Managing Pulmonary Arterial Hypertension With Cardiopulmonary Comorbidities.

Pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with left-sided heart and lung diseases are most commonly easily discriminated and treated accordingly. With the changing epidemiology of PAH, however, a growing proportion of patients at the time of diagnosis present with comorbidities of varying severity. In addition to classical PAH, two distinct phenotypes have emerged: a heart failure with preserved ejection fraction-like phenotype and a lung phenotype. Importantly, the evidence supporting the currently proposed treatment algorithm for PAH has been generated mainly from PAH trials in which patients with cardiopulmonary comorbidities have been underrepresented or excluded. As a consequence, the best therapeutic approach for patients with common PAH with cardiopulmonary comorbidities remains largely unknown and requires further investigation. The present article reviews the relevant literature on the topic and describes the authors' views on the current therapeutic approach for these patients.

Assessing the clinical benefit, safety, and patient-reported outcomes with the use of the PAHcare™ digital platform in pulmonary arterial hypertension: a pilot study.

Introduction: Digital health interventions, particularly mobile health platforms, have shown promise in supporting patients with respiratory conditions, but their application in pulmonary arterial hypertension (PAH) remains limited. We aimed to assess the feasibility, acceptability, and potential clinical benefit of the novel PAHcare™ digital platform as a patient-centred intervention for PAH management through a prospective, single-arm, multicenter pilot study conducted on 53 patients diagnosed with PAH who used the platform for 6 months. Methods: The primary objective was to assess the impact on Health-Related Quality of Life (HRQoL) through questionnaires. Secondary objectives included evaluating clinical outcomes, including disease progression, PAH signs and symptoms, the 6-min walking test, and the patient's symptom perception. Additionally, we assessed patient satisfaction and engagement with the PAHcare™ platform, interaction with health coaches, retention, costs and healthcare resource utilisation (HCRU), and safety through monitoring device incidents. Results: Minimal changes in HRQoL and clinical outcomes were observed over 6 months. A noteworthy 92.4% of patients actively used the platform in the first month, maintaining high usage throughout the study. Patient satisfaction was substantial, with more than half of the patients expressing excellence in service quality, willingness to reuse the platform, and fulfilment of their needs. Health coach interaction was high, with 76% of patients initiating contact within the first week. User retention rates were 70%, with prevalent ongoing usage and interaction with healthcare professionals even after the study. In terms of HCRU and costs, the study showed no significant changes in PAH-related hospital admissions, clinical visits, or tests. Finally, the low number of device-related incidents indicated platform safety. Conclusion: This pilot study provides compelling evidence supporting the feasibility and acceptability of the PAHcare™ digital platform to empower patients to manage their disease and significantly enhance their overall experience with PAH.

Pathophysiology and Treatment of Pulmonary Arterial Hypertension.

Pulmonary hypertension (PH) is recognized as a pathophysiological disorder encompassing a wide spectrum of clinical conditions related to various cardiovascular and respiratory diseases [...].

A Case Report of Percutaneous Right Ventricular Assist Device Utilization After Cesarean Delivery in a Patient With Severe Pulmonary Arterial Hypertension.

Physiologic changes of pregnancy are poorly tolerated in patients with pulmonary arterial hypertension (PAH), and peripartum maternal mortality is high. We present a case of a 31-year-old G3P0020 patient at 35 weeks' gestation with severe World Health Organization group I PAH who underwent cesarean delivery followed by percutaneous right ventricular assist device placement. Risks and benefits of the mode of delivery, neuraxial versus general anesthesia, and mechanical circulatory support are reviewed.

[Diagnosis and therapy of pulmonary arterial hypertension]. / Diagnostik und Therapie der pulmonalarteriellen Hypertonie.

2022, the updated guidelines for the diagnosis and treatment of pulmonary hypertension (PH) of the European Societies of Cardiology and Pneumology were published. This resulted in important innovations concerning the hemodynamic definition as well as diagnosis and therapy of PH. In the following, an overview of the definition and classification of PH will be given, followed by a discussion of risk stratification and therapy of pulmonary arterial hypertension (PAH).

[Risk stratification in pulmonary arterial hypertension - implementation of an internet-based risk calculator to guide treatment]. / Prognostisk riskstratifiering vid pulmonell arteriell hypertension.

The 2022 ESC/ERS pulmonary hypertension guidelines recommend multiparametric risk stratification at diagnosis and follow-up to guide treatment in pulmonary arterial hypertension (PAH). The goal is to maintain or achieve a low-risk status, corresponding to a 1-year mortality < 5%. Risk assessment is, however, underutilized in clinical practice, and applied only by 60% of clinicians. To overcome the barrier of underutilization and facilitate risk assessment, we have established a comprehensive internet-based risk stratification calculator (https://www.svefph.se/risk-stratification).

Restoration of right ventricular function in the treatment of pulmonary arterial hypertension.

OBJECTIVE: A 45% threshold of right ventricular ejection fraction (RVEF) is proposed clinically relevant in patients with pulmonary arterial hypertension (PAH). We aim to determine treatment response, long-term right ventricular (RV) functional stability and prognosis of patients with PAH reaching or maintaining the RVEF 45% threshold. METHODS: Incident, treatment-naive, adult PAH patients with cardiac magnetic resonance imaging at baseline and first follow-up were included (total N=127) and followed until date of censoring or death/lung transplantation. Patients were categorised into two groups based on 45% RVEF. Baseline predictors, treatment response and prognosis were assessed with logistic regression analyses, two-way analysis of variance and log-rank tests. RESULTS: Patients were 50±17 years old, 73% female, of which N=75 reached or maintained the 45% RVEF threshold at follow-up (RVEF≥45%@FU), while N=52 patients did not (RVEF<45%@FU). RV end-diastolic volume and N-terminal pro-B-type natriuretic peptide at baseline were multivariable predictors of an RVEF ≥45% at follow-up. A 40% pulmonary vascular resistance (PVR) reduction resulted in greater improvement in RV function (ΔRVEF 17±11 vs. 5±8; pinteraction<0.001) compared to a PVR reduction <40%, but did not guarantee an RVEF ≥45%. Finally, the 45% RVEF threshold was associated with stable RV function during long-term follow-up and better survival (HR: 1.91 (95% CI: 1.11 to 3.27)). Patients failing to reach or maintain the 45% RVEF threshold at first follow-up mostly stayed below this threshold over the next consecutive visits. CONCLUSION: After treatment initiation, 60% of patients with PAH reach or maintain the 45% RVEF threshold, which is associated with a long-term stable RV function and favourable prognosis.

Approach to the hospitalized patient with pulmonary arterial hypertension.

PURPOSE OF REVIEW: Hospitalization in pulmonary arterial hypertension (PAH) patients is an important clinical worsening event significantly associated with subsequent mortality. Furthermore, irrespective of the cause of hospitalization, the overall outcome is closely related to the severity of the right ventricular (RV) dysfunction. Therefore, understanding the pathophysiology of pulmonary hypertension and RV failure is paramount in successfully managing PAH patients requiring hospitalization. This review highlights diagnostic and therapeutic approaches in various clinical scenarios that might be encountered during hospitalization of the World Health Organization group I PAH patient. RECENT FINDINGS: This article covers recent literature describing risk factors, predictors of outcome and state-of the art management approach to a hospitalized PAH patients with a special focus on management of RV failure and common complications in PAH requiring hospitalization. SUMMARY: The review highlights the importance of multidisciplinary approach to a hospitalized PAH patient and highlight important implications in clinical practice and knowledge gaps for potential future research.

End-of-Life and Palliative Care Issues for Patients Living with Pulmonary Arterial Hypertension: Barriers and Opportunities.

Pulmonary arterial hypertension (PAH) is a progressive, incurable disease that results in significant symptom burden, health care utilization, and eventually premature death. Despite the advancements made in treatment and management strategies, survival has remained poor. End-of-life care is a challenging issue in management of PAH, especially when patients are in younger age group. End-of-life care revolves around symptom palliation and reducing psychosocial disease burden for a dying patient and entails advanced care planning that are often challenging. Thus, support from palliative care specialist becomes extremely important in these patients. Early introduction to palliative care in patients with high symptom burden and psychosocial suffering is suggested. Despite of the benefits of an early intervention, palliative care remains underutilized in patients with PAH, and this significantly raises issues around end-of-life care in PAH. In this review, we will discuss the opportunities offered and the existing barriers in addressing high symptom burden and end-of-life care issues. We will focus on the current evidence, identify areas for future research, and provide a call-to-action for better guidance to PAH specialists in making timely, appropriate interventions that can help mitigate end-of-life care issues.

Therapeutic effects of hypoxia-preconditioned bone marrow-derived mesenchymal stromal cells and their extracellular vesicles in experimental pulmonary arterial hypertension.

AIMS: To evaluate BM-MSCs and their extracellular vesicles (EVs) preconditioned with hypoxia or normoxia in experimental pulmonary arterial hypertension (PAH). MAIN METHODS: BM-MSCs were isolated and cultured under normoxia (MSC-N, 21%O2) or hypoxia (MSC-H, 1%O2) for 48 h. EVs were then isolated from MSCs under normoxia (EV-N) or hypoxia (EV-H). PAH was induced in male Wistar rats (n = 35) with monocrotaline (60 mg/kg); control animals (CTRL, n = 7) were treated with saline. On day 14, PAH animals received MSCs or EVs under normoxia or hypoxia, intravenously (n = 7/group). On day 28, right ventricular systolic pressure (RVSP), pulmonary acceleration time (PAT)/pulmonary ejection time (PET), and right ventricular hypertrophy (RVH) index were evaluated. Perivascular collagen content, vascular wall thickness, and endothelium-mesenchymal transition were analyzed. KEY FINDINGS: PAT/PET was lower in the PAH group (0.26 ± 0.02, P < 0.001) than in CTRLs (0.43 ± 0.02) and only increased in the EV-H group (0.33 ± 0.03, P = 0.014). MSC-N (32 ± 6 mmHg, P = 0.036), MSC-H (31 ± 3 mmHg, P = 0.019), EV-N (27 ± 4 mmHg, P < 0.001), and EV-H (26 ± 5 mmHg, P < 0.001) reduced RVSP compared with the PAH group (39 ± 4 mmHg). RVH was higher in the PAH group than in CTRL and reduced after all therapies. All therapies decreased perivascular collagen fiber content, vascular wall thickness, and the expression of endothelial markers remained unaltered; only MSC-H and EV-H decreased expression of mesenchymal markers in pulmonary arterioles. SIGNIFICANCE: MSCs and EVs, under normoxia or hypoxia, reduced right ventricular hypertrophy, perivascular collagen, and vessel wall thickness. Under hypoxia, MSCs and EVs were more effective at improving endothelial to mesenchymal transition in experimental PAH.

[Physiopathology and treatment of pulmonary arterial hypertension]. / Physiopathologie et traitements de l'hypertension artérielle pulmonaire.

Pulmonary arterial hypertension (PAH) is a rare disease affecting mainly the pre-capillary pulmonary vascular bed. However, some forms of the disease have venous/capillary involvement. It is an obstructive remodelling of the pulmonary arterioles coupled with vascular pruning, increasing right ventricular afterload and leading to right heart failure. PAH has a complex pathogeny that is detailed in this review. Current specific treatments target endothelial dysfunction, and primarily aim at vasodilatation. Promising innovative treatments targeting the pulmonary artery remodelling are under development.

Title: Physiopathologie et traitements de l'hypertension artérielle pulmonaire. Abstract: L'hypertension artérielle pulmonaire (HTAP) est une maladie rare affectant principalement le lit vasculaire pulmonaire pré-capillaire. Certaines formes de la maladie présentent néanmoins une atteinte veinulaire/capillaire. Il s'agit d'un remodelage obstructif des artérioles pulmonaires couplé à une raréfaction vasculaire, augmentant la post-charge ventriculaire1 droite et conduisant à une insuffisance cardiaque droite. La physiopathologie de l'HTAP est complexe. Les traitements spécifiques actuels ciblent la dysfonction endothéliale, avec une action essentiellement vasodilatatrice. Des traitements innovants prometteurs ciblant le remodelage vasculaire pulmonaire sont en cours de développement.

Pulmonary arterial hypertension in pregnancy.

PURPOSE OF REVIEW: Although pregnancy in pulmonary arterial hypertension (PAH) is considered high risk and contraindicated, the incidence is rising. It is paramount to understand the pathophysiology and effective management strategies to ensure optimal outcomes for maternal and fetal survival. RECENT FINDINGS: In this review, we highlight the outcomes of recent case series of PAH patients in pregnancy, with a focus on proper risk assessment and target goals of PAH therapy. These findings support the notion that the pillars of PAH management, including pulmonary vascular resistance reduction resulting in right heart functional improvement, and widening of the cardiopulmonary reserve, should serve as a blueprint for PAH management in pregnancy. SUMMARY: Multidisciplinary and tailored management of PAH in pregnancy, with emphasis on optimizing right heart function prior to delivery, can result in excellent clinical outcomes in a referral pulmonary hypertension center.

Acute Vasoreactivity Testing and Outcomes in Pulmonary Arterial Hypertension: A Call for Increased Testing.

BACKGROUND: Pulmonary arterial hypertension (PAH) has a progressive, unremitting clinical course. Vasoreactivity testing (VdT) during right heart catheterisation (RHC) identifies a subgroup with excellent long-term response to calcium channel blockade (CCB). Reporting on these patients is limited. Established in 2011, the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry offers the opportunity to assess the frequency of VdT during RHC, treatment and follow up of PAH patients. METHODS: Registry data from 3,972 PAH patients with index RHC revealed 1,194 VdT appropriate patients. Data was analysed in three groups: 1) VdT+CCB+: VdT positive, CCB treated; 2) VdT+CCB-: VdT positive, no CCB prescribed, 3) VdT-/noVdT: VdT negative, or VdT not tested. Data was reviewed for adherence to guidelines, clinical response (World Health Organization functional class [WHO FC], 6-minute-walk-distance [6MWD], RHC), and outcomes (survival or lung transplantation). RESULTS: Patients included had idiopathic (IPAH=1,087), heritable (HPAH=67) and drug or toxin-induced PAH (DPAH=40). A VdT was performed in 22% (268/1,194), with incomplete data in 26% (70/268); 28% (55/198) were VdT+. Analysis group allocation was: VdT+CCB+ (33/55), VdT+CCB- (22/55), VdT- (143)/noVdT (996). From patients with 1-year data VdT+CCB+ and VdT-/noVdT patients improved WHO FC, 6MWD and cardiac index (CI); VdT+CCB- data remained similar. Within the VdT+CCB+ group, 30% (10/33) were long-term CCB responders with a 100% 5-year survival; non-responders had a 61% survival at 5.4 years. Long-term responders were younger at diagnosis (40 yrs vs 54 yrs). CONCLUSION: Use of VdT testing and documentation is poor in this contemporary patient cohort. Nonetheless, survival in VdT+CCB+ patients from the PHSANZ registry is excellent, supporting guidelines promoting VdT testing. Strategies to promote the use of VdT are warranted.

Management of COVID-19 in Patients with Pulmonary Arterial Hypertension.

In this review, we discuss the evidence regarding the course and management of COVID-19 in patients with pulmonary arterial hypertension (PAH), the challenges in PAH management during the pandemic and, lastly, the long-term complications of COVID-19 in relation to pulmonary vascular disease. The inherent PAH disease characteristics, as well as age, comorbidities, and the patient's functional status act synergistically to define the prognosis of COVID-19 in patients with PAH. Management of COVID-19 should follow the general guidelines, while PAH-targeted therapies should be continued. The pandemic has caused a shift toward telemedicine in the chronic care of patients with PAH. Whether COVID-19 could predispose to the development of chronic pulmonary hypertension is a subject of future investigation.

Pulmonary Arterial Hypertension in Connective Tissue Diseases Beyond Systemic Sclerosis.

Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) (CTD-PAH) is a devastating condition that may progress rapidly to cause right ventricular dysfunction, resulting in significant morbidity and mortality. The pathobiology, epidemiology, natural history, early diagnosis, and treatment response of PAH associated with scleroderma (SSc-PAH) have been the subjects of intense research efforts over the previous decade. The success of these efforts has resulted in increased awareness and earlier detection of SSc-PAH. Practitioners are less aware of the risk of PAH associated with other CTDs; the aim of this article is to discuss the broader scope of CTD-PAH.

Risk stratification, prognosis, and survival in a pulmonary arterial hypertension cohort in Latin America. A multicenter study.

BACKGROUND: Pulmonary arterial hypertension (PAH) guidelines suggest that achieving a low-risk profile should be the treatment goal. Our aim was to assess a risk assessment strategy based on three non-invasive variables from the ESC/ERS 2015 guidelines in a Latin American cohort. METHODS: 92 incident patients (mean [SD] age 47, 77% female, 53% idiopathic PAH) were included in this retrospective, multicenter study. Patients were stratified at baseline and at early follow-up, within the first year, using three non-invasive variables (WHO functional class, 6-minute walking distance, BNP/NT-proBNP) from the ESC/ERS 2015 risk assessment instrument. Median (IQR) follow-up was 3.11 years (3.01 years). RESULTS: At baseline assessment, 25% of patients were at low risk, 61.9% at intermediate-risk, and 13% at high-risk. At early follow-up (median 9.5 months), 56.5% of patients were at low-risk, 40.2% at intermediate-risk, and 3.2% at high-risk (p<0.001 vs. baseline). According to risk stratification at early follow-up, one, three and five-year overall survival was 100% in the low-risk group (no deaths at five-year follow-up), and 100%, 84% (95% CI: 72-98%), and 66% (95% CI: 48-90%) respectively in the intermediate-risk group, p = 0.0003. Mortality in the high-risk patients at early follow-up was 1/3 (33.3%). One, three, and five-year event-free survival (death or transplant or first hospitalization due to worsening PAH) based on early follow-up risk assessment was higher in the low-risk group, p = 0.0003. CONCLUSION: Our study validates a risk assessment strategy based on three non-invasive variables and confirms that early achievement of a low-risk profile should be the treatment goal.