First Hospitalization For Heart Failure Research Articles

Empagliflozin after Acute Myocardial Infarction

BackgroundEmpagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safety and efficacy of empagliflozin in patients who have had acute myocardial infarction are unknown.MethodsIn this event-driven, double-blind, randomized, placebo-controlled trial, we assigned, in a 1:1 ratio, patients who had been hospitalized for acute myocardial infarction and were at risk for heart failure to receive empagliflozin at a dose of 10 mg daily or placebo in addition to standard care within 14 days after admission. The primary end point was a composite of hospitalization for heart failure or death from any cause as assessed in a time-to-first-event analysis.ResultsA total of 3260 patients were assigned to receive empagliflozin and 3262 to receive placebo. During a median follow-up of 17.9 months, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.2%) in the empagliflozin group and in 298 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years (hazard ratio, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P=0.21). With respect to the individual components of the primary end point, a first hospitalization for heart failure occurred in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Adverse events were consistent with the known safety profile of empagliflozin and were similar in the two trial groups.ConclusionsAmong patients at increased risk for heart failure after acute myocardial infarction, treatment with empagliflozin did not lead to a significantly lower risk of a first hospitalization for heart failure or death from any cause than placebo. (Funded by Boehringer Ingelheim and Eli Lilly; EMPACT-MI ClinicalTrials.gov number, NCT04509674.)

Impact of empagliflozin on insulin needs in patients with heart failure and diabetes: An EMPEROR-Pooled analysis.

To assess the effect of empagliflozin on patients with comorbid heart failure (HF) and diabetes with or without baseline insulin, and to study the impact of empagliflozin on insulin requirements over time. We performed a post-hoc analysis of pooled patient-level data from two cardiovascular outcomes trials of empagliflozin in HF (EMPEROR-Reduced and EMPEROR-Preserved trials). We undertook a subgroup analysis stratified by baseline insulin use, including all patients with diabetes. The studied endpoints included the primary composite endpoint of first hospitalization for HF or cardiovascular death, rate of decline of estimated glomerular filtration rate, composite renal outcome and rates of sustained insulin initiation. Among 4794 patients with diabetes, 1333 (658 in empagliflozin, 675 in placebo) were using insulin at baseline. The treatment effect of empagliflozin on the primary endpoint was consistent irrespective of insulin use [no insulin, hazard ratio 0.74, 95% confidence interval (CI) 0.63-0.86; using insulin, hazard ratio 0.81, 95% CI 0.66-1.00, pinteraction = .49], as was the effect on the rate of decline of the estimated glomerular filtration rate (pinteraction = .75). There was no effect of empagliflozin on the composite renal outcome in patients using or not using insulin (pinteraction = .30). Among patients not using insulin at baseline, those randomized to empagliflozin initiated insulin less frequently throughout the follow-up period compared with those receiving placebo (2.6% vs. 3.8%, odds ratio 0.66, 95% CI 0.50-0.88). Empagliflozin exerts a consistent benefit on cardiovascular outcomes and renal function decline, irrespective of baseline insulin use, and reduces the need for sustained insulin initiation in patients with HF and diabetes.

Immediate pharmacotherapy intensification after cardiac resynchronization therapy: incidence, characteristics, and impact.

Cardiac resynchronization therapy (CRT) is an established treatment for drug-refractory heart failure (HF) in patients with left bundle branch block (LBBB). Acute haemodynamic improvement after CRT implantation may enable the intensification of HF medication soon thereafter. Immediate pharmacotherapy intensification (IPI) after CRT implantation achieves a synergetic effect, possibly leading to a better prognosis. This study aimed to explore the incidence, characteristics, and impact of IPI on real-world outcomes among CRT recipients with a history of hospitalization for acute HF. This multicentre retrospective study enrolled CRT recipients with LBBB morphology, a QRS width ≥120ms, a left ventricular ejection fraction ≤35%, and New York Heart Association II-IV HF symptoms. All patients had previous HF hospitalizations within the previous year and received guideline-directed medical therapy before CRT implantation. Patient baseline characteristics, including HF medication, were collected. IPI was defined as the intensification of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists within 30days of CRT implantation. The primary endpoint was all-cause death or first hospitalization for HF; the secondary endpoint was all-cause death. We enrolled 194 patients (75% male; mean age, 65±13years; 78% with non-ischaemic cardiomyopathy). One hundred five (54%) patients received IPI. Patients who received IPI exhibited a significantly shorter QRS duration (159±26 vs. 171±32ms; P=0.004), higher estimated glomerular filtration rate (55.2±20.0 vs. 47.8±24.7mL/min/1.73m2 ; P=0.022), and more dilated cardiomyopathy. During a median follow-up period of 29months, 70 (36%) patients reached the primary endpoint and 42 (22%) patients died. Patients with IPI showed significantly better outcomes for the primary and secondary endpoints than patients without IPI. The volumetric responder ratio at 6months after implantation was not significantly different between patients with and without IPI; however, patients who received IPI had reduced mortality even at 6months after implantation. In the multivariate analysis, IPI was an independent predictor of the primary endpoint (hazard ratio, 0.51; 95% confidence interval, 0.27-0.97; P=0.043). Immediate intensification of HF medication was achieved in 54% of CRT recipients and was significantly higher in patients without excessive QRS prolongation, preserved renal function, and dilated cardiomyopathy than others. In patients with LBBB morphology and QRS≥120ms, IPI was associated with a significantly better prognosis and fewer HF hospitalizations after CRT implantation than others.

Health outcomes after myocardial infarction: A population study of 56 million people in England.

The occurrence of a range of health outcomes following myocardial infarction (MI) is unknown. Therefore, this study aimed to determine the long-term risk of major health outcomes following MI and generate sociodemographic stratified risk charts in order to inform care recommendations in the post-MI period and underpin shared decision making. This nationwide cohort study includes all individuals aged ≥18 years admitted to one of 229 National Health Service (NHS) Trusts in England between 1 January 2008 and 31 January 2017 (final follow-up 27 March 2017). We analysed 11 non-fatal health outcomes (subsequent MI and first hospitalisation for heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes mellitus, dementia, depression, and cancer) and all-cause mortality. Of the 55,619,430 population of England, 34,116,257 individuals contributing to 145,912,852 hospitalisations were included (mean age 41.7 years (standard deviation [SD 26.1]); n = 14,747,198 (44.2%) male). There were 433,361 individuals with MI (mean age 67.4 years [SD 14.4)]; n = 283,742 (65.5%) male). Following MI, all-cause mortality was the most frequent event (adjusted cumulative incidence at 9 years 37.8% (95% confidence interval [CI] [37.6,37.9]), followed by heart failure (29.6%; 95% CI [29.4,29.7]), renal failure (27.2%; 95% CI [27.0,27.4]), atrial fibrillation (22.3%; 95% CI [22.2,22.5]), severe bleeding (19.0%; 95% CI [18.8,19.1]), diabetes (17.0%; 95% CI [16.9,17.1]), cancer (13.5%; 95% CI [13.3,13.6]), cerebrovascular disease (12.5%; 95% CI [12.4,12.7]), depression (8.9%; 95% CI [8.7,9.0]), dementia (7.8%; 95% CI [7.7,7.9]), subsequent MI (7.1%; 95% CI [7.0,7.2]), and peripheral arterial disease (6.5%; 95% CI [6.4,6.6]). Compared with a risk-set matched population of 2,001,310 individuals, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (adjusted hazard ratio [aHR] 1.01; 95% CI [0.99,1.02];p = 0.468) and cancer (aHR 0.56; 95% CI [0.56,0.57];p < 0.001). The study includes data from secondary care only-as such diagnoses made outside of secondary care may have been missed leading to the potential underestimation of the total burden of disease following MI. In this study, up to a third of patients with MI developed heart failure or renal failure, 7% had another MI, and 38% died within 9 years (compared with 35% deaths among matched individuals). The incidence of all health outcomes, except dementia and cancer, was higher than expected during the normal life course without MI following adjustment for age, sex, year, and socioeconomic deprivation. Efforts targeted to prevent or limit the accrual of chronic, multisystem disease states following MI are needed and should be guided by the demographic-specific risk charts derived in this study.

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.

Meta-analysis of risk of major adverse cardiovascular events in adults with type 2 diabetes treated with bexagliflozin.

To explore the risk of major adverse cardiovascular events (MACE) associated with exposure to bexagliflozin. The analysis included 4090 participants with type 2 diabetes (T2D) enrolled in nine phase 2 and 3 double-blind randomized controlled trials. All potential MACE were adjudicated by a blinded committee. The primary endpoint for the meta-analysis was the hazard ratio (HR) for the time to first occurrence of non-fatal stroke, non-fatal myocardial infarction (MI), cardiovascular (CV) death or hospitalization for unstable angina (MACE+), tested for non-inferiority to a ratio of 1.8. The secondary endpoints were time to first occurrence of (i) non-fatal stroke, non-fatal MI or CV death (MACE), tested for non-inferiority to a ratio of 1.3; and (ii) CV death or hospitalization for heart failure, tested for superiority. The HR for the primary endpoint of MACE+ was 0.80 (95% confidence interval [CI] 0.58, 1.09), which fulfilled the non-inferiority objective with a P value of less than 0.0001. Non-inferiority for the first key secondary endpoint of MACE was also shown (HR = 0.82; 95% CI 0.59, 1.13; P = 0.0023). Superiority for time to CV death or first hospitalization for heart failure was not shown. Bexagliflozin did not increase the risk of MACE in participants with T2D when compared with placebo or active control. Both the preapproval and postapproval thresholds for CV safety were met and bexagliflozin has been approved by the US Food and Drug Administration.

Effect of eplerenone according to duration of heart failure in EMPHASIS-HF: It is never too late to start an MRA in HFrEF

Abstract Background In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF), the mineralocorticoid receptor antagonist (MRA) eplerenone reduced both the risk of death and heart failure (HF) hospitalization in patients with HF and reduced ejection fraction (HFrEF) and mild symptoms. However, many patients are still not prescribed an MRA and physicians may be reluctant to add another treatment in patients with longstanding HF who appear to be "stable" on their current therapy. Purpose As little is known about how the effect of MRA therapy varies by the duration of HF, we examined the efficacy of eplerenone according to time from HF diagnosis among patients in EMPHASIS-HF. The primary trial outcome was the composite of a first hospitalization for HF or cardiovascular death. Methods Three patient groups of similar size were created according to the duration of HF: &amp;lt;1 year, ≥1 to &amp;lt;5 years, and ≥5 years. Outcomes were analysed using Cox regression and the Kaplan-Meier estimate. Treatment effects were examined according to HF duration category and also using the duration of HF as a continuous variable. Results The number of patients in each group was: 975 (&amp;lt;1 year), 769 (1 - &amp;lt;5 years), and 988 (≥5 years), respectively. Patients with longer duration of HF were older and more frequently had an ischaemic aetiology of HF. Additionally, a longer duration of HF was associated with lower eGFR levels, wider QRS duration, and a higher proportion of atrial fibrillation at baseline. The rate of the primary outcome (per 100 person-year) increased with HF duration: 9.8 (95% CI: 8.4-11.4) for &amp;lt;1 year, 13.5 (11.6-15.7) for 1 - &amp;lt;5 years, and 17.6 (15.6-19.8) for ≥5 years. Similar trends were seen in all other outcomes (Figure 1). The hazard ratios for the effect of eplerenone compared to placebo on the primary outcome were 0.57 (95% CI: 0.42-0.79) for &amp;lt;1 year, 0.81 (0.60-1.10) for 1- &amp;lt;5 years, and 0.61 (0.48-0.78) for ≥5 years; P for interaction = 0.24. The benefits of eplerenone were also consistent across the duration of HF examined as a continuous variable (Figure 2). For the primary outcome, The number needed to treat (NNT) over the duration of the trial, for the primary outcome, was 14 for &amp;lt;1 year, 13 for 1 - &amp;lt;5 years and only 10 for ≥5 years duration. Conclusions Patients with a longer duration of HF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent in people with longer-standing HF and HF of shorter duration. These data suggest that it is never too late to start an MRA in patients with HFrEF. Figure 1. Outcomes according to heart failure duration category Abbreviations: CV cardiovascular; HF heart failure Figure 2. Treatment effects according to the duration of heart failure Abbreviations: CV cardiovascular; HF heart failureFigure 1Figure 2

Sleep apnea in patients with exacerbated heart failure and overweight

Abstract Background Exacerbated heart failure is a condition with a high frequency of hospitalizations and mortality, especially in overweight patients. Screening and treatment for sleep apnea can be helpful in these patients. Purpose To determine the frequency and the phenotypic characteristics and of sleep apnea in patients with overweight and exacerbated heart failure. To assess systolic and diastolic function in patients with obstructive and central sleep apnea. To follow patients for one year and to assess hospitalization and mortality. Methods We conducted a single-centre, prospective cohort study form 120 consecutive patients hospitalized for exacerbation heart failure in the cardiology department. 70 patients meet inclusion criteria – Apnea-Hypopnea index (AHI) &amp;gt; 5, Epworth Sleepiness Scale (ESS) &amp;gt; 6, NTproBNP&amp;gt;900 pg/ml, and Body mass index(BMI) &amp;gt;25. All patients receiving optimal medical treatment. The follow-up period was 1 year. The primary endpoint was death for any reason. Sleep apnea screening was performed with ApneaLinkTM. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and the E/e‘m ratio. Results From 70 with sleep apnea 73% (n=51) has obstructive sleep apnea (OSA) and 27% (n=19) has central sleep apnea (CSA). Detected significant changes in LVEF between the OSA group and CSA group (EF% 49.7±8.5vs43.3±9.6.4;p=0.008). Statistically significant changes there was about E/e’m ratio (E/e’m-17.01±3.7 vs 19.3±2.73; p=0.015) and BMI (BMI-38.2±6.5 vs 32.2±3.6; p&amp;lt;0.001). We found a moderate reverse correlation between the LVEF and the number of central sleep apnea events (r=-0,34;p=0,003). Simple linear regression was used to test if the left ventricular ejection fraction significantly predicted the number of central apnea events. The overall regression was statistically significant (R2 = 0.120, F(1,68) = 9.26, p = .003). It was found that the left ventricular ejection fraction significantly predicted the number of central apnea events (β = -0.06, p = .003). Patients from both groups were followed up regarding first hospitalization for heart failure and mortality over a period of 12 months. First hospitalization in patients with CSA occurs significantly sooner than in patients with OSA. The average number of months without hospitalization for HF in patients with CSA was 6.7 months versus 9.7 months in patients with OSA (Log Rank (Mental-Cox) p=0.012). The OSA group had a median survival of 10.5 months versus 9.3 months in the CSA group (Log Rank (Mental-Cox) p=0.026). Conclusion Sleep apnea is a common comorbidity in patients with exacerbated heart failure and overweight. OSA occurs to a greater extent than CSA. Patients with reduced systolic function are at higher risk of central sleep apneas events. Low LVEF% can be used as a prognostic factor regarding the occurrence of central sleep apnea events. Controlling sleep apnea can reduce patient readmissions and mortality.

Prevalence of anti-beta-1 antibody 6 months after hospitalization for acute heart failure predicts adverse outcome.

Agonistic antibodies against neurohumoral receptors can induce cardio-noxious effects by altering the baseline receptor activity. To estimate the prevalence of autoantibodies directed against the beta-1 receptor (b1-AAB) in patients admitted to the hospital for acute heart failure (HF) at (i) baseline and (ii) after 6months of follow-up (F6) and (iii) after another 12months of follow-up (i.e. 18months after index hospitalization), to estimate their prognostic impact on clinical outcome (death or first hospitalization for HF). In 47 patients, b1-AAB were serially determined in serum samples collected at index hospitalization and at 6months of follow-up (F6) with a flow cytometry-based assay: median age 71years (quartiles 60, 80), 23 (49%) women, 24 (51%) HF with preserved ejection fraction. Beta1-AAB were detected in three subjects at index hospitalization (6%), and in eight subjects at F6 (17%). There were no differences apparent between patients with and without b1-AAB at F6 with regard to age, sex, type, duration, or main cause of HF. During the 12month period following F6 (i.e. up to month 18), eight events occurred. Event-free survival was associated with prevalence of b1-AAB at F6. Compared with patients without b1-AAB at F6, age-adjusted Cox regression indicated a higher event risk in patients harbouring b1-AAB, with a hazard ratio of 8.96 (95% confidence interval 1.81-44.50, P=0.007). Our results suggest a possible adverse prognostic relevance of b1-AAB in patients with acute HF, but this observation needs to be confirmed in larger patient collectives.

Pharmacological Treatments in Heart Failure With Mildly Reduced and Preserved Ejection Fraction: Systematic Review and Network Meta-Analysis

BackgroundMedical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2is). ObjectivesThe authors aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF. MethodsThe authors performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with heart failure (HF) and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality. ResultsThe authors identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%. ConclusionsIn patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.

Growth differentiation factor-15 in patients with or at risk of heart failure but before first hospitalisation

ObjectiveIdentification of patients at risk of adverse outcome from heart failure (HF) at an early stage is a priority. Growth differentiation factor (GDF)-15 has emerged as a potentially useful biomarker....

C-Reactive Protein and Risk of Incident Heart Failure in Patients With Cardiovascular Disease

BackgroundPatients with established cardiovascular disease (CVD) are at high risk of incident heart failure (HF), which may in part reflect the impact of systemic inflammation. ObjectivesThe goal of this study was to determine the association between C-reactive protein (CRP) and incident HF in patients with established CVD. MethodsPatients from the prospective UCC-SMART (Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease) cohort with established CVD, but without prevalent HF were included (n = 8,089). Incident HF was defined as a first hospitalization for HF. The association between baseline CRP and incident HF was assessed using Cox proportional hazards models adjusted for established risk factors (ie, age, sex, myocardial infarction, smoking, diabetes mellitus, body mass index, blood pressure, cholesterol, and kidney function). ResultsDuring a median follow-up of 9.7 years (IQR 5.4-14.1 years), 810 incident HF cases were observed (incidence rate 1.01/100 person-years). Higher CRP was independently associated with an increased risk of incident HF: HR per 1 mg/L: 1.10 (95% CI: 1.07-1.13), and for last vs first CRP quartile: 2.22 (95% CI: 1.76-2.79). The association was significant for both HF with reduced (HR: 1.09; 95% CI: 1.04-1.14) and preserved ejection fraction (HR: 1.12; 95% CI: 1.07-1.18) (P for difference = 0.137). Additional adjustment for medication use and interim myocardial infarction did not attenuate the association, and the association remained consistent beyond 15 years after the CRP measurement. ConclusionsIn patients with established CVD, CRP is an independent risk marker of incident HF. These data support ongoing trial efforts to assess whether anti-inflammatory agents can reduce the burden of HF.

Effects of Angiotensin Receptor-Neprilysin Inhibitors Versus Enalapril or Valsartan on Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Recent studies have focused on treating heart failure, primarily mitigating symptoms and reducing the risk of mortality and other cardiovascular complications. A promising new treatment approach involves using LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI) comprising sacubitril and valsartan. This treatment is superior to the conventional drugs enalapril or valsartan in patients diagnosed with heart failure. A systematic search was conducted on PubMed, the Cochrane Library, and Elsevier's ScienceDirect databases to identify studies comparing sacubitril/valsartan with other drugs in heart failure patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The analyses were conducted using the random-effects model. The study's primary outcomes included all-cause mortality, death from cardiovascular causes, first hospitalization for heart failure, congestive heart failure, and changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical score. The pooled analysis showed that treatment with the sacubitril/valsartan combination was associated with a significantly decreased rate of first hospitalization for heart failure (RR: 0.86; 95% CI: 0.79, 0.98, p: 0.03; I2: 57%) and significantly increased KCCQ clinical score (WMD: 2.20; 95% CI: 0.33, 4.06, p: 0.02; I2: 100%). However, the two groups had no significant difference in all-cause mortality (RR: 0.90; 95% CI: 0.80, 1.01, p: 0.08; I2: 20%), death from cardiovascular causes (RR: 0.96; 95% CI: 0.87, 1.05, p: 0.34; I2: 0%), or congestive heart failure (RR: 0.97; 95% CI: 0.75, 1.25, p: 0.19; I2: 38%). The research findings suggest that sacubitril/valsartan (LCZ696) reduces hospitalizations due to heart failure and improves KCCQ clinical scores. This treatment also reduces the decline in renal function and side effects associated with enalapril or valsartan. Nonetheless, further high-quality randomized controlled trials with large sample sizes are needed to assess other impacts of this therapy on heart failure patients. Overall, the use of LCZ696 represents a promising new approach to the treatment of heart failure.

2-year outcomes of MitraClip as a bridge to heart transplantation: The international MitraBridge registry

BackgroundIn the first report from the MitraBridge registry, MitraClip as a bridge to heart transplantation (HTx) proved to be at 1-year an effective treatment strategy for 119 patients with advanced heart failure (HF) who were potential candidates for HTx. We aimed to determine if benefits of MitraClip procedure as a bridge-to-transplant persist up to 2-years. MethodsBy the end of the enrollment period, a total of 153 advanced HF patients (median age 59 years, left ventricular ejection fraction 26.9 ± 7.7%) with significant secondary mitral regurgitation, who were potential candidates for HTx and were treated with MitraClip as a bridge-to-transplant strategy, were included in the MitraBridge registry. The primary endpoint was the 2-year composite adverse events rate of all-cause death, first hospitalization for HF, urgent HTx or LVAD implantation. ResultsProcedural success was achieved in 89.5% of cases. Thirty-day mortality was 0%. At 2-year, Kaplan-Meier estimates of freedom from primary endpoint was 47%. Through 24 months, the annualized rate of HF rehospitalization per patient-year was 44%. After an overall median follow-up time of 26 (9–52) months, elective HTx was successfully performed in 30 cases (21%), 19 patients (13.5%) maintained or obtained the eligibility for transplant, and 32 patients (22.5%) no longer had an indication for HTx because of significant clinical improvement. ConclusionsAfter 2-years of follow-up, the use of MitraClip as a bridge-to-transplant was confirmed as an effective strategy, allowing elective HTx or eligibility for transplant in one third of patients, and no more need for transplantation in 22.5% of cases.

Disparities in Postdischarge Ambulatory Care Follow-Up Among Medicaid Beneficiaries With Diabetes, Hospitalized for Heart Failure.

Background Ambulatory follow-up for all patients with heart failure (HF) is recommended within 7 to 14 days after hospital discharge to improve HF outcomes. We examined postdischarge ambulatory follow-up of patients with comorbid diabetes and HF from a low-income population in primary and specialty care. Methods and Results Adults with diabetes and first hospitalizations for HF, covered by Alabama Medicaid in 2010 to 2019, were included and the claims analyzed for ambulatory care use (any, primary care, cardiology, or endocrinology) within 60 days after discharge using restricted mean survival time regression and negative binomial regression. Among 9859 Medicaid-covered adults with diabetes and first hospitalization for HF (mean age, 53.7 years; SD, 9.2 years; 47.3% Black; 41.8% non-Hispanic White; 10.9% Hispanic/Other [Other included non-White Hispanic, American Indian, Pacific Islander and Asian adults]; 65.4% women, 34.6% men), 26.7% had an ambulatory visit within 0 to 7 days, 15.2% within 8 to 14 days, 31.3% within 15 to 60 days, and 26.8% had no visit; 71% saw a primary care physician and 12% a cardiology physician. Black and Hispanic/Other adults were less likely to have any postdischarge ambulatory visit (P<0.0001) or the visit was delayed (by 1.8 days, P=0.0006 and by 2.8 days, P=0.0016, respectively) and were less likely to see a primary care physician than non-Hispanic White adults (adjusted incidence rate ratio, 0.96 [95% CI, 0.91-1.00] and 0.91 [95% CI, 0.89-0.98]; respectively). Conclusions More than half of Medicaid-covered adults with diabetes and HF in Alabama did not receive guideline-concordant postdischarge care. Black and Hispanic/Other adults were less likely to receive recommended postdischarge care for comorbid diabetes and HF.

Safety and Efficacy of Empagliflozin and Diuretic Use in Patients with Heart Failure and Preserved Ejection Fraction

The diuretic effect of sodium-glucose cotransporter 2 inhibitors may result in interaction with background diuretic therapy in patients with heart failure and preserved ejection fraction (HFpEF). To assess the safety and efficacy of empagliflozin in combination with background diuretic therapy and the association of empagliflozin with the need for conventional diuretics. This was a post hoc analysis of the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved). EMPEROR-Preserved was a phase 3, randomized, placebo-controlled, double-blind clinical trial conducted from March 2017 to April 2021. Patients with class II to IV heart failure and left ventricular ejection fraction greater than 40% were included. Of 5988 patients enrolled, 5815 (97.1%) had baseline data on diuretic use and were included in this analysis, which was conducted from November 2021 to August 2022. Participants in EMPEROR-Preserved were randomized to empagliflozin or placebo. In this analysis, participants were divided into 4 subgroups: no diuretics and furosemide-equivalent diuretic dose of less than 40 mg, 40 mg, and greater than 40 mg at baseline. The main outcomes of interest were first hospitalization for heart failure (HHF) or cardiovascular death (CV death) and its components. Association of empagliflozin vs placebo with outcomes by baseline diuretic status (no diuretic vs any dose) and dose (no diuretic, <40 mg, 40 mg, and > 40mg) was assessed. Association of empagliflozin use with changes in diuretic therapy was also studied. Among 5815 patients (mean [SD] age, 71.9 [9.4] years; 2594 [44.6%] female) with known baseline diuretic use, 1179 (20.3%) were not taking diuretics, 1725 (29.7%) were taking less than 40 mg, 1772 (30.5%) were taking 40 mg, and 1139 (19.6%) were taking greater than 40 mg. In the placebo arm, patients with higher diuretic doses had worse outcomes. Empagliflozin decreased the risk of HHF or CV death, regardless of background diuretic status (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93] for the diuretic group vs HR, 0.72; 95% CI, 0.48-1.06 for the nondiuretic group; P for interaction = .58). Similarly, diuretic status was not associated with changes in improvements in first HHF, total HHF, rate of decline in estimated glomerular filtration rate, and Kansas City Cardiomyopathy Questionnaire 23 clinical summary score with empagliflozin. Findings were consistent when patients were categorized by diuretic dose. Empagliflozin was associated with a decreased likelihood of diuretic dose escalation (HR, 0.74; 95% CI, 0.65-0.84) and an increased likelihood of de-escalation (HR, 1.15; 95% CI, 1.02-1.30). Empagliflozin was associated with an increased risk of volume depletion in patients taking diuretics (HR, 1.34; 95% CI, 1.13-1.59). In this study, treatment with empagliflozin was similar regardless of diuretic use or dose. Empagliflozin use was associated with decreased conventional diuretic dosing. ClinicalTrials.gov Identifier: NCT03057951.

Effectiveness of apabetalone and some other indirect epigenetic-oriented drugs in the treatment of heart failure

Epigenetic therapy for cardiovascular disease (CVD) has received increased attention from the medical community in recent years. Evidence of this is the fact that more and more controlled clinical trials evaluate the beneficial effects of: 1) direct epigenetic drugs, for example, apabetalone, and 2) repurposed drugs with possible indirect epigenetic action, for example, metformin, statins, sodium-glucose transport protein 2 (SGLT2) inhibitors and omega-3 polyunsaturated fatty acids (PUFAs) in CVD, including heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Apabetalone is the first and unique direct-acting epigenetic drug tested in patients with CVD, and the BETonMACE study showed a reduction in first hospitalization for HF (at any EF) and CVD mortality in patients with type 2 diabetes (T2D) and recent acute coronary syndrome, suggesting a possible role for this drug in secondary prevention. Patients with HFpEF appear to benefit from the addition of metformin and SGLT2 inhibitors to standard statin therapy due to their ability to reduce the death risk. In contrast, hydralazine with or without isosorbide dinitrate produced no beneficial effects. In HFrEF, metformin and SGLT2 inhibitors may reduce the risk of HF and death, while clinical trials with statins have mixed results. PUFA supplementation was associated with a significant reduction in car­diovascular risk in both HFrEF and HFpEF. However, definitive data on the benefits of direct and indirect epigenetic therapy for CVD can only be obtained from large clinical trials in the future. The purpose of this review was to provide updated information on epigenetic therapy for CVD obtained from clinical trials.

Lessons from a pre-specified meta-analysis ofsodium-glucose cotransporter-2 (SGLT2) inhibitors in heart failure: Time for new clinical recommendations.

Cardiovascular disease remains the leading cause of death worldwide with heart failure (HF) being one of the significant contributors to morbidity and mortality. The incidence of HF with preserved ejection fraction (HFpEF) is increasing, especially in young adults making it a growing public health matter. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to reduce the development, progression, and mortality of heart failure in patients with reduced EF regardless of patients' diabetes status but their clinical benefits in patients with heart failure and preserved ejection fraction are less well-established. Recent trials have shown reductions in cardiovascular death and heart failure events in patients with mildly reduced or preserved ejection fraction (EF), although with uncertainty around the consistency of clinical benefits across the classes and therapeutic effects. Study and Results: The meta-analysis used data from trials on patients with mildly reduced or preserved EF (DELIVER and EMPEROR-Preserved), reduced EF (DAPA-HF and EMPEROR-Reduced), and those hospitalized (SOLOIST-WHF). The endpoints evaluated included a composite of time to cardiovascular (CV) death or first hospitalization for heart failure, cardiovascular death, all-cause death, first and recurrent heart failure hospitalizations, and urgent heart failure visits (not requiring hospitalization). Among 12251 participants in the DELIVER and EMPEROR-Preserved trials, SGLT2 inhibitors reduced composite cardiovascular death or first hospitalization for HF (HR 0.80 [95% CI 0.73-0.87]) with consistent reductions in both components: cardiovascular death (HR 0.88 [95% CI 0.77-1.00]) and first hospitalization for HF (HR 0.74 [95% CI 0.67-0.83]). In the broader analysis of the five trials with a total of 21 947 participants, SGLT2 inhibitors reduced the risk of composite cardiovascular death or hospitalization for HF (HR 0.77 [95% CI 0.72-0.82]), cardiovascular death (0.87 [0.79-0.95]), first hospitalization for heart failure (HR 0.72 [95% CI 0.67-0.78]), and all-cause mortality (HR 0.92 [95% CI 0.86-0.99]). These treatment effects for each of the studied endpoints were consistently observed across all five trials and across the HF subgroups, including those on mildly reduced or preserved ejection fraction. SGLT2 inhibitors significantly reduce the risk of mortality and worsening of heart failure and improve patient symptoms and overall health status across the full spectrum of ejection fraction. SGLT2 inhibitors should be considered foundational therapy in all patients with heart failure, irrespective of LVEF or care setting. The results presented propose an update of the recommendations for the pharmacological treatment of heart failure, to prioritize the use of SGLT2 inhibitors in patients across the full EF spectrum. Future investigations should include the long-term benefits of the use of SGLT2 inhibitors among the different HF subgroups, including the performance of SGLT2 inhibitors in those excluded from the current heart failure trials.

P126 RADIOTHERAPY AND THE HEART: IN SEARCH OF ARIANNA‘S THREAD

Abstract Background Radiation therapy (RT) is widely diffused in the treatment of cancer; but it could lead to various negative consequences on the cardiovascular system, even several years after treatment end. They include also valvular heart diseases, arrythmias, coronary artery diseases, heart failure, pericardial diseases, systemic and pulmonary artery diseases. We report an interesting case about RT cardiotoxicity different manifestation occurred in the same patient. Case report: 79 years old patient, history of previous testicular seminoma when he was 54 years old (1997), treated through surgery and RT with betatron (total body cobalt). In 2008 aortic valve replacement with mechanical prothesis; in 2017 first hospitalization for heart failure during atrial fibrillation. In subsequent years, recurring episodes of atrial fibrillation (2 unsuccessful attempts at electrical cardioversion), and heart failure exacerbations with mild reduced ejection fraction, treated through medical therapy improvement. At follow–up echocardiogram (03/19) finding of ejection fraction mild reduced (45%), right sections increased in volumes, tricuspid valve moderate regurgitation. In January 2022, at the last cardiac check–up, he reported worsening dyspnoeic symptoms, and occasional episodes of retrosternal pain in last months. It was performed Coro–TC observing a 60% stenosis at distal tract of right coronary; in addition, patient underwent a transoesophageal echocardiogram which documented further reduction in left ventricle ejection fraction, and worsening tricuspid regurgitation to a severe degree, with anulus dilatation and partial failure of leaflets coaptation, which appeared fibro–elastic; inferior vena cava ectasia, Paps 40–45 mmHg circa. Holter–ECG showed atrial fibrillation for all 24 hours, plus 2000 BEV. The case was discussed in Heart Team, and an indication was placed for Triclip intervention. Discussion Nowadays great achievements of anticancer therapies improved patients’ survival, consequently increased the number of anticancer therapies complications; therefore, an accurate cardiac screening for early diagnosis and effective treatment of CV adverse effects is necessary. Several distinct factors contribute to determine the onset cardiotoxicity insurgence, such as the type of cancer, its anatomical localization; radiation techniques applied, total and fractional radiation doses; patient’s age and his comorbidity and risk factors for cardiovascular diseases.

Chronic heart failure: the role of di vericiguat.

The introduction of multiple new pharmacological agents over the past three decades in the field of heart failure with reduced ejection fraction (HFrEF) has led to reduced rates of mortality and hospitalizations, and consequently, the prevalence of HFrEF has increased, and up to 10% of patients progress to more advanced stages, characterized by high rates of mortality and hospitalizations and poor quality of life. Vericiguat, a novel oral soluble guanylate cyclase stimulator, has proved effective in patients with HFrEF who had recently been hospitalized or had received intravenous diuretic therapy. In these patients, vericiguat reduced the primary outcome of death from cardiovascular causes or first hospitalization for heart failure in comparison with placebo. By reducing hospital admissions in a population at a very high risk of re-hospitalization, vericiguat might have a positive impact on healthcare costs for the management of HFrEF.