Risk Factor For Heart Failure Research Articles

A fast-growing myxoma of the left atrium

Introduction: Myxoma of the left atrium is a less typical cause of mitral obstruction. If this develops, a flash pulmonary oedema can be the first manifestation. Case description: We present a case report of a 50-year-old woman who was admitted to our internal department because of dyspnoea. The patient overcame a stroke three years before the index hospitalisation with a negative transthoracic echocardiography. By anamnesis and physical examination, an exacerbation of COPD was assumed, and the patient was treated accordingly. As the patient showed numerous risk factors for heart failure with preserved ejection fraction, transthoracic echocardiography was performed. A large polypoid mass was found in the left atrium, which caused severe mitral obstruction. Subsequent transoesophageal echocardiography confirmed this finding. The patient underwent urgent cardiac surgery, and the tumour was successfully resected. A histological examination revealed a cardiac myxoma. After the cardiac surgery the patient felt well, and no recurrence of the tumour occurred. Conclusions: We provide a case report of a fast-growing myxoma that was incidentally found in a patient with dyspnoea. We highlight the fast growth rate of the tumour and the potential for misdiagnosed signs of pulmonary oedema caused by mitral obstruction.

Causal relationship between nutritional assessment phenotypes and heart failure: A Mendelian randomization study

IntroductionMalnutrition is strongly associated with heart failure (HF); however, the causal link remains unclear. We used Mendelian randomization (MR) to infer causal associations between different nutritional assessment phenotypes and HF and to analyze whether these associations were mediated by common HF risk factors. MethodsTwo-sample bidirectional MR was used to infer causal associations between nutritional assessment phenotypes and HF. Mutual influences between different nutritional assessment phenotypes and potential correlations were estimated using multivariate MR methods. Two-step MR was used to quantify the mediating effects of common HF risk factors on the causal associations. ResultsThree phenotypes were positively associated with the development of HF: waist circumference (WC) (odds ratio [OR] = 1.74; 95% confidence interval [CI], 1.60–1.90; P = 3.95 × 10−39), body mass index (BMI) (OR = 1.70; 95%CI, 1.60–1.80; P = 1.35 × 10−73), and whole body fat mass (WBFM) (OR = 1.54; 95%CI, 1.44–1.65; P = 4.82 × 10−37). Multivariate MR indicated that WBFM remained positively associated with HF after conditioning on BMI and WC (OR = 2.05; 95%CI, 1.27–3.31; P = 0.003). Three phenotypes were negatively correlated with the development of HF: usual walking pace (UWP) (OR = 0.40; 95%CI, 0.27–0.60; P = 8.41 × 10−6), educational attainment (EA) (OR = 0.73; 95%CI, 0.67–0.79; P = 2.27 × 10−13), and total cholesterol (TC) (OR = 0.90; 95%CI, 0.84–0.96; P = 4.22 × 10−3). There was a bidirectional causality between HF and UWP (Effect estimate = −0.03; 95%CI, −0.05 to −0.01; P = 1.95 × 10−3). Mediation analysis showed that common risk factors for HF (hypertension, coronary artery disease, cardiomyopathy, and valvular heart disease) mediated these causal associations (all P < 0.05). ConclusionsBMI, WC, and WBFM are potential risk factors for HF, and the correlation between WBFM and HF was significantly stronger than that between BMI and WC, and HF. EA, UWP, and TC are potential protective factors against HF. Common risk factors for HF mediate these causal pathways. Early identification of potential risk or protective factors for HF patients from the dimension of nutritional status is expected to further improve patient outcomes.

An Underappreciated Risk Factor for Heart Failure—Financial Toxicity

An Underappreciated Risk Factor for Heart Failure—Financial Toxicity

Risk factors for pregnancy-associated heart failure with preserved ejection fraction and adverse pregnancy outcomes: a cross-sectional study.

Although pregnancy-associated heart failure with preserved ejection fraction (HFpEF) is increasing and contributing to maternal morbidity, little is known about its impact on pregnancy. We examined the risk factors for and adverse pregnancy outcomes of HFpEF in pregnant women. We conducted a cross-sectional analysis of pregnancy-related hospitalizations from 2009 to 2020 using the perinatal database of seven multicenters. Cases of HFpEF were identified using the International Classification of Diseases and echocardiography findings. The patients were categorized into the HFpEF and control groups. Risk factors were evaluated using multivariate logistic regression analysis to generate odds ratios (OR) and 95% confidence intervals (CI). Furthermore, adjusted associations between HFpEF and adverse pregnancy outcomes were determined. Risk scores for the stratification of women at a high risk of HFpEF were calculated using a statistical scoring model. Of the 34,392 women identified, 258 (0.76%) were included in the HFpEF group. In multivariate analysis, HFpEF was significantly associated with old maternal age (OR, 1.04; 95% CI 1.02-1.07), multiple pregnancy (OR, 2.22; 95% CI 1.53-3.23), rheumatic disease (OR, 2.56; 95% CI 1.54-4.26), pregnancy induce hypertension (OR 6.02; 95% CI 3.61-10.05), preeclampsia (OR 24.66; 95% CI 18.61-32.66), eclampsia or superimposed preeclampsia (OR 32.74; 95% CI 21.60-49.64) and transfusion in previous pregnancy (OR 3.89; 95% CI 1.89-8.01). A scoring model to predict HFpEF with those factors achieved an area under the curve of 0.78 at cutoff value of 3. Women with HFpEF also had increased odds ratios of intensive care unit admission during the perinatal period (odds ratio, 5.98; 95% confidence interval, 4.36-8.21) and of postpartum hemorrhage (odds ratio, 5.98; 95% confidence interval, 2.02-3.64). Pregnancy-associated HFpEF is associated with adverse pregnancy outcomes. A scoring model may contribute to screening HFpEF using echocardiography and preparing adverse pregnancy outcomes.

Machine learning model and nomogram to predict the risk of heart failure hospitalization in peritoneal dialysis patients

Introduction The study presented here aimed to establish a predictive model for heart failure (HF) and all-cause mortality in peritoneal dialysis (PD) patients with machine learning (ML) algorithm. Methods We retrospectively included 1006 patients who initiated PD from 2010 to 2016. XGBoost, random forest (RF), and AdaBoost were used to train models for assessing risk for 1-year and 5-year HF hospitalization and mortality. The performance was validated using fivefold cross-validation. The optimal ML algorithm was used to construct the models to predictive the risk of the HF and all-cause mortality. The prediction performance of ML methods and Cox regression was compared. Results Over a median follow-up of 49 months. Two hundred and ninety-eight patients developed HF required hospitalization; 199 patients died during the follow-up. The RF model (AUC = 0.853) was the best performing model for predicting HF, and the XGBoost model (AUC = 0.871) was the best model for predicting mortality. Baseline moderate or severe renal disease, systolic blood pressure (SBP), body mass index (BMI), age, Charlson Comorbidity Index (CCI) score were strongly associated with HF hospitalization, whereas age, CCI score, creatinine, age, high-density lipoprotein cholesterol (HDL-C), total cholesterol, baseline estimated glomerular filtration rate (eGFR) were the most significant predictors of mortality. For all the above endpoints, the ML models demonstrated better discrimination than Cox regression. Conclusions We developed and validated a novel method to predict the risk factors of HF and all-cause mortality that integrates readily available clinical, laboratory, and electrocardiographic variables to predict the risk of HF among PD patients.

Risk Factors and Emergency Department Outcomes in Methamphetamine-Associated Cardiomyopathy: A Case-Control Study

BackgroundMethamphetamine-associated cardiomyopathy (MACM) is a known complication of methamphetamine use, however risk factors and outcomes of patients with MACM are not well understood. ObjectiveThis study aims to identify risk factors, emergency department (ED) interventions, and outcomes for MACM. MethodsThis case-control study was conducted between 2012 and 2020 at 2 academic EDs. ED patients ≥18 years with an index visit that included documented methamphetamine use were included. Patients with documented MACM during follow-up (3 months - 3 years) were considered cases (MACM). A control group comprised of patients with documented meth use but no known MACM was matched at a 2:1 ratio. Logistic regression was used to model risk factors for MACM. Results9833 patients with methamphetamine use were identified. From this, 160 MACM patients were matched to 322 controls. The mean age was 48.4 years, and 143 patients (29.7%) were female. MACM patients were more likely to be admitted on their index visit (45.6% vs 34.8%, p=0.021). Significant variables associated with MACM included: admission at the index visit (OR 1.51), diabetes (OR 3.02), kidney disease (OR 5.47), and pulmonary disease (OR 2.39). MACM patients had more ED visits in the follow-up period (10.1 versus 7, p=0.009) and were admitted at a higher rate across all visits(32.5% vs 15.4%, p=0.009). Additionally, MACM patients had significantly longer hospital stays than controls (mean 18 additional days, p=0.009). ConclusionPatients who developed MACM had traditional risk factors for heart failure and experienced significantly more ED visits, more hospitalizations, and longer hospital stays than matched controls.

Variations in serum low-density lipoprotein and sST2 among heart failure patients with different ejection fraction groups and their clinical significance.

This study aimed to examine the changes in serum Low Density Lipoprotein Cholesterol (LDL-C) and Soluble Growth Stimulating Expressed Gene 2 Protein (sST2) among Heart Failure (HF) patients with varying ejection fractions and their clinical significance, providing a reference for the clinical assessment of HF severity. A total of 238 HF patients treated in our hospital's cardiology department from September 2019 to December 2021 were selected; 68 patients hospitalized in the same period were selected as the control group. General information, LDL-C and echocardiographic results of admitted patients were collected. According to LVEF results and the latest European Society of Cardiology standards in 2021, HF patients were categorized into those with HFpEF (n = 95), HFmrEF (n = 60), and HFrEF (n = 83). Meanwhile, venous blood was collected to determine sST2 and NT-proBNP to compare and analyze the changes and clinical significance of sST2 and LDL-C across the groups. Compared to the control group, the HF group showed significant differences in age, gender, heart rate, smoking history, history of atrial fibrillation, history of diabetes, LVEDD, LVEF, sST2, and NT-proBNP levels (P < .05), but not in LDL-C levels. Significant differences (P < .05) were also found among the 3 HF groups in terms of age, gender, history of atrial fibrillation, LVEDD, LVEF, LDL-C, sST2, and NT-proBNP levels, with an increase in LVEDD, LDL-C, sST2, and NT-proBNP values as the ejection fraction decreased. ROC curve analysis indicated that the area under the curve (AUC) for sST2 in diagnosing HF was 0.915 (P < .05), with an optimal cutoff value of 23.71 ng/mL, a sensitivity of 76.5%, and a specificity of 95.6%; LDL-C was not a significant diagnostic marker for HF (P > .05). Coronary artery disease, NT-proBNP, and sST2 were identified as risk factors for HF. With each unit increase in coronary artery disease, the risk of HF increased by 36.3%; for NT-proBNP, the risk increased by 1.3% per unit; and for sST2, it increased by 18.3% per unit. As the ejection fraction decreases in HF patients, serum sST2 and LDL-C values progressively increase, which is clinically significant for predicting the severity of HF. sST2 is an independent risk factor for HF and can enhance the diagnostic accuracy for HF.

Durability of Tricuspid Valve Repair in Patients Undergoing Left Ventricular Assist Device Implantation.

Objectives: Benefits of tricuspid valve repair (TVR) in left ventricular assist device (LVAD) patients have been questioned. High TVR failure rates have been reported. Remaining or recurring TR was found to be a risk factor for right heart failure (RHF). Therefore, we assessed our experience. Methods: Since 12/2010, 195 patients have undergone LVAD implantation in our center. Almost half (n = 94, 48%) received concomitant TVR (LVAD+TVR). These patients were included in our analysis. Echocardiographic and clinical data were assessed. Median follow-up was 2.8 years (7 days-0.6 years). Results were correlated with clinical outcomes. Results: LVAD+TVR patients were 59.8 ± 11.4 years old (89.4% male) and 37.3% were INTERMACS level 1 and 2. Preoperative TR was moderate in 28 and severe in 66 patients. RV function was severely impaired in 61 patients reflected by TAPSE-values of 11.2 ± 2.9 mm (vs. 15.7 ± 3.8 mm in n = 33; p < 0.001). Risk for RHF according to EUROMACS-RHF risk score was high (>4 points) in 60 patients, intermediate (>2-4 points) in 19 and low (0-2 points) in 15. RHF occurred in four patients (4.3%). Mean duration of echocardiographic follow-up was 2.8 ± 2.3 years. None of the patients presented with severe and only five (5.3%) with moderate TR. The vast majority (n = 63) had mild TR, and 26 patients had no/trace TR. Survival at 1, 3 and 5 years was 77.4%, 68.1% and 55.6%, 30-day mortality was 11.7% (n = 11). Heart transplantation was performed in 12 patients (12.8%). Conclusions: Contrary to expectations, concomitant TVR during LVAD implantation may result in excellent repair durability, which appears to be associated with low risk for RHF.

Kidney Function Trajectories and Right Heart Failure Following LVAD Implantation.

Preoperative kidney dysfunction is a risk factor for right heart failure (RHF) after implantation of a left ventricular assist device (LVAD). However, characteristic kidney function trajectories before and after post-LVAD RHF are uncertain, so we investigated this. We identified individuals who received primary continuous-flow LVAD implantation from July 1, 2014 to December 31, 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data set. Incident RHF was ascertained using the INTERMACS definition at 1 and 3 months and classified as transient or persistent. Kidney function trajectories before and after RHF onset, and relationships of baseline kidney function with RHF risk at the different time points, were assessed. We identified 8076 LVAD recipients who met inclusion criteria. Incident RHF was present at 1 month in 26.4%. There were 4850 individuals with follow-up at 3 months, with incident RHF in 4.2%. Kidney function trajectories differed from pre-LVAD implantation to 1-month follow-up by RHF category, with those developing persistent RHF having no improvement in baseline kidney function. For trajectories before the 3-month RHF ascertainment time, the shape was similar for those with and without RHF, with lower estimated glomerular filtration rate levels among those who developed RHF. Baseline estimated glomerular filtration rate levels below the normal range were associated with higher risk of RHF at 1 and 3 months. In LVAD recipients, preimplantation kidney function and subsequent kidney function trajectories differed substantially by RHF at 1 and 3 months postimplantation, even after adjustment for several confounders. This may demonstrate bidirectional associations between kidney function and right ventricular function in LVAD recipients.

Iron Deficiency and Incident Heart Failure in Older Community-Dwelling Individuals.

Among persons with prevalent heart failure (HF), iron deficiency has been linked to HF admissions, and intravenous iron replacement improves HF outcomes. Recent studies in persons with chronic kidney disease (CKD) demonstrate that iron deficiency is associated with incident HF. This study aimed to determine the relationship of iron status with incident HF in community-dwelling older adults irrespective of their kidney function. In this case-cohort study, 1,006 Cardiovascular Health Study participants (785 from the random sub-cohort [including 193 HF cases] and 221 additional HF cases [N=414 total HF cases]) aged ≥ 65years without HF (41% with CKD), we used weighted Cox models to evaluate associations of iron status with incident HF. Participants were categorized based on quartiles of transferrin saturation and ferritin as "iron replete" (27.3%), "functional iron deficiency" (7.7%), "iron deficiency" (11.8%), "mixed iron deficiency" (5.6%), "high iron" (9.3%) and "non-classified" (38.1%), consistent with prior studies. Compared to older persons who were iron replete, those with iron deficiency were at higher risk of incident HF (HR 1.47; 1.02-2.11) in models adjusting for demographics, HF risk factors, and estimated glomerular filtration rate. Other iron categories did not associate with incident HF. The relationship of iron deficiency with incident HF did not differ by CKD status (interaction P value 0.2). Among community-dwelling elders, iron deficiency is independently associated with incident HF, an association that was similar irrespective of CKD status. Our findings support conduct of clinical trials of iron replacement for prevention of HF in older adults with iron deficiency.

Association of congestive heart failure with mortality in individuals with rheumatoid arthritis: a cohort study.

Rheumatoid arthritis (RA) is a risk factor for congestive heart failure (CHF). Evidence is lacking regarding the relationship between CHF and mortality among American adults with RA. We aimed to investigate the relationship between CHF and mortality in patients with RA. We extracted the corresponding data from the National Health and Nutrition Examination Survey (NHANES) database and calculated the hazard ratios (HR) and 95% CIs between CHF and mortality from all causes, cardiovascular disease (CVD), and cancer by using a Cox proportional risk model. A total of 2045 participants with a mean age of 60.32 ± 13.96years were included; 57.60% were female. During a median follow-up period of 109months, there were 602 deaths. After adjusting for potential confounders, compared with participants who are non-CHF, those with CHF had 60% (HR 1.60, 95% CI 1.27-2.01) and 110% (1.45, 1.45 to 3.06) higher all-cause mortality and CVD mortality, respectively. Furthermore, a significant association between CHF and all-cause mortality can also be observed in female individuals and those aged 65 and above. There was no significant association between CHF and cancer mortality. In this cohort study of US adults with RA, CHF was significantly associated with an increased risk of all-cause or CVD-related death. This finding underscores the importance of CHF in the management of patients with RA and may provide future information on maintaining the health status of patients with RA. Key messages • The study findings demonstrate a significant increase in overall mortality and cardiovascular mortality among individuals with RA who develop CHF. • This knowledge can assist healthcare professionals in identifying high-risk patients who could benefit from targeted monitoring and early intervention to prevent or manage CHF.

Sex-related differences in patients presenting with heart failure–related cardiogenic shock

BackgroundHeart failure–related cardiogenic shock (HF-CS) accounts for a significant proportion of all CS cases. Nevertheless, there is a lack of evidence on sex-related differences in HF-CS, especially regarding use of treatment and mortality risk in women vs. men. This study aimed to investigate potential differences in clinical presentation, use of treatments, and mortality between women and men with HF-CS.MethodsIn this international observational study, patients with HF-CS (without acute myocardial infarction) from 16 tertiary-care centers in five countries were enrolled between 2010 and 2021. Logistic and Cox regression models were used to assess differences in clinical presentation, use of treatments, and 30-day mortality in women vs. men with HF-CS.ResultsN = 1030 patients with HF-CS were analyzed, of whom 290 (28.2%) were women. Compared to men, women were more likely to be older, less likely to have a known history of heart failure or cardiovascular risk factors, and lower rates of highly depressed left ventricular ejection fraction and renal dysfunction. Nevertheless, CS severity as well as use of treatments were comparable, and female sex was not independently associated with 30-day mortality (53.0% vs. 50.8%; adjusted HR 0.94, 95% CI 0.75–1.19).ConclusionsIn this large HF-CS registry, sex disparities in risk factors and clinical presentation were observed. Despite these differences, the use of treatments was comparable, and both sexes exhibited similarly high mortality rates. Further research is necessary to evaluate if sex-tailored treatment, accounting for the differences in cardiovascular risk factors and clinical presentation, might improve outcomes in HF-CS.Graphical abstractSex-related differences in clinical characteristics, shock severity, and mortality in patients with heart failure–related cardiogenic shock. Summary for the main study findings. AMI, acute myocardial infarction; CI, confidence interval; HF-CS, heart failure–related cardiogenic shock; LVEF, left ventricular ejection fraction; MCS, mechanical circulatory support; SCAI, Society for Cardiovascular Angiography & Interventions.

A second chance for a new heart? The role of metabolic and bariatric surgery in patients with end-stage heart failure

Obesity is an independent risk factor for heart failure (HF). Substantial weight loss has been shown to reverse obesity-related cardiomyopathy. This study aimed to report our institution's experience with laparoscopic sleeve gastrectomy (LSG) in patients with morbid obesity and end-stage HF. Between 2018 and 2022, 26 patients with end-stage HF were referred for LSG. Of 26 patients, 16 underwent an operation, and 10 did not. After institutional review board approval, a retrospective electronic medical record review was performed to evaluate (i) age, (ii) preoperative weight, (iii) decrease in body mass index (BMI) score, (iv) whether the patient underwent heart transplantation, and (v) mortality. Data analysis was performed using Stata/SE (version 17.0; StataCorp). The Wilcoxon rank-sum test was used to compare continuous variables between the cohorts, and the Pearson chi-square test was used for binary variables with Bonferroni correction applied. The LSG and non-LSG cohorts had comparable ages (P=.088) and starting BMI score (P=.918), and a proportion of patients had a ventricular assist device (P=.191). Patients who underwent LSG lost significantly more weight than the patients who did not, with an average decrease in BMI score of 8.9kg/m2 (SD, ±6.13) and 1.1kg/m2 (SD, ±4.10), respectively (P=.040). Of note, 6 patients (37.5%) who underwent LSG eventually underwent transplantation, compared with 2 patients (20.0%) from the matched cohort (P=.884). Of the 26 patients, there were 6 deaths: 2 (12.5%) in the LSG cohort and 4 (40.0%) in the non-LSG cohort (P=.525). LSG may be safe and effective for weight loss in patients with HF. This operation may provide patients affected by obesity with end-stage HF the lifesaving opportunity to achieve transplant candidacy.

Epicardial Adipose Tissue and Heart Failure, Friend or Foe?

Heart failure (HF) management guidelines recommend individualized assessments based on HF phenotypes. Adiposity is a known risk factor for HF. Recently, there has been an increased interest in organ-specific adiposity, specifically the role of the epicardial adipose tissue (EAT), in HF risk. EAT is easily assessable through various imaging modalities and is anatomically and functionally connected to the myocardium. In pathological conditions, EAT secretes inflammatory cytokines, releases excessive fatty acids, and increases mechanical load on the myocardium, resulting in myocardial remodeling. EAT plays a pathophysiological role in characterizing both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). In HFrEF, EAT volume is reduced, reflecting an impaired metabolic reservoir, whereas in HFpEF, the amount of EAT is associated with worse biomarker and hemodynamic profiles, indicating increased EAT activity. Studies have examined the possibility of therapeutically targeting EAT, and recent studies using sodium glucose cotransporter 2 inhibitors have shown potential in reducing EAT volume. However, further research is required to determine the clinical implications of reducing EAT activity in patients with HF.

Ambient fine particulate matter chemical composition associated with in-hospital case fatality, hospital expenses, and length of hospital stay among patients with heart failure in China.

Previous studies have observed the adverse effects of ambient fine particulate matter pollution (PM2.5) on heart failure (HF). However, evidence regarding the impacts of specific PM2.5 components remains scarce. We included 58 129 patients hospitalised for HF between 2013 and 2017 in 11 cities of Shanxi, China from inpatient discharge database. We evaluated exposure to PM2.5 and its components ((sulphate (SO42-), nitrate (NO3-), ammonium (NH4+), organic matter (OM) and black carbon (BC)), along with meteorological factors using bilinear interpolation at each patients' residential address. We used multivariable logistic and linear regression models to assess the associations of these components with in-hospital case fatality, hospital expenses, and length of hospital stay. Increase equivalents to the interquartile range (IQR) in OM (odds ratio (OR) = 1.13; 95% confidence interval (CI) = 1.02, 1.26) and BC (OR = 1.14; 95% CI = 1.02, 1.26) were linked to in-hospital case fatality. Per IQR increments in PM2.5, SO42-, NO3-, OM, and BC were associated with cost increases of 420.62 (95% CI = 285.75, 555.49), 221.83 (95% CI = 96.95, 346.71), 214.93 (95% CI = 68.66, 361.21), 300.06 (95% CI = 176.96, 423.16), and 303.09 (95% CI = 180.76, 425.42) CNY. Increases of 1 IQR in PM2.5, SO42-, OM, and BC were associated with increases in length of hospital stay of 0.10 (95% CI = 0.02, 0.19), 0.09 (95% CI = 0.02, 0.17), 0.10 (95% CI = 0.03, 0.17), and 0.16 (95% CI = 0.08, 0.23) days. Our findings suggest that ambient SO42-, OM, and BC might be significant risk factors for HF, emphasising the importance of formulating customised guidelines for the chemical constituents of PM and controlling the emissions of the most dangerous components.

P 035: Prevalence and risk factors of heart failure with preserve ejection fraction (HFPEF) in type 2 diabetes mellitus (T2DM) population in Hospital AL-Sultan Abdullah

P 035: Prevalence and risk factors of heart failure with preserve ejection fraction (HFPEF) in type 2 diabetes mellitus (T2DM) population in Hospital AL-Sultan Abdullah

Sex and Age Differences in the Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Heart Failure: A Prospective Cohort Study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for heart failure (HF) occurrence, but it remains unclear whether the association between MAFLD and HF differs in different sexes and ages. A total of 96 576 participants of Kailuan Study were included. MAFLD was defined as presence of hepatic steatosis and metabolic dysfunction and classified as mild and significant by ultrasound. Hazard ratios (HRs) were calculated by Cox regression models. After a median follow-up of 14.0 years, 2939 participants developed HF. Adjusting for confounding factors, mild-MAFLD (HR, 1.27 [95% CI, 1.16-1.39]) and significant-MAFLD (HR, 1.45 [95% CI, 1.31-1.63]) were associated with a higher risk of HF in all participants, and the risk differed by sex (Pinteraction<0.05) and age (Pinteraction<0.001). Compared with non-MAFLD participants, in women, significant-MAFLD was associated with an 84% (HR, 1.84 [95% CI, 1.43-2.37]) increased risk of HF; however, in men, the risk was 36% (HR, 1.36 [95% CI, 1.20-1.53]). In participants under 45 years, mild-MAFLD and significant-MAFLD had a 55% (HR, 1.55 [95% CI, 1.07-2.25]) and 172% (HR, 2.72 [95% CI, 1.87-3.97]) increased risk of HF; however, in participants over 65 years, even significant-MAFLD did not associate with a higher risk of HF (HR, 1.11 [95% CI, 0.92-1.34]). Afterwards, we stratified all participants by both sex and age and found that the risk of MAFLD-associated HF decreased with age in men (Pinteraction<0.05) and women (Pinteraction<0.05), but the sex difference in this risk was only present in participants younger than 45 years (Pinteraction<0.05). MAFLD greatly increased the risk of HF in women, especially young women. With increasing age, MAFLD-related risk of HF decreased and the difference between men and women disappeared.

Jianpi Qinghua Formula Alleviates Diabetic Myocardial Injury Through Inhibiting JunB/c-Fos Expression.

Diabetic cardiomyopathy (DCM) represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus (DM). DCM typically manifests as myocardial fibrosis, myocardial hypertrophy, and impaired left ventricular diastolic function. While the clinical utility of the Jianpi Qinghua (JPQH) formula has been established in treating diabetes and insulin resistance, its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain. This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula (JPQHF) in ameliorating myocardial injury in nonobese diabetic rats, specifically focusing on apoptosis and inflammation. Wistar rats were assigned as the normal control group (CON), while Goto-Kakizaki (GK) rats were randomly divided into three groups: DM, DM treated with the JPQHF, and DM treated with metformin (MET). Following a 4-week treatment regimen, various biochemical markers related to glucose metabolism, cardiac function, cardiac morphology, and myocardial ultrastructure in GK rats were assessed. RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets. In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells. Cell viability was evaluated using CCK-8 assay, apoptosis was monitored via flow cytometry, and the production of inflammatory cytokines was measured using quantitative real-time PCR (qPCR) and ELISA. Protein expression levels were determined by Western blotting analysis. The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels. The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole (IVSs) and left ventricular internal diameter at end-systole and end-diastole (LVIDs and LVIDd). JPQHF effectively suppressed high glucose-induced activation of IL-1β and caspase 3 in cardiomyocytes. Furthermore, JPQHF downregulated the expression of myocardial JunB/c-Fos, which was upregulated in both diabetic rats and high glucose-treated H9c2 cells. The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK (p38 and ERK1/2) pathway.

Mycn ameliorates cardiac hypertrophy-induced heart failure in mice by mediating the USP2/JUP/Akt/β-catenin cascade

BackgroundPathological cardiac hypertrophy is associated with cardiac dysfunction and is a key risk factor for heart failure and even sudden death. This study investigates the function of Mycn in cardiac hypertrophy and explores the interacting molecules.MethodsA mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays.ResultsMycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt/β-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and β-catenin protein level, which negated the protective effects of USP2.ConclusionThis study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt/β-catenin axis and alleviating cardiac hypertrophy-induced heart failure.

CTRP3 alleviates mitochondrial dysfunction and oxidative stress injury in pathological cardiac hypertrophy by activating UPRmt via the SIRT1/ATF5 axis

Pathological cardiac hypertrophy is an independent risk factor for heart failure. Disruption of mitochondrial protein homeostasis plays a key role in pathological cardiac hypertrophy; however, the mechanism of maintaining mitochondrial homeostasis in pathological cardiac hypertrophy remains unclear. In this study, we investigated the regulatory mechanisms of mitochondrial protein homeostasis in pathological cardiac hypertrophy. Wildtype (WT) mice, knockout mice, and mice transfected with lentivirus overexpressing mouse C1q-tumor necrosis factor-related protein-3 (CTRP3) underwent transverse aortic constriction or sham surgery. After 4 weeks, cardiac function, mitochondrial function, and oxidative stress injury were examined. For mechanistic studies, neonatal rat cardiomyocytes were treated with small interfering RNA or overexpression plasmids for the relevant genes. CTRP3 overexpression attenuated transverse aortic constriction (TAC) induced pathological cardiac hypertrophy, mitochondrial dysfunction, and oxidative stress injury compared to that in WT mice. TAC or Ang II resulted in compensatory activation of UPRmt, but this was not sufficient to counteract pathologic cardiac hypertrophy. CTRP3 overexpression further induced activation of UPRmt during pathologic cardiac hypertrophy and thereby alleviated pathologic cardiac hypertrophy, whereas CTRP3 knockout or knockdown inhibited UPRmt. ATF5 was a key regulatory molecule of UPRmt, as ATF5 knockout prevented the cardioprotective effect of CTRP3 in TAC mice. In vitro, SIRT1 was identified as a possible downstream CTRP3 effector molecule, and SIRT1 knockout blocked the cardioprotective effects of CTRP3. Our results also suggest that ATF5 may be regulated by SIRT1. Our study demonstrates that CTRP3 activates UPRmt via the SIRT1/ATF5 axis under pathological myocardial hypertrophy, thus attenuating mitochondrial dysfunction and oxidative stress injury.