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Resumen Objetivo Este estudio fue disenado para determinar los predictores de la hipertension pulmonar y los signos de disfuncion cardiaca derecha causados por la embolia pulmonar (EP) que pueden conducir a la deteccion temprana de los pacientes de alto riesgo. Por lo tanto, se evaluo el valor predictivo del indice de obstruccion de la arteria pulmonar (IOAP), medido mediante angiografia pulmonar por TC (APTC) en el contexto agudo, para predecir los pacientes susceptibles de sufrir complicaciones cardiacas por EP. Tambien se investigaron otros dos indices de APTC, el diametro de la arteria pulmonar (DAP) y el strain del ventriculo derecho (VD), en estos pacientes y se demostro su valor predictivo de las complicaciones cardiacas en la ecocardiografia de seguimiento. Materiales y metodos En el estudio fueron incluidos 120 pacientes con diagnostico definitivo de EP. El IOAP, el DAP y el strain del VD se midieron mediante APTC en el momento del diagnostico inicial. Se realizo una ecocardiografia transtoracica 6 meses despues del diagnostico de EP y se midieron los indices ecocardiograficos del VD. Se utilizo la correlacion de Pearson para investigar la correlacion entre IOAP, DAP, strain del VD y los signos de disfuncion del hemicardio derecho. Resultados El IOAP estaba fuertemente correlacionado con la presion arterial pulmonar sistolica (PAPS) (r = 0,83), la presion sistolica del VD (r = 0,78) y el grosor de la pared del VD (r = 0,61) en la ecocardiografia de seguimiento a largo plazo. Se detecto una mayor tasa de disfuncion del VD y de dilatacion del VD entre los pacientes con mayor IOAP (p Conclusiones El IOAP, el DAP y el strain del VD son indices de APTC sensibles y especificos que pueden predecir el desarrollo de complicaciones a largo plazo, como la hipertension pulmonar y la disfuncion cardiaca derecha, en el momento del diagnostico inicial de la EP.

Right ventricular (RV) failure has a significant adverse impact on pulmonary hypertension (PH) prognosis. None of the currently used parameters directly assess whether RV fails to provide enough energy output to propel the blood through diseased pulmonary vascular system. Furthermore, most of the current parameters are affected by the volume status of the patient. We aimed to explore whether RV energy failure has a predictive power for mortality on top of the established prognostic risk parameters in patients with PH. We screened 723 cases from our database. A total of 3 sets of binary regression analyses were executed to determine the hazard ratios (HRs) of RV energy failure for 5-year mortality in clinical, echocardiographic, and hemodynamic context, using adjustment variables chosen according to previous studies. The final study population encompassed 549 cases. A total of 77 patients died during the 5-year follow-up (14%). RV energy failure was observed in 146 of 549 patients (26.6%). In the univariate model, RV energy failure strongly associated with increased long-term mortality (HR 4.25, 95% confidence interval [CI] 2.58 to 7.00, p

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

Several tricuspid annuloplasty (TA) techniques are used for concomitant repair of functional tricuspid regurgitation (TR). This study compared the midterm clinical and valvular outcome among 3 annuloplasty techniques.TA was performed in 307 patients (aged 75.9 ± 10.4 years) with a rigid ring (RA) in 184, a flexible band (FA) in 80, or a suture annuloplasty (SA) in 43. Study end points were survival and recurrence of TRgrade 2 at 5 years.TA was performed concomitantly to mitral valve surgery in 136 patients (44.3%), aortic valve surgery in 18 (5.9%), coronary artery bypass grafting in 13 (4.2%), or a combined procedure in 140 (45.6%). Most had TRgrade 2 (78.5%), without significant differences between the TA groups (P = .878). Within a median follow-up of 3.4 years (interquartile range, 2.2-5.0 years), the 5-year survival was 80.1% ± 3.4% for RA, 83.5% ± 4.7% for FA, and 85.1% ± 6.5% for SA (P = .471). Independent risk factors for late mortality were renal impairment (hazard ratio [HR], 2.83; 95% CI, 1.16-6.89; P = .022), diabetes (HR, 2.10; 95% CI, 1.07-4.11; P = .030), and severe right ventricular dysfunction by tricuspid annulus plane systolic excursion10 mm (HR, 11.52; 95% CI, 4.98-26.66; P.001). Pulmonary hypertension was nearly significant (HR, 1.92; 95% CI, 0.98-3.74; P = .057). The cumulative incidence of TR recurrence at 5 years was 15.9%, 19.4%, and 21.1% for RA, FA, and SA, respectively (P = .342). Severe pulmonary hypertension (HR, 2.64; 95% CI, 1.38-5.07; P = .003), preoperative TR grade (HR, 1.82; 95% CI, 1.01-3.27; P = .046), and residual TRgrade 2 at discharge (HR, 3.38; 95% CI, 1.64-6.96; P = .001) were predictive for later TR recurrence, regardless of the annuloplasty technique.This study demonstrates that advanced pathophysiological right circulatory impairment, such as severe pulmonary hypertension and right ventricular dysfunction, affects the midterm survival and TR recurrence rate more than the annuloplasty technique used for concomitant repair of functional TR.

Lung transplantation is the definitive surgical treatment for end-stage lung disease. However, infants comprise less than 5% of pediatric cases. This study sought to provide an overview of infant lung transplantation outcomes over the past 3 decades by using linked United Network for Organ Sharing (UNOS) and Pediatric Health Information System (PHIS) data.Infants undergoing lung transplantation from 1989 to 2020 in UNOS were reviewed. UNOS and PHIS records for patients who underwent lung transplantation from 1995 to 2020 were linked using date of birth, sex, and date of surgery ± 3 days. The study assessed underlying diagnoses, pretransplant and posttransplant extracorporeal membrane oxygenation support, retransplant-free survival to discharge, hospital experience (≥1 annual transplant for ≥4 years in a 5-year period), operative decade, bronchiolitis obliterans syndrome, long-term survival, and functional status at latest follow-up.A total of 112 lung transplants were performed in 109 infants over 31 years. Of these, 21 patients died before discharge, and 2 underwent repeat transplantation during the same admission. The study linked 80.6% (83 of 103) of UNOS and PHIS records. Hospital survival was lower for infants with idiopathic pulmonary hypertension and those who underwent transplant procedures at less experienced centers. All 7 infants requiring postoperative extracorporeal membrane oxygenation support died. Median freedom from bronchiolitis obliterans syndrome was 8.1 years (interquartile range, 4.6 to 11.6 years). After discharge, median survival was 10.3 years (interquartile range, 6.3 to 14.4 years), with improved 10-year survival for those patients who underwent transplantation from 2010 to 2020 (87.3%) vs 2000 to 2009 (52.4%; P = .098) and 1989 to 1999 (34.1%; P = .004). A total of 84.6% (33 of 39) of survivors had minor or no restrictions at latest follow-up.Carefully selected infants experience promising short- and long-term outcomes after lung transplantation.

The World Symposium on Pulmonary Hypertension (WSPH) was organized by the World Health Organization in 1973 in response to an increase in pulmonary arterial hypertension in Europe caused by aminorex, an appetite suppressant. The mandate of this meeting was to review the latest clinical and scientific research and to formulate recommendations to improve the diagnosis and management of pulmonary hypertension (PH).1 Since 1998, the WSPH has met every five years and in 2018, the sixth annual WSPH revised the hemodynamic definition of PH. This two-part series will review the updated definition, classification, pathophysiology, presentation, diagnosis, management, and perioperative management of patients with PH. In the first part of this series, the definition, classification, pathophysiology, and presentation will be reviewed.

Background: Right heart failure (RHF) is associated with a dismal prognosis in patients with pulmonary hypertension (PH). Exercise right heart catheterization may unmask right heart maladaptation as a sign of RHF. We sought to (1) define the normal limits of right atrial pressure (RAP) increase during exercise; (2) describe the right heart adaptation to exercise in PH owing to heart failure with preserved ejection fraction (PH-HFpEF) and in pulmonary arterial hypertension (PAH); and (3) identify the factors associated with right heart maladaptation during exercise. Methods and results: We analyzed rest and exercise right heart catheterization from patients with PH-HFpEF and PAH. Right heart adaptation was described by absolute or cardiac output (CO)-normalized changes of RAP during exercise. Individuals with noncardiac dyspnea (NCD) served to define abnormal RAP responses (>97.5th percentile). Thirty patients with PH-HFpEF, 30 patients with PAH, and 21 patients with NCD were included. PH-HFpEF were older than PAH, with more cardiovascular comorbidities, and a higher prevalence of severe tricuspid regurgitation (P < .05). The upper limit of normal for peak RAP and RAP/CO slope in NCD were >12 mmHg and ≥1.30 mmHg/L/min, respectively. PH-HFpEF had higher peak RAP and RAP/CO slope than PAH (20 mmHg [16-24 mmHg] vs 12 mmHg [9-19 mmHg] and 3.47 mmHg/L/min [2.02-6.19 mmHg/L/min] vs 1.90 mmHg/L/min [1.01-4.29 mmHg/L/min], P < .05). A higher proportion of PH-HFpEF had RAP/CO slope and peak RAP above normal (P < .001). Estimated stressed blood volume at peak exercise was higher in PH-HFpEF than PAH (P < .05). In the whole PH cohort, the RAP/CO slope was associated with age, the rate of increase in estimated stressed blood volume during exercise, severe tricuspid regurgitation, and right atrial dilation. Conclusions: Patients with PH-HFpEF display a steeper increase of RAP during exercise than those with PAH. Preload-mediated mechanisms may play a role in the development of exercise-induced RHF.

Pulmonary hypertension (PH) often complicates chronic left-sided heart failure, with a remarkable impact on quality of life, exercise capacity, and survival. PH in chronic left-sided heart failure (PH-LHD) is not only caused by backward transmission of pressures but also involves impairment of atrial function, inflammation, and vasoconstriction. Once the left atrium loses its reservoir capacity, usually pulmonary vascular resistances increase. Right atrial dilation commonly represents the first sign of PH-LHD, before right ventricle dilatation and systolic dysfunction develop, leading to right heart insufficiency, and ultimately, right heart failure.

Pulmonary hypertension (PH) is a common complication of end-stage heart failure (ESHF) and associated with increased mortality. The definition of PH has recently been changed from a mean pulmonary arterial pressure (PAPm) ≥25 mmHg to a PAPm20 mmHg. Since this change, there are no data evaluating group 2 PH subgroups on outcomes. The purpose of this study was to determine the impact of updated group 2 PH subgroups on outcomes, as well as to evaluate the clinical, echocardiographic, and haemodynamic characteristics of subgroups, and determine predictors of PH in patients with ESHF.A total of 416 patients with ESHF with left ventricular ejection fraction (LVEF) ≤25% were divided into three groups. Pulmonary hypertension was defined as PAPm20 mmHg. Primary outcome was defined as left ventricular assist device (LVAD) implantation, urgent heart transplantation (HT), or death. Secondary outcome was defined as LVAD implantation and HT.Over a median follow-up of 503.5 days, combined pre- and postcapillary PH (Cpc-PH) displayed greater risk of primary outcome than those with isolated postcapillary (Ipc-PH) (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.29-1.91; p0.001) and those with no PH (HR, 2.47; 95% CI, 1.68-3.63; p0.001). Patients with Ipc-PH demonstrated greater risk than those with no PH (HR, 1.57; 95% CI, 1.57-1.90; p0.001). Likelihood ratios of updated PH criteria and old PH criteria (PAPm ≥25 mmHg) in identifying primary outcome were 75.6 (RPulmonary hypertension increases the risk of LVAD, urgent HT, or death, and Cpc-PH further increases risk in patients with ESHF. Compared to the previous definition, a new PH definition better discriminates death, going to urgent HT, or LVAD implantation for PH subgroups.

Background/Purpose As survival rates for patients with congenital diaphragmatic hernia (CDH) increase, long-term sequelae become increasingly prevalent. We present the outcomes of patients who underwent CDH repair at our institution and discuss standardization of follow-up care in our long-term multidisciplinary follow-up clinic. Methods A retrospective review of patients followed in multidisciplinary clinic after CDH repair at our institution from January 1, 2005 to December 1, 2020. Results A total of 193 patients met inclusion criteria, 73 females (37.8%) and 120 males (62.2%). Left-sided defects were most common (75.7%), followed by right-sided defects (20.7%). Median age at repair was 4 days (IQR 3–6) and 59.6% of all defects required patch repair. Median length of stay was 29 days (IQR 16.8–50.0). Median length of follow up was 49 months (IQR 17.8–95.3) with 25 patients followed for more than 12 years. Long-term outcomes included gastroesophageal reflux disease (42.0%), diaphragmatic hernia recurrence (10.9%), asthma (23.6%), neurodevelopmental delay (28.6%), attention deficit hyperactivity disorder (7.3%), autism (1.6%), chest wall deformity (15.5%), scoliosis (11.4%), and inguinal hernia (6.7%). Conclusion As survival of patients with CDH improves, long-term care must be continuously studied and fine-tuned to ensure appropriate surveillance and optimization of long-term outcomes.

Background Of the types of pulmonary hypertension, chronic thromboembolic pulmonary hypertension (CTEPH) may be cured through pulmonary endarterectomy (PEA). In this study, we investigated patient experiences with PEA for CTEPH treatment in Taiwan. Methods We retrospectively reviewed the records of patients who underwent PEA in two medical centers between January 2005 and December 2019. We measured the following outcomes: in-hospital complications, improvements in cardiac function and exercise capacity, survival using Kaplan–Meier analysis after PEA. Results Twenty-seven patients (female: 17) with a mean age of 52.6 years underwent PEA. Pre-operatively, most patients were New York Heart Association functional class (NYHA FC) III (n = 19) and IV (n = 7). The mean periods from the onset of symptoms to diagnosis and from diagnosis to operation were 22.6 and 22.3 months, respectively. After PEA, mean intubation time, and length of intensive care unit and hospital stay were 9, 11, and 20 days, respectively. Most patients' NYHA FCs improved to I (n = 15) and II (n = 10). The mean 6-min walk test (6MWT) result improved by 60.5%. The in-hospital mortality, mean follow-up period, and 5- and 10-year overall survival rates were 3.7%, 77.0 months, 96.3%, and 84.3%, respectively. Furthermore, 5- and 10-year disease-specific survival rates were both 96.3%. Conclusion When pre-operative and post-operative statuses were compared, we found a significant improvement in NYHA FC and 6MWT distance. Our study also found a lower in-hospital mortality rate compared to other published studies, except compared to the newer data provided by the University of California, San Diego group.

γ-glutamyl transferase (GGT), the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the neutrophil-to-lymphocyte ratio (NLR) are prognostic biomarkers in several cardiovascular diseases, but their relevance in pulmonary hypertension (PH) is not fully understood. We aimed to assess their prognostic value in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH).We retrospectively analyzed 731 incident patients with idiopathic PAH or CTEPH who entered the Giessen PH registry during 1993-2019. A risk stratification score based on GGT, AST/ALT ratio, and NLR tertiles was compared with a truncated version of the European Society of Cardiology/European Respiratory Society (ESC/ERS) risk stratification scheme. Associations with survival were evaluated using Kaplan-Meier and Cox regression analyses. External validation was performed in 311 patients with various types of PAH or CTEPH from a second German center.GGT levels, AST/ALT, and NLR independently predicted mortality at baseline and during follow-up. The scoring system based on these biomarkers predicted mortality at baseline and during follow-up (both log-rank p0.001; hazard ratio [95% confidence interval], high vs low risk: baseline, 7.6 [3.9, 15.0]; follow-up, 13.3 [4.8, 37.1]). Five-year survival of low, intermediate, and high risk groups was 92%, 76%, and 51%, respectively, at baseline and 95%, 78%, and 50%, respectively, during follow-up. Our scoring system showed characteristics comparable to the ESC/ERS scheme, and predicted mortality in the validation cohort.GGT, AST/ALT, and NLR were reliable prognostic biomarkers at baseline and during follow-up, with predictive power comparable to the gold standard for risk stratification.

Pediatric pulmonary hypertension is a disease that has many etiologies and can present anytime during childhood. Its newly revised hemodynamic definition follows that of adult pulmonary hypertension: a mean pulmonary artery pressure >20 mmHg. However, the pediatric definition stipulates that the elevated pressure must be present after the age of three months. The definition encompasses many different etiologies, and diagnosis often involves a combination of noninvasive and invasive testing. Treatment often is extrapolated from adult studies or based on expert opinion. Moreover, although general anesthesia may be required for pediatric patients with pulmonary hypertension, it poses certain risks. A thoughtful, multidisciplinary approach is needed to deliver excellent perioperative care.

In patients with severe aortic stenosis (AS), pulmonary hypertension (PH) typically is indicative of a decompensated disease state with exhausted compensatory mechanisms of the left ventricle, meaning a heart failure state resulting from AS-related "cardiac injury". In the present review article, we discuss new insights into the pathophysiology of AS-induced PH, the prognostic impact, and potential options to prevent and treat PH in this setting. We emphasize recent data from studies focused on invasive hemodynamics in patients with severe AS that are being evaluated for aortic valve replacement, particularly the key relevance of combined pre- and post-capillary PH. This latter represents an advanced form of cardiac injury that is often associated with right ventricular dysfunction and poor prognosis. Given this context, we highlight the relevance of performing right heart catheterization in combination with non-invasive imaging for the comprehensive assessment of AS patients that are being evaluated for aortic valve replacement. Such comprehensive assessment plays a key role not only to precisely define the extent of AS-related cardiac injury but also to distinguish those PH forms that are unrelated to AS.

Though long-neglected, the right heart (RH) is now widely accepted as a pivotal player in heart failure (HF) either with reduced (HFrEF) or preserved (HFpEF) ejection fraction. The chronic overload of the pulmonary microcirculation results in an initial phase characterized by right ventricular (RV) hypertrophy, right atrial (RA) dilation, and diastolic dysfunction. This progresses to overt right heart failure (RHF) when RV dilation and systolic dysfunction lead to RV-pulmonary arterial uncoupling with low RV output. In the context of its established relevance to progression of HF, clinicians should consider assessment of the right heart with information from clinical assessment, biomarkers, and imaging. Notably, no single parameter can predict prognosis alone in HF. Assessments should simultaneously encompass RV systolic function, pulmonary pressures, an estimation of RV-PA coupling, and right heart morphology. Despite a large volume of evidence indicating the relevance of right heart function to the clinical syndrome of HF, evidence-based management strategies are lacking. Targeting RH dysfunction in HF should be an objective of future investigations, being an unmet need in the current management of HF.

Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Although medical therapies have improved the outlook for these patients, there still exists a cohort of patients with PAH who are refractory to these therapies. Lung transplantation (LT), and in certain cases heart-lung transplantation (HLT), is a therapeutic option for patients with severe PAH who are receiving optimal therapy yet declining. ECMO may serve as a bridge to transplant or recovery in appropriate patients. Although, the mortality within the first 3 months after transplant is higher in PAH recipients than the other indications for LT, and the long-term survival after LT is excellent for this group of individuals. In this review, we discuss the indications for LT in PAH patients, when to refer and list patients for LT, the indications for double lung transplant (DLT) versus HLT for PAH patients, types of advanced circulatory support for severe PAH, and short and long-term outcomes in transplant recipients with PAH.

Patients with advanced lung disease can develop pulmonary hypertension and succumb to right ventricular failure/cor pulmonale. Patients with pulmonary hypertension owing to chronic lung disease, or World Health Organization group 3 pulmonary hypertension, are more limited and carry a high risk of mortality. Adjunctive therapies remain the cornerstones of treatment. Recent evidence suggests that inhaled pulmonary vasodilator therapy can be helpful in patients with pulmonary hypertension owing to interstitial lung disease. Lung transplantation may be the only life-saving option in select patients, whereas palliative care and hospice should be sought for those who are not candidates as the disease progresses.

Pulmonary arterial hypertension is a rare disease characterized by pulmonary microvasculature remodeling leading to right ventricular failure and death. Medical management of pulmonary hypertension has grown increasingly complex as more therapeutic agents have been developed. Evolving treatment strategies leveraging the endothelin, nitric oxide, and prostacyclin pathways lead to improved exercise capacity and outcomes in patients; however, significant opportunities for advancement remain.

Patients with cirrhosis account for 3% of intensive care unit admissions with hospital mortality exceeding 50%; however, improvements in survival among patients with acutely decompensated cirrhosis and organ failure have been described when treated in specialized liver transplant centers. Acute-on-chronic liver failure is a distinct clinical syndrome characterized by decompensated cirrhosis associated with one or more organ failures resulting in a significantly higher short-term mortality. In this review, we will discuss the management of common life-threatening complications in the patient with cirrhosis that require intensive care management including neurologic, cardiovascular, gastrointestinal, pulmonary, and renal complications.

Pregnancy entails significant changes in maternal physiology that are not well-tolerated in patients with pulmonary arterial hypertension. The profound changes in plasma volume, cardiac output, and systemic vascular resistance can lead to increased strain placed on the right ventricle, leading to right-heart failure and cardiovascular collapse. Given the complex and sometimes opposing physiologic changes, managing these patients can be challenging. As such, these patients have a significantly increased reported maternal mortality rate. This report describes a parturient with newly diagnosed severe pulmonary arterial hypertension and her anesthetic management.

Pulmonary hypertension (PH) due to left heart disease (LHD; group 2 PH) is a common complication of heart failure with reduced ejection fraction and heart failure with preserved ejection fraction and is often related to disease severity and duration of these diseases. PH due to LHD is associated with negative impact on outcomes in addition to worse symptoms and exercise capacity. Risk factors for group 2 PH are older age, hypertension, atrial fibrillation, and features of metabolic syndrome. The main mechanisms for group 2 PH are believed to be vascular remodeling secondary to sustained elevated intravascular pressure.

BACKGROUND We examined whether the early development of exercise-induced pulmonary hypertension (EIPH) and right ventricular dysfunction during exercise stress echocardiography (ESE) may predict clinical deterioration in so-called "asymptomatic" patients with primary, at least moderate mitral regurgitation (MR). METHODS 79 consecutive patients underwent a symptom-limited, graded ESE protocol on semi-supine bicycle at the beginning of the study. During the test, we assessed symptom development, test duration, and the following echocardiographic parameters: MR severity, maximum velocity of the tricuspid regurgitation jet (TR Vmax), pulmonary artery systolic pressure (PASP), and tricuspid annulus systolic excursion (TAPSE). All patients were then followed-up for at least 12 months for clinical end-points (heart failure-related symptoms requiring pharmaceutical therapy, heart failure hospitalization, and/or mitral valve surgery in case of refractory symptoms). RESULTS After 16 ± 4 months of follow-up, 75 patients completed the study; 26 of them achieved any clinical end-point and were classified as 'high-risk', while the rest (49 patients) were assigned to the 'low-risk' group. High-risk group showed significantly higher exercise-induced TR Vmax and PASP levels at maximum workload of ESE than low-risk counterparts (p

Pulmonary hypertension (PH) commonly complicates connective tissue disease and is associated with increased morbidity and mortality in this population. The incidence of PH varies widely between connective tissue diseases; patients with systemic sclerosis are most likely to develop PH. Several different types of PH can present in CTD, including PH related to left heart disease, respiratory disease such as interstitial lung disease or chronic obstructive lung disease, chronic thromboembolic disease, and renal disease. Importantly, CTD patients are at risk for developing pulmonary arterial hypertension (PAH), in which PH is present without any of the aforementioned co-morbidities. However, despite this increased risk of development of PH, patients with PAH may benefit from specific pulmonary vasodilator therapy and thus, are an important group to identify. Unfortunately, response to pulmonary vasodilator therapy in general is less robust and survival is worse in CTD-associated PAH than in other patient populations with PAH. Still, early diagnosis and treatment of PH, if indicated, may allow for institution of pulmonary vasodilator therapy and for appropriate referral for lung transplantation.

Pediatric pulmonary hypertension (PH) is a rare disease with historically very high morbidity and mortality. In the past 20 years, there has been a growing recognition that pediatric PH, although having similarities to adult PH, is a unique entity with its own particular pathogeneses, presentation, and management. With better understanding and earlier diagnosis of pediatric PH, and as more medications have become available, survival of children with PH has also significantly improved. This article reviews the various forms of PH in childhood, with a focus on both established and investigational therapies that are available for children with PH.

OBJECTIVE Paediatric lung transplantation poses unique management challenges. Experience regarding indications and outcome is scarce, especially in younger children. The primary aim of this study was to investigate outcome after first lung transplantation in children

Pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) affects 5% to 10% of adults with CHD and is associated with significant morbidity and mortality. PAH-CHD develops as a consequence of intracardiac or extracardiac systemic-to-pulmonary shunts that lead to pulmonary vascular remodeling through a pathologic process that is similar to other causes of PAH. Eisenmenger syndrome is the most severe phenotype of PAH-CHD and is characterized by severe elevation in pulmonary vascular resistance, with shunt reversal causing hypoxemia and central cyanosis. The primary management strategy for most patients with PAH-CHD is medical therapy, although defect closure is considered in select cases.

It is important to recognize and treat human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) because of the associated morbidity and mortality. With the introduction of antiretroviral therapies (ART), improved survival has changed the focus of treatment management from immunodeficiency-related opportunistic infections to chronic cardiovascular complications, including HIV-PAH. The 2018 6th World Symposium of Pulmonary Hypertension recommended a revised definition of PAH that might result in a greater number of patients with HIV-PAH; however, the implication of this change is not yet clear. Here, we review the current literature on the diagnosis, management, and outcomes of patients with HIV-PAH.

Background Riociguat is effective in delaying the time to clinical worsening (TCW) in patients with groups 1 and 4 pulmonary hypertension. Research Question Is riociguat more effective than placebo in prolonging TCW in sarcoidosis-associated pulmonary hypertension (SAPH)? Study Design and Methods This was a double-blind placebo-controlled trial. Patients with SAPH confirmed by right heart catheterization were randomized 1:1 to riociguat or placebo. Patients underwent 6-min walk distance (6MWD) and spirometry testing every 8 weeks. The primary end point was TCW, which was defined by the time to the first of the following: (1) all-cause mortality, (2) need for hospitalization because of worsening cardiopulmonary status attributable to progression of disease, (3) > 50 m decrease in the 6MWD test, or (4) worsening of World Health Organization functional class. Results A total of 16 patients were randomized to riociguat (n = 8) or placebo (n = 8). No difference was found in pulmonary artery mean, pulmonary vascular resistance, initial 6MWD, or FVC between the two groups. Five of eight patients who received placebo met TCW criteria, whereas none of the patients who received riociguat experienced a qualifying event. By log-rank analysis, patients who received riociguat were in the study for a significantly longer period (χ 2 = 6.259; P = .0124). The 6MWD decreased in the placebo group (median, –55.9 m; range, –176.8 to 60 m), but rose in the riociguat group (median, +42.7 m; range, –7.5 to +91.4 m; P = .0149), with a placebo-corrected difference of 94 m (P 30-m improvement in 6MWD (P > .05). No significant adverse events associated with riociguat occurred. Interpretation Over the 1 year of the study, riociguat was effective in preventing clinical worsening and improving exercise capacity in patients with SAPH. Trial Registry ClinicalTrials.gov ; No.: NCT02625558 ; URL: www.clinicaltrials.gov

Objective The aim of this study was to determine the therapeutic effect of piperlongumine on hypoxic pulmonary hypertension. Methods A hypoxic pulmonary hypertension rat model was constructed, primary rat pulmonary artery smooth muscle cells (PASMCs) were isolated, and the proliferation of PASMCs was measured by Cell Counting Kit‑8 assay. The expression of autophagic proteins microtubule-associated protein 1 light chain 3B (LC3B) and P62 were examined by western blot. Autophagic flux in PASMCs was detected by tandem mRFP-GFP-LC3 fluorescence analysis. Results Hypoxia-induced proliferation of PASMCs was significantly inhibited by piperlongumine exposure. Treatment with piperlongumine elevated LC3B II/LC3B I protein ratio and decreased the expression of P62 protein in both PASMCs and rat lung tissues. Tandem mRFP-GFP-LC3 fluorescence analysis showed that piperlongumine increased autophagic flux in PASMCs. Inhibition of autophagy using 3-methyladenine (3-MA) attenuated the inhibitory effect of piperlongumine on proliferation of PASMCs. Chronic hypoxia exposure led to a significant increase in rat right ventricle systolic pressure, right ventricular hypertrophy, wall thickness and area of pulmonary artery, and muscularization of pulmonary arterioles, which was obviously suppressed by administration of piperlongumine. 3-MA attenuated the alleviating effects of piperlongumine on pulmonary vascular remodeling. Conclusions Piperlongumine attenuates vascular remodeling in hypoxic pulmonary hypertension by regulating autophagy. Piperlongumine treatment may serve as a promising therapy for hypoxic pulmonary hypertension.

BACKGROUND Left and right atrial volume indices (LAVI and RAVI) are markers of cardiac remodeling. LAVI and RAVI are associated with worse outcomes in other cardiac conditions. This study aimed to determine the associations of these atrial volume indices with survival time post-cardiac arrest. METHODS This was a single center, retrospective study of patients with a sudden cardiac arrest event during index hospitalization from 2014-2018 based on pre-arrest parameters. The analysis was stratified based on whether a pulseless ventricular tachycardia/ventricular fibrillation (pVT/VF) event or a pulseless electrical activity (PEA)/asystole event occurred. Cox proportional hazards regression and model selection with best subsets approach evaluated the association of atrial volume parameters with survival times in the context of other covariates. RESULTS Of 305 patients studied (64 ± 14 years, 37% female), the mean LAVI was 34.0 ± 15.8 mL/m2 (based on 162 reliable measurements), and mean RAVI was 25.0 ± 15.6 mL/m2 (based on 163 measurements). Increased atrial volume indices were most strongly associated with survival in patients who had sustained pVT/VF (LAVI HR 0.47, 95% CI 0.25-0.90, p = 0.020; RAVI HR 0.57, 95% CI 0.30-1.05, p = 0.074). In multivariable best subsets Cox regression with LAVI, RAVI, and 13 other scaled covariates, LAVI

Patients with borderline hypoplastic right or left ventricle and VSD may be candidates for either single ventricle palliation or staged ventricular recruitment (SVR) followed by eventual biventricular conversion. Components of SVR include restriction of atrial septal defects (ASD) without ventricular septal defects (VSD) closure and addition of accessory pulmonary blood flow. This study evaluated the impact of ASD restriction on ventricular growth and function. We retrospectively reviewed patients with borderline ventricular hypoplasia and VSD who underwent a staged ventricular recruitment (SVR) procedure from 2012 to June 2019. Pre- and post-recruitment MRI and echocardiogram data were compared and analyzed. We excluded cases in which we intentionally restricted VSD with simultaneous ASD restriction. Forty-six patients (41 with right-dominant ventricle, 25 with risk factors for Fontan procedure) underwent SVR at a median age of 15.1 months' (interquartile range (IQR), 7.2-37.2 months'). The median indexed ventricular end-diastolic volume, end-systolic volume, and stroke volume according to cardiac MRI significantly increased at median 11.0 months' (IQR:7.8~14.1 months') after recruitment. Among them, except 2 operative mortalities after SVR, 26 patients underwent bi-ventricular repair (56.5% including one and a half ventricle repair) at a median of 8.0 months' (IQR: 6.2-12.2 months') after recruitment. Fifteen patients await biventricular completion, and 3 patients underwent single ventricle palliation. Pulmonary blood flow (Qp) tended to increase after recruitment regardless of type of pulmonary blood flow modification without statistical significance. Six patients died at a median duration of 6.5 months' (IQR: 2.9-11.7) after SVR; 3 patients died after biventricular completion, 2 after recruitment, and 1 after returning to single ventricle palliation. All of them were considered poor Fontan candidates due to severe atrioventricular valve regurgitation, pulmonary hypertension, pulmonary vein stenosis, or airway stenosis. Restriction of the atrial septum leads to the growth of hypoplastic ventricle in patients with ventricular septal defects who undergo SVR regardless of the preoperative characteristics, and eventual biventricular repair can be performed in a subgroup of these patients. Future work is necessary to optimize timing of SVR and method of accessory pulmonary blood flow.

Systemic sclerosis (SSc) differs from other multisystem connective tissue/autoimmune diseases in that its clinical features result mainly from a combination of fibrosis and vascular abnormality (rather than from inflammation). This has major implications for management. SSc is associated with high morbidity and mortality, and is often very painful and disabling. There are two major subtypes, defined on the basis of the extent of skin involvement: limited (often previously referred to as CREST) and diffuse cutaneous. The two subtypes have very different natural histories, autoantibody associations and prognoses, and require different approaches to management, at least in their early stages. The two most characteristic features of SSc are Raynaud's phenomenon (which can be very severe) and skin thickening (ʻsclerodermaʼ). Although both cause troublesome, often disabling symptoms, it is the internal organ involvement of the disease that can be life-threatening. This article discusses recent advances in early diagnosis, clinical features and the approach to investigation and management. It is an exciting time for clinicians with an interest in SSc, because following on from the development of new treatments for several organ-based complications (e.g. pulmonary arterial hypertension, digital ulceration), several promising ʻdisease-modifyingʼ therapies (including antifibrotics) are currently being studied in clinical trials.

Objectives This study investigated whether pulmonary artery (PA) 18F-FDG uptake is associated with hypertension, and if it correlates to elevated pulmonary pressures. Background 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography or cardiac magnetic resonance (CMR) has been used to assess inflammation mostly in large arteries of the systemic circulation. Much less is known about inflammation of the vasculature of the pulmonary system and its relationship to pulmonary hypertension (PH). Methods In a single-center cohort of 175 patients with suspected cardiac sarcoidosis, who underwent hybrid thoracic PET/CMR, 18F-FDG uptake in the PA was quantified according to maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) and compared with available results from right heart catheterization (RHC) or transthoracic echocardiography (TTE). Results Thirty-three subjects demonstrated clear 18F-FDG uptake in the PA wall. In the subgroup of patients who underwent RHC (n = 10), the mean PA pressure was significantly higher in the group with PA 18F-FDG uptake compared with the group without uptake (34.4 ± 7.2 mm Hg vs 25.6 ± 9.3 mm Hg; P = 0.003), and 9 (90%) patients with PA 18F-FDG uptake had PH when a mean PA pressure cutoff of 25 mm Hg was used compared with 18 (45%) in the nonuptake group (P Conclusions We demonstrate that 18F-FDG uptake by PET/CMR in the PA is associated with PH and that its intensity correlates with PA pressure.

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary embolism, and pulmonary endarterectomy (PEA) is the surgical treatment. Asymmetric dimethylarginine (ADMA) levels are increased in pulmonary hypertension. This study aimed to investigate serum ADMA levels in patients with CTEPH, the effect of PEA on ADMA, and its prognostic value in long-term mortality. Method Eighty (80) patients with CTEPH and 32 healthy controls were included. Preoperative serum ADMA levels, determined using an enzyme-linked immunosorbent assay, were compared between patients with CTEPH and controls. Of 80 patients, 64 had PEA. Pre- and 6-month postoperative serum ADMA levels, 6-minute walk distance (6MWD), and haemodynamic parameters were collected from patients undergoing PEA. Patients were followed-up for survival analysis. Results Mean ± standard deviation serum ADMA levels were significantly higher in patients with CTEPH compared with controls (0.79±0.32 μmol/L vs 0.52±0.12 μmol/L; p=0.0001). Statistically significant differences were observed between preoperative and postoperative serum ADMA levels (0.78±0.30 μmol/L vs 0.62±0.22 μmol/L; p=0.0001), 6MWD (p=0.0001), and pulmonary vascular resistance (p=0.0001) in 60 patients who underwent and survived PEA. The decrease in serum ADMA levels and increase in 6MWD were significantly correlated (r=–0.286, p=0.027). No other correlation was found. Perioperative mortality was 6.3%, and the survival rate with a mean follow-up of 34.57±8.20 months was 93.3%. Patients with serum ADMA levels >0.8 μmol/L had a significantly lower survival rate (logrank: 5.86; p=0.015). Conclusions Levels of circulating ADMA might add diagnostic and prognostic information in CTEPH. Pulmonary endarterectomy is associated with an improvement in serum ADMA levels. Preoperative serum ADMA levels may be useful for estimating the outcome of PEA.

Pulmonary hypertension (PH) is an important contributor to morbidity and mortality in patients seeking emergency care, resulting in high acuity presentations and resource utilization. The objective was to characterize the rate of intensive care unit (ICU) admission for PH among adult patients presenting to the emergency department (ED) along with other important clinical outcomes.We analyzed data from the State Emergency Department Databases (SEDD) and State Inpatient Databases (SID) from two geographically separated U.S. states (New York and Nebraska). The primary outcome measure was admission to an ICU. Other measures of interest included the hospital admission rate, hospital length of stay (LOS), inpatient mortality, and rate of critical care procedures performed.From 2010 to 2014, in a sample of 34 million ED visits, patients with a diagnosis of PH accounted for 0.71% of all ED visits. Of the PH visits, 20.2% were admitted to the ICU, compared to 2.6% of all other visits (P0.001), with an aOR of 1.74 (95% CI 1. 72-1.76). The vast majority (94.6%) of PH patients were admitted to the hospital, compared to 20.5% for all other ED visits (P0.001). Hospital LOS and hospital-based mortality were higher in the PH group than for other ED patients. With the exception of invasive mechanical ventilation, a significantly higher percentage of patients with PH admitted to the ICU than other patients underwent all critical care procedures evaluated.In this study, patients with PH who sought emergency care in U.S. EDs from 2010 to 2014 were significantly more likely to require ICU admission than all other patients. They were also significantly more likely to be admitted to the hospital than all other patients, had longer hospital LOS, increased risk of inpatient mortality, and underwent more critical care procedures. These findings indicate the high acuity of PH patients seeking emergency care and demonstrate the need for additional research into this population.

Background aims Extracellular vesicles (EVs) are being tested for their use as novel therapeutics. However, the optimal source of EVs is currently under investigation. Amniotic fluid (AF) is a natural source of EVs that can be easily obtained for use in regenerative medicine, yet AF-EV characterization has not been fully explored. Methods Here the authors demonstrate AF as a rich source of EVs and identify the microRNA and proteomic cargo. Bioinformatics analysis of this cargo revealed multiple pathway targets, including immunomodulatory, anti-inflammatory and free radical scavenging networks. The authors further demonstrated the therapeutic potential of this EV product as a novel preventative agent for bronchopulmonary dysplasia (BPD). Results Intra-tracheal administration of AF-EVs preserved alveolar development, attenuated vascular remodeling and pulmonary hypertension, decreased lung pro-inflammatory cytokine expression and reduced macrophage infiltration in an experimental BPD model. Conclusions The authors’ results suggest that AF is a viable biological fluid for EV harvest and that AF-EVs have strong therapeutic potential for pulmonary diseases, such as BPD, warranting further development to transition this novel EV product into the clinic.

Objectives The aim of this study was to evaluate the clinical impact of computed tomography (CT)–derived pulmonary artery dilatation (PAD) in patients undergoing transcatheter aortic valve replacement (TAVR). Background Several studies have reported an association between pulmonary hypertension and cardiovascular events, but the prognostic value of PAD in patients undergoing TAVR remains unclear. Methods The preprocedural computed tomographic studies of patients who underwent TAVR at Cedars-Sinai Medical Center between November 2013 and December 2017 were analyzed. Patients were divided into 2 groups according to the presence of PAD assessed on CT (pulmonary artery [PA] diameter ≥29 mm). The primary endpoint was all-cause mortality at 2 years. Results A total of 895 patients were included (mean age 81.3 ± 8.5 years), with a mean Society of Thoracic Surgeons score of 4.8%. The median PA diameter was 28.0 mm, and PAD was observed in 369 patients (41.2%). Compared with the no-PAD group, the PAD group had higher Society of Thoracic Surgeons scores and higher rates of atrial fibrillation, chronic kidney disease, and chronic obstructive pulmonary disease. The PAD group had higher 2-year all-cause mortality than the no-PAD group (28.9% vs 12.8%; P 36 mm Hg). Conclusions CT-derived PAD is a significant prognostic factor in patients undergoing TAVR.

BACKGROUND: A warmup period of “priming” exercise has been shown to improve peripheral oxygen transport in older adults. We sought to determine the acute effects of priming exercise on central hemodynamics at rest and during a repeat exercise in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This is a post-hoc analysis from three studies. Subjects with HFpEF (n=42) underwent cardiac catheterization with simultaneous expired gas analysis at rest and during exercise (20W for 5 minutes, “priming” exercise). Measurements were then repeated at rest and during a second bout of exercise at 20W workload (second exercise). During priming exercise, HFpEF subjects displayed dramatic increases in biventricular filling pressures and exercise-induced pulmonary hypertension. Following priming exercise at rest, biventricular filling pressures and pulmonary artery (PA) pressures were lower and lung tidal volume was increased. During the second bout of exercise, biventricular filling (PA wedge pressure, 29±8 mmHg at 2(nd) exercise vs. 32±7 mmHg at 1(st) exercise, p=0.0003) and PA pressures were lower, and PA compliance increased. CONCLUSIONS: This study shows that short duration, submaximal priming exercise attenuates the pathologic increases in filling pressures, improving pulmonary vascular hemodynamics at rest and during repeat exercise in HFpEF. CLINICAL TRIAL REGISTRATIONS: ClinicalTrials.gov identifier: NCT01932606, NCT02262078, NCT02885636.

Background Pulmonary hypertension is a heterogeneous disease, and a significant portion of patients at risk for it have CT imaging available. Advanced automated processing techniques could be leveraged for early detection, screening, and development of quantitative phenotypes. Pruning and vascular tortuosity have been previously described in pulmonary arterial hypertension (PAH), but the extent of these phenomena in arterial vs venous pulmonary vasculature and in exercise pulmonary hypertension (ePH) have not been described. Research Question What are the arterial and venous manifestations of pruning and vascular tortuosity using CT imaging in PAH, and do they also occur in ePH? Study Design and Methods A cohort of patients with PAH and ePH and control subjects with available CT angiograms were retrospectively identified to examine the differential arterial and venous presence of pruning and tortuosity in patients with precapillary pulmonary hypertension not confounded by lung or thromboembolic disease. The pulmonary vasculature was reconstructed, and an artificial intelligence method was used to separate arteries and veins and to compute arterial and venous vascular volumes and tortuosity. Results A total of 42 patients with PAH, 12 patients with ePH, and 37 control subjects were identified. There was relatively lower (median [interquartile range]) arterial small vessel volume in subjects with PAH (PAH 14.7 [11.7-16.5; P < .0001]) vs control subjects (16.9 [15.6-19.2]) and venous small vessel volume in subjects with PAH and ePH (PAH 8.0 [6.5-9.6; P < .0001]; ePH, 7.8 [7.5-11.4; P = .004]) vs control subjects (11.5 [10.6-12.2]). Higher large arterial volume, however, was only observed in the pulmonary arteries (PAH 17.1 [13.6-23.4; P < .0001] vs control subjects 11.4 [8.1-15.4]). Similarly, tortuosity was higher in the pulmonary arteries in the PAH group (PAH 3.5 [3.3-3.6; P = .0002] vs control 3.2 [3.2-3.3]). Interpretation Lower small distal pulmonary vascular volume, higher proximal arterial volume, and higher arterial tortuosity were observed in PAH. These can be quantified by using automated techniques from clinically acquired CT scans of patients with ePH and resting PAH., Graphical Abstract

Background A mean pulmonary artery pressure >20 mm Hg now defines pulmonary hypertension. We hypothesize that echocardiographic thresholds must be adjusted. Research Question Should tricuspid regurgitation velocity thresholds to screen for pulmonary hypertension be revised, given the new hemodynamic definition? Study Design and Methods This multicenter retrospective study included 1,608 patients who underwent both echocardiography and right heart catherization within 4 weeks. The discovery cohort consisted of 1,081 individuals; the validation cohort included 527. Screening criteria for pulmonary hypertension were derived with the use of receiver operating characteristic analysis and the Youden index, assuming equal cost for false-positive and -negative classification. A lower threshold was calculated with the use of a predefined sensitivity: 95%. Results In the discovery cohort, echocardiographic tricuspid regurgitation velocity had a good discrimination for pulmonary hypertension: area under the curve, 88.4 (95% CI, 85.3-91.5). A 3.4-m/s threshold provided a 78% sensitivity, 87% specificity, and 6.13 positive likelihood ratio to detect pulmonary hypertension; 2.7 m/s had a 95% sensitivity and 0.12 negative likelihood ratio to exclude pulmonary hypertension. In the validation cohort, the discovery threshold of 2.7 m/s provided sensitivity and negative likelihood ratios of 80% and 0.31, respectively. Right cardiac size improved detection of pulmonary hypertension in the lower tricuspid regurgitation velocity groups. Interpretation Our data support a lower tricuspid regurgitation velocity of approximately 2.7 m/s for screening pulmonary hypertension, with a high sensitivity in tertiary referral centers. Right heart chamber measurements improve the diagnostic yield of echocardiography.

Background Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation , but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates. Methods Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes. Results 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p Conclusions Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

Objectives To assess the feasibility of magnetic resonance imaging (MRI) for postnatal assessment of pulmonary vascularity in infants with congenital diaphragmatic hernia (CDH). Study design Infants with prenatally diagnosed CDH (n = 24) received postnatal pulmonary MRI. Infants with nonpulmonary birth defects served as controls (n = 5). Semiautomatic segmentation was performed to obtain total vascular volume using time of flight images to assess vascularity. Results Average vascular density (vascular volume/lung volume) in control infants was 0.23 ± 0.06 mm3/mm3 compared with 0.18 ± 0.06 mm3/mm3 in infants with CDH is (P = .09). When stratified further based on CDH severity, the difference between control infants and moderate CDH group was statistically significant. (0.23 mm3/mm3 vs 0.15 mm3/mm3, P = .01). Ipsilateral vascular density on MRI in infants with CDH significantly correlated with the prenatal pulmonary hypertensive index (P = .0004, Spearman R = +0.87) and with number of days on mechanical ventilation (P = .04, Spearman R = −0.44), total days on inhaled nitric oxide (P = .02, Spearman R = −0.47), use of epoprostenol for acute pulmonary hypertension (PH) (0.14 mm3/mm3 vs 0.20 mm3/mm3, P = .005), and use of sildenafil for chronic PH (0.15 mm3/mm3 vs 0.19 mm3/mm3, P = .03). Conclusions Our results suggest that postnatal pulmonary vascularity assessed by MRI strongly correlates with prenatal and postnatal markers of PH severity and that pulmonary vascularity may serve as a direct measure of pulmonary vascular hypoplasia in infants with CDH.

Summary Background INCREASE was a randomised, placebo-controlled, phase 3 trial that evaluated inhaled treprostinil in patients with interstitial lung disease (ILD) and associated pulmonary hypertension. Treprostinil improved exercise capacity from baseline to week 16, assessed with the use of a 6-min walk test, compared with placebo. Improvements in forced vital capacity (FVC) were also reported. The aim of this post-hoc analysis was to further characterise the effects of inhaled treprostinil on FVC in the overall study population and in various subgroups of interest. Methods In this post-hoc analysis, we evaluated FVC changes in the overall study population and in various subgroups defined by cause of disease or baseline clinical parameters. The study population included patients aged 18 years and older who had a diagnosis of ILD based on evidence of diffuse parenchymal lung disease on chest CT done within 6 months before random assignment (not centrally adjudicated). All analyses were done on the intention-to-treat population, defined as individuals who were randomly assigned and received at least one dose of study drug. The INCREASE study is registered with ClinicalTrials.gov, NCT02630316. Findings Between Feb 3, 2017, and Aug 30, 2019, 326 patients were enrolled in the INCREASE trial. Inhaled treprostinil was associated with a placebo-corrected least squares mean improvement in FVC of 28·5 mL (SE 30·1; 95% CI −30·8 to 87·7; p=0·35) at week 8 and 44·4 mL (35·4; −25·2 to 114·0; p=0·21) at week 16, with associated percentage of predicted FVC improvements of 1·8% (0·7; 0·4 to 3·2; p=0·014) and 1·8% (0·8; 0·2 to 3·4; p=0·028). Subgroup analysis of patients with idiopathic interstitial pneumonia showed FVC differences of 46·5 mL (SE 39·9; 95% CI −32·5 to 125·5; p=0·25) at week 8 and 108·2 mL (46·9; 15·3 to 201·1; p=0·023) at week 16. Analysis of patients with idiopathic pulmonary fibrosis showed FVC differences of 84·5 mL (52·7; −20·4 to 189·5; p=0·11) at week 8 and 168·5 mL (64·5; 40·1 to 297·0; p=0·011) at week 16. The most frequent adverse events included cough, headache, dyspnoea, dizziness, nausea, fatigue, and diarrhoea. Interpretation In patients with ILD and associated pulmonary hypertension, inhaled treprostinil was associated with improvements in FVC versus placebo at 16 weeks. This difference was most evident in patients with idiopathic interstitial pneumonia, particularly idiopathic pulmonary fibrosis. Inhaled treprostinil appears to be a promising therapy for idiopathic pulmonary fibrosis that warrants further investigation in a prospective, randomised, placebo-controlled study. Funding United Therapeutics Corporation.

Background Pulmonary hypertension is a progressive medical condition that has been identified as a risk factor for perioperative morbidity and mortality in both cardiac and non-cardiac surgery, including hip arthroplasty. Currently, there is very limited information on the impact of pulmonary hypertension (PHTN) on patients undergoing shoulder arthroplasty. This investigation analyzed the mortality, perioperative medical complications, implant survivorship, and clinical outcomes in this medically complex cohort. Methods Between January 2000 and July 2018, 380 primary and 59 revision shoulder arthroplasties were performed at a single institution in patients with a diagnosis of pulmonary hypertension prior surgery. Average age was 72.8 ± 11.0 and 72.1 ± 9.5 years for the primary and revision SA groups, respectively (P= .65). The median American Society of Anesthesiologists (ASA) scores were predominantly class 3 in both cohorts. Descriptions of group characteristics were calculated with student tests for numerical values. Mortality after primary and revision shoulder arthroplasties were individually calculated through a cumulative incidence analysis. Implant survivorship was analyzed with a competing risk model selecting death as the competing risk. Results The 90-day mortality was 1.6% for primary and 3.4% for revision SA, respectively. The cumulative incidences of death at 2, 5, 10, and 15 years were 16.5%, 43.3%, 80.8%, and 88.5% for primary and 12.1%, 44.7%, 64.4%, and 100% for revision arthroplasties, respectively. Medical complications were observed in 13.4% of primary and 42.4% of revision shoulder arthroplasties. These included respiratory failure and/or acute respiratory distress syndrome (3.2%), arrhythmia (2.7%), deep vein thrombosis (1.8%), and pulmonary embolism (1.6%). The 10-year cumulative incidences of revision for any reason were 4.5% in primary and 10.4% in revision shoulder arthroplasties. At final follow-up, the mean VAS and ASES scores were 2.3 ± 2.5 and 72.0 ± 18.5 in primary SA and 4.1 ± 2.9 and 51.8 ± 21.8 in revision SA. Conclusions A concomitant diagnosis of PHTN in patients undergoing primary or revision shoulder arthroplasty was associated with a high rate of perioperative medical complications and mortality rates at 90 days and at 10 years in both cohorts. This information should be considered to counsel patients, optimize their perioperative management, and anticipate a more complicated and costly postoperative recovery. Level of Evidence Level IV; Case Series with no Comparison Group

Women with valvular heart disease may be more likely to have adverse obstetric and cardiovascular complications during pregnancy. Most current recommendations focus on stenotic lesions with less guidance regarding regurgitant lesions. We aimed to compare adverse events at delivery for women with various stenotic and regurgitant valvular diseases. We used the 2016 to 2018 National Inpatient Sample data to compare demographics, comorbidities, and obstetric and cardiovascular complications during delivery hospitalizations. After adjusting for clinical and socioeconomic factors, logistic regression was performed to investigate associations between valvular disease and outcomes. Among >11.2 million deliveries, 20,349 were in women with valvular disease. Women with valvular disease were older, had longer length of stays, and higher costs associated with delivery. They had higher prevalence of underlying cardiovascular comorbidities compared with women without valvular disease (hypertension: 5.1 vs 0.25%; pulmonary hypertension: 7.0 vs

BACKGROUND The United States Chronic Thromboembolic Pulmonary Hypertension Registry (US-CTEPH-R) was designed to characterize the demographic characteristics, evaluation, clinical course, and outcomes of surgical and nonsurgical therapies for patients with chronic thromboembolic pulmonary hypertension. RESEARCH QUESTION What are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects? STUDY DESIGN AND METHODS This study describes a multicenter, prospective, longitudinal, observational registry of patients newly diagnosed (< 6 months) with CTEPH. Inclusion criteria required a mean pulmonary artery pressure ≥ 25 mm Hg documented by right heart catheterization and radiologic confirmation of CTEPH. Between 2015 and 2018, a total of 750 patients were enrolled and followed up biannually until 2019. RESULTS Most patients with CTEPH (87.9%) reported a history of acute pulmonary embolism. CTEPH diagnosis delays were frequent (median, 10 months), and most patients reported World Health Organization functional class 3 status at enrollment with a median mean pulmonary artery pressure of 44 mm Hg. The registry cohort was subdivided into Operable patients undergoing pulmonary thromboendarterectomy (PTE) surgery (n = 566), Operable patients who did not undergo surgery (n = 88), and those who were Inoperable (n = 96). Inoperable patients were older than Operated patients; less likely to be obese; have a DVT history, non-type O blood group, or thrombophilia; and more likely to have COPD or a history of cancer. PTE resulted in a median pulmonary vascular resistance decline from 6.9 to 2.6 Wood units (P < .001) with a 3.9% in-hospital mortality. At 1-year follow-up, Operated patients were less likely treated with oxygen, diuretics, or pulmonary hypertension-targeted therapy compared with Inoperable patients. A larger percentage of Operated patients were World Health Organization functional class 1 or 2 at 1 year (82.9%) compared with the Inoperable (48.2%) and Operable/No Surgery (56%) groups (P < .001). INTERPRETATION Differences exist in the clinical characteristics between patients who exhibited operable CTEPH and those who were inoperable, with the most favorable 1-year outcomes in those who underwent PTE surgery. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov.