Correspondence regarding “T-box protein 4 mutation causing pulmonary arterial hypertension and lung disease”: a single-centre case series

Abstract Background There are significant risks of parenteral prostacyclin use in patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD), which may limit their use. Selexipag is an oral, selective prostacyclin analogue that has been shown to reduce disease progression and improve exercise capacity in patients with PAH-CHD. Administering Selexipag in patients with PAH-CHD could potentially overcome some of the risks of parenteral therapy while improving clinical outcomes. Case summary We report five cases highlighting the clinical uses of Selexipag in patients with PAH-CHD. In the first two cases, Selexipag was initiated as part of a Treat-to-close strategy. In the third case, initiation of Selexipag improved symptoms and objective exercise capacity in a patient with Eisenmenger syndrome. In the fourth and fifth cases, rapid cross-titration protocols were used to transition from parenteral prostacyclins to Selexipag. In the fourth case, Selexipag was initiated in the context of significant side effects limiting parenteral prostacyclin use. In the fifth case, Selexipag was used to down-titrate from parenteral prostacyclins following closure of a sinus venosus atrial septal defect and redirection of anomalous pulmonary veins. Discussion Selexipag is a promising oral therapy for patients with at various stages of the spectrum of PAH-CHD to improve symptoms, exercise capacity and, in some cases, haemodynamics. Our cases also highlight practical aspects of Selexipag use including targeting the individualized maximally tolerated dose for each patient, managing side effects and managing dose interruptions.

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EXPRESS: The transition from Parenteral Prostacyclins to Selexipag: Safety and Feasibility in Select Patients

Pulmonary Circulation ◽

10.1177/20458940211036623 ◽

2021 ◽

pp. 204589402110366

Author(s):

Nael Aldweib ◽

Nate Verlinden ◽

Hayah Kassis-george ◽

Amresh Raina

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Case Series ◽

Outpatient Setting ◽

Limited Data ◽

Standardized Protocol ◽

Pulmonary Arterial

There is limited data regarding the feasibility of transitioning from intravenous prostacyclins to selexipag in pulmonary arterial hypertension (PAH) patients. We present a case series of successful transitions from intravenous prostacyclins to selexipag in the majority of carefully selected five stable PAH patients using a standardized protocol in the outpatient setting.

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Replacing a phosphodiesterase-5 inhibitor with riociguat in patients with connective tissue disease-associated pulmonary arterial hypertension: a case series

Pulmonary Circulation ◽

10.1177/2045893217721694 ◽

2017 ◽

Vol 7 (3) ◽

pp. 741-746 ◽

Cited By ~ 9

Author(s):

Amresh Raina ◽

Raymond L. Benza ◽

Harrison W. Farber

Keyword(s):

Pulmonary Arterial Hypertension ◽

Connective Tissue ◽

Arterial Hypertension ◽

Clinical Response ◽

Connective Tissue Disease ◽

Case Series ◽

Response To Treatment ◽

Tolerability Profile ◽

Phosphodiesterase Type 5 Inhibitors ◽

Pulmonary Arterial

Patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-PAH-CTD) such as systemic sclerosis (SSc) have a poorer response to treatment and increased mortality compared with patients with idiopathic PAH. Current treatment options for PAH-CTD include prostanoids, phosphodiesterase type-5 inhibitors (PDE-5i), endothelin receptor antagonists, and the soluble guanylate cyclase stimulator riociguat. In this case series, we describe three patients with PAH-CTD related to limited scleroderma who were switched from a PDE-5i to riociguat due to insufficient clinical response. The switch to riociguat was associated with an improvement in respiratory and hemodynamic parameters and a favorable tolerability profile. These cases demonstrate that switching to riociguat is a therapeutic option in patients with PAH-CTD who have not achieved a satisfactory clinical response to a PDE-5i.

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Patients with systemic sclerosis-associated pulmonary arterial hypertension express a genomic signature distinct from patients with interstitial lung disease

Journal of Scleroderma and Related Disorders ◽

10.1177/2397198318764780 ◽

2018 ◽

Vol 3 (3) ◽

pp. 242-248 ◽

Cited By ~ 6

Author(s):

Matthew Moll ◽

Romy B Christmann ◽

Yuqing Zhang ◽

Michael L Whitfield ◽

Yu Mei Wang ◽

...

Keyword(s):

Gene Expression ◽

Systemic Sclerosis ◽

Pulmonary Arterial Hypertension ◽

Interstitial Lung Disease ◽

Arterial Hypertension ◽

Lung Disease ◽

Expression Profiles ◽

Area Under The Curve ◽

Gene Expression Profiles ◽

Pulmonary Arterial

Objective: Pulmonary arterial hypertension and interstitial lung disease are major causes of mortality in systemic sclerosis. We used a previously identified microarray biomarker to determine whether systemic sclerosis-pulmonary arterial hypertension and systemic sclerosis-interstitial lung disease patients demonstrate distinct gene expression profiles. Methods: Peripheral blood mononuclear cells were collected from healthy controls ( n = 10), systemic sclerosis patients without pulmonary hypertension (systemic sclerosis-no pulmonary arterial hypertension, n = 39), and systemic sclerosis-pulmonary arterial hypertension patients ( n = 21; mean pulmonary arterial pressure ≥25, pulmonary capillary wedge pressure ≤15, and pulmonary vascular resistance ≥3 Wood units) diagnosed by right heart catheterization. Systemic sclerosis-interstitial lung disease patients were defined as those with evidence of fibrosis on chest computed tomography and significant restriction (forced vital capacity <70% predicted, n = 11). Systemic sclerosis-pulmonary arterial hypertension biomarker included 69 genes selected by unbiased statistical screening of three publicly available microarray studies. RNA levels were measured by NanoString Technologies. Gene expression levels that were significantly correlated with pulmonary arterial hypertension (multiple statistical measures) were chosen as inputs into a forward selection logistic regression model. Results: When interstitial lung disease patients were included ( n = 64), four genes (S100P, CD8B1, CCL2, and TIMP1) and male sex predicted pulmonary arterial hypertension with a high level of accuracy (area under the curve = 0.83). Without interstitial lung disease patients ( n = 53), two genes (THBS1 and CD8B1) and male sex predicted pulmonary arterial hypertension with a high level of accuracy (area under the curve = 0.80). When examining systemic sclerosis patients with borderline elevated pulmonary pressures (mean pulmonary arterial pressure = 21–24 mmHg), gene expression changes closely resembled the systemic sclerosis-pulmonary arterial hypertension group, except for THBS1. Conclusion: Systemic sclerosis-pulmonary arterial hypertension and systemic sclerosis-interstitial lung disease have similar but distinct gene expression profiles. Many gene expression changes occur early in the disease course, potentially allowing early detection. THBS1 appears to be an important mediator in the development of pulmonary arterial hypertension-predominant phenotype. Further prospective investigation is warranted.

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