Background: Observational series suggest a mortality benefit from metformin in the heart failure (HF) population. However, the benefit of metformin in HF with preserved ejection fraction (HFpEF) has yet to be explored. We performed a systematic review and meta-analysis to identify whether variation in EF impacts mortality outcomes in HF patients treated with metformin. Methods: MEDLINE and EMBASE were searched up to October 2019. Observational studies and randomised trials reporting mortality in HF patients and the proportion of patients with an EF > 50% at baseline were included. Other baseline variables were used to assess for heterogeneity in treatment outcomes between groups. Regression models were used to determine the interaction between metformin and subgroups on mortality. Results: Four studies reported the proportion of patients with a preserved EF and were analysed. Metformin reduced mortality in both preserved or reduced EF after adjustment with HF therapies such as angiotensin converting enzyme inhibitors (ACEi) and beta-blockers (β = − 0.2 [95% CI − 0.3 to − 0.1], p = 0.02). Significantly greater protective effects were seen with EF > 50% (p = 0.003). Metformin treatment with insulin, ACEi and beta-blocker therapy were also shown to have a reduction in mortality (insulin p = 0.002; ACEi p < 0.001; beta-blocker p = 0.017), whereas female gender was associated with worse outcomes (p < 0.001). Conclusions: Metformin treatment is associated with a reduction in mortality in patients with HFpEF.

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Background Subclinical LV dysfunction (LVD) identifies heart failure (HF) risk in type 2 diabetes mellitus (T2DM). We sought the extent to which clinical scores (ARIC-HF, WATCH-DM), natriuretic peptides (NTpBNP) and troponin (hs-TnT) were associated with subclinical LV dysfunction (LVD). These associations could inform the ability of these tests to identify which patients should undergo echocardiography. Methods Participants with T2DM were prospectively recruited from three community-based populations. ARIC-HF risk at 4 years and WATCH-DM scores were calculated from clinical data. NTpBNP and hs-TnT were measured using an electro-chemiluminescence assay. All underwent a comprehensive echocardiogram. We calculated the sensitivity and specificity of clinical scores and biomarkers to identify abnormal global longitudinal strain (GLS ≥ −16%)), diastolic function (E/e’ ≥ 14 or e’ < 8 cm/s), left atrial volume index (LAV > 34 ml/m2) and LV hypertrophy (LV mass index > 88 g/m2 (F) > 102 g/m2(M)). Results Of 804 participants (median age 69 years [inter-quartile range (IQR) 65–73], 36% female), clinical scores suggested significant HF risk (median ARIC-HF 8% [IQR 4–12]; WATCH-DM 10 points [IQR 8–12]), and the median NTpBNP was 50 pg/mL [IQR 25–101] and hs-TnT 9.6 pg/mL [IQR 6.8–13.6]. Abnormal GLS was present in 126 (17%), elevated E/e’ in 114 (15%), impaired e’ in 629 (78%), increased LAV in 351 (44%) and LV hypertrophy in 113 (14%). After adjustments for age, body-mass index, and renal function, each standard deviation increase in NTpBNP was associated with a GLS increase of 0.32 (p < 0.001) and hs-TnT increase by 0.26 (p < 0.001). Similar trends were observed with ARIC-HF (standardised β = 0.22, p < 0.001) and WATCH-DM (standardised β = 0.22, p < 0.001) in univariable analyses. However, none of the risk assessment tools provided satisfactory discrimination for abnormal GLS (AUC 63%), diastolic indices (e’ AUC 54–61%) or LV mass (AUC 59–67%). At a sensitivity of 90%, there was an unacceptably low (< 50%) specificity. Conclusion Although risk assessment based on clinical scores or biomarkers would be desirable to stratify HF risk in people with T2DM, they show a weak relationship with subclinical LVD.

Background: Observational series suggest a mortality benefit from metformin in the heart failure (HF) population. However, the benefit of metformin in HF with preserved ejection fraction (HFpEF) has yet to be explored. We performed a systematic review and meta-analysis to identify whether variation in EF impacts mortality outcomes in HF patients treated with metformin. Methods: MEDLINE and EMBASE were searched up to October 2019. Observational studies and randomised trials reporting mortality in HF patients and the proportion of patients with an EF > 50% at baseline were included. Other baseline variables were used to assess for heterogeneity in treatment outcomes between groups. Regression models were used to determine the interaction between metformin and subgroups on mortality. Results: Four studies reported the proportion of patients with a preserved EF and were analysed. Metformin reduced mortality in both preserved or reduced EF after adjustment with HF therapies such as angiotensin converting enzyme inhibitors (ACEi) and beta-blockers (β = − 0.2 [95% CI − 0.3 to − 0.1], p = 0.02). Significantly greater protective effects were seen with EF > 50% (p = 0.003). Metformin treatment with insulin, ACEi and beta-blocker therapy were also shown to have a reduction in mortality (insulin p = 0.002; ACEi p < 0.001; beta-blocker p = 0.017), whereas female gender was associated with worse outcomes (p < 0.001). Conclusions: Metformin treatment is associated with a reduction in mortality in patients with HFpEF.

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Aims Fluid congestion is a leading cause of hospital admission, readmission, and mortality in heart failure (HF). We performed a systematic review and meta-analysis to determine the effectiveness of an advanced fluid management programme (AFMP). The AFMP was defined as an intervention providing tailored diuretic therapy guided by intravascular volume assessment, in hospitalized patients or after discharge. The AFMP group was compared with patients who received standard care treatment. The aim of this systematic review and meta-analysis was to determine the effectiveness of an AFMP in improving patient outcomes. Methods and results A systematic review of randomized controlled trials, case-control studies, and crossover studies using the terms 'heart failure', 'fluid management', and 'readmission' was conducted in PubMed, CINAHL, and Scopus up until November 2020. Studies reporting the association of an AFMP on readmission and/or mortality were included in our metaanalyses. Risk of bias was assessed in non-randomized studies using the Newcastle-Ottawa Scale. From 232 retrieved studies, 12 were included in the data synthesis. The 6040 patients in the included studies had a mean age of 72 ± 4 years and mean left ventricular ejection fraction of 39 ± 8%, there were slightly more men (n = 3022) than women, and the follow-up period was a mean of 4.8 ± 3.1 months. Readmission data were available in 5362 patients; of these, 1629 were readmitted. Mortality data were available in 5787 patients; of these, 584 died. HF patients who had an AFMP in hospital and/or after discharge had lower odds of all-cause readmission (odds ratio-OR 0.64 [95% confidence interval-CI 0.44, 0.92], P = 0.02) with moderate heterogeneity (I 2 = 46.5) and lower odds of all-cause mortality (OR 0.82 [95% CI 0.69, 0.98], P = 0.03) with low heterogeneity (I 2 = 0). The use of an AFMP was equally effective in reducing readmission and mortality regardless of age and follow-up duration. Effective pre-discharge diuresis was associated with significantly lower readmission odds (OR 0.43 [95% CI 0.26, 0.71], P = 0.001) compared with a fluid management plan as part of post-discharge follow-up. Conclusions An effective AFMP is associated with improving readmission and mortality in HF. Our results encourage attainment of optimal volume status at discharge and prescription of optimal diuretic dose. Ongoing support to maintain euvolaemia and effective collaboration between healthcare teams, along with effective patient education and engagement, may help to reduce adverse outcomes in HF patients.