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Chest Aug 2023Chronic thromboembolic pulmonary hypertension (CTEPH) is a treatable form of pulmonary hypertension and right heart failure. CTEPH (group 4 pulmonary hypertension) is... (Review)
Review
Chronic thromboembolic pulmonary hypertension (CTEPH) is a treatable form of pulmonary hypertension and right heart failure. CTEPH (group 4 pulmonary hypertension) is caused by persistent organized thromboembolic obstruction of the pulmonary arteries from incompletely resolved acute pulmonary embolism. CTEPH also may present without prior VTE history, which can contribute to its underrecognition. The true incidence of CTEPH is unclear, but is estimated to be approximately 3% after acute pulmonary embolism. V˙/Q˙ scintigraphy is the best screening test for CTEPH, with CT scan imaging and other advanced imaging methods now playing a larger role in disease detection and confirmation. Perfusion defects on V˙/Q˙ scintigraphy in the setting of pulmonary hypertension are suggestive of CTEPH, but pulmonary angiography and right heart catheterization are required for confirmation and treatment planning. CTEPH potentially is curative with pulmonary thromboendarterectomy surgery, with mortality rates of approximately 2% at expert centers. Advances in operative techniques are allowing more distal endarterectomies to be performed successfully with favorable outcomes. However, more than one-third of patients may be considered inoperable. Although these patients previously had minimal therapeutic options, effective treatments now are available with pharmacotherapy and balloon pulmonary angioplasty. Diagnosis of CTEPH should be considered in all patients with suspicion of pulmonary hypertension. Treatments for CTEPH have advanced with improvements in outcomes for both operable and inoperable patients. Therapy should be tailored based on multidisciplinary team evaluation to ensure optimal treatment response.
Topics: Humans; Hypertension, Pulmonary; Chronic Disease; Pulmonary Embolism; Pulmonary Artery; Lung; Angioplasty, Balloon; Endarterectomy
PubMed: 36990148
DOI: 10.1016/j.chest.2023.03.029 -
Circulation. Heart Failure Jul 2023Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion of the total pulmonary hypertension population who bring... (Review)
Review
Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion of the total pulmonary hypertension population who bring with them added complexity because of underlying anatomical and hemodynamic abnormalities. Currently, no consensus recommendations are available on how to best manage this group of patients for either the primary cardiologist or pulmonary hypertension subspecialist, including timing of referral. The purposes of this document are (1) to describe the various pulmonary hypertension groups and subgroups associated with congenital heart disease, (2) to describe imaging modalities used in patient evaluation, (3) to elucidate medical and surgical management considerations, (4) to highlight disparities within this population, and (5) to identify gaps and future research needs of patients with pulmonary hypertension associated with congenital heart disease.
Topics: United States; Humans; Hypertension, Pulmonary; American Heart Association; Heart Failure; Heart Defects, Congenital; Hemodynamics
PubMed: 37357777
DOI: 10.1161/HHF.0000000000000080 -
Clinical Medicine (London, England) Sep 2023Pulmonary hypertension (PH) is common, with an estimated prevalence of approximately 1% that increases with age. Prompt and accurate diagnosis is key to institute timely... (Review)
Review
Pulmonary hypertension (PH) is common, with an estimated prevalence of approximately 1% that increases with age. Prompt and accurate diagnosis is key to institute timely and appropriate therapy to improve symptoms and prognosis. The international guidelines for the diagnosis and management of PH have recently been updated, with a lowering of the haemodynamic threshold for diagnosis to a mean pulmonary artery pressure >20 mmHg. New diagnostic algorithms and revised indications for screening in at-risk groups have been developed to facilitate early referral to specialist PH centres. This includes fast-track referral pathways for patients who are either clinically high-risk or are at-risk for pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). This review summarises key changes in the PH guidelines for general physicians who are, most often, the first healthcare professionals to encounter these patients and consequently have a key role as referrers into specialist PH services.
Topics: Humans; Hypertension, Pulmonary; Prognosis; Physicians; Chronic Disease
PubMed: 37775164
DOI: 10.7861/clinmed.2023-23.5.Cardio4 -
Redox Biology Aug 2023Mitochondria are highly dynamic organelles essential for cell metabolism, growth, and function. It is becoming increasingly clear that endothelial cell dysfunction... (Review)
Review
Mitochondria are highly dynamic organelles essential for cell metabolism, growth, and function. It is becoming increasingly clear that endothelial cell dysfunction significantly contributes to the pathogenesis and vascular remodeling of various lung diseases, including pulmonary arterial hypertension (PAH), and that mitochondria are at the center of this dysfunction. The more we uncover the role mitochondria play in pulmonary vascular disease, the more apparent it becomes that multiple pathways are involved. To achieve effective treatments, we must understand how these pathways are dysregulated to be able to intervene therapeutically. We know that nitric oxide signaling, glucose metabolism, fatty acid oxidation, and the TCA cycle are abnormal in PAH, along with alterations in the mitochondrial membrane potential, proliferation, and apoptosis. However, these pathways are incompletely characterized in PAH, especially in endothelial cells, highlighting the urgent need for further research. This review summarizes what is currently known about how mitochondrial metabolism facilitates a metabolic shift in endothelial cells that induces vascular remodeling during PAH.
Topics: Humans; Hypertension, Pulmonary; Vascular Remodeling; Endothelial Cells; Lung; Oxidative Stress; Vascular Diseases; Pulmonary Artery; Cell Proliferation
PubMed: 37392518
DOI: 10.1016/j.redox.2023.102797 -
The European Respiratory Journal Jun 2023The 16-week randomised, placebo-controlled INCREASE trial (RCT) met its primary end-point by improving 6-min walk distance (6MWD) in patients receiving inhaled... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The 16-week randomised, placebo-controlled INCREASE trial (RCT) met its primary end-point by improving 6-min walk distance (6MWD) in patients receiving inhaled treprostinil for pulmonary hypertension due to interstitial lung disease (PH-ILD). The open-label extension (OLE) evaluated long-term effects of inhaled treprostinil in PH-ILD.
METHODS
Of 258 eligible patients, 242 enrolled in the INCREASE OLE and received inhaled treprostinil. Assessments included 6MWD, pulmonary function testing, N-terminal pro-brain natriuretic peptide (NT-proBNP), quality of life and adverse events. Hospitalisations, exacerbations of underlying lung disease and death were recorded.
RESULTS
At INCREASE OLE baseline, patients had a median age of 70 years and a mean 6MWD of 274.2 m; 52.1% were male. For the overall population, the mean 6MWD at week 52 was 279.1 m and the mean change from INCREASE RCT baseline was 3.5 m (22.1 m for the prior inhaled treprostinil arm and -19.5 m for the prior placebo arm); the median NT-proBNP decreased from 389 pg·mL at RCT baseline to 359 pg·mL at week 64; and the absolute (% predicted) mean forced vital capacity change from RCT baseline to week 64 was 51 mL (2.8%). Patients who received inhaled treprostinil placebo in the RCT had a 31% lower relative risk of exacerbation of underlying lung disease in the OLE (hazard ratio 0.69 (95% CI 0.49-0.97); p=0.03). Adverse events leading to drug discontinuation occurred in 54 (22.3%) patients.
CONCLUSIONS
These results support the long-term safety and efficacy of inhaled treprostinil in patients with PH-ILD, and are consistent with the results observed in the INCREASE RCT.
Topics: Aged; Female; Humans; Male; Antihypertensive Agents; Epoprostenol; Hypertension, Pulmonary; Lung Diseases, Interstitial; Quality of Life; Treatment Outcome
PubMed: 37080567
DOI: 10.1183/13993003.02414-2022 -
Jornal Brasileiro de Pneumologia :... Oct 2023
Topics: Humans; Hypertension, Pulmonary; Hypertension; Lung
PubMed: 37909553
DOI: 10.36416/1806-3756/e20230275 -
The Journal of Clinical Investigation Feb 2024Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in the...
Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in the development and progression of PAH, yet the underlying mechanisms are incompletely understood. The endosome-lysosome system is important to maintain cellular health, and the small GTPase RAB7 regulates many functions of this system. Here, we explored the role of RAB7 in endothelial cell (EC) function and lung vascular homeostasis. We found reduced expression of RAB7 in ECs from patients with PAH. Endothelial haploinsufficiency of RAB7 caused spontaneous pulmonary hypertension (PH) in mice. Silencing of RAB7 in ECs induced broad changes in gene expression revealed via RNA-Seq, and RAB7-silenced ECs showed impaired angiogenesis and expansion of a senescent cell fraction, combined with impaired endolysosomal trafficking and degradation, suggesting inhibition of autophagy at the predegradation level. Furthermore, mitochondrial membrane potential and oxidative phosphorylation were decreased, and glycolysis was enhanced. Treatment with the RAB7 activator ML-098 reduced established PH in rats with chronic hypoxia/SU5416. In conclusion, we demonstrate for the first time to our knowledge the fundamental impairment of EC function by loss of RAB7, causing PH, and show RAB7 activation to be a potential therapeutic strategy in a preclinical model of PH.
Topics: Animals; Humans; Mice; Rats; Familial Primary Pulmonary Hypertension; Hypertension, Pulmonary; Hypoxia; Lung; Pulmonary Artery
PubMed: 38015641
DOI: 10.1172/JCI169441 -
European Heart Journal Aug 2023The current treatment algorithm for chronic thromboembolic pulmonary hypertension (CTEPH) as depicted in the 2022 European Society of Cardiology (ESC)/European...
Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: a clinical consensus statement of the ESC working group on pulmonary circulation and right ventricular function.
The current treatment algorithm for chronic thromboembolic pulmonary hypertension (CTEPH) as depicted in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines on the diagnosis and treatment of pulmonary hypertension (PH) includes a multimodal approach of combinations of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and medical therapies to target major vessel pulmonary vascular lesions, and microvasculopathy. Today, BPA of >1700 patients has been reported in the literature from centers in Asia, the US, and also Europe; many more patients have been treated outside literature reports. As BPA becomes part of routine care of patients with CTEPH, benchmarks for safe and effective care delivery become increasingly important. In light of this development, the ESC Working Group on Pulmonary Circulation and Right Ventricular Function has decided to publish a document that helps standardize BPA to meet the need of uniformity in patient selection, procedural planning, technical approach, materials and devices, treatment goals, complications including their management, and patient follow-up, thus complementing the guidelines. Delphi methodology was utilized for statements that were not evidence based. First, an anatomical nomenclature and a description of vascular lesions are provided. Second, treatment goals and definitions of complete BPA are outlined. Third, definitions of complications are presented which may be the basis for a standardized reporting in studies involving BPA. The document is intended to serve as a companion to the official ESC/ERS guidelines.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Embolism; Pulmonary Circulation; Ventricular Function, Right; Angioplasty, Balloon; Pulmonary Artery; Chronic Disease; Cardiology
PubMed: 37470202
DOI: 10.1093/eurheartj/ehad413 -
Anatolian Journal of Cardiology Nov 2023
Topics: Humans; Hypertension, Pulmonary; Hypertension; Algorithms; Machine Learning
PubMed: 37909349
DOI: 10.14744/AnatolJCardiol.2023.11 -
Deutsches Arzteblatt International Dec 2023Up to 1% of the world population and 10% of all persons over age 65 suffer from pulmonary hypertension (PH). The latency from the first symptom to the diagnosis is more... (Review)
Review
BACKGROUND
Up to 1% of the world population and 10% of all persons over age 65 suffer from pulmonary hypertension (PH). The latency from the first symptom to the diagnosis is more than one year on average, and more than three years in 20% of patients. 40% seek help from more than four different physicians until their condition is finally diagnosed.
METHODS
This review is based on publications retrieved by a selective literature search on pulmonary hypertension.
RESULTS
The most common causes of pulmonary hypertension are left heart diseases and lung diseases. Its cardinal symptom is exertional dyspnea that worsens as the disease progresses. Additional symptoms of right heart failure are seen in advanced stages. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are rare, difficult to diagnose, and of particular clinical relevance because specific treatments are available. For this reason, strategies for the early detection of PAH and CTEPH have been developed. The clinical suspicion of PH arises in a patient who has nonspecific symptoms, electrocardiographic changes, and an abnormal (NT-pro-)BNP concentration. Once the suspicion of PH has been confirmed by echocardiography and, if necessary, differential-diagnostic evaluation with a cardiopulmonary stress test, and after the exclusion of a primary left heart disease or lung disease, the patient should be referred to a PH center for further diagnostic assessment, classification, and treatment.
CONCLUSION
If both the (NT-pro-)BNP and the ECG are normal, PH is unlikely. Knowledge of the characteristic clinical manifestations and test results of PH is needed so that patients can be properly selected for referral to specialists and experts in PH.
Topics: Humans; Aged; Hypertension, Pulmonary; Exercise Test; Dyspnea; Echocardiography; Heart Diseases; Pulmonary Embolism; Chronic Disease
PubMed: 37882345
DOI: 10.3238/arztebl.m2023.0222