Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension.

BACKGROUND: The treatment of pulmonary hypertension (PH) has improved rapidly in recent decades. There is increasing evidence to support the role of early intervention and treatment in affecting clinical outcomes in PH. OBJECTIVES: To assess treatment effects before and after the escalation of specific PH treatments using continuous heart monitoring with a Reveal LINQ loop recorder. METHODS: Patients were compared before and after treatment escalation. Treatment escalation was defined as an additional pulmonary arterial hypertension (PAH) drug, pulmonary endarterectomy, percutaneous balloon angioplasty or bilateral lung transplantation. Specifically, changes in heart rate variability (HRV), heart rate (HR) and physical activity were assessed. RESULTS: In this prospective study, 41 patients (27 with PAH and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)) were enrolled. Among them, 15 (36.6%) patients underwent PH treatment escalation. Prior to escalation, patients were monitored for a median of 100 (range: 68-100) days and after therapy escalation for a median duration of 165 (range: 89-308) days. In the escalation group, there was a significant increase in HRV, physical activity indexed by daytime HR and a significant decrease in nighttime HR assessed at baseline and after treatment escalation in both the PAH and CTEPH groups. This was paralleled by significant improvements in WHO functional class, 6-min walking distance and N-terminal pro-b-type natriuretic peptide. CONCLUSIONS: This is the first study to demonstrate an association between specific PH therapies and changes in HRV, HR nighttime and physical activity. This indicates the potential of continuous monitoring in the evaluation of treatment effects in PH.

[Consensus on the procedure of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension].

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group IV pulmonary hypertension, characterized by thrombotic occlusion of the pulmonary arteries leading to vascular stenosis or obstruction, progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, and eventual right heart failure. Unlike other types of pulmonary hypertension, the prognosis of CTEPH can be significantly improved by surgery, vascular intervention, and/or targeted drug therapy. Pulmonary endarterectomy (PEA) is the preferred treatment of choice for CTEPH. However, PEA is an invasive procedure with high operative risks, and is currently only performed in a few centers in China. Balloon pulmonary angioplasty (BPA) is an emerging interventional technique for CTEPH, serving as an alternative for patients who are ineligible for PEA or with residual pulmonary hypertension after PEA. BPA is gaining traction in China, but its widespread adoption is limited due to its complexity, operator skills, and equipment requirements, a lack of standard operating procedures and technical guidance, which limit the further improvement and development of BPA in China. To address this, a multidisciplinary panel of experts was convened to develop the Consensus on the Procedure of Balloon Pulmonary Angioplasty for the Chronic Thromboembolic Pulmonary Hypertension, which fomulates guidelines on BPA procedural qualification, perioperative management, procedural planning, technical approach, and complication prevention, with the aim of providing recommendations and clinical guidance for BPA treatment in CTEPH and standardizing its clinical application in this setting. Summary of recommendations: Recommendation 1: It is recommended that physicians who specialize in pulmonary vascular diseases take the lead in formulating the diagnostic and treatment plans for CTEPH, using a multidisciplinary approach.Recommendation 2: Training in BPA technique is critical; novice operators should undergo standardized operative training with at least 50 procedures under the guidance of experienced physicians before embarking on independent BPA procedures.Recommendation 3: BPA requires catheterization labs, angiography systems, standard vascular interventional devices and consumables, drugs, and emergency equipment.Recommendation 4: Patient selection for BPA should consider cardiac and pulmonary function, coagulation status, and comorbid conditions to determine indications and contraindications, thereby optimizing the timing of the procedure and improving safety.Recommendation 5: In experienced centers, patients deemed likely to benefit from early BPA, based on clinical and imaging features of CTEPH and without elevated D-dimer levels, could bypass standard 3-month anticoagulation therapy.Recommendation 6: BPA is a complex interventional treatment that requires thorough pre-operative assessment and preparation.Recommendation 7: The use of perioperative anticoagulants in BPA requires a comprehensive risk assessment of intraoperative bleeding by the operator for individualized decision making.Recommendation 8: A variety of venous access routes are available for BPA; unless contraindicated, the right femoral vein is usually preferred because of its procedural convenience and reduced radiation exposure.Recommendation 9: For the different types of vascular lesion in CTEPH, treatment of ring-like stenoses, web-like lesions, and subtotal occlusions should be prioritized before addressing complete occlusions and tortuous lesions, in order to reduce complications and improve procedural safety.Recommendation 10: A targeted, incremental balloon dilatation strategy based on vascular lesions is recommended for BPA.Recommendation 11: Intravascular pulmonary artery imaging technologies, such as OCT and IVUS can assist in accurate vessel sizing and confirmation of wire placement in the true vascular lumen. Pressure wires can be used to objectively assess the efficacy of dilatation during BPA.Recommendation 12: Endpoints for BPA treatment should be individually assessed, taking into account improvements in clinical symptoms, hemodynamics, exercise tolerance, and quality of life.Recommendation 13: Post-BPA routine monitoring of vital signs is essential; anticoagulation therapy should be initiated promptly post-procedure in the absence of complications. In cases of intraoperative hemoptysis, postoperative anticoagulation regimen adjustments should be adjusted according to the bleeding severity.Recommendation 14: If reperfusion pulmonary edema occurs during or after BPA, ensure adequate oxygenation, diuresis, and consider non-invasive positive-pressure ventilation if necessary, while severe cases may require early mechanical ventilation assistance or ECMO.Recommendation 15: In cases of intraoperative hemoptysis, temporary balloon occlusion to stop bleeding is recommended, along with protamine to neutralize heparin. Persistent bleeding may warrant the use of gelatin sponges, coil embolization, or covered stent implantation.Recommendation 16: For contrast imaging during BPA, non-ionic, low or iso-osmolar contrast agents are recommended, with hydration status determined by the patient's clinical condition, cardiac and renal function, and intraoperative contrast volume used.

Obstructive Sleep Apnea, Obesity Hypoventilation Syndrome, and Pulmonary Hypertension: A State-of-the-Art Review.

The pathophysiological interplay between sleep-disordered breathing (SDB) and pulmonary hypertension (PH) is complex and can involve a variety of mechanisms by which SDB can worsen PH. These mechanistic pathways include wide swings in intrathoracic pressure while breathing against an occluded upper airway, intermittent and/or sustained hypoxemia, acute and/or chronic hypercapnia, and obesity. In this review, we discuss how the downstream consequences of SDB can adversely impact PH, the challenges in accurately diagnosing and classifying PH in the severely obese, and review the limited literature assessing the effect of treating obesity, obstructive sleep apnea, and obesity hypoventilation syndrome on PH.

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.

The Initial Experience of Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension in Latvia.

Background: Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent pulmonary hypertension after pulmonary endarterectomy (PEA) include targeted medical therapy and balloon pulmonary angioplasty (BPA). BPA is an emerging treatment modality that has been reported to improve functional capacity, pulmonary hemodynamics, and right ventricular function. Reports from expert centers are promising, but more data are needed to make the results more generalizable. Materials and Methods: We conducted a prospective analysis of nine consecutive CTEPH patients who underwent balloon pulmonary angioplasty (BPA) sessions at Pauls Stradins Clinical University Hospital in Riga, Latvia between 1 April 2022 and 1 July 2023. We assessed World Health Organization (WHO) functional class, 6 min walk distance (6MWD), blood oxygen saturation (SpO2), brain natriuretic peptide (BNP) level at baseline and 3 months after the first BPA session. For two patients on whom repeated BPA sessions were performed, we additionally assessed cardiac output (CO), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (mPAP). Results: A total of 12 BPA procedures for nine patients were performed; repeated BPA sessions were performed for two patients. Our results show a reduction in BNP levels and improvement in WHO functional class, 6MWD, and SpO2 after the first BPA session. Improvement in 6MWD was statistically significant. Additionally, an improvement in pulmonary hemodynamic parameters was observed. Conclusions: Our data show that BPA is an effective interventional treatment modality, improving both the pulmonary hemodynamics and functional status. Moreover, BPA is safe and excellently tolerated.

Post-Pulmonary Embolism Syndrome: An Update Based on the Revised AWMF-S2k Guideline.

In survivors of acute pulmonary embolism (PE), the post-PE syndrome (PPES) may occur. In PPES, patients typically present with persisting or progressive dyspnea on exertion despite 3 months of therapeutic anticoagulation. Therefore, a structured follow-up is warranted to identify patients with chronic thromboembolic pulmonary disease (CTEPD) with normal pulmonary pressure or chronic thromboembolic pulmonary hypertension (CTEPH). Both are currently understood as a dual vasculopathy, that is, secondary arterio- and arteriolopathy, affecting the large and medium-sized pulmonary arteries as well as the peripheral vessels (diameter < 50 µm). The follow-up algorithm after acute PE commences with identification of clinical symptoms and risk factors for CTEPH. If indicated, a stepwise performance of echocardiography, ventilation-perfusion scan (or alternative imaging), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, cardiopulmonary exercise testing, and pulmonary artery catheterization with angiography should follow. CTEPH patients should be treated in a multidisciplinary center with adequate experience in the complex therapeutic options, comprising pulmonary endarterectomy, balloon pulmonary angioplasty, and pharmacological interventions.

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.

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.

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.

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.

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.

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.

Chronic Thromboembolic Pulmonary Hypertension.

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

Ultrasound-mediated HGF Gene Microbubbles Mitigate Hyperkinetic Pulmonary Arterial Hypertension in Rabbits.

AIM: Hyperkinetic pulmonary arterial hypertension (PAH) is a complication of congenital heart disease. Gene therapy is a new experimental treatment for PAH, and ultrasound-mediated gene-carrying microbubble targeted delivery is a promising development for gene transfer. METHODS: This study successfully established a hyperkinetic PAH rabbit model by a common carotid artery and jugular vein shunt using the cuff style method. Liposome microbubbles carrying the hepatocyte growth factor (HGF) gene were successfully constructed. An in vitro experiment evaluated the appropriate intensity of ultrasonic radiation by Western blots and 3H-TdR incorporation assays. In an in vivo experiment, after transfection of ultrasound-mediated HGF gene microbubbles, catheterisation was applied to collect haemodynamic data. Hypertrophy of the right ventricle was evaluated by measuring the right ventricle hypertrophy index. Western blot and immunohistochemistry analyses were used to detect the expression of human (h)HGF and angiogenic effects, respectively. RESULTS: The most appropriate ultrasonic radiation intensity was 1.0 W/cm2 for 5 minutes. Two weeks after transfection, both systolic pulmonary arterial pressure and mean pulmonary arterial pressure were attenuated. Hypertrophy of the right ventricle was reversed. hHGF was transplanted into the rabbits, resulting in a high expression of hHGF protein and an increase in the number of small pulmonary arteries. Ultrasound-mediated HGF gene microbubble therapy was more effective at attenuating PAH and increasing the density of small pulmonary arteries than single HGF plasmid transfection. CONCLUSIONS: Ultrasound-mediated HGF gene microbubbles significantly improved the target of gene therapy in a rabbit PAH model and enhanced the tropism and transfection rates. Thus, the technique can effectively promote small pulmonary angiogenesis and play a role in the treatment of PAH without adverse reactions.