Cases Of Heart Failure Research Articles

The burden and trends of heart failure caused by ischemic heart disease at the global, regional, and national levels from 1990 to 2021

Abstract Background Ischemic heart disease (IHD) is a major cause of heart failure (HF), a condition expected to increasingly affect global health and economics. This study evaluates the global burden, trends, and disparities of HF linked to IHD, aiming to inform health policy development. Methods Data from the Global Burden of Disease Study 2021 (GBD2021) is analyzed using Joinpoint regression, decomposition analysis, and Bayesian age-period-cohort analysis (BAPC). Health disparities are assessed through the Socio-demographic Index (SDI) via the Slope Index of Inequality (SII) and the Concentration Index (CI), with future trends projected from 2022 to 2045. Results In 2021, global HF cases due to IHD were over 19.16 million, with an age-standardized prevalence rate (ASPR) of 228.31 per 100 000 [95% UI, 188.18 to 279.55] and age-standardized years lived with disability (ASYLDs) rate of 20.43 per 100 000 [95% UI, 13.55 to 28.7].In 2021, there was a 2.87% increase in ASPR and ASYLDs compared to 1990, primarily driven by population growth and aging.Significant reductions in global ASPR and ASYLDs disparities are observed, though the disease burden has intensified in countries with lower SDI levels. Projections indicate that by 2045, while the prevalence and YLDs for HF caused by IHD will increase, while the ASPR and ASYLDs are expected to decrease. Conclusion The global burden of HF from IHD remains a significant concern. Urgent improvements in the allocation of medical resources and the implementation of effective prevention and management strategies are necessary to address this issue.

Abstract 4136932: Impact of Different Socioeconomic Metrics on Heart Failure-Related Admission and Short-Term Outcomes in Maryland

Introduction: Annually, over 500,000 Americans are hospitalized due to heart failure (HF), marking it as a major contributor to morbidity and mortality. It also poses a significant financial burden and leads to considerable losses in productivity. Objective: This study investigates the predictive accuracy of different socioeconomic metrics on the risk and outcomes of HF in Maryland. Methodology: A retrospective analysis of the Maryland State Inpatient Database (2016-2020) was conducted to assess the predictive accuracy of race/ethnicity, insurance status, household median income, and neighborhood poverty level (measured by the Distressed Communities Index) on the risk of heart failure-related hospital admissions and outcomes. Multivariate logistic regression models were also used to adjust for confounders. Result: During the study period, a total of 389,220 cases of HF were reported in the Maryland SID. The majority of these patients were white (56.8%) and female (51.1%), with a median age of 73 years (interquartile range [IQR] 62-82 years). The in-hospital mortality rate was 5.1%, while rates of atrial fibrillation, cardiac arrest and prolonged hospital stay were 34.4%, 0.3%, and 48.4%, respectively. Multivariate analysis revealed a substantial area under the ROC curve (AUC) indicating good model performance: 0.88 for predicting HF, 0.64 for atrial fibrillation, 0.64 for cardiac arrest 0.57 for prolonged hospital stays, 0.63 for mortality. Subgroup analyses showed variable predictiveness by race (AUC = 0.4378), payment method (AUC = 0.5754), income quartile (AUC = 0.5202), and deprivation composite score (AUC = 0.4751). Patients with private insurance had the highest risk of stress cardiomyopathy (odds ratio [OR] = 1.98; 95% confidence interval [CI] 1.70-2.29). Socioeconomic metrics, including neighborhood distress, showed varying predictive accuracy for the HF-related admissions and selected short-term outcomes, with the highest predictive accuracy for neighborhood distress on the risk of HF (AUC = 0.50, std: 0.006), atrial fibrillation (AUC = 0.48, std: 0.0007), cardiac arrest (AUC = 0.51, std: 0.007), and prolonged hospital stays (AUC = 0.53, std: 0.0005) and mortality (AUC = 0.50, std: 0.0015). Conclusion: Neighborhood poverty level demonstrates significant predictive power for assessing the risk of HF-related hospital admissions and the short-term outcomes among Maryland residents, exceeding factors like insurance and race/ethnicity.

Abstract 4113864: Hyperkalemia In Patients With Heart Failure Correlates to Worse Inpatient Outcomes

Background: Heart failure (HF) is one of the leading causes of hospitalizations in the States. Hyperkalemia is not an infrequent comorbidity in patients with HF, limiting the maximum benefits of guideline-directed medical therapy. This study evaluates the outcomes in patients admitted for HF with and without hyperkalemia. Methods: We used the Nationwide Readmissions Database (NRD) from 2016-2019, extracting adult patients with a primary diagnosis of HF who were admitted between January and November of each year. Survey procedures were applied using SAS 9.4. Results: We included 4,454,273 weighted hospitalizations due to HF for which 380,446 patients (8.5%) had a concurrent diagnosis of hyperkalemia. Overall, patients with hyperkalemia, compared to HF cases with hyperkalemia, were slightly younger (mean age 70 years vs. 72 years, p <0.01) with fewer women (47% vs.48%) respectively. Patients with hyperkalemia had a higher frequency of diabetes mellitus, hypertension, chronic liver disease, acute kidney injury, chronic kidney disease, end-stage renal disease, and acute encephalopathy (p<0.001). They had more inpatient complications including ventricular fibrillation and cardiac arrest (p <0.001) with longer mean lengths of stay (7 days vs. 5 days, p <0.001) and 30-day readmissions (28% vs. 22%, p<0.001). In-hospital mortality during index admission was significantly higher in the hyperkalemic group (6.4% vs. 2.5%, p < 0.001). Inpatient outcomes including mortality were also worse during first readmission (7% vs. 6%, p<0.01). Even after adjustment for the above-mentioned comorbidities, multivariable analysis reveals that hyperkalemia is an independent factor for inpatient mortality (adjusted OR 1.9 [1.8-2], p<0.001). Conclusion: Hyperkalemia in patients admitted with HF is associated with increased inpatient mortality and readmission. Further studies can investigate whether novel potassium binders may improve outcomes.

Abstract 4134744: Trends and Disparities in Mortality Among Patients with Hypertensive Heart Disease and Congestive Heart Failure in the United States from 1999 to 2020

Background: Hypertensive heart disease (HHD) poses a growing public health concern. Global data reveal a concerning rise in HHD prevalence, deaths, and disability-adjusted life years (DALYs) between 1990 and 2019. The Framingham Study highlights that hypertension is linked to approximately one-quarter of heart failure cases. This association is even stronger among older adults, in whom hypertension is responsible for up to 68% of heart failure cases. Methods: This study analyzed death certificates within the CDC WONDER database for patients in the United States from 1999 to 2020. We identified deaths among individuals aged 25 years and older caused by HHD and CHF using the International Classification of Diseases, Tenth Revision (ICD-10) code I11.0. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, race/ethnicity, and urbanization status. Results: Between 1999 and 2020, a total of 302,270 deaths were reported in patients due to HHD with CHF. Overall, AAMR increased from 37.3 to 134.9 per 1,000,000 population between 1999 and 2020, with a significant decrease from 1999 to 2004 (APC: -7.91; 95% CI: -20.16 to -1.04), followed by a significant increase from 2004 to 2007 (APC: 42.47; 95% CI: 21.27 to 55.62), a slight decrease from 2007 to 2014 (APC: -0.9; 95% CI: -9.38 to 2.39), and finally a steep increase from 2014 to 2020 (APC: 14.22; 95% CI: 10.87 to 20.84). Gender-based analysis revealed that men had slightly higher AAMRs than women (Men: 63.1; 95% CI: 62.8 to 63.5 vs. Women: 60.7; 95% CI: 60.5 to 61). Moreover, AAMRs were highest among non-Hispanic African Americans (109.6; 95% CI: 108.6 to 110.6), followed by non-Hispanic American Indian or Alaska Natives (66.6; 95% CI: 63.1 to 70.1), non-Hispanic Whites (58.5; 95% CI: 58.2 to 58.7), Hispanics (53.7; 95% CI: 52.9 to 54.5), and non-Hispanic Asian or Pacific Islanders (39; 95% CI: 38–39.9). In addition, non-metropolitan areas had higher AAMRs than metropolitan areas (non-metropolitan: 65.7; 95% CI: 65.2 to 66.3 vs. metropolitan: 62.1; 95% CI: 61.8 to 62.3) (Figure 1). Conclusions: Despite an initial decline, mortality from combined HHD and CHF has risen significantly since 1999. Notably, mortality was most pronounced among men, non-Hispanic African Americans, and individuals residing in non-metropolitan areas.

Abstract 4118341: Outcomes of Heart Failure with Preserved Ejection Fraction Patients With Concurrent Opioid Use: Insights From the National Inpatient Sample

Background: Opioid use has increased significantly in the past few decades, impacting cardiac and non-cardiac patients. As heart failure with preserved ejection fraction (HFpEF) comprises half of all heart failure cases, understanding its management and effect on outcomes is crucial. This study aims to evaluate the outcomes of chronic opioid therapy on HFpEF patients. Methods: Studying the National Inpatient Sample (2016-2020), we identified adult HFpEF patients using the appropriate ICD-10 codes -after excluding patients with end-stage renal disease (ESRD)- and compared outcomes between chronic opioid users and non-users. Multivariate logistic and linear regression analyses were performed, adjusting for multiple patient and hospital confounders. The primary outcome was all-cause in-hospital mortality while secondary outcomes included acute kidney injury/hemodialysis (AKI/HD), cardiogenic shock, cardiac arrest, mechanical ventilation, length of stay, and total charges. Results: Among 1,557,344 HFpEF patients, 21,655 (1.4%) were on opioids chronically. Inpatient mortality was not significantly different between patients who were on opioids and those who were not. (adjusted odds ratio [aOR] 1.01, 95% CI 0.85 - 1.2, p=0.89). There was a non-significant increased risk of cardiogenic shock (aOR 1.14, 95% CI 0.87 - 1.5, p=0.35) and cardiac arrest (aOR 1.05, 95% CI 0.8 - 1.36, p=0.74) in patients on chronic opioids. Chronic opioids were associated with increased risk of AKI/HD (aOR 1.12, 95% CI 1.04 - 1.2, p=0.002) and mechanical ventilation (aOR 1.29, 95% CI 1.16 - 1.43, p< 0.001). Opioid use was also associated with longer hospital stay (adjusted MD [aMD] 1.07 days, 95% CI 0.75 - 1.39, p<0.001) and a non-significant increase in total charges (aMD $2,593, 95% CI -$2,044 - $7,229, p=0.27). Conclusions: While chronic opioid use in hospitalized HFpEF patients did not significantly impact in-hospital mortality, it was associated with increased risk of other adverse events and longer hospital stay. Further research is needed to understand the impact of chronic opioid use on HFpEF patients.

Invasive haemodynamic assessment in heart failure with preserved ejection fraction

AbstractDespite the increasing prevalence and substantial burden of heart failure with preserved ejection fraction (HFpEF), which constitutes up to 50% of all heart failure cases, significant challenges persist in its diagnostic and therapeutic strategies. These difficulties arise primarily from the heterogeneous nature of the condition, the presence of various comorbidities and a wide range of phenotypic variations. Considering these challenges, current international guidelines endorse the utilization of invasive haemodynamic assessments, including resting and exercise haemodynamics, as the gold standard for enhancing diagnostic accuracy in cases where traditional diagnostic methods yield inconclusive results. These assessments are crucial not only for confirming the diagnosis but also for delineating the complex underlying pathophysiology, enabling the development of personalized treatment strategies, and facilitating the precise classification of HFpEF phenotypes. In this review, we summarize the haemodynamic changes observed in patients with HFpEF, comparing resting and exercise‐induced parameters to those of normal subjects. Additionally, we discuss the current role of invasive haemodynamics in HFpEF assessment and highlight its utility beyond diagnosis, such as identifying HFpEF comorbidities, guiding phenotype‐based personalized therapies and characterizing prognostication. Finally, we address the challenges associated with utilizing invasive haemodynamics and propose future directions, focusing on integrating these assessments into routine HFpEF care.

Results of Vertical Infra-Axillary Thoracotomy for Total Repair of Tetralogy of Fallot.

To demonstrate the efficacy of minimally invasive surgery via a vertical infra-axillary incision for complete tetralogy of Fallot (TOF) correction. In a study conducted from April to October 2023, 33 patients with TOF underwent total repair using this approach. On average, the patient age was 5.94 ± 2.68 months, weight was 6.49 ± 0.97 kg, and mean z-score index for the pulmonary valve annulus was -1.38 ± 0.92. Results also highlighted abnormal coronary artery pathways in 18.2% of cases, including 1 patient with dextrocardia and situs inversus. The average incision length was 4.01 ± 0.6 cm, with bypass and clamping times of 95.42 ± 33.19 min and 69.24 ± 28.15 min, respectively. Preservation of the pulmonary valve annulus was achieved in 67% of patients. No postoperative deaths occurred, and there were no significant ventilation differences between groups. After surgery, no severe pulmonary valve regurgitation was observed, with patients remaining in excellent condition throughout the 7-month follow-up. The pulmonary valve pressure gradient after the procedure was 23.97 ± 10.65 mm Hg, and no heart failure cases were reported per the Ross classification at the latest follow-up. The vertical infra-axillary incision approach for total TOF repair is safe, effective, and cosmetically advantageous.

Contemporary epidemiology of hospitalised heart failure with reduced versus preserved ejection fraction in England: a retrospective, cohort study of whole-population electronic health records.

Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised. In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital. We excluded individuals with less than 1 year of medical history records in primary or secondary care; admissions to NHS hospitals for which less than 10% of heart failure cases were linkable to the National Heart Failure Audit (NHFA); individuals younger than 18 years at the time of the heart failure hospitalisation; and patients who died in hospital during the index heart failure admission. For patients with new onset heart failure, we assessed incidence rates of 30-day and 1-year all-cause and cause-specific (cardiovascular, non-cardiovascular, and heart failure-related) emergency rehospitalisation and mortality after discharge, and dispensed guideline-recommended medical therapy (GRMT). Follow-up occurred from the index admission to the earliest occurrence of the event of interest, death, or end of data coverage. We estimated adjusted hazard ratios (HRs) to compare HFrEF with HFpEF. We computed population-attributable fractions to quantify the percentage of outcomes attributable to coexisting chronic medical conditions. Among 233 320 patients identified who survived the index heart failure admission across 335 NHS hospitals between Jan 1, 2019, and Dec 31, 2022, 101 320 (43·4%) had HFrEF, 71 910 (30·8%) had HFpEF, and 60 090 (25·8%) had an unknown classification. In patients with new onset heart failure, there were reductions in all-cause 30-day (-5·2% [95% CI -7·7 to -2·6] in 2019-22) and 1-year rehospitalisation rates (-3·9% [-6·6 to -1·2]). Declining 30-day rehospitalisation rates affected patients with HFpEF (-4·8% [-9·2 to -0·2]) and HFrEF (-6·2% [-10·5 to -1·6]), although 1-year rates were not statistically significant for patients with HFpEF (-2·2% [-6·6 to 2·3] vs -5·7% [-10·6 to -0·5] for HFrEF). There were no temporal trends in incidence rates of 30-day or 1-year mortality after discharge. The rates of all-cause (HR 1·20 [1·18-1·22]) and cause-specific rehospitalisation were uniformly higher in those with HFpEF than those with HFrEF. Patients with HFpEF also had higher rates of 1-year all-cause mortality after discharge (HR 1·07 [1·05-1·09]), driven by excess risk of non-cardiovascular death (HR 1·25 [1·21-1·29]). Rates of rehospitalisation and mortality were highest in patients with coexisting chronic kidney disease, chronic obstructive pulmonary disease, dementia, and liver disease. Chronic kidney disease contributed to 6·5% (5·6-7·4) of rehospitalisations within 1 year for HFrEF and 5·0% (4·1-5·9) of rehospitalisations for HFpEF, double that of any other coexisting condition. There was swift implementation of newer GRMT, but markedly lower dispensing of these medications in patients with coexisting chronic kidney disease. Rates of rehospitalisation in patients with heart failure in England have decreased during 2019-22. Further population health improvements could be reached through enhanced implementation of GRMT, particularly in patients with coexisting chronic kidney disease, who, despite being at high risk, remain undertreated. Wellcome Trust, Health Data Research UK, British Heart Foundation Data Science Centre.

Control for multiple risk factors and incident heart failure and mortality in patients with diabetes mellitus: insights from the kailuan cohort study

Abstract Purpose This study aimed to evaluate the relationship between control for multiple risk factors and diabetes-related heart failure and all-cause mortality, and to explore the extent to which the excess risk can be reduced. Methods Diabetes participants with pre-existing heart failure documented in discharge register or medical insurance records and incomplete baseline risk factor information were excluded. Each of these patients was then matched randomly to four control subjects. The degree of risk factor control was defined by attainment of target values for blood pressure, body mass index , low-density lipoprotein cholesterol, fasting blood glucose, high-sensitive C-reactive protein and smoking. The primary outcome was newly diagnosed heart failure, and the secondary outcome was all-cause mortality.Fine-Gray and Cox regression were performed to estimate the risk of heart failure and all-cause mortality among diabetes patients in relation to the degree of control for multiple risk factors respectively, and the group with ≤1 risk factor control was set as the reference group. All-cause mortality was used as a competing risk in the Fine-Gray model. Results A total of 17,676 patients with diabetes and 69,493 matched non-diabetic control subjects were included. Of these, 84.2% were men and the mean age was 56.2±10.7 years. Over a median follow-up of 11.2 (13.1-15.0) years, a total of 1,070 cases of heart failure and 4,121 cases of all-cause mortality were identified among patients with diabetes. Significant inverse associations were observed between the number of well-controlled risk factors and the risk of incident adverse outcomes in diabetes patients. For each additional risk factor that was controlled, there was an associated 16% decrease in the risk of heart failure and a 10% decrease in the risk of all-cause mortality. The incidence rate of heart failure among diabetes patients was at its lowest for those with ≥5 risk factors (HR: 0.46, 95% CI: 0.34-0.62), and it constantly increased with a lower number of well-controlled risk factors. As for all-cause mortality, the lowest risk was associated with optimal risk factor control (HR: 0.59, 95% CI: 0.50-0.68). Among diabetes patients with ≥5 risk factors that were well controlled, the adjusted hazard ratio for heart failure and all-cause mortality was 1.25 (95%CI: 0.99-1.56) and 1.17(95%CI: 1.05-1.31) respectively, as compared with controls. The protective impact of comprehensive risk factor control on the risk of heart failure was more pronounced among men than women, as well as among those using antihypertensive medications than non-users. Conclusions Control for multiple risk factors is related to a lower risk of heart failure and all-cause mortality in an accumulative and sex-specific manner. Compared to the general population, patients with diabetes mellitus remains associated with an increased risk for the outcomes in spite of the optimization of risk factor control.

Blood plasma metabolites and heart failure risk: insights from Mendelian randomization analysis

Abstract Background Heart failure remains a leading cause of mortality and disability worldwide. Blood plasma metabolites play a crucial role in influencing heart failure, yet they are subject to numerous confounding factors. Mendelian randomization analysis provides a powerful tool for assessing causal relationships between them. Methods We conducted a Mendelian randomization analysis using a meta-analysis comprising 115,150 heart failure cases (155,331 controls) and 1400 serum metabolites. Various methods including Inverse variance weighting (IVW), MR Egger, Weighted median, and Weighted mode were employed to estimate causal effects. Sensitivity analyses were conducted using Cochran’s Q test, MR Steiger test, leave-one-out analyses, funnel plot, and MR-PRESSO. Results Following rigorous selection, among the 1400 blood plasma metabolites, 71 metabolites including Sphingomyelin, Myristate, AMP to methionine ratio showed significant associations with increased risk of heart failure. Additionally, 40 metabolites including Glycine, octadecenedioylcarnitine (C18:1-DC), 1-palmitoyl-2-dihomo-linolenoyl-GPC (16:0/20:3n3 or 6) exhibited significant associations with decreased risk of heart failure. Conclusion Identified blood plasma metabolites provide crucial insights into screening and prevention strategies for heart failure. Further validation is warranted through animal models and large-scale cohorts.

Proteomic biomarkers and pathway analysis for progression to heart failure in three epidemiological representative cohorts.

Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population-based cohorts. A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow-up of 13 (11-14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS (n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case-control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28-1.71]; DD OR 1.71 [1.53-1.92]; HF HR 1.98 [1.66-2.36]); STANISLAS (LVH OR 1.20 [1.02-1.41]; DD OR 1.46 [1.12-1.90]); HOMAGE (HF HR 1.85 [1.62-2.12]). Galectin-4, growth differentiation factor 15 and suppression of tumorigenicity-2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF. In conclusion, our study reinforces the role of NT-proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT-proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets.

ICARUS registry: findings from the first 1595 cases of acute decompensated heart failure in a single center in a latin american country

Abstract Introduction Institutional aCute decompensAted HeaRt FailUre RegiStry (ICARUS) will provide information on clinical characteristics, medical practice, patterns of treatment, and outcomes of patients hospitalized with Acute Decompensated Heart Failure (ADHF) in a hospital in a middle-income country. Objective Describe the methodological aspects, sociodemographic, and clinical characteristics of patients hospitalized with ADHF and their short-term outcomes. Method Prospective cohort of patients with ADHF from the emergency service of a cardiovascular center. Descriptive statistics were used to synthesize sociodemographic characteristics, clinical characteristics during hospitalization, and outcomes. Results 1595 patients with ADHF. The median age was 68 years (Q1=58; Q3=76), and 69.28% were men. The median hospital stay was six days (Q1=4; Q3=11), with an accumulative incidence (AI) for rehospitalization at 30 days of 8.70 % (95% CI 7.18 to 10.40%), in-hospital mortality AI of 4.33% (95% CI 3.38 to 5.44%), and a median change in the quality-of-life score like Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 30 days of -20 points (Q1=-37; Q3=-5). At discharge, all patients had a percentage greater than 70% of the use of quadruple neurohormonal blockade therapy. Conclusions ICARUS is one of the first registries in Latin America since the indication of the use of SGLT2 inhibitors, evaluating the clinical and sociodemographic characteristics, treatment patterns, and outcomes of a preliminary cohort of 1595 patients hospitalized for ADHF. The results indicate that, at discharge, up to 82.79% of patients were receiving quadruple neurohormonal blockade therapy, which is considerably challenging to achieve in Latin America. Considering the results of the Safety, tolerability and efficacy of up-titration of Guideline-Directed Medical therapies for acute heart failure (STRONG-HF study), our study reinforces the benefit of discharge with Guideline-Directed Medical Therapy (GDMT) for heart failure from hospitalization. The use of GDMT for heart failure may have influenced our positive outcomes in terms of in-hospital mortality, improvement in quality of life, and the percentage of short-term rehospitalizations compared to similar cohorts.Proportion of HF drug group

Protease-activated receptor 2 (PAR2) inhibition reduces complement-associated cardiac remodelling in obesity-related heart failure

Abstract Background and Aims Obesity is considered a major risk factor for the development of heart failure (HF) due to lipid accumulation, oxidative stress and inflammation which results in cardiac remodeling. Protease activated receptor 2 (PAR2) has been linked to various cardiovascular and inflammatory diseases. The role of PAR2 has not yet been studied in obesity-related HF. Methods In the experimental mouse study, we used 1-year-old ApoE knockout (ApoE-/-) and ApoE PAR2 double knockout (ApoE-/-PAR2-/-) mice with a C57BL/6J background on a high fat (HF) diet (n=5/ group). Cell culture experiments were performed with human primary cardiac fibroblasts and HepG2 hepatocytes. Patients (n=50) included in the clinical study had a BMI > 25kg/m², symptoms of heart failure (HF), coronary angiography (CA) that excluded coronary artery disease (CAD) and endomyocardial biopsy (EMB) that confirmed the absence of active myocarditis or primary cardiac amyloidosis. Patients were divided into PAR2low (n=22) and PAR2high (n=22) based on the median PAR2 expression measured via qPCR in the EMB of the cohort, and six patients served as healthy controls. Results Evaluation of endomyocardial biopsies (EMB) from overweight/ obese non-ischemic cardiomyopathy (NICM) patients with heart failure (HF) (n=44) revealed that a reduced cardiac PAR2 expression is associated with less cardiac C3 (p≤0.054), C4 (p≤0.041) and C5 gene expression (p≤0.045), as well as plasma levels of complement C3 (1.1g/l± 0.7 vs 2.1g/l±0.2; p≤0.016) and C5b-9 (303.4ng/ml± 215.7 vs 992.7ng/ml± 756.2; p≤0.0002) and as a result, better systolic function i.e. LVEF (46.1%±17.1 vs 36.8%±15.2; p≤0.046) and LV GLS (-14.9%± 5.7 vs -9.5%± 4.6; p≤0.009), less cardiac remodeling and damage. Correspondingly, aged ApoE-/-PAR2-/-mice on a Western diet showed less hepatic and cardiac complement expression (i.e. C1q, C3, C4, C5, C9), cardiac C3 deposition (p≤0.047) and C5b-9 plasma levels (p≤0.049), as well as less cardiac necrosis (p≤0.046) and lower BNP (p≤0.016) than ApoE-/-. PAR2 overexpression in human cardiac fibroblasts (HCFs) independently enhanced and PAR2 antagonism reduced interferon γ (IFNγ)-mediated STAT1-dependent complement C3, C4 and C5 expression. Conclusions Protease-activated receptor 2 regulates complement-mediated cardiac damage and remodeling in HF. The PAR2-IFNγ/STAT1/C3-C4-C5 complement-axis might be a promising prognostic and therapeutic approach to identify and treat high-risk cases of HF in overweight/obese patients.

Prevalence and incidence of heart failure in patients with type 2 diabetes mellitus. Results of the prospective DIABET-IC study

Abstract Introduction Heart failure (HF) is one of the major health problems in our environment today. Type 2 diabetes mellitus (DM2) is an important cardiovascular risk factor and can increase the burden of HF through various mechanisms. The incidence of HF in DM2 has not been well studied. Purpose The aim of our study was to evaluate the prevalence and incidence of HF in patients with DM2 followed in hospital cardiology and endocrinology departments. Methods The DIABET-IC study is a longitudinal cohort, prospective, multicenter follow-up study that included 1,249 consecutive patients with DM2 in 2018-2019 in 30 Spanish centers in cardiology and endocrinology outpatient clinics. HF was diagnosed according to the clinical records and following the criteria of the European Society of Cardiology. The prevalence of HF at the inclusion visit was analyzed, as well as the incidence of HF (new diagnoses) during a 3-year follow-up. Results Mean age was 67.3±+9.9 years, with 31.7% of the patients being women. Cardiology clinics included 61.9% of patients and endocrinology clinics the remaining 38.1%. There was a previous history of coronary artery disease in 38.6%, hypertensive heart disease in 21% and atrial fibrillation in 31.9%. Cardiovascular and antidiabetic drugs prescribed at the baseline and 3-year visits are shown in figure 1. Figure 2 summarizes the results of the study. The prevalence of HF at the baseline visit was 39.2%, 490 cases (with reduced LVEF 17.3%, mildly reduced 8.1% and preserved 13.8%). After a follow-up of 1,935/100 persons-year of cases without baseline HF, 58 incident cases of HF were diagnosed, 7.6% (32 in the first year, 13 in the second and 13 in the third year of follow-up). The incidence rate was 3.01/100 person-years (95%CI: 2.30-3.92). Of these 58 cases, 23.7% were with reduced LVEF, 28.9% with slightly reduced LVEF and 47.4% preserved. The incidence was higher in patients followed by endocrinology (3.90 vs 2.90/100 persons-year; p=0.042). At the end of the 3-year follow-up, including baseline prevalence, 46.8% of all patients had HF. Conclusions The prevalence and incidence of HF in patients with DM2 are very high. The incidence of HF is around 3% per year, which is almost 8 times higher than the rate found in large studies in the general population. Approximately half of the new cases were HF with preserved LVEF, and the other half with LVEF < 50%. The use of new antidiabetic drugs, such as iSGLT2, which have been shown to reduce the incidence of HF, should be encouraged.

ESC Heart Failure Association age-adjusted natriuretic peptide thresholds for a new diagnosis of heart failure: diagnostic accuracy study

Abstract Background Natriuretic peptide (NP) testing is an important part of the heart failure (HF) diagnostic pathway. The European Society of Cardiology (ESC) HF guidelines currently recommend a NT-proBNP cut-off <125pg/mL to rule out HF in the community.1 However, NP level increases with age and an NT-proBNP above 125pg/mL is common in older people in the general population. The ESC Heart Failure Association (HFA) recently published a practical algorithm for early diagnosis of HF recommending age-specific rule-in NT-proBNP thresholds: ≥125pg/ml for patients aged under 50 years, ≥250pg/ml for patients aged 50-75 years, and ≥500pg/ml for patients over 75 years (Figure 1).2 Purpose Our aim was to assess NT-proBNP test performance for HF diagnosis at the ESC HFA age-specific thresholds. Method We analysed our existing diagnostic accuracy study dataset containing primary care data from the Clinical Practice Research Datalink (CPRD) linked to inpatient Hospital Episode Statistics (HES) inpatient data between 2004 and 2018. NT-proBNP results were taken from the GP record (index test) and the primary outcome (reference standard) was a HF diagnostic code entered in CPRD or HES within six months of the test. NT-proBNP accuracy for HF was assessed by calculating sensitivity, specificity, positive predictive values (PPV), and negative predictive value (NPV). Receiver operating characteristic (ROC) curves were plotted to assess overall test performance. Results In total, 229,580 patients had an NP test and 21,102 (9.2%) were diagnosed with HF. The current ESC NT-proBNP threshold ≥125pg/mL had sensitivity 94.6% (95% confidence intervals [CI] 94.2 to 95.0), specificity 50.0% (95%CI 49.7 to 50.3), PPV 16.4% (16.1 to 16.6), NPV 98.9% (98.8 to 99.0)). Area under the ROC curve was 0.874 (0.871 to 0.877). Age-specific NT-proBNP thresholds performance: Below 50 years (≥125pg/mL): 32,882 people tested, HF prevalence 3.8%. Sensitivity 83.5 % (81.3 to 85.5), specificity 77.6% (77.2 to 78.1), PPV 13.0% (12.2 to 13.7), NPV 99.2% (99.0 to 99.3). 50 to 75 years ≥250pg/mL: 105,771 people tested, HF prevalence 9.8%. Sensitivity 88.5% (87.9 to 89.1), specificity 67.8% (67.5 to 68.0), PPV 23.1% (22.6 to 23.5), NPV 98.2% (98.1 to 98.3). Above 75 years ≥500pg/mL: 16,694 people tested, HF prevalence 17.5%. Sensitivity 84.4% (83.0 to 85.7), specificity 63.5% (62.7 to 64.3), PPV 32.8% (31.7 to 33.9), NPV 95.0% (94.6 to 95.5). Conclusion The age-specific NT-proBNP thresholds in the HFA practical algorithm had higher specificity so fewer people without HF would be referred, reducing demand for echocardiography and cardiology assessment overall meaning people with HF could be seen earlier. However, lower sensitivity means some cases of HF would initially be missed. NT-proBNP was a reliable ‘rule-out’ test at population level. The optimal NT-proBNP threshold will depend on the priorities and capacity of the national healthcare system.

Hypnotic use and the risk of cardiovascular diseases in insomnia patients

Abstract Background Insomnia, commonly treated with hypnotic agents, is an independent risk factor of cardiovascular diseases. Previous research demonstrated the detrimental effect of hypnotics on the prognosis of cardiovascular patients. Purpose We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia. Methods In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting and competing risk models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of hypnotics-related genes and cardiovascular disease association. The genome-wide association data of CHD, HF, and stroke were there large-scale genome-wide association analyses. Tissue-specified expression quantitative trait loci (eQTL) data was derived from BrainSeq phase II. Results During a median follow-up of 14.3 years, the matched cohort documented a total of 1,019 CHD cases, 406 HF cases, 285 stroke cases, and 197 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality (Figure 1). The inverse probability of treatment weighting and competing risk models didn’t alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health. However, GABRG1—a drug target for benzodiazepines—was associated with heightened risks for heart failure, and ischemic stroke (Figure 2). Conclusions Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Z-meds are safe regarding the risk of cardiovascular outcomes in the UKB population with insomnia.Figure 1Figure 2

Incident heart failure: comparing management and outcome in primary care and hospital settings in Western Sweden 2008-2017

Abstract Background Heart failure (HF) is a major problem in primary care (PC) and hospital care (HC). HF patients managed in these two settings may differ in their demography, comorbidities, treatment and outcomes. Aim We aimed to compare the patient management in PC and HC in the Västra Götaland Region (VGR) in Sweden. Methods The VEGA database is an administrative database includes all patients living in VGR. Patients with a first principal or contributory diagnosis of HF (I50) ≥18 years old between 2008 and 2017 were included. One-year mortality was used as the outcome. Results In total, 62,229 new-onset HF cases were included, with 18,722 identified only in PC and 16,651 in HC. HF patients in PC were older (80.7±10.9 vs 76.1±13.6), more women (57.1% vs 44.9%), with more hypertension, musculoskeletal and mental disorders, but less myocardial infarction. Guideline directed medical therapy was more frequently used in HC despite similar medication before HF diagnosis. Patients in HC had almost 4 times higher all-cause 1-year mortality [3.92 (3.77 - 4.08), p<0.0001] compared with PC after adjustment for age and sex. Over 10-year period, despite decreasing mortality in both settings, hazard ratios for HC vs. PC were significantly increased for all patients (p for interaction 0.0004), which was more marked in female and for 70-80 years old patients. Conclusion Over a 10-year period, not withstanding decreasing mortality in HF patients in both PC and HC settings, differences remain between these two HF populations not only demographic profile and medications but also outcomes.

Sodium glucose cotransporter 2 inhibitors in the management of heart failure: Veni, Vidi, and Vici.

Heart failure (HF) is a chronic disease associated with high morbidity and mortality rates. Renin-angiotensin-aldosterone system blockers (including angiotensin receptor/neprilysin inhibitors), beta-blockers, and mineralocorticoid receptor blockers remain the mainstay of pharmacotherapy for HF with reduced ejection fraction (HFrEF). However, despite the use of guideline-directed medical therapy, the mortality from HFrEF remains high. HF with preserved ejection fraction (HFpEF) comprises approximately half of the total incident HF cases; however, unlike HFrEF, there are no proven therapies for this condition. Sodium glucose cotransporter-2 inhibitors (SGLT-2is) represent a new class of pharmacological agents approved for diabetes mellitus (DM) that inhibit SGLT-2 receptors in the kidney. A serendipitous finding from seminal trials of SGLT-2is in DM was the significant improvement in renal and cardiovascular (CV) outcomes. More importantly, the improvement in HF hospitalization (HHF) in the CV outcomes trials of SGLT-2is was striking. Multiple mechanisms have been proposed for the pleiotropic effects of SGLT-2is beyond their glycemic control. However, as patients with HF were not included in any of these trials, it can be considered as a primary intervention. Subsequently, two landmark studies of SGLT-2is in patients with HFrEF, namely, an empagliflozin outcome trial in patients with chronic HF and a reduced ejection fraction (EMPEROR-Reduced) and dapagliflozin and prevention of adverse outcomes in HF (DAPA-HF), demonstrated significant improvement in HHF and CV mortality regardless of the presence of DM. These impressive results pitchforked these drugs as class I indications in patients with HFrEF across major guidelines. Thereafter, empagliflozin outcome trial in patients with chronic HF with preserved ejection fraction (EMPEROR-Preserved) and dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction HF (DELIVER) trials successively confirmed that SGLT-2is also benefit patients with HFpEF with or without DM. These results represent a watershed as they constitute the first clinically meaningful therapy for HFpEF in the past three decades of evolution of HF management. Emerging positive data for the use of SGLT-2is in acute HF and post-myocardial infarction scenarios have strengthened the pivotal role of these agents in the realm of HF. In a short span of time, these classes of drugs have captivated the entire scenario of HF.

A machine learning tool for identifying newly diagnosed heart failure in individuals with known diabetes in primary care.

We aimed to create a predictive model utilizing machine learning (ML) to identify new cases of congestive heart failure (CHF) in individuals with diabetes in primary health care (PHC) through the analysis of diagnostic data. We used a sex- and age-matched case-control design. Cases of new CHF were identified across all outpatient care settings 2015-2022 (n=9098). We included individuals 30years and above, by sex and age groups of 30-65years and >65years. The controls (five per case) were sampled from the individuals in 2015-2022 without CHF at any time between 2010 and 2022, in total 45 490. From the stochastic gradient boosting (SGB) technique model, we obtained a rank of the 10 most important factors related to newly diagnosed CHF in individuals with diabetes, with the normalized relative influence (NRI) score and a corresponding odds ratio of marginal effects (ORME). Area under curve (AUC) was calculated. For women 30-65years and >65years, we identified 488 and 3240 new cases of CHF, respectively, and men 30-65years and >65years 1196 and 4174 new cases. Among the 10 most important factors in the four groups (divided by sex and lower and higher age) for newly diagnosed CHF, we found the number of visits 12months before diagnosis (NRI 44.3%-55.9%), coronary artery disease (NRI 2.9%-7.8%), atrial fibrillation and flutter (NRI 6.6%-12.2%) and 'abnormalities of breathing' (ICD-10 code R06) (NRI 2.6%-4.4%) were predictive in all groups. For younger women, a diagnosis of COPD (NRI 2.7%) contributed to the predictive effect, while for older women, oedema (NRI 3.1%) and number of years with diabetes (NRI 3.5%) contributed to the predictive effect. For men in both age groups, chronic renal disease had predictive effect (NRI 3.9%-5.1%) The model prediction of CHF among patients with diabetes was high, AUC around 0.85 for the four groups, and with sensitivity over 0.783 and specificity over 0.708 for all four groups. An SGB model using routinely collected data about diagnoses and number of visits in primary care, can accurately predict risk for diagnosis of heart failure in individuals with diabetes. Age and sex difference in predictive factors warrant further examination.

Perioperative changes of serum interleukin 6 levels in elderly male patients with intertrochanteric fracture

To investigate the perioperative changes in serum interleukin 6 (IL-6) levels in elderly male patients with intertrochanteric fractures, and provide evidence for inflammatory control in this patient population. The clinical data of 40 male patients aged more than 60 years with intertrochanteric fractures who met the selection criteria between January 2021 and December 2022 were retrospectively analyzed, including 25 non-osteoporosis patients (T value>-2.5, group A) and 15 osteoporosis patients (T value≤-2.5, group B). In addition, 40 healthy men aged more than 60 years old were included as controls (group C) according to the age matching rule. There was no significant difference in age, smoking history, drinking history, body mass index, complications (hypertension and diabetes), alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, and total protein among the 3 groups ( P>0.05). Serum samples were collected from group C subjects and from groups A and B patients preoperatively and on postoperative days 1, 3, 5, and 7. IL-6 levels were measured using ELISA assay. Pearson correlation analysis was used to assess the relationship between IL-6 levels and T values at various time points in groups A and B. Postoperative complications during hospitalization and 1-year mortality rates were recorded for groups A and B. Preoperative IL-6 levels were significantly higher in groups A and B than in group C ( P<0.05), with group B being significantly higher than group A ( P<0.05). In groups A and B, IL-6 levels increased significantly on postoperative day 1 compared to preoperative levels and then gradually decreased, approaching preoperative levels by postoperative day 7. IL-6 levels in group B were significantly higher than those in group A at all postoperative time points ( P<0.05). Correlation analysis showed that IL-6 levels were negatively correlated with T values at all perioperative time points in all patients from groups A and B ( P<0.05). Complications occurred in 4 patients (16.0%) in group A, including 2 cases of pulmonary infection, 1 case of urinary tract infection, and 1 case of heart failure, and in 3 patients (20.0%) in group B, including 2 cases of pulmonary infection and 1 case of gastrointestinal bleeding. There was no significant difference in the incidence of complications between the two groups ( χ 2=0.104, P=0.747). There were 2 cases (8.0%) and 4 cases (26.7%) died within 1 year after operation in groups A and B, respectively, and there was no significant difference in 1-year mortality rates between the two groups ( χ 2=2.562, P=0.109). Serum IL-6 levels significantly increase in the early postoperative period in elderly male patients with intertrochanteric fractures, especially in those with osteoporosis. Monitoring the inflammatory state and promptly controlling the inflammatory response during the perioperative period, may reduce complications and improve postoperative survival in this patient population.