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Introduction and Objectives: Outcome in patients with congenital heart diseases and pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Two-dimensional echocardiographic parameters, such as strain imaging or RV end-systolic remodeling index (RVESRI) have emerged to quantify RV function., Methods: We prospectively studied 30 patients aged 48±12 years with pretricuspid shunt and PAH and investigated the accuracy of multiple echocardiographic parameters of RV function (tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity, RV systolic-to-diastolic duration ratio, right atrial area, RV fractional area change, RV global longitudinal strain and RVESRI) to RV ejection fraction measured by cardiac magnetic resonance., Results: RV ejection fraction <45% was observed in 13 patients (43.3%). RV global longitudinal strain (ρ [Spearman's correlation coefficient]=-0.75; P=.001; R 2 =0.58; P=.001), right atrium area (ρ=-0.74; P <.0001; R 2 =0.56; P <.0001), RVESRI (ρ=-0.64; P <.0001; R 2 =0.47; P <.0001), systolic-to-diastolic duration ratio (ρ=-0.62; P=.0004; R 2 =0.47; P <.0001) and RV fractional area change (ρ=0.48; P=.01; R 2 =0.37; P <.0001) were correlated with RV ejection fraction. RV global longitudinal strain, RVESRI and right atrium area predicted RV ejection fraction <45% with the greatest area under curve (0.88; 95%CI, 0.71-1.00; 0.88; 95%CI, 0.76-1.00, and 0.89; 95%CI, 0.77-1.00, respectively). RV global longitudinal strain >-16%, RVESRI ≥ 1.7 and right atrial area ≥ 22 cm 2 predicted RV ejection fraction <45% with a sensitivity and specificity of 87.5% and 85.7%; 76.9% and 88.3%; 92.3% and 82.4%, respectively., Conclusions: RVESRI, right atrial area and RV global longitudinal strain are strong markers of RV dysfunction in patients with pretricuspid shunt and PAH., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Extracorporeal membrane oxygenation (ECMO) has become the standard of cardiopulmonary support during a sequential double lung transplant for pulmonary hypertension. Whether central or peripheral cannulation is the best strategy for these patients remains unknown. Our goal was to determine which is the best strategy by comparing 2 populations of patients., Methods: We performed a single-centre retrospective study based on an institutional prospective lung transplant database., Results: Between January 2011 and November 2016, 103 patients underwent double lung transplant for pulmonary hypertension. We compared 54 patients who had central ECMO (cECMO group) to 49 patients who had peripheral ECMO (pECMO group). The pECMO group had significantly more bridged patients who received emergency transplants (31% vs 6%, P = 0.001). The incidence of Grade 3 primary graft dysfunction requiring ECMO (14% vs 11%, P = not significant) and of in-hospital mortality (11% vs 14%, P = not significant) was similar between the groups. Groin infections (16% vs 4%, P = 0.031), deep vein thrombosis (27% vs 11%, P = 0.044) and lower limb ischaemia (12% vs 2%, P = 0.031) occurred significantly more often in the pECMO group. The number of chest reopenings for bleeding or infection was similar between the groups. The 3-month, 1-year and 5-year survival rates did not differ between the groups (P = 0.94)., Conclusions: Central or peripheral ECMO produced similar results during double lung transplant for pulmonary hypertension in terms of in-hospital deaths and long-term survival rates. Central ECMO provided satisfactory results without major bleeding provided the patient was weaned from ECMO at the end of the procedure. Despite the rate of groin and lower limb complications, peripheral cannulation remained the preferred solution to bridge the patient to transplant or for postoperative support.

Pre-capillary pulmonary hypertension (PH) in systemic sclerosis (SSc) is a heterogeneous condition with an overall bad prognosis. The objective of this study was to identify and characterize homogeneous phenotypes by a cluster analysis in SSc patients with PH. Patients were identified from two prospective cohorts from the US and France. Clinical, pulmonary function, high-resolution chest tomography, hemodynamic and survival data were extracted. We performed cluster analysis using the k-means method and compared survival between clusters using Cox regression analysis. Cluster analysis of 200 patients identified four homogenous phenotypes. Cluster C1 included patients with mild to moderate risk pulmonary arterial hypertension (PAH) with limited or no interstitial lung disease (ILD) and low DLCO with a 3-year survival of 81.5% (95% CI: 71.4-88.2). C2 had pre-capillary PH due to extensive ILD and worse 3-year survival compared to C1 (adjusted hazard ratio [HR] 3.14; 95% CI 1.66-5.94; p = 0.0004). C3 had severe PAH and a trend towards worse survival (HR 2.53; 95% CI 0.99-6.49; p = 0.052). Cluster C4 and C1 were similar with no difference in survival (HR 0.65; 95% CI 0.19-2.27, p = 0.507) but with a higher DLCO in C4. PH in SSc can be characterized into distinct clusters that differ in prognosis.

Background: Since 2006 and 2007, patients in France with severe pulmonary hypertension (PH) who are at imminent risk of death, despite optimal treatment in the intensive care unit, are placed on a high-priority list (HPL) for heart-lung transplantation (HLT) or double-lung transplantation (DLT). We assessed the effect of this approach on the waiting list and outcomes after transplantation., Methods: We conducted a single-center, retrospective, before-and-after study of consecutive patients with severe group 1, 1', or 4 PH listed for DLT or HLT between 2000 and 2013 (ie, 6 years before and 6 years after HPL implementation)., Results: We included 234 patients. HPL implementation resulted in a significant decrease of the cumulative incidence of death on the waiting list at 1 and 2 years (p < 0.0001). The cumulative incidence of transplantation increased significantly from 48% to 76% after 2 years (p < 0.0001). Overall survival after transplantation was not significantly different between the pre-HPL and post-HPL era. In the HPL period, patients on the regular list who received a transplant had a nonsignificant trend toward improved overall survival compared with those on the HPL who received a transplant (at 1, 2, 3, and 5 years: 85%, 77%, 72%, and 72% vs 67%, 61%, 58%, and 50%; p = 0.053). Finally, survival after listing improved significantly after HPL implementation (at 1, 2, 3, and 5 years: 69%, 62%, 58%, and 54% vs 54%, 45%, 34%, and 26% before the HPL; p < 0.001)., Conclusions: HPL implementation was followed by higher survival of PH patients after registration on the DLT or HLT waiting list and by a higher cumulative incidence of transplantation among waiting-list patients., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Bi-allelic mutations of the EIF2AK4 gene cause heritable pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH). We aimed to assess the effect of EIF2AK4 mutations on the clinical phenotypes and outcomes of PVOD/PCH., Methods: We did a population-based study using clinical, functional, and haemodynamic data from the registry of the French Pulmonary Hypertension Network. We reviewed the clinical data and outcomes from all patients referred to the French Referral Centre (Pulmonary Department, Hospital Kremlin-Bicêtre, University Paris-Sud) with either confirmed or highly probable PVOD/PCH with DNA available for mutation screening (excluding patients with other risk factors of pulmonary hypertension, such as chronic respiratory diseases). We sequenced the coding sequence and intronic junctions of the EIF2AK4 gene, and compared clinical characteristics and outcomes between EIF2AK4 mutation carriers and non-carriers. Medical therapies approved for pulmonary arterial hypertension (prostacyclin derivatives, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors) were given to patients according to the clinical judgment and discretion of treating physicians. The primary outcome was the event-free survival (death or transplantation). Secondary outcomes included response to therapies for pulmonary arterial hypertension and survival after lung transplantation. A satisfactory clinical response to specific therapy for pulmonary arterial hypertension was defined by achieving New York Heart Association functional class I or II, a 6-min walk distance of more than 440 m, and a cardiac index greater than 2·5 L/min per m 2 at the first reassessment after initiation of specific therapy for pulmonary arterial hypertension., Findings: We obtained data from Jan 1, 2003, to June 1, 2016, and identified 94 patients with sporadic or heritable PVOD/PCH (confirmed or highly probable). 27 (29%) of these patients had bi-allelic EIF2AK4 mutations. PVOD/PCH due to EIF2AK4 mutations occurred from birth to age 50 years, and these patients were younger at presentation than non-carriers (median 26·0 years [range 0-50.3] vs 60·0 years [6·7-81·4] years; p<0·0001). At diagnosis, both mutations carriers and non-carriers had similarly severe precapillary pulmonary hypertension and functional impairment. 22 (81%) of mutations carriers and 63 (94%) of non-carriers received therapy approved for pulmonary arterial hypertension. Drug-induced pulmonary oedema occurred in five (23%) of treated EIF2AK4 mutations carriers and 13 (21%) of treated non-carriers. Follow-up assessment after initiation of treatment showed that only three (4%) patients with PVOD/PCH reached the predefined criteria for satisfactory clinical response. The probabilities of event-free survival (death or transplantation) at 1 and 3 years were 63% and 32% in EIF2AK4 mutations carriers, and 75% and 34% in non-carriers. No significant differences occurred in event-free survival between the 2 groups (p=0·38). Among the 33 patients who had lung transplantation, estimated post-transplantation survival rates at 1, 2, and 5 years were 84%, 81%, and 73%, respectively., Interpretation: Heritable PVOD/PCH due to bi-allelic EIF2AK4 mutations is characterised by a younger age at diagnosis but these patients display similar disease severity compared with mutation non-carriers. Response to therapy approved for pulmonary arterial hypertension in PVOD/PCH is rare. PVOD/PCH is a devastating condition and lung transplantation should be considered for eligible patients., Funding: None., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Data on treatment of patients with portopulmonary hypertension (PoPH) are limited, as they are usually excluded from randomised controlled trials with pulmonary arterial hypertension (PAH)-specific therapies. This study investigated the short- and long-term efficacy/safety of bosentan in these patients, as well as its pharmacokinetics. All 34 consecutive patients with PoPH treated with first-line bosentan (December 2002 to July 2009) were retrospectively evaluated. Assessments included the New York Heart Association functional class (NYHA FC), blood tests, haemodynamics, 6-min walk distance (6MWD) and event-free status. The pharmacokinetics of bosentan in five patients with Child-Pugh (C-P) class B cirrhosis were compared with idiopathic PAH patients. Significant improvements from baseline were observed in NYHA FC, 6 MWD and haemodynamics, and were largely maintained during follow-up. Patients with C-P class B cirrhosis (n=9) had significantly larger haemodynamic improvement after mean ± SD 5 ± 2 months. Mean follow-up time was 43 ± 19 months; four patients died and seven patients had significant elevation of liver enzymes (annual rate 5.5%). Plasma concentrations of bosentan were higher in patients with C-P class B cirrhosis than those observed in idiopathic PAH. These data confirm the benefit of bosentan treatment for patients with PoPH. Haemodynamic improvements were particularly pronounced in patients with more severe cirrhosis. The safety profile of bosentan was consistent with previous studies.

Background: Precapillary pulmonary hypertension (PH) is a complication of pulmonary Langerhans cell histiocytosis (PLCH) associated with increased mortality. However, outcomes and efficacy of pulmonary arterial hypertension (PAH) therapies in patients with PH complicating PLCH(PLCH-PH) remain unknown., Methods: Consecutive patients with PLCH with PH confirmed by right-sided heart catheterization were included in the study. Characteristics at baseline and during follow-up as well as survival were analyzed., Results: Twenty-nine patients were studied. Baseline characteristics of patients with PLCH-PH wereas follows: 83% of patients in World Health Organization (WHO) functional class III to IV, mean 6-min walk distance of 355 ±95 m, mean pulmonary arterial pressure (mPAP) of 45 ±14 mm Hg,cardiac index of 3.2± 0.9 L/min/m 2 , and pulmonary vascular resistance (PVR) of 555 ±253 dyne/s/cm 5. Use of PAH therapy in 12 patients was followed by an improvement in mPAP (56±14 mm Hg and 45±12 mm Hg, P 5 .03) and PVR (701±239 dyne/s/cm 5 and 469±210 dyne/s/cm 5 , P = .01) between baseline and follow-up evaluations. No significant oxygen worsening was observed in the treated group. The 1-, 3-, and 5-year survival estimates of the 29 patients were 96%, 92%, and 73%,respectively. Except a trend toward a better survival rate associated with the use of PAH therapy,WHO functional class was the only variable significantly associated with death., Conclusions: In this group of patients, PAH therapies improved hemodynamics without oxygen worsening or pulmonary edema. WHO functional class was the only prognostic factor identified.Prospective clinical trials focusing on this population of patients are warranted

Background: Pulmonary hypertension (PH) complicating systemic sclerosis (SSc)-related interstitial lung disease (ILD) is usually associated with a poor prognosis. However, data are either lacking or scarce on prognostic factors in this condition. The objectives of this study were to compare the survival of patients with ILD-associated PH (PH-ILD) or pulmonary arterial hypertension (PAH) and to determine whether the severity of PH has prognostic value in SSc-associated PH-ILD., Methods: Consecutive patients with SSc and PH-ILD (n = 47) or PAH (n = 50) confirmed by right-sided heart catheterization were included in a cross-sectional analysis. PH was classified as mild (mean pulmonary arterial pressure [mPAP] ≤ 35 mm Hg) or moderate to severe (mPAP > 35 mm Hg)., Results: As compared with patients with PAH, subjects with PH-ILD were younger, were more frequently men with a history of smoking, had more frequently diffuse SSc, less frequently anticentromere antibodies, and a lower FVC/diffusing capacity of lung for carbon monoxide (DLCO) ratio. They had a worse prognosis than patients with PAH (3-year survival of 47% vs 71%, respectively; P = .07). Patients with mild PH-ILD had similar poor outcomes when compared with those with moderate to severe PH-ILD. Pericardial effusion (hazard ratio [HR], 2.44; P = .04) and lower DLCO (HR, 0.96; P = .01) were the only independent factors predictive of a poor survival in the PH-ILD group., Conclusions: Patients with SSc with PH-ILD had a different phenotype and a worse prognosis than those with SSc and PAH. Lower DLCO and presence of pericardial effusion were predictive of a poor outcome in PH-ILD, whereas mPAP seemed to have no prognostic significance.

Objective: Precapillary pulmonary hypertension (PH) is an important cause of death in patients with systemic sclerosis (SSc). It can occur in isolation (pulmonary arterial hypertension [PAH]) or in association with interstitial lung disease (ILD). Importantly, the outcomes and efficacy of PAH therapies in patients with SSc-related PH complicating ILD (PH-ILD) remain unknown. This study was undertaken to evaluate our experience with PH-ILD with regard to the efficacy and safety of PAH therapies in this patient cohort., Methods: We conducted a retrospective analysis of consecutive SSc patients from 2 large referral centers who had PH-ILD confirmed by right-sided heart catheterization and who received targeted PAH therapies. World Health Organization (WHO) functional class, 6-minute walk distance, and hemodynamic parameters were assessed at baseline and after a mean ± SD of 7.7 ± 6.2 months of treatment for PAH. Kaplan-Meier and Cox proportional hazards models were used to analyze survival and to identify prognostic factors., Results: Seventy patients were included in the study. No significant changes were observed in WHO functional class, 6-minute walk distance, or hemodynamic parameters after therapy. The 1-, 2-, and 3-year survival estimates were 71%, 39%, and 21%, respectively. In the multivariate model, worsening oxygenation during followup and reduced renal function were the only significant risk factors for death., Conclusion: This study represents the largest series to date in which the impact of PAH therapies in SSc-related PH-ILD was examined. In this cohort, PAH therapies were associated with no clear benefits. Deterioration in oxygenation was an important determinant of long-term survival. Prospective clinical trials focusing on this group of patients are warranted., (Copyright © 2011 by the American College of Rheumatology.)

Although pulmonary arterial hypertension (PAH) is usually considered as a late complication in limited subsets of systemic sclerosis (SSc), PAH can also occur in diffuse SSc and in early SSc. The evaluation of the velocity of the tricuspid regurgitation on echocardiography is so far the most effective screening tool for pulmonary hypertension (PH) in SSc. Nevertheless, it is not measurable in about 20% of SSc patients ; In that case, pulmonary arterial pressure can be evaluated by using the velocity of a pulmonary insufficiency and indirect signs of PH should be analyzed: pulmonary ejection time, right heart cavities dilatation and aspect of the inferior vena cava. About 10% of SSc patients with a suspected of PAH on echocardiography have post-capillary PH at right heart catheterization mainly due to left ventricular diastolic dysfunction. In some SSc patients, PAH and post-capillary PH due to left ventricular diastolic dysfunction may be associated. This can be suspected in case of post-capillary PH with a transpulmonary gradient > 12 mmHg. Lung fibrosis is another cause of PH in SSc. The distinction between PH associated to lung fibrosis from PAH is sometimes difficult, particularly in patients with a FVC between 60 and 70% of expected. Pulmonary veno-occlusive disease is a possible cause of precapillary PH in SSc. The diagnosis of pulmonary veno-occlusive disease should be discussed in each case of PAH associated ScS due to the high risk of lung edema at the introduction of specific PAH drugs.

Rationale: Pulmonary arterial hypertension (PAH) related to systemic sclerosis (SSc) has a poorer prognosis compared with other forms of PAH for reasons that remain unexplained., Objectives: To identify risk factors of mortality in a well-characterized cohort of patients with PAH related to systemic sclerosis (SSc-PAH)., Methods: Seventy-six consecutive patients with SSc (64 women and 12 men; mean age 61 +/- 11 yr) were diagnosed with PAH by heart catheterization in a single center, starting in January 2000, and followed over time. Kaplan-Meier estimates were calculated and mortality risk factors were analyzed., Measurements and Main Results: Forty (53%) patients were in World Health Organization functional class III or IV. Mean pulmonary artery pressure was 41 +/- 11 mm Hg, pulmonary vascular resistance (PVR) was 8.6 +/- 5.6 Wood units, and cardiac index was 2.4 +/- 0.7 L/min/m(2). Median follow-up time was 36 months, with 42 deaths observed. Survival estimates were 85%, 72%, 67%, 50%, and 36% at 1, 2, 3, 4, and 5 years, respectively. Multivariate analysis identified PVR (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03-1.18; P < 0.01), stroke volume index (HR, 0.94; 95% CI, 0.89-0.99; P = 0.02), and pulmonary arterial capacitance (HR, 0.43; 95% CI, 0.20-0.91; P = 0.03) as strong predictors of survival. An estimated glomerular filtration rate less than 60 ml/min/1.73 m(2) portended a threefold risk of mortality., Conclusions: Our results suggest that specific components of right ventricular dysfunction and renal impairment contribute to increased mortality in SSc-PAH. Understanding the mechanisms of right ventricular dysfunction in response to increased afterload should lead to improved targeted therapy in these patients.

Pulmonary arterial hypertension (PAH) is a devastating vascular complication of a number of connective tissue diseases, including systemic sclerosis (SSc), where it has a dramatic impact on the clinical course and overall survival and is the single most common cause of death in patients afflicted with this syndrome. Although remarkable advances have been achieved in elucidating the pathogenesis of PAH over the past 2 decades, leading to the development of disease-targeted therapies for the idiopathic form of this condition (IPAH), the response to therapy is suboptimal in SSc-related PAH (SSc-PAH), and survival remains very poor. Factors accounting for striking clinical and prognostic differences between these two syndromes are unclear but may include a more pronounced autoimmune, cellular, and inflammatory response, and a higher prevalence of comorbidities in SSc-PAH, including cardiac and pulmonary venous and parenchymal involvement. Furthermore, currently available markers of disease severity and clinical tools to assess response to therapy, which may be reliable in IPAH, are either limited or lacking in SSc-PAH. Thus, a more focused approach, including a better understanding of the pathogenesis and genetic factors underlying the development of SSc-PAH, a search for more specific and reliable tools to adequately assess functional impairment and monitor therapy, as well as the design of novel targeted therapies, are all urgently required to alter the dismal course of this syndrome.

Objective: Data on long-term efficacy of bosentan, an oral dual ET receptor antagonist, in SSc-associated pulmonary arterial hypertension (SSc-PAH) are lacking. We aimed to describe the long-term outcome of SSc-PAH treated with first-line monotherapy bosentan followed or not by the addition of prostanoids or sildenafil., Methods: A prospective analysis of 49 consecutive SSc-PAH patients treated with first-line bosentan was performed. New York Heart Association (NYHA) functional class, 6-min walk distance (6MWD) and haemodynamics were assessed at baseline and after 4 and 12 months., Results: At 4 months, significant improvements in NYHA functional class and haemodynamics were observed with stabilization at 1 year. There was no significant improvement in 6MWD. Overall survival estimates were 80, 56 and 51% at 1, 2 and 3 years, respectively, and were significantly worse than those in a cohort of patients with idiopathic PAH (92, 89 and 79% at 1, 2 and 3 years, respectively; P < 0.0001). Twenty-three patients (47%) died after a mean follow-up of 23 (18) months. In multivariate analysis, baseline and 4-month NYHA functional class and 4-month cardiac index were independent factors associated with overall survival., Conclusions: In our cohort of consecutive SSc-PAH patients treated with first-line bosentan, improvement in NYHA functional class and haemodynamics was significant after 4 months of treatment and stabilized afterwards. One-year overall survival rate was higher than previously reported in historical series. However, long-term prognosis remains poor. Our study underlines the importance of haemodynamic evaluation 4 months after the start of treatment to provide strong parameters associated with survival-like cardiac index.

Objectives: To examine baseline characteristics and outcome, and to determine variables affecting survival in patients with pulmonary arterial hypertension (PAH) associated with HIV infection (PAH-HIV) in the modern era of highly-active antiretroviral therapy (HAART) and specific PAH therapy., Design: Retrospective review of data from PAH-HIV patients without other associated risk factors for PAH, and comparison with previous series., Methods: Data were reviewed for 77 consecutive patients treated at the French Reference Centre for Pulmonary Hypertension between October 2000 and January 2008. Results were expressed as median [1st-3rd quartile] values., Results: At diagnosis of PAH, 81% patients were on HAART, 79% had a CD4+ count more than 200 cells/microl and 49% had undetectable HIV load. New York Heart Association functional class assessment was II (22%), III (69%), and IV (9%). Six-minute walk distance (6MWD) was 375 [288-421] m, and pulmonary vascular resistance was 689 [524-852] dyn s/cm(5). All patients received HAART irrespective of HIV disease stage. Specific PAH therapy was started in 50 patients and led to improvements in 6MWD and haemodynamic parameters. In patients who did not receive specific PAH therapy, 6MWD improved but haemodynamics did not change. Overall survival rate was 88% at 1 year and 72% at 3 years. On multivariate analysis, cardiac index more than 2.8 l/min per m(2) and CD4+ lymphocyte count more than 200 cells/microl were independent predictors of survival., Conclusion: In patients with PAH-HIV, HAART seems unable to improve haemodynamic parameters. Prognosis in PAH-HIV is mainly related to CD4+ lymphocyte count and cardiac function.

In France, pulmonary arterial hypertension associated with various diseases (connective-tissue diseases, congenital heart diseases, portal hypertension, HIV infection, consumption of anorectic agents) account for approximately 50% of cases of pulmonary arterial hypertension. As it is shown in idiopathic or familial pulmonary arterial hypertension, these forms of pulmonary arterial hypertension are characterized by pulmonary endothelial dysfunction and intense smooth muscle cell proliferation. Their clinical presentation and therapeutic management are similar to those of idiopathic and familial pulmonary arterial hypertension. However, their prognosis differs greatly: it is poor in scleroderma, and much better in congenital heart diseases.

Rationale: Portopulmonary hypertension (PoPH) can be defined as elevation of pulmonary arterial pressure and pulmonary vascular resistance in the setting of portal hypertension. Survival results in PoPH are contrasting, and prognostic factors need to be identified., Objectives: To analyze long-term survival in a large cohort of patients with PoPH with the aim of determining the independent variables affecting survival., Methods: We retrospectively analyzed charts of all patients referred to the French Referral Center for pulmonary arterial hypertension with the diagnosis of PoPH between 1984 and 2004., Measurements and Main Results: The study population comprised 154 patients; 57% male. Mean age at diagnosis was 49 +/- 11 years, 60% of patients were in New York Heart Association functional class III-IV, and mean 6-minute walk distance was 326 +/- 116 m. Hemodynamic measurements showed a mean pulmonary arterial pressure of 53 +/- 13 mm Hg, cardiac index of 2.9 +/- 0.9 L/min/m(2), and pulmonary vascular resistance of 752 +/- 377 dyn/s/cm(5). Portal hypertension was related to cirrhosis in 136 patients, with a severity assessed as follows: Child-Pugh class A 51%, Child-Pugh class B 38%, Child-Pugh class C 11%. Overall survival rates at 1, 3, and 5 yr were 88, 75, and 68%, respectively. Multivariate regression analysis individualized the presence and severity of cirrhosis and cardiac index as major independent prognostic factors., Conclusions: Prognosis in PoPH is mainly related to the presence and severity of cirrhosis and to cardiac function. The place of pulmonary arterial hypertension-specific therapies remains to be determined in the setting of PoPH.

Rationale: Platelet-derived growth factor (PDGF) promotes the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), and may play a role in the progression of pulmonary arterial hypertension (PAH), a condition characterized by proliferation of PASMCs resulting in the obstruction of small pulmonary arteries., Objectives: To analyze the expression and pathogenic role of PDGF in idiopathic PAH., Methods: PDGF and PDGF receptor mRNA expression was studied by real-time reverse transcription-polymerase chain reaction performed on laser capture microdissected pulmonary arteries from patients undergoing lung transplantation for idiopathic PAH. Immunohistochemistry was used to localize PDGF, PDGF receptors, and phosphorylated PDGFR-beta. The effects of imatinib on PDGF-B-induced proliferation and chemotaxis were tested on human PASMCs., Measurements and Main Results: PDGF-A, PDGF-B, PDGFR-alpha, and PDGFR-beta mRNA expression was increased in small pulmonary arteries from patients displaying idiopathic PAH, as compared with control subjects. Western blot analysis revealed a significant increase in protein expression of PDGFR-beta in PAH lungs, as compared with control lungs. In small remodeled pulmonary arteries, PDGF-A and PDGF-B mainly localized to PASMCs and endothelial cells (perivascular inflammatory infiltrates, when present, showed intensive staining), PDGFR-alpha and PDGFR-beta mainly stained PASMCs and to a lesser extent endothelial cells. Proliferating pulmonary vascular lesions stained phosphorylated PDGFR-beta. PDGF-BB-induced proliferation and migration of PASMCs were inhibited by imatinib. This effect was not due to PASMC apoptosis., Conclusions: PDGF may play an important role in human PAH. Novel therapeutic strategies targeting the PDGF pathway should be tested in clinical trials.

Objective: To describe the response to first-line immunosuppressive therapy with or without pulmonary vasodilators in pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD)., Methods: Twenty-three consecutive patients with SLE- or MCTD-associated PAH treated with first-line immunosuppressive therapy either alone (n = 16) or in combination with pulmonary vasodilators (n = 7) were evaluated according to clinical and hemodynamic criteria before and after immunosuppressive therapy. Responders were defined as patients in New York Heart Association (NYHA) functional class I or II with hemodynamic improvement after the last pulse of cyclophosphamide., Results: Among the 16 patients treated with first-line immunosuppressive therapy alone, 8 (50%) were responders. These patients had a significantly improved NYHA functional class, 6-minute walking distance, and mean pulmonary artery pressure. Patients in NYHA functional class I or II and/or a cardiac index >3.1 liters/minute/m(2) at baseline were more likely to benefit from immunosuppressive therapy. Six of the 8 nonresponders subsequently improved with pulmonary vasodilators. Among the 7 patients who were initially treated with immunosuppressive therapy and pulmonary vasodilators, 4 (57.1%) were responders., Conclusion: PAH associated with SLE or MCTD may respond to a treatment combining cyclophosphamide and glucocorticoids. Patients who could benefit from this immunosuppressive therapy could be those who have less severe disease at baseline. For patients with more severe disease, pulmonary vasodilators should be started, possibly in combination with immunosuppressants. In any case, clinical and hemodynamic evaluations are mandatory to monitor the response and adapt the treatment. These retrospective and uncontrolled data need to be confirmed by randomized controlled trials.