Clinical differences between idiopathic and scleroderma-related pulmonary hypertension (original) (raw)
Related papers
Prevalence and risk factors for left ventricular diastolic dysfunction in a scleroderma cohort
Scandinavian Journal of Rheumatology, 2016
Objectives: Left ventricular diastolic dysfunction (LVDD) is more common in systemic sclerosis (SSc) compared to the general population. Focal myocardial ischaemia and fibrosis may be important in its pathogenesis. LVDD is associated with increased mortality and little is known about the risk factors. Advanced SSc lung complications may accompany LVDD. Method: We conducted a cross-sectional study of 300 SSc outpatients with and without LVDD, seen between May 2012 and May 2014, and performed univariate and multivariate regression analyses to determine clinical factors associated with LVDD. LVDD was confirmed by the latest echocardiogram (tissue Doppler imaging) reports. Interstitial lung disease (ILD) was confirmed by high-resolution computed tomography (HRCT) and pulmonary hypertension (PH) was diagnosed by right heart catheterization (RHC). Results: Of the 300 SSc patients, there were 133 (44%) with LVDD. In the univariate analysis, advanced age, disease duration (from the onset of Raynaud's phenomenon), anti-centromere antibody, the presence of SSc lung complications, systemic hypertension, smoking, valvular heart disease, chronic kidney and thyroid diseases were all significantly associated with LVDD. However, in the multivariate regression analysis, advanced age was the most significant factor associated with LVDD, followed by systemic hypertension and SSc lung complications. There were significantly more deaths in the LVDD group (p < 0.0001). Conclusions: LVDD was more prevalent in the SSc population, especially in those with advanced age, systemic hypertension, or SSc-pulmonary complications. SSc patients with pulmonary fibrosis or pulmonary hypertension had more advanced LVDD and higher mortality. More effective therapy is needed to improve the outcome in this population.
Chest, 2018
BACKGROUND: Pulmonary arterial hypertension (PAH) is a leading cause of death in patients with systemic sclerosis (SSc). The purpose of this study was to assess long-term outcomes in patients with SSc-PAH. METHODS: Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma is a prospective registry of patients with SSc at high risk for or with incident pulmonary hypertension from right heart catheterization. Incident World Health Organization group I PAH patients were analyzed. Kaplan-Meier survival curves were generated for the overall cohort and those who died of PAH. Multivariate Cox regression models identified predictors of mortality. RESULTS: Survival in 160 patients with incident SSc-PAH at 1, 3, 5, and 8 years was 95%, 75%, 63%, and 49%, respectively. PAH accounted for 52% of all deaths. When restricted to deaths from PAH, respective survival rates were 97%, 83%, 76%, and 76%, with 93% of PAH-related deaths occurring within 4 years of diagnosis. Men (hazard ratio [HR], 3.11; 95% CI, 1.38-6.98), diffuse disease (HR, 2.12; 95% CI, 1.13-3.93), systolic pulmonary artery pressure (PAP) on ECG (HR, 1.06 95% CI, 1.01-1.11), mean PAP on right heart catheterization (HR, 1.03; 95% CI, 1.001-1.07), 6-min walk distance (HR, 0.92; 95% CI, 0.86-0.99), and diffusing capacity for carbon monoxide (HR, 0.65; 95% CI, 0.46-0.92) significantly affected survival on multivariate analysis. CONCLUSIONS: Overall survival in PHAROS was higher than other SSc-PAH cohorts. PAH accounted for more than one-half of deaths and primarily within the first few years after PAH diagnosis. Optimization of treatment for those at greatest risk of early PAH-related death is crucial.
The Journal of …, 2011
Objective. Pulmonary arterial hypertension (PAH) increases mortality in systemic sclerosis (SSc). The multicenter PHAROS registry (Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma) prospectively follows subjects with SSc at high risk for or with incident pulmonary hypertension (PH). We describe the registry design and baseline characteristics of subjects enrolled during the first 18 months since the start of the study. Methods. High-risk subjects are enrolled and classified as Pre-PAH if they have (1) carbon monoxide diffusing capacity (DLCO) < 55% predicted; (2) percentage of predicted forced vital capacity/DLCO ratio ≥ 1.6; or (3) an estimated right ventricular systolic pressure > 35 mm Hg on echocardiography. Subjects with right heart catheterization (RHC)-confirmed incident PH (mean pulmonary artery pressure ≥ 25 mm Hg within previous 6 months) are subclassified into PAH, pulmonary venous hypertension secondary to left-side heart disease (PVH), and PH due to interstitial lung disease (PH-ILD). Baseline and biannual demographic, clinical, and laboratory data and patient-reported health questionnaires are collected. Results. There are 237 subjects enrolled in PHAROS. The majority are white (73%) and women (87%). There are 166 Pre-PAH and 71 Definite PH subjects (49 PAH, 7 PVH, and 15 PH-ILD). Conclusion. PHAROS is the largest US and Canadian cohort of subjects with SSc at high risk for or with incident PAH. PAH-specific therapies are approved for 49/71 subjects with RHC-confirmed PAH. Analyses of PHAROS registry data will permit identification of risk factors for development of PAH among SSc patients at high risk for PAH and enhance understanding of the course of SSc-PAH.
Hemodynamic Predictors of Survival in Scleroderma-related Pulmonary Arterial Hypertension
American Journal of Respiratory and Critical Care Medicine, 2010
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 6 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 6 11 mm Hg, pulmonary vascular resistance (PVR) was 8.6 6 5.6 Wood units, and cardiac index was 2.4 6 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 5 0.02), and pulmonary arterial capacitance (HR, 0.43; 95% CI, 0.20-0.91; P 5 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.
Scandinavian Journal of Rheumatology, 2010
To describe the survival rate in a cohort of systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) and to evaluate possible predictors for SSc-PAH in a cohort of SSc patients. Methods: Thirty patients with SSc-PAH and 150 SSc patients without PAH were included. Survival and survival on therapy were calculated. Clinical features at baseline were correlated to the risk for development of PAH during follow-up. Results: The 1-, 2-, 3-, and 4-year survival rates were 86, 59, 39, and 22%, respectively, from diagnosis of PAH. The hazard ratio for total mortality in the SSc-PAH group was 3.2 [95% confidence interval (CI) 1.8-5.7] compared to SSc without PAH (p < 0.001). Risk factors at baseline for the development of PAH were: limited skin involvement, low diffusing capacity of the lung for carbon monoxide (DL CO ), high N-terminal pro-brain natriuretic peptide (NTProBNP), increased estimated systolic pulmonary arterial pressure (ESPAP), and the presence of teleangiectases. Severe peripheral vascular disease requiring iloprost treatment during follow-up was associated with an eightfold increased risk of PAH. Conclusion: Despite modern treatment and yearly screening by echocardiography, the survival in SSc-PAH is still low in our cohort. The identified risk factors should be assessed to select patients eligible for right heart catheterization (RHC) to make an earlier diagnosis.
Pulmonary Circulation, 2015
Patients with scleroderma (SSc)-associated pulmonary arterial hypertension (PAH) have worse survival than patients with idiopathic PAH (IPAH). We hypothesized that the right ventricle (RV) adapts differently in SSc-PAH versus IPAH. We used cardiac magnetic resonance imaging (cMRI) and hemodynamic characteristics to assess the relationship between RV morphology and RV load in patients with SSc-PAH and IPAH. In 53 patients with PAH (35 with SSc-PAH and 18 with IPAH) diagnosed by right heart catheterization (RHC), we examined cMRIs obtained within 48 hours of RHC and compared RV morphology between groups. Regression analysis was used to assess the association between diagnosis (IPAH vs. SSc-PAH) and RV measurements after adjusting for age, sex, race, body mass index (BMI), left ventricular (LV) mass, and RV load. There were no significant differences in unadjusted comparisons of cMRI measurements between the two groups. Univariable regression showed RV mass index (RVMI) was linearly associated with measures of RV load in both the overall cohort and within each group. Multivariable linear regression models revealed a significant interaction between disease type and RVMI adjusting for pulmonary vascular resistance (PVR), age, sex, race, BMI, and LV mass. This model showed a decreased slope in the relationship between RVMI and PVR in the SSc-PAH group compared with the IPAH group. RVMI varies linearly with measures of RV load. After adjusting for multiple potential confounders, patients with SSc-PAH demonstrated significantly less RV hypertrophy with increasing PVR than patients with IPAH. This difference in adaptive hypertrophy may in part explain previously observed decreased contractility and poorer survival in SSc-PAH.
Improved survival in limited scleroderma-related pulmonary artery hypertension
Internal and Emergency Medicine, 2013
Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p \ 0.01), higher mean pulmonary artery pressure (p \ 0.05), lower pulmonary artery capacitance (p \ 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p \ 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p \ 0.05), whereas cardiac index increased in Group 2 (p \ 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO 2 ) were independent predictors of survival. A value of DLco \7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p \ 0.001); for SvO 2 \63.8 %, the HR was 3.7 (p \ 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO 2 are predictors of survival and may assist in planning treatment.
Arthritis Care & Research, 2014
Methods. The Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma registry is a prospective registry of SSc patients at high risk for PAH or with definite pulmonary hypertension diagnosed by right-sided heart catheterization within 6 months of enrollment. Only patients with World Health Organization group I PAH (mean pulmonary artery pressure >25 mm Hg and pulmonary capillary wedge pressure <15 mm Hg without significant interstitial lung disease) were included in these analyses. Results. In total, 131 SSc patients with incident PAH were followed for a mean ؎ SD of 2.0 ؎ 1.4 years. The 1-, 2-, and 3-year cumulative survival rates were 93%, 88%, and 75%, respectively. On multivariate analysis, age >60 years (hazard ratio [HR] 3.0, 95% confidence interval [95% CI] 1.1-8.4), male sex (HR 3.9, 95% CI 1.1-13.9), functional class (FC) IV status (HR 6.5, 95% CI 1.8 -22.8), and diffusing capacity for carbon monoxide (DLCO) <39% predicted (HR 4.2, 95% CI 1.3-13.8) were significant predictors of mortality. Conclusion. This is the largest study describing survival in patients with incident SSc-associated PAH followed up at multiple SSc centers in the US who had undergone routine screening for PAH. The survival rates were better than those reported in other recently described SSc-associated PAH cohorts. Severely reduced DLCO and FC IV status at the time of PAH diagnosis portended a poor prognosis in these patients. Dr. Chung has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromGileadandActelionandresearchsupportfromGilead,UnitedTherapeutics,andPfizer.Dr.Bolsterhasservedasanexpertwitnessontherelationshipbetweenpulmonaryarterialhypertensionandunderlyingautoimmunediseases.Dr.Fischerhasreceivedconsultingfees,speakingfees,and/orhonoraria(morethan10,000 each) from Gilead and Actelion and research support from Gilead, United Therapeutics, and Pfizer. Dr. Bolster has served as an expert witness on the relationship between pulmonary arterial hypertension and underlying autoimmune diseases. Dr. Fischer has received consulting fees, speaking fees, and/or honoraria (more than 10,000each)fromGileadandActelionandresearchsupportfromGilead,UnitedTherapeutics,andPfizer.Dr.Bolsterhasservedasanexpertwitnessontherelationshipbetweenpulmonaryarterialhypertensionandunderlyingautoimmunediseases.Dr.Fischerhasreceivedconsultingfees,speakingfees,and/orhonoraria(morethan10,000 each) from Gilead and Actelion. Dr. Furst has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromGileadandActelion.Dr.Gomberg−Maitlandhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Gilead and Actelion. Dr. Gomberg-Maitland has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromGileadandActelion.Dr.Gomberg−Maitlandhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) and research grants from Actelion, Gilead, Glaxo-SmithKline, Medtronic, Novartis, and United Therapeutics. Dr. Khanna has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelion,Gilead,Genentech,Bristol−MyersSquibb,Bayer,Roche,Digna,andUnitedTherapeuticsandhasreceivedresearchfundingfromActelion,thePulmonaryHypertensionAssociation,theSclerodermaFoundation,andUnitedTherapeutics.Dr.Molitorhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Actelion, Gilead, Genentech, Bristol-Myers Squibb, Bayer, Roche, Digna, and United Therapeutics and has received research funding from Actelion, the Pulmonary Hypertension Association, the Scleroderma Foundation, and United Therapeutics. Dr. Molitor has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelion,Gilead,Genentech,Bristol−MyersSquibb,Bayer,Roche,Digna,andUnitedTherapeuticsandhasreceivedresearchfundingfromActelion,thePulmonaryHypertensionAssociation,theSclerodermaFoundation,andUnitedTherapeutics.Dr.Molitorhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000) from Actelion. Dr. Preston has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelion,Bayer,Gilead,Novartis,andUnitedTherapeuticsandresearchgrantsfromActelion,Aires,Gilead,Novartis,andUnitedTherapeutics.Dr.Schiopuhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Actelion, Bayer, Gilead, Novartis, and United Therapeutics and research grants from Actelion, Aires, Gilead, Novartis, and United Therapeutics. Dr. Schiopu has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelion,Bayer,Gilead,Novartis,andUnitedTherapeuticsandresearchgrantsfromActelion,Aires,Gilead,Novartis,andUnitedTherapeutics.Dr.Schiopuhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000) from United Therapeutics. Dr. Simms has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelionandGileadandhasreceivedresearchsupportfromGilead,Actelion,andUnitedTherapeutics.Dr.Steenhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Actelion and Gilead and has received research support from Gilead, Actelion, and United Therapeutics. Dr. Steen has received consulting fees, speaking fees, and/or honoraria (less than 10,000each)fromActelionandGileadandhasreceivedresearchsupportfromGilead,Actelion,andUnitedTherapeutics.Dr.Steenhasreceivedconsultingfees,speakingfees,and/orhonoraria(lessthan10,000 each) from Actelion, Gilead, and United Therapeutics and has received research support from Actelion, Gilead, Pfizer, and United Therapeutics.
Annals of the American Thoracic Society, 2017
Patients with scleroderma associated pulmonary arterial hypertension (SSc-PAH) continue to have an unacceptably high mortality despite the progress achieved with pulmonary arterial vasodilator therapies. We sought to determine whether SSc-PAH is a clinically distinct pulmonary vascular disease phenotype when compared to IPAH, based on the progression of echocardiographic right ventricular (RV) dysfunction. Retrospective analysis of echocardiographic data in 13 SSc-PAH and 11 IPAH patients was used to delineate the progression of RV dysfunction during single or combination pulmonary arterial vasodilator therapy. All patients had right heart catheterization (RHC) confirmed pulmonary arterial hypertension, complete baseline (at the time of diagnosis) and follow up (most recent) echocardiograms. We excluded patients with significant scleroderma associated interstitial lung disease. Adjusting for time of follow up and disease duration, we performed mixed model regression analyses compari...