Risk Of Heart Failure In Patients Research Articles

Association of lactate/albumin ratio with 3-month readmission risk in heart failure patients: a retrospective study.

The predictive value of the lactate/albumin ratio (LAR) in mortality is established in various conditions, yet its relevance to 3-month readmission risk in Chinese adults with heart failure (HF) remains unclear. Analysing data from 957 patients with HF at Zigong Fourth People's Hospital, Sichuan, China (December 2016 to June 2019), we assessed baseline characteristics, vital signs, comorbidities, and prescriptions. LAR demonstrated a linear correlation with 3-month readmission risk (HR=1.60, 95% CI: 1.19-2.16). Tertile 3 (≥-0.48) exhibited higher risk than tertile 1 (<-0.83) and tertile 2 [-0.83, -0.48), with HRs and 95% CI of 1.49 (1.06-2.10), 1.43 (1.01-2.02), 1.48 (1.03-2.12), respectively. Subgroup and sensitivity analyses affirmed consistent influence of LAR on 3-month readmission risk for HF. Higher LAR significantly correlates with increased 3-month readmission risk in Chinese adult patients with HF, suggesting LAR is a valuable predictor for early readmission.

Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial.

Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown. EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes. Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05). Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674.

Global IL4Rα blockade exacerbates heart failure after an ischemic event in mice and humans.

Ischemic heart failure continues to be a highly prevalent disease among westernized countries and there is great interest in understanding the mechanisms preventing or exacerbating disease progression. The literature suggests an important role for the activation of interleukin-13 or interleukin-4 signaling in improving ischemic heart failure outcomes after myocardial infarction in mice. Dupilumab, a neutralizing antibody that inhibits the shared IL13/IL4 receptor subunit IL4Rα, is widely used for conditions such as ectopic dermatitis in humans. If global depletion of IL4Rα influences ischemic heart failure, either in mice or in humans taking dupilumab, is unknown. Here, we investigated the pathophysiological effects of global IL4Rα genetic deletion in adult mice after surgically induced myocardial infarction (MI). We also determined heart failure risk in patients with ischemic heart disease and concomitant usage of dupilumab using the collaborative patient data network TriNetX. Global deletion of IL4Rα results in exacerbated cardiac dysfunction associated with reduced capillary size after myocardial infarction in mice. In agreement with our findings in mice, dupilumab treatment significantly increased the risk of heart failure development in patients with preexisting diagnosis of ischemic heart disease. Our results indicate that systemic IL4Rα signaling is protective against heart failure development in adult mice and human patients specifically following an ischemic event. Thus, the compelling evidence presented hereby advocates for the development of a randomized clinical trial specifically investigating heart failure development after myocardial ischemia in patients taking dupilumab for another underlying condition.NEW & NOTEWORTHY A body of literature suggests a protective role for IL4Rα signaling postmyocardial infarction in mice. Here, our observational study demonstrates that humans taking the IL4Rα neutralizing antibody, dupilumab, have increased incidence of heart failure following an ischemic event. Similarly, global IL4Rα deletion in mice exacerbates heart failure postinfarct. To our knowledge, this is the first study reporting an adverse association in humans of dupilumab use with heart failure following a cardiac ischemic event.

Fluid mechanics of aortic valve incompetence in the dilated left ventricle

Introduction: Aortic insufficiency (AI) occurs when the aortic valve fails to close completely, allowing backward blood flow into the left ventricle (LV). The progression of AI can lead to ventricular dysfunction and congestive heart failure, setting off a self-perpetuating cycle that worsens these conditions. This study employed models of repeatable and reversible AI within a simulated circulatory loop to analyze vortex dynamics, AI parameters, and gain insights into the efficiency of ventricular washout.Method: A transparent silicone model of an LV with an ejection fraction of 17% served as the baseline, simulating a condition without AI. Mild, moderate, and severe AI were induced using 3D-printed stents, obstructing the complete closure of the aortic valve while allowing unimpeded forward blood flow. Midplane velocity fields were analyzed to compute AI and vortex properties, energy dissipation rate, blood residence time, and shear activation potential.Results and discussion: With increasing AI severity, the regurgitant jet expanded, impeding the development and trajectory of mitral inflow. The inefficiency in fluid transport became apparent through a declining ratio of total kinetic energy rate to energy dissipation rate and an increasing residence time. Impaired ventricular washout resulted in the accumulation of fluid with elevated shear activation potential in the LV. These findings suggested that AI progressively induces abnormal intraventricular flow, heightening the thromboembolic risk in heart failure patients. The study also advocates for the potential application of mock circulatory system to explore the effects of various AI configurations, especially when combined with other cardiac implants like artificial heart valve or left ventricular assist device.

Association between underweight and risk of heart failure in diabetes patients.

The risk of heart failure (HF) in underweight diabetes mellitus (DM) patients has rarely been studied. We conducted a cohort study to investigate the association between underweight (BMI<18.5kg/m2) and BMI change over time and the risk of HF in patients with type 2 DM. We utilized the health screening data from the National Health Insurance Service and the Korean National Health Screening database from 2009 to 2012, with follow-up until December 2018. Participants with DM were categorized into four groups based on their BMI at 4years before study inclusion and BMI at the study entry: (1) Always Normal Weight (BMI at 4years ago/BMI at study entry ≥18.5/≥18.5kg/m2, reference group); (2) Transitioned to Underweight (≥18.5/<18.5kg/m2); (3) Transitioned to Normal Weight (<18.5/≥18.5kg/m2) and (4) Always Underweight (<18.5/<18.5kg/m2). Participants were followed until the development of HF or at the end of the follow-up. Initial screening data included participants with DM who had the health screening during the study period (n=2,746,079). Participants aged <20years (n=390), those who did not undergo health examination 4years prior (n=1,306,520), and those with missing data (n=77,410) were excluded. Participants diagnosed with HF before study participation (n=81,645) and within 1year of study enrolment (n=11,731) were excluded. After applying exclusion criteria, 1,268,383 participants were finally included in the analysis. The primary outcome was the development of HF. We employed Cox proportional hazards models, adjusting for various confounding factors, to assess the risk of developing HF. Median follow-up duration was 6.88years and men were 63.16%. The mean ages of each groups were as follows: Always Normal Weight (57.92±11.64years), Transitioned to Underweight (62±13.5years), Transitioned to Normal Weight (56.6±15.29years) and Always Underweight (57.76±15.35years). In comparison with the Always Normal Weight group (n=1,245,381, HF=76,360), Transitioned to Underweight group (≥18.5/<18.5kg/m2, n=9304, HF=880, adjusted Hazard Ratio (aHR)1.389, 95% confidence interval (CI) 1.3-1.485) or Transitioned to Normal Weight (<18.5/≥18.5kg/m2, n=6024, HF=478, aHR 1.385, 95% CI 1.266-1.515) exhibited an increased risk of HF. The highest risk was observed in the Always Underweight group (<18.5/<18.5kg/m2, n=7674, HF=665, aHR 1.612, 95% CI 1.493-1.740). Underweight was significantly associated with the risk of HF in the DM population. Active surveillance for HF in an underweight DM population is needed.

Determining the role of NT-proBNP levels in diabetic patients with heart failure: A study from North India.

Diabetic patients are at higher risk of cardiovascular morbidity and mortality. NT-proBNP levels measurements are useful for the assessment of risk in heart failure patients in emergency condition and give the faster result. Further, it also offers lower cost and unnecessary hospitalization and follow-up cost. The studies have shown that NT-proBNP levels are a direct predictor of outcome risk in diabetic patients with heart failure. The objective of this research was to study the role of NT-proBNP levels to determine the severity of heart failure in diabetic patients. In this study 150 patients diagnosed with symptomatic heart failure admitted to the emergency department of a tertiary care center from January 2021 to January 2022 have been included in Saraswati Institute Of Medical Sciences, Hapur, India. N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) levels were measured using an automated analyzer ranging between 60 and 3000 pg/ml. According to the European society of cardiology (ESC) guidelines, it has been defined as NT-Pro-BNP level above 125 pg/ml indicates a high possibility of heart failure and NT-Pro-BNP level below 125 pg/ml excludes the high possibility of heart failure. All the patients underwent an echocardiographic study and ejection fraction was calculated and recorded. In diabetic patients ejection fraction was significantly lower in diabetic patients: 47.15 ± 8.75% vs. 43.24 ± 9.54%, P = 0.002). We have observed statistically significant lower HDL values (40.10 ± vs. 35.94 mg/dL, P = 0.0004), however, significant higher triglycerides values were found (101.43 ± 41.7 mg/dL vs. 151.37 ± 78.85, P = 0.001). No significant difference was observed in LDL level (97.8 ± 31.23 vs. 92.35 ± 314.2, P ≥ 0.05) and total cholesterol level (161.49 ± 41.38 vs. 159.97 ± 41.12, P ≥ 0.05). We concluded that the measurement of NT-proBNP in heart failure and diabetic patients could be an economic marker for the evaluation of morbidity and mortality, facilitating better management and follow-up.

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban.

Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up. this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.

Establishment and validation of a prediction nomogram for heart failure risk in patients with acute myocardial infarction during hospitalization

BackgroundAcute myocardial infarction (AMI) with consequent heart failure is one of the leading causes of death in humans. The aim of this study was to develop a prediction model to identify heart failure risk in patients with AMI during hospitalization.MethodsThe data on hospitalized patients with AMI were retrospectively collected and divided randomly into modeling and validation groups at a ratio of 7:3. In the modeling group, the independent risk factors for heart failure during hospitalization were obtained to establish a logistic prediction model, and a nomogram was constructed. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the predictive performance and clinical value. Machine learning models with stacking method were also constructed and compared to logistic model.ResultsA total of 1875 patients with AMI were enrolled in this study, with a heart failure rate of 5.1% during hospitalization. The independent risk factors for heart failure were age, heart rate, systolic blood pressure, troponin T, left ventricular ejection fraction and pro-brain natriuretic peptide levels. The area under the curve (AUC) of the model in modeling group and validation group were 0.829 and 0.846, respectively. The calibration curve showed high prediction accuracy and the DCA curve showed good clinical value. The AUC value of the ensemble model by the stacking method in the validation group were 0.821, comparable to logistic prediction model.ConclusionsThis model, combining laboratory and clinical factors, has good efficacy in predicting heart failure during hospitalization in AMI patients.

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

Abstract Background Cardiac time intervals are sensitive markers of myocardial dysfunction that predisposes to heart failure (HF). Color tissue Doppler imaging (TDI) curved M-mode is a reliable method for measuring cardiac time intervals. Purpose We aimed to investigate the association between cardiac time intervals and HF in patients with acute coronary syndrome (ACS). Methods This was a retrospective cohort study of 580 ACS patients treated with percutaneous coronary intervention (PCI). Patients underwent an echocardiography examination performed a median of two days after PCI. By echocardiography cardiac time intervals including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI curved M-mode and used to derive the myocardial performance index (MPI). The outcome was incident HF. Patients with prevalent at baseline HF were excluded from the analysis. Results The final study sample consisted of 387 patients, 73% were male, the mean age was 64 years, 76% of the ACS events were STEMI and LVEF and GLS were 42% and -13.1%, respectively. During follow-up (median 4.3, IQR:1.0-6.7 years), 140 (36%) developed HF. In unadjusted analyses, longer combined indexes were associated with a higher risk of HF (IVRT/ET: HR 1.24 (1.07-1.43), P = 0.003, per 0.1 increase) and (IVCT/ET: HR 1.44 (1.10-1.91), P = 0.010, per 0.1 increase), and so was higher MPI (HR 1.20 (1.08-1.34),P = 0.001, per 0.1 increase). In addition, shorter ET was also associated with higher HF risk (HR 1.13 (1.07-1.18), P&amp;lt;0.001 per 10ms decrease). MPI and IVCT/ET showed a curvilinear association with the outcome, whereas a linear association was observed for ET and IVRT/ET to the outcome (figure 1). After multivariable adjustment for cardiovascular risk factors, only MPI (HR 1.13 (1.01-1.27), P = 0.034), ET (HR 1.09 (1.01-1.17), P = 0.025), and IVCT/ET (HR1.37 (1.04-1.81), P = 0.023) remained significantly associated with HF. Of note, left ventricular ejection fraction (LVEF) significantly modified the association between ET and HF (p for interaction = 0.002), such that ET was associated with HF even in those with preserved LVEF (&amp;gt;40%) (HR 1.13 (1.02-1.24, P = 0.017, per 10ms decrease), but not in those with reduced LVEF (HR 1.02 (0.96-1.08), P = 0.56, per 10ms decrease). These findings also persisted after adjustment for cardiovascular risk factors. Conclusion Shortened ET, prolongation of combined indexes, and higher MPI were associated with an increased risk of incident HF. In addition, shortening of the ET was associated with an increased risk of HF in patients with preserved systolic function by LVEF.

Abstract 16389: Inflammatory Chronic Kidney Disease is Associated With Incident Heart Failure: A Pooled Cohort Analysis

Introduction: High sensitivity C-reactive protein (hsCRP), a biomarker of inflammation, can risk stratify patients for cardiovascular disease including heart failure (HF). It is not well established if inflammation increases the risk of HF in patients with chronic kidney disease (CKD) and if hsCRP can be utilized to risk stratify patients with CKD for their risk of incident HF. Aims: We assessed the role of hsCRP in risk stratifying patients with CKD for incident HF. Methods: We studied participants of 3 major epidemiologic cohorts: Atherosclerosis Risk in Communities Study, Multi-Ethnic Study of Atherosclerosis, and Jackson Heart Study. High inflammation was classified as hsCRP &gt;3 mg/L and CKD was classified as estimated glomerular filtration rate &lt;60 mL/min/1.73m2. Participants were stratified into 3 groups: neither CKD nor high inflammation, CKD without high inflammation, or CKD with high inflammation. Cox hazards models adjusted for age, sex, race, body mass index, smoking, alcohol use, diabetes, hypertension, and coronary disease were utilized for analysis. Results: 8,692 participants with 460 incident HF events followed over a median 8.32 years were included in our analysis. Participants with CKD without high inflammation (HR = 1.45; 95% CI 1.14 to 1.85) and CKD with high inflammation (2.05; 1.61 to 2.61) were associated with an increased risk of incident HF compared with participants without CKD or high inflammation (referent, Figure). Furthermore, participants with CKD and a hsCRP &gt;3 mg/L had an increased risk of incident HF (1.41; 1.06 to 1.88) compared with participants with CKD but hsCRP ≤3 mg/L (referent). Conclusions: Patients with CKD and high levels of inflammation carry a 2-fold increased risk of incident HF. In patients with CKD, hsCRP levels &gt;3mg/L may be useful to risk stratify patients with increased risk of developing HF.

Abstract 12085: Emergency Heart Failure Mortality Risk Grade (EHMRG) Score Quintiles Correlate With Short and Long-Term Healthcare Costs

Introduction: The use of the EHMRG model in the emergency department (ED) has been demonstrated to improve outcomes for patients presenting with acute heart failure (HF). It is unknown if the EHMRG model also correlates with healthcare costs, which has not been examined in other HF risk models. Hypothesis: We hypothesized that patients with higher EHMRG risk scores, i.e., sicker, would have higher costs of care in short-term (30-day) and longer-term (up to 2 year) time horizons. Methods: We examined direct costs of care from a health payer perspective using the original EHMRG derivation cohort of 11,857 patients hospitalized with acute HF in Ontario, Canada (from 2004) and linking to population-based case-costing databases. Costs were stratified by the quintiles of the EHMRG risk score (Q1 = lowest risk, Q5 = highest risk). Costs (in 2021 Canadian dollars) were categorized into hospital, physician, drug, home care, long term care (LTC), and other costs. Results: Patients in the lowest EHMRG risk quintile (Q1), compared to higher quintiles (Q2-Q5) had lower total cost of care in both the short-term ($8,113 vs $9,442, $10,557, $12,078 and $15,005, p &lt;0.001) and long-term ($46,661 vs $55,904, $58,904, $63,286 and $64,229, p&lt;0.001). This positive correlation between EHMRG risk quintile and cost of care was also observed for hospital costs ($26,388 [Q1] vs $35,659 [Q5], p&lt;.0001) and LTC costs ($1,236 [Q1] vs $6,316 [Q5], p&lt;.0001) at all time intervals, including at 2 years shown here. Physician costs and drug costs were positively correlated with EHMRG risk quintiles at 30 days (physician: $1,241 [Q1] vs $1,762 [Q5], p&lt;0.0001; drug: $219 [Q1] vs $282 [Q5], p&lt;.0001), and negatively correlated at 2 years (physician: $7,943 [Q1] vs $7,175 [Q5], p&lt;.0001; drug: $4,539 [Q1] vs $4,377 [Q5], p&lt;.0001). There was an increasing trend of costs irrespective of the formulation of the EHMRG risk score as 7-day risk quintile, 30-day risk quintile, or 30-day risk tertile. Conclusion: The EHMRG7 risk score was positively correlated with healthcare costs from 30 days to 2 years after initial ED presentation. This novel correlational study demonstrated that in the absence of an associated intervention, higher mortality risk in HF patients portends higher costs in short and long-term follow-up.

Association between the neutrophil-to-lymphocyte ratio and risk of in-hospital heart failure and arrhythmia in patients with acute myocardial infarction.

This study was to probe into the relationship between the neutrophil-to-lymphocyte ratio (NLR) and both in-hospital and long-term heart failure risk in patients with acute myocardial infarction (AMI). 990 patients with AMI, including 386 with non-ST-segment elevation myocardial infarction (NSTEMI) and 604 with segment elevation myocardial infarction (STEMI) were recruited between January 2019 and March 2022. The in-hospital acute heart failure (AHF) and arrhythmia events were recorded. The NLR was significantly greater in the AHF group in STEMI and NSTEMI patients, with a higher frequency of arrhythmia in comparison to the non-AHF group. A high NLR was related to a high level of myocardial injury markers, accompanied with more AHF and arrhythmia events. Multivariate logistic regression analyses revealed that high NLR is independently linked with increased in-hospital AHF and arrhythmia risk. Receiver operating characteristic curve analyses revealed that the prognostic value of NLR for in-hospital AHF was 0.704 in STEMI patients and 0.766 in NSTEMI patients. However, during a median follow-up of 28 months with 32 heart failure patients, there was no significant difference between the low NLR group (n = 18) and the high NLR group (n = 14). Further analysis showed that the two groups did not significantly differ in the occurrence of heart failure within 12 months of discharge. Our results indicate that NLR is an independent risk factor of in-hospital AHF in AMI patients. However, NLR has no value in predicting long-term heart failure.

Decreased cholinesterase level combined with renal dysfunction and sympathetic denervation associated with increased cardiac mortality in systolic heart failure.

Cardiac mortality in patients with heart failure (HF) is likely to be aggravated by malnutrition, assessed by serum cholinesterase (ChE) level, as well as by kidney dysfunction or impairment of cardiac sympathetic denervation. Their prognostic interactions, however, have not been determined. A total of 991 systolic HF patients were enrolled in our HF database following clinical evaluation including evaluation of the nutrition state and assessment of standardized heart-to-mediastinum ratio (sHMR) of iodine-123-labeled meta-iodobenzylguanidine activity. Patients were followed up for an average of 43 months with the primary endpoint of fatal cardiac events (CEs). The CE patient group had a lower level of ChE, lower estimated glomerular filtration rate (eGFR) and lower late sHMR than those in the non-CE patient group. A five-parameter model with the addition of serum ChE selected in the multivariate logistic analysis (model 2) significantly increased the AUC predicting risk of cardiac events compared with a four-parameter model without serum ChE (model 1), and net reclassification analysis also suggested that the model with the addition of serum cholinesterase significantly improved cardiac event prediction. Moreover, in overall multivariate Cox hazard analysis, serum ChE, eGFR and late sHMR were identified to be significant prognostic determinants. HF patients with two or all of the prognostic variables of serum ChE < 230 U/L, eGFR < 48.8 ml/min/1.73 m2 and late sHMR < 1.90 had significantly and incrementally increased CE rates compared to those in HF patients with none or only one of the prognostic variables. Decreases in cholinesterase level and kidney function further increase cardiac mortality risk in HF patients with impairment of cardiac sympathetic innervation.

Heart failure risk in patients with atrial fibrillation treated with catheter ablation vs antiarrhythmic drugs

Atrial fibrillation (AF) increases heart failure (HF) risk. Whereas the risk of HF-related hospitalization and mortality are known in the setting of AF, the impact of AF treatment on HF development is understudied. The purpose of this study was to compare HF incidence among AF patients treated with antiarrhythmic drugs (AADs) vs catheter ablation (CA). AF patients with 1 prior AAD usage were identified in 2014-2022 Optum Clinformatics database. Patients were classified into 2 cohorts: those receiving CA vs those receiving a different AAD prescription. The 2 cohorts were matched on sociodemographic and clinical covariates using propensity score matching technique. Cox regression model was used to compare incident HF risk in the 2 cohorts. Subgroup analyses were performed by race/ethnicity, sex, AF subtype, and CHA2DS2-VASc score. After matching, 9246 patients were identified in each cohort (AAD and CA). Patients receiving CA had a 57% lower risk of incident HF than those treated with AADs (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.40-0.46). Subgroup analysis by race/ethnicity depicted similar results, with non-Hispanic White (HR 0.43; 95% CI 0.40-0.46), non-Hispanic Black (HR 0.46; 95% CI 0.35-0.60), Hispanic (HR 0.53; 95% CI 0.40-0.70), and Asian (HR 0.46; 95% CI 0.24-0.92) patients treated with CA (vs AAD) having significantly lower risk of HF, respectively. The effect size of CA remained significant in subgroups defined by sex, AF subtypes, and CHA2DS2-VASc score. AF patients receiving CA had ∼57% lower risk of developing HF than those receiving AAD. The lower risk of HF associated with CA vs AAD persisted across different race/ethnicity, sex, AF subtypes, and CHA2DS2-VASc score.

Rapid kidney function decline and increased risk of heart failure in patients with type 2 diabetes: findings from the ACCORD cohort

BackgroundImpaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors.MethodsIncluded in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7–3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI).ResultsOver 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51–4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63–5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001).ConclusionsIn patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D.

1226-P: A Rapid Rate of Kidney Function Decline Is Associated with Increased Risk of Heart Failure in Patients with Type 2 Diabetes—Results from ACCORD Study

Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D. We further assessed whether accounting for the rate of estimated glomerular filtration rate (eGFR) decline over time improved prediction of HF risk as compared to standard clinical predictors. Included in the study were 9,192 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with available baseline urinary albumin-to-creatinine ratio (UACR) data and ≥3 eGFR measurements during follow-up. The association between rapid kidney function decline (eGFR loss ≥5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during follow-up was estimated by logistic regression. We calculated integrated discrimination improvement (IDI) by adding rapid kidney function decline to HF predictors. Over a median follow-up of 5.0 years (interquartile range 4.1-5.7), 1,432 participants (15.6%) experienced rapid kidney function decline and 355 (3.9%) experienced a HF event. Rapid kidney function decline was associated with a 3.57-fold increase in HF odds (odds ratio [OR] 3.57; 95% confidence interval [CI] 2.86-4.45). This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline and censoring (OR 4.47; 95% CI 3.7-6.11). Adding rapid kidney function decline during follow-up to other predictors (WATCH-DM score, eGFR, and UACR) significantly improved HF risk classification (relative IDI=+49%, p&amp;lt;0.0001). In patients with T2D, rapid kidney function decline was associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF prediction in patients with T2D. Disclosure A.Bano: None. C.Bueno junior: None. Y.Tang: None. X.Sun: None. E.Hall: None. J.Mitri: Other Relationship; Novo Nordisk, Research Support; Kowa Company, Ltd. M.Morieri: Advisory Panel; Merck Sharp &amp; Dohme Corp., Amarin Corporation, Servier Laboratories, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. H.Shah: None. A.Doria: None. Funding National Heart, Lung, and Blood Institute (N01HC95178, N01HC95179, N01HC95180, N01HC95181, N01HC95182, N01HC95183, N01HC95184, IAAY1HC-9035, IAAY1HC1010); National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; General Clinical Research Centers

Unravelling the Interplay between Cardiac Metabolism and Heart Regeneration.

Ischemic heart disease (IHD) is the leading cause of heart failure (HF) and is a significant cause of morbidity and mortality globally. An ischemic event induces cardiomyocyte death, and the ability for the adult heart to repair itself is challenged by the limited proliferative capacity of resident cardiomyocytes. Intriguingly, changes in metabolic substrate utilisation at birth coincide with the terminal differentiation and reduced proliferation of cardiomyocytes, which argues for a role of cardiac metabolism in heart regeneration. As such, strategies aimed at modulating this metabolism-proliferation axis could, in theory, promote heart regeneration in the setting of IHD. However, the lack of mechanistic understanding of these cellular processes has made it challenging to develop therapeutic modalities that can effectively promote regeneration. Here, we review the role of metabolic substrates and mitochondria in heart regeneration, and discuss potential targets aimed at promoting cardiomyocyte cell cycle re-entry. While advances in cardiovascular therapies have reduced IHD-related deaths, this has resulted in a substantial increase in HF cases. A comprehensive understanding of the interplay between cardiac metabolism and heart regeneration could facilitate the discovery of novel therapeutic targets to repair the damaged heart and reduce risk of HF in patients with IHD.

Heart failure is associated with increased risk of all-cause mortality after transvenous lead extraction: A systematic review and meta-analysis.

Transvenous lead extraction (TLE) is increasingly considered in cardiac implantable electronic device management. Heart failure (HF) might be associated with mortality risks after the TLE procedure. This study aims to assess mortality risk in HF patients undergoing TLE. We searched MEDLINE and Embase databases from inception to June 2022 to identify articles that included patients with and without HF who underwent TLE, which reported mortality in both groups. The pooled effect size was calculated with a random-effects model and 95% CI to compare post-TLE mortality between the two groups. Eleven studies were included in the analysis. Each left ventricular ejection fraction (LVEF) increased by 1% was associated with reduced mortality by 2% (HR = 0.98, 95% CI: 0.97-0.99, I 2 = 74.9%, p < .01). The presence of HF compared to those without HF was associated with higher mortality rates (OR: 3.04, 95% CI: 2.56-3.61, I 2 = 0.0%, p < .531). There was a significant increase in the mortality rates in patients with New York Heart Association (NYHA) function class III (OR: 2.29, 95% CI: 1.29-4.06, I 2 = 0.0%, p = .498) and NYHA IV (OR: 8.5, 95% CI: 2.98-24.3, I 2 = 0.0%, p = .997). Our study found that post-TLE mortality decreases by 2% as LVEF increases by 1%, also mortality is higher in patients with NYHA III and IV.

Increased circulating phenylacetylglutamine levels elevates the predictive value of cardiovascular event risk in heart failure patients.

Phenylacetylglutamine (PAGln)-a newly discovered microbial metabolite produced by phenylalanine metabolism-is reportedly associated with cardiovascular events via adrenergic receptors. Nonetheless, its association with cardiovascular outcomes in heart failure (HF) patients remains unknown. This study aimed to prospectively investigate the prognostic value of PAGln for HF. Plasma PAGln levels were quantified by liquid chromatography-tandem mass spectrometry. We first assessed the association between plasma PAGln levels and the incidence of adverse cardiovascular events in 3152 HF patients (including HF with preserved and reduced ejection fraction) over a median follow-up period of two years. The primary endpoint was the composite of cardiovascular death or heart transplantation. We then assessed the prognostic role of PAGln in addition to the classic biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP). The correlation between PAGln levels and β-blocker use was also investigated. In total, 520 cardiovascular deaths or heart transplantations occurred in the HF cohort. Elevated PAGln levels were independently associated with a higher risk of the primary endpoint in a dose-response manner, regardless of HF subtype. Concurrent assessment of PAGln and NT-proBNP levels enhanced risk stratification among HF patients. PAGln further showed prognostic value at low NT-proBNP levels. Additionally, the interaction effects between PAGln and β-blocker use were not significant. Plasma PAGln levels are an independent predictor of an increased risk of adverse cardiovascular events in HF. Our work could provide joint and complementary prognostic value to NT-proBNP levels in HF patients. This article is protected by copyright. All rights reserved.

Relationship between remnant cholesterol and risk of heart failure in participants with diabetes mellitus.

Evidence about the association between calculated remnant cholesterol (RC) and risk of heart failure (HF) in participants with diabetes mellitus (DM) remains sparse and limited. We included a total of 22 230 participants with DM from the UK Biobank for analyses. Participants were categorized into three groups based on their baseline RC measures: low (with a mean RC of 0.41mmol/L), moderate (0.66mmol/L), and high (1.04mmol/L). Cox proportional hazards models were used to evaluate the relationship between RC groups and HF risk. We performed discordance analysis to evaluate whether RC was associated with HF risk independently of low-density lipoprotein cholesterol (LDL-C). During a mean follow-up period of 11.5 years, there were a total of 2232 HF events observed. The moderate RC group was significantly related with a 15% increased risk of HF when compared with low RC group (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.01-1.32), while the high RC group with a 23% higher HF risk (HR=1.23, 95% CI: 1.05-1.43). There was significant relationship between RC as a continuous measure and the increased HF risk (P<0.01). The association between RC and risk of HF was stronger in participants with HbA1c level ≥ 53mmol/mol when compared with HbA1c < 53mmol/mol (P for interaction=0.02). Results from discordance analyses showed that RC was significantly related to HF risk independent of LDL-C measures. Elevated RC was significantly associated with risk of HF in patients with DM. Moreover, RC was significantly related to HF risk independent of LDL-C measures. These findings may highlight the importance of RC management to HF risk in patients with DM.