BACKGROUND:Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is characterized by substantial prognostic and therapeutic heterogeneity. Conventional clinical and anatomical-pathophysiological classifications fail to fully capture these intricacies. Unsupervised clustering approaches such as latent class analysis (LCA) have been used to address this limitation. RESEARCH QUESTION:Can LCA-derived phenogroups refine risk stratification and predict PAH-targeted treatment responses in adult patients with PAH-CHD? STUDY DESIGN AND METHODS:Adult patients with PAH-CHD (N = 889) from a multicenter prospective registry were stratified into post- and pre-tricuspid shunt subsets. LCA was performed in each subset using 28 candidate clinical, laboratory, and hemodynamic variables. Ten-year survival and the effect of PAH-targeted therapy across phenogroups were evaluated. RESULTS:LCA identified 4 phenogroups in each subset with distinct phenotyping patterns. In post-tricuspid shunts, Group 1 ("adaptation with open shunt") exhibited preserved right ventricular function and the best survival despite high afterload. Group 3 ("maladaptation and failure") and Group 4 ("closed shunt and failure") faced 2- to 3-fold higher mortality than Group 1. Notably, Group 2 ("hyperkinetic state") uniquely benefited from combination therapy (Pinteraction = .026). In pre-tricuspid shunts, Group 1 ("high shunt and mild resistance") and Group 3 ("young female and low inflammation") exhibited preserved survival despite varying afterloads. However, Group 2 ("old male and comorbidities") had significantly higher mortality and an attenuated treatment response (Pinteraction = .037) despite sharing mild hemodynamics with Group 1. Group 4 ("high resistance and failure") faced severe hypoxemia and the worst prognosis. INTERPRETATION:LCA successfully stratified patients with PAH-CHD into distinct phenogroups with varied clinical profiles, survival, and treatment responses. This data-driven phenotyping system provides a novel approach for risk stratification and may guide personalized clinical decision-making. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT01417338; URL: www. CLINICALTRIALS:gov.

Pulmonary arterial compliance (PAC) reflects the pulsatile load and predicts outcome in pulmonary arterial hypertension (PAH). The prognostic role of PAC in the heterogeneous patient population of PAH associated with congenital heart disease (PAH-CHD) is poorly defined. This study aimed to explore the prognostic value of PAC in patients with PAH-CHD. Adult patients diagnosed with PAH-CHD were collected from a PAH multicenter prospective registry between August 2009 and December 2019. The primary endpoint was all-cause mortality. Multivariable Cox regression and restricted cubic spline (RCS) analysis were used to evaluate the association between PAC and the primary endpoint. Subgroup and interaction analysis between PAC and shunts or defect characteristics were explored. Incremental predictive performance was evaluated by calculating the C-index, continuous net reclassification improvement, and integrated discrimination improvement. A total of 434 adult PAH-CHD patients were enrolled. The median follow-up time was 52.2 months. The survival rate of patients in the lower PAC group was significantly worse than those in the higher PAC group (Log-rank P < 0.001). Multivariable Cox regression analysis showed that PAC independently predicted all-cause mortality after adjustment for other prognostic factors, whether as a continuous variable (HR = 0.665, 95

This study aimed to report the progress and results of the newborn screening program for congenital heart disease (CHD) in south Shanghai between 2019 and 2023, and to evaluate the accuracy of the dual-index method (pulse oximetry (POX) plus cardiac murmur auscultation) in clinical practice. Between 2019 and 2023, a total of 198,606 (99.89%) newborns were screened for CHD, of whom 3299 (1.66%) tested positive, 3043 (92.24%) underwent echocardiography for CHD diagnosis and 1109 were diagnosed with CHD in a timely manner. Among 195,307 infants with negative screening results using the dual-index method, 139 (0.07%) were later diagnosed with CHD, and none of these infants died. More than half of these false-negative infants (59.39%) were identified due to the detection of a heart murmur during routine physical examinations within six months after birth. Compared to POX testing alone, the dual-index method significantly improved the sensitivity of screening for CHD, and kept high specificity in clinical practice. This study demonstrated that newborn screening for CHD has been well conducted in Shanghai, and the dual-index method had high accuracy and reliability for neonatal CHD screening in clinical practice.

Purpose To investigate the prognostic value of cardiac MRI-derived left ventricular (LV) layer-specific strain in pulmonary arterial hypertension (PAH). Materials and Methods This study analyzed data from a subcohort of participants consecutively enrolled in the prospective PAH registry study between January 2011 and December 2017 who underwent right heart catheterization and cardiac MRI (1.5-T scanner) within 1 week. The deformable registration algorithm software was used to analyze LV layer-specific strain from acquired breath-held cine images. Each participant was followed up at intervals of 6 months plus or minus 2 weeks for all-cause mortality. Cox regression and Kaplan-Meier analyses were performed to assess the association between LV layer-specific strain and all-cause mortality. Results Eighty participants with PAH (mean age ± SD, 30.30 years ± 9.73; 62 female, 18 male) were included, with a median follow-up of 1511 days. At the end, 29 (36%) participants died by any cause. Participants who survived had significantly higher endocardial wall peak systolic radial strain rate (ewSRSR; 72.74% ± 50.64 vs 30.61% ± 67.43; P = .005) and transmural gradient from the epicardial to endocardial walls in peak late diastolic circumferential strain rate (Gepiw-ewDCSRL; -20.05% ± 22.97 vs -33.50% ± 25.71; P = .02) compared with participants who died. Multivariable Cox regression showed that ewSRSR and Gepiw-ewDCSRL were independent predictors of all-cause mortality. Kaplan-Meier analysis showed that participants with PAH with ewSRSR less than 54.48% (log-rank P = .003) or Gepiw-ewDCSRL less than -25.14% (log-rank P = .02) at baseline had a decreased likelihood of long-term survival. In the low- or intermediate-risk PAH groups, participants with LV ewSRSR less than 54.48% had a worse prognosis (log-rank P = .02). Conclusion Cardiac MRI-derived LV ewSRSR and Gepiw-ewDCSRL independently predicted all-cause mortality in participants with PAH. Keywords: Layer-specific Strain, DRA-CMR, Left Ventricle, Pulmonary Arterial Hypertension, Prognosis ClinicalTrials.gov: NCT01417338 Supplemental material is available for this article. © RSNA, 2025.

Background Aslanger’s pattern in electrocardiogram (ECG) indicates that patients may have acute inferior myocardial infarction(AMI) with concomitant critical stenoses on other coronary arteries, which needs to be evaluated the timing of revascularization as risk equivalents of ST elevation myocardial infarction(STEMI). Case Presentation The patient was a 62-year-old male with chief complaint of intermittent exertional subxiphoid pain for 20 days from 30th June. One day after the last episode (19th July), the 18-lead electrocardiogram showed ST segment elevation of 0.05-0.1mV in lead III, ST segment depression in leads I, avL, and V2-V6, T wave inversion with positive terminal vector in lead V4-V5, and positive T wave in lead V6, which indicated Aslanger’s pattern. With increased Troponin I (0.162ng/mL, 0-0.02), The patient was diagnosed as acute non-ST-segment elevation myocardial infarction (NSTEMI) and admitted to coronary ward on 20th July. The coronary angiography showed 95% stenosis in the distal left main coronary artery (LM) to the ostium of the left anterior descending artery (LAD), 90% stenosis in the proximal segment of the LAD, and 80% stenosis in the middle segment of the LAD, and TIMI blood flow was graded score 2. Three drug-eluting stents were implanted at the lesions. The patient’s ECG returned close to normal one month after revascularization. Conclusion We presented an acute coronary syndrome case whose ECG showed with Aslanger’s pattern (i.e., isolated ST-segment elevation in lead III, associated ST-segment depression in lead V4-V6 with positive T wave/terminal vector, and greater ST-segment elevation in lead V1 than in lead V2), and was confirmed severe stenosis of the LM and the proximal segment of the LAD via coronary angiography. In clinical practice, especially in the emergency, patients with ECG presenting Aslanger’s pattern should be urgently evaluated with prompt treatment, and the timing of emergency coronary angiography and revascularization should be evaluated to avoid adverse outcomes caused by delayed treatment.

Background and ObjectiveOff-label pulmonary arterial hypertension (PAH)-targeted drugs are commonly prescribed for non-operated chronic thromboembolic pulmonary hypertension (CTEPH), but their effect on the long-term prognosis of CTEPH remains unknown. This study investigated the effect of off-label PAH-targeted drugs on the long-term survival of CTEPH patients.MethodsCTEPH patients were enrolled from a prospective multicentre national registry. Except for licensed riociguat and treprostinil, other PAH-targeted drugs were off-label. In the original and propensity score-matched (PSM) samples, five-year survival was compared in two groups: (a) patients not receiving off-label PAH-targeted drugs (control) versus (b) patients receiving off-label PAH-targeted drugs (treatment). The latter group was investigated for the effect of started off-label PAH-targeted drugs at baselines (initial) or during follow-up (subsequent).ResultsOf 347 enrolled patients, 212 were treated with off-label PAH-targeted drugs initially (n = 173) or subsequently (n = 39), and 135 were untreated. The 1-, 2-, 3- and 5-year survival of the treatment group was significantly higher than that of the control group (97.1% vs. 89.4%, 92.3% vs. 82.1%, 83.2% vs. 75.1% and 71.1% vs. 55.3%, respectively, log-rank test, p = 0.005). Initial treatment was correlated with better 5-year survival after excluding patients with subsequent treatment to reduce the immortal-time bias (hazard ratio: 0.611; 95% CI: 0.397-0.940; p = 0.025). In PSM samples, patients given initial treatment showed significantly better 5-year survival than untreated patients (68.9% vs. 49.3%, log-rank test, p = 0.008).ConclusionOff-label targeted drugs contributed to improved long-term survival in CTEPH patients receiving pharmacotherapies. imageConclusionOff-label targeted drugs contributed to improved long-term survival in CTEPH patients receiving pharmacotherapies. image The study demonstrates that off-label use of pulmonary arterial hypertension medication improves long-term survival in patients with chronic thromboembolic pulmonary hypertension. This is a national, multicentre, prospective registry with a large sample size and low rate of loss to follow-up. The efficacy is more transparent after rigorously reducing bias. image

PURPOSE:To investigate the imaging characteristics and prognostic factors for the long-term survival of Behcet's disease (BD) with arterial involvement. METHODS:In this retrospective study, BD patients with arterial involvement were identified from January 2003 to January 2020. Arterial lesions were detected by ultrasonography, traditional arteriography, and/or computed tomography angiography (CTA). Cox proportional hazards regression analyses were performed to identify the prognostic factors. RESULTS:Totally, 84 BD patients with arterial involvement were identified (73.8 % males). The mean age at BD diagnosis was 39.1 ± 13.1 years. Arterial involvement was the initial manifestation in 33.3 % of the patients, and the median time from BD diagnosis to arterial involvement was 6 (IQR 1-15.5) years for the rest of patients. Systemic artery involvement and pulmonary artery involvement (PAI) were found in 64 and 27 patients, respectively. Approximately 94.0 % (79/84) of the patients had more than one artery involved concurrently or successively during the course of BD. Aneurysm/dilation was the most prevalent lesion in the aorta (76.0 %), while stenosis/occlusion was the main lesion of the coronary artery (90.9 %) and other aortic branches (74.5 %). Pulmonary hypertension was found in 70.4 % (19/27) of patients with PAI. The 5- and 10-year survival rates of BD patients with arterial involvement were 87.4 % and 84.1 %, respectively. Cardiac involvement (HR: 4.34) and pulmonary artery aneurysm/dilation (HR: 4.89) were independently associated with mortality. CONCLUSIONS:Arterial lesions associated with BD usually involve multiple arteries and manifest differently in different types of arteries. Cardiac involvement and pulmonary artery aneurysm/dilation are independent prognostic factors of BD patients with arterial involvement.

BACKGROUND: Registry-based studies of pediatric pulmonary arterial hypertension (PPAH) are scarce in developing countries, including China. The PPAH risk assessment tool needs further evaluation and improvement.RESEARCH QUESTION: What are the characteristics and long-term survival of PPAH in China and what is the performance of the PPAH risk model in Chinese patients?STUDY DESIGN AND METHODS: Patients with PAH were enrolled in the national prospective multicenter registry from August 2009 through December 2019. Children 3 months to 18 years of age at the time of PAH diagnosis were analyzed.RESULTS: A total of 247 children with PAH were enrolled. The median patient age was 14.8 years, and 58.3% of patients were female. Most patients had a diagnosis of PAH associated with congenital heart disease (CHD; 61.5%) and idiopathic or heritable PAH (37.7%). The median time from symptom onset to PAH diagnosis was 24 months. The mean pulmonary artery pressure and pulmonary vascular resistance index were 70.78 + 19.80 mm Hg and 21.82 + 11.18 Wood Units$m2, respectively. Patients with CHD-associated PAH experienced a longer diagnostic delay and demonstrated higher pulmonary artery pressure, but better cardiac performance, than those with idiopathic or heritable PAH. An increased number of patients received targeted therapy at the last follow-up compared with baseline. The 5-and 10-year survival rates of the entire cohort were 74.9% and 55.7%, respectively, with better survival in patients with CHD-associated PAH than in those with idiopathic or heritable PAH. Patients with low risk had better survival than those with high risk according to the simplified noninvasive risk score model with weight, function class, and echocardiographic right ventricular size, both at baseline and follow-up.INTERPRETATION: Patients with PPAH in China showed severely compromised hemody-namics with marked diagnostic delay. The long-term survival of PPAH is poor despite the increased usefulness of targeted drugs. The simplified noninvasive risk model demonstrated good performance for predicting survival in Chinese children with PAH.TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01417338; URL: www.clinicaltrials.gov CHEST 2023; 163(6):1531-1542

Objectives To report the 10-year survival rate and prognostic factors of pulmonary arterial hypertension associated with CTD (CTD-PAH) patients, to compare treatment and survival between patients enrolled before and after 2015, and to validate the discrimination of the recommended four-strata model in predicting 10-year survival at follow-up in Chinese CTD-PAH patients. Methods This study was derived from a Chinese national multicentre prospective registry study from 2009 to 2019. Medical records were collected at baseline and follow-up, including PAH-targeted therapy and binary therapy (both CTD and PAH-targeted therapy). Results A total of 266 CTD-PAH patients were enrolled and the 10-year survival rate was 59.9% (median follow-up time: 4.85 years). Underlying CTD (SSc), baseline 6-min walking distance and SaO(2) were independent risk factors for 10-year survival. The proportion of patients receiving PAH-targeted combination therapy increased from 10.1% (2009-2014) to 26.5% (2015-2019) and that of binary therapy increased from 14.8% to 35%. The 1-year survival rate increased from 89.8% (2009-2014) to 93.9%, and the 3-year survival rate increased from 80.1% (2009-2014) to 86.5% (both P > 0.05). The four-strata strategy performed well in predicting 10-year survival at follow-up (C-index = 0.742). Conclusion The 10-year survival rate of CTD-PAH patients was reported for the first time. The 10-year prognosis was poor, but there was a tendency for more standardized treatment and better survival in patients enrolled after 2015. The recommended four-strata model at follow-up can effectively predict 10-year survival in CTD-PAH patients.

Background: Pulmonary arterial hypertension (PAH) leads to myocardial remodeling, manifesting as mechanical dyssynchrony (M-dys) and electrical dyssynchrony (E-dys), in both right (RV) and left ventricles (LV). However, the impacts of layer-specific intraventricular M-dys on biventricular functions and its association with E-dys in PAH remain unclear. Methods: Seventy-nine newly diagnosed patients with PAH undergoing cardiac magnetic resonance scanning were consecutively recruited between January 2011 and December 2017. The biventricular volumetric and layer-specific intraventricular M-dys were analyzed. The QRS duration z-scores were calculated after adjusting for age and sex. Results: 77.22 % of patients were female (mean age 30.30 ± 9.79 years; median follow-up 5.53 years). Further, 29 (36.71 %) patients succumbed to all-cause mortality by the end of the study. At the baseline, LV layer–specific intraventricular M-dys had apparent transmural gradients compared with RV in the radial and circumferential directions. However, deceased patients lost the transmural gradients. The LV longitudinal strain rate time to late diastolic peak in the myocardial region (LVmyoLSRTTLDPintra) predicted long-term survival. The Kaplan–Meier curve revealed that patients with PAH with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. Larger right ventricle (RV) intraventricular M-dys resulted in worse RV ejection fraction. However, larger LV intraventricular M-dys in the late diastolic phase indicated remarkable exercise capacity and higher LV stroke volume index. E-dys and intraventricular M-dys had no direct correlations. Conclusions: The layer-specific intraventricular M-dys had varying impacts on biventricular functions in PAH. PAH patients with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. LV intraventricular M-dys in the late diastolic phase needs more attention to precisely evaluate LV function.

Right heart thrombus (RHT) is a rare but life-threatening condition in acute pulmonary embolism (APE) without clear management guidelines. This study aimed to address the clinical characteristics and outcomes of RHT-APE in Chinese patients. In this study, 17 RHT-APE and 329 non-RHT-APE patients, who were diagnosed between September 2015 and August 2019, were retrospectively recruited with the median follow-up was 360 days. The overall prevalence of RHT was 4.91% in APE. Its prevalence increased along the increase of APE risk stratifications. Comparisons showed that with higher proportion of male gender and younger age, RHT-APE patients also had worse hemodynamic instability and heart function, and higher risk stratification levels than non-RHT-APE patients. After adjusting by age and gender, multivariate logistic regression analysis found high/intermediate-high risk stratification, decreased right ventricular (RV) motion, NT-proBNP >600 pg/mL, and RV dysfunction were risk factors for RHT. Kaplan-Meier analysis showed non-RHT had better prognosis than RHT patients (30-day survival: log-rank: p < 0.001; 90-day survival: log-rank: p = 0.002). The multivariate logistic regression analysis showed RHT was an independent risk factor for 30-day mortality in APE. The subgroup analysis showed RHT would result in worse outcomes in patients who already had higher APE early mortality risk. RHT would increase the risk of 30- and 90-day mortality in APE. More attention should be paid to young male APE patients with decreased RV motion, NT-proBNP >600 pg/mL, RV dysfunction, or high level of risk stratification, to exclude the coexistence of RHT.

Background Our objective was to clarify the characteristics and long-term survival of idiopathic pulmonary arterial hypertension (IPAH) patients with thyroid dysfunction and compare them with IPAH without thyroid dysfunction. Methods A retrospective analysis was conducted using prospectively collected data. IPAH patients with thyroid dysfunction at baseline were included. Patients with other subgroups of PAH and Group 2–5 pulmonary hypertension were excluded. IPAH patients with euthyroid function were matched 1:1 to IPAH patients with thyroid dysfunction by age and sex. Results In total, 148 IPAH patients with thyroid dysfunction were included. Patients with hyperthyroidism, hypothyroidism, subclinical hyperthyroidism and subclinical hypothyroidism accounted for 16.2%, 18.9%, 8.1% and 56.8%, respectively. IPAH patients with hyperthyroidism showed the highest mixed venous oxygen saturation (SvO2) and the lowest pulmonary vascular resistance (PVR) at baseline among subgroups, while patients with subclinical hypothyroidism had the lowest SvO2 and highest PVR (p<0.05). Compared with IPAH without thyroid dysfunction, patients with hyperthyroidism (9.14 versus 13.86 WU; p<0.05) and hypothyroidism (10.70 versus 13.86 WU; p<0.05) showed significantly lower PVR. The haemodynamic profiles of patients with subclinical hypothyroidism were similar to IPAH with euthyroid function except for lower right atrial pressure (6 versus 8 mmHg; p=0.009). The long-term survival of patients with clinical thyroid dysfunction was better than IPAH without thyroid dysfunction, while that of those with subclinical diseases was comparable to the latter, even after adjusting for baseline haemodynamics and treatment. Conclusion IPAH patients with clinical hyper- and hypothyroidism had better haemodynamics and survival than those without thyroid dysfunction, while patients with subclinical hypothyroidism had similar haemodynamics and survival profiles to the latter.

BACKGROUND: The purpose of this registry was to provide insights into the characteristics, treatments and survival of patients with PAH-CHD in China.METHODS: Patients diagnosed with PAH-CHD were enrolled in this national multicenter prospective registry. Baseline and follow-up data on clinical characteristics, PAH-targeted treatments and survival were collected.RESULTS: A total of 1060 PAH-CHD patients (mean age 31 years; 67.9% females) were included, with Eisenmenger syndrome (51.5%) being the most common form and atrial septal defects (37.3%) com-prising the most frequent underlying defect. Approximately 33.0% of the patients were in World Health Organization functional class III to IV. The overall mean pulmonary arterial pressure and pulmonary vascular resistance were 67.1 (20.1) mm Hg and 1112.4 (705.9) dyn/s/cm5, respectively. PAH-targeted therapy was utilized in 826 patients (77.9%), and 203 patients (19.1%) received combination therapy. The estimated 1-, 3-, 5-, and 10-year survival rates of the overall cohort were 96.9%, 92.9%, 87.6% and 73.0%, respectively. Patients received combination therapy had significantly better survival than those with monotherapy (p = 0.016). NT-proBNP >1400 pg/ml, SvO2 & LE; 65% and Borg dyspnea index & GE; 3 and PAH-targeted therapy were independent predictors of mortality. Hemoglobin > 160g/L was a unique predictor for mortality in Eisenmenger syndrome.CONCLUSIONS: Chinese PAH-CHD patients predominantly exhibit Eisenmenger syndrome and have significantly impaired exercise tolerance and right ventricular function at diagnosis, which are closely associated with long-term survival. PAH-targeted therapy including combination therapy showed a favorable effect on survival in PAH-CHD. The long-term survival of Chinese CHD-PAH patients remains to be improved. J Heart Lung Transplant 2023;42:974-984 & COPY; 2023 International Society for Heart and Lung Transplantation. All rights reserved.

Nationally representative reports on the characteristics and long‐term survival of pulmonary arterial hypertension (PAH) from developing countries are scarce. The applicability of the current main risk stratifications and the longitudinal changes in goal‐oriented treatments have yet to be elucidated in real‐world settings. Therefore, we aimed to provide insights into the characteristics, goal‐oriented treatments and survival of PAH in China and to explore the applicability of the main risk stratifications in our independent cohort.

Background::Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH.Methods::Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded.Results::One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH.Conclusions::PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients.Trial Registration::ClinicalTrials.gov, NCT02164526.

Abstract Risk assessment for pulmonary arterial hypertension (PAH) utilizing noninvasive prognostic variables could be more practical in real‐world scenarios, especially at follow‐up reevaluations. Patients who underwent comprehensive evaluations both at baseline and at follow‐up visits were enrolled. The primary endpoint was all‐cause mortality. Predictive variables identified by Cox analyses were further incorporated with the French noninvasive risk prediction approach. A total of 580 PAH patients were enrolled. During a median follow‐up time of 47.0 months, 112 patients (19.3%) died. By multivariate Cox analyses, tricuspid annular plane systolic excursion (TAPSE), TAPSE/pulmonary arterial systolic pressure (PASP), and cardiopulmonary exercise testing‐derived peak oxygen consumption (VO2) remained independent predictors for survival. Regarding the French noninvasive risk prediction method, substituting N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) with the newly derived low‐risk criteria of a TAPSE ≥ 17 mm or a TAPSE/PASP > 0.17 mm/mmHg, or alternating 6‐min walking distance with a peak VO2 ≥ 44 %predicted retained the discrimination power. When recombining the low‐risk criteria, the combination of World Health Organization functional class (WHO FC), TAPSE and peak VO2 at baseline, and the combination of WHO FC, NT‐proBNP, and peak VO2 at follow‐up showed better discriminative ability than the other combinations. In conclusion, Peak VO2, TAPSE, and TAPSE/PASP are significant prognostic predictors for survival in PAH, with incremental prognostic value when incorporated with the French noninvasive risk prediction approach, especially at reevaluations. For better risk prediction, WHO FC, at least one measurement of exercise capacity and one measurement of right ventricular function should be considered.

AbstractAimsOrchestrating the transition from reversible medial hypertrophy to irreversible plexiform lesions is crucial for pulmonary arterial hypertension related to congenital heart disease (CHD‐PAH). Transgelin is an actin‐binding protein that modulates pulmonary arterial smooth muscle cell (PASMC) dysfunction. In this study, we aimed to probe the molecular mechanism and biological function of transgelin in the pathogenesis of CHD‐PAH.Methods and resultsTransgelin expression was detected in lung tissues from both CHD‐PAH patients and monocrotaline (MCT)‐plus aortocaval (AV)‐induced PAH rats by immunohistochemistry. In vitro, the effects of transgelin on the proliferation, migration, and apoptosis of human PASMCs (HPASMCs) were evaluated by the cell count and EdU assays, transwell migration assay, and TUNEL assay, respectively. And the effect of transgelin on the expression of HPASMC phenotype markers was assessed by the immunoblotting assay. (i) Compared with the normal control group (n = 12), transgelin expression was significantly overexpressed in the pulmonary arterioles of the reversible (n = 15) and irreversible CHD‐PAH group (n = 4) (reversible group vs. control group: 18.2 ± 5.1 vs. 13.6 ± 2.6%, P < 0.05; irreversible group vs. control group: 29.9 ± 4.7 vs. 13.6 ± 2.6%, P < 0.001; irreversible group vs. reversible group: 29.9 ± 4.7 vs. 18.2 ± 5.1, P < 0.001). This result was further confirmed in MCT‐AV‐induced PAH rats. Besides, the transgelin expression level was positively correlated with the pathological grading of pulmonary arteries in CHD‐PAH patients (r = 0.48, P = 0.03, n = 19). (ii) Compared with the normal control group (n = 12), TGF‐β1 expression was notably overexpressed in the pulmonary arterioles of the reversible (n = 15) and irreversible CHD‐PAH group (n = 4) (reversible group vs. control group: 14.8 ± 4.4 vs. 6.0 ± 2.5%, P < 0.001; irreversible group vs. control group: 20.1 ± 4.4 vs. 6.0 ± 2.5%, P < 0.001; irreversible group vs. reversible group: 20.1 ± 4.4 vs. 14.8 ± 4.4, P < 0.01). The progression‐dependent correlation between TGF‐β1 and transgelin was demonstrated in CHD‐PAH patients (r = 0.48, P = 0.04, n = 19) and MCT‐AV‐induced PAH rats, which was further confirmed at sub‐cellular levels. (iii) Knockdown of transgelin diminished proliferation, migration, apoptosis resistance, and phenotypic transformation of HPASMCs through repressing the TGF‐β1 signalling pathway. On the contrary, transgelin overexpression resulted in the opposite effects.ConclusionsThese results indicate that transgelin may be an indicator of CHD‐PAH development via boosting HPASMC dysfunction through positive regulation of the TGF‐β1 signalling pathway, as well as a potential therapeutic target for the treatment of CHD‐PAH.

PurposeA meta-analysis was conducted to assess the benefits and risks of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in adults with diabetes.MethodsAn extensive and systematic search was conducted in MEDLINE (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 1988 to December 2020. A detailed literature search was conducted using aspirin, cardiovascular disease (CVD), diabetes, and efficacy to identify trials of patients with diabetes who received aspirin for primary prevention of CVD. Demographic details with the primary outcome of events and bleeding outcomes were analyzed. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. Random-effects meta-analysis was used to calculate the pooled odds ratio for outcomes of cardiovascular events, death, and adverse events.FindingsA total of 8 studies were included with 32,024 patients with diabetes; 16,001 allocated to aspirin, and 16,023 allocated to the control group. There was no difference between aspirin and control groups with respect to all-cause mortality, cardiovascular mortality, or bleeding events. However, MACE was significantly lower in the aspirin group.ImplicationsAlthough aspirin has no significant risk on primary endpoints of cardiovascular events and bleeding outcomes in patients with diabetes compared to control, major adverse cardiovascular events (MACE) were significantly lower in the aspirin group. Further research on the use of aspirin alone or in combination with other antiplatelet drugs is required in patients with diabetes to supplement currently available research. Systematic Review Registrationidentifier [XU#/IRB/2020/1005].

Background: The use of Aspirin in the primary prevention of cardiovascular disease (CVD) is still a topic of debate, especially in patients with diabetes. The present meta-analysis aims to rule out the efficacy of Aspirin in patients with diabetes and to compare the effectiveness of Aspirin with a placebo (or no treatment) for the primary prevention of CVD and all-cause mortality events in people with diabetes. Materials and Methods: An extensive and systematic search was conducted in Medline (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 1988 to December 2020. A detailed literature search was conducted using Aspirin, cardiovascular disease (CVD), diabetes, and efficacy to identify trials of patients with diabetes who received Aspirin for primary prevention of CVD. Demographic details with the primary outcome of events and bleeding outcomes were analyzed. The risk of bias (RoB) in included studies was evaluated using the QUADAS-2 tool. Results: A total of 5 studies out of 13 were included with 23,570 diabetic patients; 11,738 allocated to Aspirin and 11,832 allocated to the placebo group. In patients with diabetes, there was no difference between Aspirin and placebo with respect to the risk of all-cause death with a confidence interval (CI) varying 0.63 to 1.17. In addition, there were no differences in the bleeding outcomes with an odds ratio of 1.4411 (CI 0.47 to 4.34). Conclusion: Aspirin has no significant risk on primary endpoints of cardiovascular events and the bleeding outcomes in diabetic patients compared to placebo. More research on the use of Aspirin alone or in combination with other antiplatelet drugs is required in patients with diabetes to supplement currently available research.

Pulmonary hypertension (PH) is a critical and dangerous disease in cardiovascular system. Pulmonary vascular remodeling is an important pathophysiological mechanism for the development of pulmonary arterial hypertension. Pulmonary artery smooth muscle cell (PASMC) proliferation, hypertrophy, and enhancing secretory activity are the main causes of pulmonary vascular remodeling. Previous studies have proven that various active substances and inflammatory factors, such as interleukin 6 (IL-6), IL-8, chemotactic factor for monocyte 1, etc., are involved in pulmonary vascular remodeling in PH. However, the underlying mechanisms of these active substances to promote the PASMC proliferation remain to be elucidated. In our study, we demonstrated that PASMC senescence, as a physiopathologic mechanism, played an essential role in hypoxia-induced PASMC proliferation. In the progression of PH, senescence PASMCs could contribute to PASMC proliferation via increasing the expression of paracrine IL-6 (senescence-associated secretory phenotype). In addition, we found that activated mTOR/S6K1 pathway can promote PASMC senescence and elevate hypoxia-induced PASMC proliferation. Further study revealed that the activation of mTOR/S6K1 pathway was responsible for senescence PASMCs inducing PASMC proliferation via paracrine IL-6. Targeted inhibition of PASMC senescence could effectively suppress PASMC proliferation and relieve pulmonary vascular remodeling in PH, indicating a potential for the exploration of novel anti-PH strategies.