Increase In Pulmonary Arterial Pressure Research Articles

Invasive haemodynamics at rest and exercise in cardiac amyloidosis.

Our aim was to investigate haemodynamics at rest and during exercise in patients with transthyretin cardiomyopathy (ATTR-CM) in light of the 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines on pulmonary hypertension (PH). We performed right heart catheterization (RHC) in 57 subjects with ATTR-CM. The proportion of patients with PH was 77% according to the 2022 guidelines versus 47% when applying the 2015 guidelines. Isolated post-capillary PH and combined pre- and post-capillary PH were most prevalent. Thirty-six patients underwent a supine bicycle cardiopulmonary exercise test during RHC. Exercise-induced PH was defined as an increase in mean pulmonary arterial pressure from rest to exercise per increase in cardiac output (ΔmPAP/ΔCO) of > 3mmHg/L/min. An increase in pulmonary arterial wedge pressure per change in cardiac output (ΔPAWP/ΔCO) from rest to exercise >2mmHg/L/min was considered suggestive of post-capillary exercise-induced PH. All but two patients who exercised during RHC developed exercise-induced PH. The median ΔmPAP/ΔCO was 7.2mmHg/L/min and ΔPAWP/ΔCO was 5.1mmHg/L/min. The median ΔRAP/ΔCO was 3.6mmHg/L/min and ΔRAP/ΔPAWP was 0.6mmHg/L/min. Most patients with ATTR-CM have isolated post-capillary or combined pre- and post-capillary PH at rest, and almost all patients develop exercise-induced PH with a large post-capillary component. There was a pronounced, but balanced increase in atrial pressures on exercise.

The FXYD1 protein plays a protective role against pulmonary hypertension and arterial remodeling via redox and inflammatory mechanisms.

Pulmonary hypertension (PH) consists of a heterogenous group of diseases that culminate in increased pulmonary arterial pressure and right ventricular (RV) dysfunction. We sought to investigate the role of FXYD1, a small membrane protein that modulates Na+-K+-ATPase function, in the pathophysiology of PH. We mined online transcriptome databases to assess FXYD1 expression in PH. We characterized the effects of FXYD1 knockout (KO) in mice on right and left ventricular (RV and LV) function using echocardiography and measured invasive hemodynamic measurements under normal conditions and after treatment with bleomycin sulfate or chronic hypoxia to induce PH. Using immunohistochemistry, immunoblotting, and functional assays, we examined the effects of FXYD1 KO on pulmonary microvasculature and RV and LV structure and assessed signaling via endothelial nitric oxide synthase (eNOS) and inflammatory pathways. FXYD1 lung expression tended to be lower in samples from patients with idiopathic pulmonary arterial hypertension (IPAH) compared with controls, supporting a potential pathophysiological role. FXYD1 KO mice displayed characteristics of PH including significant increases in pulmonary arterial pressure, increased muscularization of small pulmonary arterioles, and impaired RV systolic function, in addition to LV systolic dysfunction. However, when PH was stimulated with standard models of lung injury-induced PH, there was no exacerbation of disease in FXYD1 KO mice. Both the lungs and left ventricles exhibited elevated nitrosative stress and inflammatory milieu. The absence of FXYD1 in mice results in LV inflammation and cardiopulmonary redox signaling changes that predispose to pathophysiological features of PH, suggesting FXYD1 may be protective.NEW & NOTEWORTHY This is the first study to show that deficiency of the FXYD1 protein is associated with pulmonary hypertension. FXYD1 expression is lower in the lungs of people with idiopathic pulmonary artery hypertension. FXYD1 deficiency results in both left and right ventricular functional impairment. Finally, FXYD1 may endogenously protect the heart from oxidative and inflammatory injury.

Are dynamic measurements of central venous pressure in Fontan circulation during exercise or volume loading superior to resting measurements?

The main objective measure to assess the health of the Fontan circulation is the pressure measurement of the superior vena cava or pulmonary arteries. We reviewed the literature for benefits of measuring resting pressure in the Fontan circuit and explored whether dynamic measurement by volume loading or exercise has the potential to refine this diagnostic tool. PubMed was searched for articles showing a relationship between resting post-operative central venous pressure or pulmonary artery pressure and Fontan failure. Relationships between post-operative central venous pressure or pulmonary artery pressure and volume loading changes, such as during exercise or volume loading during cardiac catheterization, were also queried. A total of 44 articles mentioned relationships between resting central venous pressure or pulmonary artery pressure and Fontan failure. Only 26 included an analysis between the variables and only seven of those articles found pressure to be predictive of Fontan failure. Ten articles examined the relationship between exercise or volume loading and outcomes and demonstrated a large individual variation of pressures under these dynamic conditions. Based on current literature, there is not a lot of strong evidence to show that elevated resting central venous pressure or pulmonary artery pressure is predictive of Fontan failure. Some individuals experience dramatic increases in central venous pressure or pulmonary artery pressure under increased loading conditions with exercise or bolus fluid infusion, while others experience increases closer to that of a healthy control population. Further studies are needed to examine whether more dynamic and continuous monitoring of systemic venous pressures might better predict outcomes in patients with Fontan circulation.

The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension.

Mild-to-moderate pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). It is characterized by narrowing and thickening of the pulmonary arteries, resulting in increased pulmonary vascular resistance (PVR) and ultimately leading to right ventricular dysfunction. Pulmonary vascular remodeling in COPD is the main reason for the increase of pulmonary artery pressure (PAP). The pathogenesis of PH in COPD is complex and multifactorial, involving chronic inflammation, hypoxia, and oxidative stress. To date, prostacyclin and its analogues are widely used to prevent PH progression in clinical. These drugs have potent anti-proliferative, anti-inflammatory, and stimulating endothelial regeneration properties, bringing therapeutic benefits to the slowing, stabilization, and even some reversal of vascular remodeling. As another well-known and extensively researched prostaglandins, prostaglandin E2 (PGE2) and its downstream signaling have been found to play an important role in various biological processes. Emerging evidence has revealed that PGE2 and its receptors (i.e., EP1-4) are involved in the regulation of pulmonary vascular homeostasis and remodeling. This review focuses on the research progress of the PGE2 signaling pathway in PH and discusses the possibility of treating PH based on the PGE2 signaling pathway.

Risk of stiff left atrial syndrome following pulse-field-based ablation of atrial fibrillation in patients with pulmonary hypertension at baseline

Abstract Introduction Studies have reported development of stiff LA syndrome, defined as pulmonary hypertension (PH) secondary to reduced LA compliance, in some patients following AF ablation. Purpose We compared the risk of worsening of baseline PH in non-paroxysmal AF (persistent and long-standing persistent AF) patients undergoing repeat procedures, either pulse-field ablation (PFA) or standard radiofrequency ablation (RFA). Methods This multicenter study included 28 non-paroxysmal AF patients with PH, undergoing PFA-based ablation procedure after >1 failed radiofrequency ablations (RFA). A cohort of 28 AF patients with PH that were scheduled for repeat RF ablation were identified. Propensity scores were computed using multivariate logistic model. Twenty-eight patients from the RFA cohort were selected by 1:1 propensity score matching with the PFA group. Right heart catheterization was performed pre- and post-procedure to assess the Pulmonary artery pressure (PAP). PH was defined as resting mean PAP of ≥20 mmHg. The follow-up PAP and change from baseline were compared between PFA and RFA groups, after controlling for baseline PAP in an ANCOVA model. Results Baseline characteristics of PFA (age 62.21 ± 9.3 yrs, male 19 (67.9%), LAD 3.7 ± 0.66 cm) and propensity-matched RF groups (age 62.39 ± 9.3 yrs, male 18 (64.3%), LAD 3.7 ± 0.74 cm) were comparable. The mean pulmonary artery pressure (PAP) assessments at baseline, follow-up and change from baseline are presented in table below. The groups had comparable baseline PAP (p= 0.157). At follow-up, RF group reported 19.81 mm Hg increase in PAP (within-group p <0.001). In PFA group, follow-up PAP showed a decreasing trend (-1.67 mm Hg, within-group p= 0.114). Compared to PFA, the change was significantly higher in RFA (p <0.0001) after controlling for baseline PAP). Conclusion In this propensity-matched population, pulse-field ablation was demonstrated to be a safer option in terms of post-ablation worsening of PAP, compared to the RF ablation in AF patients with pulmonary hypertension at baseline.

Application of a novel echocardiographic scoring system to estimate left ventricular filling pressure in aortic stenosis

Abstract Background Despite the increased number of aortic stenosis (AS) patients, non-invasive estimation of the left ventricular (LV) filling pressure (FP) is often challenging partly because of unavailability of E/e' due to the presence of mitral annular calcification (MAC). Recently, an echocardiographic scoring system to estimate LVFP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score was proposed. Because VMT score can be applied for patients with significant MAC, we hypothesized that VMT score could be an alternative parameter of E/e' in AS. Purpose To test whether VMT score could be used as an alternative marker of LVFP to E/e' in AS patients. Methods We enrolled consecutive 116 patients with at least moderate AS in sinus rhythm who underwent right heart catheterization and echocardiography within 7 days. Mean pulmonary artery wedge pressure (PAWP) was measured as invasive parameter of LVFP. LV diastolic dysfunction (DD) was graded according to the ASE / EACVI guidelines. Using two-dimensional echocardiographic images, time sequence of opening of mitral and tricuspid valves was assessed and scored to 0 to 2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). This was based on the phenomenon in which early-diastolic opening of the mitral valve becomes earlier than tricuspid valve with an increase in LV FP and pulmonary artery pressure. When the inferior vena cava was dilated, 1 point was added and VMT score was finally calculated as 0 to 3. Results Overall, PAWP was 12±7 mmHg and elevated (≥15 mmHg) in 29 patients. MAC was observed in 82 patients. Although E/e' was higher in patients with elevated PAWP than in those without (23±11 vs 18±8, P=0.007), its predictive ability to elevated PAWP was non-significant (c-index: 0.59, P=0.13), resulting in low specificity of DD grading to predict elevated LVFP (sensitivity: 79%, specificity: 36%). In contrast, VMT score predicted elevated LVFP with c-index of 0.74 (P<0.001). When VMT score was used instead of E/e', diagnostic accuracy of DD grading was improved (c-index: 0.57 vs 0.82, P<0.001). Conclusion VMT score could be an alternative marker of LVFP to E/e' in AS patients.

Hypoxemia in patients with heart failure and preserved ejection fraction

Abstract Background Pulmonary abnormalities are common in patients with prevalent heart failure (HF). Arterial hypoxemia is considered rare in HF, but this has not been rigorously evaluated in patients with HF and preserved EF (HFpEF). Methods Results Patients with HFpEF (n=539) and no clinically-relevant lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxemia was defined by oxyhaeemoglobin saturation <94%. As compared to those without hypoxemia (n=403), patients with hypoxemia (n=136, 25%) were slightly older, heavier, and had higher NT-proBNP levels. They had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial O2 difference compared to those without hypoxemia. These differences were replicated in a sensitivity analysis where patients with any spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and capillary pressures were related to lower PaO2. The presence of exertional hypoxemia was associated with two-fold increased risk for death over 2.8 (IQR 0.7-5.5) years of follow up, (Adjusted:HR 2.00 (95%CI: 1.01−3.96), p=0.046). Conclusion One quarter of HFpEF patients displayed arterial desaturation during exercise. Patients with hypoxemia display more severely abnormal hemodynamics and increased mortality. Further study is required to better understand the mechanisms in patients with HFpEF.Hemodynamic changes at rest/exerciseRisk of death in HFpEF with hypoxemia

Bibliometric and visual analysis of hypoxic pulmonary hypertension from 2013 to 2022

Hypoxic pulmonary hypertension (HPH) is caused by chronic persistent hypoxia, which leads to the continuous increase of pulmonary artery pressure and pulmonary vascular resistance. In recent years, there has been a substantial increase in research on HPH. To study the trends of HPH research over the last decade, we used WOSCC to search for relevant research on this topic, and dealt with the relevant information using VOSviewer, CiteSpace, and R-tool. Our results show that the number of publications on HPH has generally increased in the last decade, albeit not significantly, while the average number of citations has been declining year by year. Researchers from the USA top the list with 5498 publications, who widely cooperate with researchers from other countries, followed by those from China. Kurt R. Stenmark has an authoritative position in this field, ranking first with 635 citations. American Journal of Physiology Lung Cellular and Molecular Physiology and Pulmonary Circulation have published 151 articles on HPH in the last 10 years, but the former has higher impact factor and article quality. Circulation proved its leadership in this field with 8812 citations. Our findings reveal the trends in HPH research and should provide researchers with plenty of useful information.

Epidemiological and clinical characteristics of pulmonary arterial hypertension in Indian patients: A hospital-based observational study

Context: Pulmonary hypertension (PH) is a condition characterized by an increase in pulmonary artery pressure, leading to morbidity and poor survival. In India, the high prevalence of certain diseases contributes to the burden of PH. To address this, this study provides epidemiological data and clinical characteristics of pulmonary artery hypertension. Materials and Methods: A cross-sectional study was conducted at a tertiary cardiac care hospital, recruiting 964 patients with severe pulmonary arterial hypertension (PAH). Patient data were obtained through a detailed history and physical examination, including 12-lead electrocardiogram, two-dimensional echocardiography, coronary angiography, right heart catheterization, and hematological and serological investigations. Results: The majority of patients (28.94%) were in the age group of 31–40 years, with a female preponderance in PAH disease. Idiopathic PAH (IPAH) was the most common type, accounting for 69.78% of all cases. The most common comorbid conditions were hypertension (48.55%) and Type-2 diabetes mellitus (44.81%). Dyspnea on exertion (98.34%) and edema of extremities (91.18%) were the most common symptoms. The mean survival rate was 50.98 months, with Type 1 PAH having the worst survival rate of 47.56 months. The statistical analysis showed a significant association between smoking and PAH. Conclusion: This study provides epidemiological data and clinical characteristics of PAH patients in India, emphasizing the need for early diagnosis, prompt management, and smoking cessation programs. The high prevalence of IPAH and female preponderance was also observed in this study. These findings can help in the development of targeted interventions and management strategies for PH patients in India.

Pulmonary arterial wedge pressure increase during exercise in patients diagnosed with pulmonary arterial or chronic thromboembolic pulmonary hypertension.

The course of pulmonary arterial wedge pressure (PAWP) during exercise in patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), further abbreviated as pulmonary vascular disease (PVD), is still unknown. The aim of the study was to describe PAWP during exercise in patients with PVD. In this cross-sectional study, right heart catheter (RHC) data including PAWP, recorded during semi-supine, stepwise cycle exercise in patients with PVD, were analysed retrospectively. We investigated PAWP changes during exercise until end-exercise. In 121 patients (59 female, 66 CTEPH, 55 PAH, 62±17 years) resting PAWP was 10.2±4.1 mmHg. Corresponding peak changes in PAWP during exercise were +2.9 mmHg (95% CI 2.1-3.7 mmHg, p<0.001). Patients ≥50 years had a significantly higher increase in PAWP during exercise compared with those <50 years (p<0.001). The PAWP/cardiac output (CO) slopes were 3.9 WU for all patients, and 1.6 WU for patients <50 years and 4.5 WU for those ≥50 years. In patients with PVD, PAWP increased slightly but significantly with the onset of exercise compared to resting values. The increase in PAWP during exercise was age-dependent, with patients ≥50 years showing a rapid PAWP increase even with minimal exercise. PAWP/CO slopes >2 WU are common in patients with PVD aged ≥50 years without exceeding the PAWP of 25 mmHg during exercise.

Acid ceramidase gene therapy ameliorates pulmonary arterial hypertension with right heart dysfunction

BackgroundUp-regulation of ceramides in pulmonary hypertension (PH), contributing to perturbations in sphingolipid homeostasis and the transition of cells to a senescence state. We assessed the safety, feasibility, and efficiency of acid ceramidase gene transfer in a rodent PH model.MethodsA model of PH was established by the combination of left pneumonectomy and injection of Sugen toxin. Magnetic resonance imaging and right heart catheterization confirmed development of PH. Animals were subjected to intratracheal administration of synthetic adeno-associated viral vector (Anc80L65) carrying the acid ceramidase (Anc80L65.AC), an empty capsid vector, or saline. Therapeutic efficacy was evaluated 8 weeks after gene delivery.ResultsHemodynamic assessment 4 weeks after PH model the development demonstrated an increase in the mean pulmonary artery pressure to 30.4 ± 2.13 mmHg versus 10.4 ± 1.65 mmHg in sham (p < 0.001), which was consistent with the definition of PH. We documented a significant increase in pulmonary vascular resistance in the saline-treated (6.79 ± 0.85 mm Hg) and empty capsid (6.94 ± 0.47 mm Hg) groups, but not in animals receiving Anc80L65.AC (4.44 ± 0.71 mm Hg, p < 0.001). Morphometric analysis demonstrated an increase in medial wall thickness in control groups in comparison to those treated with acid ceramidase. After acid ceramidase gene delivery, a significant decrease of pro-inflammatory factors, interleukins, and senescence markers was observed.ConclusionGene delivery of acid ceramidase provided tropism to pulmonary tissue and ameliorated vascular remodeling with right ventricular dysfunction in pulmonary hypertension.Graphical

Cognitive impairment in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling with resultant abnormal increase in pulmonary artery pressure and right heart dysfunction. There is evidence that PAH includes cognitive impairment. However, the cognitive impairment syndrome has not been well described, and both the underlying mechanism and the relationship between cardiopulmonary and cognitive dysfunction in PAH are unknown. We performed cognitive evaluations and same day sub-maximum cardiopulmonary exercise testing on adult subjects with PAH. A frontal-subcortical syndrome suggestive of vascular cognitive impairment was found in 26% of subjects and was associated with noninvasive markers of pulmonary vascular remodeling.

Abstract P3012: Routine Monitoring For Intracardiac Thrombosis And Pulmonary Embolism With Intraoperative Transesophageal Echocardiography In Orthotopic Liver Transplantation

Background: Intracardiac thrombosis (ICT) and pulmonary embolism (PE) are significant intraoperative complications during orthotopic liver transplantation (OLT). Despite the high mortality associated with these events, current monitoring practices are inadequate at detecting these complications during OLT. Transesophageal echocardiography (TEE) allows continuous monitoring of myocardial function and detection of ICT/PE. In this study, we aim to report the incidence of ICT/PE during OLT at our center and to advocate for the use of intraoperative TEE as a standard monitoring tool. We also propose a medical management algorithm stratified by the severity of RV dysfunction and pulmonary artery pressure (PAP) in cases of ICT with/without PE. Methods: We conducted a single-center retrospective chart review of OLT patients with intraoperative TEE monitoring from March 13, 2019 - March 13, 2023. Intraoperative data of interest included hemodynamics, RV dysfunction, PAP, presence of ICT and/or PE as identified on TEE and associated medical management. RV dysfunction was graded as mild, moderate, or severe reduction in cardiac contractility. Secondary outcome was mortality during index hospitalization. Results: We identified 99 patients at our center who had intraoperative TEE monitoring during OLT. Prevalence of ICT in this population was 9.09% (n=9), of which 44.4% (n=4) developed hemodynamically significant PE. ICT patients who remained hemodynamically stable were observed without intervention (33%, n=3). Heparin was administered to prevent thrombus enlargement in patients with an increase in PAP but no significant RV dysfunction detected on TEE (22%, n=2). Those showing signs of hemodynamically significant PE with moderate or severe RV failure were given tissue plasminogen activator (tPA) for thrombolysis (44%, n=4). Perioperative mortality among all ICT patients was 44.4% (n=4) due to hemorrhagic shock secondary to coagulopathy and heart failure. Conclusion: The results of this study show the utility of routine TEE use in intraoperative monitoring for identifying ICT and PE in OLT patients, given the high mortality associated with these complications. TEE also allows for a stepwise approach to medical management based on RV function and PAP.

Nobiletin attenuates monocrotaline-induced pulmonary arterial hypertension through PI3K/Akt/STAT3 pathway.

Nobiletin is a flavonoid found in the peel of Citrus sinensis (oranges). The purpose of this study is to investigate whether Nobiletin can alleviate the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and explore the underlying mechanisms. The PAH rat model was replicated by subcutaneous injection of MCT. Nobiletin (1, 5 and 10 mg/kg) was administered by gavage from day 1 to day 21. After 21 days of MCT injection, the mean pulmonary artery pressure, pulmonary vascular resistance, Fulton Index, pulmonary artery remodelling, blood routine parameters, liver and kidney functions was measured. The level of inflammatory cytokines and PI3K/Akt/STAT3 were detected by qPCR, ELISA and western blot, the proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by CCK-8. Nobiletin (10 mg/kg) inhibited the MCT-induced increase in mean pulmonary artery pressure and pulmonary vascular resistance, right ventricular hypertrophy and pulmonary artery remodelling in rats. Nobiletin decreased the levels of inflammatory cytokines and phosphorylation level of PI3K/Akt/STAT3 in lungs of MCT-treated rats. Nobiletin inhibited the proliferation and lowered the inflammatory cytokines level induced by PDGF-BB in PASMCs. Nobiletin attenuates MCT-induced PAH, and the potential mechanism is to inhibit inflammation through PI3K/Akt/STAT3 pathway.

The Relationship between Hyperuricemia and Echocardiographic Parameters in Patients with Chronic Atrial Fibrillation.

Purpose Uric acid serves as a marker for cardiovascular risk and is often linked to inflammation and oxidative stress. There is evidence suggesting an association between uric acid and atrial fibrillation (AF), including its severity and occurrence of crises, as well as its involvement in cardiovascular mechanisms. The objective of this study was to assess the correlation between hyperuricemia and echocardiographic features in patients with chronic AF lasting for more than 5 years. Methods This case-control study involved 107 patients diagnosed with chronic non-valvular AF. Uric acid levels were measured in all patients, and they were divided into two groups: the first group consisted of 66 patients with hyperuricemia (>7.2 mg/dL), while the second group included 41 patients with normal uric acid levels. Echocardiography (TTE) was performed to evaluate each patient. Various clinical and echocardiographic parameters, such as left ventricle telediastolic (LVTDD) and telesystolic (LVTSD) diameters, left atrial diameter (LAD), aortic diameter (AoD), ejection fraction (EF), and pulmonary artery pressure (PAP), were analyzed. Results Binary logistic regression analysis revealed a statistically significant relationship between uric acid levels (>7.2 mg/dL) and LAD. For each unit increase in LAD, the probability of having hyperuricemia increased by 9% [odds ratio (OD): 0.91, 95% confidence interval (CI): 0.84-0.99]. A significant relationship was found between uric acid levels (>8 mg/dL) and LVESD (p = 0.045) as well as PAP (p = 0.006). For every unit increase in LVESD, the likelihood of having uric acid levels greater than 8 mg/dL increased by 22% [OD: 0.82, 95% CI: 0.67-0.99, b = -0.2]. Likewise, for each unit increase in PAP, the probability of having uric acid levels greater than 8 mg/dL was 9.4% [OD: 0.91, 95% CI: 0.86-0.97, b = -0.09]. Conclusions This study demonstrates that hyperuricemia has a significant relationship with the development of atrial remodeling, with an important association observed between hyperuricemia and an increase in left atrial diameter. Hyperuricemia is also correlated with an enlargement of the left ventricle end-systolic diameter and pulmonary artery pressure, showing a possible influence that hyperuricemia might have also left ventricle morphology and right ventricle function.

Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare and progressive disease characterised by remodelling of the pulmonary arteries and progressive narrowing of the pulmonary vasculature. This leads to a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure and, if left untreated, to right ventricular failure and death. A correct diagnosis requires a complete work-up including right heart catheterisation performed in a specialised centre.Although our knowledge of the epidemiology, pathology and pathophysiology of the disease, as well as the development of innovative therapies, has progressed in recent decades, PAH remains a serious clinical condition. Current treatments for the disease target the three specific pathways of endothelial dysfunction that characterise PAH: the endothelin, nitric oxide and prostacyclin pathways.The current treatment algorithm is based on the assessment of severity using a multiparametric risk stratification approach at the time of diagnosis (baseline) and at regular follow-up visits. It recommends the initiation of combination therapy in PAH patients without cardiopulmonary comorbidities. The choice of therapy (dual or triple) depends on the initial severity of the condition. The main treatment goal is to achieve low-risk status. Further escalation of treatment is required if low-risk status is not achieved at subsequent follow-up assessments. In the most severe patients, who are already on maximal medical therapy, lung transplantation may be indicated.Recent advances in understanding the pathophysiology of the disease have led to the development of promising emerging therapies targeting dysfunctional pathways beyond endothelial dysfunction, including the TGF-β and PDGF pathways.

MANAGEMENT OF PULMONAL HYPERTENSION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) is an obstructive pulmonary disease due to inflammatory processes of the respiratory tract and lung parenchyma. In some cases of COPD, changes in the pulmonary vessels are found which are not uncommon, causing impaired gas exchange and causing pulmonary hypertension which is associated with increased morbidity and mortality. Pulmonary hypertension is an increase in the mean pulmonary artery pressure (Pulmonary Arterial Pressure) greater than or equal to 25 mmHg at rest as assessed by a right heart catheterization procedure. Pulmonary hypertension (HP) can exacerbate the occurrence of COPD where HP patients with COPD must receive optimal COPD management according to GOLD guidelines. Pulmonary hypertension can be caused by a variety of conditions which WHO divides into five major groups. Pulmonary hypertension in patients with COPD belongs to the third group. The pathophysiology of pulmonary hypertension in patients with hypoxia or chronic lung disease is caused by tunica media hypertrophy and tunica intima proliferation leading to distal pulmonary artery obstruction. Clinical and physical symptoms in HP patients in COPD usually overlap. If HP is suspected, echocardiography is the best initial examination. Definitive diagnosis obtained through right heart catheterization. In contrast to idiopathic pulmonary hypertension, examination of the vasoreactivity of blood vessels during right heart catheterization in this group is not recommended. The goal of therapy is improvement of clinical symptoms, hemodynamic status, right ventricular function and ultimately increase in quality of life and life expectancy. Oxygen therapy is the main therapy in HP and COPD after medical therapy. Providing adequate therapy for HP with COPD is expected to provide good outcomes for patients.

Hypoxaemia in patients with heart failure and preserved ejection fraction.

It is widely held that heart failure (HF) does not cause exertional hypoxaemia, based upon studies in HF with reduced ejection fraction, but this may not apply to patients with HF and preserved ejection fraction (HFpEF). Here, we characterize the prevalence, pathophysiology, and clinical implications of exertional arterial hypoxaemia in HFpEF. Patients with HFpEF (n = 539) and no coexisting lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxaemia (oxyhaemoglobin saturation <94%) was observed in 136 patients (25%). As compared to those without hypoxaemia (n = 403), patients with hypoxaemia were older and more obese. Patients with HFpEF and hypoxaemia had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial oxygen difference, increased dead space fraction, and greater physiologic shunt compared to those without hypoxaemia. These differences were replicated in a sensitivity analysis where patients with spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and pulmonary capillary pressures were related to lower arterial oxygen tension (PaO2 ), especially during exercise. Body mass index (BMI) was not correlated with the arterial PaO2 , and hypoxaemia was associated with increased risk for death over 2.8 (interquartile range 0.7-5.5) years of follow-up, even after adjusting for age, sex, and BMI (hazard ratio 2.00, 95% confidence interval 1.01-3.96; p = 0.046). Between 10% and 25% of patients with HFpEF display arterial desaturation during exercise that is not ascribable to lung disease. Exertional hypoxaemia is associated with more severe haemodynamic abnormalities and increased mortality. Further study is required to better understand the mechanisms and treatment of gas exchange abnormalities in HFpEF.

Myeloid-derived suppressor cells and pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic pulmonary vascular disorder characterized by an increase in pulmonary vascular resistance and pulmonary arterial pressure. The detailed molecular mechanisms remain unclear. In recent decades, increasing evidence shows that altered immune microenvironment, comprised of immune cells, mesenchymal cells, extra-cellular matrix and signaling molecules, might induce the development of PH. Myeloid-derived suppressor cells (MDSCs) have been proposed over 30 years, and the functional importance of MDSCs in the immune system is appreciated recently. MDSCs are a heterogeneous group of cells that expand during cancer, chronic inflammation and infection, which have a remarkable ability to suppress T-cell responses and may exacerbate the development of diseases. Thus, targeting MDSCs has become a novel strategy to overcome immune evasion, especially in tumor immunotherapy. Nowadays, severe PH is accepted as a cancer-like disease, and MDSCs are closely related to the development and prognosis of PH. Here, we review the relationship between MDSCs and PH with respect to immune cells, cytokines, chemokines and metabolism, hoping that the key therapeutic targets of MDSCs can be identified in the treatment of PH, especially in severe PH.

MicroRNA and lncRNA as the Future of Pulmonary Arterial Hypertension Treatment.

Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary arterial pressure and pulmonary vascular resistance. In a short time, it leads to right ventricular failure and, consequently, to death. The most common causes of PH include left heart disease and lung disease. Despite the significant development of medicine and related sciences observed in recent years, we still suffer from a lack of effective treatment that would significantly influence the prognosis and prolong life expectancy of patients with PH. One type of PH is pulmonary arterial hypertension (PAH). The pathophysiology of PAH is based on increased cell proliferation and resistance to apoptosis in the small pulmonary arteries, leading to pulmonary vascular remodeling. However, studies conducted in recent years have shown that epigenetic changes may also lie behind the pathogenesis of PAH. Epigenetics is the study of changes in gene expression that are not related to changes in the sequence of nucleotides in DNA. In addition to DNA methylation or histone modification, epigenetic research focuses on non-coding RNAs, which include microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Preliminary research results give hope that targeting epigenetic regulators may lead to new, potential therapeutic possibilities in the treatment of PAH.