Risk Factor For Heart Failure Research Articles

Risk factors for raised left ventricular filling pressure by cardiovascular magnetic resonance: Prognostic insights.

Cardiovascular magnetic resonance (CMR) imaging shows promise in estimating pulmonary capillary wedge pressure (PCWP) non-invasively. At the population level, the prognostic role of CMR-modelled PCWP remains unknown. Furthermore, the relationship between CMR-modelled PCWP and established risk factors for cardiovascular disease has not been well characterized. The main aim of this study was to investigate the prognostic value of CMR-modelled PCWP at the population level. Employing data from the imaging substudy of the UK Biobank, a very large prospective population-based cohort study, CMR-modelled PCWP was calculated using a model incorporating left atrial volume, left ventricular mass and sex. Logistic regression explored the relationships between typical cardiovascular risk factors and raised CMR-modelled PCWP (≥15mmHg). Cox regression was used to examine the impact of typical risk factors and CMR-modelled PCWP on heart failure (HF) and major adverse cardiovascular events (MACE). Data from 39163 participants were included in the study. Median age of all participants was 64years (inter-quartile range: 58 to 70), and 47% were males. Clinical characteristics independently associated with raised CMR-modelled PCWP included hypertension [odds ratio (OR) 1.57, 95% confidence interval (CI) 1.44-1.70, P<0.001], body mass index (BMI) [OR 1.57, 95% CI 1.52-1.62, per standard deviation (SD) increment, P<0.001], male sex (OR 1.37, 95% CI 1.26-1.47, P<0.001), age (OR 1.33, 95% CI 1.27-1.41, per decade increment, P<0.001) and regular alcohol consumption (OR 1.10, 95% CI 1.02-1.19, P=0.012). After adjusting for potential confounders, CMR-modelled PCWP was independently associated with incident HF [hazard ratio (HR) 2.91, 95% CI 2.07-4.07, P<0.001] and MACE (HR 1.48, 95% CI 1.16-1.89, P=0.002). Raised CMR-modelled PCWP is an independent risk factor for incident HF and MACE. CMR-modelled PCWP should be incorporated into routine CMR reports to guide HF diagnosis and further management.

Diagnostic and therapeutic challenges for PCPs regarding heart failure with preserved ejection fraction and obesity: results of an online internet-based survey

BackgroundObesity (body mass index ≥ 30 kg/m2) is a major risk factor for heart failure with preserved ejection fraction (HFpEF) and affects most patients with HFpEF. Patients living with obesity may experience delays in HFpEF diagnosis and management. We aimed to understand the clinical journey of patients with obesity and HFpEF and the role of primary care providers (PCPs) in diagnosing and managing patients with both conditions.MethodsAn anonymous, US population-based online survey was conducted in September 2020 among 114 patients with self-reported HFpEF and obesity and 200 healthcare providers, 61 of whom were PCPs who treat patients with HFpEF and obesity.ResultsHalf of patients (51%) with HFpEF reported waiting an average of 11 months to discuss their symptoms with a PCP; 11% then received their diagnosis from a PCP. PCPs initiated treatment and oversaw the management of HFpEF only 35% of the time, and 44% of PCPs discussed obesity treatment medication options with their patients. Only 20% of PCPs indicated they had received formal obesity management training, and 79% of PCPs indicated they would be interested in obesity management training and support.ConclusionPCPs could play a valuable role in addressing obesity and referring patients with obesity and signs and symptoms of HFpEF to cardiologists. Increased awareness of HFpEF and its link to obesity may help PCPs more quickly identify and diagnose their patients with these conditions.Graphical

Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical siabetic cardiomyopathy

IntroductionPersons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown.MethodsIn this prespecified subgroup analysis of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial, 685 participants with asymptomatic DbCM underwent baseline echocardiography data, laboratory investigations, and functional assessments. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test.ResultsThe median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/E’, or right ventricular systolic pressure. In contrast, NT-proBNP was significantly correlated with overall Kansas City Cardiomyopathy Questionnaire score (rho = − 0.10; p = 0.007), the Physical Activity Scale in the Elderly (rho = − 0.12; p = 0.004), duration of cardiopulmonary exercise testing (rho = − 0.28; p < 0.001), peak VO2 (rho = − 0.26; p < 0.001), and ratio of minute ventilation/carbon dioxide production (rho = 0.12; p = 0.002). After adjustment for known confounders, the correlation with Physical Activity Scale in the Elderly and overall Kansas City Cardiomyopathy Questionnaire score was no longer significant.ConclusionAmong patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals.Trial registrationARISE-HF, NCT 04083339 Date Registered August 23, 2019.Graphical abstractAbnormal ECHO defined as Myocardial Global Longitudinal Strain < − 16 or left ventricular mass index > 95 for females or > 115 for males or E/e’ >13 or left atrial volume index > 34. †Normal ECHO is defined as the absence of these abnormalities. Low NT-proBNP is defined as < 71 ng/L while high NT-proBNP is defined as ≥ 71 ng/L.

Abstract Mo107: Age-Related Impairment of Mitochondrial Protein Turnover Exacerbates Pathogenesis of Heart Failure with Preserved Ejection Fraction in Old Mice

Introduction: Age is recognized as a major risk factor for heart failure with preserved ejection fraction (HFpEF), yet the precise role of aging in HFpEF development remains unknown. Disruption of mitochondrial protein turnover affects the quality and quantity of proteins crucial for energy metabolism. Although mitochondrial dysfunction is a key feature of both aging and HFpEF heart, the influence of age-related disturbances in mitochondrial protein turnover on HFpEF pathogenesis remains unclear. Hypothesis: Age-related impairment of mitochondrial protein turnover intensifies proteostatic perturbations induced by hypertensive and metabolic stress (2-hit stress) to exacerbate pathogenesis of cardiometabolic HFpEF. Methods: Young (3 mo.) and old (19 mo.) C57BL/6J male mice were exposed to high-fat diet and L-NAME to induce HFpEF development. Deuterium oxide (D 2 O) labeling coupled with mass spectrometry was used to investigate bulk and individual mitochondrial protein synthesis. The changes in individual mitochondrial protein abundance and protein degradation pathways were also studied. Results: Old mice presented exacerbated HFpEF characteristics compared to young mice, with higher mortality and worsened cardiac and extra-cardiac phenotypes. Regardless of age, mice subjected to 2-hit stress had 24% higher bulk mitochondrial protein synthesis compared to controls. Old control and HFpEF mice showed 17% lower mitochondrial protein synthesis compared to younger counterparts, potentially hindering the replacement of dysfunctional mitochondrial proteins. Aging reduced the synthesis rates of 30 out of 115 proteins synthesized more rapidly with HFpEF, including those involved in mitochondrial metabolism. Despite slower synthesis of numerous mitochondrial proteins with age, the overall abundance of these proteins remained unchanged or elevated compared to young counterparts, indicating impaired protein degradation. We found that aging and 2-hit stress differentially inhibited degradation pathways, including autophagy and the ubiquitin-proteasome system, further impairing protein turnover. Conclusion: Aging impairs mitochondrial protein turnover in cardiometabolic HFpEF and contributes to poorer disease outcomes.

Abstract We072: Effects of electronic cigarettes on mouse cardiac lymphatic vessels after TAC surgery

Introduction: Heart failure is a public health concern worldwide. It is known that tobacco smoking is a risk factor of heart failure. Tobacco smoking also causes inflammation reaction and lymphatic dysfunction in the lung. However, the effects of electronic cigarettes (ECIG), as a new method of smoking, on the heart and cardiac lymphatic vessels (lymphatics) are not clear yet. The lymphatic vessels play an important role in maintaining cardiac function by modulating fluid homeostasis and transporting macromolecules. It has been reported that cardiac lymphatic vessel formation limits pressure overload-induced heart failure in C57Bl/6 but not in Balb/c mice. How cardiac lymphatics might contribute to the pathogenesis induced by ECIG is not known. Research Questions: The roles of cardiac lymphatic vessels in responses to ECIG exposure are not investigated. I hypothesize that the toxic effects of ECIG on the heart are partially caused by damaging the cardiac lymphatic vessels. Aim: To determine the effects of ECIG exposure on cardiac lymphatics after Transverse aortic constriction (TAC). Methods: I perform TAC surgery on mice as a heart hypertrophy and chronic heart failure model. Mice after TAC or Sham surgery are treated with different vaping components from ECIG: ECIG, propylene glycol and glycerin (PGVG) as vehicle, and air. After 4 weeks of treatment, hearts were harvested for histological analyses. The lymphatic vessel coverage percentage and morphology were examined by immunostaining. Results: Prior research suggested that genetic background in mice might affect the responses of cardiac lymphatic vessels to TAC-induced heart failure. I have established the TAC model using CD-1 mice. My results showed that CD-1 mice treated with PGVG after TAC do not show a significant difference in cardiac lymphatic vessel density compared to Sham group (p value=0.5951). ECIG treatment also did not affect the lymphatic density significantly compared to PGVG treated mice after sham operation (p value=0.8937). ECIG treated mice after TAC surgery showed a trend of increased lymphatic coverage and more mice are still being processed and will be presented at the conference. Conclusion: PGVG treated CD-1 mice do not show changes in lymphatic vessel density 4 weeks post TAC. Longer time points and more mouse numbers are needed to compare the effects of PGVG and ECIG after TAC induced hypertrophy and heart failure. This research is supported by California TRDRP grant.

Risk of mortality associated to chronic kidney disease in patients with complete left bundle branch block

Chronic kidney disease (CKD) is associated with cardiac conduction defects and is a strong risk factor for heart failure. Complete left bundle branch block (cLBBB), a cardiac conduction abnormality, may have an unfavorable effect on ventricular mechanical synchrony and lead to the progression of heart failure. Once heart failure develops, it seems to act together with underlying CKD in a vicious circle. Therefore, this study aimed to explore the influence of CKD in patients with cLBBB by assessing the estimated glomerular filtration rate (eGFR). We examined a hospital-based sample of 416 adult patients with cLBBB from 2010 to 2013. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cox proportional hazard models were used to estimate the hazard ratio for all-cause mortality and cardiovascular mortality. A total of 416 adult patients with a mean age of 71 ± 13 years were enrolled. The median follow-up period was 3.6 years. After adjusting for clinical, electrocardiographic parameters, and medication use, cox regression analysis showed that total mortality was significantly associated with older age (Hazard Ratio (HR) = 1.03, 95% CI = 1.01–1.05, p = 0.002), presence of congestive heart failure (HR = 2.39, 95% CI = 1.63–3.49, p < 0.001), advanced CKD (HR = 2.48, 95% CI = 1.71–3.59, p < 0.001), higher HR (HR = 1.02, 95% CI = 1.01–1.03, p < 0.001) and without use of ACEI/ARB (HR = 0.59, 95% CI = 0.41–0.85, p = 0.005) were independent predictors of the total mortality. Multivariate Cox hazard regression analysis demonstrated that, in comparison to patients lacking cLBBB, the coexistence of CKD (eGFR < 60 mL/min/1.73 m2) among those with LBBB significantly heightened the risks of both total mortality (HR ratio of 5.01 vs. 2.40) and CV death (HR ratio of 61.78 vs. 14.41) even following adjustment for clinical covariates and ECG parameters. In summary, within patients exhibiting cLBBB, the presence of CKD serves as a significant risk factor for all-cause mortality.

Comparative analysis of heart failure prediction using machine learning models

Heart failure is a critical health problem worldwide, and its prediction is a major challenge in medical science. Machine learning has shown great potential in predicting heart failure by analyzing large amounts of medical data. Heart failure prediction with the help of machine learning classification algorithms involves the use of models such as decision trees, logistic regression, and support vector machines to identify and analyze potential risk factors for heart failure. By analyzing large datasets containing medical and lifestyle-related variables, these models can accurately predict the likelihood of heart failure occurrence in individuals. In our research, the heart failure prediction and comparison are done using Logistic Regression, KNN, SVM, decision tree and random forest The accurate identification of high-risk individuals enables early intervention and better management of heart failure, reducing the risk of mortality and morbidity associated with this condition. Overall, machine learning algorithms play a major role in improving the accuracy of heart failure risk assessment, allowing for more personalized and effective prevention and treatment strategies.

Role of Conventional Heart Failure Risk Factors in Cancer Survivors and Other At-Risk Groups

Role of Conventional Heart Failure Risk Factors in Cancer Survivors and Other At-Risk Groups

Recurrence of left ventricular systolic dysfunction and its risk factors in heart failure with improved ejection fraction patients receiving guideline-directed medical therapy: A trajectory analysis based on echocardiography

BackgroundDespite the better prognosis of heart failure (HF) with improved ejection fraction (HFimpEF), remnant cardiovascular risks, including cardiovascular death, rehospitalization, and future deterioration of left ventricular (LV) systolic function, remain in HFimpEF. However, for HFimpEF patients, especially for those receiving guideline-directed medical therapy (GDMT), the recurrent LV systolic dysfunction and its risk factors is still unclear. MethodsA total of 1098 HF patients under HF follow-up management system were initially screened. Echocardiography was re-evaluated at 3-, 6-, and 12-month follow-up. After exclusion, a total of 203 HFimpEF patients on GDMT were enrolled in our final analysis. Cox regression analysis was conducted to select risk factors. ResultsDuring the 1-year follow-up, a total of 28 (13.8%) patients had recurrent LV systolic dysfunction. The trajectory analysis of echocardiographic parameters illustrated that persistent decline of left ventricular ejection fraction (LVEF) and worsening LV remodeling was observed in patients with recurrent LV systolic dysfunction. Multivariable Cox regression analysis identified that ischemic cardiomyopathy, atrial fibrillation, higher left ventricular end-diastolic diameter index (LVEDDI), elevated serum potassium, and a lack of sodium-glucose co-transporter-2 inhibitors (SGLT2i) treatment were confirmed as independent risk factors for recurrent LV systolic dysfunction. Recurrent LV systolic dysfunction was associated with higher rehospitalization rate. ConclusionIn our longitudinal cohort study, almost 14% HFimpEF receiving GDMT suffered recurrent LV systolic dysfunction. Ischemic cardiomyopathy, atrial fibrillation, higher LVEDDI, higher serum potassium, and a lack of SGLT2i therapy were tightly associated with recurrence of LV systolic dysfunction. Relapse of LV systolic dysfunction correlated with poor prognosis.

Association of baseline and longitudinal changes in insulin-like growth factor-binding protein-7 with the risk of incident heart failure: Data from the PREVEND study.

Senescence is a major risk factor for heart failure (HF), and insulin-like growth factor-binding protein-7 (IGFBP7) has been identified as an important senescence-inducing factor. The aim of this study was to examine the value of baseline and repeat IGFBP7 measurements in predicting future HF among community-dwelling Dutch adults from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. Individuals without prevalent HF who attended PREVEND visits 2 and 4 median of 5.1 years apart (25th-75th percentile, 4.9-5.2) with measurements of IGFBP7 were included. We used Cox proportional hazards models to investigate the association between IGFBP7 and HF incidence. A total of 6125 participants attending visit 2 (mean ± standard deviation [SD] age 53.1 ± 12.2 years; 3151 [51.4%] men) were followed for a median of 8.4 (7.8-8.9) years, and 194 participants (3.2%) developed incident HF. Median baseline IGFBP7 concentration was 87.0 (75.1-97.3) ng/ml, and baseline IGFBP7 levels were significantly associated with risk for incident HF (HF risk factors adjusted hazard ratio [HR] per 1 SD change in log-transformed IGFBP7: 1.22, 95% confidence interval [CI] 1.03-1.46). Baseline IGFBP7 was also significantly associated with incident HF in individuals with N-terminal pro-B-type natriuretic peptide <125 ng/L. Among 3879 participants attending both visits 2 and 4 (mean ± SD age 57.5 ± 11.3 years; 1952 [50.3%] men), 93 individuals developed HF (after visit 4) during a median follow-up of 3.2 (2.8-3.9) years. Median increase in IGFBP7 concentration between visits was 0.68 (-7.09 to 8.36) ng/ml, and changes in IGFBP7 levels were significantly associated with risk for incident HF (HF risk factors adjusted HR per 1 SD change in log-transformed IGFBP7: 1.68, 95% CI 1.19-2.36). Both baseline as well as repeat IGFBP7 measurements provide information about the risk of developing HF.

Triglyceride glucose index is a risk factor for heart failure: A prospective cohort study.

This study aimed to investigate the relationship between the triglyceride glucose (TyG) index and all-cause mortality in patients with heart failure (HF). A total of 1274 patients with HF diagnosed at Hebei General Hospital were enrolled in this study. The patients were divided into four groups by quartiles based on the TyG index. The endpoint was all-cause mortality during the follow-up period. The median follow-up period was 1079days, with a total of 543 (42.7%) patients experiencing all-cause mortality. The survival curves showed no significant difference in endpoint events among the four groups (log-rank P=0.329). The adjusted survival curves revealed that after adjusting for the variables in Model 3, the group with a higher TyG index exhibited a higher risk of death (log-rank P<0.001). The multivariate-adjusted Cox proportional hazard models revealed a positive correlation between the TyG index and all-cause mortality. After complete adjustment, patients with the highest TyG index exhibited a higher risk of all-cause mortality than those in the lowest quartile [hazard ratio (HR)=1.6, 95% confidence interval (CI): 1.22-2.09; P=0.001]. Restricted cubic spline analysis showed that the risk of all-cause mortality increased linearly with the TyG index (P for non-linear=0.207). Exploratory subgroup analyses revealed that, as a continuous variable, the TyG index was significantly associated with all-cause mortality in female patients (HR=1.31, 95% CI: 1.08-1.58, P=0.029) and older patients (HR=1.25, 95% CI: 1.1-1.43, P=0.027). The TyG index was positively associated with increased all-cause mortality in hospitalized patients with HF. Subgroup analyses indicated that the TyG index was strongly associated with all-cause mortality in older and female patients.

Assessment of left atrial function provides incremental value: the left atrial volumetric/mechanical coupling index in patients with chronic kidney disease.

Heart failure is a common cause of adverse cardiovascular outcomes in patients with chronic kidney disease (CKD). Left atrial (LA) characteristics are thought to be involved in the development of heart failure. However, LA assessment is complex. Though a variety of parameters have been defined, there is no single parameter that best defines LA function. Pilot data indicate that left atrial volumetric/mechanical coupling index (LACI) may be useful, but data with CKD are lacking. The objective of this study was to define LACI in a cohort of patients with CKD and to assess its value in evaluating LA function and predicting heart failure. A cohort of patients with CKD was enrolled at our hospital between 2021 and 2023. Follow-up was performed for heart failure. LACI is a volumetric to mechanical coupling index, calculated as the ratio of the LA volume index to the tissue-Doppler myocardial velocity at atrial contraction. Spearman's rank correlation or Pearson's correlation was used to calculate the correlation between LACI and echocardiographic/hemodynamic variables. Receiver operating characteristic curve (ROC) analysis was utilised to derive the area under the curve (AUC) for LACI, LVGLS, LASr, LASct and LASI for the detection of heart failure. Kaplan-Meier survival curves were employed to compare clinical outcomes based on LACI thresholds. A multivariable logistic regression analysis was employed to assess the relationship between risk factors and elevated LACI. Cox proportional hazards regression was used to identify risk factors for heart failure. LACI showed a positive correlation with NT-proBNP, CK-MB, LAVI, E/e' and LASI (r = 0.504, 0.536, 0.856, 0.541 and 0.509, p < 0.001); and a negative correlation with LASr (r = -0.509, p < 0.001). On the ROC analysis for the determination of heart failure, the AUC of LACI was comparable to those of LVGLS (0.588 vs. 509, p = 0.464), LASr (0.588 vs. 0.448, p = 0.132), LASct (0.588 vs. 0.566, p = 0.971) and LASI (0.588 vs. 0.570, p = 0.874). The cardiovascular risk factors increased by LACI were age, BMI, diabetes, triglycerides, LA size, LASr, LASI, E/A, E/e' and EF (p < 0.05). During a median follow-up of 16 months (range, 6-28 months), the event-free survival curves demonstrated a higher risk of heart failure in the group with LACI > 5.0 (log-rank test: P < 0.001). LACI > 5.0 was an independent predictor of heart failure [OR: 0.121, 95% CI (0.020-0.740), p = 0.022]. LACI may prove to be a valuable tool for assessing LA function in patients with CKD, and could be integrated into the routine assessment of LA for the purpose of prognostic assessment and clinical decision-making in patients with CKD.

Incidence of clinical outcomes in heart failure patients with and without advanced chronic kidney disease.

Chronic kidney disease (CKD) is a well-established risk factor for heart failure (HF); however, patients with an estimated glomerular filtration rate (eGFR)<30mL/min/1.73m2 have been systematically excluded from clinical trials. This study investigated the incidence of HF and kidney outcomes in HF patients with and without advanced CKD, that is, eGFR<30. From nationwide registries, HF patients were identified from 2014 to 2018 and categorized into three groups according to baseline eGFR (eGFR≥60, 60>eGFR≥30 and eGFR<30). The incidence of primary outcomes (all-cause mortality, HF hospitalization, end-stage kidney disease and sustained 50% eGFR decline) was estimated using cumulative incidence functions. Of the 21959 HF patients included, the median age was 73.9years, and 30% of patients had an eGFR between 30 and 60 and 7% had an eGFR<30. The 4year incidence of all-cause mortality was highest for patients with eGFR<30 (28.3% for patients with eGFR≥60, 51.6% for patients with 60>eGFR≥30 and 72.2% for patients with eGFR<30). The 4year incidence of HF hospitalization was comparable between the groups (25.8%, 29.8% and 26.1% for patients with eGFR≥60, 60>eGFR≥30 and eGFR<30, respectively). For patients with eGFR<30, kidney outcomes were four times more often the first event than patients with eGFR>30 (4year incidence of kidney outcome as the first event was 5.0% for eGFR≥60, 4.8% for 60>eGFR≥30 and 20.1% for eGFR<30). Patients with advanced CKD had a higher incidence of mortality and poorer kidney outcomes than those without advanced CKD, but a similar incidence of HF hospitalizations.

Association between glycated albumin and adverse outcomes in patients with heart failure.

Diabetes mellitus is a traditional risk factor for heart failure (HF), and glycated albumin (GA) is a marker to assess short-term glycemic control. Whether GA has prognostic significance in patients with HF remains unclear. A total of 717 patients with HF were enrolled in the prospective cohort study. Patients were grouped by the normal upper limit of GA (17%). Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate the association between GA and prognosis. During a mean follow-up of 387 days, 232 composite endpoint events of hospitalization for HF or all-cause death occurred. Kaplan-Meier analysis showed a higher rate of adverse events in the higher GA group (GA >17%; log-rank test P < 0.001). GA was an independent predictor of adverse events, both as a continuous variable (per 1% change: hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.00-1.06, P = 0.030) and as a categorical variable (GA >17%: HR 1.36, 95% CI 1.03-1.80, P = 0.032). Restricted cubic splines showed a linear association between GA and adverse events (P for non-linearity = 0.231). There was no significant difference in adverse outcome risk between those with diabetes and GA ≤17% and those without diabetes, whereas the prognosis was worse in those with diabetes and GA >17% (HR 1.56, 95% CI 1.16-2.11, P = 0.004). Compared to the group with normal levels of GA and glycated hemoglobin, the group with GA >17% and glycated hemoglobin >6.5% had a higher risk of adverse events (HR 1.49, 95% CI 1.06-2.10, P = 0.022). GA was an independent predictor of HF prognosis. Combining GA and glycated hemoglobin might improve the predictive power of adverse outcomes in patients with HF.

Screening of Secretory Proteins Linking Major Depressive Disorder with Heart Failure Based on Comprehensive Bioinformatics Analysis and Machine Learning.

Major depressive disorder (MDD) plays a crucial role in the occurrence of heart failure (HF). This investigation was undertaken to explore the possible mechanism of MDD's involvement in HF pathogenesis and identify candidate biomarkers for the diagnosis of MDD with HF. GWAS data for MDD and HF were collected, and Mendelian randomization (MR) analysis was performed to investigate the causal relationship between MDD and HF. Differential expression analysis (DEA) and WGCNA were used to detect HF key genes and MDD-associated secretory proteins. Protein-protein interaction (PPI), functional enrichment, and cMAP analysis were used to reveal potential mechanisms and drugs for MDD-related HF. Then, four machine learning (ML) algorithms (including GLM, RF, SVM, and XGB) were used to screen candidate biomarkers, construct diagnostic nomograms, and predict MDD-related HF. Furthermore, the MCPcounter algorithm was used to explore immune cell infiltration in HF, and MR analysis was performed to explore the causal effect of immunophenotypes on HF. Finally, the validation of the association of MDD with reduced left ventricular ejection fraction (LVEF) and the performance assessment of diagnostic biomarkers was accomplished based on animal models mimicking MDD. The MR analysis showed that the MDD was linked to an increased risk of HF (OR = 1.129, p < 0.001). DEA combined with WGCNA and secretory protein gene set identified 315 HF key genes and 332 MDD-associated secretory proteins, respectively. Through PPI and MCODE analysis, 78 genes were pinpointed as MDD-related pathogenic genes for HF. The enrichment analysis revealed that these genes were predominantly enriched in immune and inflammatory regulation. Through four ML algorithms, two hub genes (ISLR/SFRP4) were identified as candidate HF biomarkers, and a nomogram was developed. ROC analysis showed that the AUC of the nomogram was higher than 0.90 in both the HF combined dataset and two external cohorts. In addition, an immune cell infiltration analysis revealed the immune dysregulation in HF, with ISLR/SFRP4 displaying notable associations with the infiltration of B cells, CD8 T cells, and fibroblasts. More importantly, animal experiments showed that the expression levels of ISLR (r = -0.653, p < 0.001) and SFRP4 (r = -0.476, p = 0.008) were significantly negatively correlated with LVEF. The MR analysis indicated that MDD is a risk factor for HF at the genetic level. Bioinformatics analysis and the ML results suggest that ISLR and SFRP4 have the potential to serve as diagnostic biomarkers for HF. Animal experiments showed a negative correlation between the serum levels of ISLR/SFRP4 and LVEF, emphasizing the need for additional clinical studies to elucidate their diagnostic value.

Risk factors and incidence of new-onset heart failure with conventional pacemaker implant: A nationwide study

BackgroundStudies have shown that the risk of new-onset heart failure (HF) is higher post-implant for patients receiving right ventricular pacing. ObjectiveThis study aimed to investigate incidence, risk factors and implications for long-term prognosis of new-onset HF in patients after pacemaker-implant. MethodsPatients without preexisting HF who received a pacemaker in Sweden during the period 2005-2020 were identified via the nationwide Pacemaker Registry. Data was crossmatched with the population registry and national disease registries. Primary outcome was new-onset HF within 5 years, and a risk score for this was developed and validated.. ResultsIn all, 65579 patients met the inclusion criteria (10351 single chamber ventricular and 55228 dual chamber pacemakers). 13792 (21.0%) patients were diagnosed with HF within five years post-implant. Of these, 6244 (45.3%) were hospitalized for HF. Patients with new-onset heart failure were more likely to die within five years (41.2% vs. 19.7%, p<0.0001). Risk factors for new-onset HF included increasing age, male sex, hypertension, diabetes, atrial fibrillation, chronic lung- and kidney disease, ischemic heart disease, and AV block. In a combined score using these variables, patients in the highest risk-score quartile had a hazard ratio of 5.36 [4.91-5.86] (p<0.001) and an absolute risk of 32% for developing HF. ConclusionPacemaker therapy is associated with >20% risk of new-onset HF within five years, and we identified nine risk factors associated with the diagnosis of new-onset HF. The proposed score based on these variables can be used to identify patients at high risk for new-onset heart failure.

SNX5-Rab11a protects against cardiac hypertrophy through regulating LRP6 membrane translocation

BackgroundsPathological cardiac hypertrophy is considered one of the independent risk factors for heart failure, with a rather complex pathogenic machinery. Sorting nexins (SNXs), denoting a diverse family of cytoplasmic- and membrane-associated phosphoinositide-binding proteins, act as a pharmacological target against specific cardiovascular diseases including heart failure. Family member SNX5 was reported to play a pivotal role in a variety of biological processes. However, contribution of SNX5 to the development of cardiac hypertrophy, remains unclear. MethodsMice underwent transverse aortic constriction (TAC) to induce cardiac hypertrophy and simulate pathological conditions. TAC model was validated using echocardiography and histological staining. Expression of SNX5 was assessed by western blotting. Then, SNX5 was delivered through intravenous administration of an adeno-associated virus serotype 9 carrying cTnT promoter (AAV9-cTnT-SNX5) to achieve SNX5 cardiac-specific overexpression. To assess the impact of SNX5, morphological analysis, echocardiography, histological staining, hypertrophic biomarkers, and cardiomyocyte contraction were evaluated. To unravel potential molecular events associated with SNX5, interactome analysis, fluorescence co-localization, and membrane protein profile were evaluated. ResultsOur results revealed significant downregulated protein level of SNX5 in TAC-induced hypertrophic hearts in mice. Interestingly, cardiac-specific overexpression of SNX5 improved cardiac function, with enhanced left ventricular ejection fraction, fraction shortening, as well as reduced cardiac fibrosis. Mechanistically, SNX5 directly bound to Rab11a, increasing membrane accumulation of Rab11a (a Rab GTPase). Afterwards, this intricate molecular interaction upregulated the membrane content of low-density lipoprotein receptor-related protein 6 (LRP6), a key regulator against cardiac hypertrophy. Our comprehensive assessment of siRab11a expression in HL-1 cells revealed its role in antagonism of LRP6 membrane accumulation under SNX5 overexpression. ConclusionsThis study revealed that binding of SNX5 with LRP6 triggers their membrane translocation through Rab11a assisting, defending against cardiac remodeling and cardiac dysfunction under pressure overload. These findings provide new insights into the previously unrecognized role of SNX5 in the progression of cardiac hypertrophy.

Prevalence and Risk Factors of Heart Failure with Preserved Ejection Fraction in Middle-Aged Maintenance Haemodialysis Patients on a Twice-Weekly Schedule: Experience from a Single Indian Centre.

Background. Data on the prevalence of cardiac failure with preserved ejection in the haemodialysis population, which impacts treatment strategy, mortality, and morbidity, are scarce. Aims and Objectives. Estimate the prevalence of heart failure with preserved ejection fraction (HFpEF) in haemodialysis patients Classify cardiac failure and ascertain the risk factors influencing HFpEF in haemodialysis patients. Methods. All consenting individuals on haemodialysis over 18 years of age were included. Lung ultrasound was performed as per the LUST study protocol, and the labs were documented. Echocardiographic parameters were measured using two-dimensional (2D ECHO). Results. A total of 102 patients consented to participate in the study, which included 63 males (61.8%) and 39 females (38.2%). The mean patient age was 53 ± 13.1 years. The dialysis vintage of the participants was 38.92 ± 6.947 months. 47 (46.1%) patients had diabetes and 88 (80.4%) had hypertension. ECG findings included sinus rhythm (51/102, 50%), sinus tachycardia (22/102, 21.6%), ST-T wave abnormalities (18/102, 17.6%), and atrial fibrillation (11/102, 10.8%). Heart failure with preserved ejection fraction (HFpEF) was present in 44/102 (43.14%), heart failure with mid-range EF in 14/102 (13.72%), and heart failure with reduced EF in 13/102 (12.7%) patients. The ejection fraction was positively associated with haemoglobin (r = 0.23; p = 0.044), and calcium levels (r = 0.25; p =0 .03). E/lateral e' ratio was positively correlated with NT pro-BNP (r = 0.63; p < 0.001), systolic blood pressure (r = 0.44; p = 0.003) and age (r = 0.353; p = 0.003) and negatively correlated with transferrin saturation (r = -0.353; p = 0.027) and diastolic blood pressure (r = -0.31; p = 0.040). Binary logistic regression analysis revealed that the odds of diastolic dysfunction increased by 2.3 times with each unit increase of creatinine, and diabetics have 7.66 times higher risk for diastolic dysfunction. Binary logistic regression involving ejection fraction (EF) and all laboratory and clinical parameters revealed odds of HFpEF increased by 1.93 times with each unit increase in age, odds of HFpEF increases by 1.53 times with each unit increase in phosphorous and odds of HFpEF increased by 1.1 times with a unit increase of systolic blood pressure. Conclusion. HFpEF is the predominant form of heart failure in haemodialysis patients. Haemoglobin and calcium were positively associated with ejection fraction. Advancing age, elevated creatinine and diabetes mellitus levels are independent predictors of diastolic dysfunction in haemodialysis patients.

Association of body adiposity with left ventricular concentric remodeling and diastolic dysfunction

AbstractBackgroundObesity is a significant risk factor for heart failure with preserved ejection fraction (HFpEF). In this study, we explore the relationships between body mass index (BMI) and adipose tissue compartments such as visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT), with respect to left ventricular (LV) structure and function in subjects with preserved LV systolic function.MethodsBetween January and December 2020, this retrospective study included 749 participants who exhibited preserved LV systolic function and underwent transthoracic echocardiography along with abdominal computed tomography. LV structural and functional variables as well as EAT, VAT, and SAT thickness were evaluated using echocardiography and computed tomography.ResultsSAT decreased, while VAT and EAT progressively increased with age. There were significant correlations between BMI and various adipose tissues, with the strongest correlation observed with SAT (r = .491, p &lt; .001) compared to VAT (r = .371, p &lt; .001) or EAT (r = .135, p &lt; .001). However, EAT demonstrated the most substantial association with decreased LV end‐diastolic dimension, LV end‐systolic dimension, and septal mitral annular velocity and increased relative wall thickness (all p &lt; .05), while VAT and SAT did not show significant associations with LV remodeling and functional parameters after adjusting for clinical variables.ConclusionEAT is the most critical adipose tissue influencing LV geometric and functional changes, compared with VAT or SAT. Thick EAT is associated small LV chamber size, concentric remodeling, and relaxation abnormalities.

TNIP3 protects against pathological cardiac hypertrophy by stabilizing STAT1

Pathological cardiac hypertrophy is one of the major risk factors of heart failure and other cardiovascular diseases. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. Here, we identified the first evidence that TNFAIP3 interacting protein 3 (TNIP3) was a negative regulator of pathological cardiac hypertrophy. We observed a significant upregulation of TNIP3 in mouse hearts subjected to transverse aortic constriction (TAC) surgery and in primary neonatal rat cardiomyocytes stimulated by phenylephrine (PE). In Tnip3-deficient mice, cardiac hypertrophy was aggravated after TAC surgery. Conversely, cardiac-specific Tnip3 transgenic (TG) mice showed a notable reversal of the same phenotype. Accordingly, TNIP3 alleviated PE-induced cardiomyocyte enlargement in vitro. Mechanistically, RNA-sequencing and interactome analysis were combined to identify the signal transducer and activator of transcription 1 (STAT1) as a potential target to clarify the molecular mechanism of TNIP3 in pathological cardiac hypertrophy. Via immunoprecipitation and Glutathione S-transferase assay, we found that TNIP3 could interact with STAT1 directly and suppress its degradation by suppressing K48-type ubiquitination in response to hypertrophic stimulation. Remarkably, preservation effect of TNIP3 on cardiac hypertrophy was blocked by STAT1 inhibitor Fludaradbine or STAT1 knockdown. Our study found that TNIP3 serves as a novel suppressor of pathological cardiac hypertrophy by promoting STAT1 stability, which suggests that TNIP3 could be a promising therapeutic target of pathological cardiac hypertrophy and heart failure.