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Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein initially identified in nonmetastatic melanomas and has been associated with human heart failure; however, its role in cardiac injury and function remains unclear. Here we show that GPNMB expression is elevated in failing human and mouse hearts after myocardial infarction (MI). Lineage tracing and bone-marrow transplantation reveal that bone-marrow-derived macrophages are the main source of GPNMB in injured hearts. Using genetic loss-of-function models, we demonstrate that GPNMB deficiency leads to increased mortality, cardiac rupture and rapid post-MI left ventricular dysfunction. Conversely, increasing circulating GPNMB levels through viral delivery improves heart function after MI. Single-cell transcriptomics show that GPNMB enhances myocyte contraction and reduces fibroblast activation. Additionally, we identified GPR39 as a receptor for circulating GPNMB, with its absence negating the beneficial effects. These findings highlight a pivotal role of macrophage-derived GPNMBs in post-MI cardiac repair through GPR39 signaling.

BACKGROUND: Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. METHODS AND RESULTS: Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P

BACKGROUND: Abnormal diastolic function is an independent predictor of adverse postoperative outcomes. Mitral annular tissue Doppler velocity (e) is a key parameter for assessing diastolic function. The purpose of this study was to confirm that an acute increase in preload did not significantly impact the intraoperative measurement of e and secondarily evaluate the impact of this acute intravascular volume increase on the clinical assessment of diastolic function using a previously described simplified algorithm. METHODS: This was a prospective, non-randomized study in adult patients undergoing elective cardiac surgeries requiring transesophageal echocardiographic monitoring, arterial pressure and Swan-Ganz catheter placements as part of the surgical procedure. Following baseline echocardiographic and hemodynamic measurements, 500 ml of crystalloid solution was infused over 10 min. Hemodynamic and echocardiographic measurements were repeated 5 min after fluid administration. RESULTS: Complete data sets were available from 84 of the 100 patients who were enrolled in this study. There was no significant change in the values of e. The average baseline was 7.8 ± 2.0 cm/s (95%CI: 7.4, 8.2) and 8.1 ± 2.4 (95%CI: 7.6, 8.6) following the fluid bolus (p = 0.10). All hemodynamic variables associated with increased intravascular volume (central venous pressure, pulmonary arterial pressures and stroke volume variation) changed significantly. The overall distribution of diastolic function grades did not change following fluid administration (p = 0.69). However, there were many individual patient differences. When using this simplified algorithm, functional grading changed in 35 patients. Thirty of these 35 changes were only a single grade shift. 22 patients had worse functional grading after fluid administration while 13 had improved grading. Nine patients with normal diastolic function at baseline demonstrated diastolic dysfunction after fluid administration while 6 patients with baseline dysfunction normalized following the fluid bolus. CONCLUSION: We confirmed that e is a robust measurement that is reproducible in the intraoperative setting despite variable vascular volume loading conditions, however, the clinical assessment of diastolic function was still altered in 42% of the patients following an intravenous fluid bolus.

Objective: We retrospectively analyzed the clinical features and prognosis of SLE patients with HF. Methods: Patients with SLE and HF who were hospitalized in Jinling Hospital from January 2013 to May 2021 and followed up for 2 years after discharge were included. Risk factors for death and ESKD were analyzed. According to cardiac ultrasound, patients were subdivided into the HFrEF, HFmrEF and HFpEF groups, and differences in clinical features and prognosis among the three groups were analyzed. Results: Among 376 SLE patients with HF, the distribution was 13.30% HFrEF, 14.89% HFmrEF, and 71.81% HFpEF. Median ages at SLE and HF diagnosis were 29.00 (21.25, 42.00) and 35.25 (27.29, 49.31) years, with a median SLE duration of 49 (7, 120) months. The 2-year overall and renal survival rates were 86.97% and 63.56%, respectively. Multivariate COX analysis identified age, NPSLE, blood NT-proBNP, CD20+ B cells, Alb, and UA as death risk factors, and Scr, PCT, CD20+ B cells, urine RBP, and right kidney size as ESKD risk factors. The 2-year survival rates were 70% for HFrEF, 82.14% for HFmrEF, and 91.11% for HFpEF; renal survival rates were 46%, 58.93%, and 67.78%, respectively. HFrEF had lower survival rates than HFpEF, while HFmrEF showed intermediate rates and clinical features, with some significantly different from HFpEF but not HFrEF. No significant differences in SLE remission or relapse rates were found among non-ESKD survivors. Conclusions: SLE patients with HF tend to have an early disease onset, high SLE activity and long course, with HFpEF being the predominant phenotype. HFrEF has a poorer prognosis compared to HFpEF, while HFmrEF has an intermediate prognosis and shares more clinical similarities with HFrEF. [ABSTRACT FROM AUTHOR]

Background: To date, the clinical implications of the long-lasting non-alcoholic fatty liver disease (NAFLD) such as the left ventricular diastolic dysfunction (LVDD) in the course of type 2 diabetes mellitus (T2DM) are yet to be determined. The main aim of this study was to investigate the correlation between NAFLD and early LVDD progression along with demographic characteristics. Methods: This cross-sectional study was performed on ninety consecutive diabetic outpatients referred to the endocrinology clinic. Demographic data were collected using a designed checklist. Ultrasound imaging was performed to assess the fatty liver condition. To assess LV diastolic function, echocardiography was performed, using a trans-thoracic tissue Doppler echocardiography. Results: The results showed that the majority of participants were females (61.1%). The fasting blood glucose (FBG, mg/dl) level was 174.65 ±51.1. Also, the mean body mass index (BMI) was 28.92±4.19, which was significantly associated with NAFLD. It has been also estimated that 76.7% and 81.1% of diabetic patients had NAFLD and simultaneous LVDD, respectively. However, the statistical results did not show a significant association between non-progressive NAFLD and LVDD (p<0.05). Conclusion: There was no correlation between NAFLD and LVDD progression. However, timely evaluation of LVDD in T2DM outpatients with NAFLD can strongly help to prevent possible cardiomyopathy in high-risk populations. [ABSTRACT FROM AUTHOR]

ABSTRACT Children with indications of pacing often require epicardial pacemakers with generators implanted in the abdominal wall due to small body size or challenging anatomy because of congenital heart diseases. However, left ventricle (LV) systolic dyssynchrony induced by epicardial pacing may result in adverse remodeling and LV dysfunction. Recently, distal His bundle pacing (dHBP) has been shown to restore normal ventricular function in adult patients with pacemaker induced ventricular dysfunction. Nevertheless, the effects and relevance of HBP in pediatric patients are largely unresolved, with only limited data analyzing the feasibility and efficacy of HBP in the pediatric population. We report the case of a young girl with congenital atrioventricular (AV) block who developed LV dysfunction induced by prolonged epicardial stimulation. After upgrading to dHBP, she improved her LV ejection fraction from 40% to 60% and maintained stable pacing‐sensing parameters over‐time. We here provide a review of existing literature on the topic. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusions Atrial fibrillation and atrial flutter are relatively rare in young people and the incidence of thromboembolic complications is unknown. These issues contribute to the limited utility of present guidelines regarding anticoagulation in this population.To report the number of thromboembolic complications in a cohort of pediatric and young adult patients presenting with atrial fibrillation (AFib) or atrial flutter (AFl) while also assessing anticoagulation practice in a multicenter cohort of young patients with these arrhythmias.Multicenter, retrospective cohort of patients aged < 25 years old who presented with atrial flutter (AFl) or atrial fibrillation (AFib) between 2000 and 2019 to several large, quaternary pediatric centers, excluding episodes occurring within 30 days of an invasive cardiac procedure.There were 311 episodes of AFib/AFl among 210 patients with a median age of 17 (IQR 14, 20) years. Structural heart disease (SHD) was present in 120 patients (57%) and 20 patients (10%) had a primary cardiomyopathy. Twelve AFib/AFl episodes (8 with AFL, 4 with AFib) were associated with a thrombus, of which 8 (67%) patients had SHD, 2 (17%) had cardiomyopathy and 5 (42%) ventricular dysfunction. The CHADSVASc score was 0–3 for all patients with a thrombus. Of patients with no thrombus at presentation who were cardioverted, 102 (34%) patients were discharged on aspirin and 80 (27%) on anticoagulation. Two patients had symptoms concerning for a thromboembolic event on follow‐up, but none had a newly documented thrombus.Thromboembolic complications occur in children and young adults presenting with AFib/AFl. The majority are associated with SHD, cardiomyopathy, and/or ventricular dysfunction. CHADSVASc was calculated for each patient and was of limited utility. Thromboembolic complications at follow up after cardioversion are rare, and anticoagulation strategies at discharge varied. [ABSTRACT FROM AUTHOR]

Background: The relationship between diastolic function parameters and the severity of coronary artery disease (CAD) is controversial. This study aimed to determine the relationship between left ventricular diastolic function and the severity of CAD. Methods: This cross-sectional study included 63 patients with Ischemic heart disease (IHD) or those suspected of having IHD, who underwent angiography. The study was conducted in Shafa Hospital, Kerman, Iran, from 2021 to 2022. Two-dimensional (2D) strain echocardiography was used to assess left ventricular (LV) function parameters, followed by coronary angiography. Based on the severity of the disease, patients with significant CAD were placed in the case group, and patients with insignificant CAD were placed in the control group. The correlation between the CAD severity and the severity of LV diastolic dysfunction was computed. Descriptive tests, independent t tests, and Spearman correlation coefficients were used. P<0.05 was considered statistically significant. Results: The results indicated that there was no correlation between E/e' (P=0.103), left atrial volume index (LAVI) (P=0.168), tricuspid regurgitation velocity (TRV) (P=0.217), myocardial performance index (MPI) (P=0.106), E wave deceleration time (dt) (P=0.644), and late diastolic strain rate (P=0.502) with CAD severity based on SYNTAX score. However, there was a correlation between left atrial (LA) strain (P=0.017), global longitudinal strain (GLS) (P<0.001), early diastolic strain rate (P<0.001), and systolic strain rate (P=0.047) with SYNTAX score. Besides, there was a correlation between LA strain (P=0.017), GLS (P<0.001), early diastolic strain rate (P<0.001), and late diastolic strain rate (P=0.035) with numbers of epicardial coronary arteries with significant lesions. Conclusion: In contrast with 2D strain echocardiography, this study showed that conventional echocardiography parameters had no significant relationship with CAD severity. GLS had the strongest correlation with CAD severity, and diastolic strain rates had a weaker correlation with CAD severity. [ABSTRACT FROM AUTHOR]

Background: Limited data exists to evaluate the optimal management of outpatient beta blocker therapy when patients with heart failure with reduced ejection fraction (HFrEF) are admitted for acute decompensated heart failure (ADHF). Objective: This study aimed to compare the effects of holding or decreasing the dose of outpatient beta blocker therapy vs continuation of therapy on rates of tachyarrhythmias during admission for ADHF. Methods: This single-center, retrospective cohort study divided patients with HFrEF (left ventricular ejection fraction less than or equal to 40%) admitted for ADHF into two cohorts: one that had their outpatient beta blocker continued at the same dose upon admission and one that had it held or dose decreased. The primary outcome was a composite of non-sustained or sustained ventricular tachycardia, ventricular fibrillation, or atrial fibrillation or flutter with rapid ventricular response during the hospitalization. Secondary outcomes included the individual tachyarrhythmias in the primary outcome, in-hospital mortality, and 90-day re-admission for heart failure. Results: Of the 137 patients included, 82 were in the continuation cohort and 55 in the discontinuation/reduction cohort. The median length of stay was 5.3 days (interquartile range, 3.8-7.6). No significant difference in the primary composite outcome was found between the discontinuation/reduction and continuation cohorts (29.1% vs 22.0%; relative risk [95% confidence interval], 1.33 [.74-2.37]; P =.420). No significant differences were seen between the two cohorts for any of the secondary outcomes. Conclusion: Beta blocker therapy adjustment on admission for ADHF may not affect the occurrence of tachyarrhythmias in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Congenital interventricular septal aneurysms (IVSA) of the muscular septum are rare and can be associated with other familial abnormalities of the ventricular septum, arrhythmias, additional congenital heart disease, and chromosomal abnormalities. IVSA is also linked to ventricular dysfunction and non-compaction, although there are limited reports of this association presenting in utero. We describe a case of fetal ventricular septal aneurysm associated with ventricular dysfunction and pericardial effusion. [ABSTRACT FROM AUTHOR]