Aims Obesity is related to better prognosis in heart failure with either reduced (HFrEF; left ventricular ejection fraction (LVEF) <40%) or preserved LVEF (HFpEF; LVEF ≥50%). Whether the obesity paradox exists in patients with heart failure and mid-range LVEF (HFmrEF; LVEF 40–49%) and whether it is independent of heart failure aetiology is unknown. Therefore, we aimed to test the prognostic value of body mass index (BMI) in ischaemic and non-ischaemic heart failure patients across the whole spectrum of LVEF. Methods Consecutive ambulatory heart failure patients were enrolled in two tertiary centres in Italy and Spain and classified as HFrEF, HFmrEF or HFpEF, of either ischaemic or non-ischaemic aetiology. Patients were stratified into underweight (BMI <18.5 kg/m2), normal-weight (BMI 18.5–24.9 kg/m2), overweight (BMI 25–29.9 kg/m2), mild-obese (BMI 30–34.9 kg/m2), moderate-obese (BMI 35–39.9 kg/m2) and severe-obese (BMI ≥40 kg/m2) and followed up for the end-point of five-year all-cause mortality. Results We enrolled 5155 patients (age 70 years (60–77); 71% males; LVEF 35% (27–45); 63% HFrEF, 18% HFmrEF, 19% HFpEF). At multivariable analysis, mild obesity was independently associated with a lower risk of all-cause mortality in HFrEF (hazard ratio, 0.78 (95% confidence interval (CI) 0.64–0.95), p = 0.020), HFmrEF (hazard ratio 0.63 (95% CI 0.41–0.96), p = 0.029), and HFpEF (hazard ratio 0.60 (95% CI 0.42–0.88), p = 0.008). Both overweight and mild-to-moderate obesity were associated with better outcome in non-ischaemic heart failure, but not in ischaemic heart failure. Conclusions Mild obesity is independently associated with better survival in heart failure across the whole spectrum of LVEF. Prognostic benefit of obesity is maintained only in non-ischaemic heart failure.

Important differences in comorbidities and clinical characteristics exist between women and men with heart failure (HF). In particular, differences in the kinetics of biological circulating biomarkers—a critical component of cardiovascular care—are highly relevant. Most circulating HF biomarkers are assessed daily by clinicians without taking sex into account, despite the multiple gender-related differences observed in plasma concentrations. Even in health, compared to men, women tend to exhibit higher levels of natriuretic peptides and galectin-3 and lower levels of cardiac troponins and the cardiac stress marker, soluble ST2. Many biological factors can provide a reliable explanation for these differences, like body composition, fat distribution, or menopausal status. Notwithstanding, these sex-specific differences in biomarker levels do not reflect different pathobiological mechanisms in HF between women and men, and they do not necessarily imply a need to use different diagnostic cut-off levels in clinical practice. To date, the sex-specific prognostic value of HF biomarkers for risk stratification is an unresolved issue that future research must elucidate. This review outlines current evidence regarding gender-related differences in circulating biomarkers widely used in HF, the pathophysiological mechanisms underlying these differences, and their clinical relevance.

Several heart failure (HF) web-based risk scores are currently used in clinical practice. Currently, we lack head-to-head comparison of the accuracy of risk scores. This study aimed to assess correlation and mortality prediction performance of Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score, which includes clinical variables + medications; Seattle Heart Failure Model (SHFM), which includes clinical variables + treatments + analytes; PARADIGM Risk of Events and Death in the Contemporary Treatment of Heart Failure (PREDICT-HF) and Barcelona Bio-Heart Failure (BCN-Bio-HF) risk calculator, which also include biomarkers, like N-terminal pro B-type natriuretic peptide (NT-proBNP).