Higher Risk Of Heart Failure Research Articles

Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction

Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac dysfunction which precede HF are not well-defined. Among older individuals without HF in the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of 47 circulating metabolites measured by 1H-NMR with echocardiographic measures of cardiac structure and function. We then evaluated associations of significant metabolites with circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a separate cohort, we evaluated differences between top metabolites in patients with HF with preserved ejection fraction (HFpEF) and comorbidity-matched controls. Genetic variants associated with top metabolites (mQTLs) were then related to echocardiographic measures and NT-proBNP. Among 3440 individuals with metabolic and echocardiographic data in MESA (62 ± 10 years, 52% female, 38% White), 10 metabolites broadly reflective of glucose and amino acid metabolism were associated with at least 1 measure of cardiac structure or function. Of these 10 metabolites, 4 (myo-inositol, glucose, dimethylsulfone, carnitine) were associated with higher NT-proBNP and 2 (d-mannose, acetone) were associated with lower NT-proBNP. In a separate cohort, patients with HFpEF had higher circulating myo-inositol levels compared with comorbidity-matched controls. Genetic analyses revealed that 1 of 6 known myo-inositol mQTLs conferred risk of higher NT-proBNP. In conclusion, metabolomic profiling identifies several novel metabolites associated with cardiac dysfunction in a cohort at high risk for HF, revealing pathways potentially relevant to future HF risk.

Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial

BackgroundPeople with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent ≥50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m2, kidney replacement therapy, and kidney or CV death) by 24%. ObjectivesThis prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population. MethodsParticipants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee. ResultsA total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment. ConclusionsSemaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153)

Prevalence, Cardiac Phenotype, and Outcomes of Transthyretin Variants in the UK Biobank Population

The population prevalence of cardiac transthyretin amyloidosis (ATTR) caused by pathogenic variation in the TTR gene (vATTR) is unknown. To estimate the population prevalence of disease-causing TTR variants and evaluate associated phenotypes and outcomes. This population-based cohort study analyzed UK Biobank (UKB) participants with whole-exome sequencing, electrocardiogram, and cardiovascular magnetic resonance data. Participants were enrolled from 2006 to 2010, with a median follow-up of 12 (IQR, 11-13) years (cutoff date for the analysis, March 12, 2024). Sixty-two candidate TTR variants were extracted based on rarity (minor allele frequency ≤0.0001) and/or previously described associations with amyloidosis if more frequent. Carrier status for TTR variants. Associations of TTR carrier status with vATTR prevalence and cardiovascular imaging and electrocardiogram traits were explored using descriptive statistics. Associations between TTR carrier status and atrial fibrillation, conduction disease, heart failure, and all-cause mortality were evaluated using adjusted Cox proportional hazards models. Genotypic and diagnostic concordance was examined using International Statistical Classification of Diseases, Tenth Revision codes from the hospital record. The overall cohort included 469 789 UKB participants (mean [SD] age, 56.5 [8.1] years; 54.2% female and 45.8% male). A likely pathogenic/pathogenic (LP/P) TTR variant was detected in 473 (0.1%) participants, with Val142Ile being the most prevalent (367 [77.6%]); 91 individuals (0.02%) were carriers of a variant of unknown significance . The overall prevalence of LP/P variants was 0.02% (105 of 444 243) in participants with European ancestry and 4.3% (321 of 7533) in participants with African ancestry. The LP/P variants were associated with higher left ventricular mass indexed to body surface area (β = 4.66; 95% CI, 1.87-7.44), and Val142Ile was associated with a longer PR interval (β = 18.34; 95% CI, 5.41-31.27). The LP/P carrier status was associated with a higher risk of heart failure (hazard ratio [HR], 2.68; 95% CI, 1.75-4.12) and conduction disease (HR, 1.88; 95% CI, 1.25-2.83). Higher all-cause mortality risk was observed for non-Val142Ile LP/P variants (HR, 1.98; 95% CI, 1.06-3.67). Thirteen participants (2.8%) with LP/P variants had diagnostic codes compatible with cardiac or neurologic amyloidosis. Variants of unknown significance were not associated with outcomes. This study found that approximately 1 in 1000 UKB participants were LP/P TTR variant carriers, exceeding previously reported prevalence. The findings emphasize the need for clinical vigilance in identifying individuals at risk of developing vATTR and associated poor outcomes.

Associations between dimensions of the social environment and cardiometabolic health outcomes: a systematic review and meta-analysis

ObjectivesThe social environment (SE), that is, the social relationships and social context in which groups of people live and interact, is an understudied element of the broader living environment which...

Progression of Heart Failure in People with Type 2 Diabetes in Germany: An Analysis Using German Health Insurance Claims Data.

Background: Individuals with type 2 diabetes (T2D) show high risk of heart failure (HF). Left ventricular ejection fraction is a major factor for disease progression. In Germany, no recent longitudinal data are available. Objectives: To (1) measure the proportion of individuals with T2D who acquire HF over 2 years and (2) categorize ejection fraction using routine data and an algorithm, and (3) understand progression of HF in 5-year follow-up. Methods: This descriptive, retrospective study used longitudinal data from German statutory health insurance claims. A model using coded data classified the patients with HF into ejection fraction (EF) categories. Individuals were selected during 2013, with an inclusion period from 2014 to 2015 and a follow-up from 2016 to 2020. Baseline characteristics included demographic data, disease stage, comorbidities, and risk factors. Follow-up criteria included major adverse cardiac events (MACEs), EF category, and mortality. Disease progression was visualized by Sankey plots. Results: Among the 173 195 individuals with T2D identified in 2013, 6725 (median age, 74 years) developed HF in 2014 or 2015. 34.4% of individuals had MACEs, and 42.9% died over 5 years. Myocardial infarction (42%) was the most common event, followed by stroke (32%) and hospitalization (28%). A total of 5282 (78.54%) patients were classified into preserved EF and 1443 (21.46%) into reduced EF. Survival after 5 years was 71% in HF for preserved EF patients, and 29% in the HF for those with reduced EF. Conclusion: Heart failure is relevant in individuals with diabetes. A high number of patients may likely not survive a 5-year period. Validation of the model with German data is highly desirable. New ways of close monitoring could help improve outcomes.

Relationship of the trajectory of the triglyceride-glucose index with heart failure: the Kailuan study

BackgroundA high triglyceride-glucose index (TyG) is associated with a higher risk of incident heart failure. However, the effects of longitudinal patterns of TyG index on the risk of heart failure remain to be characterized. Therefore, in the present study, we aimed to characterize the relationship between the trajectory of TyG index and the risk of heart failure.MethodsWe performed a prospective study of 56,149 participants in the Kailuan study who attended three consecutive surveys in 2006–2007, 2008–2009, and 2010–2011 and had no history of heart failure or cancer before the third wave survey (2010–2011). The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2], and we used latent mixture modeling to characterize the trajectory of the TyG index over the period 2006–2010. Additionally, Cox proportional risk models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for incident heart failure for the various TyG index trajectory groups.ResultsFrom 2006 to 2010, four different TyG trajectories were identified: low-stable (n = 13,554; range, 7.98–8.07), moderate low-stable (n = 29,435; range, 8.60–8.65), moderate high-stable (n = 11,262; range, 9.31–9.30), and elevated-stable (n = 1,898; range, 10.04–10.25). A total of 1,312 new heart failure events occurred during a median follow-up period of 10.04 years. After adjustment for potential confounders, the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident heart failure for the elevated-stable, moderate high-stable, and moderate low-stable groups were 1.55 (1.15, 2.08), 1.32 (1.08, 1.60), and 1.17 (0.99, 1.37), respectively, compared to the low-stable group.ConclusionsHigher TyG index trajectories were associated with a higher risk of heart failure. This suggests that monitoring TyG index trajectory may help identify individuals at high risk for heart failure and highlights the importance of early control of blood glucose and lipids for the prevention of heart failure.

Prediction of 28-Day All-Cause Mortality in Heart Failure Patients with Clostridioides difficile Infection Using Machine Learning Models: Evidence from the MIMIC-IV Database.

Heart failure (HF) may induce bowel hypoperfusion, leading to hypoxia of the villa of the bowel wall and the occurrence of Clostridioides difficile infection (CDI). However, the risk factors for the development of CDI in HF patients have yet to be fully illustrated, especially because of a lack of evidence from real-world data. Clinical data and survival situations of HF patients with CDI admitted to ICU were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. For developing a model that can predict 28-day all-cause mortality in HF patients with CDI, the Recursive Feature Elimination with Cross-Validation (RFE-CV) method was used for feature selection. And nine machine learning (ML) algorithms, including logistic regression (LR), decision tree, Bayesian, adaptive boosting, random forest (RF), gradient boosting decision tree, XGBoost, light gradient boosting machine, and categorical boosting, were applied for model construction. After training and hyperparameter optimization of the models through grid search 5-fold cross-validation, the performance of models was evaluated by the area under curve (AUC), accuracy, sensitivity, specificity, precision, negative predictive value, and F1 score. Furthermore, the SHapley Additive exPlanations (SHAP) method was used to interpret the optimal model. A total of 526 HF patients with CDI were included in the study, of whom 99 cases (18.8%) experienced death within 28 days. Eighteen of the 57 variables were selected for the model construction algorithm for model construction. Among the ML models considered, the RF model emerged as the optimal model achieving the accuracy, F1-score, and AUC values of 0.821, 0.596, and 0.864, respectively. The net benefit of the model surpassed other models at 16%-22% threshold probabilities based on decision curve analysis. According to the importance of features in the RF model, red blood cell distribution width, blood urea nitrogen, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment, and white blood cell count were highlighted as the five most influential variables. We developed ML models to predict 28-day all-cause mortality in HF patients associated with CDI in the ICU, which are more effective than the conventional LR model. The RF model has the best performance among all the ML models employed. It may be useful to help clinicians identify high-risk HF patients with CDI.

Sodium-glucose cotransporter 2 inhibitors reduce the risk of incident type 2 diabetes in people with heart failure without diabetes: An analysis of real-world, cohort data.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is), used as a glucose-lowering therapy in people with type 2 diabetes (T2D), have significant cardiorenal benefits, reducing hospitalization for heart failure (HF) and cardiovascular mortality in patients with and without T2D. Recent clinical trial evidence suggests their potential utility in preventing incident T2D among the high-risk HF populations. Therefore, we aimed to assess whether this finding was reproducible in a real-world setting. We performed a retrospective cohort analysis of 484 643 patients with HF, without baseline diabetes, prescribed either angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers with/without SGLT2is (treatment, n = 42 018; reference, n = 442 625) across 95 global health care organizations, using a large real-world ecosystem. Propensity score matching balanced arms 1:1 for confounders (n = 39 168 each arm). Subgroup analysis further evaluated the impact on patients with prediabetes and the efficacy of dapagliflozin/empagliflozin, specifically, on incident T2D and secondary outcomes, including all-cause mortality, acute pulmonary oedema and hospitalization. Treatment with SGLT2is significantly reduced incident T2D {hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.63, 0.75]} in patients with HF. The analysis of patients with prediabetes found that SGLT2is further reduced incident T2D [HR 0.62 (95% CI 0.45, 0.80)]. The magnitude of reduction in incident T2D was higher in patients prescribed dapagliflozin [HR 0.47 (95% CI 0.39, 0.56)] versus empagliflozin [HR 0.81 (95% CI 0.70, 0.93)]. Treatment with SGLT2is in patients with HF was associated with a reduced risk of incident T2D, most strikingly in people with prediabetes.

Association between cardiac time intervals and incident heart failure after acute coronary syndrome

BackgroundCardiac time intervals are sensitive markers of myocardial dysfunction that predispose to heart failure (HF). We aimed to investigate the association between cardiac time intervals and HF in patients with acute coronary syndrome (ACS).MethodsThis study included 386 ACS patients treated with percutaneous coronary intervention (PCI). Patients underwent an echocardiography examination a median of two days after PCI. Cardiac time intervals including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and systolic ejection time (ET), and myocardial performance index (MPI) were obtained by tissue Doppler echocardiography. The outcome was incident HF.ResultsDuring follow-up (median 4.3, IQR:1.0-6.7 years), 140 (36%) developed HF. In unadjusted analyses, IVRT was not associated with HF (HR 1.02 (0.95–1.10), p = 0.61, per 10ms increase), and neither was IVCT (HR 0.07 (0.95–1.22), p = 0.26, per 10ms increase). Increasing MPI was associated with a higher risk of HF (HR 1.20 (1.08–1.34), P = 0.001, per 0.1 increase), and so was decreasing ET (HR 1.13 (1.07–1.18), P < 0.001 per 10ms decrease). After multivariable adjustment for cardiovascular risk factors, MPI (HR 1.13 (1.01–1.27), P = 0.034) and ET (HR 1.09 (1.01–1.17), P = 0.025) remained significantly associated with incident HF. LVEF modified the association between ET and HF (p for interaction = 0.002), such that ET was associated with HF in patients with LVEF ≥ 36% (HR = 1.15 (1.06–1.24), P = 0.001, per 10ms decrease).ConclusionIn patients admitted with ACS, shortened ET and higher MPI were independently associated with an increased risk of incident HF. Additionally, ET was associated with incident HF in patients with LVEF above 36%.Graphical

Abstract Mo048: Cereblon as a potential biomarker for early detection of diabetic cardiomyopathy

Type 2 diabetes mellitus (T2DM) patients have a higher risk of heart failure and cause cardiomyopathy without other cardiac disease. There is no specific biomarker for discriminating patients with diabetic cardiomyopathy (DCM). In this study, we investigated the cereblon (CRBN) level in mice and human samples to determine its potential as a biomarker for early detection of diabetic cardiomyopathy (DCM). C57BL/db/db male mice at 6 and 8 weeks of age, as the early DCM model with obesity and T2DM were investigated. We confirmed that mitochondrial function was decreased in the 8 weeks old db/db mice without alterations of cardiac function and structures. Compared to the control mice, CRBN protein level was significantly increased and phosphorylation of AMPK, a negative regulator by CRBN, was significantly decreased in the heart tissue of 8 weeks old db/db mice. Blood CRBN level was also significantly increased in both 6 and 8 weeks old db/db mice compared with control mice. In blood of diabetic patients, CRBN level was significantly correlated with IL-6, IL-1b, TNF-a, IGFBP-7, and adiponectin, which are previously reported biomarkers of DCM. However, CRBN level was not correlated with cardiac troponin I, NT-proBNP, and ST2, which are biomarkers of myocardial injury and heart failure. Furthermore, the CRBN level showed a higher tendency in patients with diastolic dysfunction without systolic dysfunction compared to patients with normal function and systolic dysfunction, although the difference was not statistically significant. In conclusion, cardiac mitochondrial dysfunction occured and CRBN levels of heart and blood increased prior to cardiac functional and structural changes in the early DCM mouse model, and CRBN might serve as a potential biomarker for the early detection of DCM in T2DM patients.

Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study.

Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown. The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method. Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61-1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59-1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56-0.98] and 0.65 [95% CI, 0.44-0.97], respectively). In an older population with additional stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Predicting cardiovascular events in out-of-hospital patients presenting with atypical chest pain and complete left bundle branch block: role of CTA and echocardiographic Global Longitudinal Strain.

Out-of-hospital patients presenting with atypical chest pain and complete left bundle branch block (LBBB) have to be stratified for the presence of coronary artery disease and the risk of developing heart failure (HF). We investigated the prognostic role of coronary CT-angiography (CTA) and echocardiographic global longitudinal strain (GLS) in those patients in a mid-term follow-up. Out-of-hospital patients with LBBB underwent echocardiography and a 64-slice CT angiography were evaluated retrospectively. Development of HF or a cardiovascular death were the events scheduled. Seventy-eight patients (32 female; mean age: 66.0 ± 10.4 years were enrolled. During a follow-up of 33 months (IQR: 17-77), one patient (1.5%) experienced a cardiovascular death, 14 patients (17.9%) required urgent outpatient visits due to acute decompensated HF (12 hospitalizations). Echocardiography showed a slightly reduced left ventricular ejection fraction (LVEF) (50.0% ± 9.8%) and GLS within the normal range (-16.2% ± 4.1%). CTA analysis showed coronary stenosis > 50% in 28 patients (35.9%). A high Agatston score (> 100) was observed in 29.5%. Notably, 25 patients (32.1%) were diagnosed with left main coronary artery disease and 15 patients (16.7%) underwent revascularization during the follow up. Significant associations were observed between events and LVEF (P = 0.001), diastolic dysfunction grade ≥ 2 (P = 0.02), GLS (P < 0.001), multiple coronary stenosis (P = 0.04) and Agatston score (P = 0.05). Multivariate analysis confirmed the relationships with LVEF (R2 = 0.89, P < 0.001), diastolic dysfunction (R2 = 3.30, P = 0.04), GLS (R2 = 1.43, P < 0.001), and Agatston score (R2 = 1.01, P = 0.05). In patients with complete LBBB, CTA and GLS identified those at a high risk of development HF.

Determinants of transthyretin levels and their association with adverse clinical outcomes among UK Biobank participants

Transthyretin is a transport protein whose misfolding has been implicated in the development of cardiac amyloidosis. Here, we examine the clinical correlates of transthyretin levels, the differences in transthyretin levels according to the pathogenic V142I TTR variant carrier status, and the association of transthyretin levels with outcomes among 35,206 UK Biobank participants who underwent plasma profiling and were free from prevalent cardiovascular disease and chronic renal disease. Transthyretin levels are lower in females, decrease with increasing C-reactive protein levels, and increase with body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, albumin levels, triglyceride levels, and creatinine levels. V142I non-carriers [n = 35,167, mean: −0.1 (0.3)] have higher adjusted transthyretin levels compared with the carriers [n = 39, mean: −0.5 (0.3)] (p:<0.001). A standard deviation decrease in transthyretin levels increases the risk of heart failure [HRadj: 1.17 (95% Confidence Interval = 1.08–1.26)] and all-cause mortality [HRadj: 1.18 (95% Confidence Interval = 1.14–1.24)]. This study shows that individuals with low transthyretin levels, such as those carrying the V142I variant, are at a higher risk of heart failure and mortality.

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.

Cardiovascular disease risk factors in congenital heart disease survivors are associated with heart failure.

Despite advances in treatment and survival, individuals with congenital heart defects (CHD) have a higher risk of heart failure (HF) compared to the general population. To evaluate comorbidities associated with HF in patients with CHD with a goal of identifying potentially modifiable risk factors that may reduce HF-associated morbidity and mortality. Five surveillance sites in the United States linked population-based healthcare data and vital records. Individuals with an ICD-9-CM code for CHD aged 11-64 years were included and were stratified by presence of HF diagnosis code. Prevalence of death and cardiovascular risk factors based on diagnosis codes were compared by HF status using log-linear regression. A total of 25,343 individuals met inclusion/exclusion criteria. HF was documented for 2.2% of adolescents and 12.9% of adults with CHD. Adolescents and adults with HF had a higher mortality than those without HF. In both age groups, HF was positively associated with coronary artery disease, hypertension, obesity, diabetes, and increased healthcare utilization compared to those without HF. Within this population-based cohort, over 1 in 50 adolescents and 1 in 8 adults with CHD had HF, which was associated with increased mortality. Modifiable cardiovascular comorbidities were associated with HF. Five sites in the United States linked population-based healthcare data and vital records to establish surveillance network for identifying the factors which influence congenital heart disease (CHD) outcomes. Survivors of CHD frequently develop heart failure across the lifespan. Over 1 in 50 adolescent and 1 in 8 adult survivors of CHD have heart failure which is associated with increased mortality compared to CHD survivors without heart failure. Heart failure development is associated with potentially modifiable cardiovascular risk factors such as hypertension, coronary artery disease, and diabetes. Controlling modifiable cardiovascular risk factors may serve to lower the risk of heart failure and mortality in survivors of congenital heart disease of all ages.

Adiposity, fat-free mass and incident heart failure in 500 000 individuals

Background and aimsThe independent role of body fat distribution and fat-free mass in heart failure (HF) risk is unclear. We investigated the role of different body composition compartments in risk...

Echocardiography-Derived Hemodynamic Forces Are Associated with Clinical Outcomes in Patients with Non-Ischemic Dilated Cardiomyopathy.

Introduction: Non-ischemic dilated cardiomyopathy (NIDCM) is characterized by a reduced left ventricular (LV) ejection fraction (LVEF, <50%) and a high risk for heart failure (HF) and death. Echocardiography-derived hemodynamic forces (HDFs) may provide important information on LV mechanics, but their prognostic value is unknown. Aim: To explore the features of echocardiography-derived HDFs in NIDCM and their association with clinical endpoints. Methods: Asymptomatic, non-hospitalized NIDCM patients free from coronary artery disease and moderate or severe valvular heart disease were included in this single-center observational retrospective longitudinal study. Those with atrial fibrillation and a follow-up <12 months were excluded. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death, HF hospitalization, and ambulatory intravenous diuretics administration. LV HDFs were analyzed with a prototype software. Apex-base (HDFs-ab), lateral-septal (HDFs-ls), and HDFs-angle were computed. Results: Ninety-seven patients were included, sixty-seven (69%) were males, mean age was 62 ± 14 years, and mean LVEF was 39.2 ± 8.6%. During a median follow-up of 4.2 (3.1-5.1) years, 19 (20%) patients experienced MACE. These patients had a higher HDFs-angle (71.0 (67.0-75.0) vs. 68.0 (63.0-71.0)°, p = 0.005), lower HDFs-ls (1.36 (1.01-1.85) vs. 1.66 ([1.28-2.04])%, p = 0.015), but similar HDFs-ab (5.02 (4.39-6.34) vs. 5.66 (4.53-6.78)%, p = 0.375) compared to those without MACE. in a Cox regression analysis, HDFs-angle (HR 1.16 (95%-CI 1.04-1.30), p = 0.007) was associated with MACE, while other conventional echocardiography parameters, including LVEF and LV longitudinal strain, were not. Conclusions: HDFs-angle is associated with clinical endpoints in NIDCM. A higher HDFs-angle may be a marker of impaired myocardial performance in patients with reduced LVEF.

Effects of ankylosing spondylitis on cardiovascular disease: aMendelian randomization study.

Accumulating evidence suggests that patients with ankylosing spondylitis (AS) have an elevated risk for cardiovascular disease (CVD) and cardiovascular death, however, whether AS has causal effects on the risk of CVD is unclear.Two-sample Mendelian randomization (MR) was utilizedto examine the probable causal link between them. Summary statistics from publicly released genome-wide association studies (GWAS) was used to perform MR analyses. Genetically predicted AS was selected as the exposure variable from published GWAS meta-analyses. CVD was adopted as the outcome variable. The inverse variant weighted method was employed to obtain the casual estimates. The robustness of the results was also examined by evaluating the pleiotropy and heterogeneity of single-nucleotide polymorphisms. According to MR analyses, genetic susceptibility to AS was associated with a high risk of heart failure and ischemic stroke, while negativelygenetic susceptibility was found between AS and peripheral atherosclerosis. No statistical relationship was found between AS and venous thromboembolism, atrial fibrillation, coronary atherosclerosis, and valvular heart disease. Sensitivity analysis showed no evidence of horizontal pleiotropy or heterogeneity. The present study suggests that AS exerts causal effects on the risk of CVD, including heart failure, ischemic stroke, and peripheral atherosclerosis.

An Early Accumulation of Serum Uric Acid Confers More Risk of Heart Failure: A 10-year Prospective Cohort Study.

Evidence on the longitudinal association of serum uric acid (SUA) with the risk of heart failure (HF) was limited and controversial. This study aimed to investigate the associations of cumulative SUA (cumSUA), incorporating its time course of accumulation, with the risk of HF. This prospective study enrolled 54,606 participants from the Kailuan study. The magnitude of SUA accumulation was expressed as cumSUA, exposure duration, and cumulative burden from baseline to the third survey, with cumSUA, calculated by multiplying mean values between consecutive examinations by time intervals between visits, as the primary exposure. During a median follow-up of 10.00 years, 1,260 cases of incident HF occurred. A higher risk of HF was observed in participants with the highest versus the lowest quartile of cumSUA (adjusted hazard ratio [aHR], 1.54; 95% confidence interval [CI], 1.29-1.84), 6-years (6 years) versus 0-year exposure duration (aHR, 1.87; 95% CI, 1.43-2.45), cumulative burden >0 versus =0 (aHR, 1.55; 95 CI, 1.29-1.86), and those with a negative versus positive SUA slope (aHR, 1.12; 95% CI, 1.02-1.25). When cumSUA was incorporated with its time course, those with cumSUA≥median and a negative SUA slope had the highest risk of HF (aHR, 1.55; 95% CI, 1.29-1.86). Incident HF risk was associated with the magnitude and time course of cumSUA accumulation. Early accumulation resulted in a greater risk of HF than later accumulation, indicating the importance of optimal SUA control earlier in life.

Identification of differentially expressed genes to predict the risk of heart failure in older patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common heart disease. Old people with HCM are at high risk of heart failure (HF). This study aimed to identify differentially expressed genes (DEGs) to evaluate the risk of HF in older patients with HCM. GSE89714 and GSE116250 were downloaded from Gene Expression Omnibus (GEO) database, and DEGs were identified by using limma R package with P < 0.05 and logFC> 1 as cut off. Protein-protein interaction (PPI) network, Genome Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the identified DEGs. NetworkAnalyst online tool was applied for Gene Set Enrichment Analysis (GSEA) analysis. We identified 124 overlap DEGs from the 2 datasets. PPI network showed that COL1A1, COL3A1, COL1A2, BGN, COL5A1, LUM, TGFB2, FMOD, ASPN, and COL14A1 were the top ten genes related to HCM and HF compared with control. Functional and pathway analyses showed that the overlap genes were mainly related to ECM-receptor interaction, ECM organization, Focal adhesion, PI3K-Akt signaling, TGF-beta signaling, and Platelet activation signaling and aggregation. Among the overlap genes, COL5A1 and LUM were significantly upregulated, while TGFB2, FMOD, ASPN, and COL14A1 were significantly downregulated in HF dataset compared with HCM dataset. Bioinformatics-based analysis revealed potential genes associated with HCM and HF, which could be utilized to evaluate the risk of HF in older patients with HCM.