Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis

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 p = 0.017), whereas female gender was associated with worse outcomes (p Conclusions: Metformin treatment is associated with a reduction in mortality in patients with HFpEF

Comparative prediction of cardiac events by wall motion, wall motion plus coronary flow reserve, or myocardial perfusion analysis: a multicenter study of contrast stress echocardiography

ObjectivesThis study sought to determine whether the increasing difficulty of assessing wall motion (WM), Doppler coronary flow reserve on the left anterior descending coronary artery (CFR-LAD), and myocardial perfusion (MP) during stress echocardiography (SE) was justified by increasing prognostic information in patients with known or suspected coronary artery disease.BackgroundThe use of echocardiographic contrast agents during SE permits the assessment of both CFR-LAD and MP, but their relative incremental prognostic value is undefined.MethodsThis study followed a multicenter cohort of 718 patients for 16 months after high-dose dipyridamole contrast SE for evaluation of known or suspected coronary artery disease. The ability of WM, CFR-LAD, and MP to predict cardiac events was studied by multivariable models and risk reclassification.ResultsAbnormal SE was detected as a reversible WM abnormality in 18%, reversible MP defect in 27%, and CFR-LAD <2 in 38% of subjects. Fifty cardiac events occurred (annualized event rate 6.0%). A normal MP stress test had a 1-year hard event rate of 1.2%. The C-index of outcomes prediction based on clinical data was improved with MP (p < 0.001) and WM/CFR-LAD (p = 0.037), and MP (p = 0.003) added to clinical and WM data. Net risk reclassification was improved by adding MP (p < 0.001) or CFR-LAD (net reclassification improvement p = 0.001) in addition to clinical and WM data. The model including clinical data, WM/CFR-LAD, and MP performed better than that without MP did (p = 0.012).ConclusionsThe multiparametric assessment of WM, CFR-LAD and MP during stress testing in patients with known or suspected coronary artery disease is feasible. Contrast SE allowed better prognostication, irrespective of the use of CFR-LAD or MP. The addition of either CFR-LAD or MP assessment to standard WM analysis and clinical parameters yielded progressively higher values for the prediction of cardiac events and may be required in today's intensively treated patients undergoing SE, because their average low risk of future cardiac events requires methods with higher predictive sensitivity than that available with standalone WM assessment

Association of ambient particulate matter with heart failure incidence and all-cause readmissions in Tasmania: an observational study

Objectives: We sought to investigate the relationship between air quality and heart failure (HF) incidence and rehospitalisation to elucidate whether there is a threshold in this relationship and whether this relationship differs for HF incidence and rehospitalisation.Methods: This retrospective observational study was performed in an Australian state-wide setting, where air pollution is mainly associated with wood-burning for winter heating. Data included all 1246 patients with a first-ever HF hospitalisation and their 3011 subsequent all-cause readmissions during 2009-2012. Daily particulate matter 2.5), temperature, relative humidity and influenza infection were recorded. Poisson regression was used, with adjustment for time trend, public and school holiday and day of week.Results: Tasmania has excellent air quality (median PM2.5=2.9 µg/m3 (IQR: 1.8-6.0)). Greater HF incidences and readmissions occurred in winter than in other seasons (p2.5 was detrimentally associated with HF incidence (risk ratio (RR)=1.29 (1.15-1.42)) and weakly so with readmission (RR=1.07 (1.02-1.17)), with 1 day time lag. In multivariable analyses, PM2.5 significantly predicted HF incidence (RR=1.12 (1.01-1.24)) but not readmission (RR=0.96 (0.89-1.04)). HF incidence was similarly low when PM 3 and only started to rise when PM2.5≥4 µg/m3. Stratified analyses showed that PM2.5 was associated with readmissions among patients not taking beta-blockers but not among those taking beta-blockers (pinteraction=0.011).Conclusions: PM2.5 predicted HF incidence, independent of other environmental factors. A possible threshold of PM2.5=4 µg/m3 is far below the daily Australian national standard of 25 µg/m3. Our data suggest that beta-blockers might play a role in preventing adverse association between air pollution and patients with HF

Risk factors for left ventricular dysfunction in adulthood: role of low birth weight

Aims: This study aimed to determine the relationship of low birth weight (LBW) with adult cardiac structure and function andinvestigate potential causal pathways.Methods and results: A population-based sample of 925 Australians (41.3% male) were followed from childhood (aged7–15 years) to young adulthood (aged 26–36 years) and mid-adulthood (aged 36–50 years). Left ventricular (LV) globallongitudinal strain (GLS, %), LV mass index (LVMi, g/m2.7), LV filling pressure (E/e╯), and left atrial volume index (g/m2) weremeasured by transthoracic echocardiography in mid-adulthood. Birth weight category was self-reported in young adulthoodand classified as low (≤5 lb or ≤2270 g), normal (5–8 lb or 2271–3630 g), and high (>8 lb or >3630 g). Of the 925participants, 7.5% (n = 69) were classified as LBW. Compared with participants with normal birth weight, those with LBWhad 2.01-fold (95% confidence interval: 1.19, 3.41, P = 0.009) higher risks of impaired GLS (GLS > 18%) and 2.63-fold(95% confidence interval: 0.89, 7.81, P = 0.08) higher risks of LV hypertrophy (LVMi > 48 g/m2.7 in men or >44 g/m2.7 inwomen) in adulthood, independent of age, sex, and any socio-economic factors. Participants with LBW significantlyincreased body fat from childhood to adulthood relative to their peers and had greater levels of triglycerides, fastingglucose, and arterial stiffness in adulthood. These risk factors were the strongest mediators and explained 54% of the LBWeffect size on adult GLS and 33% of the LBW effect size on LVMi. The remaining of these associations was independent ofany of the measured risk factors.Conclusions: Low birth weight was associated with impaired cardiac structure and function in mid-adulthood. This association was only partially explained by known risk factors

Variations in subclinical left ventricular dysfunction, functional capacity, and clinical outcomes in different heart failure aetiologies

Aims: Patients with heart failure (HF) risk factors are described as being in Stage A of this condition (SAHF). Management is directed towards prevention of HF progression, but to date, no evidence has been described to align the intensity of this intervention to HF risk. We sought to what extent SAHF of Type 2 diabetes mellitus (T2DM) and other HF risks showed differences in subclinical left ventricular function, exercise capacity, and prognosis.Methods and Results: We recruited 551 elder asymptomatic SAHF patients (age 71 ± 5 years, 49% men, 290 T2DM) with at least one risk factor from a community-based population with preserved ejection fraction. All underwent a comprehensive echocardiogram including global longitudinal strain (GLS) and a 6 min walk test and were followed for 2 years. The primary endpoints were new-onset HF and all-cause mortality. The T2DM group was associated with reduced 6 min walk test distance (451 ± 111 vs. 493 ± 87 m, P P = 0.028), and impaired GLS (-17.7 ± 2.6% vs. -19.0 ± 2.6%, P P = 0.021). In Cox models, obesity [hazard ratio (HR) = 2.46; P = 0.007], atrial fibrillation (HR = 2.39; P = 0.028), 6 min walk distance (HR = 0.99; P = 0.034), and GLS (HR = 1.14; P = 0.033) were independently associated with the primary endpoint in T2DM-SAHF, independent of age and glycaemic control.Conclusions: The T2DM-SAHF has worse subclinical left ventricular function, exercise capacity, and prognosis than other-SAHF. Impaired GLS, atrial fibrillation, exercise capacity, and obesity are associated with a worse prognosis in T2DM-SAHF but not in other-SAHF

Association between electrocardiographic and echocardiographic markers of stage B heart failure and cardiovascular outcome

Aims: The detection of non-ischaemic (mainly hypertension, diabetes, and obesity) stage B heart failure (SBHF) may facilitate the recognition of those at risk of progression to overt HF and HF prevention. We sought the relationship of specific electrocardiographic (ECG) markers of SBHF to echocardiographic features of SBHF and their prognostic value for development of HF. The ECG markers were Cornell product (Cornell-P), P-wave terminal force in lead V1 (PTFV1), ST depression in lead V5 V6 (minSTmV5V6), and increased heart rate. Echocardiographic assessment of SBHF included left ventricular hypertrophy (LVH), impaired global longitudinal strain (GLS), and diastolic dysfunction (DD).Methods and Results: Asymptomatic subjects ≥65 years without prior cardiac history, but with HF risks, were recruited from the local community. At baseline, they underwent clinical assessment, 12-lead ECG, and comprehensive echocardiography. New HF was assessed clinically at mean follow-up of 14 ± 4 months, and echocardiography was repeated in subjects with HF. Of the 447 study subjects (age 71 ± 5, 47% men) with SBHF, 13% had LVH, 32% impaired GLS, and 65% ≥grade I DD (10% ≥grade II DD). Forty were lost to follow-up. Clinical HF developed in 47 of 407, of whom 20% had echocardiographic LVH, 51% abnormal GLS, and 76% DD at baseline. Baseline LVH and abnormal GLS (not grade I DD) were independently associated with outcomes (clinical HF and cardiovascular death). Cornell-P and heart rate (not minSTmV5V6 nor PTFV1) were independently associated with LVH, impaired GLS, and DD. Cornell-P and minSTV5V6 (not heart rate nor PTFV1) were independently associated with outcomes. More ECG abnormalities improved sensitivity, but ECG-markers were not independent of or incremental to echocardiographic markers to predict HF in SBHF.Conclusions: In this elderly study population, ECG markers showed low diagnostic sensitivity for non-ischaemic SBHF and low prognostic value for outcomes. Cornell-P and minSTmV5V6 had predictive value for outcomes in non-ischaemic SBHF independent of age, gender, and common comorbidities but were not incremental to echocardiography