Risk Of Heart Failure Hospitalization Research Articles

Participation in a clinical trial is associated with lower mortality but not lower risk of HF hospitalization in patients with heart failure: observations from the ESC EORP Heart Failure Long-Term Registry.

Abstract

Sacubitril-valsartan versus enalapril for the treatment of acute decompensated heart failure in Chinese settings: A cost-effectiveness analysis.

Background: The episode of acute decompensated heart failure (ADHF) is the main cause of hospitalization for heart failure (HF). Sacubitril-valsartan has been proven to be effective in reducing the risks of hospitalization for HF in ADHF. When to initiate sacubitril-valsartan in ADHF to make it the most cost-effective in China remains unclear. Methods: A lifetime Markov model with a 1-month cycle length was developed to evaluate the cost-effectiveness of early or late initiation of sacubitril-valsartan versus enalapril in ADHF. Early initiation of sacubitril-valsartan meant that it was initiated after stabilization from ADHF, and late initiation of sacubitril-valsartan meant that it was initiated after stabilization from HF, which includes no hospitalization for at least three consecutive months. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as the ratio of incremental cost to incremental effectiveness. The secondary outcomes were total costs and total effectiveness. Three times of per capita GDP of China in 2021 was set as the willingness-to-pay threshold. One-way sensitivity analysis and probabilistic sensitivity analysis were employed to test the robustness of the results. Results: The early initiation of sacubitril-valsartan treatment resulted in an ICER of 3,662.4 USD per quality-adjusted life year, lower than the willingness-to-pay threshold, and the late initiation of sacubitril-valsartan treatment gained an ICER of 4,444.4 USD/QALY, still lower than the willingness-to-pay threshold. One-way sensitivity analysis showed that our results were robust, and probabilistic sensitivity analysis suggested that early initiation of sacubitril-valsartan in ADHF was cost-effective under a 97.4% circumstance. Conclusion: Early initiation of sacubitril-valsartan after stabilization of ADHF is highly cost-effective compared with the use of enalapril; late initiation of sacubitril-valsartan after stabilization of HF is still cost-effective but not as cost-effective as early initiation of sacubitril-valsartan in ADHF. For Chinese ADHF patients, the time to initiate sacubitril-valsartan should be when the patient is stabilized from ADHF rather than when stabilized from HF, from the perspective of economic evaluation.

Efficacy and safety of drugs for people with type 2 diabetes mellitus and chronic kidney disease on kidney and cardiovascular outcomes: A systematic review and network meta-analysis of randomized controlled trials

AimTo evaluate the comparative efficacy and safety of promising kidney protection drugs, including sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl-peptidase IV Inhibitors (DPP-4Is), aldosterone receptor agonists (MRAs), endothelin receptor antagonist (ERAs), pentoxifylline (PTF), and pirfenidone (PFD), on cardiovascular and kidney outcomes in type 2 diabetes (T2DM) and chronic kidney disease (CKD) population. MethodsPubMed, Embase, and Cochrane Library were searched from inception to August 12, 2022. We used the Bayesian model for network meta-analyses, registered in the PROSPERO (CRD42022343601). ResultsThis network meta-analysis identified 2589 citations, and included 27 eligible trials, enrolling 50,237 patients. All results presented below were moderate to high quality. For kidney outcomes, SGLT-2Is were optimal in terms of reducing composite kidney events (RR 0.69, 95%CI 0.61–0.79), and slowing eGFR slope (MD1.34, 95%CI 1.06–1.62). Then MRAs (RR 0.77, 95%CI 0.68–0.88; MD 1.31, 95%CI 0.89–1.74), GLP-1RAs (RR 0.78, 95%CI 0.62–0.97; MD 0.75, 95%CI 0.46–1.05), and ERAs (RR 0.75, 95%CI 0.57–0.99; MD 0.7, 95%CI 0.3–1.1) were followed in parallel. For cardiovascular outcomes, SGLT-2 inhibitors were also among the best for lowing the risk of heart failure hospitalization (RR 0.67, 95%CI 0.57–0.78), followed by GLP-1RAs (RR 0.73, 95%CI 0.55–0.97) and MRAs (RR 0.79, 95%CI 0.67–0.92). SGLT-2Is (RR 0.8, 95%CI 0.71–0.89) and GLP-1RAs (RR 0.72, 95%CI 0.6–0.86) had comparable effects to reduce the risk of major adverse cardiovascular events. MRAs were possibly associated with increased drug discontinuation due to adverse events (RR 1.21, 95%CI 1.05–1.38). For the hyperkalemia outcome, MRAs (RR 2.08, 95%CI 1.86–2.33) were linked to the risk of hyperkalemia, whereas SGLT-2Is (RR 0.78, 95%CI 0.65–0.93) were in contrast. ConclusionsSGLT-2Is significantly reduced kidney and cardiovascular risk in T2DM and CKD, subsequently GLP-1RAs and MRAs. SGLT-2Is-MRAs combination might be a recommended treatment regimen for maximizing kidney and cardiovascular protection but with a low risk of hyperkalemia in T2DM and CKD.

Prognostic value of mitral valve haemodynamic parameters obtained by intraprocedural echocardiography in transcatheter edge-to-edge repair.

To assess whether intraprocedural transesophageal echocardiographic (TEE)-derived haemodynamic parameters predict outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) for mitral regurgitation (MR). This is a single-centre, retrospective analysis encompassing 458 (IQR, 104-1035) days of follow-up after 926 consecutive patients [481 (52%) with functional MR] referred to an isolated mitral TEER between 2013 and 2020. Cases without actual clip deployment, or in whom prior mitral procedures had taken place, were excluded. The primary outcome was the combined rate of all-cause mortality or heart failure (HF) hospitalizations. Secondary endpoints included single components of the primary outcome, as well as MR severity at one month and one year following the procedure. A multivariable analysis identified two intraprocedural echocardiographic observations made after clip deployment as independent predictors of the primary outcome: an above mild MR (HR for whole study period 1.49, 95% CI 1.05-2.13, P = 0.026) and a 100% or more increase from baseline in the transmitral mean pressure gradient (TMPG) (HR for whole study period 1.32, 95% CI 1.01-1.72, P = 0.039). Also, MR grade of above mild and the absence of a normal pulmonary venous flow pattern (PVFP) bilaterally were associated with an increased risk for HF hospitalizations and greater-than-mild 1-month MR. No prognostic role was demonstrated for the change in MR severity, the absolute TMPG, or the mere improvement in PVFP. Immediate post-TEER MR severity and the relative change in TMPG are predictive of clinical and echocardiographic outcomes following the procedure.

Glucagon-Like Peptide 1 Receptor Agonists Versus Sodium-Glucose Cotransporter 2 Inhibitors for Atherosclerotic Cardiovascular Disease in Patients With Type 2 Diabetes.

Beyond improving hemoglobin A1c (HbA1c) in adults with type 2 diabetes, glucagon-like peptide 1 receptor agonists (GLP-1RA) have been approved for reducing risk of major adverse cardiovascular events (MACE) with established cardiovascular disease (CVD) or multiple CV risk factors. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) also reduced the risk for the primary composite CV outcome in patients with type 2 diabetes at high risk for CV events. In the American Diabetes Association (ADA) and European Association of Study in Diabetes (EASD) consensus report 2022, there is the description "In people with established atherosclerotic CVD (ASCVD) or with a high risk for ASCVD, GLP-1RA were prioritized over SGLT2i"; however, the evidence supporting such statement is limited. Therefore, we studied the superiority of GLP-1RA over SGLT2i for prevention of ASCVD from various viewpoints. We could not find a meaningful difference in the risk reduction in three-point MACE (3P-MACE), mortality due to any cause, mortality due to CV cause and nonfatal myocardial infarction between GLP-1RA and SGLT2i trials. The risk of nonfatal stroke decreased in all five GLP-1RA trials; however, two of three SGLT2i trials showed an increase in risk of nonfatal stroke. The risk of hospitalization for heart failure (HHF) decreased in all three SGLT2i trials, and one GLP-1RA trial showed an increase in risk of HHF. The risk reduction of HHF in SGLT2i trials was greater than that in GLP-1RA trials. These findings were consistent with current systematic reviews and meta-analyses. The risk reduction of 3P-MACE was significantly and negatively correlated with changes in HbA1c (R = -0.861, P = 0.006) and body weight (R = -0.895, P = 0.003) in GLP-1RA and SGLT2i trials. The studies using SGLT2i failed to reduce carotid intima media thickness (cIMT), the surrogate marker for atherosclerosis; however, several studies using GLP-1RA successfully reduced cIMT in patients with type 2 diabetes. Compared with SGLT2i, GLP-1RA had a higher probability of decreasing serum triglyceride. GLP-1RA have multiple vascular biological anti-atherogenic properties.

Door-to-furosemide time and clinical outcomes in acute heart failure.

Acute heart failure (AHF) is one of the main causes of unplanned hospitalization in patients >65 years of age and is associated with adverse outcomes in this population. Observational studies suggest that intravenous diuretic therapy given in the first hour of presentation for AHF was associated with favorable outcomes. To study the short-term prognostic associations of the timing of intravenous diuretic therapy in patients admitted to the emergency department (ED) for acute AHF. Patients treated in the ED with intravenous diuretics were selected from the Estratificação de Doentes com InsuFIciência Cardíaca Aguda (EDIFICA) registry, a prospective study including AHF hospitalized patients. Early and non-early furosemide treatment groups were considered using the 1-h cutoff: door-to-furosemide ≤1 h and >1 h. Primary outcomes were a composite of heart failure re-hospitalizations or cardiovascular death at 30- and 90-days. Four-hundred ninety-three patients were included in the analysis. The median (interquartile range) door-to-furosemide time was 85 (41-220) min, and 210 (43%) patients had diuretics in the first hour. Patients in the ≤1 h group had higher evaluation priority according to the Manchester Triage System, presented more often with acute pulmonary edema, warm-wet clinical profile, higher blood pressure, and signs of left-side heart failure, while >1 h group had higher Get With the Guidelines-heart failure risk score, more frequent signs of right-side heart failure, higher circulating B-type natriuretic peptides and lower albumin. Door-to-furosemide ≤ 1 h was independently associated with lower 30-day heart failure hospitalizations and composite of heart failure hospitalizations or cardiovascular death (adjusted analysis Heart Failure Hospitalizations: odds ratios (OR) 3.65; 95% confidence interval (CI), 1.22-10.9; P = 0.020; heart failure hospitalizations or cardiovascular death: OR 3.15; 95% CI, 1.49-6.64; P < 0.001). These independent associations lost significance at 90 days. Door-to-furosemide ≤1 h was associated with a lower short-term risk of heart failure hospitalizations or cardiovascular death in AHF patients. Our findings add to the existing evidence that early identification and intravenous diuretic therapy of AHF patients may improve outcomes.

Association of pulmonary transit time by cardiac magnetic resonance with heart failure hospitalization in a large prospective cohort with diverse cardiac conditions

BackgroundLonger pulmonary transit time (PTT) is closely associated with hemodynamic abnormalities. However, the implications on heart failure (HF) risk have not been investigated broadly in patients with diverse cardiac conditions. In this study we examined the long-term risk of HF hospitalization associated with longer PTT in a large prospective cohort with a broad spectrum of cardiac conditions. MethodsAll subjects were prospectively recruited to undergo cardiac magnetic resonance (CMR). The dynamic images of first-pass perfusion were acquired to assess peak-to-peak pulmonary transit time (PTT) which was subsequently normalized to RR interval duration. The risk of HF was examined using Cox proportional hazards models adjusted for baseline confounding risk factors. ResultsAmong 506 consecutively consented patients undergoing clinical cardiac MR with diverse cardiac conditions, the mean age was 63 ± 14 years and 373 (73%) were male. After a mean follow up duration of 4.5 ± 3.0 years, 70 (14%) patients developed hospitalized HF and of these 6 died. A normalized PTT ≥ 8.2 was associated with a significantly increased adjusted HF hazard ratio of 3.69 (95% CI 2.02, 6.73). The HF hazard ratio was 1.26 (95% CI 1.18, 1.33) for each 1 unit increase in PTT which was higher among those preserved (1.70, 95% CI 1.20, 2.41) compared to those with reduced left ventricular ejection fraction (< 50%) (1.18, 95% CI 1.09, 1.27). PTT remained a significant risk factor of hospitalized HF after additional adjustment for N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) or left ventricular global longitudinal strain with additionally demonstrated incremental model improvement through likelihood ratio testing. ConclusionsOur findings support the role of PTT in assessing HF risk among patients with broad spectrum of cardiac conditions with reduced as well as preserved ejection fraction. Longer PTT duration is an incremental risk factor for HF when baseline global longitudinal strain and NT-proBNP are taken into consideration.

Evolution of sodium-glucose co-transporter 2 inhibitors from a glucose-lowering drug to a pivotal therapeutic agent for cardio-renal-metabolic syndrome.

Cardio-renal-metabolic (CRM) syndrome, which involves type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and heart failure (HF), is a serious healthcare issue globally, with high morbidity and mortality. The disorders that comprise CRM syndrome are independent can mutually affect and accelerate the exacerbation of each other, thereby substantially increasing the risk of mortality and impairing quality of life. To manage CRM syndrome by preventing vicious interactions among individual disorders, a holistic treatment approach that can simultaneously address multiple disorders underpinning CRM syndrome is of great importance. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) lower blood glucose levels by inhibiting glucose reabsorption in the renal proximal tubule and were first indicated for the treatment of T2DM. Several cardiovascular outcome trials have demonstrated that SGLT2i not only lower blood glucose but also reduce the risk of hospitalization for HF and worsening renal function in patients with T2DM. Results have also suggested that the observed cardiorenal benefits of SGLT2i may be independent of their blood glucose-lowering effects. Several randomized controlled trials subsequently assessed the efficacy and safety of SGLT2i in patients without T2DM, and revealed considerable benefits of SGLT2i treatment against HF and CKD, regardless of the presence of T2DM. Thus, SGLT2i have become an essential therapeutic option to prevent the onset, slow the progression, and improve the prognosis of CRM syndrome. This review assesses the evolution of SGLT2i from a glucose-lowering drug to a therapeutic agent for CRM syndrome by evaluating epoch-making clinical studies, including randomized control trials and real-world studies.

Intravenous iron supplementation in heart failure patients induces temporary endothelial dysfunction with release of endothelial microvesicles.

Intravenous iron supplementation is an established therapy for patients with heart failure (HF) and concomitant iron deficiency reducing the risk of HF hospitalization. However, concerns persist regarding potential adverse vascular effects, since iron may induce oxidative stress, inflammation, and apoptosis of endothelial cells. To assess endothelial health following ferric carboxymaltose (FCM) administration, we analyzed the profile of circulating endothelial microvesicles (EMVs) and endothelial progenitor cells (EPCs) in a cohort of 23 HF patients using flow cytometry. Compared to healthy subjects, baseline levels of CD31+/CD41- EMVs were higher and EMVs featured a more apoptotic phenotype in HF patients. Following FCM administration, EMV levels showed a rapid but transient increase and displayed an altered phenotype profile with dominant augmentation of EMVs expressing inducible markers CD62E and CD54, indicating endothelial inflammatory 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. Levels of EMVs and EPCs returned to baseline values within two and four weeks, respectively. HF patients with additional chronic kidney disease showed an elevated EMV/EPC ratio and diminished EPC mobilization, suggesting impaired vascular repair capacity. Providing a mechanistic link, in vitro experiments with cultured endothelial cells revealed that FCM dose-dependently promotes endothelial apoptosis, increases expression of adhesion molecules and CXCL12, and triggers generation of EMVs. Intravenous iron supplementation with FCM in HF patients induces a biphasic response with initial increased release of CD62E+ and CD54+ enriched EMVs and subsequent mobilization of EPCs, indicating endothelial dysfunction upon FCM and suggesting consecutive engagement of a defense program aimed to reconstitute vascular health.

Longitudinal HbA1c trajectory modelling reveals the association of HbA1c and risk of hospitalization for heart failure for patients with type 2 diabetes mellitus.

Inconsistent conclusions in past studies on the association between poor glycaemic control and the risk of hospitalization for heart failure (HHF) have been reported largely due to the analysis of non-trajectory-based HbA1c values. Trajectory analysis can incorporate the effects of HbA1c variability across time, which may better elucidate its association with macrovascular complications. Furthermore, studies analysing the relationship between HbA1c trajectories from diabetes diagnosis and the occurrence of HHF are scarce. This is a prospective cohort study of the SingHealth Diabetes Registry (SDR). 17,389 patients diagnosed with type 2 diabetes mellitus (T2DM) from 2013 to 2016 with clinical records extending to the end of 2019 were included in the latent class growth analysis to extract longitudinal HbA1c trajectories. Association between HbA1c trajectories and risk of first known HHF is quantified with the Cox Proportional Hazards (PH) model. 5 distinct HbA1c trajectories were identified as 1. low stable (36.1%), 2. elevated stable (40.4%), 3. high decreasing (3.5%), 4. high with a sharp decline (10.8%), and 5. moderate decreasing (9.2%) over the study period of 7 years. Poorly controlled HbA1c trajectories (Classes 3, 4, and 5) are associated with a higher risk of HHF. Using the diabetes diagnosis time instead of a commonly used pre-defined study start time or time from recruitment has an impact on HbA1c clustering results. Findings suggest that tracking the evolution of HbA1c with time has its importance in assessing the HHF risk of T2DM patients, and T2DM diagnosis time as a baseline is strongly recommended in HbA1c trajectory modelling. To the authors' knowledge, this is the first study to identify an association between HbA1c trajectories and HHF occurrence from diabetes diagnosis time.

Increased Risk of Heart Failure in Elderly Patients Treated with Beta-Blockers After AV Node Ablation.

Controversy exists regarding the indication of beta-blockers (BB) in different scenarios in patients with cardiovascular disease. We sought to evaluate the effect of BB on survival and heart failure (HF) hospitalizations in a sample of pacemaker-dependent patients after AV node ablation to control ventricular rate for atrial tachyarrhythmias. A retrospective study including consecutive patients that underwent AV node ablation was conducted in a single center between 2011 and 2019. The study's primary endpoints were the incidence of all-cause mortality, first HF hospitalization and the cumulative incidence of subsequent hospitalizations for HF. Competing risk analyses were employed. A total of 111 patients with a mean age of 73.9 years were included in the study. After a median follow-up of 45.5 months, 43 patients had died (38.7%) and 31 had been hospitalized for HF (27.9%). The recurrent HF hospitalization rate was 74/1000 patients/year. Patients treated with BB had a non-significant trend to higher mortality rates and a higher risk of recurrent HF hospitalizations (incidence rate ratio 2.23, 95% confidence interval 1.12-4.44; p = 0.023). After an AV node ablation, the use of BB is associated with an increased risk of HF hospitalizations in a cohort of elderly patients.

Efficacy and safety of low-dose sacubitril/valsartan in heart failure patients: A systematic review and meta-analysis.

Controversy has persisted over the clinical benefits of low-dose sacubitril/valsartan in patients with heart failure (HF). Low-dose sacubitril/valsartan might also be effective and safe in HF patients. Electronic databases including PubMed, Ovid, and Cochrane Library were systematically retrieved from inception to August 5, 2021. Review manager 5.4 and Stata 15.1 were employed in this systematic review and meta-analysis. Key efficacy outcomes of interest included HF hospitalization, all-cause mortality, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), together with New York Heart Association (NYHA) functional class. The safety outcome was systolic blood pressure (SBP). The grading of recommendations assessment, development, and evaluationapproach was conducted to evaluate the quality of evidence for each outcome. A total of 1269 studies were screened and 9 real-world studies met the inclusion criteria were included in the meta-analysis, with 1697 participants. Compared with low-dose sacubitril/valsartan, high-dose sacubitril/valsartan significantly reduced the risk of HF hospitalization (odds ratio[OR]: 0.4, 95%confidence interval[CI]: 0.27-0.61, p < .0001) and the risk of all-cause mortality (OR: 0.23, 95%CI: 0.11-0.47, p < .0001). However, there were no appreciable differences in improvements of NYHA (OR: 0.59, 95%CI: 0.15-2.35, p = .45), changes of LVEF (mean difference[MD]: 2.73%, 95%CI: -2.24% to 7.7%, p = .28), changes of NT-proBNP (MD: 43.09, 95%CI: -28.41 to 114.59, p = .24) and changes of SBP (MD: 3.01, 95%CI: -4.62 to 10.64, p = .44) between groups with low-dose and high-dose sacubitril/valsartan. Compared with high-dose sacubitril/valsartan, low-dose sacubitril/valsartan was associated with increased risks of HF hospitalization and all-cause mortality. However, no distinct between-group differences in improvements of NYHA, changes of LVEF, changes of NT-proBNP and changes of SBP were observed.

Association between the risk of heart failure hospitalization and end-stage renal disease with digoxin usage in patients with cardiorenal syndrome: A population-based study.

The management of the coexistence of heart disease and kidney disease is increasingly challenging for clinicians. Chronic kidney disease (CKD) is not only a prevalent comorbidity of patients with heart failure but has also been identified as a noteworthy risk factor for all-cause mortality and poor clinical outcomes. Digoxin is one of the commonest treatments for heart disease. There are few trials investigating the role of digoxin in patients with cardiorenal syndrome (CRS). This study aims to examine the association between digoxin usage and clinical outcomes in patients with CRS in a nationwide cohort. We conducted a population-based study that included 705 digoxin users with CRS; each patient was age, sex, comorbidities, and medications matched with three non-users who were randomly selected from the CRS population. Cox proportional hazards regression analysis was conducted to estimate the effects of digoxin on the incidence of all-cause mortality, congestive heart failure (CHF) hospitalization, coronary artery disease (CAD) hospitalization, and end-stage renal disease (ESRD). The all-cause mortality rate was significantly higher in digoxin users than in non-users (adjusted hazard ratio [aHR] = 1.26; 95% confidence interval [CI] = 1.09-1.46, p = 0.002). In a subgroup analysis, there was significantly high mortality in the 0.26-0.75 defined daily dose (DDD) subgroup of digoxin users (aHR = 1.49; 95% CI = 1.23-1.82, p<0.001). Thus, the p for trend was 0.013. With digoxin prescription, the CHF hospitalization was significantly higher [subdistribution HR (sHR) = 1.17; 95% CI = 1.05-1.30, p = 0.004], especially in the >0.75 DDD subgroup (sHR = 1.19; 95% CI = 1.01-1.41, p = 0.046; p for trend = 0.006). The digoxin usage lowered the coronary artery disease (CAD) hospitalization in the > 0.75 DDD subgroup (sHR = 0.79; 95% CI = 0.63-0.99, p = 0.048). In renal function progression, more patients with CRS entered ESRD with digoxin usage (sHR = 1.34; 95% CI = 1.16-1.54, p<0.001). There was a significantly greater incidence of ESRD in the < 0.26 DDD and 0.26-0.75 DDD subgroups of digoxin users (sHR = 1.32; 95% CI = 1.06-1.66, p = 0.015; sHR = 1.44; 95% CI = 1.18-1.75; p for trend<0.001). Digoxin should be prescribed with caution to patients with CRS.

Cardiovascular, renal, and lower limb outcomes in patients with type 2 diabetes after percutaneous coronary intervention and treated with sodium-glucose cotransporter 2 inhibitors vs. dipeptidyl peptidase-4 inhibitors.

Patients with type 2 diabetes (T2D) who undergo percutaneous coronary intervention (PCI) are at higher risk of adverse cardiovascular and renal events than non-diabetic patients. However, limited evidence is available regarding the cardiovascular, renal, and limb outcomes of patients with T2D after PCI and who were treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i). We compare the specified outcomes in patients with T2D after PCI who were treated with SGLT2i vs. dipeptidyl peptidase-4 inhibitors (DPP4i). In this nationwide retrospective cohort study, we identified 4248 and 37037 consecutive patients with T2D who underwent PCI with SGLT2i and DPP4i, respectively, for 1 May 2016-31 December 2019. We used propensity score matching (PSM) to balance the covariates between study groups. After PSM, SGLT2i, and DPP4i were associated with comparable risks of ischaemic stroke, acute myocardial infarction, and lower limb amputation. However, SGLT2i was associated with significantly lower risks of heart failure hospitalization [HFH; 1.35% per year vs. 2.28% per year; hazard ratio (HR): 0.60; P=0.0001], coronary revascularization (2.33% per year vs. 3.36% per year; HR: 0.69; P=0.0003), composite renal outcomes (0.10% per year vs. 1.05% per year; HR: 0.17; P<0.0001), and all-cause mortality (2.27% per year vs. 3.80% per year, HR: 0.60; P<0.0001) than were DPP4i. Our data indicated that SGLT2i, compared with DPP4i, were associated with lower risks of HFH, coronary revascularization, composite renal outcomes, and all-cause mortality for patients with T2D after PCI. Further randomized or prospective studies can investigate the effects of SGLT2i in patients with T2D after PCI.

Emerging concepts in heart failure management and treatment: focus on SGLT2 inhibitors in heart failure with preserved ejection fraction.

The role of sodium-glucose cotransporter 2 inhibitors (SLTG2i), developed initially as glucose-lowering agents, has represented a novelty in patients with heart failure (HF) and reduced ejection fraction (HFrEF) since dapagliflozin (DAPA-HF study) and empagliflozin (EMPEROR-Reduced study) were able to reduce morbidity and mortality in this setting regardless of the presence or absence of diabetes. In previous large clinical trials (EMPA-REG OUTCOME study, CANVAS, DECLARE-TIMI 58), SGLT2i have been shown to attenuate HF progression expressed by reducing the risk of HF hospitalizations in patients with type 2 diabetes mellitus mostly without HF at baseline. This benefit was then corroborated with positive results in HF outcomes (cardiovascular mortality and HF hospitalizations) in patients with HF with preserved ejection fraction (HFpEF) in the EMPEROR-Preserved (empagliflozin) and DELIVER (dapagliflozin) trials. Several biological mechanisms apart from the glycosuria are attributed to these agents in this last context, including anti-inflammatory effects, reduction of fibrosis and apoptosis, improvement of myocardial metabolism, mitochondrial function optimization, and oxidative stress protection. Moreover, SGLT2i can also improve ventricular loading conditions by forcing diuresis and natriuresis, and by enhancing vascular and renal function. In addition, SGLT2i can reduce myocardial passive stiffness (diastolic function) by enforcing the phosphorylation of myofilament modulatory proteins. This article provided an overview of the main pathophysiological characteristics of HFpEF and of the diverse mechanisms of action of SGLT2i in this setting. The supporting clinical evidence of SGLT2i in HFpEF (EMPEROR-Preserved and DELIVER trials) is also reviewed. This article is part of the Emerging concepts in heart failure management and treatment Special Issue: https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment.

Iron Deficiency in Heart Failure: A Korea-Oriented Review.

Iron deficiency (ID) occurs at high frequency across the spectrum of heart failure (HF), with HF severity and race being potentially important predictors for its development. ID, irrespective of anaemia status, leads to poor outcomes in patients with HF, including exacerbated reduction in exercise capacity, poor quality of life (QoL) and increased risk of HF hospitalisation. As ID has a large public health and economic burden in Asia, and patients hospitalised with acute HF in the Asia Pacific vs. other regions commonly present with more severe clinical symptoms, there is a clear need to identify and treat ID promptly in Asian patients with HF. The biomarkers serum ferritin and transferrin saturation are used for ID diagnosis, and periodic screening is recommended in all patients with HF. The intravenous iron treatments, ferric carboxymaltose (FCM) and ferric derisomaltose, have demonstrated efficacy and tolerability in patients with acute or chronic HF and ID, with FCM shown to be cost-effective (and in some cases cost-saving). Meta-analyses support the likely benefits of intravenous FCM for improving QoL and reducing HF hospitalisation, without reducing mortality risk in patients with HF and ID. Accordingly, European Society of Cardiology guidelines recommend considering intravenous FCM for patients with symptomatic HF with left ventricular ejection fraction ≤50% who were recently hospitalised for HF and have ID. Although analyses of Asian patients with HF and ID are limited, the effects of intravenous iron would be expected to be similar to that in White populations; further clarifying studies may be of interest.

Sodium-Glucose Co-transporter 2 Inhibitors in Patients with Heart Failure with Preserved Ejection Fraction: Proposed Mechanisms, Recent Evidence, and Clinical Implications.

Heart failure (HF) affects approximately 6 million Americans and is projected to increase in prevalence as the population ages. While progress has been made in the treatment of heart failure with reduced ejection fraction (HFrEF), treatments for heart failure with preserved ejection fraction (HFpEF) are few and far between. Since HFpEF makes up half of all heart failure cases, its management may be the biggest unmet need in cardiology. Results from the recent EMPEROR-Preserved trial are encouraging. After 26 months, patients with HFpEF who used the sodium-glucose co-transporter 2 inhibitor empagliflozin had a lower risk of hospitalization for HF than patients taking a placebo. However, the trial did not show empagliflozin to reduce the risk of cardiovascular death, unlike the EMPEROR-Reduced trial, in which empagliflozin was associated with a reduced risk of both cardiac death and hospitalization for patients with HFrEF. The outcomes of these trials highlight the dissimilarities between the two diseases. While HFrEF is mainly a disease of cardiomyocyte injury and systolic dysfunction, HFpEF is a multifactorial syndrome of inflammation and endothelial dysfunction stemming from chronic diseases like hypertension, diabetes and obesity. While trials of empagliflozin for HFpEF did not show a mortality benefit, sodium-glucose co-transporter 2 inhibitors are promising additions to the management of HFpEF for their effects on the disease's risk factors through weight loss, natriuresis, blood pressure lowering, and glycemic control.

Physical Performance in Black and Hispanic Outpatients With Heart Failure: The SCAN-MP Study

BackgroundDeficits of physical function are associated with poor quality of life and adverse health outcomes, but data informing the association of these assessments among Black and Hispanic outpatients with heart failure (HF) are limited. MethodsThe multicentre, prospective Screening for Cardiac Amyloidosis With Nuclear Imaging for Minority Populations (SCAN-MP) study identified Black and Hispanic subjects with stable HF, collected baseline characteristics, and took measures using the short physical performance battery. Subjects completed a Kansas City Cardiomyopathy Questionnaire (KCCQ), and the clinical outcomes of HF hospitalization and death were ascertained by telephone and review of the electronic health record. ResultsOf 320 participants, 227 (70.9%) had physical deficits, defined by a battery score of ≤ 9. Patients with severe physical deficits reported overall lower KCCQ scores compared to those with no deficits (KCCQ score of 57.0 vs 72.4, P < 0.001). Physical limitation was significantly associated with risk of HF hospitalization, after adjustments for age, sex, and New York Heart Association class (severe physical deficit hazard ratio, 3.61; 95% confidence interval [CI], 1.19-10.93; P = 0.024; mild physical deficit hazard ratio, 2.59; 95% CI, 0.86-7.75; P = 0.090). ConclusionsReduced physical performance is highly prevalent among Black and Hispanic outpatients with HF, and it is associated with overall KCCQ score, as well as an increased risk for HF hospitalization.

Pharmacotherapies in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Network Meta-Analysis.

Various pharmacotherapies exist for heart failure with preserved ejection fraction (HFpEF), but with unclear comparative efficacy. We searched EMBASE, Medline, and Cochrane Library from inception through August 2021 for all randomized clinical trials in HFpEF (EF >40%) that evaluated beta-blockers, mineralocorticoid receptor antagonist (MRA), angiotensin-converting enzyme inhibitors (ACE), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Outcomes assessed were cardiovascular mortality, all-cause mortality, and HF hospitalization. A frequentist network meta-analysis was performed with a random-effects model. We included 22 randomized clinical trials (30,673 participants; mean age = 71.7 ± 4.2 years; females = 49.3 ± 7.7%; median follow-up = 24.4 ± 11.1 months). Compared with placebo, there was no statistically significant difference in cardiovascular mortality [beta-blockers; odds ratio (OR) 0.79 (0.46-1.34), MRA; OR 0.90 (0.70-1.14), ACE OR 0.95 (0.59-1.53), ARB; OR 1.02 (0.87-1.19), ARNI; OR 0.97 (0.74-1.26) and SGLT2i; OR 1.00 (0.84-1.18)] or all-cause mortality [beta blockers; OR 0.75 (0.54-1.04), MRA; OR 0.90 (0.75-1.08) ACE; OR 1.05 (0.71-1.54), ARB; OR 1.03 (0.91-1.15), ARNI; OR 0.99 (0.82-1.20) and SGLT2i; OR 1.00 (0.89-1.13)]. The certainty in these estimates was low or very low. There was a significantly reduction in HF hospitalization with the use of SGLT2i [OR 0.71 (0.62-0.82), moderate certainty], ARNI [OR 0.77 (0.63-0.94), low certainty], and MRA [OR 0.81 (0.66-0.98), moderate certainty]; with corresponding P scores of 0.84, 0.68, and 0.58, respectively. In HFpEF, the use of beta-blockers, MRA, ACE/ARB/ARNI, or SGLT2i was not associated with improved cardiovascular or all-cause mortality. SGLT2i, ARNI, and MRA reduced the risk of HF hospitalizations.

Comparison the effects of finerenone and SGLT2i on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus: A network meta-analysis.

Finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), while the relative efficacy has not been determined. The databases of PubMed, Embase and Cochrane were searched for relevant cardiovascular or renal outcome trials of SGLT2i or finerenone. The end points were major adverse cardiovascular events (MACE), nonfatal stroke (NS), myocardial infarction (MI), hospitalization for heart failure (HHF), cardiovascular death (CVD), and renal composite outcome (RCO). Network meta-analysis was performed using Bayesian networks to obtain pooled hazard ratios (HR) and 95% confidence intervals (CI). The probability values for ranking active and placebo interventions were calculated using cumulative ranking curves. 1024 articles were searched, and only 9 studies were screened and included in this meta-analysis with 71793 randomized participants. Sotagliflozin (HR 0.72 95%CI 0.59-0.88, SUCAR=0.93) and canagliflozin (HR 0.80 95%CI 0.67-0.97, SUCAR=0.73) can significantly reduce the risk of MACE compared with placebo. Canagliflozin (HR 0.64 95%CI 0.48-0.86, SUCAR=0.73), sotagliflozin (HR 0.66 95%CI 0.50-0.87, SUCAR=0.69) and empagliflozin (HR 0.65 95%CI 0.43-0.98, SUCAR=0.68) can significantly reduce the risk of HHF compared with placebo. Empagliflozin (HR 0.62 95%CI 0.43-0.89, SUCAR=0.96) can significantly reduce the risk of CVD compared with placebo. Empagliflozin (HR 0.61 95%CI 0.39-0.96, SUCAR=0.74), canagliflozin (HR 0.66 95%CI 0.46-0.92, SUCAR=0.63), and dapagliflozin (HR 0.53 95%CI 0.32-0.85, SUCAR=0.88) can significantly reduce the risk of RCO compared with placebo. Finerenone has reduced the risk of MACE, MI, HHF, CVD and RCO to varying degrees, but they do not show significant difference from placebo and each SGLT2i. Both SGLT2i and finerenone could reduce the risk of MACE, HHF, MI, CVD, RCO. Finerenone has no obvious advantage than SGLT2i on the effects of cardiovascular and renal protective. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022375092.