Forms Of Pulmonary Arterial Hypertension Research Articles

Функція зовнішнього дихання та дифузійна здатність легень у пацієнтів із різними формами легеневої гіпертензії

The aim – to compare pulmonary function test (PFT) results and diffusion capacity of the lungs for carbon monoxide (DLCO) in patients with various forms of pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH) and healthy individuals; to establish correlations between PFT, DLCO and parameters used to stratify the risk of death in pulmonary hypertension (PH).Materials and methods. 74 patients were included: 18 with idiopathic PAH (IPAH), 15 with PAH associated with congenital heart defects (PAH-CHD), 21 with CTEPH and 20 healthy persons (control group). All participants underwent an assessment of PFT (vital capacity (VC), forced vital capacity (FVC), forced expiratory volume during one second (FEV1), peak expiratory velocity (PEV), maximum expiratory flow (MEF) 75, MEF-50, MEF-25) and measurement of DLCO. For all PH patients the standard examinations were provided, including N-terminal brain natriuretic peptide (NT-proBNP) assessment and right heart catheterization. Results. Patients of all PH groups had significantly lower parameters of PFT and DLCO, compared to the control group. The most pronounced and reliable decrease in PFT was observed among patients with PAH-CHD. The lowest DLCO was observed in CTEPH group. PH patients with DLCO < 64 %, compared with DLCO ≥ 64 %, had significantly lower distance of the 6-minute walk test (6MWT) (p = 0.014), TAPSE (р = 0.015), SpO2 during pulse oximetry and direct measurement (p = 0.023 and 0.032, respectively), hemoglobin level (p = 0.031). They had a significantly higher level of NT-proBNP (p = 0.012) and they were somewhat older (p = 0.053). DLCO < 64 % correlated with hemoglobin level (r = –0.31, p = 0.022), 6MWT distance (r = –0.35, p = 0.012), SpO2 (r = –0.29, p = 0.036), TAPSE (r = –0.34, p = 0.012) and NT-proBNP (r = 0.27, p = 0.048). Independent predictors of reduced DLCO were hemoglobin level (β = 0.95, CI 0.90-0.99), SpO2 (β = 0.75, CI 0.58-0.95) and TAPSE (β = 0.75, CI 0.63-0.91).Conclusions. Parameters of PFT and DLCO were significantly lower in patients of all PH groups compared to the healthy individuals. Patients with PAH-CHD had significantly worse PFT parameters. In the general population of patients with PH, PFT indicators, which characterize inspiratory capabilities, were independently correlated with the area of ​​the right atrium. The reduced DLCO (< 64 %) correlated with the level of hemoglobin, SpO2 and indicators of the patient functional state. However, low levels of hemoglobin, SpO2, and TAPSE were independent predictors of low DLCO.

Genetic testing in pulmonary hypertension in adults and children

Abstract Pathogenic genetic variants have been found in patients with different forms of pulmonary arterial hypertension (PAH). Our aim was to define the genetic background of patients with idiopathic PAH (IPAH), heritable PAH (HPAH), pulmonary veno-occlusive disease (PVOD) and PAH associated with congenital heart disease (PAH-CHD); both in adult and pediatric age. REHAP and REHIPED are Spanish, voluntary, multicenter registries that include patients with PAH. REHAP started in 2007 and includes patients over 18 years of age. REHIPED started in 2009 and collects patients between 2 months and 18 years of age. Patients with IPAH, HPAH, PVOD and PAH-CHD who have undergone a genetic testing were included. 413 adults and 122 children were analyzed. From 2011, Sanger sequencing and multiplex ligation-dependent probe amplification were used to detect genetic variants in the BMPR2, TBX4, and KCNK3 genes. Since 2014, a next generation sequencing (NGS) panel of 21 genes was applied. In 2017 this panel was expanded to cover 35 genes, and in 2019, it was expanded to 37 genes. Since 2020, whole-exome sequencing has been applied for the previously followed-up patients without known pathogenic/likely pathogenic (P/LP) genetic variants, and for each incident case. There was a statistically significant difference (p 0.031) in the etiologies among adults and children. The etiologies in adults were 242 (59%) IPAH, 25 (6%) HPAH, 83 (20%) PAH-CHD, 63 (15%) PVOD. The etiologies in children were 66 (54%) IPAH, 8 (7%) HPAH, 38 (31%) PAH-CHD, and 10 (8%) PVOD. The genetic testing had a variant in 121 (29%) adults (56% pathogenic, 9% likely pathogenic, 32% VUS) and 63 (52%) children (65% pathogenic, 16% LP, 19% VUS) (adults vs children p < 0.001). BMPR2 was the most frequent variant in both populations, followed by EIF2AK4. Patients with HAPH and PVOD are more likely to have a genetic variant, while PAH-CHD are the less likely to have one; both in adults and children (p<0.001). The etiology was reclassified after the genetic testing in 13% adults and 19% children (p 0.08); including 6 adults and 4 children initially classified as IPAH and then diagnosed of PVOD when a P/LP variant was found in EIF2AK4. Also, 5 children were initially diagnosed as IPAH and then reclassified as multisystemic disorders (4 NFU1 and 1 MECP2) In conclusion, a significant number of patients with PAH have a variant in genetic testing, especially if they are diagnosed in pediatric age. BMPR2 is the most frequent variant in our cohort, followed by EIF2AK4. Knowing the genetic background of our patients enables a better classification and understanding of the disease. This is especially important in patients initially diagnosed of PAHI who are then classified as PVOD. Also, knowing the genetic background may help develop new treatments in the future.

An overview of treatment for atrial septal defect with pulmonary hypertension

Background: Atrial Septal Defect (ASD) is a congenital heart defect which can be the cause of comorbidities in the form of Pulmonary Arterial Hypertension (PAH) and therapy cannot be done simply by correcting the ASD but requires further study and evaluation.Purpose: Describe the treatment given to patients with ASD and PAH and the correlation between the administration of interventional therapy and the patient's probability of PH.Method: This study is a descriptive quantitative using a cross-sectional research design. The sampling technique was total sampling method. The samples were 41 ASD patients with PAH at Prof. Ngoerah General Hospital in Denpasar in 2022. Patients under 18 years of age and those with other congenital heart disease will be excluded. The demographic characteristics assessed were the patient's age and gender. The therapy data included information on medical therapy and intervention therapy.Results: Focus of medical therapy was supportive therapy rather than specific PAH therapy. Percutaneous ASD closure was the most widely-used intervention therapy compared to surgical ASD closure. Based on statistical analysis, the p value > 0.05 is 0.284, so there is no significant correlation between the probability of the patient's pH and the provision of intervention therapy.Conclusion: At Prof Ngoerah General Hospital Denpasar, the majority of ASD patients with complications of pulmonary hypertension were females aged between 21 to 30 years. The medical therapy given is adjusted based on the severity of PH as assessed through echocardiography examination. Majority of patients received supportive therapy compared to specific therapy for PAH. Medical therapy is prioritized for patients who have contraindication criteria for interventional therapy. Percutaneous ASD Closure was found to be the largest percentage in interventional therapy regardless of the severity, except for patients who were indicated to undergo surgical ASD closure. There is no significant relationship between the patient's PH probability level and the choice of intervention therapy.

Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies.

Portopulmonary hypertension (PoPH) carries a worse prognosis than other forms of pulmonary arterial hypertension (PAH). Data regarding use of PAH-specific therapies in patients with PoPH are sparse as they are usually excluded from clinical trials. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles in patients with PoPH newly initiating macitentan in the USA using the OPUS/OrPHeUS combined dataset. OPUS was a prospective, US, multicenter, observational drug registry (April 2014-June 2020); OrPHeUS was a retrospective, US, multicenter chart review (October 2013-March 2017). Additional information regarding patients' liver disease was retrospectively collected for patients with PoPH in OPUS. The OPUS/OrPHeUS dataset included 206 patients with PoPH (median age 58years; 52.4% female), with baseline cirrhosis and liver test abnormalities reported in 72.8% and 31.6% of patients respectively. Macitentan was initiated as combination therapy in 74.8% of patients and median (Q1, Q3) exposure to macitentan was 11.9 (3.1, 26.0) months. One-year Kaplan-Meier estimates (95% confidence limit, CL) of patients free from all-cause hospitalization and survival were 48.6% (40.7, 56.0) and 82.2% (75.1, 87.4). Of the 96 patients with PoPH in OPUS, 29.2% were classified as in need of liver transplant due to underlying liver disease during the study; transplant waitlist registration was precluded because of PAH severity for 32.1% and 17.9% were transplanted. Hepatic adverse events (HAE) were experienced by 49.0% of patients; the most common being increased bilirubin (16.0%), ascites (7.3%), and hepatic encephalopathy (5.8%); 1.5% and 21.8% of patients discontinued macitentan as a result of HAE and non-hepatic adverse events. There were no unexpected safety findings in patients with PoPH treated with macitentan. These data add to the evidence supporting the safety and tolerability of macitentan in patients with PoPH. A graphical abstract is available with this article. OPsumit® Users Registry (OPUS): NCT02126943; OPsumit® Historical Users cohort (OrPHeUS): NCT03197688; www. gov .

Clinical features of pulmonary arterial hypertension associated with systemic sclerosis.

Systemic sclerosis is an autoimmune disorder of the connective tissue characterized by disordered inflammation and fibrosis leading to skin thickening and visceral organ complications. Pulmonary involvement, in the form of pulmonary arterial hypertension and/or interstitial lung disease, is the leading cause of morbidity and mortality among individuals with scleroderma. There are no disease-specific therapies for pulmonary involvement of scleroderma, and pulmonary arterial hypertension in this cohort has typically been associated with worse outcomes and less clinical response to modern therapy compared to other forms of Group I pulmonary hypertension in the classification from the World Symposium on Pulmonary Hypertension. Ongoing research aims to delineate how pathologic microvascular remodeling and fibrosis contribute to this poor response and offer a window into future therapeutic targets.

Pregnancy in Patients with Moderate and Highly Complex Congenital Heart Disease.

Although not completely devoid of risk, pregnancy can be managed in virtually all patients affected by even the most complex forms of congenital heart disease. It is not however advisable in patients with any form of pulmonary arterial hypertension. Pregnancy is even manageable in patients with univentricular heart converted to Fontan circulation. A personalised risk stratification should be performed, and patients affected by advanced NYHA functional class appropriately warned of the potential risks. In this setting, metabolomics might represent a novel tool for use in conducting personalised risk stratification. All pregnancies, particularly those at higher risk, should be managed in a tertiary care centre capable of providing the necessary assistance to both the mother and infant. With a few rare exceptions, vaginal delivery is to be preferred over caesarean section due to the lower degree of maternal and foetal complications. The desire for motherhood, at times extreme in women with congenital heart disease, may often be accomplished, thus providing a ray of hope in the lives of these patients.

Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive Disease.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary arterial hypertension (PAH) occurring in a heritable form (hPVOD) due to biallelic inactivating mutations of EIF2AK4 (encoding GCN2, general control nonderepressible 2) or in a sporadic form in older age (sPVOD), following exposure to chemotherapy or organic solvents. In contrast to PAH, PVOD is characterized by a particular remodeling of the pulmonary venous system and the obliteration of small pulmonary veins by fibrous intimal thickening and patchy capillary proliferation. The pathobiological knowledge of PVOD is poor, explaining the absence of medical therapy for PVOD. Lung transplantation remains the only therapy for eligible PVOD patients. As we recently demonstrated, respiratory diseases, chronic obstructive pulmonary disease, or cystic fibrosis exhibit lipointoxication signatures characterized by excessive levels of saturated phospholipids contributing to the pathological features of these diseases, including endoplasmic reticulum stress, pro-inflammatory cytokines production, and bronchoconstriction. In this study, we investigated and compared the clinical data and lung lipid signature of control (10 patients), idiopathic PAH (7 patients), heritable PAH (9 BMPR2 mutations carriers), hPVOD (10 EIF2AK4 mutation carriers), and sPVOD (6 non-carriers) subjects. Mass spectrometry analyses demonstrated lung lipointoxication only in hPVOD patients, characterized by an increased abundance of saturated phosphatidylcholine (PC) at the expense of the polyunsaturated species in the lungs of hPVOD patients. The present data suggest that lipointoxication could be a potential player in the etiology of PVOD.

PORTOPULMONARY HYPERTENSION PRACTICE PATTERNS AFTER LIVER TRANSPLANTATION

PORTOPULMONARY HYPERTENSION PRACTICE PATTERNS AFTER LIVER TRANSPLANTATION

Porto-pulmonary arterial hypertension: Translation of pathophysiological concepts to the bedside

Porto-pulmonary arterial hypertension (PoPAH) is a form of pulmonary arterial hypertension (PAH) that affects patients with cirrhosis, and — to a lesser extent — patients with non-cirrhotic liver diseases. Compared with other forms of PAH, PoPAH is more prevalent in male, in older subjects, and is characterized by lower mean pulmonary arterial pressure (mPAP) and lower pulmonary vascular resistance (PVR) with higher cardiac output. Despite more favorable hemodynamics and functional class, patients with PoPAH have a significantly worse survival than patients with other forms of PAH, likely because of liver-related events and therapeutic barriers to PAH-specific therapy. Furthermore, here cardiopulmonary and hepatic complications may affect treatment efficacy. These patients have been excluded from most randomized clinical trials testing PAH-specific treatments. To date, there is only one study investigating efficacy, safety, tolerability and pharmacokinetics of PAH-specific therapy in patients with PoPAH in a randomized placebo-controlled setting. In this trial the use of the endothelin-1 receptor antagonist macitentan showed clear hemodynamic benefit without safety concerns. However, the drug effects on functional capacity and mortality remain unclear. Here we review the current knowledge on the pathophysiology and management of PoPAH and report a case vignette of a patient with PoPAH due to hepatorenal polycystic disease.

Combined Heart-Lung Transplantation: A Single-Center Experience of 50 Patients over 30 Years

<h3>Purpose</h3> To analyze our institutional outcomes in heart-lung transplantation (HLTx). <h3>Methods</h3> We performed a single-center retrospective analysis of all patients who underwent HLTx at the University Hospitals Leuven (UZL) from 1991 to 2018 and compared our results to ISHLT registry data. <h3>Results</h3> 50 patients underwent HLTx in UZL. In-hospital mortality was 24% vs 72% in the ISHLT database (p<1.10^-5). On average baseline characteristics of donors and receptors were comparable between UZL and ISHLT. Kaplan-Meier survival curves for both are depicted in figure 1. When considering the eras 1991-2003 and 2004-2018, 1-, 5, and 10-year survival rates of UZL were more favorable for the latter era; 15-year survival was significantly better for era 2004-2018, as depicted in figure 2. Over time, we observed an increase in cardiac-related indications with Eisenmenger syndrome being the most important (56% vs 25% in the ISHLT registry, p<1.10^-5). Other forms of pulmonary arterial hypertension (PAH) were an important indication to perform HLTx (24% in both groups). The major cause of late mortality in our population was rejection (41.4%), more specifically chronic lung allograft dysfunction. <h3>Conclusion</h3> Between 1991 and 2018, we performed 50 HLTx's. The most frequent indication was Eisenmenger syndrome, but with a twofold higher proportion in our population compared to the ISHLT registry. The proportion of other forms of PAH was comparable. While over time the indications shifted from pulmonary to cardiac conditions, our survival continues to improve.

Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.

Diagnostic value of right heart and pulmonary artery catheterization in patients with suspected pulmonary hypertension. Part 2. Invasive study of parameters of hemodynamics and oxygen transport

The aim – evaluate the parameters of pulmonary and systemic hemodynamics obtained in patients with various forms of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Ukraine.Materials and methods. The study included 195 patients: IPAH was in 68 patients; PAH associated with connective tissue diseases (CTD) – in 21 patients; PAH associated with HIV infection – in 4 patients; PAH associated with portal hypertension (PH) – in 4 patients; PAH associated with congenital heart disease – in 25 patients; CTEPH – in 51 patients, pulmonary hypertension (PH) associated with left heart disease (LHC) – in 5 patients and 17 patients who were excluded from the diagnosis of PH. From 2014 to 2019, these patients underwent 220 procedures of right heart catheterization (RHC) in accordance with current European Guidelines. Also, all patients underwent echocardiographic examination and determined the gas composition of blood and indicators of acid-base balance using the ABL 735 analyzer, calculated the parameters of the affinity of hemoglobin to oxygen (p50).Results and discussion. The lowest level of arterial blood oxygen saturation was in the group of patients with PH due to LHD – 88.9 % (p&lt;0.05); in other groups it averaged 94–97 %. The oxygen content in arterial blood was the lowest in the group of patients with PH due to LHD – 15.7 ml/L (p&lt;0.05); in other groups this indicator was equal to 17.4–18.7 ml/L. The lowest oxygen saturation of mixed venous blood (SvO2) was in the PAH group associated with HIV – 58 % (p&lt;0.05), and close to critical (&lt; 65 %) SvO2 level was observed in the IPAH group – 66.3 %. CTEPH – 66.0 %. The highest level of this indicator was in the PAH group associated with portal hypertension – 81.1 %. The arterio-venous difference was highest in the PAH associated with HIV group – 5.6 ml/L, and the smallest in the PAH associated with PH group – 2 ml/L. On the other hand, the oxyhemoglobin dissociation curve was almost normal in all groups, except for the group of patients with PAH associated with portal hypertension.Conclusions. The most severe disorders of hemodynamics and oxygen transport were observed in the group of PAH patients associated with HIV compared with other forms of PAH and CTEPH. The IPAH and CTEPH groups were similar in terms of hemodynamics, despite a different pathophysiological mechanism. In the group of patients with PAH associated with CTD, the results of the RHC were slightly better than in the group of patients with IPAH, reflecting that the hemodynamic component is not the leading one for prognosis in these patients. Also, the performance of the right ventricle was significantly higher in patients with PAH compared with the group without PH.

The biventricular dysfunction evaluation in the different types of pulmonary hypertension

Abstract Background Right ventricular (RV) function is well-known prognostic factor in patients with pulmonary hypertension (PH). However, situation becomes critical when underfilling of left ventricle (LV) leads to systemic hypoperfusion and scenario worsening. Objective To evaluate the relationship of RV and LV dysfunction in patients with the different forms of PH. Methods We evaluated parameters of RV and LV function and their relationship during right heart catheterization (RHC) in 125 patients with different forms of pulmonary arterial hypertension (PAH) and 51 patients with chronic thromboembolic PH (CTEPH), 7 patients with PH associated with left heart disease (LHD) and 17 patients in whom PH was excluded after procedure. In all patients recommended echocardiography protocol (Echo) and NT-proBNP level evaluation were performed. Results In the group without PH the RV stroke work index (RVSWI) level and its ratio to the LV stroke work index (LVSWI) were lowest and in the normal range: 7,0±0,7 ml·mmHg/m2 and 0,13±0,02 respectively. In all patients with PH, we noted the significant elevation of RVSWI &amp;gt;20 ml·mmHg/m2. Patients with PAH and CTEPH had a smaller left atrium, LV volumes on Echo and decreased stroke volume and pulmonary artery wedge pressure. The underfilling of LV in IPAH and CTEPH groups accompanied by severe lowering of LWSWI to 35–45 ml·mmHg/m2 (p&amp;lt;0,05 compared with LHD group and patients without PH). In spite of the levels of cardiac index were similar in patients with LHD and without PH, the RVSWI (23,1±2,7 ml·mmHg/m2) and its RVSWI/LVSWI ratio (0,53±0,09) were significantly higher in LHD group and confirmed severe RV overload. Only in HIV infection group observed severe depression of the pumping function of both heart's sides and levels of RWSWI and LVSWI were lowest, but the ratio was elevated (0,53) and indicated RV overload. Similar data were observed when we compare pumping coefficients of RV and LV in different groups. We did not find any association between NT-proBNP level and the LV volume and function. Conclusion The simultaneous evaluation of parameters of RV and LV function and their ratio during RHC in patients with different types of PH allowed not just to estimate the degree of RV overload and dysfunction, but also LV underfilling and dysfunction. Funding Acknowledgement Type of funding sources: None.

Cardiovascular outcomes in women with the highest classification of maternal cardiovascular risk in pregnancy

Abstract Introduction The modified world health organization (mWHO) classification of maternal risk is used to estimate morbidity and mortality in pregnant women with cardiovascular disease. Those in the highest risk category (mWHO Risk Class IV) are at greatest risk. Pregnancy is contraindicated in this patients. Methods This was a retrospective review of pregnant women classified as mWHO risk class IV, who were managed in a tertiary joint cardiac-obstetric pathway between 2008 and 2018. Results In total, there were 35 pregnancies in 30 women with the highest cardiovascular risk for adverse maternal outcomes. The mean maternal age at delivery was 29.3±5.2 years. Eleven (36%) patients were diagnosed with cardiovascular disease during pregnancy. Fourteen had a form of pulmonary arterial hypertension (46%), 6 (20%) had severe systemic ventricular dysfunction, 4 (13%) had severe mitral or aortic stenosis, 4 (13%) had aortic dilatation or inherited aortopathy, 1 (3%) had a history of peri-partum cardiomyopathy and 1 (3%) had severe native coarctation of the aorta. In the 30 pregnancies followed up in our centre, 29 (96%) were single foetus pregnancies and 1 (4%) was a twin pregnancy. There were 30 live births, 1 foetus was lost in the twin pregnancy. Of these 29 (96%) patients underwent elective caesarean section and 1 (4%) emergency caesarean section. Cardiovascular complications occurred in 18 (60%) women. Of these, 5 (28%) had atrial arrhythmias during pregnancy, 6 (33%) had worsening of pulmonary hypertension, 6 (33%) had decompensated heart failure. Three women had interventions during pregnancy: 1 had percutaneous intervention for coarctation of aorta due to foetal and maternal compromise, 1 had electrophysiological ablation for atrial arrhythmias to improve systemic ventricular function and 1 had an electrical cardioversion for atrial fibrillation. There were no deaths during pregnancy or in the peripartum period. One patient who presented at 34 weeks gestation with severe peripartum cardiomyopathy required early inotropic support followed by extracorporeal membrane oxygenation (ECMO) support post-delivery, died at 2 months post-partum. Conclusions With appropriate pre-pregnancy optimization, antepartum surveillance individualised peripartum care plans and multidisciplinary care throughout pregnancy, women at the highest risk for cardiovascular outcomes can have successful pregnancies, although the risk of cardiovascular complications remains high. Funding Acknowledgement Type of funding sources: None.

TO DRAIN OR NOT TO DRAIN: A THERAPEUTIC CONUNDRUM IN A PATIENT WITH PERICARDIAL TAMPONADE AND EISENMENGER SYNDROME

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: PAH is diagnosed when mean pulmonary artery pressure is greater or equal to 20 mmHg at rest with a pulmonary vascular resistance =3 Wood units. In regions without endemic schistosomiasis, it is commonly idiopathic (1). Eisenmenger syndrome (ES) is the most advanced form of pulmonary arterial hypertension (PAH) and is associated with several congenital heart defects such as ASDS, VSDS etc. CASE PRESENTATION: We present the case of a 30-year-old patient with a past medical history of Trisomy-21, unrestricted ventricular septal defect (VSD) complicated by Eisenmenger Syndrome, PAH (On Treprostinil and Bosentan), chronic hypoxia and Hashimoto's Thyroiditis, who presented from his group home for acute on chronic shortness of breath and fever. Initially, he was hypoxic and hypotensive with signs of severe volume overload on physical exam. Oxygen saturations improved mildly on high flow nasal cannula (HFNC). CT chest and bedside echocardiogram showed a massive pericardial effusion (4.5 cm at the largest point) with tamponade physiology, and pulsus paradoxus (Figure 1,2,3). He was started on vasopressors, inotropes, intravenous prostacyclin and inhaled epoprostenol. Extracorporeal membrane oxygen (ECMO) was planned to stabilize him and drain the effusion, but the family refused ECMO. A Swanz Ganz catheter was placed under fluoroscopic guidance to help guide management but it crossed the VSD and inadvertently ended up in the aorta after which it was removed. After multiple discussions with adult congenital heart disease experts, it was decided that draining the pericardial effusion was not an option given the concern for acute right ventricular failure which could precipitate hemodynamic collapse and cardiac arrest. Another concern was bleeding complications especially bleeding into the pericardial cavity from inadvertently puncturing the multiple collateral vessels that such patients develop. The patient gradually developed increasing vasopressor requirements and eventually passed away. DISCUSSION: A pericardial effusion develops when fluid accumulates between the two layers of pericardium. In PAH, it may develop due to elevated right atrial pressures or underlying connective tissue disease. Its presence in PAH is associated with a significantly increased risk of death and the decision to drain such an effusion remains highly controversial. Multiple studies have reported dismal prognosis of patients who have had such effusions drained (2). The Euro heart survey reported that mortality was particularly high in patients with Eisenmenger's, and they had an increased frequency of major bleeding events as well (2). CONCLUSIONS: Pericardial effusion drainage in patients with pulmonary arterial hypertension is controversial and is associated with poor outcomes. Mortality is particularly high in patients with Eisenmenger's, and a multidisciplinary approach should be utilized to manage such patients. REFERENCE #1: Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913. REFERENCE #2: Engelfriet PM, Duffels MG, Möller T, et al. Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart. 2007;93(6):682-687. DISCLOSURES: No relevant relationships by Saad Farooq, source=Web Response No relevant relationships by ELLIOT SULTANIK, source=Web Response No relevant relationships by Guy Weigold, source=Web Response No relevant relationships by Omar Yacob, source=Web Response

Progress in the treatment of pulmonary vascular diseases

Multiple progresses have been achieved in pulmonary vascular diseases in the last decades, including the areas of pulmonary hypertension and pulmonary thromboembolic disease. The increase in knowledge has been accomplished in pathophysiological, clinical and treatment domains and has included as examples the discovery of gene mutations related to the hereditary forms of pulmonary arterial hypertension and the proposals of personalized treatment algorithms in patients with acute pulmonary embolism, chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension, validated in this specific area by more than 45 randomized controlled trials. The diagnostic processes have been refined, increasing the awareness that appropriate and precise diagnosis is essential for the optimal treatment strategy. The drugs approved for pulmonary arterial hypertension are recommended in this group and in specific patients with chronic thromboembolic pulmonary hypertension but are contraindicated in patients with pulmonary hypertension due to left heart and lung diseases. In pulmonary vascular diseases, the therapy cannot be considered as a simple prescription of medications and interventions but is a complex strategy which includes baseline patients' risk stratification, initial therapy, long-term follow-up and treatment adjustments when required. Today, computed tomography pulmonary artery angiography is the gold standard for diagnosis in both acute pulmonary embolism and chronic thromboembolic pulmonary hypertension. In this last condition, the combination with data derived from the right heart catheterization and the traditional pulmonary artery angiography, allows to a team of experts to decide if the patient is a candidate to surgical pulmonary endarterectomy or to percutaneous pulmonary artery balloon angioplasty which may improve symptoms, quality of life and prognosis.

Murine models of sickle cell disease and beta-thalassemia demonstrate pulmonary hypertension with distinctive features.

Sickle cell anemia and β-thalassemia intermedia are very different genetically determined hemoglobinopathies predisposing to pulmonary hypertension. The etiologies responsible for the associated development of pulmonary hypertension in both diseases are multi-factorial with extensive mechanistic contributors described. Both sickle cell anemia and β-thalassemia intermedia present with intra and extravascular hemolysis. And because sickle cell anemia and β-thalassemia intermedia share features of extravascular hemolysis, macrophage iron excess and anemia we sought to characterize the common features of the pulmonary hypertension phenotype, cardiac mechanics, and function as well as lung and right ventricular metabolism. Within the concept of iron, we have defined a unique pulmonary vascular iron accumulation in lungs of sickle cell anemia pulmonary hypertension patients at autopsy. This observation is unlike findings in idiopathic or other forms of pulmonary arterial hypertension. In this study, we hypothesized that a common pathophysiology would characterize the pulmonary hypertension phenotype in sickle cell anemia and β-thalassemia intermedia murine models. However, unlike sickle cell anemia, β-thalassemia is also a disease of dyserythropoiesis, with increased iron absorption and cellular iron extrusion. This process is mediated by high erythroferrone and low hepcidin levels as well as dysregulated iron transport due transferrin saturation, so there may be differences as well. Herein we describe common and divergent features of pulmonary hypertension in aged Berk-ss (sickle cell anemia) and Hbbth/3+ (intermediate β-thalassemia) mice and suggest translational utility as proof-of-concept models to study pulmonary hypertension therapeutics specific to genetic anemias.

Optimization of specific therapy for pulmonary hypertension: the possibilities of riociguat

Pulmonary hypertension (PH) is a severe and often rapidly progressive disease with fatal outcome. Endothelial dysfunction in PH is associated with decreased nitric oxide production. After reviewing the mechanisms of action and the evidence base for specific therapy with phosphodiesterase 5 inhibitors (PDE-5) and soluble guanylate cyclase stimulators, a reseach review on switching from PDE-5 to riociguat is conducted. A potential advantage of riociguat is its independence from endogenous nitric oxide and from the other (besides PDE-5) isoenzymes of phosphodiesterases. The favorable efficacy profile of sildenafil has been proven for the main forms of pulmonary arterial hypertension, of riociguat for the main forms of pulmonary arterial hypertension and chronic thromboembolic PH. The clinical efficacy of replacing PDE-5 with riociguat has been demonstrated in uncontrolled trials and in the randomized controlled study REPLACE. The possibility of therapy optimization by switching from IFDE-5 to riociguat is fixed in the Russian (class and level of evidence B-3) and Eurasian (class and level of evidence IIb-B) clinical guidelines, as well as in the materials of the Cologne Expert Consensus. An additional argument for switching is the lower cost as compared to combination therapy in the Russian Federation. According to the Russian and Eurasian guidelines for PH and the Russian instructions for the use of riociguat, the drug should be taken at least 24 hours after sildenafil discontinuation.

Radiological Findings in Multidetector Computed Tomography (MDCT) of Hereditary and Sporadic Pulmonary Veno-Occlusive Disease: Certainties and Uncertainties.

Pulmonary veno-occlusive disease (PVOD) is a very infrequent form of pulmonary arterial hypertension with an aggressive clinical course, poor response to specific vasodilator treatment, and low survival. Confirming a definitive diagnosis is essential to guide treatment and assess lung transplantation. However, in the absence of histological or genetic confirmation, the diagnosis is complex, requiring a clinical suspicion. Multidetector computed tomography (MDCT) is an essential part of the non-invasive diagnostic tools of PVOD. We retrospectively reviewed the MDCT findings from a consecutive series of 25 patients diagnosed with PVOD, 9 with the sporadic form and 16 with the hereditary form of the disease. The presence and extent of typical findings of the diagnostic triad were assessed in all patients (ground glass parenchymal involvement, septal lines, and lymphadenopathy). In our series, 92% of patients showed at least two of the radiological findings described as typical of the disease. All patients presented at least one typical radiological characteristic. The incidence of radiological findings considered typical is very high, however was not associated with greater hemodynamic severity nor to the development of acute lung edema. No significant differences were found between the two groups. A poorly expressive MDCT does not exclude the disease.

Autopsy study of pulmonary capillary hemangiomatosis with inflammatory cell infiltration into the myocardium

Pulmonary capillary hemangiomatosis is a rare form of pulmonary artery hypertension; to date, only few descriptions of myocardial pathology in pulmonary capillary hemangiomatosis have been reported in the literature. We report the case of a Japanese female patient who was diagnosed with pulmonary capillary hemangiomatosis combined with acute myocardial inflammation on performing autopsy. She was admitted to our hospital because of acute pneumonia and subsequently suddenly developed severe hypoxemia with breathing difficulty and died 13 days after admission. At autopsy, the histology of the lung was consistent with pulmonary capillary hemangiomatosis. Additionally, a diffuse severe infiltration of inflammatory cells was associated with edema in the myocardium. Myocytolysis was limited and fibrosis was absent. To the best of our knowledge, pulmonary capillary hemangiomatosis with acute myocarditis-like histological findings has been described for the first time through our case.