Reduce Heart Failure Research Articles

The in-hospital administration of sacubitril/valsartan in acute myocardial infarction: A meta-analysis.

There is a need to address the evidence gap regarding the in-hospital administration of sacubitril/valsartan in acute myocardial infarction patients. After searching MEDLINE, Google Scholars and Scopus, a random-effects meta-analysis of randomized controlled trials comparing the in-hospital administration of the angiotensin receptor-neprilysin inhibitors (ARNis) versus the standard therapy in patients with reduced heart failure due to myocardial infarction was performed. The primary outcome was major adverse cardiovascular events. All-cause mortality, cardiac death, rehospitalization for heart failure, non-fatal myocardial infarction (MI), changes in left ventricular ejection fraction, left ventricular volumes, N terminal pro brain natriuretic peptide and adverse events were the secondary endpoints. Nine studies (eight randomized controlled trials and one echo-substudy) with a total 6597 individuals (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker: 3300 patients vs. ARNis: 3297 patients) were included for quantitative analysis. Median follow-up was 6months. Patients receiving an in-hospital coadministration of ARNi had a lower risk of major cardiovascular event [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.32-0.63, P<0.0001] and lower rate of repeat rehospitalization for heart failure (OR 0.40, 95% CI 0.26-0.62, P<0.0001), compared with a standard regimen. Additionally, left ventricle volumes were significantly lower in the ARNi group [left ventricular end-diastolic volume, mean difference (MD) 11.48mL, 95% CI 6.10-16.85, P<0.0001; left ventricular end-systolic volume, MD 7.09mL, 95% CI 2.89-11.29, P=0.0009] with a significant change in left ventricular ejection fraction (MD 3.07, 95% CI 1.61-4.53, P<0.0001), compared with standard therapy. No significant differences were observed in terms of cardiac death, all cause of mortality, non-fatal myocardial infarction and N terminal pro brain natriuretic peptide. Higher rates of iatrogenic hypotensive events were observed in the ARNi group compared with the standard therapy (OR 1.42, 95% CI 1.26-1.60, P value<0.00001). In patients with acute myocardial infarction related heart failure, the in-hospital administration of ARNis was associated with a reduced risk of major cardiovascular events and re-hospitalization for heart failure, as well as cardiac remodelling, but higher rates of hypotensive events compared with standard therapy.

Serum transferrin concentration: a new prognostic biomarker in heart failure with reduced ejection fraction

Abstract Introduction Iron deficiency (ID) is a common comorbidity in patients with reduced heart failure (HFrEF), and is associated with poor clinical status and outcomes, but there is not enough data investigating serum transferrin concentration (STC) as a biomarker HFrEF to predict prognosis and mortality. Purpose We investigated relationship between STC at admission and all-cause mortality during follow-up in HFrEF. Methods We reviewed the medical data of 420 patients hospitalised in our institution for HFrEF over a period of 18 months. Laboratory tests were performed on the first 24 hours of admission. Patients were divided into two groups according to STC, using the value of 199 μg/dl as the cut-off. This value was determined from the ROC analysis to be the value with the highest sensitivity and specificity. Then we analysed relationship between STC at admission and all-cause mortality during follow-up between the two groups, after adjustment of the various variables described in the literature. Results Of 420 patients with HFrEF, 18.6% had STC ≤ 199 μg/dl (group 1) and 81.4% had STC &amp;gt; 199 μg/dl (group 2) with no difference in age and sex distribution (p = 0.873 ; p = 0.304). Patients with low STC were more likely to be diabetic (70.5% vs 46.5% ; p &amp;lt; 0.001), have dyslipidemia (52.6% vs 33%; p = 0.002), and history of chronic renal failure (6.4% vs 2.0% ; p = 0.045). There was no relation between STC and NYHA class (p = 0.776), hospital stay (p = 0.491) nor EF (p = 0.146). Biologically, lower STC was significantly associated with higher serum ferritin (292.77 vs 198.17 ; p &amp;lt; 0.001), TSAT (68.30 vs 22.21 ; p = 0.020) and C-reactive protein (CRP) (124.91 vs 39.98 ; p = &amp;lt; 0.001), lower plasma B-type natriuretic peptide (BNP) (5798.32 vs 6449.97 ; p = 0.002), with no difference in haemoglobin level (p = 0.272) and estimated glomerular filtration rate (eGFR) (p = 0.260). The prevalence of iron deficiency by the ESC criteria was lower in those with low STC; ferritin &amp;lt; 100 μg/l (15.4% vs 29.2% ; p = 0.015) or TSAT &amp;lt; 20% (33.3% vs 51,8% ; p = 0.004). There was no difference between the two groups in term of NYHA class and EF at three months (p = 0.87, p = 0.108). However, all-cause mortality during follow-up was significantly associated with low STC (37.2% vs 17.0% ; p &amp;lt;0.001). (Figure 1) In multivariable analysis, all-cause mortality was independently associated with STC ≤ 199 μg/dl (HR 1.71; 95% CI : 1.08 ; 2.7 ; p = 0.02). This is the same finding for the ischaemic origin of HFrEF (HR 2.1 ; p = 0.001), therapeutic inertia during follow-up (HR 5.53 ; p &amp;lt;0.001) and EF &amp;lt; 36% (HR 1.03 ; p = 0.047) (Figure 2). Conclusion More data are required before the routine use of STC as a biomarker of prognosis in HFrEF, but it may represent a reliable and cost-effective option to predict mortality.FIGURE 1FIGURE 2

Prognostic importance of persistent elevations in high-sensitivity troponin T in the early convalescent phase (two weeks) following high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Myocardial infarction (MI) is defined by a rise and fall in cardiac troponin (cTn) with clinical evidence of acute myocardial ischemia. How often cTn remains elevated in high-risk patients stabilized following MI and the relation between convalescent cTn levels and subsequent clinical outcomes in these patients is unknown. Aims To evaluate the prognostic importance of high-sensitivity cTn T (hs-cTnT) in the early convalescent phase of a MI for a range of cardiovascular (CV) outcomes in patients enrolled in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Patients ≥18 years without prior heart failure (HF) (n=5661) were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of MI complicated by transient pulmonary congestion, LVEF ≤40%, or both. Hs-cTnT was measured using the Roche Elecsys Troponin T-high-sensitive assay in 1093 patients two weeks after randomization (median 2.6 weeks after the index MI). Associations between log (2)-transformed hs-cTnT and clinical outcomes were investigated in landmark analyses using Cox regression models adjusted for clinical covariates of known prognostic importance and NT-proBNP (Figure). Results Median week 2 hs-cTnT concentration was 34 ng/L [IQR 17-94 ng/L] and exceeded the 99th percentile upper reference limit in 69% of patients. Patients with persistently elevated hs-cTnT concentrations (n=753) were older, more likely men, more commonly had atrial fibrillation and lower estimated glomerular filtration rate and less likely had a prior MI. They more commonly had presented with ST-segment elevation MI and pulmonary congestion and had higher concentrations of NT-proBNP. Rates of primary reperfusion were similar. Log(2)-transformed hs-cTnT was only weakly correlated with LVEF (rho = -0.15, p&amp;lt;0.001), irrespective of the type of MI. hs-cTnT was independently and linearly associated with the primary composite outcome of CV death or incident HF (adj HR 1.17 per doubling; 95% CI, 1.03 – 1.34), all-cause death (adj HR 1.20; 95% CI, 1.01 – 1.44) and CV death (adj HR 1.25; 95% CI, 1.02 – 1.52) but not with non-CV death (adj HR 1.04; 95% CI, 0.70-1.54). hs-cTnT was not significantly associated with recurrent fatal or non-fatal MI (adj HR 1.00; 95% CI, 0.85-1.18) (Figure). Concentrations of week 2 hs-cTnT were not altered by sacubitril/valsartan relative to ramipril (+4%; 95% CI, -8% to 18%). Conclusions Persistent elevations in hs-cTnT during the early convalescent phase following high-risk MI are common and are associated with heightened risk of all-cause death, CV death and incident HF but not of recurrent MI or non-CV death. hs-cTnT measured ~2.5 weeks after high-risk MI provides incremental prognostic information beyond traditional risk factors and NT-proBNP.

Differences in risk profiles and clinical outcomes according to age in patients with high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Temporal declines in rates of rehospitalization and death after acute myocardial infarction (MI) have not been uniform across age groups. A better understanding of how risk profiles and clinical outcomes differ after MI by age may allow for targeted treatment and prevention strategies. Aims To investigate risk profiles and clinical outcomes following high-risk MI according to age in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Adults without prior heart failure (HF) were randomized to sacubitril/valsartan versus ramipril within 0.5 to 7 days of a MI complicated by transient pulmonary congestion and/or left ventricular systolic dysfunction and additional risk-augmenting factors. Associations between age and clinical outcomes were analyzed using Cox proportional hazards regression models, which were additionally adjusted for baseline demographic and clinical covariates (Figure). Results The mean age of the 5,661 PARADISE-MI participants was 64 ± 11 years. Patients aged ≥75 years (n=1051) were more likely women, had more hypertension and atrial fibrillation and lower estimated glomerular filtration rate, were less likely to present with ST-segment elevation MI and regardless of type of MI were less likely to receive primary reperfusion and guideline-based medical therapy (Table). Age was significantly associated with all-cause death (HR 1.54 per 10-year increase; 95% CI, 1.41-1.68) and was more strongly associated with non-CV death (HR 2.09; 95% CI, 1.70-2.56) than with CV death (HR 1.43; 95% CI, 1.29-1.57). Age was also associated with incident HF (HR 1.37; 95% CI, 1.25-1.49) (Figure). Multivariable adjustment attenuated the risk relationship of age with recurrent fatal or non-fatal MI (HR 1.08; 95% CI, 0.96-1.21) and the coronary composite outcome (HR 1.01; 95% CI, 0.93-1.09). The relative treatment effect of sacubitril/valsartan versus ramipril on the primary composite outcome of CV death or incident HF was not significantly modified by age (p-interaction = 0.19). Conclusions Following high-risk MI, age was most strongly associated with subsequent non-CV death followed by CV death and incident HF, but was not independently associated with recurrent coronary events. The heightened risk of CV death and HF with advancing age was not explained by differences in clinical characteristics. Older patients may require closer surveillance and more aggressive treatment after MI to mitigate the elevated risk of CV death and HF.

The efficacy of IV iron in anemic heart failure patients: a systemic review and meta-analysis of randomised controlled trials

Abstract Introduction Iron deficiency in the context of heart failure is a multifaceted concern, where the intricate interplay between diminished iron stores, impaired absorption mechanisms, and reduced recycled iron in the reticuloendothelial system adds a layer of complexity to patient management. Initial attempts to address this issue with oral iron treatments have been questioned due to its poor absorption. Intravenous iron therapy is now preferred, as it has been shown to reduce heart failure hospitalisations and cardiovascular mortality. However, there is a lack of randomised studies specifically focused on heart failure patients, highlighting the need for more targeted investigations. Purpose The aim of this review is to provide reliable evidence from published randomised controlled trials (RCTs) regarding the beneficial effect of IV iron in heart failure patients. Methods We systematically searched PubMed, Web of Science, Scopus, and Cochrane Central, and EMBASE from inception until December 2023. We included randomised controlled trials (RCTs) comparing the effect of IV iron in heart failure patients versus placebo. The primary outcomes were 6MWT mean change, ferritin concentration mean change, transferrin saturation mean change and worsening heart failure. All data were pooled as either Mean difference in the random effect model with the corresponding SD or pooled as RR and 95% CI for dichotomous data. Results Twelve RCTs involving 6800 patients were included in the analysis. The overall effect on the measured primary outcomes was in favour of IV iron in terms of 6MWT mean change (MD= 34.45, 95% CI [ 29.58 to 39.31], P=&amp;lt;0.0001), ferritin concentration mean change (MD= 219.18, 95% CI [ 208.7 to 229.66], P=&amp;lt;0.0001), transferrin saturation mean change (MD= 9.77, 95% CI [ 8.14 to 1.39], P=&amp;lt;0.0001) and worsening heart failure (RR= 0.46, 95% CI [ 0.31 to 0.69], P=0.002). Conclusion The introduction of the IV iron therapy to heart failure patients showed a beneficial effect in terms of the measured haematological and cardiovascular metrics, which include 6MW test mean change, ferritin concentration mean change, and worsening heart failure.6MWT mean changeFerritin mean change

Combination of diuretics to overcome diuretic resistance in acute heart failure: systematic review and updated network meta-analysis

Abstract Background Diuretic resistance in acute heart failure (AHF) presents a significant therapeutic challenge. While randomized clinical trials (RCTs) have compared various diuretics against furosemide, direct comparisons among these therapies are lacking. This network meta-analysis aims to fill this knowledge gap. Purpose To evaluate the efficacy and safety of various diuretic combination therapies in overcoming diuretic resistance in acute heart failure patients. Methods We conducted a systematic review and network meta-analysis of RCTs from January 2000 to December 2023. These RCTs included hospitalized AHF patients with evidence of diuretic resistance. We applied a frequentist random effects model to perform a network meta-analysis combining a total of 11 diuretic strategies compared with low-dose furosemide (reference group). Primary outcomes were urine output and weight loss at 72 hours. Secondary outcomes included cardiovascular mortality and heart failure hospitalization. The safety endpoint was the incidence of acute kidney injury across different diuretic strategies. Results Empagliflozin and high-dose furosemide showed the highest increase in urine output (SMDs: 363.94, P-score=0.64; and 306.31, P-score=0.68). For weight loss, hydrochlorothiazide led to the greatest losses (SMD: 1.33; P-score=0.20), followed by tolvaptan + furosemide low-dose (SMD: 0.85; P-score=0.43). Dapagliflozin ranked best for reducing heart failure hospitalizations (OR 0.15; P-score=0.94), and empagliflozin had the highest rank for mortality reduction (OR 0.31; P-score=0.91) but without statistical significance for mortality. Empagliflozin also showed a better safety profile (OR: 0.74; 95% CI: 0.32 to 1.71 P-score=0.87), (Figure 1 and 2). Conclusion Our findings indicate that SGLT2 inhibitors are a promising therapeutic avenue to mitigate the challenges of diuretic resistance in AHF, demonstrating potential benefits in enhancing urine output, reducing hospitalization rates, and maintaining favourable safety profile.Network and forest plots for U.O/ weightNetwork and forest plots for HHF/ AKI

Angiotensin receptor-neprilysin inhibitor (Sacubitril/Valsartan) in cancer therapy-related cardiac dysfunction: real-world experience from a nurse-led cardio-oncology clinic

Abstract Introduction Cancer therapy-related cardiac dysfunction (CTRCD) is a common toxicity amongst patients receiving anti-cancer treatment1. Angiotensin receptor-neprilysin inhibitor (ARNI) Sacubitril/Valsartan is recommended to reduce Heart Failure (HF) admissions and cardiovascular mortality2. However, patients with active cancer were excluded from the key trials of ARNI. This study aims to provide a real-world experience of ARNI prescription and management from the perspective of a nurse-led Cardio-Oncology clinic. Methods This is a single centre, retrospective, observational cohort study performed at a Cardio-Oncology specialist centre between the period of 2021 to 2024. Adult cancer patients receiving anti-cancer therapy were included if they had symptomatic HF or asymptomatic CTRCD, were initiated on ARNI and followed up in the nurse-led Cardio-Oncology clinic. Results Twenty-nine patients were started on ARNI (see Figure 1). The mean age of the patients was 66+11 years and 17 (59%) were male. Cardiovascular risk factors were common: hypertension (45%), hyperlipidaemia (35%), diabetes mellitus (21%), and smoking (17%). Haematological and breast malignancies were most common (31% and 21% respectively), followed by gynaecological malignancies (14%). Twenty-one (72%) were treated with cytotoxic chemotherapy including 10 (35%) received anthracyclines. Five (17%) patients received human epidermal growth factor receptor 2 (HER2) targeted therapies, 3 (10%) were on tyrosine kinase inhibitors, and 2 (7%) received immunotherapy. Twenty-five (86%) patients presented with symptomatic HF while 4 (14%) had asymptomatic CTRCD. The median N-terminal-pro B-type natriuretic peptide (NTproBNP) level was elevated at 1325(806-4330)ng/L. Thirteen (45%) patients tolerated the maximum dose of 200mg twice daily, while 16 (56%) could only tolerate middle and lowest dosages. ARNI dose up titration to the maximum tolerated dose took 26 (15-79) days. Twenty-eight (97%) patients were on beta blockers, 26 (90%) received SGLT2 inhibitors, 25 (86%) on mineralocorticoid receptor antagonists, and 10 (35%) patients required diuretics. The most common side effect was symptomatic hypotension in 11 (38%) patients. Two (7%) had hyperkalemia, 1 (3%) acute kidney injury following initiation, and 1 (3%) had dizziness without significant hypotension. Nine (31%) required dose reduction allowing ARNI to be continued, while 3 (10%) patients had to permanently discontinue ARNI. There were no cardiovascular deaths, cancer deaths or HF admissions. Conclusion The Cardio-Oncology nurse-led clinic permits rapid up-titration of ARNI to target dosages in patients with CTRCD, resulting in significant improvements in cardiac function. The nurse lead clinic education, support and side effect management allowed uninterrupted continuation of cancer treatment. Whether this approach translates into be better cardiac and cancer outcomes requires further study.

Efficacy and limitation of nonparoxysmal atrial fibrillation ablation in patients with heart failure with preserved ejection fraction.

Catheter ablation for atrial fibrillation (AF) reduces heart failure (HF) hospitalization in patients with HF with preserved ejection fraction (HFpEF). However, the long-term outcomes and subclinical HF after nonparoxysmal AF ablation in HFpEF patients have not been fully evaluated. One-hundred-ninety nonparoxysmal AF patients with left ventricular ejection fraction ≥50% who underwent first-time AF ablation were studied. HFpEF was diagnosed from a history of congestive HF and/or combined criteria of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and transthoracic echocardiogram parameters, including average septal-lateral E/e' and tricuspid regurgitation peak velocity. Ninety-five patients with HFpEF (HFpEF group) were compared with 95 patients without HF (CNT group). Low voltage area (LVA) was defined as an area with a bipolar electrogram of <0.5 mV covering >5% of the total left atrial surface. The primary endpoint was a composite of death from any cause or hospitalization for worsening HF. The secondary endpoint was subclinical HFpEF defined from NT-proBNP concentration and average septal-lateral E/e' or tricuspid regurgitation peak velocity at 6-12 months after the procedure irrespective of the rhythm. Kaplan-Meier curves showed that the primary composite endpoint did not differ between the two groups (mean follow-up period 707 ± 75 days, log-rank p = 0.5330). However, significantly more patients in the HFpEF group reached the secondary endpoint (42 [44%] vs. 13 [14%], p < 0.0001). Multivariate analysis revealed that a high preablation NT-proBNP (odds ratio [OR] 1.001, 95% confidence interval [CI] 1.001-1.002, p = 0.0040) and the existence of LVA (OR 5.983, 95% CI 1.463-31.768, p = 0.0194) independently predicted the secondary endpoint in HFpEF patients. After nonparoxysmal AF ablation, mortality of HFpEF patients was not inferior compared to patients without coexisting HF. However, subclinical HF occasionally persisted especially in HFpEF patients with a high preprocedure NT-proBNP concentration and LVA.

Effective tricuspid regurgitation reduction is associated with renal improvement and reduced heart failure hospitalization.

Several studies have demonstrated an association between tricuspid regurgitation (TR) and organ dysfunction including hepatic and renal insufficiency. Improvement of liver function following transcatheter edge-to-edge repair (T-TEER) has already been linked to reduction of venous congestion due to TR reduction. This study analyzes whether TR-reduction using T-TEER is also associated with improved renal function. The TRIC-ULM registry includes 92 selected patients undergoing T-TEER between March 2017 and May 2023. Estimated glomerular filtration rate (eGFR) improvement was evident in 53 patients (57%) at 3-months follow-up (FU) and defined by FU eGFR > baseline eGFR. Median age was 80 [interquartile range 75-83] years, pre- and postinterventional TR grades were 4 [3-5] and 1 [1-2], baseline eGFR was 36 [30-53] ml/min and New Yeark Heart Association (NYHA) IV was evident in 15% of patients. Multiple logistic regression analysis revealed TR vena contracta reduction (Odds ratio (OR) 1.35 [95% CI: 1.12-1.64] per mm, p = 0.002) and reduced preinterventional tricuspid annular plane systolic excursion (TAPSE) [OR 0.89 (95% CI: 0.79-0.99) per mm, p = 0.033] to independently predict renal improvement at FU. An eGFR improvement threshold of >9 ml/min was associated with reduced 1-year heart failure hospitalization rates [adjusted hazard ratio 0.22 (95% CI: 0.07-0.62) p = 0.005]. Effective tricuspid edge-to-edge repair is associated with improved renal function and reduced heart failure hospitalization. In patients without renal improvement at 3-months follow-up, residual tricuspid regurgitation should be reevaluated for reintervention.

Cardioprotective strategies in the management of chemotherapy-induced cardiotoxicity: Current approaches and future directions

Background: Chemotherapy-induced cardiotoxicity (CIC) is a significant challenge in cancer treatment, leading to heart failure and myocardial infarction. With rising cancer survival rates, the long-term cardiovascular health of survivors has gained importance. While several cardioprotective medications have been studied to mitigate chemotherapy’s harmful effects on the heart, more research is needed to confirm their effectiveness and optimal use. Methodology: This review synthesizes evidence on cardioprotective drugs in managing CIC. We conducted a comprehensive literature search of peer-reviewed articles, clinical trials, and meta-analyses published between January 2000 and May 2024. Studies were selected based on relevance, quality, and focus on mechanisms, efficacy, and clinical outcomes of cardioprotective agents such as beta-blockers, ACE inhibitors, ARBs, statins, and dexrazoxane. Results and Discussion: Cardioprotective medications show potential in alleviating the impact of chemotherapy on heart function. Beta-blockers and ACE inhibitors effectively reduce heart failure incidence and improve cardiac outcomes. Statins, with their anti-inflammatory and antioxidative properties, and dexrazoxane, which reduces anthracycline-induced cardiotoxicity, also show promise. However, variability in study designs, patient groups, and chemotherapy treatments complicates the establishment of standardized treatment protocols. Conclusion: Cardioprotective drugs hold significant promise in managing CIC and improving cardiac outcomes for cancer patients. Current evidence supports the efficacy of beta-blockers, ACE inhibitors, statins, and dexrazoxane. Further research is needed to establish standardized protocols, evaluate long-term safety, and optimize treatment timing. Integrating cardioprotective strategies into oncological care can enhance the quality of life and prognosis for cancer survivors.

Causal Association of Chronic Venous Insufficiency and Cardiovascular Diseases: A Univariable and Multivariable Mendelian Randomization Study.

The causal relationship between chronic venous insufficiency (CVI) and cardiovascular diseases (CVDs) has yet to be elucidated. Herein, we implement Mendelian randomization (MR) analysis to investigate the causal association. A two-sample MR approach using genetic data from FinnGen and genome-wide association studies (GWAS) Catalog was applied to investigate the causal relationship between CVI and CVDs. This study assessed 77 single nucleotide polymorphisms (SNPs) as instrumental variables, employing random-effect inverse-variance-weighted MR, weighted median, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and Robust Adjusted Profile Score (RAPS) methods. Multivariable MR (MVMR) considered confounding factors. Genetically predicted CVI was associated with reduced heart failure risk (odds ratio (OR) = 0.96, 95% confidence interval (95% CI): 0.93-0.99, p = 0.025) and increased atrial fibrillation risk (OR = 1.06, 95% CI: 1.03-1.09, p = 0.0002). MVMR, adjusting for venous thromboembolism (VTE), lower limb ulceration, obesity, smoking, and alcohol, attenuated these associations. No significant links were found with hypertension, aortic aneurysm, coronary artery disease, myocardial infarction, valvular heart disease, or stroke. This MR study supports an association between CVI and CVDs, which may imply CVI should be monitored during the treatment of heart failure and atrial fibrillation.

Changes in the Treatment and Prevention of Heart Failure Based on the 2023 Focused Update of the 2021 European Society of Cardiology Guidelines

Introduction and Objective:The 2023 update to the 2021 ESC Guidelines for diagnosing and treating acute and chronic heart failure introduces significant changes in pharmacotherapy and prevention. Staying informed about these updates is crucial given the evolving landscape of heart failure management. This review provides an overview of the latest recommendations and supporting evidence. Review Methods:A comprehensive review of scientific publications and guidelines from PubMed, Google Scholar, Clinical Key, Via Medica Journals, and relevant clinical guidelines was conducted to ensure the most recent evidence is considered. Brief Description of the State of Knowledge:Heart failure is a growing global concern. The 2023 update highlights key management changes. Recent trials, including EMPEROR-Preserved and DELIVER, show empagliflozin and dapagliflozin reduce heart failure hospitalization and cardiovascular death in patients with mildly reduced and preserved ejection fraction. The guidelines now recommend intravenous iron for patients with reduced or mildly reduced ejection fraction and iron deficiency. For those with type 2 diabetes and chronic kidney disease, SGLT2 inhibitors and finerenone, a non-steroidal mineralocorticoid antagonist, are recommended to reduce heart failure hospitalization and prevent renal function decline. Summary:The 2023 ESC Guidelines update offers revised recommendations for heart failure management and prevention, integrating the latest clinical trial data and meta-analyses. Key areas include the use of SGLT2 inhibitors, iron deficiency management, and preventive strategies for high-risk populations. Implementing these guidelines can significantly improve preventive and therapeutic outcomes for heart failure patients.

Exploring the Potential Effects and Mechanism of Astragalus Membranaceus in Treating Ischemic Heart Failure Based on Network Pharmacology and Experimental Verification.

Astragalus membranaceus (AM) is a traditional Chinese medicine that has been clinically utilized as an adjunctive therapy for the treatment of myocardial ischemia and heart failure; however, its precise molecular mechanism of action remains unknown. This study aims to investigate the potential pharmacological effects and molecular mechanism of AM in the treatment of ischemic heart failure (IHF) using network pharmacology methods, molecular docking technology, and in vitro experiments. The active components and targets of AM were obtained from the TCMSP databases, while the disease targets of IHF were retrieved from GeneCards and OMIM databases. The analysis of overlapping targets between AM and IHF mainly included active compounds-targets network, PPI network, and GO and KEGG enrichment analysis. The association between active compounds and target proteins was verified through molecular docking. Additionally, an in vitro experimental model was used to evaluate the accuracy of the forecast results. The network pharmacological analysis revealed that quercetin, kaempferol, 7-Omethylisomucronulatol, formononetin, and isorhamnetin were the core active components of AM in treating IHF. The core targets included AKT1, IL6, IL1B, PTGS2, CASP3, MMP9, and HIF1A. The molecular docking results demonstrated a strong binding affinity between these active components and targets. The KEGG pathway analysis suggested that the PI3K-AKT signaling pathway might play a central role in mediating AM's therapeutic effects on IHF. In vitro experiments demonstrated that AM treatment enhanced cell viability, reduced heart failure biomarkers, and suppressed cell apoptosis. Furthermore, the western blot analyses indicated that AM treatment effectively regulated AKT1 phosphorylation in an experimental model of IHF. Through integrated network pharmacological analysis, molecular docking technology, and in vitro experimental validation, it was demonstrated that AM can effectively mitigate IHF through activating PI3K-AKT signaling pathway. These findings significantly advance our understanding of the molecular mechanisms in IHF treatment and contribute further to promoting the clinical application of AM.

Conduction system pacing associated with reduced heart failure hospitalizations and all-cause mortality compared with traditional right ventricular pacing in the Medicare population

BackgroundConduction system pacing (CSP) has emerged as an alternative therapy to traditional right ventricular (RV) pacing. However, most CSP studies reflect small cohorts or single-center experience. ObjectiveThis analysis compared CSP with dual-chamber (DC) RV pacing in a large, population-based cohort using data from the Micra Coverage with Evidence Development study. MethodsMedicare administrative claims data were used to identify patients implanted with a DC RV pacemaker. Lead placement data from Medtronic’s device registration system identified patients treated with CSP (n = 6197) using a 3830 catheter–delivered lead or DC RV (non–3830 lead, non–CSP placement; n = 16,989) at the same centers. CSP patients were stratified into left bundle branch area pacing (LBBAP; n = 4738) and His bundle pacing (HBP; n = 1459). Incident heart failure hospitalizations, all-cause mortality, complication rates, and reinterventions at 6 months were analyzed. ResultsCSP patients with a 3830 catheter–delivered lead experienced significantly lower rates of incident heart failure hospitalization (hazard ratio [HR], 0.70; P = .02) and all-cause mortality at 6 months compared with DC RV patients (HR, 0.66; P < .0001). There was no difference in chronic complications (HR, 0.97; P = .62) or need for reintervention (HR, 0.95; P = .63) with CSP compared with DC RV, although LBBAP patients experienced significantly lower rates of complications (HR, 0.71; P = .001) compared with HBP. ConclusionDC pacemaker patients treated with CSP using a 3830 catheter–delivered lead experienced significant all-cause mortality and heart failure hospitalization benefits compared with DC RV pacing. LBBAP had lower complications compared with HBP. These real-world results align with findings in small clinical studies demonstrating the benefits of CSP.

Revisiting secondary mitral regurgitation threshold severity: insights and lessons from the RESHAPE-HF2 trial.

This article revisits the severity threshold for secondary mitral regurgitation (MR), focusing on insights and lessons from the RESHAPE-HF2 trial. It aims to challenge the traditional effective regurgitant orifice area (EROA) threshold of ≥0.40 cm2 used for intervention, suggesting that earlier intervention may benefit patients with lower EROA. It also explores how transcatheter edge-to-edge repair (TEER) improves outcomes in patients with secondary MR and assesses the impact of left ventricular (LV) remodeling on treatment success. The RESHAPE-HF2 trial evaluated the use of TEER in patients with moderate-to-severe secondary MR, comparing outcomes in those with an EROA ≥0.2 cm2 and no extensive LV remodeling. TEER significantly reduced heart failure hospitalizations and improved quality of life in these patients. This supports the notion that patients with less severe MR, who still show symptoms despite optimal medical therapy, may benefit from earlier intervention. Comparisons with COAPT and MITRA-FR trials underscored the importance of selecting patients based on MR severity relative to LV dilatation. The RESHAPE-HF2 trial highlights the need to reconsider the current EROA threshold for secondary MR intervention. TEER has shown to be beneficial even in patients with lower MR severity, suggesting that earlier intervention could improve outcomes. A more dynamic and integrated approach, considering both MR severity and LV remodeling, is essential for optimizing patient selection and treatment success.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure.

Sodium-dependent glucose transporter 2 inhibitors (SGLT2i) have shown efficacy in reducing heart failure (HF) burden in a very heterogeneous groups of patients, raising doubts about some contemporary assumptions of their mechanism of action. We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy. Two groups of patients were included in the study: the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control. To evaluate the outcomes regarding natriuretic peptide, oxidative stress, inflammation, blood pressure, heart rate, cardiac function, and body weight. The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain (GLS), N-terminal pro-brain natriuretic peptide, myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), and systolic and diastolic blood pressure. To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up, a rise in stroke volume index, body mass index (BMI) decrease, and lack of heart rate increase, linear regression analysis was performed. There was a greater reduction of MPO, hsCRP, GLS, and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up. Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI, while the predictor of stroke volume index increase was SGLT2i therapy itself. SGLT2i affect body composition, reduce cardiac load, improve diastolic/systolic function, and attenuate the sympathetic response. Glycemic control contributes to the improvement of heart function, blood pressure control, oxidative stress, and reduction in inflammation.

Abstract We107: Reduction of Six-Month Heart Failure Readmission Rates in Patients Undergoing MitraClip with Beta Receptor Blockade

Introduction: MitraClip has been shown to reduce heart failure readmissions in patients with moderate to severe mitral valve regurgitation. Likewise, beta-blocker (BB) therapy has been shown to reduce morbidity and mortality in select heart failure patients. At the cellular level, chronic myocardial insult from ongoing heart failure and mitral regurgitation leads to persistent overstimulation of myocardial beta-receptors, ultimately reducing cardiac inotropic reserve and contributing to myocardial injury. Thus, we hypothesized that patients on beta-blocker therapy before the MitraClip procedure would have fewer heart failure-related readmissions. Hypothesis: We assessed the hypothesis that beta-blocker therapy before the MitraClip procedure would lead to fewer heart failure-related readmissions by conducting a retrospective cohort study. This would help us better understand the pathogenesis of re-admissions in this patient population as well as help us decide whether prophylactic initiation of BB therapy before the procedure would reduce the risk of heart failure readmissions. Methods: We reviewed the records of patients who underwent the MitraClip procedure at our institution from January 2017 to July 2022. Patients without listed home medications, as well as non-heart failure-related readmissions and deaths, were excluded. Patients were split into those on BB therapy and those with no BB therapy. Of the 401 charts screened, 324 met the inclusion criteria. Results: From those who met the inclusion criteria, 226 patients were on beta-blocker therapy, while 98 patients were not. Of those who had at least one heart failure-related readmission within 6 months of the MitraClip procedure, 18 patients were on beta-blocker therapy and 16 patients were not. Meaning a 7.96% readmission rate for patients on beta-blocker therapy, and a 16.32% readmission rate for those who were not (OR 2.05, 95% CI: 1.004 to 4.186, p&lt;0.05), with the number needed to treat being 11.9. Conclusions: Our data shows that the use of beta-blocker therapy was associated with a statistically significant decrease in 6-month heart failure readmissions in those undergoing the MitraClip procedure. This suggests that at the cellular level, cardiac beta receptor dysfunction plays an integral part in future hospitalizations in this population. In conclusion, beta-blocker therapy should be considered in heart failure patients planning to undergo the MitraClip procedure to reduce heart failure-related readmissions.

800.71 - Tricuspid Edge-to-Edge Repair Improves Renal Function and Reduces Heart Failure Hospitalization

800.71 - Tricuspid Edge-to-Edge Repair Improves Renal Function and Reduces Heart Failure Hospitalization

Focus on heart failure with preserved ejection fraction: from trials to the real world of the Friuli-Venezia Giulia Cardiovascular Observatory

Heart failure with preserved ejection fraction (HFpEF) has been for decades a nosological entity lacking specific therapy, with some even questioning its existence. Recently, targeted therapies have been introduced for specific, albeit rare, phenotypes such as Fabry disease, hypertrophic cardiomyopathy and amyloidosis. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), originally developed as anti-diabetic drugs, have fortuitously emerged as effective molecules in improving the prognosis for both patients with heart failure with reduced ejection fraction (HFrEF) and those with HFpEF, reducing heart failure exacerbations by almost a third. Although there are some epidemiological differences, depending on the country and the context analyzed, it is generally agreed that HFpEF is the most represented phenotype of heart failure, and its prevalence has been increasing in recent years due to the increase in life expectancy, improved diagnostic sensitivity and accuracy, and an exponential increase in risk factors such as diabetes, hypertension, renal failure, chronic obstructive pulmonary disease and obesity. These are often associated, turning out to be an epiphenomenon of a more complex cardio-nephro-metabolic disease. However, data and characteristics from major trials are not always aligned with the features and needs of these patients in real-world settings.The Cardiovascular Observatory of Friuli-Venezia Giulia is a powerful clinical governance tool that allows us to specifically characterize these patients, identifying and directing them towards the most appropriate diagnostic and therapeutic pathways, contributing significantly to improved prognosis and reduced expenditure paid by the National Health System.The use of SGLT2i in HFrEF patients is poised to match that of historic neurohormonal treatments, while, being the only class of drugs currently recommended by the international guidelines, they should even surpass them in HFpEF patients. However, given the high prevalence of HFpEF, it is unlikely for its treatment to be a prerogative of cardiologists alone. In this regard, it will be crucial in the near future to implement shared and integrated pathways with other medical specialists (internists, diabetologists, and nephrologists), and especially with general practitioners, who most frequently encounter these patients, to select the cases with greater complexity and potential for effective therapeutic intervention.

Vericiguat in heart failure with reduced ejection fraction: hope or solid reality?

In recent years, thanks to the advent of new classes of drugs (ARNI and SGLT2-i), the prognosis of patients suffering from heart failure with reduced ejection fraction (HFrEF) has gradually improved. Nonetheless, there is a residual risk that is not targeted by these therapies. Currently, it is recognized that vericiguat, an oral stimulator of soluble guanylate cyclase (sGC), can restore the NO-sGC-cGMP pathway, through stimulation and activation of sGC, aiming to increase cGMP levels with a reduction in heart failure-related oxidative stress and endothelial dysfunction. Even though the Victoria trial demonstrated that HFrEF patients in treatment with vericiguat showed a 10% reduction in the composite of cardiovascular mortality and rehospitalization for heart failure, statistically significantly reducing heart failure hospitalization, the international guidelines limit its use as a second-line drug for patients with worsening symptomatology despite optimized medical therapy. Furthermore, vericiguat has proved to be a valid therapeutic ally especially in those patients with comorbidities such that they cannot receive the classic four-pillar therapy of HF (in particular renal failure). In this review, the authors report on randomized clinical trials, substudies, and meta-analysis about vericiguat in HFrEF, emphasizing the strengths that would suggest the possible role of vericiguat as the fifth pillar of the HFrEF treatment, acknowledging that there are still gaps in the evidence that need to be clarified.