Pulmonary hemodynamics and transplant‐free survival in sarcoidosis‐associated pulmonary hypertension: Results from an international registry

Gayen, Shameek K.; Baughman, Robert P.; Nathan, Steven D.; Wells, Athol U.; Kouranos, Vasilis; Alhamad, Esam H.; Culver, Daniel A.; Barney, Joseph; Carmoma, Eva M.; Cordova, Francis C.; Huitema, Marloes; Scholand, Mary Beth; Wijsenbeek, Marlies; Ganesh, Sivagini; Birring, Surinder S.; Price, Laura C.; Wort, Stephen J.; Shlobin, Oksana A.; Gupta, Rohit

doi:10.1002/pul2.12297

Cited by 6 publications

(6 citation statements)

References 20 publications

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“…This change in definition results from studies demonstrating that a PVR threshold of 5 WU is a better predictor of mortality in patients with COPD-PH and ILD-PH [ 4 , 6 ]. This finding was also found in patients with sarcoidosis-associated PH [ 5 ]. Severe PH as defined by the 2022 ESC/ERS guidelines was a strong independent predictor of mortality in our cohort of patients, even when accounting for underlying lung disease and lung function.…”

Section: Discussionsupporting

confidence: 67%

“…Pulmonary hypertension (PH) often accompanies chronic lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary sarcoidosis, and other interstitial lung diseases (ILDs) [ 1 ]. The presence of PH in chronic lung disease portends unfavorable outcomes [ 2 , 3 , 4 , 5 , 6 , 7 ]. Notably, hemodynamic parameters may play a more integral role than lung function in long-term outcomes [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, elevated pulmonary vascular resistance (PVR) is significantly associated with mortality including lung transplant waitlist mortality in patients with COPD, even when accounting for spirometry [ 4 , 15 ]. Beyond COPD, elevated PVR is also associated with increased mortality in patients with ILD and sarcoidosis [ 5 ]. The diagnosis of IPF, 6 min walk distance (6MWD), and reduced diffusing capacity of the lung for carbon monoxide (DLCO) may prognosticate patients with chronic lung disease and PH [ 3 , 13 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Predictors of Mortality in Pulmonary Hypertension-Associated Chronic Lung Disease

Pescatore,

Bittner,

D’Alonzo

et al. 2024

JCM

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Background/Objectives: Pulmonary hypertension (PH) often accompanies chronic lung diseases. Several chronic lung diseases with PH portends unfavorable outcomes. We investigated which variables in this cohort of patients with chronic lung disease and PH predicts mortality. Methods: This is a retrospective analysis of patients with chronic lung disease and PH at a single tertiary, academic center. The underlying lung disease included were COPD, IPF, other fibrotic ILD, non-fibrotic ILD, fibrotic sarcoidosis, and CPFE. All patients had right heart catheterization diagnostic of PH as well as pulmonary function testing data including 6 min walk testing. Univariable and multivariate Cox regression was performed to identify variables associated with mortality. Results: We identified 793 patients with chronic lung disease and PH. In total, 144 patients died prior to potential lung transplant. In multivariable Cox regression IPF, other fibrotic ILD, non-fibrotic ILD, and CPFE were significantly associated with an increased risk of mortality. Severe PH (PVR > 5 WU), FEV1 < 30% predicted, FVC < 40% predicted, 6 min walk distance < 150 m were also significantly associated with an increased risk of mortality. Conclusions: Carrying a diagnosis of IPF, CPFE, fibrotic ILD, or non-fibrotic ILD with PH has an increased risk of mortality as compared to COPD with PH. Hemodynamic, PVR > 5 WU, 6 min walk test less than 150 m, as well as spirometric data including FEV1 < 30% and FVC < 40% predicted were independently associated with an increased risk of death.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predictors of Mortality in Pulmonary Hypertension-Associated Chronic Lung Disease

Pescatore,

Bittner,

D’Alonzo

et al. 2024

JCM

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“…In the international registry including unselected patients with SAPH, 115/159 (72.3%) received PAH-targeted therapy, which consisted of monotherapy in 88.2% (PDE5-i: n = 86, ERA: n = 56), bitherapy in 17.6% (PDE5i + ERA: n = 28), and tritherapy in 6.3% (PDE5-I + ERA + prostanoid: n = 10) [45]. In both registries, PAH-targeted therapy was not associated with decreased mortality, provided that treated patients had a significantly worse condition at baseline than the untreated ones [41,45,84].…”

Section: Treatment Of Vascular Disease and Use Of Pah Agentsmentioning

confidence: 98%

“…As far as the definition of severe SAPH goes, with the foreseeable impact of therapeutic measures and timing on LTx evaluation, one study showed that both mPAP ≥ 40 mmHg and PVR ≥ 5 WU were strongly associated with a shorter transplant-free survival and increased risk of death or LTx [84]. Interestingly, and in contrast to common definitions of severe PH in chronic lung diseases, neither a mPAP > 35 mmHg nor mPAP > 25 mmHg with cardiac index ≤ 2 L/min/m 2 were associated with these outcomes.…”

Section: Rhcmentioning

confidence: 99%

Sarcoidosis-Associated Pulmonary Hypertension

Israël-Biet,

Pastré,

Nunes

2024

JCM

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Sarcoidosis-associated pulmonary hypertension (SAPH) is a very severe complication of the disease, largely impacting its morbidity and being one of its strongest predictors of mortality. With the recent modifications of the hemodynamic definition of pulmonary hypertension (mean arterial pulmonary pressure >20 instead of <25 mmHg,) its prevalence is presently not precisely known, but it affects from 3 to 20% of sarcoid patients; mostly, although not exclusively, those with an advanced, fibrotic pulmonary disease. Its gold-standard diagnostic tool remains right heart catheterization (RHC). The decision to perform it relies on an expert decision after a non-invasive work-up, in which echocardiography remains the screening tool of choice. The mechanisms underlying SAPH, very often entangled, are crucial to define, as appropriate and personalized therapeutic strategies will aim at targeting the most significant ones. There are no recommendations so far as to the indications and modalities of the medical treatment of SAPH, which is based upon the opinion of a multidisciplinary team of sarcoidosis, pulmonary hypertension and sometimes lung transplant experts.

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Dissecting the lung transcriptome of pulmonary fibrosis-associated pulmonary hypertension

Brownstein,

Mura,

Ruffenach

et al. 2024

American Journal of Physiology-Lung Cellular and Molecular Phys

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Integrative multiomics can help elucidate the pathophysiology of pulmonary fibrosis (PF) associated pulmonary hypertension (PH) (PF-PH). Weighted gene co-expression network analysis (WGCNA) was performed on a transcriptomic dataset of explanted lung tissue from 116 patients with PF. Patients were stratified by pulmonary vascular resistance (PVR) and differential gene expression analysis was conducted. Gene modules were correlated with hemodynamics at the time of transplantation and tested for enrichment in the lung transcriptomics signature of an independent pulmonary arterial hypertension (PAH) cohort. We found 1,250 differentially expressed genes between high and low PVR groups. WGCNA identified that black and yellowgreen modules negatively correlated with PVR, while the tan and darkgrey modules positively correlated with PVR. Additionally, the tan module showed the strongest enrichment for an independent PAH gene signature, suggesting shared gene expression patterns between PAH and PF-PH. Pharmacotranscriptomic analysis using the Connectivity Map implicated the tan and darkgrey modules as potentially pathogenic in PF-PH, given their combined module signature demonstrated a high negative connectivity score for Treprostinil, a medication used in the treatment of PF-PH, and a high positive connectivity score for Bone morphogenetic protein loss of function. Pathway enrichment analysis revealed that inflammatory pathways and oxidative phosphorylation were downregulated, whereas epithelial mesenchymal transition was upregulated in modules associated with increased PVR. Our integrative systems biology approach to the lung transcriptome of PF with and without PH identified several PH-associated co-expression modules and gene targets with shared molecular features with PAH warranting further investigation to uncover potential new therapies for PF-PH.

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Pulmonary hemodynamics and transplant‐free survival in sarcoidosis‐associated pulmonary hypertension: Results from an international registry

Cited by 6 publications

References 20 publications

Predictors of Mortality in Pulmonary Hypertension-Associated Chronic Lung Disease

Predictors of Mortality in Pulmonary Hypertension-Associated Chronic Lung Disease

Sarcoidosis-Associated Pulmonary Hypertension

Dissecting the lung transcriptome of pulmonary fibrosis-associated pulmonary hypertension

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