Increase In Pulmonary Arterial Pressure Research Articles

Exercise postcapillary pulmonary hypertension in patients with chronic thromboembolism. Role of multimodal resting and exercise assessment

Abstract Introduction Chronic thromboembolic pulmonary disease refers to the presence of thrombotic material after a pulmonary embolism (PE), exercise limitation and the absence of resting pulmonary hypertension (PH) but impaired right ventricular and pulmonary vascular reserve during exercise causing exercise precapillary PH (exprecapPH). However, in some patients, PH arises from an abnormal increase in pulmonary arterial wedge pressure (PAWP) with exercise in relation to underlying diastolic dysfunction, with thrombotic material not playing a substantial role. Whether these patients present distinct non-invasive and resting invasive parameters remains largely unknown. Purpose To compare the different exercise hemodynamic profiles of patients with chronic thromboembolism to identify clinical, echocardiographic, functional and hemodynamic parameters associated with exercise postcapillary PH (expostcapPH). Methods Data come from a prospective cohort of 71 symptomatic patients with perfusion defects in lung scintigraphy and computed tomographic confirmation of chronic thrombi despite anticoagulation ≥3 months after PE without or mild resting PH, undergoing exercise cardiac catheterization via supine cycle ergometry. A multipoint mean pulmonary artery pressure (mPAP)/cardiac output (CO) and mean PAWP/CO slope were calculated. Simultaneous stress echocardiography was available in 43 patients. Cardiopulmonary exercise test (CPET) was performed 24 hours before catheterization. Results Mean age was 53±13.9 years, 46 (64.8%) were males. 37 patients showed normal exercise hemodynamics, while 26 developed exprecapPH and 8 expostcapPH. Mean mPAP/CO slope was 3.1±1.6 mmHg/L/min, mean PAWP/CO slope 1.5±0.9 mmHg/L/min. Patients with expostcapPH were older, had a higher body mass index and hypertension. Comparison of hemodynamics, CPET and resting echocardiography is depicted in the table. Patients with expostcapPH, similar to those without exercise PH, had significantly lower resting pulmonary pressures and pulmonary vascular resistance than those with exprecapPH. These differences remained at peak exercise; however, while resting PAWP did not differ between groups, a significant increase in PAWP was unmasked in patients with expostcapPH compared to the other groups, and accordingly a significant difference in the PAWP/CO slope. Regarding CPET, patients with expostcapPH had higher baseline systolic blood pressure and lower functional capacity (VO2 max, VO2 at VT1, O2 pulse, OUES). Resting TAPSE/PASP was higher in patients with expostcapPH compared to those with exprecapPH. Conclusions Patients with chronic thromboembolism and expostcapPH exhibit distinct clinical features and have lower functional capacity, while resting PAWP did not allow differentiation between groups. Further studies are warranted to delineate characteristic elements of patients with underlying diastolic dysfunction due to its distinct prognosis and treatment.

Time Interval Between Right Ventricular Early Diastolic Velocity by Tissue and Pulse Wave Doppler: An Index of Right Atrial Pressure in Pulmonary Hypertension Patients

Background: A reversal of time difference between the onset of early diastolic velocity (e’) during tissue Doppler imaging and the onset of mitral inflow (E) has been observed in cases of elevated left atrial pressure. Whether this interval (Te’-E) may be useful to assess right atrial pressure has never been investigated, neither in healthy subjects nor in pulmonary hypertension patients. Methods: Right ventricular Te’-E was assessed in patients with pre-capillary pulmonary hypertension and compared with healthy volunteers who underwent comprehensive echocardiography examination. Te’-E is the difference between the interval from R wave at the superimposed electrocardiogram to the e’ wave during right ventricular tissue Doppler imaging and the interval from the R wave to transtricuspid E wave during pulsed wave Doppler imaging. Right atrial pressure was invasively measured in pulmonary hypertension patients. Results: Fifty-six patients were enrolled. Te’-E was prolonged in pulmonary hypertension subjects compared with healthy subjects (p < 0.001). Amongst the pulmonary hypertension patients, strong correlations were found between Te’-E and right atrial pressure (r = −0.885, p < 0.001), systolic pulmonary pressure (r = −0.85, p < 0.001) and the duration of tricuspid regurgitation (r = 0.72, p < 0.001). The area under the receiver operating characteristic curve of Te’-E in identifying right atrial pressure higher than 15 mm of mercury was 0.992 (sensitivity 100%, specificity 83%). Conclusions: In contrast to the left ventricle, there is a delay in the proto-diastolic filling in pulmonary hypertension patients, which correlates with the increase in systolic pulmonary arterial pressure, right atrial pressure, tricuspid regurgitation duration and restrictive diastolic pattern.

MTOR in the Development of Hypoxic Pulmonary Hypertension Associated with Cardiometabolic Risk Factors.

The pathophysiology of pulmonary hypertension is complex and multifactorial. It is a disease characterized by increased pulmonary vascular resistance at the level due to sustained vasoconstriction and remodeling of the pulmonary arteries, which triggers an increase in the mean pulmonary artery pressure and subsequent right ventricular hypertrophy, which in some cases can cause right heart failure. Hypoxic pulmonary hypertension (HPH) is currently classified into Group 3 of the five different groups of pulmonary hypertensions, which are determined according to the cause of the disease. HPH mainly develops as a product of lung diseases, among the most prevalent causes of obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), or hypobaric hypoxia due to exposure to high altitudes. Additionally, cardiometabolic risk factors converge on molecular mechanisms involving overactivation of the mammalian target of rapamycin (mTOR), which correspond to a central axis in the development of HPH. The aim of this review is to summarize the role of mTOR in the development of HPH associated with metabolic risk factors and its therapeutic alternatives, which will be discussed in this review.

Pulmonary Hypertension: Diagnosis and Management

Pulmonary hypertension (PH) affects 1% of people worldwide. Changes in the pulmonary vasculature, obstructive lesions in the pulmonary arteries, and an increase in pulmonary artery pressure are the hallmarks of PH, a progressive and deadly cardiovascular illness. These modifications result in a rise in right ventricular afterload, which frequently causes unfavorable right ventricular remodeling, right ventricular dysfunction and, in the end, mortality. One of the more severe and well-researched types of PH is pulmonary arterial hypertension (PAH), which is treatable with medication. The mechanisms involved in the regulation of pulmonary vascular tone and proliferation are the focus of PAH as well as some other forms of PH. The main characteristics of PAH (group 1) are discussed in this article, along with new and existing treatment options for the condition.

343 The relationship between pulmonary arterial pressure phenotypes and oxygen consumption in beef cattle

Abstract The objective of this study was to determine if a phenotypic relationship between pulmonary arterial pressure (PAP) and oxygen consumption exists in beef cattle. Pulmonary arterial pressure is used as an indicator of pulmonary hypertension in cattle which is indicative of the susceptibility to both high-altitude disease and feedlot heart failure of an individual. Cattle with greater PAP are typically hypoxic and have initiated expression of compensatory mechanisms their cardio-pulmonary systems employ to combat this alveolar hypoxia. In turn, this causes an increase in PAP and, ultimately, right-sided heart failure. If hypoxic individuals consume more oxygen as a compensation mechanism, oxygen consumption as a trait could be used as an indicator of the prediction of PAP and feedlot heart failure and would be especially useful for cattle in deep phenotyping systems. Data used in the study included cattle with PAP measures on a total of 132 individuals. The data consisted of both steers (n = 99) and heifers (n = 33) from a ranch located in southern Wyoming at an elevation of approximately 2,195 m. After weaning on the ranch, cattle were transported to Colorado State University’s Agriculture Research, Development and Education Center located in Fort Collins, CO (elevation: 1,558 m). Oxygen consumption was measured using a Greenfeed system (C-Lock, Rapid City, South Dakota). To determine if a relationship exists between oxygen consumption and PAP, a simple linear regression model was used to regress PAP on average daily oxygen consumption. Effects included in the model were sex and phenotypic PAP. Average daily oxygen consumption was measured in kilograms per day and averaged 6.6 ± 1.66 kg with a range of 2.3 to 10.45 kg. Pulmonary arterial pressure averaged 42.6 ± 7.96 mm Hg and ranged from 33 to 81 mm Hg. In this data, sex did not account for a significant amount of variability in phenotypic PAP (P > 0.05). Oxygen consumption did account for a significant amount of variability in PAP (P < 0.05), and it was found that with every 1 kg increase of oxygen consumption, PAP is estimated to increase 1.02 mm Hg. These results indicate that a statistical relationship between oxygen consumption and PAP exists. Although these findings suggest that greater oxygen consumption leads to greater PAP, further research is required to fully comprehend the relationship between beef cattle PAP and oxygen consumption.

The Hemodynamic Effects of Bolus Dose Calcium in Patients Undergoing Pulmonary Artery Reconstruction and Unifocalization Surgery: A Pilot Study

Objectives: To determine if bolus administration of calcium increases pulmonary artery pressures after unifocalization procedures or pulmonary artery reconstruction surgery. Design: Retrospective cohort study using Stanford University's data warehouse. Setting: A large pediatric heart center within an academic quaternary care facility. Participants: All patients undergoing pulmonary artery reconstruction or unifocalization procedure identifiable within the data warehouse. Interventions: We collected data from Stanford University's data repository; we formatted it and analyzed it using RStudio (v 2023.06.1+524). Measurements and Main Results: Our primary outcome is the change in pulmonary artery systolic pressure (PASP) after a bolus administration of calcium. Secondary endpoints include changes in pulmonary arterial to systemic arterial pressure ratio, mean arterial pressure, right sided filling pressure, and left atrial pressure. We used the Friedman test to assess differences and the Durbin-Conover rank-sum for pairwise comparisons. We found a difference in PASP after a bolus dose of calcium (Friedman X2 = 13.67, p = 0.003), with a higher PASP five minutes after calcium administration when compared to two minutes before the administration (35 mmHg versus 33 mmHg, p = 0.01), and a higher PASP 10 minutes after calcium administration when compared to two minutes before the administration (35 mmHg versus 33 mmHg, p = 0.008). Conclusions: Calcium bolus administration led to an increase in pulmonary arterial pressure in patients after pulmonary artery reconstruction or unifocalization surgeries. It may be prudent to avoid bolus administration in this patient population immediately after repair or in patients with right ventricular dysfunction.

New and Emerging Therapeutic Drugs for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review.

Pulmonary arterial hypertension (PAH) is a serious, progressive, and potentially fatal lung disease characterized by a gradual increase in mean pulmonary arterial pressure to over 20 mmHg at rest. The pathogenesis of PAH is multifactorial. It involves dynamic obstruction of the pulmonary vasculature through vasoconstriction, structural obstruction due to adverse vascular remodeling, and pathological obstruction caused by vascular fibrosis and stiffening, which reduces compliance. PAH often presents with vague initial symptoms and is frequently diagnosed at an advanced stage. The increased pulmonary arterial pressure leads to vascular remodeling, eventually resulting in right ventricular hypertrophy and failure. PAH is a rare condition with a median life expectancy of three years, underscoring the need for effective treatment alternatives. Several FDA-approved therapeutic options are available, including prostacyclin analogs (epoprostenol, iloprost, and treprostinil), the non-prostanoid IP receptor agonist selexipag, selective endothelin receptor antagonists (ERA) (ambrisentan, bosentan, and macitentan), phosphodiesterase 5 inhibitors (sildenafil and tadalafil), and the soluble guanylate cyclase (sGC) stimulator riociguat. Despite these advancements, current medications do not provide a permanent cure. This study presents an overview of current and emerging PAH therapies through a systematic literature review. It involved an analysis of nine studies and a review of 800 papers from reputable journals published between 2013 and June 2023. The research focused on drug effects on the six-minute walk distance (6-MWD) and associated side effects in randomized controlled trials. The review found that while udenafil, imatinib, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were evaluated, imatinib was notably associated with adverse side effects. Conversely, udenafil, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were found to be safe, well-tolerated, and effective in improving hemodynamic measures and 6-MWDs. This study aims to summarize the developing treatment options currently under clinical trials, highlighting the need for further trials before their application in clinical practice.

Effects of Modulating BMP9, BMPR2, and AQP1 on BMP Signaling in Human Pulmonary Microvascular Endothelial Cells.

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive increase in mean pulmonary arterial pressure. Mutations in the BMPR2 and AQP1 genes have been described in familial PAH. The bone morphogenetic proteins BMP9 and BMP10 bind with high affinity to BMPR2. Administration of BMP9 has been proposed as a potential therapeutic strategy against PAH, although recent conflicting evidence dispute the effect of such a practice. Considering the involvement of the above molecules in PAH onset, progression, and therapeutic value, we examined the effects of modulation of BMP9, BMPR2, and AQP1 on BMP9, BMP10, BMPR2, AQP1, and TGFB1 expression in human pulmonary microvascular endothelial cells in vitro. Our results demonstrated that silencing the BMPR2 gene resulted in increased expression of its two main ligands, namely BMP9 and BMP10. Exogenous administration of BMP9 caused the return of BMP10 to basal levels, while it restored the decreased AQP1 protein levels and the decreased TGFB1 mRNA and protein expression levels caused by BMPR2 silencing. Moreover, AQP1 gene silencing also resulted in increased expression of BMP9 and BMP10. Our results might possibly imply that the effect of exogenously administered BMP9 on molecules participating in the BMP signaling pathway could depend on the expression levels of BMPR2. Taken together, these results may provide insight into the highly complex interactions of the BMP signaling pathway.

Pulmonary vasodilation during cardiopulmonary resuscitation – A randomized, controlled porcine study

BackgroundDuring resuscitation pulmonary artery pressure (PAP) increases. This reduces left ventricular filling, leading to decreased blood flow. Inhaled nitric oxide (iNO) produces selective pulmonary vasodilation. We hypothesized that iNO would lower PAP during resuscitation resulting in increased survival. Methods30 pigs (40 kg) were subjected to cardiac arrest for 9.5 min after myocardial ischemia induced by coronary artery occlusion of the left anterior descending artery and ventricular fibrillation. During resuscitation, the pigs were randomized to 40 ppm iNO or placebo. The primary outcome was return of spontaneous circulation (ROSC). Pigs achieving ROSC underwent 4-hours intensive care. ResultsThe ROSC rate was 9/14 (64%) in the control group and 11/16 (69%) in the iNO group (OR 1.2 95%CI [0.3;5.6], p > 0.99). There was no difference in diastolic aorta pressure/PAP ratio (mean difference −0.99 [95% CI: −2.33–0.36], p = 0.14). Mean pulmonary artery pressure was lower in the iNO group 60 and 120 min after ROSC (mean difference: −12.18 mmHg [95%CI: −16.94; −7.43] p < 0.01 and −5.43 [95%CI: −10.39; −0.46] p = 0.03). Troponin I levels in the iNO group were significantly higher 60 and 120 min after ROSC (mean difference: 266105 ng/l [95%CI: 6356; 525855] p = 0.045 and 420049 ng/l [95%CI: 136779; 703320], p = 0.004). The area at risk of the heart was 33% (SD 1) in controls and 34% (SD 1) in the iNO group. The infarct size divided by the area at risk was 55% (SD 3) in controls and 86% (SD 1) in the iNO group, p = 0.01. ConclusionApplication of iNO did not improve the rate of ROSC or hemodynamic function but increased myocardial injury.

Melatonin effects on oxidative stress and on TLR4/NF-kβ inflammatory pathway in the right ventricle of rats with pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure and a compromised the right ventricle (RV), together with progression to heart failure and premature death. Studies have evaluated the role of melatonin as a promising therapeutic strategy for PAH. The objective of this study was to evaluate melatonin's effects on oxidative stress and on the TLR4/NF-kβ inflammatory pathway in the RV of rats with PAH. Male Wistar rats were divided into the following groups: control, monocrotaline (MCT), and monocrotaline plus melatonin groups. These two last groups received one intraperitoneal injection of MCT (60 mg/kg) on the first day of experimental protocol. The monocrotaline plus melatonin group received 10 mg/kg/day of melatonin by gavage for 21 days. Echocardiographic analysis was performed, and the RV was collected for morphometric analysis oxidative stress and molecular evaluations. The main findings of the present study were that melatonin administration attenuated the reduction in RV function that was induced by monocrotaline, as assessed by TAPSE. In addition, melatonin prevented RV diastolic area reduction caused by PAH. Furthermore, animals treated with melatonin did not show an increase in ROS levels or in NF-kβ expression. In addition, the monocrotaline plus melatonin group showed a reduction in TLR4 expression when compared with control and monocrotaline groups. To our knowledge, this is the first study demonstrating a positive effect of melatonin on the TLR4/NF-kβ pathway in the RV of rats with PAH. In this sense, this study makes it possible to think of melatonin as a possible ally in mitigating RV alterations caused by PAH.

Early detection of pulmonary arterial hypertension through [18F] positron emission tomography imaging with a vascular endothelial receptor small molecule.

The objective of this study is to provide a positron emission tomography (PET) imaging modality targeting vascular endothelial growth factor receptors (VEGFR) for the early noninvasive detection and assessment of pulmonary arterial hypertension (PAH) severity. To validate the effectiveness of the [18F]VEGFR PET tracer, we utilized a monocrotaline (MCT)-induced PAH rat model. Molecular optical imaging, using a Cy5.5-conjugated VEGFR targeting agent, was employed to demonstrate the uptake of the agent at pulmonary arterioles, correlating with the onset and progression of PAH. Histological examinations of the MCT-PAH rat lung revealed a significant correlation between VEGFR2 expression and the pathogenesis of PAH. Molecular optical imaging demonstrated heightened uptake of the Cy5.5-conjugated VEGFR targeting agent at pulmonary arterioles, corresponding with the onset and progression of PAH. [18F]VEGFR PET showed increased lung uptake detectable in early-stage PAH before increase in pulmonary artery pressures, and this uptake correlated with increased PAH severity. Moreover, when compared to [18F]FDG PET, [18F]VEGFR PET exhibited markedly lower background cardiac signal, enhancing imaging sensitivity for lung abnormalities. Our study provides a compelling evidence for the potential utility of the innovative [18F]VEGFR PET tracer, in non-invasively detecting early signs of PAH, and monitoring its progression. The observed correlations between VEGFR2 expression, molecular optical imaging results, and [18F]VEGFR PET findings support the use of this tracer for early detection, and assessment of PAH severity. The lower background cardiac signal observed with [18F]VEGFR PET further enhances its imaging sensitivity, emphasizing its potential clinical significance.

Safety and Outcomes with Direct Oral Anticoagulants Versus Vitamin-K Antagonists in Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review, Meta-Analysis, and Meta-Regression.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by organized thrombi inside the pulmonary vasculature, leading to an increase in pulmonary artery pressure. CTEPH is seen in about 3-4% of patients with acute pulmonary embolism and is associated with poor outcomes. Apart from surgical intervention, lifelong anticoagulation is the mainstay of CTEPH management. Traditionally, CTEPH is managed with vitamin-K antagonists (VKA); however, direct oral anticoagulants (DOACs) are recently gaining popularity. However, the current literature comparing DOACs versus VKAs in CTEPH has inconsistent results. An electronic search of the major bibliographic databases was performed to retrieve studies comparing DOACs versus VKAs in CTEPH patients. For dichotomous outcomes, the odds ratio (ORs) with 95% confidence intervals (CI) were pooled using the DerSimonian and Laird random-effects model to generate forest plots. Statistical significance was considered at P < 0.05. Ten studies were included with 3936 patients (1269 in the DOAC group and 2667 in the VKA group). Treatment with DOAC was associated with no statistically significant difference in the risk of all-cause mortality (OR, 0.78; 95% CI, 0.35-1.71; P < 0.53), venous thromboembolism (OR, 1.19; 95% CI, 0.59-2.40; P = 0.63), major bleeding (OR, 0.68; 95% CI, 0.38-1.22; P = 0.20), and clinically relevant nonmajor bleeding (OR, 1.22; 95% CI, 0.80-1.86; P = 0.37). Our analysis demonstrates that DOACs are noninferior to VKAs in terms of their safety and outcomes profile in CTEPH. Further trials are needed to evaluate more robust evidence and to compare additional outcomes.

Effects of Ranolazine and Ivabradine on Pulmonary Microhemodynamics in Experimental Model of Pulmonary Thromboembolism.

We studied changes of pulmonary microhemodynamics when modeling pulmonary artery thromboembolism on perfused isolated rabbit lungs after pretreatment with ranolazine and ivabradine. The increase in pulmonary artery pressure, pulmonary vascular resistance, and pre- and postcapillary resistance was less pronounced than in control animals, but was close to that in case of pulmonary thromboembolism after pretreatment with voltage-gated Na+ channel blockers lidocaine and ropivacaine. The increase of capillary filtration coefficient inversely correlated with values of capillary hydrostatic pressure. Thus, ranolazine and ivabradine exhibit the properties of voltage-gated Na+ channel blockers mainly in smooth muscles of pulmonary arterial vessels and promote the decrease in endothelial permeability.

Symposium review: high altitude travel with pulmonary vascular disease.

Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension are the main precapillary forms of pulmonary hypertension (PH) summarized as pulmonary vascular diseases (PVD). PVDs are characterized by exertional dyspnoea and oxygen desaturation, and reduced quality of life and survival. Medical therapies improve life expectancy and physical performance of PVD patients, of whom many wish to participate in professional work and recreational activities including traveling to high altitude. The exposure to the hypobaric hypoxic environment of mountain regions incurs the risk of high altitude adverse events (AEHA) due to severe hypoxaemia exacerbating symptoms and further increase in pulmonary artery pressure, which may lead to right heart decompensation. Recent prospective and randomized trials show that altitude-induced hypoxaemia, pulmonary haemodynamic changes and impairment of exercise performance in PVD patients are in the range found in healthy people. The vast majority of optimally treated stable PVD patients who do not require long-term oxygen therapy at low altitude can tolerate short-term exposure to moderate altitudes up to 2500m. PVD patients that reveal persistent severe resting hypoxaemia ( <80% for >30min) at 2500m respond well to supplemental oxygen therapy. Although there are no accurate predictors for AEHA, PVD patients with unfavourable risk profiles at low altitude, such as higher WHO functional class, lower exercise capacity with more pronounced exercise-induced desaturation and more severely impaired haemodynamics, are at increased risk of AEHA. Therefore, doctors with experience in PVD and high-altitude medicine should counsel PVD patients before any high-altitude sojourn. This review aims to summarize recent literature and clinical recommendations about PVD patients travelling to high altitude.

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.

Changes in the pulmonary circulation due to gravitational loads in high altitude conditions.

The impact of gravity on the existence of all living things has long been of interest to scientists. The force of the Earth's gravity combined with hypoxia significantly affects blood circulation and blood accumulation in various parts of the human and animal body. To date, the relationship between body position and blood circulation in pulmonary circulation under hypobaric hypoxia has not been sufficiently studied. Therefore, the research aims to determine the possibility of changing the body position in space on the reactions in the pulmonary circulation in the plains and highlands. For this purpose, research was conducted on male Wistar rats, 44 of whom spent 150 days at an altitude of 3200 m above sea level, and 25 representatives of the control group - at an altitude of 164 m. The study revealed that gravitational redistribution of blood in mountainous conditions is less pronounced compared to the control group. This is explained by the remodeling of the vascular wall and an increase in its stiffness. It was found that a change in pulmonary artery pressure at the time of a change in body position was recorded both on the plains and in the highlands. On the plains, when the body position of rats was changed to passive orthostatic, a decrease in systolic and diastolic pulmonary artery pressure was noted, and when the body position was changed to passive anti-orthostatic, an increase in pulmonary artery pressure was observed. The increase in pulmonary artery pressure was a compensatory mechanism due to the increased stiffness of the pulmonary vasculature. The practical significance of this research is to expand the understanding of the pathogenesis of pulmonary hypertension in high-altitude hypoxia.

Impact of modulating pulmonary artery pressure on resting right ventricular function in endurance-trained and untrained individuals

Prolonged endurance training is associated with critical adaptations to right ventricular (RV) structure and function that facilitate the achievement of higher exercise capacity, peak cardiac output, and RV stroke volume in the face of large increases in pulmonary artery pressures (afterload) and RV wall stress. Compared to the left ventricle, the RV is more sensitive to increases in afterload during exercise. However, the independent effect of increased afterload on RV function in endurance trained (Trained) vs untrained individuals remain unknown. Trained were considered those with a maximal oxygen consumption ( V̇O2max) &gt;60ml/kg/min (male) or &gt;55ml/kg/min (female) while untrained were defined as V̇O2max &lt;45ml/kg/min. Using echocardiography, this retrospective study sought to evaluate RV systolic function (RV global longitudinal strain [GLS]) and ventriculo-arterial coupling (ratio of RV GLS to pulmonary artery systolic pressure [PASP]) in Trained and untrained individuals while manipulating PASP. Ten participants (5 Trained and 5 Untrained) underwent resting echocardiography while breathing moderate (pressure of inspired oxygen; PiO2=89 mmHg) and severe hypoxia (PiO2=79 mmHg; order randomized) to increase PASP. Separately, eight participants (4 Trained and 4 untrained) inhaled nitric oxide (iNO; 40ppm) during echocardiography to lower PASP. Moderate and severe hypoxia increased PASP by 2.3 ± 1.3mmHg and 3.5 ± 1.8mmHg, respectively, while iNO decreased PASP by 2.6 ± 2.4mmHg, with no between group differences observed. Cardiac output was not different between any condition. A fitness-by-hypoxia interaction was observed in RV GLS in moderate hypoxia suggesting Trained had lower RV function during moderate hypoxia as compared to untrained (Untrained: -23.1 ± 4.4% vs. Trained: -20.2 ± 2.7%; p&lt;0.01). No differences in RV GLS were observed with iNO (p=0.98). The ratio of RV GLS to PASP was significantly different between groups at moderate hypoxia (Untrained: -1.06 ± 0.09%/mmHg vs. Trained: -0.85 ± 0.12%/mmHg; p=0.04) but not severe hypoxia (p=0.78). These findings suggest reducing PASP did not alter RV function or ventriculo-arterial coupling, however, Trained individuals experienced differential RV function responses when PASP is experimentally increased with hypoxia. Natural Sciences and Engineering Research Council of Canada. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Persistent iatrogenic atrial septal defect after cryoballoon ablation for atrial fibrillation

Aims: Pulmonary vein isolation (PVI) by cryoballoon ablation (CB) technology is effective and safe treatment option for atrial fibrillation (AF). CB is performed by large diameter, 15Fr (4.95mm) transseptal sheath that may lead to creation of iatrogenic atrial septal defect (iASD). The objective of this study was to assess the incidence of iASD in patients who had undergone CB. Methods: Patients with AF having undergone Arctic Front® CB ablation and a subsequent transesophageal echocardiography (TEE) examination during post-ablation follow up period were consecutively enrolled. During all CB procedures, 15Fr transseptal sheath (Flex Cath, Medtronic, Minneapolis, MN) was utilized via single transseptal puncture (TsP). Results: Twenty-eight patients (15 females, mean age 55.8+15.5) with paroxysmal (n=24) or persistent (n=4) AF formed study group. iASD was present 11 (39.3%) of them after mean follow-up time of 17.3+6.2 months. The procedural time is significantly longer in patient with iASD (119.0+8.8 minutes, p=0.01). No patients died or suffered from any clinically significant cerebral ischemic event. There was no sign of increase in systolic pulmonary arterial pressure (sPAP). Conclusion: iASD after CB was found to be present in 39.3% of patient during a mean follow-up time of 17.3+6.2 months. The prolonged CB procedural time was the only factor that predicted iASD in our study. No adverse clinic events that might be related to iASD was observed during follow-up period.

Management of Pregnant Women with Atrial Septal Defect and Pulmonary Hypertension: A Case Report

Background: Pulmonary Hypertension (PH) is a condition where there is an increase in Pulmonary Vascular Resistance (PVR) and an increase in the mean Pulmonary Arterial Pressure (mPAP) to more than 20 mmHg. PH can occur in someone with Congenital Heart Disease (CHD). PH conditions can aggravate pregnancy in women with CHD. Women with PH are recommended not to undergo pregnancy. However, it is possible for women with CHD with PH conditions to undergo pregnancy. In these conditions, optimizing PH therapy is essential so that pregnant women with PH do not experience a worsening of the condition and can carry out their pregnancy well until delivery. Case presentation: A 38-year-old female patient with a history of Atrial Septal Defect-Pulmonary Hypertension came for common control to the cardiac clinic with the pregnancy condition of her 4th child, who was just discovered when she was six months pregnant. Since giving birth to her third child, the patient began complaining of being quickly tired when doing activities accompanied by swollen legs that disappeared with rest. The patient went to a cardiologist for an echocardiography examination and was diagnosed with Atrial Septal Defect (ASD)-Pulmonary Hypertension (PH). Since then, the patient has been routinely treated by a cardiologist with Pulmonary Hypertension drugs, including Phospodiesterase5 (PDE5) inhibitors (Sildenafil) and Prostacyclin Analogue (Dorner). The patient had done Transesophageal Echocardiography (TEE) with the results of ASD secundum suitable for closure by the device. Patients with Right Heart Catheterization (RHC) results, ASD secundum with PH High Flow High Resistance reactive to Vasoreactivity Test. Since the patient was found to be pregnant, the patient continued to use Sildenafil and discontinued the use of Dorner. The patient then continued treatment in a multidisciplinary team. Conclusion: Management of pregnant women with CHD and PH is essential because the condition of PH itself further aggravates the condition of pregnancy. Medical management for PH in pregnant women follows the guidelines for the safety of drugs in pregnancy so that the choice of therapy is crucially related to the goal of treatment to control the PH condition in the patient but still pay attention to safety in pregnancy conditions. Keyword: Congenital Heart Disease, Phosphodiesterase-5 (PDE-5)- Inhibitor, Prostacyclin Analogue, Pulmonary Hypertension.

Clinical Features and Multimodality Diagnostic Tools of Pulmonary Hypertension

Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure (mPAP) above normal (&gt; 20 mmHg) and an increase in pulmonary vascular resistance (pulmonary vascular resistance / PVR) above normal in resting settings. The pathophysiology of PH involves remodeling of the pulmonary vessels, from the main pulmonary arteries, lobar arteries, segmental arteries, distal arteries, pulmonary arterioles, capillaries to the postcapillary pulmonary veins. In general, the epidemiological figures for PH are not known with certainty. The United Kingdom reported a PH prevalence of 97 cases per one million people, with a female-to-male ratio of 1.8. The diagnostic strategy for PH focuses primarily on two issues. The primary objective is to improve the early detection of PH and expedite the transfer of patients at high risk for PAH, CTEPH, or other forms of severe PH to a PH center. The second objective is to identify the underlying disease, including left heart disease (Group 2 PH) and lung disease (Group 3 PH), as well as comorbidities, in order to assure proper classification, risk assessment, and therapy. The gold standard for detecting and categorizing pulmonary hypertension is right heart catheterization (RHC). Clinical scoring in the form of shortness of breath without any obvious cause accompanied by physical examination, ECG and Thorax X-ray images which depict an enlarged right heart have good specificity and sensitivity for the diagnosis of pulmonary hypertension in patients with congenital heart disease. A high right ventricular pressure, mean PAP, and BNP values during observation, as well as heart size on chest X-ray can be predictors of a poorer prognosis in this population. Keyword: Clinical Risk Scoring, Pulmonary Hypertension, Right Heart Catheterization.