed with IPF, a relative decrease in FVC of 4.8% (p < 0.001) was found between measurements performed before and after the procedure. The mean FVC decrease was 156 ± 386 mL in an average period of 185 days, representing an annualized decline of 363 ± 764 mL/year. A significant decrease was also observed after SLB in FEV1, TLC, and DLCO. Complications within 30 days of SLB occurred in 14.4% of patients. Two patients (1.7%) died within 30 days, where one of them had poor lung function. Survival at 1 year was significantly poorer in patients with FVC <50% at baseline. CONCLUSION: In this uncontrolled study in patients ultimately diagnosed with IPF, SLB was followed by a significant decline in FVC, which appears to be numerically greater than the average decline in the absence of treatment in the literature. Summary at a Glance: This study evaluated the change in lung function in 118 consecutive patients diagnosed with idiopathic pulmonary fibrosis by surgical lung biopsy. Forced vital capacity decreased by 156 ± 386 mL in a mean of 185 days between the last measurement before and first measurement after biopsy, representing an annualized decline of 363 ± 764 mL/year.

Impact of comorbidities and delay in diagnosis in elderly patients with pulmonary hypertension.

Patient age at diagnosis of pulmonary hypertension is steadily increasing. The present study sought to analyse clinical characteristics, time to diagnosis and prognosis of pulmonary hypertension in elderly and very elderly patients. A study was conducted in a French regional referral centre for pulmonary hypertension. All consecutive patients diagnosed with pre-capillary pulmonary hypertension were included and categorised according to age: <65 years ("young"), 65-74 years ("elderly") and ≥75 years ("very elderly"). Over a 4-year period, 248 patients were included: 101 (40.7%) were young, 82 (33.1%) were elderly and 65 (26.2%) were very elderly. The median age at diagnosis among the total population was 68 years. Compared with young patients, elderly and very elderly patients had a longer time to diagnosis (7±48, 9±21 and 16±32 months, respectively; p<0.001). Patients ≥75 years also more often had group 4 pulmonary hypertension. The median overall survival was 46±1.4 months, but was only 37±4.9 months in elderly patients and 28±4.7 months in very elderly patients. Survival from the first symptoms and survival adjusted to comorbidity was similar across age groups. Patient age should be taken into account when diagnosing pulmonary hypertension as it is associated with a specific clinical profile and a worse prognosis. The difference in prognosis is likely to be related to a delay in diagnosis and a greater number of comorbidities.

Safety of right heart catheterization for pulmonary hypertension in very elderly patients.

Right heart catheterization (RHC) is the reference test in diagnosing pulmonary hypertension (PH). The increasing age of patients at the time of diagnosis raises the issue of the morbidity of this invasive test in elderly individuals. We hypothesized that the morbidity associated with RHC would be increased in elderly patients and highlight differences in hemodynamic characteristics compared to younger patients. A retrospective study was conducted in a regional referral center for PH. Data for all consecutive RHCs performed during the study period were analyzed. Over a five-year period, 1060 RHCs were performed. Of the patients, 228 (21.5%) were aged ≥75 years and 832 (78.5%) were aged <75 years. Duration of the procedure and site of puncture did not differ according to age group (all P > 0.05). Nine procedures (0.9%) led to complications: three (1.3%) in patients aged >75 years and six (0.7%) in younger patients aged ( P = 0.5). Eight were local vascular injuries, directly related to a femoral vein puncture ( P < 0.001). Pulmonary arterial pressure and cardiac output were lower in patients aged >75 years than in younger patients ( P = 0.001). RHC may be performed regardless of patient age. The rate of RHC complications is not increased in individuals aged >75 years. As most complications were related to femoral vein puncture, this route should be avoided whenever possible.

Pulmonary hypertension in chronic lung diseases: comparison to other pulmonary hypertension groups.

Group 3 pulmonary hypertension (PH) is a common complication of advanced chronic lung disease. Our hypothesis was that group 3 PH is associated with a more severe baseline presentation and a more severe prognosis compared to group 1 pulmonary arterial hypertension (PAH), chronic thromboembolic PH (group 4), and group 5 PH. We retrospectively analyzed consecutive incident PH patients in a single center between January 2006 and November 2014. Data were acquired from a prospective database. Clinical, functional, and hemodynamic characteristics, as well as survival, were compared between the four groups of precapillary PH. A total of 363 patients were analyzed; 164 patients (45.2%) belonged to group 1 PAH, 109 (30%) to group 3 PH, 65 (17.9%) to group 4 PH, and 25 (6.9%) to group 5 PH. Group 3 patients were predominantly male and were more frequently in New York Heart Association (NYHA) class III/IV. Patients with group 3 and 4 PH were older, had significantly lower 6-min walking distance (6MWD), higher mean pulmonary arterial pressure, higher pulmonary vascular resistance (PVR), and lower cardiac index (CI) than PAH patients. Group 3 and 5 patients had significantly lower total lung capacity (TLC), forced vital capacity (FVC), and FEV1; group 3 patients had the lowest carbon monoxide transfer coefficient values. PH therapy was used in 90.9% of group 3 patients. Univariate analysis of prognostic factors in the overall population showed that age, male gender, NYHA class, groups 3 and 4 PH (vs. PAH), 6MWD, FVC, TLC, carbon monoxide transfer coefficient (KCO), PVR, CI, and venous oxygen saturation were significantly associated with greater mortality. Multivariate analysis showed that age, PH group 4, 6MWD, and KCO but no longer PH group 3 were significantly associated with mortality. Patients with group 3 PH are older, have more severe baseline presentation and lower survival rates than PAH patients in univariate analysis, that seemed to be related to older age.

Presence of Kidney Disease as an Outcome Predictor in Patients with Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) may lead to right heart failure and subsequently alter glomerular filtration rates (GFR). Chronic kidney disease (CKD, GFR <60 mL/min/1.73 m2) may also adversely affect PAH prognosis. This study aimed to assess how right heart hemodynamics was associated with reduced estimated GFR (eGFR) and the association of CKD with survival in PAH patients. METHODS: In a prospective PAH cohort (2003-2012), invasive hemodynamics and eGFR were collected at diagnosis (179 patients) and during follow-up (159 patients). The prevalence of CKD was assessed at PAH diagnosis. Variables, including hemodynamics, associated with reduced eGFR at diagnosis and during follow-up were tested in multivariate analysis. The association of CKD with survival was evaluated using a multivariate Cox regression model. RESULTS: At diagnosis, mean age was 60.4 ± 16.5 years, mean pulmonary arterial pressure was 43 ± 12 mm Hg, and eGFR was 74.4 ± 26.4 mL/min/1.73 m2. CKD was observed in 52 incident patients (29%). Independent determinants of reduced eGFR at diagnosis were age, systemic hypertension, and decreased cardiac index. Independent determinants of reduced eGFR during follow-up were age, female gender, PAH etiology, systemic hypertension, decreased cardiac index, and increased right atrial pressure. Age ≥60 years, female gender, NYHA 4, and CKD at diagnosis were independently associated with decreased survival. The adjusted hazards ratio for death associated with CKD was 1.81 (95% confidence interval [1.01-3.25]). CONCLUSION: CKD is frequent at PAH diagnosis and is independently associated with increased mortality. Right heart failure may induce renal hypoperfusion and congestion, and is associated with eGFR decrease.