Lower Pulmonary Artery Pressure Research Articles

Intervention control of aerobic exercise in maintaining quality of life and pulmonary hypertension in hemodialysis patients.

Pulmonary hypertension is a serious complication in the treatment of maintenance hemodialysis patients, which seriously affects the quality of life of patients and threatens their life safety. Prevention, treatment and improvement of pulmonary hypertension are of great significance to improve the quality of life of patients. To investigate the intervention and control of pedal-powered bicycle in maintaining quality of life and pulmonary hypertension in hemodialysis patients. 73 patients with maintenance hemadialysis combined with pulmonary arterial hypertension at a hemodialysis center in a certain hospital from May 2021 to May 2022 are selected. Patients are divided into two groups, 37 cases in the control group (group C) and 36 cases in the intervention group (group I). Patients are divided into two groups, group C is treated with oral administration of betaglandin sodium combined with routine nursing care. Based on group C, group I conducts power cycling exercises. After treatment, group I patients had higher muscle strength, 36-Item Short Form Health Survey scores, and Kidney Disease Targets Areas scores; The 6-minute walk distance test index level was higher and the Borg score was lower; The group I had lower systolic blood pressure, greater vital capacity, higher positive emotion, lower systolic pulmonary artery pressure index level, higher arterial partial oxygen pressure level, lower pulmonary vascular resistance index level, and higher blood oxygen saturation level [158.91 ± 11.89 vs 152.56 ± 12.81, 1795.01 ± 603.18 vs 1907.20 ± 574.15, 24.00 (22.00, 29.00) vs 24.00 (22.00, 28.00), P < 0.001]. Aerobic exercise combined with Western medicine treatment can effectively improve patients' pulmonary hypertension, alleviate their negative emotions, and enable them to achieve a higher level of quality of life.

The impact of cardiovascular and lung comorbidities in patients with pulmonary arterial hypertension: A systematic review and meta-analysis

BackgroundContemporary patients with pulmonary arterial hypertension (PAH) are older and exhibit cardiovascular and/or lung comorbidities. Such patients have typically been excluded from major PAH drug trials. This systematic review compares baseline characteristics, hemodynamic parameters, and mortality rate between PAH patients with significant number of comorbidities compared to those with fewer or no comorbidities. ΜethodsA systematic literature search in PubMed and Cochrane databases was conducted searching for studies comparing PAH patients with more than two cardiovascular comorbidities and/or at least a lung comorbidity against those with fewer comorbidities. ResultsSeven observational studies were included. PAH patients with comorbidities were older, with an almost equal female-to-male ratio, shorter 6-minute walk distance, higher NT-proBNP levels, and lower lung diffusion for carbon monoxide. In terms of hemodynamics, they had higher mean right atrial pressure and pulmonary artery wedge pressure, lower mean pulmonary arterial pressure, pulmonary vascular resistance and mixed venous oxygen saturation. Pooled analysis of six studies demonstrated a higher mortality risk for PAH patients with comorbidities compared to those without (HR 1.86, 95% CI 1.20 to 2.89, p<0.001, I²=92%), with the subgroup of PAH patients with lung comorbidities having an even higher mortality risk (test for subgroup differences: p<0.001). Combination drug therapy for PAH was less frequently used in patients with comorbidities. ConclusionsCardiovascular and lung comorbidities impact the clinical characteristics and outcomes of PAH patients, highlighting the need for optimal phenotyping and tailored management for this high-risk population.

Flow-activated endothelial Piezo1-Pannexin1-TRPV4 signaling is impaired in pulmonary hypertension

Pulmonary hypertension (PH) is a progressive and debilitating disease, characterized by elevated pulmonary arterial pressure (PAP), increased pulmonary artery (PA) contractility and endothelial cell (EC) dysfunction. Endothelial Ca2+ signals dilate resistance-size PAs (rPAs, ~ 50 μm O.D.) and maintain a low PAP. Impaired endothelial Ca2+ signaling mechanisms contribute to exacerbated rPA contraction and elevated PAP in PH. Studies in systemic arteries show that flow/shear stress (F/SS) activates endothelial Ca2+ signals to cause vasodilation. Although rPAs are a “high-flow” vascular bed, flow-induced endothelial Ca2+ signaling mechanisms have not been investigated in PH. In this regard, we recently showed that Ca2+ influx through endothelial transient receptor potential vanilloid 4 (TRPV4EC) ion channels dilates rPAs and lowers resting PAP (Daneva et al., PNAS, 2021). Moreover, F/SS activates the efflux of adenosine triphosphate (ATP, an endogenous vasodilator) through endothelial Pannexin 1 (Panx1EC) in rPAs (Daneva et al., eLife, 2021). Direct mechanosensitivity of Panx1 has been disputed, suggesting the need for an upstream endothelial mechanosensor that responds to increased flow. In this regard, pulmonary endothelial cells express Piezo1, a well-known mechanosensitive ion channel. Therefore, we hypothesized that endothelial Piezo1 (Piezo1EC)-Panx1EC-TRPV4EC signaling mediates flow-induced dilation (FID) of rPAs and regulates PAP. Cannulated and pressurized (15 mmHg) rPAs from inducible EC-specific Piezo1, Panx1 and TRPV4 mice did not dilate to incremental increases of F/SS (4 - 14 dynes/cm2) in comparison to wildtype mice, providing the first evidence that Piezo1EC-Panx1EC-TRPV4EC signaling is necessary for FID of rPAs. Confocal Ca2+ imaging studies in pressurized rPAs from mice expressing GCaMP8, a calcium biosensor, in ECs showed enhanced TRPV4EC sparklet activity (individual Ca2+ influx signals through TRPV4EC channels) in response to F/SS, demonstrating flow-induced activation of TRPV4EC channels in rPAs. Flow-induced TRPV4EC sparklet activity and FID were reduced in rPAs from a mouse model of PH (Sugen 5416 + chronic hypoxia or Su+CH; 4 weeks; 10% O2) when compared to normoxic control mice, suggesting impaired flow-induced endothelial signaling in PH. Bioluminescence measurements of extracellular ATP concentration showed lower baseline ATP levels in rPAs from Su+CH mice suggesting a decrease in ATP efflux in PH. Importantly, F/SS increased the efflux of ATP in rPAs from normal mice, but not in rPAs from Su+CH mice, indicating that F/SS-Panx1EC signaling is also impaired in PH. Together, these data support the idea that flow-induced Piezo1EC-Panx1EC-TRPV4EC signaling is impaired in PH. Future studies will assess the individual signaling linkages in the flow-induced Piezo1EC-Panx1EC-TRPV4EC signaling axis in PH. R01 HL146914, R01 HL157407, R01 HL167208 to SKS; APS Postdoctoral Fellowship to ZD. 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.

Effects of SGLT2 inhibitors on right ventricular function in heart failure patients: Updated meta-analysis of the current literature.

There is some discrepancy in current studies concerning the effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on right ventricular (RV) functions in heart failure (HF) patients. Hence, this meta-analysis was focused on determining the impact of SGLT2i on RV functions in such individuals. Two independent investigators searched PubMed, Google Scholar, and the Cochrane Library for articles of interest. To analyze heterogeneity, Higgins' I2 as well as prediction intervals and Egger's test were used to assess heterogeneity. The Newcastle-Ottawa standard ratings approach was used to assess the quality of observational studies. The ROBINS-I risk of bias algorithm was used to assess bias risks of randomized studies. This meta-analysis evaluated 8 studies in total. Over the follow-up time frame, patients who used SGLT2i had substantially lower systolic pulmonary artery pressure and higher tricuspid annular plane systolic excursion values (mean difference [MD] = -5.23 [-7.81; -2.66] and, MD = 1.47 [1.01; 1.93]; P <0.01, respectively). There was no significant difference in RVS' values between follow-up and baseline (MD = 1.54 [-0.19; 3.26]; P = 0.08). However, as compared to the baseline period, fractional area contraction values were substantially larger at the end of the follow-up (MD = 5.52 [4.23; 6.82]; P <0.01). To the best of our knowledge, this is the first meta-analysis assessing the impact of SGLT2i on RV function in HF patients. Our findings suggest that SGLT2i may improve RV performance in HF patients.

Insights Into Differences in Pulmonary Hemodynamics in Hispanic Patients With Pulmonary Arterial Hypertension.

Emerging data suggest that Hispanic patients with pulmonary arterial hypertension (PAH) exhibit improved survival rates compared to individuals of other ethnicities with similar baseline hemodynamics. However, the underlying reasons for this survival advantage remain unclear. This study focused on comparing pulmonary hemodynamics in Hispanic and non-Hispanic PAH patients and how these differences may contribute to varied clinical outcomes. A retrospective analysis of right heart catheterization data was conducted on a treatment-naive PAH patient cohort from a single center. Over a 10-year period, a total of 226 PAH patients were identified, of which 138 (61%) were Hispanic and 88 (39%) were non-Hispanic. Hispanic patients presented with lower pulmonary artery pressures, lower pulmonary vascular resistance, and exhibited significantly higher pulmonary arterial compliance (PAc). Hispanic patients had better 5-year survival rates. This study highlights the importance of exploring phenotypic differences in ethnically diverse PAH cohorts.

Exercise capacity-hemodynamics mismatch in elderly patients with pulmonary hypertension: A nationwide multicenter study from Taiwan Society of Cardiology Pulmonary Hypertension Registry (TAIPANS)

BackgroundDemographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. MethodsThis multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45–65 years, and >65 years). ResultsThe mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45–65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45–65: 14.5, >65: 31.6 %; p < 0.0001) than young patients. Elderly patients had shorter 6-min walking distance (6 MWD) (≤45 vs. >65, mean difference, 77.8 m [95% confidence interval (CI), 2.1–153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37–15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45–65, mean difference, −2.1 mmHg [95% CI, −3.9 to −0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45–65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. ConclusionsElderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.

Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis.

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.

Modifiers of the Association between E/e' Ratio and Survival among Patients with No Apparent Structural or Functional Cardiac Abnormality

BackgroundThe ratio between early mitral flow wave to early diastolic mitral annulus velocity (E/e’ ratio) varies according to age and sex and is associated with mortality in heart failure. We sought to describe the association between E/e’ and mortality in patients with no apparent structural or functional cardiac abnormality and explore possible modifiers of this association. MethodsA retrospective study of 104,315 patients who underwent echocardiographic evaluation during 2009-2021 in the largest tertiary center in Israel. Patients with cancer, ventricular dysfunction, significant valvular or structural heart disease, or evidence of pulmonary hypertension were excluded. ResultsThe final analysis included 32,836 patients with a median age of 56 (43-66) years, and 13,547 (41%) were female. The median E/e’ was 8.3 (6.8-10.3), and 9,306 (28%) had an E/e’ >10. During a median follow-up of 5.7 (3.3-8.5) years, 2,396 (7.3%) individuals died. E/e’ >10 was associated with mortality (adjusted hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.07-1.27, p<0.001). The mortality risk associated with E/e’ >10 was significantly higher in those aged ≤70 (HR 1.26, 95% CI 1.12-1.42, p<0.001), males (HR 1.34, 95% CI 1.19-1.49, p<0.001), a normal left ventricular mass (HR 1.13, 95% CI 1.02-1.24, p = 0.017), and pulmonary artery pressure <30 mmHg (HR 1.18, 95% CI 1.06-1.30, p = 0.003). ConclusionAn elevated E/e’ is associated with mortality, specifically in younger individuals, males, and those with a normal left ventricular mass and lower pulmonary artery pressure. This suggests that an elevated E/e’ might be a marker of subclinical risk in these subgroups. Further studies are needed to identify whether an elevated E/e' is useful in shared decision-making regarding the management of cardiovascular risk factors.

Abnormalities of Coagulation and Fibrinolysis Assessed by Thromboelastometry in an Endotoxic Shock Model in Piglets Treated with Nitric Oxide and Hydrocortisone.

This is an animal model study to investigate changes in hemostasis during endotoxemic shock and to determine whether the combination of inhaled nitric oxide (iNO) + intravenous hydrocortisone had an effect on clot formation and fibrinolysis. iNO selectively decreases pulmonary artery pressure, without affecting cardiac index or systemic vascular resistance; however, the results of studies on the possible consequences of iNO administration on coagulation are inconsistent and require further research. Thirty-four piglets were included. Administering endotoxin caused severe hypodynamic shock. Half of the animals received iNO (30 ppm) + hydrocortisone, starting 3 h after endotoxin infusion and continuing to the end of the study. All animals developed coagulation disorders, manifested by a tendency to hypocoagulation; at the same time, fibrinolysis was impaired. Coagulation and fibrinolysis disorders persisted after endotoxin infusion was discontinued, with worse severity in the animals that died before the study was terminated. Administering iNO + hydrocortisone did not cause further changes in coagulation and fibrinolysis parameters, either during or after the endotoxin challenge, suggesting that potential therapeutic interventions with iNO to lower pulmonary arterial pressure will not affect hemostasis.

Echo-derived hemodynamic categorization for risk stratification in transthyretin cardiac amyloidosis

Abstract Background Transthyretin cardiac amyloidosis (TTR-CA) is a rare disease characterized by the deposition of abnormal proteins in the heart, which can lead to heart failure (HF) and death. Echocardiography provides valuable diagnostic and prognostic information in CA, but indices of left ventricular performance alone cannot thoroughly characterise patients with restrictive cardiomyopathy. Evaluating the hemodynamic profile by studying the forward flow and left ventricular filling pressure (LVFP) already proved its value in stratifying disease severity in patients with heart failure (HF). Purpose This study evaluated the prognostic relevance of a non-invasive hemodynamic categorization of TTR-CA patients based on the estimation of stroke volume index (SVi) and systolic pulmonary artery pressure (PAPs). Methods Baseline clinical, transthoracic echocardiogram and laboratory data were collected prospectively in patients with diagnosed TTR-CA. Patients were classified into four groups based on forward flow (SVi &amp;lt; or ≥30 ml/m2) and systolic pulmonary artery pressure (PAPs ≥ or &amp;lt;40 mmHg). The four profiles obtained were Profile-A, normal-flow, normal-pressure; Profile-B, low-flow, normal-pressure; Profile-C, normal-flow, high-pressure; Profile-D, low-flow, high-pressure. We assessed the incidence of the composite endpoint of cardiovascular death and HF hospitalization accordingly to the hemodynamic profile. We performed univariate and multivariate Cox regression using profile A as a reference for HR estimation (profile A corresponding to HR=1). Results Fifty-nine patients were enrolled in the analysis (Table). Over a mean follow-up of 35.9 months (IQR 11.7 - 51.2 months) 23 patients met the composite endpoint (10%, 23%, 43%, 60% for Profile A, B, C and D respectively). Compared to Profile A, Profile D showed the greatest risk of CV mortality and HF hospitalization (HR 10.17), followed by Profile C (HR 6.77) and B (HR 3.45), with P-value=0.015. The C-statistic for the model was 0.72. Kaplan-Meier curves confirmed that patients with PAPs &amp;gt;40 mmHg and SVi&amp;lt; 30 ml/m2 presented the highest risk of the composite endpoint (Log-rank P = 0.010) (Figure). Hemodynamic profiling remained an independent predictor of outcome even after adjusting for the NAC stage (Profile B, HR 2.26; Profile C, HR 6.96; Profile D, HR 17.13; P-value=0.0012). Conclusions The proposed echocardiographically-derived hemodynamic classification based on forward-flow and LVFP estimation is useful for TTR-CA patients risk stratification. Patients with low SVi and high PAPs have the greatest risk of CV death and HF hospitalization, even after adjustment for NAC stage. These findings highlight the importance of early detection and monitoring of hemodynamic changes in TTR-CA patients for tailored management and to improve outcomes.Table.Figure.

129 The Relationship Between Pulmonary Arterial Pressure Expected Progeny Differences and Methane Emissions

Abstract The objective of this study was to determine the relationship between pulmonary arterial pressure (PAP) expected progeny differences (EPD) and methane emissions. Pulmonary arterial pressure is an indicator of pulmonary arterial hypertension in cattle and is especially relevant at high altitudes, with increasing importance in moderate elevation feedlot and finishing systems. Enteric methane emissions from cattle are increasingly emphasized due to their contribution of greenhouse gases in the agricultural sector. As pulmonary arterial hypertension continues to be an issue in high altitudes and feedlots, understanding relationships with methane emission rates will be useful for both concomitant selection with the goal of improving environmental sustainability. The PAP EPD data were collected on 123 total heifers (n = 37) and steers (n = 86) located on a ranch in southern Wyoming at an elevation of 2,194.56 meters. Gas emissions were collected using a GreenFeed system (C-Lock, Rapid City, South Dakota), which measures the gas fluxes of individual animals at the CSU ARDEC facility at an elevation of 1,557.53 meters. Individual animal methane emissions were measured as grams/day. A generalized linear regression model was used to regress average daily methane emissions (mean = 163.08, SD = 38.74, min = 87.72, max = 247.03) on PAP EPD (mean = -0.464, SD = 1.565, min = -6.382, max = 4.286), pen, and age in days (mean = 258.2, SD = 20.009, min = 200, max = 298). The PAP EPD (P = 0.484) did not account for a significant amount of variation in methane emissions. Additionally, the effect of pen (P &amp;lt; 0.05) and age (P &amp;lt; 0.05) were significant sources of variation for methane production. The effects of pen had a range of 60.916 units of methane emission/day (P &amp;lt; 0.05). Age of the individual was evaluated as a linear covariate and had a solution of 0.678 units of methane emission/day (P &amp;lt; 0.05), suggesting that older individuals had increased methane emissions. These results show no statistical relationship between PAP EPD and methane in these data. While preliminary results suggest that selection for low PAP EPD individuals will have no adverse effects on sustainability metrics, future research is needed to fully understand the relationship between beef cattle production traits and sustainability metrics.

Clinical and Hemodynamic Improvement in Pulmonary Hypertension After Switching to Sacubitril/Valsartan in Patients With Heart Failure With Preserved Ejection Fraction.

Patients with heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension have poor survival, and established medical therapies for both conditions are not available. In this retrospective study of 69 patients with HFpEF and either isolated postcapillary pulmonary hypertension (IpcPH, n = 53) or combined postcapillary and precapillary pulmonary hypertension (CpcPH, n = 16), we investigated the effects of sacubitril/valsartan on pulmonary hypertension measured using right heart catheterization at baseline (ie, presacubitril/valsartan) and 99 (94-123) days after switching to sacubitril/valsartan. After switching to sacubitril/valsartan, right heart catheterization showed significantly lower pulmonary artery pressures (systolic/diastolic/mean) in both patient groups compared with presacubitril/valsartan [IpcPH: 44 (38-52)/15 (12-19)/28 (22-33) mm Hg vs. 47 (40-55)/18 (15-23)/31 (26-35) mm Hg, P < 0.01; CpcPH: 54 (43-57)/18 (12-23)/34 (30-36) mm Hg vs. 61 (50-79)/24 (19-30)/40 (31-53) mm Hg, P < 0.05]. The median sacubitril/valsartan dose at follow-up was 24/26 (24/26-49/51) mg twice daily in both patients with IpcPH and CpcPH. Clinically, the New York Heart Association functional class improved by at least 1 class in 32 of 69 patients ( P < 0.01). In conclusion, sacubitril/valsartan therapy improves pulmonary hypertension in patients with HFpEF and either IpcPH or CpcPH. Further prospective randomized trials are needed for confirmation of our results.

#5203 THE INCESSANT QUEST FOR DRY WEIGHT: SHOULD WE ADOPT NEW STRATEGIES?

Abstract Background and Aims The estimate of the hydration state in the chronic hemodialysis patient is a key point of his care. Currently, there is no Gold Standard feasable in daily routine despite the increasingly numerous tools such as impedancemetry and pulmonary cardiac ultrasound. The objective of our study is to compare the results of the clinical estimation of dry weight with the results of impedancemetry and cardiac ultrasound results. Method This is a transverse study in the dialysis unit of Taher Sfar Mahdia hospital. The estimation of the hydration state was assessed before and after the hemodialysis session by the three above methods. The volume evaluation was carried out by a clinical score (NYHA&amp;gt; III dyspnea, orthopnee; jugular turgor (TJ), hepato-jugular reflux (HRJ), crackling in auscultation, peripheral edema and pre-dialysis hypertension); as well as by cardiac ultrasound (diameter of the lower vein, E/E ratio and systolic pulmonary arterial pressures). Results The values ​​measured by the different techniques decreased significantly after the hemodialysis session (p &amp;lt;0.001). At the two -stroke studied, we have objectified a significant correlation between the results of the impedancemetry, the index of the lower vein and its compliance. A significant difference between the results provided by the techniques studied and the results of the clinical evaluation was found in 64 % of patients. Only the orthopnee (p = 0.03) and the hepato-jugular reflux (p = 0.04) were significantly associated with the ultrasound overload diagnosis. Conclusion The existence of a difference between the subjective and objective target weight suggests the incessant need for a mixture between the different techniques evaluated. Our strategy requires to be adapted to the particularities of each patient.

Endothelial IK and SK channel activation decreases pulmonary arterial pressure and vascular remodeling in pulmonary hypertension.

Endothelial cells (ECs) from small pulmonary arteries (PAs) release nitric oxide (NO) and prostacyclin, which lower pulmonary arterial pressure (PAP). In pulmonary hypertension (PH), the levels of endothelium-derived NO and prostacyclin are reduced, contributing to elevated PAP. Small-and intermediate-conductance Ca2+-activated K+ channels (IK and SK)-additional crucial endothelial mediators of vasodilation-are also present in small PAs, but their function has not been investigated in PH. We hypothesized that endothelial IK and SK channels can be targeted to lower PAP in PH. Whole-cell patch-clamp experiments showed functional IK and SK channels in ECs, but not smooth muscle cells, from small PAs. Using a SU5416 plus chronic hypoxia (Su + CH) mouse model of PH, we found that currents through EC IK and SK channels were unchanged compared with those from normal mice. Moreover, IK/SK channel-mediated dilation of small PAs was preserved in Su + CH mice. Consistent with previous reports, endothelial NO levels and NO-mediated dilation were reduced in small PAs from Su + CH mice. Notably, acute treatment with IK/SK channel activators decreased PAP in Su + CH mice but not in normal mice. Further, chronic activation of IK/SK channels decreased PA remodeling and right ventricular hypertrophy, which are pathological hallmarks of PH, in Su + CH mice. Collectively, our data provide the first evidence that, unlike endothelial NO release, IK/SK channel activity is not altered in PH. Our results also demonstrate proof of principle that IK/SK channel activation can be used as a strategy for lowering PAP in PH.

Clinicopathological Correlation of Chronic Thromboembolic Pulmonary Hypertension: A Retrospective Study.

The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. Although pulmonary endarterectomy (PEA) is potentially curative, inoperable patients and persistent pulmonary hypertension (PH) following surgery remain a significant problem. In this study, we aim to describe the histopathological characteristics of CTEPH and explore the potential relationship between pulmonary arterial lesions, radiological parameters, and clinical manifestations. Endarterectomized tissues from 81 consecutive patients of CTEPH were carefully collected, sectioned, and examined by experienced pathologists. Pertinent clinical and radiological data were obtained from medical records and operative reports. Neointima, fresh/organized thrombi, recanalized regions, and atherosclerotic lesions were microscopically examined as previously described. Thrombi and atherosclerosis were dominant in UCSD classification level I PEA materials, while recanalized neo-vessels were more frequently observed in UCSD classification level III cases. Degenerative changes of the extracellular matrix were also noticed in the vascular bed. Atherosclerotic lesions were more frequently observed in cases with higher ratio of the pulmonary artery diameter to ascending aorta diameter (PA/AA) reflected by computed tomographic pulmonary arterial scanning. Furthermore, the removal of pulmonary artery complex lesions (with the combination of three to four types of lesions) by PEA was associated with lower postoperative mean pulmonary arterial pressure (mPAP) and decreased incidences of persistent PH. Our study demonstrates that the histopathological features of CTEPH are strongly linked with clinical manifestations and the postoperative outcome after PEA. These data may provide possible evidence for further studies in searching for appropriate causal factors underlying this disease.

Abstract 14039: The Cardioprotective and Anti-Inflammatory Effect of Inhaled Nitric Oxide During Fontan Surgery: A Prospective Randomized Study

Introduction: Open heart surgery that requires cardiopulmonary by-pass (CPB) evokes tremendous stress and inflammatory responses, affecting postoperative organ function, morbidity, and mortality. Although part of this reaction triggers protective and anti-inflammatory phenomena, it is harmful, particularly in patients with single ventricle congenital heart defects during Fontan surgery. Unfortunately, there is no perfect anti-inflammatory and stress defence strategy despite decades of research. Hypothesis: This study aimed to investigate the influence of nitric oxide (NO) inhaled directly into the oxygenator during CPB on a proteome profile of inflammatory cytokines, metabolic response markers, heart and lung protection indicators, and the early clinical outcomes. Methods: The study involved 115 patients randomized to the Fontan-NO group, receiving NO inhalation (n=48) and the Fontan group, not receiving NO (n=49). Eighteen patients were excluded from the study. The clinical data were prospectively analyzed. Proteome profiler essays were used for repeated measurements of investigated analytes. Results: Fontan-NO patients had significantly lower levels of lactate (p=0.04) and glucose (p=0.02), lower pulmonary artery pressure (p=0.03) and catecholamine index (p=0.042), shorter ventilatory support time (p=0.03) and ICU stay (p=0.04). Plasma factors analysis has shown a significantly higher concentration of interleukin-10, tissue inhibitor of metalloproteinase, prolactin, and angiopoietin and a lower concentration of interleukin-6, interleukin-8, interleukin-1β, granulocyte-macrophage colony-stimulating factor, pentraxin, matrix metalloproteinase-8, troponin-I, CK-MB, and insulin in Fontan-NO group. Multiple regression analysis revealed the influence of Il-6 and Il-8 on respiratory support time and ICU stay and the relationship between catecholamine index, duration of effusions, and indicators of myocardial damage. Conclusions: NO inhaled into the oxygenator during CPB can alleviate the inflammatory response, improve myocardial and lung protection, and reduce metabolic stress in patients with a single ventricle undergoing Fontan surgery. The observed effects can influence short-term clinical outcomes.

7 Evaluation of Finishing Performance and Carcass Characteristics of Beef Heifers with Variable Degrees of Heart Failure Risk and Differing Reproductive Tract Type

Abstract Tremendous economic loss is attributed to high altitude disease mortality of calves in the Mountain West and Great Plains region. Additional economic losses may be associated with changes in feed efficiency and carcass quality in animals at higher risk of heart failure during the finishing phase. Thus, the objective of the current study is to evaluate economically relevant traits throughout the finishing period to determine inefficiencies associated with variable levels of heart failure risk and reproductive tract type of beef heifers. Both intact reproductive tract (n = 19) and ovariectomized (n = 18) heifers were stratified by risk category, where initial pulmonary arterial pressure (PAP) levels at or below 42 mmHg were designated as low risk and those above 42 mmHg as moderate/high risk. Heifers were fed a grain-based diet for 125 d before transportation to the harvest facility on d 126. All heifers were weighed in 2 wk intervals. Heifers were PAP tested by a qualified veterinarian in approximately 3 mo intervals during the feeding period. Feed intake data was collected for the last 55 d prior to harvest using the Vytelle SENSETM bunk system. Time of harvest was determined based on live weight and final ultrasound 12th rib fat thickness. Data were analyzed using the ANOVA function of R with tract type and risk as fixed effects. Comparisons were tested using a significance level of α = 0.05 and 0.05 (P ≤ 0.10) were considered tendencies. There were no interactions of risk category and tract type on performance or carcass characteristics (P ≥ 0.14). There was a tendency for higher total intake (P = 0.07) and relative growth rate (P = 0.04) among moderate/high risk heifers compared to the low-risk category. Hot carcass weight, marbling score, ribeye area, and USDA yield grade were not impacted (P ≥ 0.16) by risk category. Intact heifers had greater (P = 0.02) total gain than their ovariectomized contemporaries. However, marbling scores were higher (P = 0.04) among ovariectomized heifers compared to those from intact heifers. These data suggest that risk category and tract type minimally influence performance and carcass characteristics in a population that selects sires with low PAP scores. It remains unclear if more initial divergence in PAP scores would elicit greater impacts on performance and carcass characteristics in feedlot heifers.

Safety and efficacy of pulse-induced contour cardiac output monitoring in elderly patients with coronary artery disease and severe heart failure at coronary care units

The optimal treatment for elderly patients with severe heart failure depends on the accurate assessment of their hemodynamic status. Due to its less invasive nature, the safety and efficacy of invasive pulse-induced contour cardiac output (PiCCO)-based hemodynamic monitoring remains uncertain. This was a prospective observational study. Between January 2016 and July 2020, 190 elderly patients with severe heart failure were consecutively enrolled. The PiCCO group (89 patients) and non-invasive hemodynamic monitoring group (101 patients) were observed. Hospital stays results were evaluated. No significant difference in clinical data (P > 0.05) or the incidence of 1-month mortality (16.0 vs. 35.0%, P = 0.141) were observed between groups. The coronary care unit (CCU) stay was shorter in the PiCCO group than in the non-invasive group (40.0 vs. 43.0%, P = 0.049). Indicators such as low Extravascular Lung Water Index (EVLWI), high Body Mass Index (BMI), low Pulmonary Artery Pressure (PAP), and high Left Ventricular Ejection Time (LVET), were associated with favorable clinical results. Early invasive PiCCO monitoring is safe in critically ill elderly patients with severe heart failure. The hospital stay was reduced using PiCCO monitoring. These encouraging PiCCO results favor its use in elderly patients with severe heart failure at CCUs.

The cardioprotective and anti-inflammatory effect of inhaled nitric oxide during Fontan surgery in patients with single ventricle congenital heart defects: a prospective randomized study

BackgroundFontan surgery with cardiopulmonary bypass (CPB) causes tremendous systemic stress and inflammatory responses, affecting postoperative organ function, morbidity, and mortality. Although this reaction triggers partially protective anti-inflammatory responses, it is harmful in patients with single ventricle congenital heart defects. Despite decades of research, an effective anti-inflammatory and stress defense strategy is lacking. This study investigated the influence of inhaled nitric oxide (NO) during CPB on early clinical results, including the duration of postoperative respiratory support as a primary outcome and a panel of laboratory analytes.MethodsIn this study, 115 patients were randomized to the Fontan-NO group (n = 48) and the Fontan group (n = 49). Eighteen patients were excluded from the study. The Fontan-NO group received NO inhaled directly into the oxygenator during CPB. Clinical data were collected, and blood samples were drawn for analysis at repeated intervals. Multiplex assays were used to analyze a proteome profile of molecules involved in stress response, inflammation, metabolic reactions, as well as heart and lung protection.ResultsFontan-NO patients had significantly shorter respiratory support time with a median of 9.3 h (7.0; 13,2) vs 13.9 h (3.7; 18.5) by the absolute difference of 4.6 h [95% confidence interval, − 30.9 to 12.3; (p = 0.03)]. In addition, they have a shorter time in intensive care (p = 0.04) and lower pulmonary artery pressure after CPB discontinuation (p = 0.04), 4 h (p = 0.03) and 8 h (p = 0.03) after surgery. Fontan-NO patients also had a lower concentration of lactates (p = 0.04) and glucose after separation from CPB (p = 0.02) and lower catecholamine index (p = 0.042). Plasma factors analysis has shown a significantly higher concentration of interleukin-10, and a lower concentration of interleukin-6, interleukin-8, interleukin-1β, pentraxin, matrix metalloproteinase-8, troponin-I, creatine kinase myocardial band (CK-MB), and insulin in Fontan-NO group.ConclusionsNO inhaled into the oxygenator during CPB can improve short-term clinical outcomes. It shortens intubation time and intensive care time. It reduces inflammatory response, improves myocardial and lung protection, and diminishes metabolic stress in patients with a single ventricle undergoing Fontan surgery.Trial registration number: The trial was preregistered, supervised, and supported by The Polish National Science Center (NCN/01/B/NZ5/04246).

Reduction of Atrial Septal Defect Size After Catheter Ablation for Atrial Tachyarrhythmia and Its Predictive Factors

<h2>Abstract</h2> The prevalence of atrial tachyarrhythmia is high in patients with atrial septal defect (ASD), and catheter ablation (CA) is often performed before percutaneous ASD closure. We aimed to clarify the effect of CA on the ASD size. We analysed 16 patients with secundum ASD who had a history of CA for atrial tachyarrhythmia and underwent ASD size evaluation before and after CA. The size of ASD significantly decreased after CA. Younger age and lower tricuspid regurgitation pressure gradients and pulmonary arterial systolic pressures were associated with size reduction. These factors are crucial for making strategies of percutaneous ASD closure.