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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 -
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 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 -
British Journal of Anaesthesia Dec 2023Flow-directed, balloon-tipped pulmonary artery catheters allow measuring cardiac output and other haemodynamic variables including intracardiac pressures. We propose...
Flow-directed, balloon-tipped pulmonary artery catheters allow measuring cardiac output and other haemodynamic variables including intracardiac pressures. We propose classifying pulmonary artery catheters by generations and specifying additional measurement modalities. Based on the method used to measure cardiac output, pulmonary artery catheters can be classified into three generations: first-generation using intermittent pulmonary artery thermodilution; second-generation using a thermal filament for automated pulmonary artery thermodilution; and third-generation combining thermal filament-based automated pulmonary artery thermodilution and pulmonary artery pulse wave analysis. Each of these pulmonary artery catheter generations can include additional measurements, such as continuous mixed venous oxygen saturation, right ventricular ejection fraction and end-diastolic volume, and right ventricular pressure. This classification should help define indications for pulmonary artery catheters in clinical practice and research.
Topics: Humans; Stroke Volume; Pulmonary Artery; Ventricular Function, Right; Catheterization, Swan-Ganz; Cardiac Output; Thermodilution; Catheters
PubMed: 37714751
DOI: 10.1016/j.bja.2023.08.017 -
Interventional Cardiology Clinics Jul 2024Pulmonary artery stent implantation has become integral in the treatment of pulmonary artery stenosis and is probably the most efficacious therapy for these lesions.... (Review)
Review
Pulmonary artery stent implantation has become integral in the treatment of pulmonary artery stenosis and is probably the most efficacious therapy for these lesions. Advancements in technology involving stent design and the equipment used for stent delivery have made this procedure much safer and more effective. Strategies to mitigate and successfully treat adverse events related to pulmonary artery stent implantation are reasonably well-established. Pulmonary artery stent implantation remains one of the most complex and technically challenging of congenital cardiac interventions.
Topics: Humans; Stents; Pulmonary Artery; Stenosis, Pulmonary Artery; Prosthesis Design
PubMed: 38839173
DOI: 10.1016/j.iccl.2024.03.008 -
The European Respiratory Journal Dec 2023Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well...
BACKGROUND
Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS.
METHODS
We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected.
RESULTS
44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 40 mmHg; p<0.001) and pulmonary vascular resistance (760 514 dyn·s·cm; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively.
CONCLUSIONS
In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.
Topics: Adult; Female; Humans; Child; Stenosis, Pulmonary Artery; Hypertension, Pulmonary; Constriction, Pathologic; Pulmonary Artery; Familial Primary Pulmonary Hypertension; Pulmonary Arterial Hypertension
PubMed: 38061784
DOI: 10.1183/13993003.00763-2023 -
BMJ (Clinical Research Ed.) Feb 2024
Topics: Humans; Pulmonary Embolism; Pulmonary Artery
PubMed: 38331462
DOI: 10.1136/bmj-2022-071662 -
Journal of Translational Medicine Jul 2023Pulmonary arterial hypertension (PAH) is a multifactorial disease associated with the remodeling of pulmonary blood vessels. If left unaddressed, PAH can lead to right... (Review)
Review
Pulmonary arterial hypertension (PAH) is a multifactorial disease associated with the remodeling of pulmonary blood vessels. If left unaddressed, PAH can lead to right heart failure and even death. Multiple biological processes, such as smooth muscle proliferation, endothelial dysfunction, inflammation, and resistance to apoptosis, are associated with PAH. Increasing evidence suggests that epigenetic factors play an important role in PAH by regulating the chromatin structure and altering the expression of critical genes. For example, aberrant DNA methylation and histone modifications such as histone acetylation and methylation have been observed in patients with PAH and are linked to vascular remodeling and pulmonary vascular dysfunction. In this review article, we provide a comprehensive overview of the role of key epigenetic targets in PAH pathogenesis, including DNA methyltransferase (DNMT), ten-eleven translocation enzymes (TET), switch-independent 3A (SIN3A), enhancer of zeste homolog 2 (EZH2), histone deacetylase (HDAC), and bromodomain-containing protein 4 (BRD4). Finally, we discuss the potential of multi-omics integration to better understand the molecular signature and profile of PAH patients and how this approach can help identify personalized treatment approaches.
Topics: Humans; Pulmonary Arterial Hypertension; Precision Medicine; Hypertension, Pulmonary; Transcription Factors; Nuclear Proteins; Pulmonary Artery; Epigenesis, Genetic; Vascular Remodeling; Cell Cycle Proteins
PubMed: 37461108
DOI: 10.1186/s12967-023-04339-5 -
European Respiratory Review : An... Dec 2023Pulmonary hypertension (PH) is defined by the presence of a mean pulmonary arterial pressure >20 mmHg. Current guidelines describe five groups of PH with shared... (Review)
Review
Pulmonary hypertension (PH) is defined by the presence of a mean pulmonary arterial pressure >20 mmHg. Current guidelines describe five groups of PH with shared pathophysiological and clinical features. In this paper, the first of a series covering all five PH classification groups, the clinical, radiological and pathological features of pulmonary arterial hypertension (PAH) will be reviewed. PAH may develop in the presence of associated medical conditions or a family history, following exposure to certain medications or drugs, or may be idiopathic in nature. Although all forms of PAH share common histopathological features, the presence of certain pulmonary arterial abnormalities, such as plexiform lesions, and extent of co-existing pulmonary venous involvement differs between the different subgroups. Radiological investigations are key to diagnosing the correct form of PH and a systematic approach to interpretation, especially of computed tomography, is essential.
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Familial Primary Pulmonary Hypertension; Pulmonary Artery
PubMed: 38123231
DOI: 10.1183/16000617.0138-2023 -
Clinical and Experimental Hypertension... Dec 2023To explore the correlation between pulmonary vascular performance and hemodynamics in patients with pulmonary arterial hypertension (PAH), using right heart...
OBJECTIVE
To explore the correlation between pulmonary vascular performance and hemodynamics in patients with pulmonary arterial hypertension (PAH), using right heart catheterization (RHC) and intravascular ultrasound (IVUS).
METHOD
A total of 60 patients underwent RHC and IVUS examinations. Of these, 27 patients were diagnosed with PAH associated with connective tissue diseases (PAH-CTD group), 18 patients were diagnosed with other types of PAH (other-types-PAH group), and 15 patients were without PAH (control group). The hemodynamics and morphological parameters of pulmonary vessels in PAH patients were assessed using RHC and IVUS.
RESULTS
There were statistically significant differences in right atrial pressure (RAP), pulmonary artery systolic pressure (sPAP), pulmonary artery diastolic pressure (dPAP), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) values between the PAH-CTD group, other-types-PAH group, and the control group (P < .05). No statistically significant difference was noticed in pulmonary artery wedge pressure (PAWP) and cardiac output (CO) values between these three groups (P > .05). The mean wall thickness (MWT), wall thickness percentage (WTP), pulmonary vascular compliance, dilation, elasticity modulus, stiffness index β, and other indicators were significantly different between these three groups (P < .05). Pairwise comparison showed that the average levels of pulmonary vascular compliance and dilation in PAH-CTD group and other-types-PAH group were lower than those in control group, while the average levels of elastic modulus and stiffness index β were higher than those in control group.
CONCLUSION
Pulmonary vascular performance deteriorates in PAH patients, and the performance is better in PAH-CTD patients than in other types of PAH.
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hemodynamics; Pulmonary Artery; Lung
PubMed: 36906960
DOI: 10.1080/10641963.2023.2185253