Search

Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap Syndrome (BCOS) is a complex pulmonary condition that merges bronchiectasis and chronic obstructive pulmonary disease (COPD), presenting unique clinical challenges. Patients with BCOS typically exhibit a range of symptoms from both conditions, including a chronic productive cough, reduced lung function, frequent exacerbations, and diminished exercise tolerance. The etiology of BCOS involves multiple factors such as genetic predisposition, respiratory infections, tobacco smoke, air pollutants, and other inflammatory mediators. Accurate diagnosis requires a comprehensive approach, incorporating pulmonary function tests to evaluate airflow limitation, radiographic imaging to identify structural lung abnormalities, and blood eosinophil counts to detect underlying inflammation. Treatment strategies are tailored to individual symptom profiles and severity, potentially including bronchodilators, inhaled corticosteroids, and pulmonary therapy to improve lung function and quality of life. Patients with BCOS are also at an increased risk for cardiovascular complications, such as stroke, ischemic heart disease, and cor pulmonale. Additionally, medications like beta-agonists and muscarinic antagonists used in COPD treatment can further affect cardiac risk by altering heart rate. This paper aims to provide a thorough understanding of BCOS, addressing its development, diagnosis, treatment, and associated cardiovascular complications, to aid healthcare providers in managing this multifaceted condition and improving patient outcomes. [ABSTRACT FROM AUTHOR]

RNA methylation is a widespread regulatory mechanism that controls gene expression in physiological processes. In recent years, the mechanisms and functions of RNA methylation under diseased conditions have been increasingly unveiled by RNA sequencing technologies with large scale and high resolution. In this review, the fundamental concept of RNA methylation is introduced, and the common types of transcript methylation and their machineries are described. Then, the regulatory roles of RNA methylation, particularly N6-methyladenosine and 5-methylcytosine, in the vascular lesions of ocular and cardiopulmonary diseases are discussed and compared. The ocular diseases include corneal neovascularization, retinopathy of prematurity, diabetic retinopathy, and pathologic myopia; whereas the cardiopulmonary ailments involve atherosclerosis and pulmonary hypertension. This review hopes to shed light on the common regulatory mechanisms underlying the vascular lesions in these ocular and cardiopulmonary diseases, which may be conducive to developing therapeutic strategies in clinical practice. [ABSTRACT FROM AUTHOR]

Pneumonia is one of the causes of acute respiratory distress syndrome (ARDS) in pediatrics, which can progress to severe conditions such as pulmonary hypertension, leading to right ventricular failure or cor pulmonale. Pediatric patients requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support are challenging in our country, from the time of initiation to another critical dilemma between managing massive bleeding and preventing clotting in the ECMO circuit. An 18-month-old boy presented in a ward with a 5-day history of fever, cough, and increased work of breathing over the prior 24 hours. He was diagnosed with bronchopneumonia and treated with antibiotic therapy. The patient had a rapid deterioration, requiring endotracheal intubation. Blood gas analysis showed oxygenation and ventilation failure with . pulmonary hypertension resulting in cor pulmonale. The patient then underwent cannulation to central VA-ECMO via sternotomy. During the 11-day intensive care unit (ICU) stay, massive bleeding occurred from the cannulation site, with the team attempting to balance between hemorrhage and preventing clot formation in the circuit. The patient died from the failure of the oxygenator, as lung rest could not be achieved due to systemic complications from massive bleeding. For pediatric patients with acute cor pulmonale, it is necessary to be more aggressive in the timing of ECMO initiation, as indicated in the guidelines, and to evaluate the indications for VA-ECMO carefully. This evaluation should consider the benefits and drawbacks from all aspects, including the complications of bleeding that can lead to multiple organ failures in the patient. [ABSTRACT FROM AUTHOR]

Background In recent years, numerous studies have indicated that hyperuricemia (HUA) is a contributing factor to certain diseases. However, whether HUA is a contributing factor to chronic pulmonary heart disease (CPHD) still requires further investigation. Objective To explore the association between HUA and CPHD, aiming to provide a theoretical basis for the management of serum uric acid (SUA) levels in patients with CPHD. Methods A total of1 171 patients with chronic obstructive pulmonary disease (COPD) admitted to the First Affiliated Hospital of Xinjiang Medical University from 2019 to 2023 were included in the study. They were divided into a CPHD group (470 cases) and a COPD group (701 cases) based on whether they had CPHD. General information, laboratory test results, and echocardiographic findings of the patients were collected. LASSO regression was used to select variables, and propensity score matching (PSM) was employed to eliminate the influence of confounding factors. Multivariate Logistic regression analysis was conducted to explore the influencing factors of CPHD in COPD patients. Results The CPHD group had lower proportions of females, Han ethnicity, smokers, drinkers, idiopathic pulmonary fibrosis, chronic bronchitis, bronchial asthma, lymphocyte percentage, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, cardiac output, left ventricular ejection fraction compared to the COPD group. Higher proportions of heart function class 3-4, HUA, pulmonary embolism, congenital heart disease, red blood cell count, neutrophil percentage, SUA, blood urea nitrogen, D-dimer, N-terminal pro-B-type natriuretic peptide, right atrial diameter, right ventricular diameter, left atrial diameter, right ventricular outflow tract diameter, and pulmonary artery diameter were observed in the CPHD group, with statistically significant differences (P381.29 μmol/L) had a 1.421-fold inScrsed risk of having CPHD. Conclusion HUA is a contributing factor to the occurrence and development of CPHD. Actively controlling SUA levels may help prevent the occurrence and development of CPHD.

BACKGROUND: Pulmonary hypertension (PH) is a major complication linked to adverse outcomes in heart failure with preserved ejection fraction (HFpEF), yet no specific therapies exist for PH associated with HFpEF (PH-HFpEF). We have recently reported on the role of skeletal muscle SIRT3 (sirtuin-3) in modulation of PH-HFpEF, suggesting a novel endocrine signaling pathway for skeletal muscle modulation of pulmonary vascular remodeling. METHODS: Using skeletal muscle-specific Sirt3 knockout mice (Sirt3skm-/-) and mass spectrometry-based comparative secretome analysis, we attempted to define the processes by which skeletal muscle SIRT3 defects affect pulmonary vascular health in PH-HFpEF. RESULTS: Sirt3skm-/- mice exhibited reduced pulmonary vascular density accompanied by pulmonary vascular proliferative remodeling and elevated pulmonary pressures. Comparative analysis of secretome by mass spectrometry revealed elevated secretion levels of LOXL2 (lysyl oxidase homolog 2) in SIRT3-deficient skeletal muscle cells. Elevated circulation and protein expression levels of LOXL2 were also observed in plasma and skeletal muscle of Sirt3skm-/- mice, a rat model of PH-HFpEF, and humans with PH-HFpEF. In addition, expression levels of CNPY2 (canopy fibroblast growth factor signaling regulator 2), a known proliferative and angiogenic factor, were increased in pulmonary artery endothelial cells and pulmonary artery smooth muscle cells of Sirt3skm-/- mice and animal models of PH-HFpEF. CNPY2 levels were also higher in pulmonary artery smooth muscle cells of subjects with obesity compared with nonobese subjects. Moreover, treatment with recombinant LOXL2 protein promoted pulmonary artery endothelial cell migration/proliferation and pulmonary artery smooth muscle cell proliferation through regulation of CNPY2-p53 signaling. Last, skeletal muscle--specific Loxl2 deletion decreased pulmonary artery endothelial cell and pulmonary artery smooth muscle cell expression of CNPY2 and improved pulmonary pressures in mice with high-fat diet--induced PH-HFpEF. CONCLUSIONS: This study demonstrates a systemic pathogenic impact of skeletal muscle SIRT3 deficiency in remote pulmonary vascular remodeling and PH-HFpEF. This study suggests a new endocrine signaling axis that links skeletal muscle health and SIRT3 deficiency to remote CNPY2 regulation in the pulmonary vasculature through myokine LOXL2. Our data also identify skeletal muscle SIRT3, myokine LOXL2, and CNPY2 as potential targets for the treatment of PH-HFpEF. [ABSTRACT FROM AUTHOR]

Objective: Congenital defects/diseases. Background: Pulmonary artery sling (PAS) is an anatomical vascular anomaly due to the origin of the left pulmonary artery from the right pulmonary artery, which runs posteriorly between the esophagus and trachea, resulting in compression of adjacent structures. Accurate evaluation for malformation of the pulmonary artery and severity of airway obstruction is essential to surgical strategy. This report presents the diagnosis and surgical management of pulmonary artery sling in a 12-year-old boy. Case Report: A 12-year-old boy had chest tightness and wheezing after exercise for 6 years. He was diagnosed with PSA based on findings from imaging tests, demonstrating the left pulmonary artery originated from the middle of the right pulmonary artery and the tracheal carina was located at the site of the T6 thoracic vertebra. The main bronchus and esophagus were compressed by the left pulmonary artery due to its ectopic origin. Then, after comprehensive preoperative assessment, the patient underwent surgical repair of PAS. Conclusions: This report highlights the importance of pulmonary artery sling diagnosis, imaging, and surgical planning, and the role of a multidisciplinary team in preoperative and postoperative patient management. An individualized strategy based on the preoperative assessment, intraoperative coordination among cardiologists, surgeons, and perfusionists, and careful postoperative management are the core elements for successful PAS repair. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome‐wide association study in the INTERVAL study. The results were validated using a case–control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo‐blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin‐dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019–1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD. [ABSTRACT FROM AUTHOR]

Abstract Aims Sodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study. Methods Randomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed. Results 19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p

Objective To explore the application effect of combined detection of platelet count (PLT),mean platelet volume (MPV) and B-type natriuretic peptide (BNP) in patients with pulmonary heart disease. Methods A toatl of 180 patients hospitalized in the respiratory department of the hospital from March 2019 to April 2022 due to dyspnea were selected and divided into the non-pulmonary heart disease group (95 cases) and the pulmonary heart disease group (85 cases) . Meanwhile, the pulmonary heart disease group was further divided into the acute exacerbation group (85 cases) and the remission group (85 cases) based on the treatment time. The changes in PLT,MPV,and BNP indicators among different groups were compared, and the correlation between BNP levels and MPV and PLT levels was analyzed. Results The PLT levels in the acute exacerbation and remission groups were significantly lower than those in the non-pulmonary heart disease group, while the MPV and BNP levels were significantly higher than those in the non-pulmonary heart disease group, with statistically significant differences (P＜0. 05) . There were statistically significant differences in PLT,MPV and BNP levels between the acute exacerbation group and the remission group (P＜0. 05) . The levels of BNP [ (332. 24±37. 10) pg/mL] and MPV[ (11. 92±1. 26) fL] in the pulmonary heart disease group were significantly higher than those in the non-pulmonary heart disease group, while the levels of PLT [ (142. 25±31. 32) ×10~9/L] were significantly lower than those in the non-pulmonary heart disease group, and the differences were statistically significant (P＜0. 05) . After excluding the non-pulmonary heart disease group, the correlation analysis showed that the BNP levels were positively correlated with the MPV levels (r=0. 357,P＜0. 001),the BNP levels were negatively correlated with the PLT levels (r=-0. 260,P=0. 048),and the PLT levels were negatively correlated with the MPV levels (r=-0. 340,P＜0. 001) . Conclusion BNP is of great significance in the diagnosis of pulmonary heart disease and the assessment of disease status. When combined with PLT and BNP,MPV can become an important clinical indicator for evaluating heart failure and susceptibility to thrombosis in patients with pulmonary heart disease. [ABSTRACT FROM AUTHOR]

Acute decompensated cor pulmonale is a clinical syndrome manifested by acute signs of severe congestive heart failure in chronic pulmonary disease with a high mortality rate. A patient with a history of uncontrolled bronchiectasis presented with generalized edema, severe shortness of breath, cardiogenic shock, and gradual loss of consciousness. Laboratory findings showed severe uncompensated respiratory acidosis and signs of infection. An echocardiography study. showed signs of pulmonary hypertension with right ventricular (RV) dysfunction. Early tracheostomy in combination with the holistic approach (infection control, increased RV afterload prevention, RV contractility improvement, and RV preload optimization) were performed and were able to control the disease progression. This case report showcased the beneficial effect of early tracheostomy in managing acute decompensated cor pulmonale. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Sichuan University (Medical Science Edition) is the property of Editorial Board of Journal of Sichuan University (Medical Sciences) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The epidemiology of HIV-infected individuals on the Medical Intensive Care Units (MICU) has changed after profound progress in treatment of AIDS-defining illnesses and anti-retroviral therapy (ART). Changes of MICU utilization of Hepatitis C (HCV) patients following roll-out of direct-acting antivirals (DAA) are yet to evaluate. Methods: We performed a retrospective study on all patients with HIV, HIV/HCV and HCV admitted to the MICU of University Hospital Bonn 2014–2019. We assessed sociodemographic data, available clinical data from HIV patients (CDC stage, CD4 + lymphocyte cell count, HIV-1-RNA, ART) and HCV patients (HCV-RNA, stage of liver cirrhosis, treatment history) and outcome. Results: 237 patients (46 HIV, 22 HIV/HCV, 169 HCV; 168 male, median age 51.3 years) with 325 MICU admissions were included. Admission criteria for HIV patients were infections (39.7% AIDS-associated, 23.8% with controlled HIV-infection) and cardiopulmonary diseases (14.3%). HIV/HCV coinfected patients had infections in controlled/uncontrolled HIV-infection (46.4%), cardiopulmonary diseases and intoxication/drug abuse (17.9% each). Reasons for HCV-mono-infected patients were infections (24.4%), sequelae of liver disease (20.9%), intoxication/drug abuse (18.4%) and cardiopulmonary diseases (15%). 60 patients deceased; most important risk factor was need for mechanical ventilation. The number of HCV-patients admitted to MICU with chronic active disease and sequelae of liver disease decreased while the proportion of patients with completed DAA-treatment increased. Conclusion: Infections remain the most important reason for MICU admission in patients with HIV and/or HCV infection while non-AIDS related conditions increased. DAA roll-out has a beneficial effect on liver-associated morbidity in HCV patients admitted to MICU. [ABSTRACT FROM AUTHOR]

Background: Acute cor pulmonale (ACP) is prognostic in patients with acute respiratory distress syndrome (ARDS). Identification of paradoxical septal motion (PSM) using two-dimensional echocardiography is highly subjective. We sought to describe feature-engineered metrics derived from LV radial strain changes related to PSM in ARDS patients with ACP of various severity and to illustrate potential diagnostic and prognostic yield. Methods: This prospective bicentric study included patients under protective ventilation for ARDS related to COVID-19 who were assessed using transesophageal echocardiography (TEE). Transgastric short-axis view at mid-papillary level was used to visually grade septal motion, using two-dimensional imaging, solely and combined with LV radial strain: normal (grade 0), transient end-systolic septal flattening (grade 1), prolonged end-systolic septal flattening or reversed septal curvature (grade 2). Inter-observer variability was calculated. Feature engineering was performed to calculate the time-to-peak and area under the strain curve in 6 LV segments. In the subset of patients with serial TEE examinations, a multivariate Cox model analysis accounting for new-onset of PSM as a time-dependent variable was used to identify parameters associated with ICU mortality. Results: Overall, 310 TEE examinations performed in 182 patients were analyzed (age: 67 [60–72] years; men: 66%; SAPSII: 35 [29–40]). Two-dimensional assessment identified a grade 1 and grade 2 PSM in 100 (32%) and 48 (15%) examinations, respectively. Inter-rater reliability was weak using two-dimensional imaging alone (kappa = 0.49; 95% CI 0.40–0.58; p < 0.001) and increased with associated LV radial strain (kappa = 0.84, 95% CI 0.79–0.90, p < 0.001). The time-to-peak of mid-septal and mid-lateral segments occurred significantly later in systole and increased with the grade of PSM. Similarly, the area under the strain curve of these segments increased significantly with the grade of PSM, compared with mid-anterior or mid-inferior segments. Severe acute cor pulmonale with a grade 2 PSM was significantly associated with mortality. Requalification in an upper PSM grade using LV radial strain allowed to better identify patients at risk of death (HR: 6.27 [95% CI 2.28–17.2] vs. 2.80 [95% CI 1.11–7.09]). Conclusions: In objectively depicting PSM and quantitatively assessing its severity, TEE LV radial strain appears as a valuable adjunct to conventional two-dimensional imaging. [ABSTRACT FROM AUTHOR]

Aortopulmonary collateral arteries are persistent embryological vessels supplying lung parenchyma in various cardiopulmonary diseases with underlying pulmonary hypoperfusion. Their identification and mapping are important because of associated clinical implications and tendency to affect the surgical outcome. This article describes the embryological development and clinical relevance of aortopulmonary collaterals in various congenital cardiopulmonary conditions, along with the significance for treatment planning. Roles, strength, and shortcomings of the various imaging options and image-guided interventions are discussed, with a focus on presurgical planning and preparation, as well as postsurgical management. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Nursing in Practice is the property of Journal of Clinical Nursing in Practice (Editorial Board, Shanghai Jiao Tong University Press) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An elderly woman with preinvasive breast cancer, atrial fibrillation, coronary artery-pulmonary artery fistula, pulmonary hypertension and Stage 4 diabetic nephropathy underwent a mastectomy and sentinel lymph node biopsy. Managing her perioperative fluid balance and anticoagulation treatment were challenging. Having a malignancy, atrial fibrillation plus underhydration will increase her risk of hypercoagulation. However, fluid overload will lead to pulmonary oedema which will decrease her oxygenation further in pulmonary hypertension. Cessation of anticoagulation also increased the risk of hypercoagulation. Anticoagulant therapy increases the risk of a perioperative wound haematoma, which may require another general anaesthesia for identification and arrest of the bleeding source and haematoma evacuation. A haematoma will also increase the risk of surgical site infection; especially as a diabetic. Her anticoagulant therapy (rivoroxaban) was stopped four days preoperatively. Her ejection fraction was 50%, with Grade II diastolic dysfunction and TAPSE 0.6 cm. Her CHA2DS2-VASc Score was 5. Perioperatively, intraarterial cannulation was connected to the FloTrac™ sensor and EV1000™ monitor. Her fluid management was monitored using goal directed (GD) fluid therapy. The patient underwent surgery successfully and her anticoagulant therapy was recommenced 14 days postoperatively. [ABSTRACT FROM AUTHOR]

Introduction: Due to the challenge of choosing the optimal treatment regimen as well as the accurate dose calculation algorithm (DCA), this study aimed to evaluate the DCAs to compare the conventional fractionation radiotherapy (CFRT) and hypofractionation radiotherapy (HFRT) of breast cancer (BC) in the prediction of cardio-pulmonary complications. Material and Methods: For 19 patients with left-sided BC, treatment regimens, CFRT (50Gy/25frs) vs. HFRT (42.5Gy/16frs), were simulated. Normal tissue complication probability (NTCP) and tumor control probability (TCP) values for each regimen using radiobiological models were calculated via Monte Carlo (MC) and Collapsed Cone Convolution (CCC) algorithms. For statistical comparison of the results obtained from the regimens and algorithms, the t-test and Wilcoxon test were used in SPSS Statistics. Statistical significance was defined as p<0.05. Results: The mean NTCP and TCP calculated in CFRT and HFRT were as follows: cardiac mortality (MC: CFRT=0.0374±0.0134 vs. HFRT=0.0173±0.0066; p<0.001) and (CCC: CFRT=0.0373±0.0134 vs. HFRT=0.0168±0.0064; p<0.001), pneumonitis (MC: CFRT=0.1201±0.0322 vs. HFRT=0.0756±0.0221; p<0.001) and (CCC: CFRT=0.1131±0.0310 vs. HFRT=0.0697±0.0120; p<0.010), and TCP (MC: CFRT=0.9979±0.0087 vs. HFRT=0.9997±0.0092; p=0.593) and (CCC: CFRT=0.9982±0.0029 vs. HFRT=0.9986±0.0016; p=0.821). Conclusion: The comparison of CFRT and HFRT using MC and CCC algorithms showed that the risk of cardiac mortality and pneumonitis in CFRT was significantly higher than in HFRT, and TCP was not significantly different in the two regimens. Applications of MC-based DCAs along with suitable biological parameters can help physicists in the prediction of radiation-induced complications accurately and precisely. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension is a complex syndrome that encompasses a diverse group of pathophysiologies predisposed by different environmental and genetic factors. It is not clear to which extent the universal risk classification schemes can be applied to cohorts in individual pulmonary hypertension centers with differing environmental backgrounds, genetic pools, referral networks. Aims: To explore whether the recommended risk classification schemes could reliably be used for mortality prediction in an unselected pulmonary hypertension population of a tertiary pulmonary hypertension center. Study Design: A retrospective cross-sectional study. Methods: We retrospectively screened our hospital database for the patients with pulmonary hypertension between 2015 and 2022. The grouping of pulmonary hypertension was made as follows in accordance with current guidelines: Group 1: patients with pulmonary arterial hypertension, Group 2: patients with pulmonary hypertension associated with left heart disease, Group 3: patients with pulmonary hypertension associated with lung disease and/or hypoxia, and Group 4: patients with pulmonary hypertension associated with pulmonary artery obstructions. Then, we compared the predicted and observed mortality rates of four different risk classification schemes (REVEAL, REVEAL-Lite, ESC/ERS and COMPERA). Results: We identified 723 cases in our pulmonary hypertension database, the final study population consisted of 549 patients. The REVEAL, REVEAL-Lite and European Society of Cardiology/ European Respiratory Society risk scores significantly underestimated the mortality risk in the low-risk stratum (5.3% vs. 1.9%, P < 0.001; 5.3% vs. 2.9%, P = 0.015 and 6.3% vs. 1%, P < 0.001, respectively) and overestimated the mortality risk in the high-risk stratum (11.8% vs. 25.8%, P < 0.001; 10.4% vs. 25.1%, P < 0.001 and 13.2% vs. 30%, P < 0.001, respectively). Although the COMPERA 4-strata model significantly underestimated the risk in low- and intermediatelow risk strata (4.9% vs. 1.5%, P < 0.001 and 6.8% vs. 2.8%, P = 0.001, respectively), it was accurate in intermediate-high and highrisk groups (10.1% vs. 8.7%, P = 0.592 and 15.6% vs. 22%, P = 0.384, respectively). The analyses limited only to group 1 pulmonary hypertension patients gave similar results. Conclusion: The established risk classification schemes may not perform as good as expected in unselected pulmonary hypertension populations and this may have important implications on management decisions. Tertiary centers should not uncritically accept the published risk prediction models and consider modifying current risk scores according to their own patient characteristics. [ABSTRACT FROM AUTHOR]

The natural history of pulmonary vascular disease associated with congenital heart disease (CHD) depends on associated hemodynamics. Patients exposed to increased pulmonary blood flow (PBF) and pulmonary arterial pressure (PAP) develop pulmonary vascular disease more commonly than patients exposed to increased PBF alone. To investigate the effects of these differing mechanical forces on physiologic and molecular responses, we developed two models of CHD using fetal surgical techniques: 1) left pulmonary artery (LPA) ligation primarily resulting in increased PBF and 2) aortopulmonary shunt placement resulting in increased PBF and PAP. Hemodynamic, histologic, and molecular studies were performed on control, LPA, and shunt lambs as well as pulmonary artery endothelial cells (PAECs) derived from each. Physiologically, LPA, and to a greater extent shunt, lambs demonstrated an exaggerated increase in PAP in response to vasoconstricting stimuli compared with controls. These physiologic findings correlated with a pathologic increase in medial thickening in pulmonary arteries in shunt lambs but not in control or LPA lambs. Furthermore, in the setting of acutely increased afterload, the right ventricle of control and LPA but not shunt lambs demonstrates ventricular-vascular uncoupling and adverse ventricular-ventricular interactions. RNA sequencing revealed excellent separation between groups via both principal components analysis and unsupervised hierarchical clustering. In addition, we found hyperproliferation of PAECs from LPA lambs, and to a greater extent shunt lambs, with associated increased angiogenesis and decreased apoptosis in PAECs derived from shunt lambs. A further understanding of mechanical force-specific drivers of pulmonary artery pathology will enable development of precision therapeutics for pulmonary hypertension associated with CHD.