Mean Pulmonary Artery Pressure Values Research Articles

The acute effect of inhaled nitric oxide on the exercise capacity of patients with advanced interstitial lung disease: a randomized controlled trial

BackgroundInhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease.MethodsIn a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension.ResultsOverall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33).ConclusionIn patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects.Trial registration(NCT03873298, MOH_2018-04-24_002331).

Exploring the impacts of fescue toxicosis on the pulmonary arterial pressure of angus cows.

Vasoconstriction of peripheral blood vessels is one of the hallmark symptoms of fescue toxicosis in cattle. Thus, it was hypothesized that exposure to ergot alkaloids would increase the pulmonary arterial pressure (PAP). The objectives of this study were to examine the relationship between PAP and different physiological parameters of cows grazing either endophyte-infected (EI) or novel-endophyte (EN) fescue, then evaluate changes in PAP and other physiological measurements in cows exposed to EI pastures and deemed as susceptible or tolerant based on animal performance. Pregnant Angus cows at 2 different locations grazed either EI or EN fescue pastures for 14 consecutive weeks starting in early April of 2022. Forage measurements were collected to assess ergot alkaloid exposure throughout the study. In addition to measuring PAP, weekly measurements and blood samples were collected to evaluate physiological responses to ergot alkaloid consumption. The Fescue Toxicosis Selection Method (FTSM) was used for a post hoc analysis to identify cattle as either tolerant (EI-TOL) or susceptible (EI-SUS) when challenged with ergot alkaloid exposure. Data were analyzed using a MIXED procedure of SAS with repeated measures. Cows grazing on EN pastures had greater mean PAP values than EI cows, (P < 0.01), whereas a location effect was identified when comparing both EI-TOL and EI-SUS groups (P < 0.01). Cows exposed to EN pastures had greater average daily gain (ADG) (P = 0.04) and progesterone (P4) concentrations (P < 0.01), and lower hair shedding scores (HSS; P < 0.01) than EI cows. The EI-TOL cows tended to have greater final body weight, ADG and had lower HSS (P < 0.01) than EI-SUS cows. While cattle consuming EI tall fescue exhibited classical physiological changes, the decrease in PAP of cattle consuming EI fescue was unexpected and contradicted the initial hypothesis. Furthermore, the FTSM provides a means to identify animals with superior performance in spite of the chronic exposure to ergot alkaloids. Continued investigations examining the interaction between ergot alkaloid exposure and cardiovascular parameters will lead to a fuller understanding of the disease and are pivotal for developing innovative strategies that enhance best management practices to help guarantee the sustainability of the U.S. beef industry.

Gut Dysbiosis and Hemodynamic Changes as Links of the Pathogenesis of Complications of Cirrhosis.

The aim was to evaluate the relationship between gut dysbiosis and hemodynamic changes (hyperdynamic circulation) in cirrhosis, and between hemodynamic changes and complications of this disease. This study included 47 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Echocardiography with a simultaneous assessment of blood pressure and heart rate was performed to assess systemic hemodynamics. Patients with hyperdynamic circulation had more severe cirrhosis, lower albumin, sodium and prothrombin levels, higher C-reactive protein, aspartate aminotransferase and total bilirubin levels, and higher incidences of portopulmonary hypertension, ascites, overt hepatic encephalopathy, hypoalbuminemia, hypoprothrombinemia, systemic inflammation, and severe hyperbilirubinemia than patients with normodynamic circulation. Patients with hyperdynamic circulation compared with those with normodynamic circulation had increased abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Fusobacteria, Micrococcaceae, Intestinobacter, Clostridium sensu stricto, Proteus and Rumicoccus, and decreased abundance of Bacteroidetes, Bacteroidaceae, Holdemanella, and Butyrivibrio. The systemic vascular resistance and cardiac output values correlated with the abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Micrococcaceae, and Fusobacteria. Heart rate and cardiac output value were negatively correlated with the abundance of Bacteroidetes. The mean pulmonary artery pressure value was positively correlated with the abundance of Proteobacteria and Micrococcaceae, and negatively with the abundance of Holdemanella.

Pulmonary Vasodilator Response of Combined Inhaled Epoprostenol and Inhaled Milrinone in Cardiac Surgical Patients.

Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. Intraoperative management of patients at high risk of RV failure should aim to reduce RV afterload and optimize RV filling pressures, while avoiding systemic hypotension, to facilitate weaning from cardiopulmonary bypass (CPB). Inhaled epoprostenol and inhaled milrinone (iE&iM) administered in combination before CPB may represent an effective strategy to facilitate separation from CPB and reduce requirements for intravenous inotropes during cardiac surgery. Our primary objective was to report the rate of positive pulmonary vasodilator response to iE&iM and, second, how it relates to perioperative outcomes in cardiac surgery. This is a retrospective cohort study of consecutive patients with PH or RV dysfunction undergoing on-pump cardiac surgery at the Montreal Heart Institute from July 2013 to December 2018 (n = 128). iE&iM treatment was administered using an ultrasonic mesh nebulizer before the initiation of CPB. Demographic and baseline clinical data, as well as hemodynamic, intraoperative, and echocardiographic data, were collected using electronic records. An increase of 20% in the mean arterial pressure (MAP) to mean pulmonary artery pressure (MPAP) ratio was used to indicate a positive response to iE&iM. In this cohort, 77.3% of patients were responders to iE&iM treatment. Baseline systolic pulmonary artery pressure (SPAP) (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.24-2.16 per 5 mm Hg; P = .0006) was found to be a predictor of pulmonary vasodilator response, while a European System for Cardiac Operative Risk Evaluation (EuroSCORE II) score >6.5% was a predictor of nonresponse to treatment (≤6.5% vs >6.5% [reference]: OR, 5.19; 95% CI, 1.84-14.66; P = .002). Severity of PH was associated with a positive response to treatment, where a higher proportion of responders had MPAP values >30 mm Hg (42.4% responders vs 24.1% nonresponders; P = .0237) and SPAP values >55 mm Hg (17.2% vs 3.4%; P = .0037). Easier separation from CPB was also associated with response to iE&iM treatment (69.7% vs 58.6%; P = .0181). A higher proportion of nonresponders had a very difficult separation from CPB and required intravenous inotropic drug support compared to responders, for whom easy separation from CPB was more frequent. Use of intravenous inotropes after CPB was lower in responders to treatment (8.1% vs 27.6%; P = .0052). A positive pulmonary vasodilator response to treatment with a combination of iE&iM before initiation of CPB was observed in 77% of patients. Higher baseline SPAP was an independent predictor of pulmonary vasodilator response, while EuroSCORE II >6.5% was a predictor of nonresponse to treatment.

Prognostic Implications of the Novel Pulmonary Hypertension Definition in Patients with Aortic Stenosis after Transcatheter Valve Replacement.

Introduction: Pulmonary hypertension (PH), traditionally defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg, is associated with poor outcomes in patients undergoing a transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Recently, a novel definition for PH has been proposed, placing the cut-off value of mean PAP at 20 mmHg, and introducing pulmonary vascular resistance as an exclusive indicator for the pre-capillary involvement. In light of the novel criteria, whether PH still preserves its prognostic significance remains unknown. Methods: The study population consisted of 380 patients with AS, who underwent a right heart catheterization before TAVR. The cohort was divided according to the presence of PH (n = 174, 45.7%) or not. Patients with PH were further divided into the following groups: (1) Pre-capillary PH ((Pre-capPH), n = 46, 12.1%); (2) Isolated post-capillary PH ((IpcPH), n = 78, 20.5%); (3) Combined pre and post-capillary PH ((CpcPH), n = 82, 21.6%). The primary endpoint was all-cause mortality at 1 year. Results: A total of 246 patients (64.7%) exhibited mean PAP > 20 mmHg. Overall, the presence of PH was associated with higher 1-year mortality rates (hazard ratio (HR) 2.8, 95% CI: 1.4–5.8, p = 0.004). Compared to patients with no PH, Pre-capPH and CpcPH (but not IpcPH) were related to higher 1-year mortality (HR 2.7, 95% CI: 1.0–7.2, p = 0.041 and HR 3.9, 95% CI: 1.8–8.5, p = 0.001, respectively). This remained significant even after the adjustment for baseline comorbidities. Conclusions: Pre-interventional PH according to the novel hemodynamic criteria, is linked with poor outcomes in patients undergoing TAVR for severe AS. However, this is mainly driven by patients with mean PAP ≥ 25 mmHg. Patients with a pre-capillary PH component as defined by increased PVR present an even worse prognosis as compared to patients with isolated post-capillary or no PH who present comparable 1-year mortality rates.

Assessment of pulmonary hemodynamics and stress-induced pulmonary hypertension in clinical practice

Pulmonary hypertension (PH) is currently determined by the mean pulmonary artery pressure (PAPmean) increase, which in turn is associated with a number of parameters, such as cardiac output (CO), pulmonary vascular resis-tance (PVR) and left atrial pressure. Therefore, changes in PAP mean during exercise cannot be discussed apart from the listed indicators. Probably, this was one of the reasons for the absence of an accurate hemodynamic de-termination of stress-induced PH. However, today it has been revealed that PAP at rest increases only when ≥50% of pulmonary microcirculation is off, and for the earliest detection of the problem it is advisable to use factors that lead to increase of CO and PVR, one of them is exercise. Moreover, clinicians often observe that the anamnesis of PH starts from complaints, associated with exercise. Mo-dern non-invasive technologies (stress-echocardiogra-phy, cardiopulmonary exercise testing) provide very de-tailed data not only about the pulmonary circulation, but also about ventilator function, blood gas composition, structural and functional changes in the heart. Stress-in-duced PH is defined as combination of normal mean pulmonary artery pressure values (PAPmean &lt;25 mm Hg) at rest and increase of PAPmean &gt;30 mm Hg during exercise, as well as PVR &gt;3 WU, however, this definition isn’t generally accepted. As an alternative, to determine stress-induced PH, it was proposed to evaluate PAPmean/CO curve, that excludes the influence of peak hemody-namic parameters. The pulmonary vessels distensibility and ventriculo-arterial coupling represent promising pa-rameters for complete characterization of the pulmonary circulation changes during exercise.

Mildly Elevated Pulmonary Arterial Pressure Is Associated With a High Risk of Progression to Pulmonary Hypertension and Increased Mortality: A Systematic Review and Meta-Analysis.

BackgroundPulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (PAP) ≥25 mm Hg measured by right heart catheterization. However, the upper limit of a normal mean PAP is 20 mm Hg. There is a gap between the upper limit of normal and the threshold for diagnosing PH. Therefore, we aimed to investigate whether individuals with a mildly elevated PAP, defined as 20 mm Hg < mean PAP <25 mm Hg, are at an increased risk of progression to PH or mortality than those with a normal PAP.Methods and ResultsWe reviewed studies evaluating the risk of progression to PH and/or mortality in individuals with a mildly elevated PAP versus those with a normal PAP. The mean PAP value of each participant was confirmed by right heart catheterization. We reviewed 1213 studies and 8 fulfilled our inclusion criteria. Our results indicated that individuals with a mildly elevated PAP were 1.81 to 2.45 times more likely to progress to PH than individuals with a normal PAP. There was a statistically significant difference in mortality between the mildly elevated PAP and normal PAP groups (hazard ratio, 2.48; 95% CI, 1.69–3.64). We also pooled survival probabilities in each arm to obtain a summary survival curve for each group, and the pooled survival rates in the mildly elevated PAP group were numerically lower than those in the normal PAP group.ConclusionsOur study revealed that individuals with a mildly elevated PAP were at an increased risk of progression to PH and mortality than those with a normal PAP.

Usefulness of mean pulmonary artery pressure for predicting outcomes of transcatheter closure of atrial septal defect with pulmonary arterial hypertension.

This study aimed to provide a simple index for predicting the definitive indication for transcatheter closure of atrial septal defect (ASD) with pulmonary arterial hypertension (PAH). A positive response after attempted occlusion was defined as mean pulmonary artery pressure (MPAP) ≤30 mmHg or the decrement percentage of it ≥20% compared with baseline. If a positive response was achieved, the occluder would be released, and the procedure was defined as successful. In 209 patients who underwent a successful procedure without PAH-specific medicine, there was a dramatic decrease in the percentage of patients with pulmonary arterial systolic pressure (PASP) ≥50 mmHg from baseline to the one-year follow-up (79.4% to 14.0%, p<0.001). The optimal cut-off value of MPAP to predict a positive response without PAH-specific medicine was 35.0 mmHg, with an area under the curve (AUC) of 0.919 (p<0.001). Administration of inhaled iloprost extended the cut-off point to 50.0 mmHg to reach a positive response, with an AUC of 0.774 (p=0.003). This large-scale study indicated that MPAP could be a simple but powerful index to predict benefit from closure in adult ASD patients with PAH.

THE PULMONARY CIRCULATION PECULIARITIES IN MEN UNDER 60 YEARS OLD WITH PULMONARY HYPERTENSION, DEVELOPED DURING MYOCARDIAL INFARCTION

Relevance. Formation of pulmonary hypertension (PH) in myocardial infarction (MI) remains poorly understood. Aim. To evaluate changes in pulmonary circulation indicators (PCI) in men under 60 years old (y.o) with PH that is developing in subacute MI period to improve understanding of developmental options and prevention. Material and methods. The study included men aged 19-60 y.o. with MI and various dynamics of mean pulmonary ar-tery pressure (MPAP), determined by echocardiography (A. Kitabatake) in the first 48 hours (1) and completion of third week (2) of MI. Patients were divided into four groups: studied (I) included 84 patients (mean age 50.4±7.1 y.o) with PH (MPAP2 25 and more mm Hg) and normal level of MPAP1. Group II included patients with a normal level of MPAP in both phases of the study (88 men, 52.1±6.6 y.o); group III – with elevated levels of MPAP at both points of study (184 men, 51.2±5.5 y.o) and IV – with increased levels of MPAP1 and normal levels of MPAP2 (94 men, 50.5±6.8 y.o). A comparative assessment of PCI in selected groups was performed. Results. In first 48 hours of MI, the minimum values of MPAP (I: 21.9±3.3; II: 20.3±2.5; III: 39.0±11.2 (mm Hg)) and total pulmonary resistance (TPR) ) (I: 380.0±171.0; II: 306.8±136.3; III: 616.0±279.8 (dyn×sec×cm-5)) were noted in group II, and the maximum - in III (p˂0.0001). When considering their dynamics at the end of the third week of MI, MPAP increased in I (39.5%; p˂0.0001), decreased in III (16.0%; p˂0.0001) and IV groups (42.9%; p˂0.0001). TPR decreased in II (12.1%), III (28.6%) and IV (54.2%) groups (p ˂0.0001). Conclusions. The study group is distinguished by unfavorable changes in PCI during observation period, in contrast to other groups, which confirms expediency of assessing dynamics of these parameters as possible marker of negative prognosis for PH.

Intraoperative Extracorporeal Circulatory Support in Lung Transplantation for Pulmonary Fibrosis

Venous-arterial extracorporeal membrane oxygenation (ECMO) is an established technique for intraoperative cardiopulmonary support in patients undergoing lung transplantation. Patients with pulmonary fibrosis have a higher risk to require it. The aim of this study was to identify risk factors for the need of intraoperative ECMO use. Records of patients undergoing lung transplantation for pulmonary fibrosis at our institution between January 2010 and May 2018 were retrospectively reviewed. Univariate logistic regression analysis was used for statistical identification of risk factors. There were 105 patients (34%) who required intraoperative ECMO support (ECMO+ group), and 203 (66%) did not (ECMO- group). Preoperative proof of pulmonary hypertension was identified as a risk factor for intraoperative ECMO support (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.2-6.5; P < .01). Revealed mean pulmonary arterial pressure values exceeding 50 mm Hg and pulmonary vascular resistance values exceeding 9.4 Wood units were identified as risk factors for the need of intraoperative ECMO use with a prediction probability of 70%. Increased recipient body surface area (OR, 0.2; 95% CI, 0.1-0.5; P < .01) emerged as a protective factor against intraoperative ECMO (Hosmer-Lemeshow statistic, P= .71) as well as higher cardiac output (OR, 0.7; 95% CI, 0.6-0.9; P < .01). The postoperative course was more complicated in the ECMO+ group, whereas survival at 5 years did not differ among groups (70% vs 69%, P= .79). Pulmonary hypertension with elevated pulmonary vascular resistance values predicts the need of intraoperative ECMO in patients receiving lung transplantation for pulmonary fibrosis. Although the postoperative course was more complicated in the ECMO+ group, long-term survival did not differ significantly.

P925Cardiac autonomic dysfuntion in adult patient with uncorrected atrial septal defect : a role of pulmonary arterial hypertension

Abstract Background Atrial Septal Defect (ASD) is a congenital heart disease that often under-diagnosed in youth. Atrial septal defect has a poor clinical manifestation at Pulmonary Arterial Hypertension (PAH) condition. Cardiac autonomic dysfunction may occur in PAH due to over sympathetic activation. This condition in general population is associated with increase risk of sudden cardiac death. Despite the case, there are only limited studies which associated cardiac autonomic dysfunction and PAH in adult patient with uncorrected ASD. Purpose This study aims to compare cardiac autonomic dysfunction, using heart rate variability, in adult patient with uncorrected ASD between PAH and non-PAH group. Methods Adult (18+) patient with uncorrected ASD who listed in ASD registry in Indonesia, were selected in this analytical observational study. Patients in whom no other congenital defect and atrial fibrillation in electrocardiogram were eligible for inclusion. Diagnose of PAH was established when mean pulmonary arterial pressure value from right heart catheterization is ≥ 25 mmHg. Arrhythmias and heart rate variability, using Standard Deviation of Normal-Normal (SDNN), High Frequency (HF) and Low Frequency (LF) parameters, were collected from holter monitoring. These procedures were performed on the same day. Results We enrolled 55 adult patients with uncorrected ASD (mean age: 33.3 ± 10.3 years, 89.1% women), consist of 51 secundum ASD, 3 sinus venosus ASD and 1 primum and secundum ASD patient. They were divided into PAH group (28 patients) and non-PAH group (27 patients). Patients in PAH group had a higher incidence of paroxysmal atrial fibrillation and ventricular extrasystole compare to those in non-PAH group (28.5% vs. 14.8% and 75% vs. 70%). All parameters of heart rate variability was significantly reduced in PAH group compare to non-PAH group (SDNN : mean difference 14.5 ± 2.98 ms, CI 95%, P &amp;lt; 0.001; HF : median difference 99.5 ms2, P &amp;lt; 0.001; LF : median difference 129.6 ms2, P &amp;lt; 0.001). Conclusion A marked reduction in cardiac autonomic function occur in adult uncorrected ASD patient with PAH compare to patient with non-PAH, that might be the result of decreasing baroreceptor and increasing chemoreceptor function in PAH.

Soluble P-Selectin Levels in Patients with Sickle Cell Disease Reflect Platelets' Activation Rather Than Endothelial Dysfunction

Background: Vascular occlusion is a major cause of the morbidity associated with sickle-cell disease (SCD). The tendency of sickle red blood cells to adhere to the vascular endothelium is believed to be a major contributor and possibly primary cause of the vaso-occlusive process. Therefore mediators of adhesion have become a potential new target for pharmacological therapy to combat the complications of SCD. One of the molecules involved in this process is P-Selectin or CD62P, a cell adherence molecule that is rapidly and chronically expressed on the surface of endothelial cells and platelets when activated. P-Selectin is found in the plasma of normal individuals at ng/mL concentrations. Circulating soluble P-Selectin (sP-Selectin) appears to be slightly smaller than native P-Selectin. An alternatively spliced mRNA encoding a form of human P-Selectin lacking the transmembrane anchoring domain has been reported for both megakaryocytes and endothelial cells, and evidence suggests that the majority of circulating sP-Selectin arises in this manner. We and others have reported elevated sP-Selectin levels in SCD even in steady phase. Recently, a humanized monoclonal antibody that binds to P-Selectin and blocks its interaction with P-selectin glycoprotein ligand 1 (PSGL-1) has been administered to patients with SCD, resulting in an amelioration of painful VOC. In this context we aimed to explore if sP-Selectin levels could be used to choose among the SCD patients those who might benefit from the new therapy. Patients and Methods: Eighty adult Caucasian patients with HbS/βthal at steady phase [40 patients under hydroxyurea (HU+) treatment and 40 patients without hydroxyurea (HU-) treatment] were included in this study, while 20 apparently healthy individuals of similar age and gender served as controls. Along with sP-Selectin levels, measured with the same method as reported previously (Human sP-Selectin/CD62P Immunoassay, R&amp;D Systems, Minneapolis, MN, USA), other parameters of hemolysis, inflammation, endothelial dysfunction, iron accumulation and clinical features of the disease were evaluated. Results are expressed as median values ± SEM. Results: We found that sP-Selectin levels were elevated in 45/80 (56%) patients with HbS/βthal compared to controls (108.2±6.3 vs. 69.3±4.1ng/mL, respectively, p&lt;0.001), independently of patients' βthal genotype and correlated strongly with PLT count (r=0.760, p&lt;0.001). Regarding HU treatment, sP-Selectin levels did not differ between (HU+) and (HU-) patients (112.5±9.8 vs. 100.3±7.4ng/mL, respectively, p&gt;0.07). No significance correlation was found between sP-Selectin levels and markers of: hemolysis (RPI: r=0.191, p&gt;0.100); LDH: r=0.103, p&gt;0.360 and bilirubin: r=0.171, p&gt;0.130); inflammation (hs-CRP: r= 0.002, p&gt;0.842); endothelial dysfunction (vWF:antigen: r=0.141, p&gt;0.210 and ADAMTS-13: r=0.089, p&gt;0.507). Regarding iron accumulation no correlation was found between sP-Selectin and ferritin levels (r=0.090, p&gt;0.438), while a weak negative correlation was found with hepcidin-25 levels (r=-0.283, p=0.018). Furthermore, no correlation was found between sP-Selectin levels and history of clinical complications such as VOC (p&gt;0.795), acute chest syndrome, venous and arterial thrombosis and mean pulmonary artery pressure values, (p&gt;0.402). Conclusion: In this study, we proceeded with an external validation procedure of sP-Selectin determination in patients with HbS/βthal (keeping the same methodology in a different cohort of patients), and we found elevated levels of sP-Selectin with the evidence of PLTs' secretion origin, as no correlation found with other markers of endothelial dysfunction and inflammation. Interestingly, we failed to find a significant link of sP-Selectin levels with other markers of disease severity and/or clinical features of SCD. Thus, we consider that the use sP-Selectin as a biomarker of assessment and treatment of endothelial dysfunction in patients with SCD is of almost negligible importance. Disclosures Voskaridou: Genesis: Consultancy, Research Funding; Protagonist: Research Funding; Celgene Corporation: Consultancy, Research Funding; Acceleron: Consultancy, Research Funding; Addmedica: Membership on an entity's Board of Directors or advisory committees.

P4718Inadequate response of pulmonary artery pressure after percutaneous mitral valvuloplasty: determinant factors and prognostic impact

Abstract Introduction Pulmonary hypertension (HP) has long been known to be a marker of poor outcome in patients with mitral stenosis (MS). Percutaneous mitral valvuloplasty (PMV) is currently the treatment of choice for MS, which results in improvement in HP. However, despite the successful valve opening, the regression of PH may be incomplete. This has been attributed to irreversible morphologic changes within the pulmonary vasculature. Purpose To assess the clinical, echocardiographic and hemodynamic parameters associated with an inadequate response of the pulmonary artery pressure (PAP) immediately after a successful PMV, and also the impact of residual PH on long-term outcome in these patients. Methods 181 patients undergoing PMV for rheumatic MS were enrolled. Invasive hemodynamic and echocardiographic measures were examined in all patients. Inadequate response of PAP was defined as the mean pulmonary artery pressure (mPAP) values unchanged at the end of the procedure. Long-term outcome was a composite endpoint of death, mitral valve replacement, repeat PMV, new onset of atrial fibrillation (AF), or stroke. Results The mean age was 44.1±12.6 years, and 157 patients were women (86.7%). In the overall population, mPAP decreased from 33.4±13.1 mmHg pre to 27.6±9.8 mmHg post (p&lt;0.001), as mitral valve increased from 0.96±0.2 cm2 pre to 1.68±0.2 cm2 post (p&lt;0.001) PMV. Following PMV, 10 patients developed severe mitral regurgitation and were excluded from the analysis. Of the 171 patients analyzed, 52 (30%) did not present reduction of mPAP immediately after the PMV. Transmitral pressure gradients were significantly greater and mitral valve area was smaller in those patients with unchanged mPAP after PMV than in those whose PAP had decreased. Systolic, diastolic and mPAP pressures as well as left atrial pressure were higher in those patients who had improvement in pulmonary pressures after PMV. Multivariate analysis revealed the following independent predictors of unchanged mPAP: AF (Odds ratio [OR] 2.7, 95% [confidence interval] CI 1.1 to 6.4), mitral valve area (OR 1.3, 95% CI 1.1 to 1.5), maximum mitral valve leaflets displacement (OR 0.8, 95% CI 0.7 to 0.9), and left ventricular compliance after PMV (OR 0.8, 95% CI 0.6 to 0.9). During a mean follow-up of 28 months, the endpoint was reached in 48 patients (26%). The pulmonary pressure response to PMV was not predictor of long-term events. Conclusions In a large cohort of patients with MS undergoing PMV, mean pulmonary artery pressure values do not reduce immediately after the procedure in 30% of the cases, despite adequate opening of the valve. The factors associated with inadequate PAP response following PMV were presence of AF, larger mitral valve area, reduced valve leaflets mobility and post procedural low left ventricular compliance. The early non-reduction of mPAP after PMV is not associated with adverse outcome.

Reduced Right Ventricular Output Reserve in Patients With Systemic Sclerosis and Mildly Elevated Pulmonary Artery Pressure.

This prospective study was undertaken to evaluate right ventricular function and pulmonary arterial compliance (PAC; ratio of stroke volume to pulse pressure) at rest and during exercise in patients with systemic sclerosis (SSc) with normal mean pulmonary artery pressure (PAP), patients with SSc with mildly elevated mean PAP, and patients with SSc with manifest pulmonary hypertension (PH). Patients with SSc (n = 112) underwent clinical assessment and right-sided heart catheterization at rest and during exercise and were divided into 3 groups according to their resting mean PAP values: normal mean PAP (≤20 mm Hg), mildly elevated mean PAP (21-24 mm Hg), and PH (mean PAP ≥25 mm Hg). Results were compared between groups by analysis of variance followed by post hoc Student's t-test. Compared to patients with normal mean PAP, patients with mildly elevated mean PAP had a lower 6-minute walking distance (P = 0.008), lower cardiac index (P = 0.027) and higher pulmonary vascular resistance (P = 0.0002) during exercise, and lower PAC at rest (P = 0.016) and different stages of exercise (P = 0.033 for 25W and P = 0.024 for 75W). The results of this study suggest that impaired 6-minute walking distance in SSc patients with mildly elevated mean PAP might be caused by reduced PAC during exercise and reduced right ventricular output reserve, presumably due to impaired coupling between the right ventricle and the pulmonary vasculature. These findings provide further evidence of the clinical relevance of mildly elevated mean PAP in patients with SSc.

Rapid Improvement of Pulmonary Functions in Children After Transcatheter Closure of an Atrial Septal Defect.

There are very few studies in the literature on respiratory system functions and complications of children with an atrial septal defect (ASD). The aim of this study is to investigate the pulmonary functions and pulmonary complications before and after transcatheter closure in children with an ASD. In this study, pulmonary function test parameters of 30 ASD patients between 5 and 18years of age who were eligible to be treated by transcatheter ASD closure were compared with 30 healthy children. The patients undergoing transcatheter ASD closure received pulmonary function tests (PFT) at baseline (1 day before ASD closure), and 3months after the procedure. Forced vital capacity (FVC), forced expired volume in 1s (FEV1), peak expiratory flow, and mean forced expiratory flow during the middle half of FVC were measured. The mean age of the 30 ASD patients was 9.59±3.1years; and 20 (66.6%) were female and 10 (33.3%) were male. The mean age of the control group was 10.15±2.21years, and 19 (63.3%) were girls and 11 (36.6%) were males. ASD patients had significantly reduced FVC (73.11±24.6%; 86.05±26.1; p=0.001, respectively), and FEV1 (81.34±26.2% and 99.2±19.6%; p=0.001; respectively) at baseline. But significant improvement was observed in FVC values in the 3rd-month post-closure comparison of the patient group with the control group (73.11±24.6%; and 88.36±14.5%; p=0.01, respectively); FEV1 values (81.34±26% and 99.54±18.2%; p=0.005, respectively) and mean forced expiratory flow between 25 and 75% of vital capacity (MEF25-75) values (94.6±33.4% and 124.2±-24.1%; p=0.01, respectively) were also improved. There was no statistically significant relationship between the PFT measurements at baseline and after closure of the defect and age at transcatheter closure, gender, body height, body weight, ASD diameter, Q p/Q s, right ventricle systolic pressure, or mean pulmonary artery pressure values. At the 3rd month of ASD closure, there was no significant difference in the comparison of the PFT values of the patient and control group. Disturbance in the significant flow limitation of the peripheral airway of ASD patients was observed with PFT. Better pulmonary outcomes were observed in ASD patients after transcatheter closure.

Isolated decrease of the lung diffusing capacity in patients with systemic sclerosis without pulmonary arterial hypertension: a long-term prospective study

The objective of this 5year prospective study was to investigate a clinical role of isolated decrease of DLCO in patients with systemic sclerosis (SS) without pulmonary arterial hypertension (PAH).Methods. We selected 48 out of 142 patients with SS: 35 (73%) with limited SS and 13 (27%) with diffuse SS. The average length of the disease was 12.9 ± 7.9 years. Inclusion criteria were DLCO &lt; 80% pred., forced vital capacity (FVC) ≥ 80% pred. and systolic pulmonary artery pressure (PAP) ≤ 35 mm Hg according to echocardiographic examination (echoCG). High resolution computed tomography (HRCT), spirometry, DLCO measurement, and echoCG were obtained at baseline and after 4.7 ± 1 year of follow up. All patients were treated with standard therapy.Results. CT signs of interstitial lung disease (ILD) were found in 43 (89.6%) patients at baseline and newly developed in 3 other patients during the followup. During the followup, lung CT improved in 5 (10.4%) patients and progressed in 15 (31.3%) patients. Over 5 years, FVC did not change significantly (97.6 ± 10.7% and 100.8 ± 18.9%; р = 0.15), while DLCO significantly decreased both in limited and diffuse SS groups (59.8 ± 13.5% and 56.3 ± 12%; р = 0.006). Mean PAP values remained within normal range in majority of patients. Clinically significant FVC reduction (≥ 10%) was found in 5 patients; of them, CT signs of ILD at baseline were seen in 3 patients and newly developed during the followup in 2 others. Clinically significant DLCO reduction (≥ 10%) was documented in 11 (23%) patients, all had CT signs of ILD at baseline, although CT progression during the followup was noted only in six of them. Contemporary deterioration in FVC, DLCO and CT was found in 3 patients.Conclusion. Clinical course of ILD in SS patients with isolated DLCO reduction and without PAH was relatively benign, with respiratory volumes being preserved within normal range for long time. Comparison of radiological and functional changes in a prospective study has suggested that DLCO is a more sensitive tool to determine ILD progression compared to HRCT. Regular DLCO measurements could be used as a reliable tool for monitoring of ILD associated with SS.

Methylene blue compared to norepinephrine in the management of vasoplegic syndrome in pediatric patients after cardiopulmonary bypass: a randomized controlled study

Background and aimVasoplegic syndrome (VS) is a frequent complication following cardiopulmonary bypass (CPB) requiring escalating dose of vasopressor support. The guanylate cyclase inhibitor methylene blue (MB) could be an attractive alternative treatment in such cases. This study examines the efficacy and safety of using MB compared to the commonly used norepinephrine in VS in pediatric population following CPB.MethodsForty patients of pediatric age group who developed VS following CPB for elective corrective cardiac surgeries received 0.5 μg/kg/min norepinephrine intravenous infusion for 5 min without improvement (Time 1). Patients were randomly assigned to two equal groups. Group MB received 1.5 mg/kg methylene blue by intravenous infusion over 20 min. Group N did not receive MB. Norepinephrine infusion was continued in both groups and titrated according to the response of patients with a maximum dose of 2 μg/kg/min (Time 2). Heart rate, mean arterial pressure (MAP), central venous pressure (CVP), cardiac output (CO), cardiac index (CI), mean pulmonary artery pressure (MPAP), systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI) were calculated in both groups. Side effects related to the study drug were recorded.ResultsTime 2 values of norepinephrine dose were significantly lower in MB group compared to N group. Time 2 values of MAP were significantly higher in MB group compared to N group with a significant decrease in HR in MB group compared to N group. No change in the rhythm was detected in the two groups. Time 2 values of CVP were higher in MB group compared to N group. Time 2 values of CO and CI were significantly lower in MB group compared to N group and SVR and SVRI were significantly higher in MB group compared to N group. Time 2 values of MPAP were comparable in both groups and showed no significant change. No side effects from using MB were recorded as pulmonary edema and respiratory distress.ConclusionIn this study, MB showed superior efficacy and safety in managing VS in pediatrics following CPB compared to the conventionally used norepinephrine.

The presence or severity of pulmonary hypertension does not affect outcomes for single-lung transplantation

Advanced lung disease (ALD) that requires lung transplantation (LTX) is frequently associated with pulmonary hypertension (PH). Whether the presence of PH significantly affects the outcomes following single-lung transplantation (SLT) remains...

Abstract 267: Inhaled Nitric Oxide Lowers Pulmonary Artery Pressure During Cardiopulmonary Resuscitation but Does Not Increase Survival in a Model of Prolonged Cardiac Arrest in Pigs

Introduction: We have previously shown that thoracic chest compressions during cardiac arrest (CA) result in elevated pulmonary vascular resistance (PVR), potentially impeding a return of spontaneous circulation (ROSC) by limiting circulation. Hypothesis: Applying inhaled nitric oxide (iNO) will lower PVR during cardiopulmonary resuscitation (CPR). Methods: 8 pigs were instrumented with an arterial line and a pulmonary artery catheter. CA was electrically induced and left untreated for 10 minutes before CPR was performed employing mechanical chest compressions and mechanical ventilation. Animals were randomized to either receive 20ppm of iNO (n = 3, iNO) or 100% Oxygen (n = 5, Control) during CPR. After 6 minutes of CPR, defibrillation was attempted. When no ROSC was achieved, chest compressions were restarted and continued for up to 30 minutes. Results: Mean pulmonary artery pressure (MPAP) rose significantly from 9 ± 4 following 10 minutes of VF to 21 ± 7 mmHg following 1 minute of CPR in Control animals (p=0.01). Animals receiving iNO showed a significantly lesser increase in MPAP from 5 ± 1 following 10 minutes of VF to 8 ± 3 mmHg following 1 minute of CPR (p=0.18). While MPAP did not differ on baseline or during 10 minutes of VF, iNO treatment resulted in significantly lower MPAP values averaged over the first 6 minutes of CPR (10 ± 1 vs. 22 ± 1 mmHg, p&lt;0.01 ; see Figure ; * indicates p&lt;0.01 for MPAP iNO vs. Control). This was reflected by similar changes in PVR, which remained significantly lower in iNO treated animals during CPR (80 ± 9 vs. 188 ± 17 dyn x sec x cm-5, p&lt;0.01). While no animal achieved ROSC in the iNO group, two of the five control animals could be successfully resuscitated. Conclusion: Ventilation with 20ppm nitric oxide during CPR reduces MPAP and PVR following prolonged CA, but does not improve survival in these preliminary experiments. Expanding the sample size will be necessary to determine potential impact of this intervention on survival or neurocognitive outcome.

Echocardiography of the Pulmonary Circulation and Right Ventricular Function: Exploring the Physiologic Spectrum in 1,480 Normal Subjects

<h3>Background</h3> Although transthoracic echocardiography (TTE) is an excellent noninvasive screening test for pulmonary hypertension, the physiologic range of Doppler echocardiography-derived pulmonary pressures remains not completely investigated. The aim of the present study was, therefore, to explore the full spectrum of pulmonary pressures and right ventricular (RV) functional indexes by TTE in healthy subjects and to investigate clinical and echocardiographic correlates. <h3>Methods</h3> A random sample of 1,480 healthy individuals (mean age, 36.1 ± 15.5 years; range, 20-80 years; 905 men) underwent a comprehensive TTE. Pulmonary artery systolic pressure (PASP), mean pressure, and pulmonary vascular resistance were estimated by standard Doppler echocardiography formulas. In addition, RV diastolic (Doppler transtricuspid inflow measurements) and systolic indexes (RV fractional area change, RV tissue Doppler peak systolic velocity, tricuspid annular plane systolic excursion) were calculated. <h3>Results</h3> PASP and mean pulmonary artery pressure values were significantly higher in subjects aged > 50 years and in those with a BMI > 30 kg/m². In particular, a PASP > 40 mm Hg was found in 118 subjects (8%) of those aged > 50 years and in 103 (7%) of those with a BMI > 30 kg/m². No differences by age were registered in RV systolic indexes and in pulmonary vascular resistances. On multivariate analysis, in the overall study population, age, BMI, mitral E/e′ ratio, and left ventricular stroke volume were the only independent predictors of PASP. <h3>Conclusions</h3> This study delineates an estimate of pulmonary hemodynamics in a wide age range cohort of healthy subjects. Pulmonary pressures increased with age and BMI, as expected.