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BackgroundA sex-based evaluation of prognosis in heart failure (HF) is lacking.Methods and resultsWe analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72–7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women).ConclusionsS-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

Heart failure (HF) is a complex and progressive disease marked by substantial morbidity and mortality rates, frequent episodes of decompensation, and a reduced quality of life (QoL), with severe financial burden on healthcare systems. In recent years, several large-scale randomized clinical trials (RCTs) have widely expanded the therapeutic armamentarium, underlining additional benefits and the feasibility of rapid titration regimens. This notwithstanding, mortality is not declining, and hospitalizations are constantly increasing. It is widely acknowledged that even with guideline-directed medical therapy (GDMT) on board, HF patients have a prohibitive residual risk, which highlights the need for innovative treatment options. In this scenario, groundbreaking devices targeting valvular, structural, and autonomic abnormalities have become crucial tools in HF management. This has led to a full-fledged translational boost with several novel devices in development. Thus, the aim of this review is to provide an update on both approved and investigated devices.