Mauro Riccardi

Mauro Riccardi, MD, John W Ostrominski, MD, Safia Chatur, MD, Carlo M Lombardi, MD, Maurizio Volterrani, MD, Marco Metra, MD, Gianluigi Savarese, MD, PhD,

Sex differences are reported in patients with heart failure (HF), but gaps remain in clinical practice and evidence, in particular, in those with advanced HF. The HELP-HF registry enrolled consecutive patients with HF and at least one high-risk ‘I NEED HELP’ marker, evaluated at four Italian centres between 1 January 2020 and 30 November 2021. Patients’ characteristics and outcomes were compared in men vs women. The primary endpoint was the composite of all-cause mortality or first HF hospitalization. A total of 1149 patients were included (mean age 75.1 ± 11.5 years, median left ventricular ejection fraction 35%). Among them, 773 patients (67.3%) were males. Males were younger, had more cardiovascular diseases and a lower left ventricular ejection fraction (32%, [interquartile range 25–45] vs 45% [interquartile range 30–55]), while females showed a higher prevalence of non-cardiac conditions, neurocognitive and depressive disorders. The 1-year rate of the primary composite endpoint was 43.2% in males and 43.1% in females (log-rank P = .857). Multivariable analysis confirmed the lack of a significant impact of sex on the primary endpoint (adjusted hazard ratio 1.03, 95% confidence interval 0.85–1.27, P = .740). No significant differences were also observed in men vs women for the individual endpoints. In our registry enrolling patients with markers of advanced HF, despite differences in clinical and echocardiographic characteristics, no sex-related differences in clinical outcomes were observed. Sex differences in advanced heart failure (HF) patients enrolled in the HELP-HF (Assessment of the I Need Help markers in Heart Failure) registry. Consecutive patients with HF who were hospitalized or evaluated as outpatients between January 2020 and November 2021 at four Italian high-volume centres and had at least one ‘I NEED HELP’ high-risk marker (n = 1149) were included in registry. Among the included patients, 773 patients (67.3%) were males, and 376 patients (32.7%) were females (upper left panel). The 1-year rate of the primary composite endpoint was 43.2% in males and 43.1% in females, without significant difference between the two groups (right panel). Multivariable analysis confirmed the lack of a significant impact of sex on the primary composite endpoint and on the two individual endpoints (lower left panel).

Introduction: To evaluate the short-term clinical, structural, and functional cardiac changes following intermittent levosimendan infusion and their prognostic implications in patients with advanced heart failure (AdHF). Methods: In this prospective, multicentre, observational study, patients with AdHF treated with intermittent levosimendan infusion (12.5 mg at a rate of 0.1 μg/kg/min, without a bolus) were enrolled. Clinical, laboratory, and comprehensive echocardiographic assessments were performed at baseline, 48 h, and 30 days post-infusion. The primary endpoint was to evaluate the extent of clinical and cardiac structure and function changes during the first 30 days after levosimendan infusion. Secondary outcome of interest was the association of cardiac changes and a composite endpoint of decompensated HF, urgent HF rehospitalization, cardiogenic shock, cardiac arrest, and cardiovascular death at 6 months. Results: A total of 37 patients with AdHF were included (mean age 71.1 ± 9.0 years; 59.5% male). A non-significant trend reduction in mean arterial pressure values was observed over time (81.3 ± 9.5 mmHg vs 80.9 ± 7.7 mmHg after 48 h vs 79.1 ± 6.9 mmHg at 30 days, P-value for trend = .079). NT-proBNP levels significantly decreased at 48 h and rose again by 30 days [from 1802 (1127–4436) ng/l to 1060 (830–3864) ng/l at 48 h and 1661 (1015–4245) ng/l at 30 days, P-value for trend = .006]. The main left ventricular (LV) and right ventricular (RV) structure and function parameters improved at 48 h but returned to baseline or a slight improvement by 30 days (LV ejection fraction: 30.9 ± 11.3% vs 32.2 ± 11.2%, vs 30.9 ± 11.3%, P-value for trend = .001; LV global longitudinal strain: −8.0 ± 3.5% vs −9.2 ± 3.5% vs −8.0 ± 3.3%, P-value for trend < .001; tricuspid annular plane systolic excursion: 16.9 ± 3.1 mm vs 17.7 ± 3.4 vs 17.0 ± 3.5, P-value for trend .007; systolic pulmonary artery pressure: 48.7 ± 15.8 mmHg vs 41.6 ± 12.7 mmHg vs 46.1 ± 15.0, P-value for trend <.001). Overall, 17 (45.9%) patients experienced CV events. After accounting for confounders, ΔLV global longitudinal strain (GLS) after 48 h (adjusted odds ratio (OR) 0.26, 95% confidence interval (CI) 0.10–0.67, P = .006) and ΔRV free wall longitudinal strain (FWLS) (adjusted OR 0.75, 95% CI 0.57–0.99, P = .041) were significantly associated with a lower risk of events. Conclusions: In patients with AdHF, intermittent levosimendan infusion resulted in early improvements in NT-proBNP levels and biventricular function, which tended to wane by 30 days. Early enhancements in LVGLS and RVFWLS were independently associated with better clinical outcomes, suggesting their potential role as markers to guide patient selection and therapeutic response.

Heart failure (HF) and valvular heart disease (VHD) often coexist and share complex pathophysiological pathways. Traditional management strategies follow a step-by-step approach, prioritizing guideline-directed medical therapy (GDMT) and reserving interventional (surgical or percutaneous) options only in case of persistent symptoms or worsening HF after GDMT. However, greater experience with the use of percutaneous procedures, even in high-risk patients, could support a more integrated approach, which exploits the synergistic effects of medical and interventional therapies to increase the tolerability of one vs the other, thereby improving quality of life and outcomes through their synergic effects. This expert opinion paper summarizes current data and evolving practices in the management of VHD in patients with HF, including secondary mitral regurgitation, aortic stenosis, aortic regurgitation, and tricuspid regurgitation.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with increasing prevalence and substantial morbidity and mortality. Recent advances in pharmacotherapy have transformed its management. This review summarizes current evidence supporting the use of sodium–glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists, alongside selected use of angiotensin receptor–neprilysin inhibitors. Emphasis is placed on early initiation of disease-modifying therapies, phenotypic tailoring, and comorbidity-targeted strategies, especially in obese and diabetic patients. Together, these approaches define a new era of guideline-directed, personalized care for patients with HFpEF.

Acute kidney injury (AKI) is a sudden loss of renal function limited to 7 days with increased basal serum creatinine levels and/or decreased urinary production. AKI is a frequent condition in the intensive care unit (ICU) ranging from 13% to 36% in patients hospitalized with acute heart failure, up to 80% in patients with cardiogenic shock (CS). AKI requiring dialysis is also common (5% to 8%) and can exceed 13% in patients with CS. AKI is consistently associated with increased mortality in both the short-term, especially when dialysis is needed, and the long-term. The aim of this review is to provide an update on step-by-step management, from pharmacological treatment to renal replacement therapy, in patients with severe AKI in ICU patients with fluid overload.