Normal Mean Pulmonary Artery Pressure Research Articles

Mean pulmonary artery pressure estimated by echocardiogram rapidly exceeds 20mmHg from the normal range in patients with connective tissue disease.

Earlier intervention for pulmonary hypertension (PH) has been reported to improve the prognosis of patients with connective tissue disease (CTD). However, it is not fully elucidated how rapidly PH develops in patients showing normal mean pulmonary arterial pressure (mPAP) at the index investigation. We evaluated 191 CTD patients with normal mPAP retrospectively. The mPAP was estimated by the formerly defined method employing echocardiography (mPAPecho). We investigated predictive factors that predict increasing mPAPecho at follow-up transthoracic echocardiography (TTE) using uni- and multi variable analysis. The mean age was 61.5years old, and 160 patients were female. The percentage of patients in whom mPAPecho exceeded 20mmHg at follow-up TTE was 38%. Multivariable analysis revealed that acceleration time/ejection time (AcT/ET) measured at the right ventricular outflow tract at initial TTE was independently associated with the consequent increase of mPAPecho at the follow-up TTE. When using 0.43 of best cutoff value in AcT/ET calculated by receiver operating characteristic analysis, the change in mPAPecho in patients with low AcT/ET was significantly higher than in those with high AcT/ET (3.05mmHg in patients with AcT/ET < 0.43 and 1.00mmHg in patients with AcT/ET ≥ 0.43, p < 0.001). Thirty-eight percent of CTD patients who show the normal estimated mPAP by TTE develop gradual elevation of mPAP to the level to consider early intervention within 2years. AcT/ET at initial TTE can predict increasing mPAP at follow-up TTE.

Outcomes of Catheter-Based Pulmonary Artery Embolectomy in Patients With Sub-Massive to Massive Pulmonary Embolism.

Background Pulmonary embolism (PE) is the third leading cause of cardiovascular death after myocardial infarction and stroke. The ideal therapeutic approach for these patients remains undetermined. We report our single-center outcome data for using a catheter-based pulmonary artery thrombectomy using the FlowTriever (Inari Medical, Irvine, CA) device asmanagement for patients with submassive PE. Methods We retrospectively collected data from a single center of patients who underwent thrombectomy using INARI FlowTriever device. The data on baseline characteristics, procedural and clinical outcomes was collected and analysed Results A total of 38 patients with PE treated endovascularly with the FlowTriever device were identified: 33 with submassive PE and five with massive PE. The mean age was 65.9 years (95% CI 61.9 - 69.8), and most patients were male (73.7%). All patients had right heart strain as the main indication for thrombectomy. Four patients (10.53%) required pressor support before the procedure. In 31 patients, pre- and post-thrombectomy average mean pulmonary artery pressure (mPAP) was improved significantly by 22% (p < 0.01). Two patients had significant adverse events at 48 hours (5.26%). One patient experienced procedure-related access site hematoma and life-threatening bleeding, while another developed intraprocedural-related massive hemoptysis and cardiopulmonary arrest. Overall post-procedural length of stay was 7.7 ± 5.6 days; 52.63% of patients (n = 20) required intensive care. Three patients (7.89%) required pressor support before the procedure, and 78.9% of patients (n = 30 of 38) survived hospital discharge. Thirty patients who survived were discharged with oral anticoagulation. There were no device-related complications. Conclusion Randomized trials of interventional devices for submassive PE are warranted to either support or alert the medical community of the safety and efficacy of their use for patients with submassive and massive PE. In time, pulmonary embolismresponse team (PERT)may generate outcome data that better inform treatment decisions.

Man-machine interaction-based phenotyping preprocedurally identifies patients with severe aortic stenosis, who will not recover from cardiac damage following transcatheter aortic valve replacement

Abstract Background Severe aortic stenosis (AS) can lead to left heart dysfunction, pulmonary hypertension (PH), and eventually right heart failure. Clinical phenotypes therefore appear heterogeneous, depending on disease progression and comorbidities. Purpose This study therefore sought to improve diagnostic and prognostic resolution in patients undergoing transcatheter aortic valve replacement (TAVR) for severe AS by developing a man-machine interaction-based phenotyping approach. Methods Unsupervised agglomerative clustering was applied to preprocedural data from echocardiography and right heart catheterization from 366 consecutively enrolled patients undergoing TAVR for severe AS. Echocardiographic follow-up data, obtained on day 147±75.1 after TAVR, were available from 247 patients (67.5%). Results Cluster analysis revealed four distinct phenotypes, reflecting various extents of disease severity, and hence differing in mortality. Patients from cluster 1 presented with preserved left ventricular ejection fraction (LVEF; 57.2±6.4%) and with normal mean pulmonary artery pressure (mPAP) levels (21.2±6.5 mmHg). In contrast, patients in cluster 2 suffered from postcapillary PH (mPAP: 34.2±7.8 mmHg). Left heart failure (LVEF: 42.4±15.7%), severe PH (mPAP: 46.9±8.5 mmHg), and right heart dysfunction (tricuspid annular plane systolic excursion [TAPSE]: 16.1±4.57 mm) characterized patients in cluster 3. Patients from cluster 4 showed mild postcapillary PH (mPAP: 27.5±9.2 mmHg), yet dilatation of all heart chambers, biventricular dysfunction (LVEF: 47.3±12.2%, TAPSE: 16.8±4.5 mm), and a high prevalence of both mitral and tricuspid regurgitation (12.5% and 14.8%, respectively). Correction of severe AS by TAVR significantly reduced the proportion of patients suffering from concurrent severe mitral regurgitation (from 9.29% to 3.64%, p-value: 0.0015). Moreover, pulmonary artery pressures were ameliorated (estimated systolic pulmonary artery pressure: from 47.2±15.8 mmHg to 43.3±15.1 mmHg, p-value: 0.0079). However, right heart dysfunction as well as the proportion of patients with severe tricuspid regurgitation remained unchanged. Clusters 3 and 4 with persistent right heart dysfunction ultimately displayed 2-year survival rates of 69.2% (95% CI: 56.6–84.7%) and 74.6% (95% CI: 65.9–84.4%), which were significantly lower compared to clusters 1 and 2 with little or no persistent cardiopulmonary impairment (88.3% [95% CI: 83.3–93.5%] and 85.5% [95% CI: 77.1–94.8%]). Conclusion This phenotyping approach preprocedurally identifies patients with severe AS, who will not recover from extra-aortic valve cardiac damage following TAVR and whose survival is therefore significantly reduced. Importantly, not the degree of PH at initial presentation, but the irreversibility of right heart dysfunction determines prognosis. Funding Acknowledgement Type of funding sources: None.

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.

Safety and feasibility of hemodynamic pulmonary artery pressure monitoring using the CardioMEMS device in LVAD management.

BackgroundThere is a clinical need for additional remote tools to improve left ventricular assist device (LVAD) patient management. The aim of this pilot concept study was to assess the safety and feasibility of optimizing patient management with add‐on remote hemodynamic monitoring using the CardioMEMS in LVAD patients during different treatment stages.MethodsTen consecutive patients accepted and clinically ready for (semi‐) elective HeartMate 3 LVAD surgery were included. All patients received a CardioMEMS to optimize filling pressure before surgery. Patients were categorized into those with normal mean pulmonary artery pressure (mPAP) (≤25 mmHg, n = 4) or elevated mPAP (>25 mmHg, n = 6), and compared to a historical cohort (n = 20). Endpoints were CardioMEMS device safety and a combined endpoint of all‐cause mortality, acute kidney injury, renal replacement therapy and/or right ventricular failure at 1‐year follow‐up. Additionally, we investigated hospital‐free survival and improvement in quality of life (QoL) and exercise tolerance.ResultsNo safety issues or signal interferences were observed. The combined endpoint occurred in 60% of historical controls, 0% in normal and 83% in elevated mPAP group. Post‐discharge, the hospital‐free survival was significantly better, and the QoL improved more in the normal compared to the elevated mPAP group.ConclusionRemote hemodynamic monitoring in LVAD patients is safe and feasible with the CardioMEMS, which could be used to identify patients at elevated risk of complications as well as optimize patient management remotely during the out‐patient phase with less frequent hospitalizations. Larger pivotal studies are warranted to test the hypothesis generated from this concept study.

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.

THE CLINICAL COURSE OF MYOCARDIAL INFARCTION PECULIARITIES IN MEN UNDER 60 YEARS OLD WITH PULMONARY HYPERTENSION

Relevance. Pulmonary hypertension (PH) negatively affects the prognosis of myocardial infarction (MI). Aim. To evaluate MI clinical features (CF) in men under 60 years old (y.o.) with PH, arising during MI to improve pre-vention and outcomes. Material and methods. The study included men 19-60 y.o. with MI and various dynamics of mean pulmonary artery pressure (MPAP), determined by echocardiography (A. Kitabatake) in first 48 hours (1) and completion of third week (2). Patients were divided into four groups: studied (I) included 67 patients (mean age 50.4±7.1 y.o) with PH (MPAP2 25 and more mm Hg) and normal of MPAP1 level. Group II included patients with a normal MPAP in both phases of study (70; 52.1±6.6 y.o); group III – with elevated MPAP at both study points (149; 51.2±5.5 y.o) and IV – with in-creased MPAP1 and normal MPAP2 (61, 50.5±6.8 y.o). A comparative assessment of the MI CF frequency in selected groups were performed. Results. The study group occupied intermediate place frequency in medical history presence: coronary heart disease (I: 59.5; II: 61.4; III: 63.6 and IV: 48.9%; p = 0.04), chronic heart failure (CHF) (35.7 ; 34.1; 51.1 and 24.5%, respec-tively; p=0.001), repeated (45.2; 42.0; 47.3 and 29.8%) and early recurrent (3.6; 3.4 ; 6.0 and 3.2%; pIII-IV=0.006) MI, Q-MI (44.0; 35.2; 58.7 and 56.4; p=0.001), anginal MI phenotype (75.0; 74.7; 54.3 and 77.7%; p˂0.0001) and acute HF (ACF) (45,2; 36,8; 50,5 и 48,9%; р=0,002). No pulmonary edema was detected in it (p˂0.0001). Conclusions. Men under 60 y.o. with PH resulting from MI occupy an intermediate place in frequency of complica-tions, ACF and CHF in first 56 days of MI during routine examination compared with other MPAP dynamics patients. This confirms the need for additional verification of PH genesis for the appropriate treatment.

Impact of the updated hemodynamic definitions on diagnosis rates of pulmonary hypertension.

We evaluated whether updated pulmonary hypertension definitive criteria proposed in sixth World Symposium on Pulmonary Hypertension had an impact on diagnosis of overall pulmonary hypertension and pre-capillary and combined pre- and post-capillary phenotypes as compared to those in European Society of Cardiology/European Respiratory Society 2015 pulmonary hypertension Guidelines. Study group comprised the retrospectively evaluated 1300 patients (age 53.1 ± 18.8 years, female 807, 62.1%) who underwent right heart catheterization with different indications between 2006 and 2018. Mean pulmonary arterial pressure ≥25 mmHg (European Society of Cardiology) and PAMP (mean pulmonary arterial pressure) >20 mmHg (World Symposium on Pulmonary Hypertension) right heart catheterization definitions criteria were used, respectively. For pre-capillary pulmonary hypertension, pulmonary artery wedge pressure ≤15 mmHg and pulmonary vascular resistance ≥3 Wood units criteria were included in the both definitions. Normal mean pulmonary arterial pressure (<21 mmHg), borderline mean pulmonary arterial pressure elevation (21–24 mmHg), and overt pulmonary hypertension (≥25 mmHg) were documented in 21.1, 9.8, and 69.1% of the patients, respectively. The pre-capillary and combined pre- and post-capillary pulmonary hypertension were noted in 2.9 and 1.1%, 8.7 and 2.5%, and 34.6 and 36.6% of the patients with normal mean pulmonary arterial pressure, borderline, and overt pulmonary hypertension subgroups, respectively. The World Symposium on Pulmonary Hypertension versus European Society of Cardiology/European Respiratory Society definitions resulted in a net 9.8% increase in the diagnosis of overall pulmonary hypertension whereas increases in the pre-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension diagnosis were only 0.8 and 0.3%, respectively. The re-definition of mean pulmonary arterial pressure threshold seems to increase the frequency of the overall pulmonary hypertension diagnosis. However, this increase was mainly originated from those in post-capillary pulmonary hypertension subgroup whereas its impact on pre-capillary and combined pre- and post-capillary pulmonary hypertension was negligible. Moreover, criteria of pre-capillary pulmonary vascular disease and combined pre- and post-capillary phenotypes were still detectable even in the presence of normal mean pulmonary arterial pressure. The obligatory criteria of pulmonary vascular resistance ≥3 Wood units seems to keep specificity for discrimination between pre-capillary versus post-C pulmonary hypertension after lowering the definitive mean pulmonary arterial pressure threshold to 20 mmHg.

Exercise intolerance in chronic thromboembolic pulmonary hypertension after pulmonary angioplasty.

Exercise pulmonary hypertension is common in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who experience shortness of breath during exercise and reduced exercise capacity despite normalised pulmonary arterial pressure (PAP) at rest; however, the relationship between exercise pulmonary hypertension and exercise capacity remains unclear. Here we aimed to determine whether exercise pulmonary hypertension is related to exercise capacity and ventilatory efficiency in CTEPH patients with normalised resting haemodynamics after pulmonary balloon angioplasty (BPA). In total, 249 patients with CTEPH treated with BPA (mean±sd age 63±14 years; male:female 62:187) with normal mean PAP (mPAP) (<25 mmHg) and pulmonary arterial wedge pressure (≤15 mmHg) at rest underwent cardiopulmonary exercise testing with right heart catheterisation. mPAP-cardiac output (CO) during exercise was plotted using multipoint plots. Exercise pulmonary hypertension was defined by a mPAP-CO slope >3.0. At rest, pulmonary vascular resistance was significantly higher in the exercise pulmonary hypertension group (n=116) than in the non-exercise pulmonary hypertension group (n=133). Lower peak oxygen consumption (13.5±3.8 versus 16.6±4.7 mL·min-1·kg-1; p<0.001) was observed in the former group. The mPAP-CO slope was negatively correlated with peak oxygen consumption (r= -0.45, p<0.001) and positively correlated with the minute ventilation versus carbon dioxide output slope (r=0.39, p<0.001). Impaired exercise capacity and ventilatory efficiency were observed in patients with CTEPH who had normalised PAP at rest but exercise pulmonary hypertension.

How did the updated hemodynamic definitions affect the frequency of pulmonary hypertension in patients with systemic sclerosis?

Pulmonary hypertension (PH) is a one of the major causes of death in patients with systemic sclerosis (SSc). In this study, we investigated the impact of updated hemodynamic definition proposed by the 6th PH World Symposium (6th WSPH) on the frequency of PH and its subtypes in patients with SSc. Patients with SSc admitted between 2015 and 2019 and who underwent right heart catheterization (RHC) were included. The frequency of PH and its subgroups based on the hemodynamic definitions of both 2015 European Society of Cardiology/European respiratory Society (ESC/ERS) PH guidelines and 6th WSPH was compared. Of the 65 patients with SSc, 23 (35.4%) had normal mean pulmonary arterial pressure (mPAP), 20 (30.8%) had mildly elevated mPAP (21-24 mm Hg), and 22 (33.8%) had PH [pulmonary arterial hypertension (PAH) (n=16, 24.6%), group 2 PH (n=5, 7.7%), group 3 PH (n=1, 1.5%)] according to the 2015 ESC/ERS PH definition. Based on the updated criteria, 7 (10.8% of total cohort) additional patients were reclassified as having PH [PAH (n=3), group 2 PH (n=3), group 3 PH (n=1)]. The impact of the updated definition on the frequency of PH and PAH in our cohort was greater than previously reported, which may be caused by the difference in screening strategies for PAH.

A beneficial technique for preventing the device protrusion to the aorta during percutaneous patent ductus arteriosus closure: "Balloon-assisted device releasing technique".

Although percutaneous closure of patent ductus arteriosus is an established safe procedure, protrusion of the device to descending aorta may occur in various degrees during these procedures, especially in small infants. The aim of our study is to evaluate the benefits of balloon-assisted device releasing technique in the era of preventing device protrusion and conditions related to protrusion. One hundred and fifty-five infants, who underwent patent ductus arteriosus closure with Amplatzer duct occluder I device between January, 2012 and December, 2018, were retrospectively analysed. Balloon-assisted device releasing technique was used in 20 cases (group 1, 12.9%), between January, 2015 and December, 2018. Procedures in which the technique had been used were compared with the remaining ones (group 2, 87.1%, n = 135) with regard to device stabilisation, aortic disc protrusion to the aorta, iatrogenic coarctation, and device embolisation. There was no significant difference by means of gender, age, weight, and the ductal diameter, whereas the average mean pulmonary artery pressure was significantly higher in group 1. Device protrusion and related complications were significantly higher in group 2; thus, additional catheterisations or surgical interventions were required, while no additional intervention was required in group 1. The balloon-assisted device releasing technique provides a good device stabilisation and prevents protrusion of the device and related complications during percutaneous patent ductus arteriosus closure in selected cases.

Safety and Efficacy of Acute Pulmonary Embolism Treated via Large-Bore Aspiration Mechanical Thrombectomy Using the Inari FlowTriever Device.

To report initial experience with safety and efficacy in the treatment of pulmonary embolism (PE) using the FlowTriever device. A single-center retrospective study was performed in all patients with acute central PE treated using the FlowTriever device between March 2018 and March 2019. A total of 46 patients were identified (massive= 8; submassive= 38), all with right ventricular (RV) strain and 26% with thrombolytic contraindications. Technical success (according to SIR reporting guidelines) and clinical success (defined as mean pulmonary artery pressure intraprocedural improvement) are reported, as are major device and procedure-related complications within 30 days after discharge. Technical success was achieved in 100% of cases (n= 46). Average mean pulmonary artery pressure improved significantly from before to after the procedure for the total population (33.9 ± 8.9 mm Hg before, 27.0 ± 9.0 mm Hg after; P < .0001; 95% confidence interval [CI], 5.0-8.8), submassive cohort (34.7 ± 9.1 mm Hg before, 27.4 ± 9.2 mm Hg after; P < .0001; 95% CI, 5.2-9.5) and massive cohort (30.4 ± 6.9 mm Hg before, 25.4 ± 8.2 mm Hg after; P < .05; 95% CI:0.4-9.6). Intraprocedural reduction in mean pulmonary artery pressure was achieved in 88% (n= 37 of 42). A total of 100% of patients (n= 46 of 46) survived to hospital discharge. In total, 71% of patients (n= 27 of 38) experienced intraprocedural reduction in supplemental oxygen requirements. Two major adverse events (4.6%) included hemoptysis requiring intubation, and procedure-related blood loss requiring transfusion. No delayed procedure-related complications or deaths occurred within 30 days of hospital discharge. Initial clinical experience using the FlowTriever to perform mechanical thrombectomy showed encouraging trends with respect to safety and efficacy for the treatment of acute central, massive, and submassive pulmonary embolism.

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.

Exercise capacity in COPD patients with exercise-induced pulmonary hypertension

BackgroundPulmonary hypertension (PH) in patients with COPD is associated with reduced exercise capacity. A subgroup of COPD patients has normal mean pulmonary artery pressure (mPAP) at rest, but develops high mPAP relative to cardiac output (CO) during exercise, a condition we refer to as exercise-induced pulmonary hypertension (EIPH). We hypothesized that COPD patients with EIPH could be identified by cardiopulmonary exercise test (CPET) and that these patients have lower exercise capacity and more abnormal CPET parameters compared to COPD patients with normal hemodynamic exercise response.MethodsNinety-three stable outpatients with COPD underwent right heart catheterization with the measurement of mPAP, CO, and capillary wedge pressure at rest and during supine exercise. Resting mPAP <25 mmHg with ΔmPAP/ΔCO slope above or below 3 mmHg/L/min were defined as COPD-EIPH and COPD-normal, respectively. Pulmonary function tests and CPET with arterial blood gases were performed. Linear mixed models were fitted to estimate differences between the groups with adjustment for gender, age, and airflow obstruction.ResultsEIPH was observed in 45% of the study population. Maximal workload was lower in COPD-EIPH compared to COPD-normal, whereas other CPET measurements at peak exercise in % predicted values were similar between the two groups. After adjustment for gender, age, and airflow obstruction, patients with COPD-EIPH showed significantly greater increase in oxygen uptake, ventilation, respiratory frequency, heart rate, and lactate with increasing work load, as well as more reduction in pH compared to those with normal hemodynamic responses.ConclusionCOPD-EIPH could not be discriminated from COPD-normal by CPET. However, COPD-EIPH experienced a higher cost of exercise in terms of higher oxygen uptake, ventilation, respiratory frequency, heart rate, and lactate for a given increase in workload compared to COPD-normal.

ACUTE VASODILATOR TESTING: AN OPPORTUNITY TO REFINE STUDY DESIGN AND PROVIDE PRECISION CARE IN PULMONARY HYPERTENSION

SESSION TITLE: Pulmonary Vascular Disease SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/07/2018 10:45 AM - 11:45 AM INTRODUCTION: Inhaled nitric oxide is currently used to acutely evaluate pulmonary vascular reactivity and identify patients with pulmonary arterial hypertension who may be appropriate candidates for long-term treatment with a calcium channel blocker (CCB). However, some patients with an acute decrease in mean pulmonary arterial pressure (MPAP) with nitric oxide fail to improve, or progressively worsen over time, with a CCB alone. Here we present a patient with severe pulmonary arterial hypertension who develops a normal MPAP while breathing nitric oxide. We describe the acute and long-term effects of other agents on her MPAP. CASE PRESENTATION: The patient presented at 8 years of age in 2003 with decreased exercise tolerance and syncope. Non-invasive studies were consistent with a diagnosis of idiopathic pulmonary arterial hypertension. Her hemodynamic measurements during heart catheterization and acute vasodilator testing are shown along with interim therapy in the table. See tableThe patient's MPAP has consistently decreased to normal during acute vasodilator testing with nitric oxide. There was little or no acute improvement in MPAP with nitroglycerin and sildenafil, and a corresponding failure with therapy long-term. There was moderate acute improvement with diltiazem and riociguat, and a corresponding moderate improvement with amlodipine long-term. The dose of amlodipine and the dose of riociguat have been limited by adverse side effects (gingival hyperplasia and gastroesophageal reflux). Nighttime nitric oxide therapy was safely used in her home for 4 months when an increase in MPAP was temporally associated with an adverse reaction to minocycline. Unfortunately, a reliable delivery system was not available to continue long-term therapy at that time.She has a polymorphism in endothelial nitric oxide synthase (Glu298Asp), a normal cytogenomic microarray and elevated levels of asymmetric dimethylarginine. Genetic testing for specific variants associated with pulmonary arterial hypertension has not been performed. DISCUSSION: Our patient's response to nitric oxide is consistent with a phenotype of decreased endothelial nitric oxide synthase function. Her clinical course illustrates how acute vasodilator testing may be used to guide therapy, even if a corresponding genotype is unknown. In this case, long-term inhaled nitric oxide may be more effective and less likely to cause adverse systemic effects than other agents. Any agent may fail to demonstrate a beneficial effect in a heterogeneous population of patients, but may have a meaningful effect in a subset of responsive patients. For example, a combination of inhaled nitric oxide and a CCB might prevent long-term treatment failures that occur with a CCB alone. CONCLUSIONS: Acute vasodilator testing identified appropriate medications for the long-term therapy of our patient. There is a need to design trials with a focus on precision care. Reference #1: Day, RW. Differences in the acute pulmonary vascular effects of oxygen with nitric oxide and diltiazem: Implications for the long-term treatment of pulmonary arterial hypertension. Congenit Heart Dis 2013;8:71-77. DISCLOSURES: No relevant relationships by Meghan Cirulis, source=Web Response No relevant relationships by Nicole Day, source=Web Response No relevant relationships by Ronald Day, source=Web Response No relevant relationships by Lynda Jorgensen, source=Web Response

Clinical diagnostic value of circulating serum miR-509-3p in pulmonary arterial hypertension with congenital heart disease

ObjectiveMost pulmonary arterial hypertension (PAH) biomarkers are used for risk stratification and prognosis prediction. We aimed to evaluate the diagnostic value of circulating serum miR-509-3p in PAH with congenital heart disease. MethodsPreoperative blood samples were collected from patients who were diagnosed as having PAH and had to receive right ventricular catheterization. According to right ventricular catheterization results, these patients were divided into a control group with normal mean pulmonary artery pressure (mPAP < 20 mmHg) and a PAH group (mPAP ≥ 25 mmHg). The expression of serum miR-509-3p was detected by real-time quantitative PCR. The receiver operating characteristic curve was plotted. A dichotomous logistic regression model was also established. ResultsThe expression level of circulating serum miR-509-3p in the PAH group was significantly lower than that of the control group. Based on the relative expression of miR-509-3p in serum, the area under the curve (AUC) for single-factor diagnosis of PAH was 0.694 (95% confidence interval [CI]: 0.555–0.883, P = 0.01), which was approximately 0.81 (AUC of noninvasive screening by echocardiography). When the relative expression of miR-509-3p was 0.79, the sensitivity and specificity were 80% and 60%, respectively. Based on the established model, AUC of serum miR-509-3p combined with echocardiography was 0.844, thus indicating a high diagnostic value. Compared with two individual indices, the combination further enhanced the diagnostic efficiency. ConclusionsThe expression of miR-509-3p decreased in the serum of patients with PAH along with congenital heart disease. The diagnostic value of circulating serum miR-509-3p in PAH was close to that obtained by echocardiography. Combining the two indices further increased the diagnostic efficiency of PAH.

Mild Elevation of Pulmonary Arterial Pressure as a Predictor of Mortality.

Normal mean pulmonary arterial pressure (mPAP) is 14.0 ± 3.3 mm Hg (mean ± SD). The prognostic relevance of mildly elevated mPAP not fulfilling the definition of pulmonary hypertension (PH; mPAP ≥ 25 mm Hg) has not been prospectively evaluated in a real-world setting. To assess the association of resting mPAP with all-cause mortality in a retrospective and a prospective cohort of patients with unexplained dyspnea and/or at risk of PH. Prognostic cutoffs were calculated by means of 1) classification and regression tree (CART) analysis without any preset thresholds, and 2) preset thresholds on the basis of literature data defining mPAP as lower-normal (≤mean + 1 SD), upper-normal (between mean + 1 SD and mean + 2 SD), borderline (between mean + 2 SD and 25 mm Hg), and manifest PH (≥25 mm Hg). We performed univariate and multivariate survival analysis adjusted for age and comorbidities. We enrolled 547 patients, of whom 137, 56, 64, and 290 presented with lower-normal, upper-normal, or borderline mPAP, and manifest PH, respectively. The CART analysis on mPAP discriminated three prognostic groups: mPAP less than 17 mm Hg, 17 to 26 mm Hg, and greater than 26 mm Hg, with significantly decreasing survival. The univariate analysis on the basis of preset thresholds showed that upper-normal mPAP, borderline mPAP, and manifest PH were significantly associated with poor survival compared with lower-normal mPAP. In the multivariate model, considering age and comorbidities, only borderline mPAP (hazard ratio, 2.37; 95% confidence interval, 1.14-4.97; P = 0.022) and manifest PH (hazard ratio, 5.05; 95% confidence interval, 2.79-9.12; P < 0.001) were significantly associated with poor survival. In patients at risk for PH and/or with unexplained dyspnea, CART analysis detects prognostic thresholds at a resting mPAP of 17 mm Hg and 26 mm Hg, and values between 20 mm Hg and 25 mm Hg represent an independent predictor of poor survival. Clinical trial registered with www.clinicaltrials.gov (NCT 01607502).

P2-2 - The Roles of IL-18 and Ferritin in Systemic Sclerosis Patients With Pulmonary Hypertension

Backgrounds: Systemic sclerosis (SSc), a disease that causes fibrosis in various organs, can develop pulmonary hypertension (PH) due to lung fibrosis. We found that IL-18 induced pulmonary hypertension in a hypoxia model mouse. The association between IL-18 and ferritin in patients with viral infections has recently been reported. However, the roles of IL-18 and ferritin in SSc patients with PH are not fully elucidated. The purpose of this study is to investigate the relationships among IL-18, ferritin, and PH in SSc patients. Methods: We enrolled 18 SSc patients who visited our hospital between January 2014 and June 2016 and presented tricuspid regurgitation jet velocity >2.5 m/s in this retrospective observational study. We measured the serum levels of ferritin and IL-18, and the parameters of right heart catheterization (RHC). Results: Mean age of the patients was 66 y.o. and 16 patients were female. Average mean pulmonary artery pressure were 24.0 ± 3.5 mmHg and pulmonary vascular resistance index (PVRI) 4.6 ± 1.9 wood. Serum IL-18 levels were 288.4 ± 49.8 pg/mL and serum ferritin levels were 47.0 ± 25.9 ng/mL. levels of serum IL-18 and serum ferritin were correlated with PVRI respectively (IL-18 r = 0.674, ferritin r = 0.734). In addition, serum IL-18 was correlated with serum ferritin (r = 0.481). Conclusion: In SSc patients, IL-18 as well as ferritin was associated with PH.

α1-A680T variant in GUCY1A3 as a candidate conferring protection from pulmonary hypertension among Kyrgyz highlanders.

Human variation in susceptibility to hypoxia-induced pulmonary hypertension is well recognized. High-altitude residents who do not develop pulmonary hypertension may host protective gene mutations. Exome sequencing was conducted on 24 unrelated Kyrgyz highlanders living 2400 to 3800 m above sea level, 12 (10 men; mean age, 54 years) with an elevated mean pulmonary artery pressure (mean±SD, 38.7±2.7 mm Hg) and 12 (11 men; mean age, 52 years) with a normal mean pulmonary artery pressure (19.2±0.6 mm Hg) to identify candidate genes that may influence the pulmonary vascular response to hypoxia. A total of 140 789 exomic variants were identified and 26 116 (18.5%) were classified as novel or rare. Thirty-three novel or rare potential pathogenic variants (frameshift, essential splice-site, and nonsynonymous) were found exclusively in either ≥3 subjects with high-altitude pulmonary hypertension or ≥3 highlanders with a normal mean pulmonary artery pressure. A novel missense mutation in GUCY1A3 in 3 subjects with a normal mean pulmonary artery pressure encodes an α1-A680T soluble guanylate cyclase (sGC) variant. Expression of the α1-A680T sGC variant in reporter cells resulted in higher cyclic guanosine monophosphate production compared with the wild-type enzyme and the purified α1-A680T sGC exhibited enhanced sensitivity to nitric oxide in vitro. The α1-A680T sGC variant may contribute to protection against high-altitude pulmonary hypertension and supports sGC as a pharmacological target for reducing pulmonary artery pressure in humans at altitude.

S46 Outcome after pulmonary endarterectomy (PEA): Long term follow-up of the UK national cohort

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is a life threatening condition that historically has a poor outcome with supportive medical treatment. Pulmonary endarterectomy (PEA) is the treatment of choice and offers...