Risk Of Heart Failure Hospitalization Research Articles

Regurgitant volume to LA volume ratio in patients with secondary MR: the COAPT trial.

The conceptual framework of proportionate vs. disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with 'disproportionate' MR and a higher risk of events. The objectives, therefore, were to investigate the prognostic impact of MR severity to LAV ratio on outcomes among HF patients with severe secondary MR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip™ device plus guideline-directed medical therapy (GDMT) vs. GDMT alone in the COAPT trial. The ratio of pre-procedural regurgitant volume (RVol) to LAV was calculated from baseline transthoracic echocardiograms. The primary endpoint was 2-year covariate-adjusted rate of HF hospitalization (HFH). Among 567 patients, the median RVol/LAV was 0.67 (interquartile range 0.48-0.91). In patients randomized to GDMT alone, lower RVol/LAV was independently associated with an increased 2-year risk of HFH (adjHR: 1.77; 95% CI: 1.20-2.63). RVol/LAV was a stronger predictor of adverse outcomes than RVol or LAV alone. Treatment with TEER plus GDMT compared with GDMT alone was associated with lower 2-year rates of HFH both in patients with low and high RVol/LAV (Pinteraction = 0.28). Baseline RVol/LAV ratio was unrelated to 2-year mortality, health status, or functional capacity in either treatment group. Low RVol/LAV ratio was an independent predictor of 2-year HFH in HF patients with severe MR treated with GDMT alone in the COAPT trial. TEER improved outcomes regardless of baseline RVol/LAV ratio. Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier NCT01626079URL https://clinicaltrials.gov/ct2/show/NCT01626079.

The Evolving Role of Vericiguat in Patients With Chronic Heart Failure.

Heart failure (HF) is a chronic and progressive clinical disorder characterized by an inability to pump sufficient blood to meet metabolic demands. It poses a substantial global healthcare burden, leading to high morbidity, mortality, and economic impact. Current treatments for HF include lifestyle modifications, guideline-directed medical therapies (GDMT), and device interventions, but the need for novel therapeutic approaches remains significant. The introduction of vericiguat, a soluble guanylate cyclase stimulator, has shown promise in improving outcomes for heart failure patients. Vericiguat addresses the underlying pathophysiological mechanisms of heart failure by augmenting the cyclic guanosine monophosphate (cGMP) pathway, leading to enhanced cardiac contractility and vasodilation. Clinical trials evaluating the efficacy and safety of vericiguat, such as the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial, have demonstrated promising results. It has been shown that vericiguat, when added to standard therapy, reduces the risk of HF hospitalization and cardiovascular death in patients with symptomatic chronic HF with reduced ejection fraction (HFrEF). The addition of vericiguat to the current armamentarium of HF treatments provides clinicians with a novel therapeutic option to further optimize patient outcomes. Its potential benefits extend beyond symptom management, aiming to reduce hospitalizations and mortality rates associated with HF. As with any new treatment, the appropriate patient selection, monitoring, and management of potential adverse effects are essential. Further research is warranted to determine the long-term benefits, optimal dosing strategies, and potential combination therapies involving vericiguat. Its ability to target the cGMP pathway provides a unique mechanism of action, offering potential benefits in improving clinical outcomes for HF patients. Continued investigation and clinical experience will further elucidate the role of vericiguat in the management of HF and its overall impact on reducing the healthcare burden associated with this debilitating condition.

Effect of SGLT2 inhibitors on cardiovascular events in patients with atrial fibrillation:A systematic review and meta-analysis of randomized controlled trials.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is reported to reduce incident atrial fibrillation (AF) in patients with or without diabetes; however, its cardiovascular (CV) benefit for AF patients remains unclear. To investigate the effect of SGLT2i on the incidence of CV events in patients with AF. Six randomized controlled trials (RCTs) assessing the effects of SGLT2i on CV outcomes in patients with or without AF were included (PROSPERO: CRD 42023431535). The primary endpoint was the composite outcome of heart failure (HF) hospitalization and CV death. Additionally, we assessed the effects of treatment in prespecified subgroups on HF hospitalization, CV death, and all-cause mortality. Among 38,529 participants from all trials, 5018 patients with AF were treated with SGLT2i. The follow-up period of these trials ranged from 2.3 to 3.3 years. SGLT2i treatment was significantly associated with the risk reduction of primary endpoint in patients with AF (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.74-0.88; p<0.001), consistent with the finding in the general population (p for interaction=0.76). SGLT2i was also associated with a consistent reduction in the risk of HF hospitalization in patients with AF (RR 0.76, 95% CI 0.69-0.84; p<0.001) or not (RR 0.72, 95% CI 0.64-0.80; p<0.0001), with no statistical difference between them (p for interaction=0.41). Meta-regression further revealed no significant association between the prevalence of HF with reduced ejection fraction or diabetes and the effect size of SGLT2i. The treatment effects of SGLT2i were associated with a lower incidence of CV events, especially HF hospitalization, in patients with AF.

Plain language summary of the EMPEROR-Preserved study looking at the effect of empagliflozin in patients with heart failure with preserved ejection fraction, with and without diabetes.

The EMPEROR-Preserved study looked at the effects of empagliflozin in participants with heart failure with a preserved ejection fraction (HFpEF). This is when the lower left part of the heart (left ventricle) squeezes normally or near normally but does not fill with enough blood between heartbeats. Therefore, not enough blood is pumped around the body. For this study, HFpEF was defined as a condition in which more than 40% of blood in the left ventricle was pumped around the body. When researchers started the EMPEROR-Preserved study, there was no treatment for HFpEF. Also, researchers did not know if empagliflozin was more or less effective in people with and without diabetes, a condition where there are high levels of sugar (glucose) in the blood. This study included participants with HFpEF with and without diabetes to see if empagliflozin had a positive effect on the heart compared with a placebo (a pill that looked like empagliflozin but did not contain any active medication). Nearly 50% of participants had diabetes. The researchers looked at: How many people needed to be hospitalized for heart failure (HF) or died from conditions that affect the heart and blood vessels (cardiovascular disease) If peoples' kidneys worked less over time (the decline in kidney function) The side effects of empagliflozin. Empagliflozin reduced the risk of either being hospitalized for HF or dying from cardiovascular disease. The decrease in this risk was due to fewer hospitalizations for HF. This was true regardless of whether or not participants had diabetes. Empagliflozin also slowed the decline in kidney function, regardless of whether the participant had diabetes, but the effect was larger in participants with diabetes. There were no differences in side effects in participants taking empagliflozin or placebo, and the results were similar regardless of whether or not participants had diabetes. The results showed that treatment with empagliflozin reduced the risk of hospitalization for HF and there were no major side effects in participants with HFpEF, regardless of whether or not they had diabetes.

Neuropeptide Y is elevated in heart failure and is an independent predictor of outcomes.

Neuropeptide Y (NPY) is the most abundant neuropeptide found in the heart and is released alongside norepinephrine following prolonged sympathetic activation, a process that is implicated in the pathophysiology of heart failure (HF). In patients with severely impaired left ventricular ejection fraction (LVEF) undergoing cardiac resynchronization therapy, higher levels of NPY measured in coronary sinus blood, are associated with poorer outcome. The aim was to examine the association of peripheral venous NPY levels and outcomes in a HF population with a range of LVEF, using a highly sensitive and specific assay. The association between NPY and the composite outcome of cardiovascular death or HF hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 833 patients using a threshold of elevated NPY identified through binary recursive partitioning adjusted for prognostic variables including estimated glomerular filtration rate (eGFR), ejection fraction and B-type natriuretic peptide (BNP). The mean value of NPY was 25.8 ± 18.2 pg/ml. Patients with high NPY levels (≥29 pg/ml) compared with low values were older (73 ± 10 vs. 71 ± 11 years), more often male (58.5% vs. 55.6%), had higher BNP levels (583 [261-1096] vs. 440 [227-829] pg/ml), lower eGFR (46.4 ± 13.9 vs. 52.4 ± 11.7 ml/min/1.73 m2 ), and were more often treated with diuretics. There was no associated risk of HF hospitalization with NPY levels ≥29 vs. <29 pg/ml. Higher NPY levels were associated with a greater risk of cardiovascular and all-cause death (adjusted hazard ratio 1.56 [95% confidence interval 1.21-2.10], p = 0.003 and 1.30 [1.04-1.62], p = 0.02, respectively). There was no associated risk of HF hospitalization with higher NPY levels. Peripherally measured NPY is an independent predictor of all-cause and cardiovascular death even after adjustment for other prognostic variables, including BNP.

Cardiovascular Outcomes of α-Blockers vs 5-α Reductase Inhibitors for Benign Prostatic Hyperplasia

The most prescribed class of medications for benign prostatic hyperplasia (BPH) is α-blockers (ABs). However, the cardiovascular safety profile of these medications among patients with BPH is not well understood. To compare the safety of ABs vs 5-α reductase inhibitors (5-ARIs) for risk of adverse cardiovascular outcomes. This active comparator, new-user cohort study was conducted using insurance claims data from a 20% random sample of Medicare beneficiaries from 2007 to 2019 to evaluate the 1-year risk of adverse cardiovascular outcomes. Males aged 66 to 90 years were indexed into the cohort at new use of an AB or 5-ARI. Twelve months of continuous enrollment and at least 1 diagnosis code for BPH within 12 months prior to initiation were required. Data were analyzed from January 2007 through December 2019. Exposure was defined by a qualifying prescription fill for an AB or 5-ARI after at least 12 months without a prescription for these drug classes. Follow-up began at a qualified refill for the study drug. Primary study outcomes were hospitalization for heart failure (HF), composite major adverse cardiovascular events (MACE; hospitalization for stroke, myocardial infarction, or death), composite MACE or hospitalization for HF, and death. Inverse probability of treatment and censoring-weighted 1-year risks, risk ratios (RRs), and risk differences (RDs) were estimated for each outcome. Among 189 868 older adult males, there were 163 829 patients initiating ABs (mean [SD] age, 74.6 [6.2] years; 579 American Indian or Alaska Native [0.4%], 5890 Asian or Pacific Islander [3.6%], 9179 Black [5.6%], 10 610 Hispanic [6.5%], and 133 510 non-Hispanic White [81.5%]) and 26 039 patients initiating 5-ARIs (mean [SD] age, 75.3 [6.4] years; 76 American Indian or Alaska Native [0.3%], 827 Asian or Pacific Islander [3.2%], 1339 Black [5.1%], 1656 Hispanic [6.4%], and 21 605 non-Hispanic White [83.0%]). ABs compared with 5-ARIs were associated with an increased 1-year risk of MACE (8.95% [95% CI, 8.81%-9.09%] vs 8.32% [95% CI, 7.92%-8.72%]; RR = 1.08 [95% CI, 1.02-1.13]; RD per 1000 individuals = 6.26 [95% CI, 2.15-10.37]), composite MACE and HF (RR = 1.07; [95% CI, 1.03-1.12]; RD per 1000 individuals = 7.40 [95% CI, 2.88-11.93 ]), and death (RR = 1.07; [95% CI, 1.01-1.14]; RD per 1000 individuals = 3.85 [95% CI, 0.40-7.29]). There was no difference in risk for HF hospitalization alone. These results suggest that ABs may be associated with an increased risk of adverse cardiovascular outcomes compared with 5-ARIs. If replicated with more detailed confounder data, these results may have important public health implications given these medications' widespread use.

Sex hormone-binding globulin and heart failure hospitalizations in patients with dysglycemia: Experiences from the outcome reduction with an Initial Glargine Intervention trial

IntroductionSex hormone-binding globulin (SHBG), which binds most of circulating testosterone in blood, has been linked to dysglycemia and cardiovascular disease but the relationship with heart failure remains unclear. AimTo study the relation between SHBG and heart failure hospitalizations. MethodsSHBG levels were analysed in dysglycemic participants at high cardiovascular risk (n = 8401) followed for a median of 6.2 years in the Outcome Reduction with an Initial Glargine Intervention trial. Cox regression was used to estimate hazard ratios (HRs) per one standard deviation increase for heart failure hospitalizations adjusted for age, comorbidities, biochemical data (including testosterone) and pharmacological treatment. Results5553 men and 2848 women were included. Heart failure hospitalizations occurred in 349 (6.3 %) men and 123 (4.3 %) women. One standard deviation increase in SHBG was independently associated with an increased risk of heart failure hospitalizations in men (HR 1.15, 95 % CI 1.03–1.28; p = 0.011) but not in women (HR 1.15; 95 % CI 0.96–1.39; p = 0.14). ConclusionsIn patients with dysglycemia and high cardiovascular risk, increasing SHBG was associated with greater risk of HF hospitalizations independent of testosterone concentrations in men but not in women, suggesting the effects could be mediated through androgen-independent pathways.

Contrasting patterns of symptoms compared to mortality in women and men with Congestive Heart Failure (the G-CHF registry)

Abstract Background There is a paucity of data on the clinical characteristics, management, and outcomes of women compared with men with heart failure, especially in low-and middle-income countries. Purpose In this study from the Global Congestive Heart Failure registry, we examined sex differences in risk factors, clinical characteristics, treatments, and the risk of heart failure hospitalization and mortality by country economic status and by left ventricular ejection fraction (LVEF) category. Methods In the prospective Global-Congestive Heart Failure (G-CHF) study, participants with established heart failure were considered for inclusion from 40 high-, middle-, and low-income countries. We recorded information on the demographic characteristics, medical history, and treatments of participants. We report data on heart failure hospitalization and mortality by sex overall, by country economic status, and by LVEF category. Results From December 2016 to July 2022, 23,000 participants were recruited and followed up. The average age of women in the study was 62 years compared to 64 years in men. Fewer women than men had a LVEF ≤40 (51.7% women vs 66.3% men). By contrast, more women than men had an LVEF≥ 50 (33.2% women vs 18.6% men). Hypertensive heart failure was the most common etiology in women (25.5% women vs 16.8% men), and ischemic heart failure was the most common etiology in men (45.6% men vs 26.6% women). Signs and symptoms of heart failure were more common in women than men: 42.6% of women were NYHA functional class III/IV compared to 37.9% of men. Among participants with a LVEF &amp;lt;35, use of implantable cardiac defibrillator (ICD) was lower in women than men in the overall study (8.7% women vs 17.2% men), and within countries categorized by economic status. However, the use of heart failure medicines and cardiac tests did not differ systematically by sex. Differences by sex were not observed in the adjusted risk of heart failure hospitalization overall (women-to-men adjusted hazard ratio 1.0 (95% CI 0.94 to 1.07)). This pattern was consistent within countries categorized by economic status, geographic region, and by LVEF category. Women had a lower adjusted risk of mortality overall (women-to-men adjusted hazard ratio 0.82 (95% CI 0.77 to 0.87), which was consistently observed within countries categories by economic status, geographic region, and LVEF levels. Conclusions There are differences between women and men in heart failure symptoms, underlying causes, ejection fraction categories, and use of an ICD. However, use heart failure medications, cardiac tests, and hospitalization were similar in women and men; but women had a lower risk of death.

Clinical Outcomes of Left Bundle Branch Area Pacing Compared with Biventricular Pacing in Patients with Heart Failure Requiring Cardiac Resynchronization Therapy: Systematic Review and Meta-Analysis.

Biventricular pacing (BVP) is recommended for patients with heart failure (HF) who require cardiac resynchronization therapy (CRT). Left bundle branch area pacing (LBBAP) is a novel pacing strategy that appears to ensure better electrical and mechanical synchrony in these patients. Our aim was to systematically review and meta-analyze the existing evidence regarding the clinical outcomes of LBBAP-CRT compared with BVP-CRT. Medline, Embase, Cochrane Central Register of Controlled Trials and Web of Science databases were searched for studies comparing LBBAP-CRT with BVP-CRT. Outcomes were all-cause mortality, heart failure hospitalizations (HFH) and New York Heart Association (NYHA) class improvement. We included randomized controlled trials (RCTs) and observational studies with participants that had left ventricular ejection fraction (LVEF) 40% and (i) symptomatic HF or (ii) expected ventricular pacing 40%. Random and fixed effects models pairwise meta-analysis was conducted. Cochrane Risk of Bias 2 assessment tool (ROB 2.0) and the Newcastle-Ottawa scale (NOS) were used to assess the quality of the studies. Eleven studies (10 observational studies and 1 RCT) with 3141 patients were included in the analysis. Compared with BVP-CRT, LBBAP-CRT was associated with lower risk of all-cause mortality (risk ratio (RR): 0.71, 95% CI: 0.57 to 0.87; p = 0.001), lower risk of HFH (RR: 0.59, 95% CI: 0.50 to 0.71; p 0.00001) and more improvement in NYHA class (weighed mean difference (WMD): -0.36, 95% CI: -0.59 to -0.13; p 0.00001) compared with patients who received BVP-CRT. Compared with BVP-CRT, receipt of LBBAP-CRT in patients with HF is associated with a lower risk of mortality, and HFH and greater improvement in NHYA class.

Prognostic implications of angiopoietin-2 in heart failure and the influence of empagliflozin: the EMPEROR program

Abstract Background Heart failure (HF) development and progression is associated with endothelial dysfunction, oxidative stress, and inflammation. The mechanisms involved in endothelial repair in HF are not fully understood. Emerging evidence suggests that angiopoietin-2 (Angpt2), a vascular destabilizing factor, may be related to outcome in HF. Aim To assess the association between Angpt2 and clinical outcomes in a pooled analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials, and to evaluate if the response to empagliflozin therapy in HF is modulated by Angpt2 levels. Methods and results Angpt2 levels (ng/ml) were measured in serum samples from 1131 EMPEROR study participants by using Roche Cobas Elecsys assay, within biomarker research agreement between Boehringer Ingelheim and Roche Diagnostics International Ltd, at baseline, week 12 and week 52. Patients were divided into tertiles of baseline Angpt2 levels (&amp;lt;2.58 ng/mL; ≥2.58 ng/mL &amp;lt;4.71 ng/mL and ≥4.71 ng/mL). Patients in the highest tertile were more frequently white people, had a higher prevalence of New York Heart Association class III-IV symptoms, HF hospitalization within 12 months, obesity, diabetes, atrial fibrillation, elevated natriuretic peptides, worse renal function, and lower prevalence of coronary disease, compared to the lowest tertile (p&amp;lt;0.05 for all). Higher tertile at baseline was associated with increased risk for adverse HF and kidney events (Table 1). Empagliflozin treatment was associated with reduction of the serum Angpt2 versus placebo at week 12 (adjusted gMean 0.872 [0.828-0.917], p&amp;lt;0.0001) but not at week 52 (adjusted gMean ratio 0.946, [0.879-1.019], p=0.145). Empagliflozin significantly reduced the risk of hospitalization for HF and cardiovascular death particularly for patients with highest baseline Angpt2 levels (lowest tertile HR 1.21 [0.63-2.31]; middle tertile HR 0.65 [0.37-1.16]; highest tertile HR 0.64 [0.42-0.97], P-trend=0.139). Conclusion Higher Angpt2 levels at baseline were associated with more advanced HF and worse prognosis. Treatment with empagliflozin was associated with reduction of Angpt2 level at week 12. The benefit of empagliflozin on major HF events was consistent across baseline Angpt2 levels.Table 1

Choice of cardiac implantable electronic device and age-stratified clinical outcome in patients with known heart failure prior to implant

Abstract Background Patients with heart failure (HF) and bradycardia may be eligible for different types of cardiac implantable devices, depending on presence of AV conduction disease, left ventricular ejection fraction, severity of heart failure symptoms, other comorbidities, and age. Once a pacing device is in place, there is a risk that ensuing heart failure progression or worsening of symptoms do not always prompt a device upgrade to resynchronization or conduction system pacing therapy, even if this should be warranted. We therefore aimed to compare prognosis in a national cohort of patients with prior HF diagnosis, who received a pacemaker or defibrillator with or without resynchronization therapy. Methods All patients with preexisting HF diagnosis who received a pacemaker 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. Primary outcome was 5-year mortality, and secondary was mode of death and hospitalization for heart failure. Cox regression and Kaplan Meier curves with log rank test were used for time dependent outcome analyses. Demography variables were compared with Chi2 test or Mann Whitney U test, as appropriate. Adjustment was done for history of atrial fibrillation, diabetes, hypertension, malignancy, age, gender, ischemic heart disease, renal disease, lung disease and cerebrovascular disease. Separate analyses were made for patients with complete AV block, based on the assumption of 100% ventricular pacing in this group, regardless of choice of implanted device. Results 37745 patients were included in the study (see figure 1). Demographic data was similar for the different device groups, except that patients with single chamber pacemaker were older, and all those with single chamber devices (pacemaker, ICD) were more likely to have a history of atrial fibrillation. All listed comorbidities, male sex and higher age were associated with lower 5-year survival in multivariable Cox regression analyses. Unadjusted 5-year mortality was 40% (highest for single chamber pacemakers (61%), and lowest for dual chamber ICDs (17%), p=0.001). When stratified by age group, and adjusted for relevant covariables, patients with single-chamber pacemakers still had higher mortality in all age decile groups (ranging from &amp;lt;60 to &amp;gt;90 years old, all p&amp;lt;0.001). Proportion of device upgrades to CRT was very low; 2.9% for dual- and 0.8% for single-chamber pacemakers. 17% of patients with traditional pacemakers died from HF, and 31% were hospitalized for HF. Conclusions Survival for patients with prior HF diagnosis who receive traditional pacemakers is poor, risk of HF hospitalization is high, whereas upgrades to CRT are scarce. This highlights the need for choosing correct device type at the primary implant, if ventricular pacing is anticipated.Flowchart of included patientsAge stratified survival per device group

Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular outcomes in patients with atrial fibrillation and type 2 diabetes mellitus

Abstract Background A sodium-glucose cotransporter-2 inhibitor (SGLT2i) improves clinical outcomes in patients with type 2 diabetes (T2DM) and cardiovascular disease. Also use of SGLT2i was associated with a reduction of atrial fibrillation (AF) burden. We investigated the effect of SGLT2is on clinical outcomes in patients with T2DM and AF. Methods This was a retrospective study using a clinical data warehouse (CDW) constructed from 7 medical centers. We analyzed 11,043 patients with AF and T2DM. The patients were classified to the SGLT2i group and the control group according to the SGLT2i use. We performed 1:2 propensity score matching analysis. The primary endpoint was a composite of all-cause death or hospitalization due to heart failure events. The secondary endpoints were acute myocardial infarction, stroke, renal function decline and an initiation of dialysis. Results The propensity score matched population consisted of 467 patients in the SGLT2i group and 848 patients in the control group. During a mean follow up of 31.8 (± 21.0) months, the incidence of the primary endpoint was significantly lower in the SGLT2i group (9.6% vs. 16.9%, hazard ratio [HR] 0.624 [0.446 – 0.873]). SGLT2i was associated with reduced all-cause death (HR 0.292 [0.144 – 0.591]) and non-significantly lower risk of heart failure hospitalization (HR 0.734 [0.509 – 1.060]). There was no significant difference in the incidence of myocardial infarction, ischemic stroke, renal function decline and an initiation of dialysis between the two groups. In multivariate analysis, age, renal dysfunction, prior heart failure, and the absence of SGLT2i were independent predictors for the worse outcome. Conclusion SGLT2 inhibitor was associated with a lower incidence of all-cause mortality or heart failure hospitalization in patients with AF and T2DM.Freedom from the primary endpoint in the

Temporal association between atrial fibrillation burden in cardiac implantable electronic devices and the risk of heart failure hospitalization

Abstract Background high daily atrial fibrillation (AF) burden measured in cardiac implantable electronic devices (CIEDs) has been shown to be temporally associated with increased stroke risk.1 Purpose We investigated whether AF burden is temporally associated with an increased risk of heart failure (HF) events in a large real-world cohort of patients with CIED devices. Methods We linked a de-identified database of aggregated electronic health records from 2007-2021 to a manufacturer’s device data warehouse with device based continuous diagnostic monitoring data. Patients with dual or triple chamber CIED implants with capability to measure daily AF burden and having HF events with 120 days of AF burden data prior to the HF event were included in this study. HF event was defined as an inpatient admission, emergency department presentation, or observation unit stay in a hospital with primary diagnosis of HF with intravenous diuretics administration. AF burden of ≥5.5 hours (as defined in earlier studies) on any given day was compared during days 1-30 before (case period) and days 91-120 days (control period) before the first HF event in each patient in this case-crossover study.2 Results A total of 7257 earliest HF events with AF burden available in the case and control period were included. The average age of patients was 72 ±12years, with 74% being males, and following co-morbidities diagnosed prior to the HF event: 83% hypertension, 48% diabetes, 74% coronary artery disease, 31% stroke/TIA, 45% CKD, and 27% vascular disease. Comparison of occurrence of AF above threshold (≥5.5 hours on any given day) on days 1-30 versus 91-120 pre-HF event is shown in table to illustrate the effect of temporally proximate AF on risk of HF event. A total of 957 (13%) had discordant arrhythmic state between case and control period, with 763 (11%) having AF ≥5.5 hours on a day in case period versus 194 (2%) in the control period (OR: 3.93; 95% CI: 3.36-6.60). Higher odds of HF event was observed closer the day with AF ≥5.5 hours is to the HF event (table 1). Conclusions In a large real-world population of patients with CIED devices, AF burden of ≥5.5 hours or more on a given day increases risk of worsening HF.Table 1:odds ratio of HF eventFigure 1:Temporal association

Sex hormone-binding globulin and heart failure hospitalizations in patients with dysglycemia - Experiences from the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial

Abstract Background Sex hormone-binding globulin (SHBG), which binds most of the circulating testosterone in blood, is linked to both dysglycemia and a variety of cardiovascular (CV) events. However, few studies have investigated the link between SHBG and heart failure. Purpose To investigate the relationship between SHBG levels and heart failure hospitalizations in men and women with dysglycemia. Methods The Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial followed individuals with dysglycemia (impaired fasting glucose, impaired glucose tolerance or diabetes) and high cardiovascular risk for a median of 6.2 years. Incident CV events, including heart failure hospitalizations (defined as heart failure requiring overnight stay at hospital or attendance in an acute care setting) were collected and adjudicated. A subset of patients (n = 8,494) in whom blood samples were stored had SHBG levels analysed. Cox regression was used to estimate hazard ratios (HRs) of heart failure hospitalizations per standard deviation increase of SHBG. Adjustments were made for age, comorbidities, biochemical data (including testosterone) and pharmacological treatment. Analyses were performed separately in men and women. Results A total of 5,553 men and 2,848 women were included in whom heart failure hospitalizations were reported in 349 men and 123 women. Median SHBG levels were 35 nmol/L (25-47) in men and 39 nmol/L (27-55) in women. The primary outcome was more frequent in men with SHBG levels above median (n = 208/349 [59.6 %]; p&amp;lt;0.01) whilst no difference was seen for women (n = 69/123 [56.1%]; p = 0.24). A higher SHBG was associated with increased risk of heart failure hospitalizations in men (adjusted HR 1.15, 95% CI 1.03-1.28; p = 0.011) but not in women (adjusted HR 1.13; 95% CI 0.96-1.39; p = 0.14). Conclusions In this biomarker substudy within the ORIGIN trial comprising patients with dysglycemia and at high CV risk, increasing levels of SHBG were associated with heart failure hospitalizations independent of testosterone levels in men but not in women.

Association of CA-125 with markers of congestion, and effect of empagliflozin on CA-125 in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF)

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure hospitalisation and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on carbohydrate antigen 125 (CA-125) are uncertain. CA-125 has a potential role in HFrEF in the assessment of congestion, guiding decongestive therapies, and predicting outcome. Purpose This exploratory biomarker substudy of the SUGAR-DM-HF trial investigated the relationship of CA-125 levels with markers of congestion, and the effect of the SGLT2 inhibitor empagliflozin on serum CA-125 levels. Methods We conducted a multicentre, randomised, double-blind, placebo-controlled trial investigating the effects of empagliflozin in patients with New York Heart Association functional class II-IV, left ventricular ejection fraction (LVEF) ≤40%, and type 2 diabetes or prediabetes.[1] Patients were randomly assigned 1:1 to empagliflozin 10mg daily or placebo. Blood biomarker samples were collected at baseline, weeks 12 and 36. Other measures of congestion assessed included cardiovascular magnetic resonance (CMR), kidney magnetic resonance imaging (MRI), transthoracic echocardiography (TTE), lung ultrasound (LUS), and bioelectrical impedance analysis (BIA). Results Among 105 patients [mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% (9.8%)], median [IQR] CA-125 was 11.2 [8.9-17.6] U/mL. At baseline, those with higher CA-125 had a longer duration of diabetes, higher heart rate, lower LVEF, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP), were more likely to have a pleural effusion and be on a loop diuretic, but serum creatinine was similar. At baseline, CA-125 levels weakly correlated with NT-proBNP, the presence of a pleural effusion, number of B-lines, inferior vena cava (IVC) diameter, tricuspid regurgitation velocity, E/e’ average, apparent extracellular volume (aECV) of the right whole kidney,[2] and total body water (FIGURE 1). CA-125 levels were not significantly different between groups at week 12 or 36 (FIGURE 2). The beneficial effect of empagliflozin on reducing left ventricular end-systolic volume index (LVESVi) was not modified by baseline CA-125 (p interaction = 0.93). Change in CA-125 was not associated with change in the co-primary outcomes (LVESVi and left ventricular global longitudinal strain) at week 36, nor with change in NT-proBNP or change in body weight at week 12 or 36. Conclusion Among patients with HFrEF, CA-125 levels were not strongly associated with markers of congestion assessed with CMR, kidney MRI, TTE, LUS and BIA. CA-125 levels were not different between groups at week 12 or 36, although this trial was not powered for this outcome.Correlation heatmap (Spearman’s rho).Change in CA-125 levels.

Clinical outcomes of left bundle branch area pacing compared with biventricular pacing in patients with heart failure requiring cardiac resynchronization therapy: systematic review and meta-analysis

Abstract Background Biventricular pacing (BVP) is recommended from the most recent ESC guidelines as the first line pacing strategy in patients with heart failure (HF) that require cardiac resynchronization therapy (CRT). (1) Many studies have shown its beneficial effects regarding morbidity and mortality in this population. (2, 3) However, 10% of patients cannot be treated by BVP due to unsuitable coronary sinus vein, while 30-40% are non-responders to BVP and experience no benefit from this treatment.(4) Left bundle branch area pacing (LBBAP) is a new pacing modality (5) that can achieve narrow QRS and improve left ventricular function in patients with HF, by engaging the intrinsic conduction pathway of the heart. Also, it appears to have better results in electrical and mechanical synchrony compared with BVP. Purpose We conducted a systematic review and meta-analysis to compare the two pacing modalities in terms of hard clinical outcomes, in patients with heart failure that require CRT. Methods Medline, Embase, Cochrane Central Register of Controlled Trials and Web of Science databases were systematically searched for studies comparing LBBAP with BVP for CRT in patients with HF. Outcomes of interest were all-cause mortality, Heart Failure Hospitalizations (HFH) and New York Heart Association (NYHA) class improvement. Two independent investigators identified studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias 2 tool for randomized clinical trials and the Newcastle-Ottawa-Scale for observational studies. Pairwise meta-analysis was conducted using random and fixed effects models. Risk Ratios (RRs) and weighted mean difference (WMD) with 95% confidence intervals (CIs) were used to report dichotomous and continuous variables respectively. Heterogeneity was assessed with the I² statistic. Results In total, 764 studies were retrieved and finally 9 trials with 992 individuals (365 in LBBAP and 627 in BVP group) were included in the analysis. The mean follow-up duration was 13 ± 5.82 months and the average procedural success rate in the LBBAP group was 89.8%. The baseline characteristics were similar between the two groups. Pooled analysis showed that the two methods had no difference in terms of all-cause mortality (RR:0.87 CI 95%:0.38 to 2.02; I²=0%; p=0.750, Figure 1) with 8 (2.4%) vs 17 (2.9%) events occurring in LBBAP and BVP group respectively. However, LBBAP was found to have significantly lower risk for HFH (RR:0.58 CI 95%:0.38 to 0.91; I²=0%; p=0.020, Figure 2A) and to achieve more improvement in NYHA class compared with BVP (WMD: -0.40, CI 95%: -0.68 to -0.12; I²=72%; p=0.005; Figure 2B). Conclusions To the best of our knowledge this is the first meta-analysis that assesses exclusively the clinical outcomes of LBBAP compared to BVP in such an important number of patients. LBBAP presents better outcomes in HFH and NYHA class improvement, but it has no difference in all-cause mortality in comparison with BVP.Figure 1.All-cause mortalityFigure 2.A.HFH B.NYHA class improvement

The gender difference in risk factor and incidence rate of hospitalization for heart failure in Japanese atrial fibrillation patients: The Fushimi AF Registry

Abstract Background Gender-specific medicine is of concern in cardiovascular medicine. However, the gender difference in risk factor and incidence rate of hospitalization for heart failure (HF) in Japanese atrial fibrillation (AF) patients is little known. The aim of this study is to compare the risk factor and incidence rate of HF hospitalization in male and female. Method In the Fushimi AF Registry, we started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. In the entire cohort, 2,677 were male and 1,819 were female. We compared clinical characteristics and risk factor and incidence rate of HF hospitalization between the two groups. Result Male patients were younger (male vs, female; 71.5 years vs. 76.7 years, p&amp;lt;0.001), greater in body weight (65.0 kg vs. 51.2 kg, p&amp;lt;0.001), had lower pulse rate (77.5 bpm vs. 79.4 bpm, p=0.008), more often persistent/permanent type (52.0% vs. 48.2%, p=0.044), more likely to have previous stroke/systemic embolism (21.1% vs. 18.6%, p=0.039), diabetes mellitus (DM) (26.2% vs. 19.9%, p&amp;lt;0.001), coronary artery disease (CAD) (16.0% vs. 12.3%, p&amp;lt;0.001) and less likely to have prior HF (24.0% vs. 32.3%, p&amp;lt;0.001), chronic kidney disease (CKD) (33.7% vs. 39.3%, p&amp;lt;0.001) and had lower CHADS2 score (1.96 vs. 2.15, p&amp;lt;0.001). In prescription data, male patients more often received oral anticoagulant (58.2% vs. 52.1%, p&amp;lt;0.001) and less in diuretics. Systolic blood pressure, hypertension, prescription of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta blocker were comparable between the two groups. During the median follow-up of 1,824 days, the incidence rate of HF hospitalization was lower in male than female group (male vs. female: 1.74 vs. 2.09 per 100 person-years, log rank p=0.005). On multivariate Cox regression analysis, age, sustained type of AF, prior HF, DM, CAD and CKD were significantly associated with an increased risk of HF hospitalization in male group. On the other hand, age, prior HF, DM, CKD were significantly associated with an increased risk of HF hospitalization but neither sustained type of AF nor CAD was in female group. Conclusion The incidence rate of HF hospitalization was lower in male patients than female patients. The risk factor associated with HF hospitalization were different between male and female in Japanese AF patients.

The prognostic association of atrial fibrillation on heart failure hospitalizations after acute myocardial infarction

Abstract Aims The association of atrial fibrillation (AF) with heart failure (HF) specific hospitalizations after acute myocardial infarction (AMI) is unclear. We aim to study the association of AF and 6-month HF hospitalization after an AMI in a large American cohort. Methods and Results Adult survivors of a AMI hospitalization without cardiogenic shock were identified from the 2019 US Nationwide Readmissions Database. The unadjusted association of AF (pre-existing and denovo) with baseline characteristics and primary outcome of rate of 6-month HF admission, and secondary outcomes of fatal HF admission, composite of HF peri-AMI or a 6-month HF admission, and a composite of 6-month HF or death during a non−HF-related admission was evaluated using chi square tests or t-tests, and independent associations of AF on outcomes were evaluated using multivariable logistic regression. Cox proportional hazards models were used to identify the association of AF on cumulative incidence risk on HF readmission. Of 262,390 AMI survivors, AF was present in 18.0%. By 6-months, HF hospitalization occurred in 5.4% of all patients. AF was associated with a higher adjusted risk for 6-month HF admission (OR 1.42, 95% CI: 1.34-1.50). In the adjusted time-to-event analysis, AF was associated with a higher risk for 6-month HF readmission (HR 1.39, 95% CI 1.31-1.46, P&amp;lt;0.001). AF was associated with a higher risk for fatal HF and the composite outcomes. Conclusions AF was present in 1 in 6 AMI survivors without cardiogenic shock and AF was associated with a higher risk of HF hospitalization in the subsequent 6-month period.Cumulative Incidence CurvesOutcomes Table

LGE in CMR and outcomes in cardiac sarcoidosis

Abstract Background Late-gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a predictor of adverse events in patients with cardiac sarcoidosis (CS). This meta-analysis evaluated the correlation between LGE and mortality, ventricular arrhythmias (VA), sudden cardiac death (SCD), and heart failure (HF) outcomes. Methods A literature search was conducted for studies reporting the association between LGE in CS and the study endpoints. The endpoints are: mortality, VA and SCD, and HF hospitalization. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. The minimum follow-up duration was one year. Results A total of 17 studies and 1,915 CS patients (595 with LGE vs 1,320 without LGE) were included; mean follow-up was 3.3 years (ranging between 17 to 84 months). LGE was associated with increased all-cause mortality (OR 6.05, 95% CI 3.16-11.58; P&amp;lt;0.01), cardiovascular mortality (OR 5.83, 95% CI 2.89-11.77; P&amp;lt;0.01) and VA and SCD (OR 16.48, 95% CI 8.29-32.73; P&amp;lt;0.01). The presence of LGE in the right ventricle is associated with higher risk of VT (OR 6.11, 95% CI 1.14-32.68; P 0.035). LGE was associated with an increased risk of HF hospitalization (OR 17.47, 95% CI 5.54-55.03; P&amp;lt;0.01). Conclusion LGE in CS patients is associated with increased mortality, VA and SCD, and HF hospitalization during long-term follow up. The presence of LGE in the right ventricle is associated with higher risk of VT.

Intravenous iron administration in patients with heart failure alters endothelial homeostasis with early release of endothelial microvesicles and subsequent mobilization of endothelial progenitor cell

Abstract Background Intravenous iron supplementation is an established therapy for patients with heart failure (HF) with reduced ejection fraction (LV-EF&amp;lt;50%) and iron deficiency, resulting in reduced risk of HF hospitalization. Since iron may induce oxidative stress, inflammation and apoptosis in endothelial cells, concerns persist regarding potential adverse vascular effects of iron therapy. To evaluate endothelial health following ferric carboxymaltose (FCM) administration, we assessed the profile of circulating endothelial microvesicles (EMVs) and endothelial progenitor cells (EPCs) in a cohort of 23 HF patients using flow cytometry. Results Compared to healthy control subjects (HC; n=15), baseline levels of CD31+/CD41- EMVs were significantly higher and EMVs featured a more apoptotic phenotype in HF patients. Following administration of 1000mg FCM, EMV levels showed an early but transient increase (Fig. 1) and displayed an altered phenotype profile with dominant augmentation of EMVs expressing the inducible markers CD62E and CD54, indicating endothelial activation and injury. Levels of circulating vasoregenerative CD45lowCD34+KDR+ EPCs were lower in HF patients and FCM application resulted in an early decrease of EPCs followed by substantial mobilization into the circulation after one week (Fig. 2). Levels of EMVs and EPCs returned to baseline values within two and four weeks, respectively. Compared to HF patients with preserved renal function, the EMV/EPC ratio was higher in HF patients whereas EPC mobilization was diminished with additional chronic kidney disease, suggesting impaired vascular repair capacity. In vitro experiments with cultured endothelial cells revealed that FCM at therapeutic concentrations dose-dependently promotes endothelial apoptosis, increases expression of adhesion molecules and CXCL12, and triggers the generation of EMVs. Conclusion Intravenous iron supplementation with FCM in HF patients provokes a biphasic response with early release of CD62E+ and CD54+ enriched EMVs and subsequent mobilization of EPCs, suggesting temporary aggravation of endothelial dysfunction upon FCM supplementation and consecutive engagement of a vascular defense program.