Advanced Pulmonary Hypertension Research Articles

Clinical and instrumental factors associated with sinus rhythm maintenance following direct current cardioversion of late persistent non-valvular atrial fibrillation at 6-months follow-up

Abstract Purpose To study the clinical and instrumental factors, associated with sinus rhythm (SR) maintenance following direct current cardioversion (DCCV) in patients with late persistent non-valvular atrial fibrillation (AF) at 6-months follow-up. Methods The cohort single-center study analyzed clinical and instrumental data from 59 late persistent AF patients (with duration of its episode ≥90 days [up to 12 months]), who underwent an elective DCCV. At 6-months follow-up, 32 (54 %%) patients succeeded to maintain SR, in contrast to 27 (46 %) patients with a failure to its maintenance. Results The univariate logistic regression analysis revealed, that the absence of heart failure (HF) stage C (i.e., the presence of its stage B), the higher left ventricular ejection fraction (LVEF) (by transthoracic echocardiography [TTE]), left atrial appendage flow velocity (LAAFV) >40 cm/s and the freedom from left atrial spontaneous echo contrast (LASEC) (by transesophageal echocardiography), ‒ all were associated with the higher chance to maintain SR at 6-months follow-up (Figure). At the same time, the higher baseline left atrial dimension (LAD) and more advanced pulmonary hypertension (PH) (by TTE) were associated with the failure of its maintenance to be more probable (Figure). At multivariate analysis, the following predictors of SR maintenance after DCCV at 6-months follow-up were identified: higher LVEF (OR 1,07 (95 % CI 1,01-1,13); р=0,021); LAAFV >40 cm/s (OR 4,33 (95 % CI 1,06-17,78); р=0,042), and less advanced PH (OR 0,24 (95% CI 0,06-0,93); р=0,038). Conclusion Better LV systolic function, LAAFV >40 cm/s and less advanced PH were the predictors of SR maintenance following DCCV in patients with late persistent (with duration of its episode ≥90 days) non-valvular AF at 6-months follow-up.

Arrhythmias in Patients with Pulmonary Hypertension and Right Ventricular Failure: Importance of Rhythm Control Strategies.

Arrhythmias frequently complicate the course of advanced pulmonary hypertension, often leading to hemodynamic compromise, functional impairment, and mortality. Given the importance of right atrial function in this physiology, the restoration and maintenance of sinus rhythm are of critical importance. In this review, we outline the pathophysiology of arrhythmias and their impact on right heart performance; describe considerations for antiarrhythmic drug selection, anesthetic and periprocedural management; and discuss the results of catheter ablation techniques in this complex and challenging patient population.

Abstract 19060: Single-Nuclei RNA-Seq Provides Novel Insights Into Cellular Composition and Transcriptional Changes in Human Right Ventricular Failure

Introduction: Right ventricular failure (RVF) is a common consequence of pulmonary hypertension, but effective treatment options are currently lacking. To develop precise molecular and cellular targets for therapeutic development, a comprehensive investigation of cell type-specific responses and cellular heterogeneity in RVF is needed. Hypothesis: Cellular heterogeneity exists within the myocardium of RVF patients with pulmonary hypertension, and identifying specific genes contributing to failure can be aided by studying these distinct subpopulations. Methods: To test this hypothesis, we performed single-nucleus transcriptome analysis of 120,000 nuclei from ventricle samples of RVF patients with advanced or end-stage pulmonary hypertension with severe right heart failure undergoing heart double lung transplantation and normal control (NC) subjects. Single nuclei RNA sequencing was performed using 10x genomics, and bioinformatics tools were used for analysis. Results: Unsupervised clustering of 120,000 nuclei led to the identification of transcriptionally distinct subpopulations within 6 major cell types. We identified a unique fibroblast subpopulation expressing SERPINE1 in RVF and observed extensive crosstalk between the fibroblast cells and the other cardiac cell types through Visfatin signaling. In addition, other major cardiac cell types, such as cardiomyocytes, endothelial cells, and macrophages within the failing hearts also exhibited significant alterations in the signaling pathways compared with the control hearts. Conclusions: Our study provides novel insights into the single-cell landscape within the myocardium of RVF patients, revealing remarkable changes in the expression patterns of fibroblast genes. The identified sub-cluster of the fibroblast cell population could serve as a specific and potential therapeutic target in the clinic.

Update on Management and Outcomes of Congenital Diaphragmatic Hernia.

Infants with congenital diaphragmatic hernia (CDH) benefit from comprehensive multidisciplinary teams that have experience in caring for the unique and complex issues associated with CDH. Despite prenatal referral to specialized high-volume centers, advanced ventilation strategies and pulmonary hypertension management, and extracorporeal membrane oxygenation, mortality and morbidity remain high. These infants have unique and complex issues that begin in fetal and infant life, but persist through adulthood. Here we will review the literature and share our clinical care pathway for neonatal care and follow up. While many advances have occurred in the past few decades, our work is just beginning to continue to improve the mortality, but also importantly the morbidity of CDH.

Lung transplantation in pulmonary sarcoidosis

Sarcoidosis is a systemic inflammatory disease of unknown etiology and variable clinical course. Pulmonary sarcoidosis is the most common presentation and accounts for most morbidity and mortality related to sarcoidosis. While sarcoidosis generally has good outcomes, few patients experience chronic disease. A minority of patients progress to a specific phenotype of sarcoidosis referred to advanced pulmonary sarcoidosis (APS) which includes advanced fibrosis, pulmonary hypertension and respiratory failure, leading to high morbidity and mortality. In patients with advanced disease despite medical therapy, lung transplantation may be the last viable option for improvement in quality of life. Though post-transplant survival is similar to that of other end-stage lung diseases, it is imperative that patients are evaluated and referred early to transplant centers with experience in APS. A multidisciplinary approach and clinical experience are crucial in detecting the optimal timing of referral, initiating comprehensive transplantation evaluation and listing, discussing surgical approach, and managing perioperative and post-transplant care. This review article seeks to address these aspects of lung transplantation in APS.

Evaluation of a pharmacist-provider collaborative clinic for treatment of iron deficiency in patients with heart failure.

Intravenous iron therapy is recommended to improve symptoms and exercise tolerance in patients with heart failure (HF) with -reduced ejection fraction and iron deficiency (ID), but there are limited published data on the implementation of intravenous iron therapy in practice. A pharmacist-provider collaborative ID treatment clinic was established within an advanced HF and pulmonary hypertension service to optimize IV iron therapy. The objective was to evaluate the clinical impacts of the pharmacist-provider collaborative ID treatment clinic. A retrospective cohort study was performed to compare clinical outcomes among patients of the collaborative ID treatment clinic (the postimplementation group) and a cohort of patients who received usual care (the preimplementation group). The study included patients 18 years of age or older with diagnosed HF or pulmonary hypertension who met prespecified criteria for ID. The primary outcome was adherence to institutional intravenous iron therapy guidance. A key secondary outcome was ID treatment goal achievement. A total of 42 patients in the preimplementation group and 81 in the postimplementation group were included in the study. The rate of adherence to the institutional guidance was significantly improved in the postimplementation group (93%) compared to the preimplementation group (40%). There was no significant difference in the ID therapeutic target achievement rate between the pre- and postimplementation groups (38% vs 48%). Implementing a pharmacist-provider collaborative ID treatment clinic significantly increased the number of patients who adhered to intravenous iron therapy guidance compared to usual care.

MKI67 as a potential diagnostic biomarker in pulmonary hypertension.

Right heart failure results from advanced pulmonary hypertension (PH) and has a poor prognosis. There are few available treatments for right heart failure. Pulmonary artery remodeling, including changes in pulmonary artery endothelial cells to endothelial-mesenchymal cells, and aberrant fibroblast and pulmonary artery smooth muscle cell (PASMC) proliferation, are characteristics of the pathophysiological process of PH. As a result, the clinical situation requires novel PH diagnostic and treatment targets. Monocrotaline was used to create an animal model of PH, and lung tissue was removed for transcriptome sequencing. The targets with the highest differences were chosen for transfection after possible targets were identified using bioinformatic techniques and confirmed by qPCR to examine their function in hypoxic PASMCs. After sequencing 781 differentially expressed mRNAs, we compared them with the GEO dataset and found 43 differentially expressed genes. We chose the top three scores for further study and verification and discovered that MKI67, a crucial element of the cell cycle that regulates PASMC proliferation, had the greatest effect. After suppressing MKI67 in PASMCs, both cell proliferation and migration decreased. Several potential targets were chosen for this study, and MKI67 was found to play a regulatory role in cell migration and proliferation. This implies that PH can be diagnosed and treated using MKI67.

Role of Veno-arterial Extracorporeal Membrane Oxygenation in Left Ventricular Conditioning after Lung Transplantation

End-stage pulmonary hypertension alters intracardiac pressures, leading to distention and failure of the right ventricle, leftward shifting of the intraventricular septum, and, thus, underfilling of the left ventricle (LV). Following the resolution of severely elevated pulmonary vascular resistance with bilateral lung transplantation, the LV is exposed to relatively high filling pressures from a potentially hypertrophic right ventricle pushing blood through normalized pulmonary vascular resistance. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) may be a valuable tool to provide a more gradual exposure of the LV to the newly available preload in the immediate postoperative phase of transplantation, thereby reducing the likelihood of primary graft dysfunction developing from the LV diastolic dysfunction. This paper presents a case in which V-A ECMO was initiated during cardiac arrest in a patient with advanced pulmonary hypertension and right ventricular failure and maintained for two days for postoperative patient stability and cardiac conditioning. The discussion includes data from transplant programs using this method to reduce the need for dual organ transplantation and postoperative primary graft dysfunction in the allograft.

Complications associated with peripherally inserted central catheters and Hickman™ in patients with advanced pulmonary hypertension treated with intravenous prostanoids

BackgroundEpoprostenol requires continuous infusion and may lead to catheter-related complications. Evidence regarding the comparison between peripherally inserted central catheters (PICC) or tunneled central catheters in Pulmonary Hypertension (PH) is scarce. We sought to study the incidence of mechanical and infectious complications associated with PICC and Hickman catheters in patients with PH under epoprostenol treatment. MethodsThis is a single-center retrospective study of patients with PH who received continuous treatment with intravenous epoprostenol for at least 24 h between January 2010 and July 2020. Mechanical and infectious complications were analyzed according to the catheter type: PICC and Hickman. The incidence of catheter-related complications was calculated per 1000 exposure-days of risk. Results175 catheters were implanted in 109 patients, of which 100 (57.1%) were Hickman and 75 (42.9%) were PICC. After a median follow-up of 334 [130–798] days, there were no differences in the rates of local (0.22 vs 0.21; p = 0.904) or blood-stream infections (0.13 vs 0.21; p = 0.405). Mechanical complications were more frequent in the PICC group (0.98 vs 0.23 p=<0.001), including venous thrombosis (0.16 vs 0.00 p = 0.003) and catheter occlusion (0.66 vs 0.04 p=<0.001). These complications were associated with a greater need for hospitalization (1.48 vs 0.50; p=<0.001), without differences in mortality during follow-up (0.33 vs 0.21; p = 0.288). ConclusionIn patients with PH treated with intravenous epoprostenol, both Hickman and PICC catheters were associated with high rate of complications. Although there were no differences in the frequency of infectious-related complications, PICC was associated with a higher frequency of catheter occlusion and deep venous thrombosis.

PH Roundtable: Conundrums and Controversies in PH-ILD: To Treat or Not to Treat—Identifying Optimal Treatment Candidates

PH Roundtable: Conundrums and Controversies in PH-ILD: To Treat or Not to Treat—Identifying Optimal Treatment Candidates

Coarctation of aorta is associated with left ventricular stiffness, left atrial dysfunction and pulmonary hypertension

Brachial systolic blood pressure (BP) is the most commonly used metric for monitoring hypertension. However, recent studies suggest that brachial systolic BP underestimates left ventricle (LV) systolic load in patients with coarctation of aorta (COA). Since brachial systolic BP is used as a surrogate of arterial afterload in clinical practice, it is important to determine how well it correlates with LV remodeling and stiffness in patients with COA as compared to patients with idiopathic hypertension. This is cross-sectional study of COA patients with hypertension (COA group) and adults with idiopathic hypertension (control group). Both groups were matched 1:1 based on age, sex, BMI and systolic BP. We hypothesized that the COA group will have higher LV systolic and diastolic stiffness, and more advanced left atrial remodeling and pulmonary hypertension. We assessed LV systolic stiffness using end-systolic elastance, and diastolic stiffness using LV stiffness constant and chamber capacitance (LV-end-diastolic volume at an end-diastolic pressure of 20mm Hg) RESULTS: There were 112 patients in each group. Although both groups had similar systolic BP, the COA group had a higher end-systolic elastance (2.37 ± 0.74 vs 2.11 ± 0.54 mm Hg/mL, P= .008), higher LV stiffness constant (6.91 ± 0.81 vs 5.93 ± 0.79, P= .006) and lower LV-end-diastolic volume at an end-diastolic pressure of 20mm Hg (58 ± 9 vs 67 ± 11 mL/m2, P< .001). Additionally, the COA group had more advanced left atrial remodeling and higher pulmonary artery pressures which is corroborating evidence of high LV filling pressure. COA patients have more LV stiffness and abnormal hemodynamics compared to non-COA patients with similar systolic BP, suggesting that systolic BP may underestimate LV systolic load in this population. Further studies are required to determine whether the observed LV stiffness and dysfunction translates to more cardiovascular events during follow-up, and whether adopting a stricter systolic BP target in clinical practice or changing threshold for COA intervention will lead to less LV stiffness and better clinical outcomes.

Stable Gastric Pentadecapeptide BPC 157 Therapy for Monocrotaline-Induced Pulmonary Hypertension in Rats Leads to Prevention and Reversal.

Background. Monocrotaline selectively injures the lung’s vascular endothelium and induces pulmonary arterial hypertension. The stable gastric pentadecapeptide BPC 157 acts as a prototype cytoprotective agent that maintains endothelium, and its application may be a novel therapy. Besides, BPC 157 prevents and reverses thrombosis formation, maintains platelet function, alleviates peripheral vascular occlusion disturbances, and has anti-arrhythmic and anti-inflammatory effects. Monocrotaline-induced pulmonary arterial hypertension in rats (wall thickness, total vessel area, heart frequency, QRS axis deviation, QT interval prolongation, increase in right ventricle systolic pressure and bodyweight loss) can be counteracted with early or delayed BPC 157 therapy. Methods and Results. After monocrotaline (80 mg/kg subcutaneously), BPC 157 (10 μg/kg or 10 ng/kg, days 1–14 or days 1–30 (early regimens), or days 14–30 (delayed regimen)) was given once daily intraperitoneally (last application 24 h before sacrifice) or continuously in drinking water until sacrifice (day 14 or 30). Without therapy, the outcome was the full monocrotaline syndrome, marked by right-side heart hypertrophy and massive thickening of the precapillary artery’s smooth muscle layer, clinical deterioration, and sometimes death due to pulmonary hypertension and right-heart failure during the 4th week after monocrotaline injection. With all BPC 157 regimens, monocrotaline-induced pulmonary arterial hypertension (including all disturbed parameters) was counteracted, and consistent beneficial effects were documented during the whole course of the disease. Pulmonary hypertension was not even developed (early regimens) as quickly as the advanced pulmonary hypertension was rapidly attenuated and then completely eliminated (delayed regimen). Conclusions. Thus, pentadecapeptide BPC 157 prevents and counteracts monocrotaline-induced pulmonary arterial hypertension and cor pulmonale in rats.

Influence of advanced pulmonary vascular remodeling on accuracy of echocardiographic parameters of left ventricular filling pressure.

Evaluation of left ventricular filling pressure plays an important role in the clinical management of pulmonary hypertension. However, the accuracy of echocardiographic parameters for the determination of left ventricular filling pressure in the presence of pulmonary vascular lesions has not been fully addressed. We retrospectively investigated 124 patients with pulmonary hypertension due to pulmonary vascular lesions (noncardiac pulmonary hypertension group) and 113 patients with ischemic heart disease (control group) who underwent right heart catheterization and echocardiography. The noncardiac pulmonary hypertension group was subdivided into less-advanced and advanced groups according to median pulmonary vascular resistance. Pulmonary artery wedge pressure was determined as left ventricular filling pressure. As echocardiographic parameters of left ventricular filling pressure, the ratio of early- (E) to late-diastolic transmitral flow velocity (E/A), ratio of E to early-diastolic mitral annular velocity (E/e′), and left atrial volume index were measured. In the less-advanced noncardiac pulmonary hypertension and control groups, positive correlations were observed between pulmonary artery wedge pressure and late-diastolic transmitral flow velocity (R = 0.41, P = 0.002 and R = 0.71, P < 0.001, respectively) and left atrial volume index (R = 0.53, P < 0.001 and R = 0.41, P < 0.001), whereas in the advanced noncardiac pulmonary hypertension group, pulmonary artery wedge pressure was only correlated with left atrial volume index (R = 0.27, P = 0.032). In the controls, only pulmonary artery wedge pressure determined E (β = 0.48, P < 0.001), whereas both pulmonary artery wedge pressure and pulmonary vascular resistance were independent determinants of E (β = 0.29, P < 0.001 and β = –0.28, P = 0.001, respectively) in the noncardiac pulmonary hypertension group. In conclusion, in the presence of advanced pulmonary vascular lesions, conventional echocardiographic parameters may not accurately reflect left ventricular filling pressure. Elevated pulmonary vascular resistance would lower the E, even when pulmonary artery wedge pressure is elevated, resulting in blunting of echocardiographic parameters for the detection of elevated left ventricular filling pressure.

Determinants of Sudden Cardiac Death in Adult Patients With Eisenmenger Syndrome.

BackgroundPatients with Eisenmenger syndrome are known to have a high incidence of sudden cardiac death (SCD), yet the underlying causes are not well understood. We sought to define the predictors of SCD in this population.Methods and ResultsA retrospective analysis of all patients with Eisenmenger syndrome from 2 large tertiary referral centers was performed. ECGs, prolonged ambulatory recordings, echocardiograms, and clinical histories were reviewed; and the cause of death was identified. A total of 246 patients (85 [34.6%] men) with a mean age of 37.3 (±14.2) years were followed up for a median of 7 years. Over the study period, 136 patients died, with 40 experiencing SCD and 74 experiencing cardiac death (sudden and nonsudden). Age, atrial fibrillation, prolonged QRS duration, complete heart block, right atrial enlargement, right bundle branch block, increased right atrial pressure, impaired biventricular function, and the presence of a pacemaker were associated with increased risk of SCD, whereas advanced pulmonary hypertension therapies were protective. Atrial fibrillation (11.45‐fold increased risk; P<0.001) and QRS duration ≥120 ms (2.06‐fold increased risk; P=0.034) remained significant predictors of SCD in the multivariate analysis, whereas advanced pulmonary hypertension therapies were strongly protective against SCD (P<0.001).ConclusionsAtrial arrhythmias, impaired ventricular function, and conduction system disease were associated with increased risk of SCD in this cohort of patients with Eisenmenger syndrome, providing an opportunity for early risk stratification and potential intervention. Clinical heart failure symptoms (New York Heart Association class ≥II) were predictive of increased mortality but not of SCD, suggesting a potential arrhythmic cause behind SCD.

Shunts: When to Close Them and When to Create Them for Palliation

Pulmonary hypertension, despite specific therapies, remains an incurable disease with a dreadful prognosis. A systemic-to-pulmonary shunt, if left unrepaired, can cause pulmonary arterial hypertension. With time, pulmonary vascular disease develops, and closure of the shunt becomes contraindicated. Operability criteria are not well defined and rely mainly on hemodynamic values that fail to predict long-term survival. Shunts can also be created in selected cases of advanced pulmonary hyper-tension, in view of off-loading the right ventricle and improving cardiac output at the cost of cyanosis. Shunt creation is not without risks and remains indicated only in selected severe cases.

P6311Is the new PH classification useful to assess the need for heart transplantation? Looking for harder markers for hard patients

Abstract Background Pulmonary hypertension (PH) is an important prognostic marker among patients (pts) with heart failure. Recent ESC guidelines have introduced the concept of diastolic transpulmonary gradient (DPG) to differentiate combined (CpC) and isolated (IpC) post-capillary PH. However, its validation in a setting of patients evaluated for heart transplantation (HT) has been poorly explored; moreover, it doesn't incorporate right ventricular (RV) function. Purpose To analyze the prognostic role of current classification of PH and its interplay with RV function and diuretic therapy in pts with advanced heart failure referred for HT. Methods We included all pts evaluated for HT in our Center (2002–16) undergoing to a right heart cath (RHC), collecting data at first evaluation. Patients were divided into three groups: no PH (mPAP&lt;25 mmHg), IpC-PH (mean PAP &gt;25 mmHg, PVR&lt;3 WU), CpC-PH (mean PAP&gt;25 mmHg, PVR ≥3 WU and/or DPG ≥7 mmHg). Pulmonary artery pulsatility index (PAPi) was analyzed as a marker of RV function; oral furosemide&gt;125 mg/day (median value) or i.v. diuretics/dialysis were considered as high-dose diuretics (HDD). The study endpoint was the combined incidence of death or need for high urgent HT, expressed as 2-yrs survival rate. Results Among the overall cohort of 458 pts (53.1±10.9 yrs, 82,6% males, 40.3% CAD, 9.3% on IABP), 57.9% had PH: 30.8% IpC-PH, 27.1% CpC-PH. Only 8 pts (0.2%) had DPG≥7, one with PVR&lt;3. The use of HDD differed significantly according to PH classes (44.6% vs 56.3% vs 68.3%, no PH vs IpC vs CpC-PH respectively, p&lt;0.01) and was associated with a worse outcome (p&lt;0.01). The incidence of the primary endpoint in the overall cohort was 74.1±2.5%. While pts with CpC-PH had the worst prognosis, DPG≥7 did not predict the primary endpoint. At multivariate analysis, PVR ≥3 WU (HR: 16.7), PAPi &lt;3.8 (median value, HR: 4.1), HDD (HR: 5.6) were independent predictors of the primary endpoint, (p&lt;0.04 for all) as well as need for IABP (HR: 19.0, p&lt;0.01), even adjusting for clinical variables. Lower PAPi values carried an higher risk at 2 years both in IpC and CpC PH groups, thus allowing to better stratify the need for urgent HT (81.6±6.6% vs 78.6±5.7% vs 67.3±6.7% vs 49.1±7.9% respectively, p&lt;0.001) (Fig.1). Figure 1 Conclusion Our results suggest that, even if current definition of type 2 PH predicts the need of urgent HT, the incorporation of DPG ≥7 is epidemiologically irrelevant and doesn't increase accuracy, whereas combining an indirect marker of RV function (PAPi) with PVR assessment, even correcting for diuretic therapy, could help to better stratify the need of a rare resource like HT in patients with advanced heart failure and pulmonary hypertension.

Extracorporeal life support bridge for pulmonary hypertension: A high-volume single-center experience.

Application of extracorporeal life support (ECLS) for advanced pulmonary hypertension (PH) is evolving and may be deployed as a bridge to transplantation (BTT) or in one of several non-BTT uses, such as bridge to recovery (BTR) to the chronic PH clinical state in the setting of an acute PH trigger, bridge through non-transplant surgery (BTNTS), or bridge post-transplantation (BPT). We conducted a retrospective analysis of all adult patients with World Symposium on Pulmonary Hypertension Group 1, 3, 4, or 5 PH who received ECLS at Columbia University Medical Center/New York Presbyterian Hospital between January 1, 2010 and August 18, 2018. We describe patient characteristics, outcomes, and our approach to medical and surgical management of these patients. There were 98 patients with significant PH in the cohort (54 female; median age, 48 years [interquartile range, 32-58]). Of these, 44 (45%) patients with PH received ECLS as non-BTT with intent to recover back to their baseline functional state, optimize therapy, or support through a definitive surgery, including 19 BTR, 17 BTNTS, and 8 BPT, and 54 (55%) patients received ECLS as BTT. In the overall cohort, 67 (68.4%) patients received venoarterial ECLS and 31 (31.6%) received venovenous (VV) ECLS. Out of 83 patients, 52 (63%) were liberated from invasive mechanical ventilation, and 85.2% of BTT patients with PH ambulated while on ECLS. Management of PH medications was individualized, often requiring titration with use of inhaled pulmonary vasodilators increased after cannulation in non-BTT. Overall 30-day survival was 73.5%, survival to ECLS decannulation was 66.3%, and survival to hospital discharge was 54.1%. All 8 BPT patients (100%) survived to hospital discharge, 64.7% of BTNTS patients survived to hospital discharge, and 32 (59.3%) BTT patients survived to lung transplantation. Early-era use of VV-ECLS for BTT had worse survival to discharge than those initially configured with venoarterial ECLS, impacting the overall survival and leading to limited use of VV-ECLS in the current era for BPT, BTNTS, and select BTR cases. ECLS instituted by a specialized, multidisciplinary team has a role in the management of advanced PH as BTT or as non-BTT (including BTR, BTNTS, and BPT). Careful selection of ECLS cannulation configurations, patient-specific optimization of PH medical therapies, and avoidance of endotracheal intubation may be effective strategies in managing these complex patients.

Outcome of pregnancies in women with pulmonary hypertension: a single-centre experience from South India.

To study maternal complications and pregnancy outcome in women with pulmonary hypertension, attending a tertiary centre in south India. Retrospective observational study. Tertiary centre in south India. Pregnant women with pulmonary hypertension. Data regarding demographics, clinical course, medication received, and echocardiographic diagnosis regarding pulmonary hypertension and antenatal care received were collected from the records. Details of labour and delivery, and postpartum follow up were retrieved. We compared the outcome based on the presence or absence of cyanosis and right ventricular systolic pressure levels. Maternal mortality, occurrence of complications such as heart failure, fetal growth restriction. There were 81 pregnancies in 73 women with pulmonary hypertension. The majority of them had pulmonary hypertension secondary to congenital heart disease (80.8%); 17.8% had Eisenmenger syndrome. An advanced pulmonary artery hypertension (PAH) medication, sildenafil, was administered in 25 (31.3%) pregnancies. There were four maternal deaths, of which three had Eisenmenger syndrome. Heart failure complicated 6.3% and fetal growth restriction 26.3% of pregnancies. Morbidity was significantly increased in women with pulmonary hypertension associated with a cyanotic cardiac lesion or with right ventricular systolic pressure >70mmHg. Despite advances in care, mortality in pregnant women with pulmonary hypertension is a matter of concern, especially in those with Eisenmenger syndrome. Multidisciplinary team management in tertiary centres and the use of advanced PAH medications even in low- to middle-income countries with limited resources, could lead to a reduction in morbidity and mortality related to pulmonary hypertension. Multidisciplinary care and use of new medication may improve outcomes in pregnant women with pulmonary hypertension.

Outcome of children with systemic rheumatic diseases admitted to pediatric intensive care unit

ObjectiveTo report the outcome of children with rheumatic diseases admitted to pediatric intensive care unit (PICU) in a tertiary hospital.MethodsDatabase from PICU and pediatric rheumatology section used to retrieve all candidate patients admitted to PICU from June 2000 to December 2017. Medical records of all enrolled patients reviewed for diagnosis, organ involvement, reason of PICU admission, the length of stay, and outcome.ResultsTwenty-five patients (17 female, 8 male) with total of 41 admissions identified. The median PICU stay was 13.5 days (range, 3–24). The most frequent diagnoses were systemic lupus erythematosus (SLE) (48%), followed by systemic vasculitis (16%). Most admissions were from the medical ward (68.3%), while 24.4% from the emergency room. The main reason of PICU admission was a disease flare or related complications (48.8%), followed by infection (34.2%). Fifty one percent of the admissions were due to respiratory dysfunction, 46% required non-invasive respiratory support while 38% was in need for mechanical ventilation. During PICU stay, anti-microbial agents used 90.3%, immunosuppressive treatment adjustment 75.6%, anti-hypertensive 24.4% and vasopressors 12.2%. Twelve patients (48%) fully recovered and 40% partially recovered while three patients died during their PICU stay. The causes of death were macrophage activation syndrome complicated by sepsis in two patients and advanced pulmonary hypertension in one patient.ConclusionOur data showed that children with rheumatic diseases, particularly SLE, are mostly admitted to PICU with serious disease exacerbation or severe infection. To improve the outcome, early diagnosis of critical condition and proper intervention are fundamental in reducing mortality.

Sulfur dioxide reduces lipopolysaccharide-induced acute lung injury in rats.

IntroductionRecent studies suggested that sulfur dioxide (SO2) can be produced endogenously by pulmonary vessels and attenuate acute lung injury (ALI) with vasorelaxant effects. This study was conducted to determine whether SO2 can inhibit lung inflammation and relax pulmonary arteries via inhibition of the mitogen-activated protein kinase (MAPK) pathway.Material and methodsForty-eight adult male Sprague Dawley rats (250~300 g) were randomly divided into six treatment groups: control (n = 8), control + SO2 (n = 8), control + L-aspartic acid-β-hydroxamate (HDX) (n = 8), LPS (n = 8), LPS + SO2 (n = 8) and LPS + HDX (n = 8).ResultsSix hours after LPS treatment, rats exhibited elevated pulmonary artery hypertension (PAH), marked pulmonary structure injury with elevated pulmonary myeloperoxidase (MPO) activity and increased expression of intercellular adhesion molecule 1 (ICAM-1) and CD11b, along with decreased pulmonary SO2 production and reduced pulmonary aspartate aminotransferase (AAT) activity. Pretreatment with SO2 saline solution significantly reduced, while HDX (AAT inhibitor) aggravated, the pathogenesis of LPS-induced ALI. Moreover, SO2 saline solution significantly down-regulated expression of Raf-1, MEK-1 and phosphorylated ERK (p-ERK). It also prevented pulmonary hypertension in association with an up-regulated SO2/AAT pathway. However, HDX advanced pulmonary hypertension and inflammatory responses in the lung were associated with a down-regulated SO2/AAT pathway.ConclusionsOur results suggest that SO2 markedly relieved inflammatory responses, in association with Raf-1, MEK-1 and p-ERK during ALI induced by LPS. The down-regulation of the SO2/AAT pathway may be involved in the mechanism(s) of LPS-induced lung injury.