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JACC. Heart Failure Aug 2023
Topics: Humans; Hypertension, Pulmonary; Pulmonary Artery; Heart Failure; Denervation
PubMed: 37480880
DOI: 10.1016/j.jchf.2023.06.015 -
Vascular Medicine (London, England) Aug 2023Over a third of patients surviving acute pulmonary embolism (PE) will experience long-term cardiopulmonary limitations. Persistent thrombi, impaired gas exchange, and...
Over a third of patients surviving acute pulmonary embolism (PE) will experience long-term cardiopulmonary limitations. Persistent thrombi, impaired gas exchange, and altered hemodynamics account for aspects of the postpulmonary embolism syndrome that spans mild functional limitations to debilitating chronic thromboembolic pulmonary hypertension (CTEPH), the most worrisome long-term consequence. Though pulmonary endarterectomy is potentially curative for the latter, less is understood surrounding chronic thromboembolic disease (CTED) and post-PE dyspnea. Advances in pulmonary vasodilator therapies and growing expertise in balloon pulmonary angioplasty provide options for a large group of patients ineligible for surgery, or those with persistent postoperative pulmonary hypertension. In this clinical review, we discuss epidemiology and pathophysiology as well as advances in diagnostics and therapeutics surrounding the spectrum of disease that may follow months after acute PE.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Embolism; Angioplasty, Balloon; Chronic Disease; Endarterectomy; Syndrome
PubMed: 37036116
DOI: 10.1177/1358863X231165105 -
Current Opinion in Pulmonary Medicine Sep 2023Chronic thromboembolic disease (CTED) is distinct from chronic thromboembolic pulmonary hypertension (CTEPH) and is defined by dyspnea on exertion after acute pulmonary... (Review)
Review
PURPOSE OF REVIEW
Chronic thromboembolic disease (CTED) is distinct from chronic thromboembolic pulmonary hypertension (CTEPH) and is defined by dyspnea on exertion after acute pulmonary embolism with the presence of residual perfusion defects and absence of resting pulmonary hypertension. Here, we review clinical features and diagnostic criteria for CTED and summarize treatment options.
RECENT FINDINGS
The optimal management for CTED is unclear as the long-term outcomes of conservative vs. invasive treatment for this disease have not been reported. There are a few studies evaluating outcomes of pulmonary thromboendarterectomy and balloon pulmonary angioplasty (BPA) in CTED, concluding that these procedures are safe and effective in select patients. However, these trials are small nonrandomized observational studies, reporting outcomes only up to 1 year after the intervention. Conservative management of CTED with observation, pulmonary hypertension-targeted therapy, or cardiopulmonary rehabilitation has not been studied. It is unknown whether these treatments are as effective or superior to pulmonary thromboendarterectomy or BPA in CTED.
SUMMARY
The management of CTED is individualized and based on symptoms and exercise limitations. Early referral of patients with CTED to a specialized CTEPH center is recommended to determine if watchful waiting, BPA, or pulmonary thromboendarterectomy is most beneficial.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Embolism; Lung; Dyspnea; Angioplasty, Balloon; Chronic Disease; Pulmonary Artery
PubMed: 37461845
DOI: 10.1097/MCP.0000000000000987 -
Seminars in Thrombosis and Hemostasis Nov 2023Survivors of acute pulmonary embolism (PE) are at risk of developing persistent, sometimes disabling symptoms of dyspnea and/or functional limitations despite adequate... (Review)
Review
Survivors of acute pulmonary embolism (PE) are at risk of developing persistent, sometimes disabling symptoms of dyspnea and/or functional limitations despite adequate anticoagulant treatment, fulfilling the criteria of the post-PE syndrome (PPES). PPES includes chronic thromboembolic pulmonary hypertension (CTEPH), chronic thromboembolic pulmonary disease, post-PE cardiac impairment (characterized as persistent right ventricle impairment after PE), and post-PE functional impairment. To improve the overall health outcomes of patients with acute PE, adequate measures to diagnose PPES and strategies to prevent and treat PPES are essential. Patient-reported outcome measures are very helpful to identify patients with persistent symptoms and functional impairment. The primary concern is to identify and adequately treat patients with CTEPH as early as possible. After CTEPH is ruled out, additional diagnostic tests including cardiopulmonary exercise tests, echocardiography, and imaging of the pulmonary vasculature may be helpful to rule out non-PE-related comorbidities and confirm the ultimate diagnosis. Most PPES patients will show signs of physical deconditioning as main explanation for their clinical presentation. Therefore, cardiopulmonary rehabilitation provides a good potential treatment option for this patient category, which warrants testing in adequately designed and executed randomized trials. In this review, we describe the definition and characteristics of PPES and its diagnosis and management.
Topics: Humans; Chronic Disease; Risk Factors; Pulmonary Embolism; Acute Disease; Comorbidity; Hypertension, Pulmonary
PubMed: 35820428
DOI: 10.1055/s-0042-1749659 -
Cardiology in the Young Nov 2023The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare... (Meta-Analysis)
Meta-Analysis
The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare the efficacy and safety of pulmonary vasodilators in PAH-CHD. PubMed and EMBASE databases were searched through May 2022 and a network meta-analysis was conducted. The primary outcomes were mean difference of changes in 6-minute walk distance, NYHA functional class, and N-terminal pro-brain natriuretic peptide. The secondary outcomes included pulmonary vascular resistance, mean pulmonary arterial pressure, and resting oxygen saturation. We identified 14 studies, yielding 807 patients with PAH-CHD. Bosentan and sildenafil were associated with a significant increase in 6-minute walk distance from baseline compared with placebo (MD 48.92 m, 95% CI 0.32 to 97.55 and MD 59.70 m, 95% CI 0.88 to 118.53, respectively). Bosentan, sildenafil, and combination of bosentan and sildenafil were associated with significant improvement in NYHA functional class compared with placebo (MD -0.33, 95% CI -0.51 to -0.14, MD -0.58, 95% CI -0.75 to -0.22 and MD -0.62, 95% CI -0.92 to -0.31, respectively). Bosentan and sildenafil were also associated with significant improvements in secondary outcomes. These findings were largely confirmed in the subgroup analysis. Various adverse events were reported; however, serious adverse event rates were relatively low (4.8-8.7%), including right heart failure, acute kidney injury, respiratory failure, hypotension, and discontinuation of pulmonary vasodilators. In conclusion, bosentan and sildenafil were the most effective in improving prognostic risk factor such as 6-minute walk distance and NYHA class. Overall, pulmonary vasodilators were well tolerated in PAH-CHD.
Topics: Humans; Vasodilator Agents; Bosentan; Sildenafil Citrate; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Antihypertensive Agents; Sulfonamides; Network Meta-Analysis; Treatment Outcome; Familial Primary Pulmonary Hypertension
PubMed: 36721907
DOI: 10.1017/S1047951123000124 -
Therapeutic potential and protective role of GRK6 overexpression in pulmonary arterial hypertension.Vascular Pharmacology Dec 2023Abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a key mechanism in the development of pulmonary arterial hypertension (PAH). Signal...
Abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a key mechanism in the development of pulmonary arterial hypertension (PAH). Signal transducer and activator of transcription 3 (STAT3) signalling plays a critical role in modulating PASMC proliferation, and G-protein-coupled receptor kinase 6 (GRK6) regulates the STAT3 pathway. However, the mechanism underlying the relationship between GRK6 and PAH remains unclear. In this study, we aimed to investigate the role of GRK6 in PAH and determine its potential as a therapeutic target. We utilised hypoxia- and SU5416-induced PAH mouse models and a monocrotaline-induced PAH rat model to analyse the involvement of GRK6. We conducted gain- and loss-of-function experiments using mouse PASMCs. Modulation of GRK6 expression was achieved via a lentiviral vector in vitro and an adeno-associated virus serotype 1 encoding GRK6 in vivo. GRK6 was significantly downregulated in the lung tissues of PAH mice and rats, predominantly in PASMCs. Knockout of GRK6 exacerbated PAH, while both therapeutic and prophylactic overexpression of GRK6 alleviated PAH, as evidenced by a reduction in right ventricular systolic pressure, right ventricular wall to left ventricular wall plus ventricular septum ratio, pulmonary vascular media thickness, and pulmonary vascular muscularisation. Mechanistically, GRK6 overexpression attenuated hypoxia-induced PASMC proliferation and STAT3 phosphorylation. Conversely, knockdown of GRK6 promoted hypoxia-induced proliferation, which was mitigated by a STAT3 inhibitor. Our findings highlight the potential protective and beneficial roles of GRK6 in PAH; we propose a lung-targeted GRK6 gene therapy utilizing adeno-associated virus serotype 1 as a potential treatment approach for patients with PAH.
Topics: Humans; Rats; Mice; Animals; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Rats, Sprague-Dawley; Cell Proliferation; Mice, Knockout; Pulmonary Artery; Hypoxia; Myocytes, Smooth Muscle; Cells, Cultured
PubMed: 37742818
DOI: 10.1016/j.vph.2023.107233 -
Autoimmunity Reviews Apr 2024Pulmonary arterial hypertension (PAH), corresponding to group 1 of pulmonary hypertension classification, is a rare disease with a major prognostic impact on morbidity... (Review)
Review
Pulmonary arterial hypertension (PAH), corresponding to group 1 of pulmonary hypertension classification, is a rare disease with a major prognostic impact on morbidity and mortality. PAH can be either primary in idiopathic and heritable forms or secondary to other conditions including connective tissue diseases (CTD-PAH). Within CTD-PAH, the leading cause of PAH is systemic sclerosis (SSc) in Western countries, whereas systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are predominantly associated with PAH in Asia. Although many advances have been made during the last two decades regarding classification, definition early screening and risk stratification and therapeutic aspects with initial combination treatment, the specificities of CTD-PAH are not yet clear. In this manuscript, we review recent literature data regarding the updated definition and classification of PAH, pathogenesis, epidemiology, detection, prognosis and treatment of CTD-PAH.
Topics: Humans; Connective Tissue Diseases; Pulmonary Arterial Hypertension; Prognosis; Hypertension, Pulmonary; Scleroderma, Systemic
PubMed: 38135175
DOI: 10.1016/j.autrev.2023.103506 -
Catheterization and Cardiovascular... Sep 2023The efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) for Takayasu arteritis-associated pulmonary hypertension (TA-PH) remain unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) for Takayasu arteritis-associated pulmonary hypertension (TA-PH) remain unclear.
OBJECTIVES
To examine the efficacy and safety of PTPA in TA-PH.
METHODS
PubMed, Embase, and the Cochrane Central Register of Controlled Trials Library were searched from inception to August 18, 2022, for articles investigating the efficacy and safety of PTPA for TA-PH. The primary efficacy outcomes were pulmonary vascular resistance (PVR) changes from baseline to re-evaluation and 6-minute walking distance (6MWD). The safety outcome was procedure-related complications.
RESULTS
Five articles comprising 104 patients with TA-PH who underwent PTPA were included. The scores of article quality, as assessed using the methodological index for nonrandomized studies tool, were high, ranging from 13 to 15 points. The pooled treatment effects of PVR (weighted mean difference [WMD]: -4.8 WU; 95% confidence interval [CI]: -6.0 to -3.5 WU; I = 0.0%), 6MWD (WMD: 101.9 m; 95% CI: 60.3-143.6 m; I = 70.4%) significantly improved. Procedure-related complications, which predominantly present as pulmonary artery injury and pulmonary injury, occurred in 32.0% of the included patients. Periprocedural death occurred in one patient (1.0%, 1/100).
CONCLUSIONS
Patients with TA-PH could benefit from PTPA in terms of hemodynamics and exercise tolerance, at the expense of procedure-related complications. PTPA should be encouraged to enhance the treatment response in TA-PH. These findings need to be confirmed by further studies, ideally, randomized controlled trials.
REGISTRATION
PROSPERO CRD42022354087.
Topics: Humans; Hypertension, Pulmonary; Takayasu Arteritis; Treatment Outcome; Angioplasty; Pulmonary Arterial Hypertension
PubMed: 37522190
DOI: 10.1002/ccd.30773 -
Seminars in Respiratory and Critical... Dec 2023Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure, with or without...
Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure, with or without preserved left ventricular ejection fraction. Initially driven by a passive increase in left atrial pressure (postcapillary PH), several mechanisms may lead in a subset of patient to significant structural changes of the pulmonary vessels or a precapillary component. In addition, the right ventricle may be independently affected, which results in right ventricular to pulmonary artery uncoupling and right ventricular failure, all being associated with a worse outcome. The differential diagnosis of PH associated with left heart disease versus pulmonary arterial hypertension (PAH) is especially challenging in patients with cardiovascular comorbidities and/or heart failure with preserved ejection fraction (HFpEF). A stepwise approach to diagnosis is proposed, starting with a proper clinical multidimensional phenotyping to identify patients in whom hemodynamic confirmation is deemed necessary. Provocative testing (exercise testing, fluid loading, or simple leg raising) is useful in the cath laboratory to identify patients with abnormal response who are more likely to suffer from HFpEF. In contrast with group 1 PH, management of PH associated with left heart disease must focus on the treatment of the underlying condition. Some PAH-approved targets have been unsuccessfully tried in clinical studies in a heterogeneous group of patients, some even leading to an increase in adverse events. There is currently no approved therapy for PH associated with left heart disease.
Topics: Humans; Hypertension, Pulmonary; Heart Failure; Stroke Volume; Ventricular Function, Left; Hemodynamics
PubMed: 37709283
DOI: 10.1055/s-0043-1772754 -
Chest Jun 2024The global surge in methamphetamine use is a critical public health concern, particularly due to its robust correlation with methamphetamine-associated pulmonary... (Review)
Review
TOPIC IMPORTANCE
The global surge in methamphetamine use is a critical public health concern, particularly due to its robust correlation with methamphetamine-associated pulmonary arterial hypertension (MA-PAH). This association raises urgent alarms about the potential escalation of MA-PAH incidence, posing a significant and imminent challenge to global public health.
REVIEW FINDINGS
This comprehensive review meticulously explores MA-PAH, offering insights into its epidemiology, pathophysiology, clinical presentation, diagnostic intricacies, and management strategies. The pathogenesis, yet to be fully described, involves complex molecular interactions, including alterations in serotonin signaling, reduced activity of carboxylesterase 1, oxidative stress, and dysregulation of pulmonary vasoconstrictors and vasodilators. These processes culminate in the structural remodeling of the pulmonary vasculature, resulting in pulmonary arterial hypertension. MA-PAH exhibits a more severe clinical profile in functional class and hemodynamics compared with idiopathic pulmonary arterial hypertension. Management involves a multifaceted approach, integrating pulmonary vasodilators, cessation of methamphetamine use, and implementing social and rehabilitation programs. These measures aim to enhance patient outcomes and detect potential relapses for timely intervention.
SUMMARY
This review consolidates our understanding of MA-PAH, pinpointing knowledge gaps for future studies. Addressing these gaps is crucial for advancing diagnostic accuracy, unraveling mechanisms, and optimizing treatment for MA-PAH, thereby addressing the evolving landscape of this complex health concern.
Topics: Humans; Methamphetamine; Pulmonary Arterial Hypertension; Amphetamine-Related Disorders; Central Nervous System Stimulants; Hypertension, Pulmonary
PubMed: 38211700
DOI: 10.1016/j.chest.2024.01.014