RESUMEN
Pulmonary hypertension (PH) is a progressive cardiovascular disease, which may lead to severe cardiopulmonary dysfunction. As one of the main PH disease groups, pulmonary artery hypertension (PAH) is characterized by pulmonary vascular remodeling and right ventricular dysfunction. Increased pulmonary artery resistance consequently causes right heart failure, which is the major reason for morbidity and mortality in this disease. Although various treatment strategies have been available, the poor clinical prognosis of patients with PAH reminds us that further studies of the pathological mechanism of PAH are still needed. Inflammation has been elucidated as relevant to the initiation and progression of PAH, and plays a crucial and functional role in vascular remodeling. Many immune cells and cytokines have been demonstrated to be involved in the pulmonary vascular lesions in PAH patients, with the activation of downstream signaling pathways related to inflammation. Consistently, this influence has been found to correlate with the progression and clinical outcome of PAH, indicating that immunity and inflammation may have significant potential in PAH therapy. Therefore, we reviewed the pathogenesis of inflammation and immunity in PAH development, focusing on the potential targets and clinical application of anti-inflammatory and immunosuppressive therapy.
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Inmunoterapia , Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/terapia , Hipertensión Arterial Pulmonar/etiología , Inmunoterapia/métodos , Animales , Inflamación/terapia , Inflamación/patología , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/inmunología , Remodelación VascularRESUMEN
PURPOSE OF REVIEW: The endotracheal intubation of patients with pulmonary arterial hypertension (PAH) in respiratory distress is a highly morbid procedure that can precipitate hemodynamic collapse. Here we review our strategy for confronting this difficult clinical situation. RECENT FINDINGS: There are no clinical trials that explore best practices in the management of patients with PAH and respiratory failure. Here we provide a practical approach to respiratory support, inopressor and pulmonary vasodilator selection, hemodynamic considerations, point-of-care ultrasound monitoring, and endotracheal intubation in patients with PAH in respiratory failure.
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Intubación Intratraqueal , Insuficiencia Respiratoria , Humanos , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/etiología , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/terapia , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/terapia , Hemodinámica , Vasodilatadores/uso terapéuticoRESUMEN
INTRODUCTION: Extrapulmonary manifestations of pulmonary arterial hypertension (PAH) may play a critical pathobiological role and a deeper understanding will advance insight into mechanisms and novel therapeutic targets. This manuscript reviews our understanding of extrapulmonary manifestations of PAH. AREAS COVERED: A group of experts was assembled and a complimentary PubMed search performed (October 2023 - March 2024). Inflammation is observed throughout the central nervous system and attempts at manipulation are an encouraging step toward novel therapeutics. Retinal vascular imaging holds promise as a noninvasive method of detecting early disease and monitoring treatment responses. PAH patients have gut flora alterations and dysbiosis likely plays a role in systemic inflammation. Despite inconsistent observations, the roles of obesity, insulin resistance and dysregulated metabolism may be illuminated by deep phenotyping of body composition. Skeletal muscle dysfunction is perpetuated by metabolic dysfunction, inflammation, and hypoperfusion, but exercise training shows benefit. Renal, hepatic, and bone marrow abnormalities are observed in PAH and may represent both end-organ damage and disease modifiers. EXPERT OPINION: Insights into systemic manifestations of PAH will illuminate disease mechanisms and novel therapeutic targets. Additional study is needed to understand whether extrapulmonary manifestations are a cause or effect of PAH and how manipulation may affect outcomes.
Asunto(s)
Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/terapia , Inflamación/fisiopatología , AnimalesRESUMEN
A comprehensive evaluation of risk, using multiple indices, is necessary to provide reliable prognostic information and guide therapy in pulmonary arterial hypertension (PAH). The current ESC/ERS guidelines suggest using a three-strata model for incident (newly diagnosed) patients and a four-strata model for prevalent patients with PAH. The four-strata model serves as a fundamental risk-stratification tool and relies on a minimal dataset of indicators that must be considered during follow-up. Nevertheless, there are still areas of vagueness and ambiguity when classifying and managing patients in the intermediate-risk category. For these patients, considerations should include right heart imaging, hemodynamics, as well as individual factors such as age, sex, genetic profile, disease type, comorbidities, and kidney function. The aim of this report is to present case studies, with a specific focus on patients ultimately classified as intermediate risk. We aim to emphasize the challenges and complexities encountered in the realms of diagnosis, classification, and treatment for these particular patients.
Asunto(s)
Antihipertensivos , Guías de Práctica Clínica como Asunto , Hipertensión Arterial Pulmonar , Humanos , Factores de Riesgo , Medición de Riesgo , Antihipertensivos/uso terapéutico , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/terapia , Hipertensión Arterial Pulmonar/epidemiología , Femenino , Masculino , Valor Predictivo de las Pruebas , Medicina Basada en la Evidencia/normas , Resultado del Tratamiento , Persona de Mediana Edad , Toma de Decisiones Clínicas , Arteria Pulmonar/fisiopatología , Presión Arterial/efectos de los fármacos , Técnicas de Apoyo para la DecisiónRESUMEN
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.
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Cardiopatías , Insuficiencia Cardíaca , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/epidemiología , Hipertensión Arterial Pulmonar/terapia , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar Primaria Familiar/complicaciones , Cardiopatías/complicaciones , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapiaRESUMEN
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.
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Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/terapia , Proyectos Piloto , Estudios Prospectivos , Calidad de Vida , Medición de Resultados Informados por el PacienteRESUMEN
Pulmonary hypertension (PH) is recognized as a pathophysiological disorder encompassing a wide spectrum of clinical conditions related to various cardiovascular and respiratory diseases [...].
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/terapia , Hipertensión Pulmonar Primaria Familiar , Hipertensión Pulmonar/terapiaRESUMEN
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.
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Corazón Auxiliar , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Embarazo , Femenino , Humanos , Adulto , Hipertensión Arterial Pulmonar/terapia , Cesárea , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar Primaria FamiliarRESUMEN
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).
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Cardiología , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Neumología , Humanos , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/terapia , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , HemodinámicaRESUMEN
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).
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/terapia , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Medición de RiesgoRESUMEN
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.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Disfunción Ventricular Derecha , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/terapia , Volumen Sistólico/fisiología , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar/complicaciones , Función Ventricular Derecha , Hipertensión Pulmonar Primaria Familiar/complicaciones , Disfunción Ventricular Derecha/terapia , Disfunción Ventricular Derecha/complicacionesRESUMEN
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.
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Hipertensión Arterial Pulmonar , Cuidado Terminal , Humanos , Cuidados Paliativos/métodos , Cuidados Paliativos/psicología , Hipertensión Arterial Pulmonar/terapia , Calidad de Vida/psicología , Cuidado Terminal/métodos , Cuidado Terminal/psicología , MuerteRESUMEN
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.
Asunto(s)
Insuficiencia Cardíaca , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Disfunción Ventricular Derecha , Humanos , Hipertensión Arterial Pulmonar/terapia , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Pulmonar Primaria Familiar , Hipertensión Pulmonar/diagnóstico , Insuficiencia Cardíaca/complicaciones , Disfunción Ventricular Derecha/etiologíaRESUMEN
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.
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Vesículas Extracelulares , Hipertensión Pulmonar , Células Madre Mesenquimatosas , Hipertensión Arterial Pulmonar , Ratas , Animales , Masculino , Hipertensión Arterial Pulmonar/terapia , Hipertensión Arterial Pulmonar/metabolismo , Hipertrofia Ventricular Derecha , Médula Ósea/metabolismo , Células Cultivadas , Ratas Wistar , Hipertensión Pulmonar Primaria Familiar , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/metabolismo , Colágeno/metabolismo , Hipoxia/metabolismoRESUMEN
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.
Asunto(s)
Hipertensión Arterial Pulmonar , Humanos , Insuficiencia Cardíaca , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/terapiaRESUMEN
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.