Interaction of sex and diabetes in Asian patients with heart failure with mildly reduced left ventricular ejection fraction.

INTRODUCTION: The impact of sex and diabetes mellitus (DM) on patients with heart failure with mildly reduced ejection fraction (HFmrEF) is not well elucidated. This study aims to evaluate sex differences in the clinical profile and outcomes in Asian HFmrEF patients with and without DM. METHODS: Patients admitted nationally for HFmrEF (ejection fraction 40-49%) between 2008 and 2014 were included and followed up until December 2016. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular (CV) death and/or heart failure (HF) rehospitalisations. RESULTS: A total of 2,272 HFmrEF patients (56% male) were included. More women had DM than men (60% versus 55%, P=0.013). Regardless of DM status, HFmrEF females were older, less likely to smoke, had less coronary artery disease, narrower QRS and lower haemoglobin compared to men. The odds of having DM decreases in smokers who are women as opposed to men (Pinteraction =0.017). In multivariate analysis, DM reached statistical analysis for all-cause mortality and combined CV mortality or HF rehospitalisation in both men and women. However, the results suggest that there may be sex differences in terms of outcomes. DM (vs non-DM) was less strongly associated with increased all-cause mortality (adjusted hazards ratio [adj HR] 1.234 vs adj HR 1.290, Pinteraction <0.001] but more strongly associated with the combined CV death/HF rehospitalisation (adj HR 1.429 vs adj HR 1.317, Pinteraction =0.027) in women (vs men). CONCLUSION: Asian women with HFmrEF had a higher prevalence of DM, with differences in clinical characteristics, compared to men. While diabetes conferred poor outcomes regardless of sex, there were distinct sex differences. These highlight the need for sex-specific management strategies.

Nitrates in combination with hydralazine in cardiorenal syndrome: a randomized controlled proof-of-concept study.

AIMS: Cardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine-isosorbide dinitrate (H-ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof-of-concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H-ISDN compared with standard of care in CRS. METHODS AND RESULTS: This multi-centre, single-blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 ]. The primary outcome was 6 min walk test (6MWT) distance measured at 6 months. Secondary outcomes included study feasibility; efficacy outcomes which included renal, cardiac, and endothelial functions, health-related quality of life using Short Form-36, clinical outcomes; and adverse events. Forty-four patients [71 ± 10 years; 75% male; median (inter-quartile range) N-terminal prohormone brain natriuretic peptide 1346 (481-2272) pg/mL] with CRS (left ventricular ejection fraction 42 ± 12% and eGFR 46 ± 15 ml/min/1.73 m2 ) were randomized into two equal groups. Of these, 39 (89%) had hypertension, 27 (61%) had diabetes mellitus, and 17 (39%) had atrial fibrillation. Six (27%) discontinued H-ISDN owing to intolerance and poor compliance. There was a trend towards improved 6MWT distance with H-ISDN compared with standard of care at 6 months (mean difference 27 m; 95% CI, -12 to 66), with little differences in secondary efficacy outcomes. Giddiness and hypotension occurred more frequently with H-ISDN, but HF hospitalizations and mortality were less. CONCLUSIONS: Our pilot study does not support the addition of H-ISDN on top of standard medical therapy to improve exercise capacity in patients with CRS.