Pulmonary hypertension survival and hospitalisations in people living with HIV: a systematic review and meta-analysis.

INTRODUCTION: People living with HIV (PLHIV) have a higher risk of developing pulmonary hypertension (PH) with subsequent poorer prognosis. This review aimed to determine the (1) survival outcomes and (2) proportion of emergency department (ED) visits and hospitalisations of PLHIV and PH. METHODS: We conducted a systematic review and meta-analysis of observational studies reporting survival outcomes for PLHIV and PH. Electronic databases (Medline, EMBASE, PubMed, Web of Science, Global Index Medicus and Cochrane Library), trial registries and conference proceedings were searched until 22 July 2023. We pooled similar measures of effect, assessed apriori subgroups and used meta-regression to determine mortality and associated variables. RESULTS: 5248 studies were identified; 28 studies were included with a total of 5459 PLHIV and PH. The mean survival (95% CI) of PLHIV and PH was 37.4 months (29.9 to 44.8). Participants alive at 1, 2 and 3 years were 85.8% (74.1% to 95.0%), 75.2% (61.9% to 86.7%) and 61.9% (51.8% to 71.6%), respectively. ED visits and hospitalisation rates were 73.3% (32.5% to 99.9%) and 71.2% (42.4% to 94.2%), respectively. More severe disease, measured by echocardiogram, was associated with poorer prognosis (ß -0.01, 95% CI -0.02 to 0.00, p=0.009). Survival was higher in high-income countries compared with lower-income countries (ß 0.50, 95% CI 0.28 to 0.73, p<0.001) and in Europe compared with the America (ß 0.56, 95% CI 0.37 to 0.75, p<0.001). CONCLUSION: Our study confirms poor prognosis and high healthcare utilisation for PLHIV and PH. Prognosis is associated with country income level, geographic region and PH severity. This highlights the importance of screening in this population. PROSPERO REGISTRATION NUMBER: CRD42023395023.

Effects of right ventricular remodeling in chronic thromboembolic pulmonary hypertension on the outcomes of balloon pulmonary angioplasty: a 2D-speckle tracking echocardiography study.

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.

Pulmonary Hypertension in Women.

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by elevated pulmonary artery pressure and increased pulmonary vascular resistance. Females have a higher incidence of PAH, which is reflected globally across registries in the United States, Europe, and Asia. However, despite female predominance, women had better outcomes compared with male patients, a finding that has been labeled the "estrogen paradox." Special considerations should be given to women with PAH regarding sexual health, contraception, family planning, and treatment before, during, and after pregnancy. Pregnant women with PAH should be referred to a pulmonary hypertension care center; a multidisciplinary team approach is recommended, and Cesarean section is the preferred mode of delivery. While pregnancy outcomes have improved over the years with PAH-specific therapy, pregnancy portends a high-risk for those with PAH. Continued research is needed to tailor PAH treatment for women.

Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease With and Without Pulmonary Hypertension: A Scientific Statement From the American Heart Association.

Balloon pulmonary angioplasty continues to gain traction as a treatment option for patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. Recent European Society of Cardiology guidelines on pulmonary hypertension now give balloon pulmonary angioplasty a Class 1 recommendation for inoperable and residual chronic thromboembolic pulmonary hypertension. Not surprisingly, chronic thromboembolic pulmonary hypertension centers are rapidly initiating balloon pulmonary angioplasty programs. However, we need a comprehensive, expert consensus document outlining critical concepts, including identifying necessary personnel and expertise, criteria for patient selection, and a standardized approach to preprocedural planning and establishing criteria for evaluating procedural efficacy and safety. Given this lack of standards, the balloon pulmonary angioplasty skill set is learned through peer-to-peer contact and training. This document is a state-of-the-art, comprehensive statement from key thought leaders to address this gap in the current clinical practice of balloon pulmonary angioplasty. We summarize the current status of the procedure and provide a consensus opinion on the role of balloon pulmonary angioplasty in the overall care of patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. We also identify knowledge gaps, provide guidance for new centers interested in initiating balloon pulmonary angioplasty programs, and highlight future directions and research needs for this emerging therapy.

The role of immune cells and inflammation in pulmonary hypertension: mechanisms and implications.

Pulmonary hypertension (PH) is a malignant disease with progressive increase of pulmonary vascular pressure, which eventually leads to right heart failure. More and more evidences show that immune cells and inflammation play an important role in the occurrence and development of PH. In the context of pulmonary vascular diseases, immune cells migrate into the walls of the pulmonary vascular system. This leads to an increase in the levels of cytokines and chemokines in both the bloodstream and the surrounding tissues of the pulmonary vessels. As a result, new approaches such as immunotherapy and anti-inflammatory treatments are being considered as potential strategies to halt or potentially reverse the progression of PH. We reviewed the potential mechanisms of immune cells, cytokines and chemokines in PH development. The potential relationship of vascular cells or bone morphogenetic protein receptor 2 (BMPR2) in immune regulation was also expounded. The clinical application and future prospect of immunotherapy were further discussed.

Comment on: Severe pulmonary hypertension in pulmonary alveolar microlithiasis: A comprehensive literature review.

This letter commends the study "Severe pulmonary hypertension in pulmonary alveolar microlithiasis: A comprehensive literature review" for its thorough exploration of Pulmonary Alveolar Microlithiasis (PAM) and its association with pulmonary hypertension (PH). The study offers insights into PAM's genetics, clinical manifestations, diagnostic approaches, and treatment modalities. It highlights the importance of early diagnosis and management while discussing limitations such as its retrospective nature and small sample size. Despite these limitations, the study contributes significantly to understanding PAM and PH, emphasizing the need for larger prospective studies to validate findings and explore novel therapeutic avenues.

[Nerve growth factor (NGF) in pulmonary hypertension (PH)]. / Le facteur de croissance des nerfs (NGF) dans l'hypertension pulmonaire (HTP).

Pulmonary hypertension (PH) is the main pathology in lung circulation, characterized by increased pressure in pulmonary arteries and ultimately resulting in right heart failure with potentially fatal outcomes. Given the current lack of available curative treatments, it is of paramount importance to identify novel therapeutic targets. Due to its involvement in pulmonary arterial remodeling, hyperreactivity, and inflammation, our explorations have focused on the nerve growth factor (NGF), offering promising avenues for innovative therapeutic approaches.

Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial.

INTRODUCTION: Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control 'on-demand' arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental 'systematic' arm, VA-ECMO will be pre-emptively initiated. We hypothesise a 'systematic' strategy will increase the number of ventilatory-free days at day 28. METHODS AND ANALYSIS: We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events. ETHICS AND DISSEMINATION: The sponsor is the Assistance Publique-Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT05664204.

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.

Pulmonary Hypertension in Adult Congenital Heart Disease-Related Heart Failure.

Already a challenging condition to define, adult congenital heart disease (ACHD) -associated heart failure (HF) often incorporates specific anatomies, including intracardiac and extracardiac shunts, which require rigorous diagnostic characterization and heighten the importance of clinicians proactively considering overall hemodynamic impacts of using specific therapies. The presence of elevated pulmonary vascular resistance dramatically increases the complexity of managing patients with ACHD-HF. Total circulatory management in patients with ACHD-HF requires input from multidisciplinary care teams and thoughtful and careful utilization of medical, interventional, and surgical approaches.

Chronic Thromboembolic Pulmonary Hypertension.

This JAMA Insights discusses the symptoms, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension.

[ANMCO/SIC Consensus statement on pulmonary arterial hypertension]. / Documento di consenso ANMCO/SIC sull'ipertensione arteriosa polmonare.

Pulmonary hypertension (PH) is a frequent pathological condition worldwide, mainly secondary to cardiovascular and respiratory diseases, with a poor prognosis. Pulmonary arterial hypertension (PAH) is a rare form that affects the arterial pulmonary vasculature. PH and PAH are characterized by non-specific symptoms and a progressive increase of pulmonary vascular resistance that results in progressive, sometimes irreversible, right ventricular dysfunction. In recent years, a growing medical and social commitment on this disease allowed more accurate diagnosis in shorter times. However, the gap between guidelines and clinical practice remains a challenge for all medical doctors involved in the disease management. Considering the needs to share and describe diagnostic and therapeutic pathways, to measure the results obtained and to address the economical and organizational problems of this disease, all involved figures should collaborate to improve its prognostic impact and health expenses. In this consensus document, the PH experts of the Italian Association of Hospital Cardiologists (ANMCO) together with those of the Italian Society of Cardiology (SIC), address 1) definition, classification and unmet needs of PH and PAH; 2) classification and characteristics of centers involved in the diagnosis and treatment of the disease; 3) proposal of organization of a diagnostic-therapeutic pathway, based on robust and recent scientific evidence.

Survival of Infants With Severe Congenital Kidney Disease After ECMO and Kidney Support Therapy.

Congenital kidney failure not only affects the homeostatic functions of the kidney, but also affects neonatal respiratory integrity. Until recently, extracorporeal membrane oxygenation (ECMO) support was not used in this population because the need for ECMO clearly established nonviability. Since 2016, 31 neonates have been admitted to the NICU at Children's of Alabama with congenital kidney failure. Five patients were placed on ECMO for severe respiratory distress unresponsive to conventional interventions. We evaluated neonates with congenital kidney failure and pulmonary hypoplasia/hypertension refractory to conventional therapies who received ECMO support within the first 9 postnatal days. We describe the pre and postnatal diagnoses, ECMO course details, dialysis modalities, complications, procedures, and long-term outcomes of these patients. All 5 patients received kidney support therapy by postnatal day 7. Diagnoses included posterior urethral valves, bilateral renal dysplasia, and autosomal recessive polycystic kidney disease. Gestational age ranged from 35.6 to 37.1 weeks. Birth weight ranged from 2740 to 3140 g. Days on ECMO ranged from 4 to 23. Four survived and are living today. Pulmonary hypertension resolved in surviving patients. Three surviving patients require no oxygen support, and 1 patient requires nocturnal oxygen. Three survivors received a kidney transplant, and 1 awaits transplant evaluation. Patients with congenital kidney failure with severe pulmonary hypoplasia/pulmonary hypertension no longer warrant a reflexive assignment of nonviability. Meticulous ECMO, respiratory, nutritional, and kidney support therapies may achieve a favorable long-term outcome. Further investigation of strategies for optimal outcome is needed.

Chronic thromboembolic pulmonary hypertension and balloon pulmonary angioplasty - Where are we in 2024?

Pulmonary endarterectomy (PEA) is the first-line treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, some patients with CTEPH are considered inoperable, and in the last decade, balloon pulmonary angioplasty (BPA) has emerged as a viable therapeutic option for these patients with prohibitive surgical risk or recurrent pulmonary hypertension following PEA. Numerous international centers have increased their procedural volume of BPA and have reported improvements in pulmonary hemodynamics, patient functional class and right ventricular function. Randomized controlled trials have also demonstrated similar findings. Recent refinements in procedural technique, increased operator experience and advancements in procedural technology have facilitated marked reduction in the risk of complications following BPA. Current guidelines recommend BPA for patients with inoperable CTEPH and persistent pulmonary hypertension following PEA. The pulmonary arterial endothelium plays a vital role in the pathophysiologic development and progression of CTEPH.

Asphyxia, Therapeutic Hypothermia, and Pulmonary Hypertension.

Neonates with a perinatal hypoxic insult and subsequent neonatal encephalopathy are at risk of acute pulmonary hypertension (aPH) in the transitional period. The phenotypic contributors to aPH following perinatal asphyxia include a combination of hypoxic vasoconstriction of the pulmonary vascular bed, right heart dysfunction, and left heart dysfunction. Therapeutic hypothermia is the standard of care for neonates with moderate-to-severe hypoxic ischemic encephalopathy. This review summarizes the underlying risk factors, causes of aPH in neonates with perinatal asphyxia, discusses the unique phenotypical contributors to disease, and explores the impact of the initial insult and subsequent therapeutic hypothermia on aPH.

Congenital Diaphragmatic Hernia: Pulmonary Hypertension and Pulmonary Vascular Disease.

This review provides a comprehensive summary of the current understanding of pulmonary hypertension (PH) in congenital diaphragmatic hernia, outlining the underlying pathophysiologic mechanisms, methods for assessing PH severity, optimal management strategies, and prognostic implications.

Pulmonary Hypertension in Established Bronchopulmonary Dysplasia: Physiologic Approaches to Clinical Care.

Preterm infants with bronchopulmonary dysplasia (BPD) are prone to develop pulmonary hypertension (PH). Strong laboratory and clinical data suggest that antenatal factors, such as preeclampsia, chorioamnionitis, oligohydramnios, and placental dysfunction leading to fetal growth restriction, increase susceptibility for BPD-PH after premature birth. Echocardiogram metrics and serial assessments of NT-proBNP provide useful tools to diagnose and monitor clinical course during the management of BPD-PH, as well as monitoring for such complicating conditions as left ventricular diastolic dysfunction, shunt lesions, and pulmonary vein stenosis. Therapeutic strategies should include careful assessment and management of underlying airways and lung disease, cardiac performance, and systemic hemodynamics, prior to initiation of PH-targeted drug therapies.