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This article discusses the role of anti-obesity drugs in heart failure, specifically focusing on heart failure with preserved ejection fraction (HFpEF). Obesity is a significant risk factor for cardiovascular diseases, including HFpEF, and is associated with unfavorable clinical characteristics and worse symptoms. The pathophysiology of obesity-related HFpEF involves impaired left ventricular function, oxidative stress, inflammation, and adipose tissue dysfunction. The article also explores the potential benefits of anti-obesity drugs in improving outcomes for patients with HFpEF. However, the use of these drugs in heart failure with reduced ejection fraction (HFrEF) is less clear, and further research is needed to determine their efficacy and safety in this population. [Extracted from the article]

Aim: The RESHAPE‐HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE‐HF2 trial compared to those enrolled in the COAPT and MITRA‐FR trials. Methods and results: The RESHAPE‐HF2 study is an investigator‐initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate‐to‐severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8–9.0) and median plasma N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) was 2745 (1407–5385) pg/ml. Most patients were prescribed beta‐blockers (96%), diuretics (96%), angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor–neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium–glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end‐diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA‐FR, those enrolled in RESHAPE‐HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT‐proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. Conclusion: Patients enrolled in RESHAPE‐HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate‐to‐severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA‐FR trials. The results of RESHAPE‐HF2 will provide crucial insights regarding broader application of the transcatheter edge‐to‐edge repair procedure in clinical practice. [ABSTRACT FROM AUTHOR]

This article discusses the challenges and effectiveness of early post-discharge follow-up for patients hospitalized with heart failure (HF). While guidelines recommend early follow-up visits after discharge, the evidence supporting their effectiveness is limited. A study from France found that combined follow-up with a general practitioner and cardiologist was associated with a lower risk of death or rehospitalization, but a higher risk of HF readmission. The article emphasizes the importance of optimizing guideline-directed medical therapy (GDMT) during these visits and initiating GDMT prior to discharge to improve outcomes for HF patients. However, the article acknowledges the limitations of the study and the need for further research in this area. [Extracted from the article]

Aims: The therapeutic mechanism of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on left cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF) is not well‐established. This study meta‐analysed the impact of SGLT2i on left cardiac structure and function in patients with HFrEF. Methods and results: Online databases were queried up to April 2023 for trials reporting indicators of left cardiac structure and function in patients with HFrEF treated with SGLT2i. Data from studies were pooled using a random‐effects model to derive weighted mean differences (WMDs) and 95% confidence intervals (CIs). Six trials were included (n = 555). Compared with control, SGLT2i significantly improved left ventricular end‐diastolic volume (LVEDV; WMD: −17.07 ml [−23.84, −10.31]; p < 0.001), LVEDV index (WMD: −5.62 ml/m2 [−10.28, −0.97]; p = 0.02), left ventricular end‐systolic volume (LVESV; WMD: −15.63 ml [−26.15, −5.12]; p = 0.004), LVESV index (WMD: −6.90 ml/m2 [−10.68, −3.11]; p = 0.001), left ventricular ejection fraction (WMD: 2.71% [0.70, 4.72]; p = 0.008), and left atrial volume index (WMD: −2.19 ml/m2 [−4.26, −0.11]; p = 0.04) in patients with HFrEF. SGLT2i use was associated with a non‐significant trend towards a reduction in left ventricular mass index (WMD: −6.25 g/m2 [−12.79, 0.28]; p = 0.06). No significant impact on left ventricular global longitudinal strain was noted (WMD: 0.21% [−0.25, 0.67]; p = 0.38). Conclusions: Sodium–glucose cotransporter 2 inhibitors improve cardiac structure and function in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Aims: Iron deficiency is common in patients with heart failure (HF) and reduced ejection fraction (HFrEF) and is associated with a poor prognosis. Whether intravenous iron replacement improves recurrent HF hospitalizations and cardiovascular mortality of these patients is uncertain although several trials were conducted. Moreover, none of the trials were powered to assess the effect of intravenous iron in clinically important subgroups. Therefore, we conducted a Bayesian analysis to derive precise estimates of the effect of intravenous iron replacement on recurrent HF hospitalizations and cardiovascular mortality in iron‐deficient HFrEF patients using consistent subgroup definitions across trials. Methods and results: Individual participant data were used from the FAIR‐HF (n = 459), CONFIRM‐HF (n = 304) and AFFIRM‐AHF (n = 1108) trials. These data were re‐analysed following as closely as possible the approach taken in the analyses of IRONMAN (n = 1137), for which study level data were used. Definitions of outcomes and subgroups from the FAIR‐HF, CONFIRM‐HF and AFFIRM‐AHF were matched with those used in IRONMAN. The primary endpoint was recurrent HF hospitalizations and cardiovascular mortality. The analysis of recurrent events was based on rate ratios (RR) derived from the Lin‐Wei‐Yang‐Ying model, and the data were pooled using Bayesian random‐effects meta‐analysis. Compared with placebo, intravenous iron significantly reduced the rates of recurrent HF hospitalizations and cardiovascular mortality (RR 0.73, 95% credible interval [CI] 0.48–0.99; between‐trial heterogeneity tau = 0.16). The pooled treatment effects did not provide evidence for any differential effects for subgroups based on sex (ratio of rate ratios [RRR] 1.49 [95% CI 0.95–2.37], age <69.4 vs. ≥69.4 years) (RRR 0.68 [0.40–1.15]), ischaemic versus non‐ischaemic aetiology of HF (RRR 0.73 [0.42–1.33]), transferrin saturation <20% vs. ≥20% (RRR 0.75 [0.40–1.34]), estimated glomerular filtration rate ≤60 versus >60 ml/min/1.73 m2 (RRR 0.97 [0.56–1.68]), haemoglobin <11.8 versus ≥11.8 (RRR 0.95 [0.53–1.60]), ferritin <35 versus ≥35 μg/L (RRR 1.26 [0.72–2.48]) and New York Heart Association class II versus III/IV (RRR 0.91 [0.54–1.56]). Conclusions: Treatment of iron‐deficient HFrEF patients with intravenous iron – namely with ferric carboxymaltose or ferric derisomaltose – results in significant reduction in recurrent HF hospitalizations and cardiovascular mortality. Results were nominally consistent across the subgroups studied, but for several of these subgroups uncertainty remains present. [ABSTRACT FROM AUTHOR]

Pulmonary arterial pressures are often used as surrogates for intravascular blood volume. However, the relationship between pressure and volume remains controversial. To contextualize and provide concrete examples and impact on clinical management, we report two cases of heart failure (one in heart failure with reduced ejection fraction and one in heart failure with preserved ejection fraction) where pressure‐based measurements did not accurately represent the intravascular status and affected clinical management. [ABSTRACT FROM AUTHOR]

Although chronic kidney disease is characterized by low glomerular filtration rate (GFR) or albuminuria, estimated GFR (eGFR) is more widely utilized as a marker of risk profile in cardiovascular diseases, including heart failure (HF). The presence and magnitude of albuminuria confers a strong prognostic association in forecasting risk of incident HF as well as its progression, irrespective of eGFR. Despite the high prevalence of albuminuria in HF, whether it adds incremental prognostic information in clinical practice and serves as an independent risk marker, and whether there are any therapeutic implications of assessing albuminuria in patients with HF is less well-established. In this narrative review, we assess the potential role of albuminuria in risk profiling for development and progression of HF, strengths and limitations of utilizing albuminuria as a risk marker, its ability to serve in HF risk prediction models, and the implications of adopting albuminuria as an effective parameter in cardiovascular trials and practice. [Display omitted] • Albuminuria is prevalent in patients with heart failure and confers a strong, consistent and independent association with risk. • The causes of albuminuria in patients with heart failure are incompletely understood, as are the mechanisms linking it to disease progression and adverse outcomes. • Interventions that reduce albuminuria may potentially lower the risk of incident heart failure or prevent progression of existing heart failure. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty and limited data regarding initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors among patients hospitalized with acute heart failure (AHF). This systematic review and meta-analysis aim to establish the efficacy and safety of SGLT2 inhibitors initiated in patients hospitalized for AHF. Methods: PubMed/Medline, Embase, and Cochrane library were searched using the following terms: ("sglt2" and "acute heart failure") and ("sglt2" and "worsening heart failure") from inception till November 15th, 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of initiating an SGLT2 inhibitor compared with placebo in patients with AHF. Major cardiovascular and diabetes scientific meetings in 2021 were also searched for relevant studies. Prespecified efficacy outcomes were all-cause mortality, rehospitalization for heart failure, and improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scale score. Prespecified safety outcomes were acute kidney injury (AKI), hypotension, and hypoglycemia. Random effects odds ratio (OR) and mean difference with 95% confidence intervals (CIs) were calculated. Results: Three RCTs with a total of 1831 patients were included. Initiation of SGLT2 inhibitors in patients with AHF reduced the risk of rehospitalization for heart failure (OR 0.52; 95% CI [0.42, 0.65]) and improved Kansas City Cardiomyopathy Questionnaire scores (mean difference 4.12; 95% CI [0.1.89, 6.53]). There was no statistically significant effect for initiation of SGLT2 inhibitors in patients with AHF on all-cause mortality (OR 0.70; 95% CI [0.46, 1.08]). Initiation of SGLT2 inhibitors in patients with AHF did not increase the acute kidney injury (OR 0.76; 95% CI [0.50, 1.16]), hypotension (OR 1.17; 95% CI [0.80, 1.71]), or hypoglycemia (OR 1.51; 95% CI [0.86, 2.65]). Conclusion: Initiation of SGLT2 inhibitors in patients hospitalized for AHF during hospitalization or early post-discharge (within 3 days) reduces the risk of rehospitalization for heart failure and improves patient-reported outcomes with no excess risk of adverse effects. [ABSTRACT FROM AUTHOR]

Aims: The Carillon Mitral Contour System has been shown to reduce mitral regurgitation and left ventricular volumes in symptomatic heart failure patients with functional mitral regurgitation. We sought to evaluate the effects of the Carillon device on quality of life and functional capacity in these patients. Methods and results: An individual participant data meta‐analysis was conducted utilizing data from REDUCE‐FMR, TITAN, and TITAN II studies. The main outcomes assessed were changes from baseline in Kansas City Cardiomyopathy Questionnaire overall summary scores (KCCQ‐OSS), 6 min walk test (6MWT) distance, and New York Heart Association (NYHA) classification at Months 1 and 12 after device implantation. Subgroup analyses were conducted for patients with severe functional mitral regurgitation (Grade 3 or 4). Pooled estimates were calculated using a random‐effects model and are presented as weighted proportions or weighted mean differences along with 95% confidence intervals (CIs). Among 139 patients included in the analysis, Carillon device significantly improved the 6MWT distance (63.0 m; 95% CI 18.8–107.2, P = 0.0056) and KCCQ‐OSS score (15.1; 95% CI 5.6–24.7, P = 0.0022) at 1 month from baseline. These benefits were sustained at 12 months (64.1 m; 95% CI 13.2–115.0, P = 0.0141, for 6MWT distance, and 12.3; 95% CI 4.7–19.8, P = 0.0019, for KCCQ‐OSS score). More than 50% of the patients had improvements in KCCQ‐OSS by ≥5 (60.4%; 95% CI 47.4–72.1) and 10 points (50.5%; 95% CI 34.9–66.0) at 12 months. Almost half of the patients experienced a ≥1 class improvement in NYHA class after implantation of the device at 1 month (67.9%; 95% CI 37.3–88.3) and at 12 months (48.8%; 95% CI 31.8–66.2). Results remained similar for KCCQ‐OSS, 6MWT distance, and NYHA classification when only patients with Grade 3 or 4 mitral regurgitation were analysed. The pooled estimates of 30 day and 1 year all‐cause mortality were 2.2% (95% CI 0.7–6.5) and 17.3% (95% CI 11.8–24.5), respectively. Conclusions: The Carillon Mitral Contour System significantly improved patient‐reported quality‐of‐life outcomes in heart failure patients with functional mitral regurgitation. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the reporting of subgroup analyses in heart failure (HF) randomized controlled trials (RCTs) and to determine the strength and credibility of subgroup claims. Methods and results: All primary HF RCTs published in nine high‐impact journals from 1 January 2008 to 31 December 2017 were included. Multivariable regression analysis was used to identify factors that may favour the reporting of results in specific subgroups. Strength of the subgroup effect claimed was classified into (i) strong, (ii) likely, or (iii) suggestive. Credibility of subgroup claim was scored using a pre‐specified 10 pointer criteria. Of the 261 HF RCTs studied, 107 (41%) reported subgroup analyses. Twenty‐five (23%) RCTs claimed a subgroup effect for the primary outcome of which six (24%) made a strong claim, eight (32%) claimed a likely effect, and 11 (44%) suggested a possible subgroup effect. Seven of the 25 RCTs did not employ interaction testing for subgroup claims of the primary outcome. Three out of 10 pre‐specified credibility criteria were satisfied by half of the trials. Fourteen trials justified the choice of subgroups, and 10 explicitly stated they were underpowered to detect differences within subgroups. Source of funding did not influence the frequency of reporting subgroup analyses (OR 0.53, 95% CI 0.78–3.62, P = 0.52). Conclusions: Appropriate credibility criteria were rarely met even by HF RCTs that held strong subgroup claims. Subgroup analyses should be pre‐specified, be adequately powered, present interaction terms, and be replicated in independent data before being integrated into clinical decision making. [ABSTRACT FROM AUTHOR]

Aims: Discontinuation or non‐publication of trials may hinder scientific progress and violates the commitment made to research participants. We sought to identify the prevalence of discontinuation and non‐publication of heart failure (HF) clinical trials. Methods and results: We conducted a cross‐sectional search of ClinicalTrials.gov to identify all completed and discontinued HF clinical trials. We limited our search to only include trials that were completed by 31 December 2017. Trials were investigated to identify reasons for discontinuation. Informative termination was defined as trial termination due to safety or efficacy concerns. Data pertaining to the trial phase, funding, intervention, enrolment, and trial completion date were extracted for each trial. A total of 572 trials were included. Of these, 21% (n = 118) were discontinued before completion. Patient accrual was the most frequently cited reason (n = 42; 36%) for trial discontinuation, followed by informative termination (n = 16; 14%) and funding (n = 14; 12%). Overall, 24 780 patients were enrolled in trials that were terminated. Of trials that were completed and not terminated, nearly one‐third (n = 131/454; 29%) were not published. Seventy‐nine (24%) trials were published within 12 months, 192 (59%) within 24 months, and 252 (78%) trials within 36 months. Conclusions: Discontinuation and non‐publication of HF trials is common. This raises ethical concerns towards participants who volunteer for research and are exposed to potential risks, inconvenience, and discomfort without furthering scientific progress. [ABSTRACT FROM AUTHOR]

Aims: We sought to conduct a meta‐analysis regarding the safety and efficacy of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors in patients with heart failure (HF). Methods and results: MEDLINE, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched from their inception to November 2020 for placebo‐controlled randomized controlled trials of SGLT2 inhibitors. Randomized controlled trials were selected if they reported at least one of the prespecified outcomes in patients with HF. Hazard ratios (HRs) or risk ratios and their corresponding 95% confidence intervals were pooled using a random‐effects model. A total of seven trials including 16 820 HF patients (N = 8884 in the SGLT2 inhibitor arms; N = 7936 in the placebo arms) were included. In the overall HF cohort, SGLT2 inhibitors compared with placebo significantly reduced the risk of the composite endpoint of first HF hospitalization or cardiovascular death [HR: 0.77 (0.72–0.83); P < 0.001; I2 = 0%], time to first HF hospitalization [HR: 0.71 (0.64–0.78); P < 0.001; I2 = 0], cardiovascular mortality [HR: 0.87 (0.79–0.96); P = 0.005; I2 = 0%], and all‐cause mortality [HR: 0.89 (0.82–0.96); P = 0.004; I2 = 0%]. Results remained consistent across HF‐specific trials and according to diabetes mellitus status. A trend towards benefit was observed in patients with HF with preserved ejection fraction for the composite of HF hospitalization and cardiovascular death [HR: 0.80 (0.63–1.00); P = 0.05; I2 = 29%]. No increased risk of hypovolaemia, hyperkalaemia, and hypotension was seen with SGLT2 inhibitors compared with placebo. Conclusions: SGLT2 inhibitors significantly improve cardiovascular outcomes including cardiovascular and all‐cause mortality in patients with HF without an increased risk of serious adverse events. A trend towards benefit was observed in patients with HF with preserved ejection fraction. [ABSTRACT FROM AUTHOR]

Aims: Intravenous ferric carboxymaltose (FCM) has been shown to improve functional capacity and quality of life in iron deficient heart failure patients. However, FCM's effect on hospitalizations and mortality remains unclear as previous randomized controlled trials (RCTs) and their meta‐analyses have been underpowered to detect significant differences. We sought to conduct an updated meta‐analysis using recently published RCT data. Methods and results: Online databases were searched from inception until November 2020 for RCTs evaluating the effects of FCM on clinical outcomes in iron‐deficient heart failure patients. Outcomes of interest included heart failure hospitalizations, all‐cause mortality, and cardiovascular mortality. Meta‐analysis was performed using a fixed‐effect model and estimates were reported as odds ratios (ORs), hazard ratios, or rate ratios (RRs) along with corresponding 95% confidence intervals (CIs). A total of 1947 patients (n = 1062 in the FCM group; n = 885 in the placebo group) were included. FCM, compared with placebo, significantly reduced the risk of the composite endpoint of time to first heart failure hospitalization or cardiovascular death (hazard ratio = 0.76; 95% CI = 0.63–0.90; I2 = 55%). FCM also significantly reduced the risk of recurrent heart failure hospitalizations (RR = 0.68; 95% CI = 0.54–0.85; I2 = 71%) and recurrent cardiovascular hospitalizations (RR = 0.71; 95% CI = 0.59–0.86; I2 = 56%). However, FCM had no significant effect on the risk of all‐cause (OR = 0.97; 95% CI = 0.73–1.28; I2 = 0%) or cardiovascular mortality (OR = 0.93; 95% CI = 0.69–1.27; I2 = 0%). Conclusions: Ferric carboxymaltose reduces heart failure hospitalizations and cardiovascular hospitalizations with no beneficial effect on all‐cause and cardiovascular mortality in iron‐deficient heart failure patients. These findings reinforce the role of FCM as a therapeutic option in heart failure patients. [ABSTRACT FROM AUTHOR]

Aims: While the associations of health-related quality of life scores in heart failure (HF) [e.g. the Kansas City Cardiomyopathy Questionnaire (KCCQ)] with clinical outcomes are well established, their interpretation in the context of what magnitudes of change are clinically important to patients is less clear. The main objective of this study was to correlate the changes in the KCCQ and Patient Global Assessment (PGA) in patients with HF with reduced ejection fraction (HFrEF) to determine minimal clinically important difference (MCID).Methods and Results: We analysed data from 459 patients of the FAIR-HF trial. Both KCCQ and PGA were assessed at 4 and 24 weeks after enrolment. An anchor-based approach was used to calculate MCID at week 4 and 24. PGA was chosen as the clinical anchor against which changes in the KCCQ scores were calibrated. For each category of change in PGA, the corresponding differences were calculated by the mean scores of various domains of KCCQ along with 95% confidence intervals (CIs). There was fair correlation between PGA and changes in overall summary scores (OSS) (r = 0.31; P < 0.001), clinical summary scores (CSS) (r = 0.36; P < 0.001) and physical limitation scores (PLS) (r = 0.31; P < 0.001) from baseline to week 4. KCCQ OSS, CSS and PLS MCID for 'little improvement' at week 4 were 3.6 (1.0-6.2), 4.5 (1.8-7.2) and 4.7 (1.4-8.0) points, respectively. OSS, CSS and PLS MCID for 'little improvement' at week 24 were 4.3 (0.2-8.4), 4.5 (0.5-8.5) and 4.0 (-0.9-9.0) points, respectively.Conclusion: The MCID threshold for KCCQ score was generally consistent and numerically lower than the threshold of 5-point change considered for clinical outcome prognosis and were stable between 4 and 24 weeks. This suggests that even changes smaller than the traditional 5-point improvements in KCCQ may be clinically meaningful. Also, these results can aid in the clinical interpretation of patient-reported outcomes, and better endpoint selection in future studies. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is causing considerable morbidity and mortality worldwide. Multiple reports have suggested that patients with heart failure (HF) are at a higher risk of severe disease and mortality with COVID-19. Moreover, evaluating and treating HF patients with comorbid COVID-19 represents a formidable clinical challenge as symptoms of both conditions may overlap and they may potentiate each other. Limited data exist regarding comprehensive management of HF patients with concomitant COVID-19. Since these issues pose serious new challenges for clinicians worldwide, HF specialists must develop a structured approach to the care of patients with COVID-19 and be included early in the care of these patients. Therefore, the Heart Failure Association of the European Society of Cardiology and the Chinese Heart Failure Association & National Heart Failure Committee conducted web-based meetings to discuss these unique clinical challenges and reach a consensus opinion to help providers worldwide deliver better patient care. The main objective of this position paper is to outline the management of HF patients with concomitant COVID-19 based on the available data and personal experiences of physicians from Asia, Europe and the United States. [ABSTRACT FROM AUTHOR]

Restricting dietary sodium is a common recommendation given by clinicians to patients with heart failure and is one supported by current guidelines. However, the quality of evidence for this recommendation is suboptimal, and there is no consensus on the optimal level of sodium intake. Though excessive sodium intake is associated with left ventricular hypertrophy and hypertension, recent data have suggested that very low sodium intake is paradoxically associated with worse outcomes for patients with heart failure. This is possibly explained by the association between low sodium intake and activation of the sympathetic and renin-angiotensin-aldosterone systems. Nevertheless, sodium restriction is routinely recommended and remains a cornerstone of heart failure and blood pressure therapy. In this review we discuss the pros and cons of sodium restriction for patients with heart failure from the current literature. [ABSTRACT FROM AUTHOR]

Objectives: To compare percutaneous mitral valve repair (PMVR) with optimal medical therapy (OMT) in patients with heart failure (HF) and severe functional mitral regurgitation (FMR).Background: Many patients with HF and FMR are not suitable for surgical valve replacement and remain symptomatic despite maximal OMT. PMVR has recently emerged as an alternative solution.Methods: We performed a systematic review and a meta-analysis to address this question. Cochrane CENTRAL, MEDLINE, and Scopus were searched for randomized (RCT) and nonrandomized studies comparing PMVR with OMT in patients with HF and FMR. Primary endpoint was all-cause midterm mortality (at 1 and 2 years). Secondary endpoints were 30-day mortality and cardiovascular mortality and HF hospitalizations, at maximum follow-up. Studies including mixed cohort of degenerative and functional MR were allowed initially but were excluded in a secondary sensitivity analysis for each of the study's end points. This meta-analysis was performed following the publication of two RCTs (MITRA-FR and COAPT).Results: Eight studies (six observational, two RCTs) comprising 3,009 patients were included in the meta-analysis. In comparison with OMT, PMVR significantly reduced 1-year mortality (RR: 0.70 [0.56, 0.87]; p=0.002; I2=47.6%), 2-year mortality (RR: 0.63 [0.55, 0.73]; p<0.001; I2=0%), and cardiovascular mortality (RR: 0.32 [0.23, 0.44]; p<0.001; I2=0%). No significant difference between PMVR+OMT and OMT was noted in HF hospitalization (HR: 0.69 [0.40, 1.20]; p=0.19; I2=85%) and 30-day mortality (RR: 1.13 [0.68, 1.87]; p=0.16; I2=0%).Conclusions: In comparison with OMT, PMVR significantly reduces 1-year mortality, 2-year mortality, and cardiovascular mortality in patients with HF and severe MR. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic status influences the magnitude of their benefits on heart failure and renal events.Methods: Patients with Class II-IV heart failure and a left ventricular ejection fraction ≤40% were randomized to receive empagliflozin (10 mg daily) or placebo in addition to recommended therapy. We prespecified a comparison of the effect of empagliflozin in patients with and without diabetes.Results: Of the 3730 patients enrolled, 1856 (50%) had diabetes, 1268 (34%) had prediabetes (hemoglobin A1c [HbA1c] 5.7-6.4%), and 606 (16%) had normoglycemia (HbA1c <5.7%). The risks of the primary outcome (cardiovascular death or hospitalization for heart failure), total hospitalizations for heart failure, and adverse renal outcomes were higher in patients with diabetes, but were similar between patients with prediabetes and normoglycemia. Empagliflozin reduced the risk of the primary outcome in patients with and without diabetes (hazard ratio, 0.72 [95% CI, 0.60-0.87] and 0.78 [95% CI, 0.64-0.97], respectively, P-interaction=0.57). Patients with and without diabetes also did not differ with respect to the effect of empagliflozin on total hospitalizations for heart failure, on the decline in estimated glomerular filtration rate over time, and on the risk of serious adverse renal outcomes. Among these end points, the effects of the drug did not differ in patients with prediabetes or normoglycemia. When analyzed as a continuous variable, baseline HbA1c did not significantly modify the benefits of empagliflozin on the primary outcome (P-interaction=0.40). Empagliflozin did not lower HbA1c in patients with prediabetes or normoglycemia and was not associated with increased risk of hypoglycemia.Conclusions: In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977. [ABSTRACT FROM AUTHOR]