Risk Of Heart Failure Hospitalization Research Articles

Cardiovascular Burden of the V142I Transthyretin Variant.

Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments. To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population. A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024. V142I carrier status (n = 754, 3.2%). Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data. Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant. Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.

Dynamic Risk Stratification of worsening heart failure using a Deep learning enabled Implanted Ambulatory Single lead ECG

Abstract Background and Aims Implantable loop recorders (ILRs) provide continuous single-lead ambulatory electrocardiogram (aECG) monitoring. It is unknown whether these aECGs could be used to identify worsening heart failure. Methods and results We linked ILR aECG from Medtronic device database to the LVEF measurements in Optum® de-identified electronic health record dataset. We trained an AI algorithm (aECG-CNN) on a dataset of 35,741 aECGs from 2247 patients to identify left ventricular ejection fraction (LVEF) ≤ 40% and assessed its performance using the area under the receiver operating characteristic curve (AUROC). aECG-CNN was then used to identify patients with increasing risk of heart-failure hospitalization in a real-world cohort of 909 patients with prior heart failure diagnosis. This dataset provided 12,467 follow up monthly evaluations, with 201 heart failure hospitalizations. For every month, time series features from these predictions were used to categorize patients into high and low risk groups and predict heart failure hospitalization in the next month. The risk of heart-failure hospitalization in the next 30 days was significantly higher in the cohort that aECG-CNN identified as high risk (hazard ratio 1·89; 95% confidence interval 1·28-2·79; p = 0·001) compared to low risk, even after adjusting patient demographics. (Hazard ratio 1·88, 1.27 to 2·79 p = 0·002). Conclusion An AI algorithm trained to detect LVEF ≤40% using ILR aECGs can also readily identify patients at increased risk for HF hospitalizations by monitoring changes in the probability of heart failure over 30 days.

Predictive value of quality of life as measured by KCCQ in heart failure patients: A meta-analysis.

Studies on the predictive ability of disease-specific health quality of life (QoL) in patients with heart failure (HF) have produced conflicting results. To address these gaps in knowledge, we conducted a meta-analysis to evaluate the predictive value of QoL measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with HF. We searched PubMed, and Embase databases to identify studies investigating the predictive utility of baseline QoL measured by the KCCQ in HF patients. The outcome measures were all-cause mortality and HF hospitalisation. The predictive value of QoL was expressed by pooling the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the bottom versus the top category of KCCQ score or for per 10-point KCCQ score decrease. Twelve studies reporting on 11 articles with a total of 34,927 HF patients were identified. Comparison of the bottom with the top KCCQ score, the pooled adjusted HR was 2.34 (95% CI 2.10-2.60) and 2.53 (95% CI 2.23-2.88) for all-cause mortality and HF hospitalisation, respectively. Additionally, a 10-point decrease in KCCQ score was associated with a 12% (95% CI 7%-16%) increased risk of all-cause mortality and a 14% (95% CI 13%-15%) increased risk of HF hospitalisation. Poor health-related QoL as determined by the lower KCCQ score, was associated with an increased risk of all-cause mortality and HF hospitalisation in patients with HF. Measuring disease-specific health-related QoL using the KCCQ score may provide valuable predictive information for HF patients.

Antiarrhythmic and Anti-Inflammatory Effects of Sacubitril/Valsartan on Post-Myocardial Infarction Scar.

Sacubitril/valsartan (Sac/Val) is superior to angiotensin-converting enzyme inhibitors in reducing the risk of heart failure hospitalization and cardiovascular death, but its mechanistic data on myocardial scar after myocardial infarction (MI) are lacking. The objective of this work was to assess the effects of Sac/Val on inflammation, fibrosis, electrophysiological properties, and ventricular tachycardia inducibility in post-MI scar remodeling in swine. After MI, 22 pigs were randomized to receive β-blocker (BB; control, n=8) or BB+Sac/Val (Sac/Val, n=9). The systemic immune response was monitored. Cardiac magnetic resonance data were acquired at 2-day and 29-day post MI to assess ventricular remodeling. Programmed electrical stimulation and high-density mapping were performed at 30-day post MI to assess ventricular tachycardia inducibility. Myocardial samples were collected for histological analysis. Compared with BB, BB+Sac/Val reduced acute circulating leukocytes (P=0.009) and interleukin-12 levels (P=0.024) at 2-day post MI, decreased C-C chemokine receptor type 2 expression in monocytes (P=0.047) at 15-day post MI, and reduced scar mass (P=0.046) and border zone mass (P=0.043). It also lowered the number and mass of border zone corridors (P=0.020 and P=0.05, respectively), scar collagen I content (P=0.049), and collagen I/III ratio (P=0.040). Sac/Val reduced ventricular tachycardia inducibility (P=0.026) and the number of deceleration zones (P=0.016). After MI, compared with BB, BB+Sac/Val was associated with reduced acute systemic inflammatory markers, reduced total scar and border zone mass on late gadolinium-enhanced magnetic resonance imaging, and lower ventricular tachycardia inducibility.

Representativeness of the PIONEER-HF and PARAGLIDE-HF in patients hospitalized with acute heart failure.

The PIONEER-HF and PARAGLIDE-HF trials aimed to determine the efficacy and safety of the in-hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real-world routine care is unclear. This study aimed to investigate the applicability of the PIONEER-HF and PARAGLIDE-HF trials to real-world AHF patients. We identified 28293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER-HF eligible (n=3683) and non-eligible (n=3502) patients with an LVEF ≤40%, and PARAGLIDE-HF eligible (n=5191) and non-eligible (n=5832) patients with an LVEF >40%. Over a mean follow-up of 3.5years, the PIONEER-HF non-eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88-1.04). No significant difference was found in the composite outcome between PARAGLIDE-HF non-eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90-1.04). Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril-valsartan. Yet, non-eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril-valsartan benefits in non-eligible AHF patients.

Kidney and Cardiovascular Effectiveness of Empagliflozin Compared With Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes

Placebo-controlled trials of sodium-glucose cotransporter-2 inhibitors (SGLT2i) demonstrate kidney and cardiovascular benefits for people with type 2 diabetes (T2D) and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4i), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare outcomes for empagliflozin and DPP4i initiators with T2D between 2016 and 2020. The primary composite kidney outcome included 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease (ESKD), or all-cause mortality through 2 years or censoring. We also assessed cardiovascular and safety outcomes. Among 62,197 new users, 20,279 initiated empagliflozin, and 41,918 initiated DPP4i. Over a median follow-up of 1.1 years, empagliflozin prescription was associated with a lower risk of the primary outcome (HR 0.75, 95% CI 0.65-0.87) compared with DPP4i. Risks for mortality (HR 0.76, 95% CI 0.62-0.92) and a cardiovascular composite of stroke, myocardial infarction, or all-cause mortality (HR 0.81, 95% CI 0.70-0.95) were also lower for empagliflozin initiators. No difference in heart failure hospitalization risk between groups was observed. Genital mycotic infections were more common in patients prescribed empagliflozin (HR 1.72, 95% CI 1.58 - 1.88). Empagliflozin was associated with a lower risk of the primary outcome in patients with CKD (HR 0.68, 95% CI 0.53-0.88) and those without CKD (HR 0.79, 95% CI 0.67 - 0.94). In conclusion, initiation of empagliflozin was associated with a significantly lower risk of kidney and cardiovascular outcomes compared with DPP4i over a median of just over 1 year. The association with a lower risk for clinical outcomes was apparent even for people without known CKD at baseline.

Age-stratified clinical outcome in patients with known heart failure who receive pacemaker-, resynchronization therapy- or defibrillator implants.

Introduction Patients with heart failure (HF) and bradycardia may be eligible for different types of cardiac implantable electronic devices (CIED), depending on presence of AV conduction disease, age and comorbidities. We aimed to assess prognosis for these patients, after CIED implantation, stratified for type of CIED device. Methods All patients with preexisting HF diagnosis who received a CIED with a right ventricular lead during the period 2005-2018 in Sweden were identified via the Pacemaker-registry. Data was crossmatched with the population registry and national disease registries. Outcome was 5-year risk of HF hospitalization, and mortality. Results 37745 patients were included in the study. Comparing demographics for ICD vs. pacemaker implants, median age was 66 years vs. 83 years, 20% vs. 41% were female, 64% vs. 50% had ischemic heart disease and 35% vs. 67% had atrial fibrillation (all p<0,001). 5-year mortality was highest in single-chamber pacemaker recipients (61% compared to average 40%, p<0.001) but proportion of cardiovascular mortality was highest for CRT recipients (68% vs 63% p<0.001). Adjusted mortality was higher for pacemaker-patients in all age decile groups (ranging from <60 to >90 years old, all p<0.001). HF hospitalization occurred in 28% (dual-chamber pacemaker) to 39% (CRT-P) of patients, and cause of death was HF in 15% (dual-chamber pacemaker) to 25% (CRT-D), all p<0.001. Conclusion In this large real-world cohort of CIED treated patients with prior heart failure, demography- and mortality-data indicate that clinicians chose devices according to the overall status of the patient. Heart failure related events occurred in all groups, but were more common in CRT-treated patients.

Understanding The Role of SGLT2 Inhibitors in Cardiovascular Risk Reduction for Type 2 Diabetes Patients-A Literature Review

Introduction: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular events and heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a novel class of antidiabetic agents with potential cardiovascular benefits. This systematic review aims to evaluate the impact of SGLT2 inhibitors on reducing cardiovascular events and heart failure hospitalizations in patients with T2DM. Aims: The review aims to comprehensively evaluate the impact of SGLT2 inhibitors on reducing cardiovascular events, including MACE, and HF hospitalizations in patients with T2DM. Methods: A comprehensive literature search was conducted in major electronic databases like PubMed, Google Scholar and Science Direct to identify relevant studies. Studies investigating the cardiovascular outcomes of SGLT2 inhibitors in T2DM patients were included. Data extraction and quality assessment were performed independently by three reviewers using predefined criteria. Results: A total of 17 studies met the inclusion criteria and were included in the review. The analysis of clinical trials, including EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, demonstrated significant reductions in MACE and HF hospitalizations with SGLT2 inhibitors compared to placebo or standard care. Real-world evidence from studies such as the CVD-REAL and EASEL studies further supported these findings, showing consistent cardiovascular benefits of SGLT2 inhibitors in routine clinical practice. The findings suggest that SGLT2 inhibitors are associated with a reduction in cardiovascular events, including myocardial infarction, stroke, and cardiovascular mortality, as well as a decreased risk of heart failure hospitalizations in patients with T2DM. Conclusion: This systematic review provides evidence supporting the cardiovascular benefits of SGLT2 inhibitors in T2DM management. The findings underscore the importance of considering these agents as part of comprehensive cardiovascular risk reduction strategies in T2DM patients. Further research is necessary to explicate the mechanisms underlying these benefits and optimize their clinical use.

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

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

SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits.

An increasing number of individuals is at high risk of type 2 diabetes (T2D) and its cardiovascular complications, including heart failure (HF), chronic kidney disease (CKD), and premature death. The sodium-glucose cotransporter-2 (SGLT2) protein sits in the proximal tubule of human nephrons to regulate glucose reabsorption, and its inhibition by gliflozins represents the cornerstone of contemporary T2D and HF management. Herein, we aim to provide an updated view on the pleiotropy of gliflozins, provide mechanistic insights and delineate related cardiovascular (CV) benefits. By discussing contemporary evidence obtained in preclinical models and landmark randomized controlled trials, we move from bench to bedside across the broad spectrum of cardio- and cerebrovascular diseases. With robust trials confirming a reduction in major adverse CV events (MACE; composite endpoint of CV death, non-fatal myocardial infarction, and non-fatal stroke), SGLT2 inhibitors strongly mitigate the risk for heart failure hospitalization in diabetics and non-diabetics alike while conferring renoprotection in specific patient populations. Along four major pathophysiological axes (ie, at cardiac, vascular, renal, and systemic levels), we provide insights into key mechanisms that may underlie their beneficial effects, including gliflozins' role in the modulation of vascular inflammation, oxidative stress, cellular energy metabolism and housekeeping mechanisms. We also discuss how this drug class controls hyperglycaemia, ketogenesis, natriuresis, and hyperuricaemia, contributing to their pleiotropic effects. Finally, evolving data in the setting of cerebrovascular diseases and arrythmias are presented, and potential implications for future research and clinical practice are comprehensively reviewed.

Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry

There is a paucity of data on the clinical characteristics, management, and outcomes of women compared with men with heart failure in low-income and middle-income countries compared with high-income countries. We examined sex differences in risk factors, clinical characteristics, and treatments, and prospectively assessed the risk of heart failure hospitalisation and mortality in patients with heart failure in 40 high-income, middle-income, and low-income countries. Participants aged 18 years or older with heart failure were enrolled from Dec 20, 2016, to Sept 9, 2020 in the prospective Global Congestive Heart Failure (G-CHF) study from 257 centres in 40 high-income, middle-income, and low-income countries. Participants were followed up until May 25, 2023. We recorded the demographic characteristics, medical history, and treatments of participants. We prospectively recorded data on heart failure hospitalisation and mortality by sex in the overall study, according to country economic status, and according to level of left ventricular ejection fraction (LVEF). 23 341 participants (9119 [39·1%] women and 14 222 [60·1%] men) were recruited and followed up for a mean of 2·6 years (SD 1·4). The mean age of women in the study was 62 years (SD 17) compared with 64 years (14) in men. Fewer women than men had an LVEF of 40% or lower (51·7% women vs 66·2% men). By contrast, more women than men had an LVEF of 50% or higher (33·2% women vs 18·6% men). Hypertensive heart failure was the most common aetiology in women (25·5% women vs 16·8% men), whereas ischaemic heart failure was the most common aetiology in men (45·6% men vs 26·6% women). Signs and symptoms of congestion were more common in women than men: 42·6% of women had a New York Heart Association functional class of III or IV compared with 37·9% of men. The use of heart failure medications and cardiac tests did not differ systematically between the sexes, although implantable cardioverter defibrillator (ICD) implantation was lower among women than men (8·7% women vs 17·2% men). The adjusted risk of heart failure hospitalisation was similar in women and men (women-to-men adjusted hazard ratio [HR] 0·99 [95% CI 0·92-1·05]). This pattern was consistent within groups of countries categorised by economic status, geographical region, and by LVEF level. However, women had a lower adjusted risk of mortality (women-to-men adjusted HR 0·79 [95% CI 0·75-0·84]) despite adjustments for prognostic factors-a pattern which was consistently observed across groups of countries irrespective of economic status, geography, and LVEF levels of patients. The underlying cause of heart failure and ejection fraction phenotype differ between women and men, as do the severity of symptoms. Heart failure treatments (except ICD use) were not consistently in favour of one sex. Paradoxically, while the rates of hospitalisations were similar among women and men, the risk of death was lower among women. These patterns were consistent regardless of the economic status of the countries. The higher mortality among men is unexplained and warrants further study. Bayer.

Prognostic significance of growth differentiation factor-15 across age in chronic heart failure.

Growth differentiation factor-15 (GDF15), a cytokine in the transforming growth factor family, is up-regulated in stress and inflammatory conditions and is elevated in patients with heart failure (HF). However, the age-specific attributes and prognostic significance of GDF15 across age remain unknown in chronic HF (CHF). Serum levels of GDF15 were examinedin 942 hypertensive patients (median 68years) with CHF from the SUPPORT trial across the four age groups [under 50 (n=73), 51-59 (n=158), 60-69 (n=296), and 70-79years (n=415)] and in the continuous spectrum. Clinical correlates of GDF15 were explored using the classic stepwise and LASSO (least absolute shrinkage and selection operator) regression approaches. Interaction terms with age were tested in the LASSO regression approach. The associations with the composite outcome of HF hospitalization or all-cause death were investigated across ages. Median GDF15 levels (pg/mL) increased along with aging, from 691 in under 50years to 855 in 51-59years, 1114 in 60-69years, and 1516 in 70-79years (trend P<0.001). Age, sex, systolic blood pressure, history of diabetes, ischaemic heart disease, left ventricular (LV) end-systolic dimension, LV ejection fraction, estimated glomerular filtration rate, haemoglobin, N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin, C-reactive protein, and the use of angiotensin-converting enzyme inhibitors, diuretics, and statins were mutually selected as clinical covariates of GDF15. The LASSO regression analysis identified significant interactions between age and the history of diabetes and NT-proBNP, with particularly robust associations in patients aged between 60 and 70years. During the mean follow-up of 8.6years, 474 composite endpoints of HF hospitalization or death occurred. GDF15 was associated with a higher risk of HF hospitalization or all-cause death [adjusted hazard ratio 1.84 (95% confidence interval 1.45-2.33)], with a particularly heightened risk in patients aged around 70years (Pinteraction =0.0008). The model with GDF15 on top of other established risk factors yielded marginally higher C-statistics compared with the model without GDF15 (0.803 and 0.796, P=0.045). The additive value of GDF15 on top of other established risk factors appeared similar across ages. A universal cut-off value of 1400pg/mL performed well in discriminating between those with and without HF hospitalization or death. Some clinical correlates of GDF15 have an interaction with age. GDF15 is an important determinant of cardiovascular endpoints, particularly in patients aged around 70years. The additive value of GDF15 appeared consistent across ages, suggesting the use of a universal cut-off value.

Risk of supranormal left ventricular ejection fraction in patients with aortic stenosis.

Cardiovascular events are increasing in patients with supranormal left ventricular ejection fraction (snLVEF). However, the effect of snLVEF in patients with aortic stenosis (AS) remains unclear, especially in patients with moderate AS. This study aimed to evaluate the prognosis of mortality and heart failure (HF) in patients with LVEF ≥ 50% and moderate or severe AS. This retrospective study targeted patients with moderate or severe AS and LVEF > 50%. LVEF of 50%-65% was classified as normal LVEF (nLVEF, nEF group) and >65% as snLVEF (snEF group). AS severity was stratified based on the aortic valve area into moderate (1.0-1.5 cm²) and severe (<1.0 cm²). Primary outcomes included all-cause mortality and HF hospitalization. A total of 226 participants were included in this study. There were 67 and 65 participants with moderate AS in snEF (m-snEF) and nEF groups (m-nEF), respectively, and 41 and 53 participants with severe AS in the snEF (s-snEF) and nEF groups (s-nEF), respectively. During the observation period (median: 554 days), the primary composite outcome occurred in 108 individuals. Cox hazard analysis revealed no significant differences among the four groups in primary composite outcomes. With respect to HF hospitalization, the adjusted hazard ratios (95% confidence intervals) with m-snEF as the reference were as follows: m-nEF, 0.41 (0.19-0.89); s-nEF, 1.43 (0.76-2.67); and s-snEF, 1.83 (1.00-3.35). The risk of HF hospitalization for m-snLVEF was higher than m-nLVEF and not significantly different from s-nLVEF.

Association of left atrial enlargement with heart failure events in non-valvular atrial fibrillation patients with preserved left ventricular ejection fraction.

Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little is known regarding the risk stratification for incident HF in AF patients, especially with preserved left ventricular ejection fraction (LVEF). The Fushimi AF Registry is a community-based prospective survey of AF patients. From the registry, 3002 non-valvular AF patients with preserved LVEF and with the data of antero-posterior left atrial diameter (LAD) at enrolment were investigated. Patients were stratified by LAD (<40, 40-44, 45-49, and ≥50 mm) with backgrounds and HF hospitalization incidences compared between groups. Of 3002 patients [mean age, 73.5 ± 10.7 years; women, 1226 (41%); paroxysmal AF, 1579 (53%); and mean CHA2DS2-VASc score, 3.3 ± 1.7], the mean LAD was 43 ± 8 mm. Patients with larger LAD were older and less often paroxysmal AF, with a higher CHA2DS2-VASc score (all P < 0.001). Heart failure hospitalization occurred in 412 patients during the median follow-up period of 6.0 years. Larger LAD was independently associated with a higher HF hospitalization risk [LAD ≥ 50 mm: hazard ratio (HR), 2.36; 95% confidence interval (CI), 1.75-3.18; LAD 45-49 mm: HR, 1.84; 95% CI, 1.37-2.46; and LAD 40-44 mm: HR, 1.34; 95% CI, 1.01-1.78, compared with LAD < 40 mm) after adjustment by age, sex, AF type, and CHA2DS2-VASc score. These results were also consistent across major subgroups, showing no significant interaction. Left atrial diameter is significantly associated with the risk of incident HF in AF patients with preserved LVEF, suggesting the utility of LAD regarding HF risk stratification for these patients.

Daprodustat and Heart Failure in CKD.

Patients with chronic kidney disease (CKD) are at higher risk for heart failure. The hypoxia inducible factor prolyl hydroxylase inhibitor daprodustat is an orally acting alternative to conventional injectable erythropoietin-stimulating agents (ESA) for the treatment of anemia in patients with CKD. Whether daprodustat affects the risk of heart failure hospitalization is unknown. The ASCEND-D (n=2,964) and ASCEND-ND (n=3,872) trials compared daprodustat to conventional ESA in patients with anemia of CKD who did or did not require dialysis, respectively. We identified risk factors for heart failure hospitalization and assessed the effect of daprodustat compared to conventional ESA on heart failure hospitalizations. History of heart failure, diabetes, and higher systolic blood pressure were independently associated with heart failure hospitalization in both trials, irrespective of treatment assignment. The number of first heart failure hospitalizations was greater in the daprodustat arm in patients not receiving dialysis (hazard ratio [HR] 1.22 [0.95-1.56], p=0.12] and in patients receiving dialysis (HR 1.10 [0.84-1.45], p=0.47), though these differences were not statistically significant. HRs in patients with and without history of heart failure were 1.37 (0.89-2.11) vs 1.08 (0.79-1.46) (p-interaction=0.36) in ASCEND-ND, and 1.52 (0.97-2.38) vs 0.93 (0.66-1.30) (p-interaction=0.09) in ASCEND-D, respectively. In post hoc analyses, daprodustat increased total (first and recurrent) heart failure hospitalizations in participants not receiving dialysis (rate ratio 1.46 [1.11-1.92], p=0.007) ) but not in participants receiving dialysis (rate ratio 1.01 [0.74-1.39], p=0.93). Daprodustat did not significantly affect the risk of a composite outcome of first heart failure hospitalization or death. A greater number of first heart failure hospitalization events occurred in patients treated with daprodustat compared with conventional ESA, but this difference did not reach statistical significance. Differences in the number of heart failure hospitalization events were most apparent in patients not receiving dialysis and in patients with history of heart failure.

Catheter Ablation for Atrial Fibrillation in Patients with Left Ventricular Ejection Fraction ≤ 45%: A Meta-Analysis of Randomized Controlled Trials.

Atrial fibrillation (AF) and heart failure (HF) frequently coexist, resulting in adverse outcomes. However, controversies remain regarding the efficacy of catheter ablation (CA) in AF patients with severe left ventricular dysfunction. The purpose of this study was to perform a meta-analysis of prospective randomized controlled trials to evaluate the efficacy of CA versus medical therapy (MT) in AF patients with left ventricular ejection fraction (LVEF) ≤45%. We searched the literature for studies that compared CA to MT in AF patients with LVEF ≤45%. A meta-analysis of 7 clinical trials was performed, including 1163 patients with AF and HF. Subgroup analysis was performed based on baseline LVEF. All tests were 2-sided; only the p-value <0.05 was considered statistically significant. We found that CA was associated with lower all-cause mortality (risk ratio: 0.52, 95% CI: 0.37 to 0.72; p<0.01) and greater improvements in LVEF (mean difference: 4.80%, 95% CI: 2.29% to 7.31%; p<0.01) compared to MT. Patients in the CA group had a lower risk of HF hospitalization and AF recurrence and a significantly better quality of life than those in the MT group. The results of subgroup analysis indicated that patients with milder left ventricular dysfunction improved LVEF after AF ablation (mean difference: 6.53%, 95% CI: 6.18% to 6.88%; p<0.01) compared to patients with more severe disease (mean difference: 2.02%, 95% CI: 0.87% to 3.16%; p<0.01). Our meta-analysis demonstrated that CA was associated with significant improvements in outcomes of AF patients with LVEF ≤45%. Additionally, AF patients with milder left ventricular dysfunction could benefit more from CA.

Atrial fibrillation and risk of adverse outcomes in heart failure with reduced, mildly reduced, and preserved ejection fraction: A systematic review and meta-analysis.

Heart failure (HF) and atrial fibrillation (AF) frequently co-exist. Contemporary classification of HF categorizes it into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). Aggregate data comparing the risk profile of AF between these three HF categories are lacking. We conducted a systematic review and meta-analysis aimed at determining any significant differences in AF-associated all-cause mortality, HF hospitalizations, cardiovascular mortality (CV), and stroke between HFrEF, HFmrEF, and HFpEF. A systematic search of PubMed, EMBASE, and Cochrane Library databases until February 28, 2023. Data were combined using DerSimonian-Laird random effects model. A total of 22 studies comprising 248 323 patients were retained: HFrEF 123 331 (49.7%), HFmrEF 40 995 (16.5%), and HFpEF 83 997 (33.8%). Pooled baseline AF prevalence was 36% total population, 30% HFrEF, 36% HFmrEF, and 42% HFpEF. AF was associated with a higher risk of all-cause mortality in the total population with pooled hazard ratio (HR) = 1.13 (95% confidence interval [CI] = 1.07-1.21), HFmrEF (HR = 1.25, 95% CI = 1.05-1.50) and HFpEF (HR = 1.16, 95% CI = 1.09-1.24), but not HFrEF (HR = 1.03, 95% CI = 0.93-1.14). AF was associated with a higher risk of HF hospitalizations in the total population (HR = 1.29, 95% CI = 1.14-1.46), HFmrEF (HR = 1.64, 95% CI = 1.20-2.24), and HFpEF (HR = 1.46, 95% CI = 1.17-1.83), but not HFrEF (HR = 1.01, 95% CI = 0.87-1.18). AF was only associated with CV in the HFpEF subcategory but was associated with stroke in all three HF subtypes. AF appears to be associated with a higher risk of all-cause mortality and HF hospitalization in HFmrEF and HFpEF. With these findings, the paucity of data and treatment guidelines on AF in the HFmrEF subgroup becomes even more significant and warrant further investigations.

Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study

BackgroundNo randomized clinical trials have directly compared the cardiorenal effectiveness of empagliflozin and GLP-1RA agents with demonstrated cardioprotective effects in patients with a broad spectrum of cardiovascular risk. We reported the final-year results of the EMPRISE study, a monitoring program designed to evaluate the cardiorenal effectiveness of empagliflozin across broad patient subgroups.MethodsWe identified patients ≥ 18 years old with type 2 diabetes who initiated empagliflozin or GLP-1RA from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we evaluated risks of outcomes including myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE – MI, stroke, or cardiovascular mortality), a composite of HHF or cardiovascular mortality, and progression to end-stage kidney disease (ESKD) (in patients with chronic kidney disease stages 3–4). We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years, overall and within subgroups of age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF).ResultsWe identified 141,541 matched pairs. Compared with GLP-1RA, empagliflozin was associated with similar risks of MI or stroke [HR: 0.99 (0.92, 1.07); RD: -0.23 (-1.25, 0.79)], and lower risks of HHF [HR: 0.50 (0.44, 0.56); RD: -2.28 (-2.98, -1.59)], MACE [HR: 0.90 (0.82, 0.99); RD: -2.54 (-4.76, -0.32)], cardiovascular mortality or HHF [HR: 0.77 (0.69, 0.86); RD: -4.11 (-5.95, -2.29)], and ESKD [0.75 (0.60, 0.94); RD: -6.77 (-11.97, -1.61)]. Absolute risk reductions were larger in older patients and in those with baseline ASCVD/HF. They did not differ by sex.ConclusionsThe cardiovascular benefits of empagliflozin vs. cardioprotective GLP-1RA agents were larger in older patients and in patients with history of ASCVD or HF, while they did not differ by sex. In patients with advanced CKD, empagliflozin was associated with risk reductions of progression to ESKD.

Association Between Age at Diagnosis of Type 2 Diabetes and Hospitalization for Heart Failure: A Population-Based Study.

The relation between age at diagnosis of type 2 diabetes (T2D) and hospitalization for heart failure (HHF) is unclear. We assessed the association between age at diagnosis of T2D and HHF. We conducted a population-based cohort study using administrative health databases from the Canadian province of Ontario, including participants without prior heart failure. We identified people with new-onset T2D between April 1, 2005 and March 31, 2015, and matched each person with 3 diabetes-free adults, according to birth year and sex. We estimated adjusted hazard ratios (HRs) and rate ratios (RRs) for the association between age at T2D diagnosis and incident HHF, which was assessed until March 31, 2020. Among 743 053 individuals with T2D and 2 199 539 matched individuals without T2D, 126 241 incident HHF events occurred over 8.9 years. T2D was associated with a greater adjusted hazard of HHF at younger ages (eg, HR at age 30 years: 6.94 [95% CI, 6.54-7.36]) than at older ages (eg, HR at age 60 years: 2.50 [95% CI, 2.45-2.56]) relative to matched individuals. Additional adjustment for mediators (hypertension, coronary artery disease, and chronic kidney disease) marginally attenuated this relationship. Age at T2D diagnosis was associated with a greater number of HHF events relative to matched individuals at younger ages (eg, RR at age 30 years: 6.39 [95% CI, 5.76-7.08]) than at older ages (eg, RR at age 60 years: 2.65 [95% CI, 2.54-2.76]). Younger age at T2D diagnosis is associated with a disproportionately elevated HHF risk relative to age-matched individuals without T2D.

High-Sensitivity C-Reactive Protein Is Associated With Heart Failure Hospitalization in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease and Normal Left Ventricular Ejection Fraction Undergoing Coronary Angiography.

Systemic chronic inflammation plays a role in the pathophysiology of both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease. This study aimed to investigate whether serum hs-CRP (high-sensitivity C-reactive protein) levels were associated with the future risk of heart failure (HF) hospitalization in patients with metabolic dysfunction-associated fatty liver disease and a normal left ventricular ejection fraction. The study enrolled consecutive individuals with metabolic dysfunction-associated fatty liver disease and normal left ventricular ejection fraction who underwent coronary angiography for suspected coronary heart disease. The study population was subdivided into non-HF, pre-HFpEF, and HFpEF groups at baseline. The study outcome was time to the first hospitalization for HF. In 10 019 middle-aged individuals (mean age, 63.3±10.6 years; 38.5% women), the prevalence rates of HFpEF and pre-HFpEF were 34.2% and 34.5%, with a median serum hs-CRP level of 4.5 mg/L (interquartile range, 1.9-10 mg/L) and 5.0 mg/L (interquartile range, 2.1-10.1 mg/L), respectively. Serum hs-CRP levels were significantly higher in the pre-HFpEF and HFpEF groups than in the non-HF group. HF hospitalizations occurred in 1942 (19.4%) patients over a median of 3.2 years, with rates of 3.7% in non-HF, 20.8% in pre-HFpEF, and 32.1% in HFpEF, respectively. Cox regression analyses showed that patients in the highest hs-CRP quartile had a ≈4.5-fold increased risk of being hospitalized for HF compared with those in the lowest hs-CRP quartile (adjusted-hazard ratio, 4.42 [95% CI, 3.72-5.25]). There was a high prevalence of baseline pre-HFpEF and HFpEF in patients with metabolic dysfunction-associated fatty liver disease and suspected coronary heart disease. There was an increased risk of HF hospitalization in those with elevated hs-CRP levels.