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Aim: Persistent symptoms despite guideline‐directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real‐world data on GDMT use, dose, and prognostic implications are lacking. Methods and results: We included 699 consecutive patients with HFrEF and at least one 'I NEED HELP' marker for advanced HF enrolled in a multicentre registry. Beta‐blockers (BB) were administered to 574 (82%) patients, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor–neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonists (MRA). Overall, ≥50% of target doses were reached in 41%, 22%, and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41%, and 55% for BB, ACEi/ARB/ARNI and MRA, respectively). The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA‐ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48–0.84, and HR 0.74, 95% CI 0.58–0.95, respectively). Conclusions: In a large, real‐world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were undertreated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity. [ABSTRACT FROM AUTHOR]

Aims: Patients with heart failure (HF) with reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) may all progress to advanced HF, but the impact of EF in the advanced setting is not well established. Our aim was to assess the prognostic impact of EF in patients with at least one 'I NEED HELP' marker for advanced HF. Methods and results: Patients with HF and at least one high‐risk 'I NEED HELP' criterion from four centres were included in this analysis. Outcomes were assessed in patients with HFrEF (EF ≤ 40%), HFmrEF (EF 41–49%), and HFpEF (EF ≥ 50%) and with EF analysed as a continuous variable. The prognostic impact of medical therapy for HF in patients with EF < 50% and EF > 50% was also evaluated. All‐cause death was the primary endpoint, and cardiovascular death was a secondary endpoint. Among 1149 patients enrolled [mean age 75.1 ± 11.5 years, 67.3% males, 67.6% hospitalized, median follow‐up 260 days (inter‐quartile range 105–390 days)], HFrEF, HFmrEF, and HFpEF were observed in 699 (60.8%), 122 (10.6%), and 328 (28.6%) patients, and 1 year mortality was 28.3%, 26.2%, and 20.1, respectively (log‐rank P = 0.036). As compared with HFrEF patients, HFpEF patients had a lower risk of all‐cause death [adjusted hazard ratio (HRadj) 0.67, 95% confidence interval (CI) 0.48–0.94, P = 0.022], whereas no difference was noted for HFmrEF patients. After multivariable adjustment, a lower risk of all‐cause death (HRadj for 5% increase 0.94, 95% CI 0.89–0.99, P = 0.017) and cardiovascular death (HRadj for 5% increase 0.94, 95% CI 0.88–1.00, P = 0.049) was observed at higher EF values. Beta‐blockers and renin–angiotensin system inhibitors or sacubitril/valsartan were associated with lower mortality in both EF < 50% and EF ≥ 50% groups. Conclusions: Among patients with HF and at least one 'I NEED HELP' marker for advanced HF, left ventricular EF is still of prognostic value. [ABSTRACT FROM AUTHOR]

Background: The new heart failure (HF) therapies of sodium-glucose cotransporter 2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil do not act primarily through the neuro-hormonal blockade, but have shown clinical benefits in patients with HF with reduced ejection fraction (HFrEF). However, their respective efficacies remain unclear. Our aim was to evaluate the relative efficacy of new drugs for HFrEF. Methods: We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing SGLT2i, vericiguat, omecamtiv mecarbil, and placebo in HFrEF patients. The primary endpoint was the composite of cardiovascular death (CVD) or HF hospitalization (CVD-HF); secondary endpoints were CVD, all-cause death, and HF hospitalization (HFH). Results: Twelve RCTs (n = 23,861 patients) were included. A significant reduction in CVD-HF was observed with SGLT2i compared with placebo (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.71–0.83), vericiguat (RR 0.84, 95% CI 0.75–0.93), and omecamtiv mecarbil (RR 0.80, 95% CI 0.72–0.88). No significant difference was observed between vericiguat and omecamtiv mecarbil (RR 0.95, 95% CI 0.87–1.04). SGLT2i were superior to placebo and omecamtiv mecarbil for all individual secondary endpoints (CVD, all-cause death, and HFH), and also to vericiguat for HFH. SGLT2i ranked as the most effective therapy for all endpoints, and vericiguat, omecamtiv mecarbil, and placebo ranked as the second, third, and last options, respectively, for the primary endpoint. Conclusions: In patients with HFrEF on standard-of-care therapy, SGLT2i therapy was associated with a reduced risk of CVD-HF compared to placebo, vericiguat, and omecamtiv mecarbil. Furthermore, SGLT2i were superior to placebo and omecamtiv mecarbil for CVD, all-cause death, and HFH, and also to vericiguat for HFH. [ABSTRACT FROM AUTHOR]

Introduction: Left atrial (LA) remodeling is generally considered a consequence of left ventricular (LV) impairment or relevant mitral regurgitation (MR), acting an adaptive buffer phenomenon able to modulate pulmonary circulation Hypothesis: We assessed the hypothesis that the interaction between LA remodeling and the consequences on pulmonary hemodynamics is also effective when MR is less than moderate. Methods: Consecutive patients in sinus rhythm undergoing comprehensive echocardiography, were prospectively enrolled. Echocardiographic parameters of LV systolic and diastolic function were obtained. Mitral effective regurgitant orifice area (ERO) and estimation of systolic pulmonary artery pressure were also calculated. LA strain-derived peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) were obtained in all patients. Counduit strain (CS) was calculated by the differences of PALS and PACS. Results: The study population included 154 patients (mean age 67 ± 14 years). Mean Ejection fraction (EF) was 54 ± 12 %. MR was detectable in 102 patients (66%). It was classified as organic (primary MR) due to mitral prolapse in 14 patients (14%) and functional (secondary MR) in 88 patients (86%). Mean ERO was 0.08 ± 0.12 cm2 and 87 patients (85%) had an ERO ≤ 0.2 cm2. A close negative correlation between LA functional remodeling (PALS, PACS and CS) and ERO was found (r = - 0.44, p <0.0001; r = - 0.46, p < 0.0001 and r = - 0.30, p < 0.0001 respectively), with lower correlation of LA volume (r = 0.34, p < 0.0001)(Figure 1). The stronger association between LA derived strain parameters and ERO was found in functional MR. On multivariate regression analysis using clinical and echocardiographic models, ERO was independently correlated with LA structural and functional remodeling in spite of the lower degree of MR of our population.Furthermore, we also demonstrated a significant correlation between PALS and PASP (r = - 0.62, p < 0.0001). PALS independently predict PASP, on top of the degree of MR. Conclusions: In conclusion, even mild degree of MR contribute to LA remodeling independently from the main parameters of LV systolic and diastolic function. Remodeling itself plays an active role on pulmonary circulation modulating pressure degree. [ABSTRACT FROM AUTHOR]

Aims: Accurate selection of patients with severe heart failure (HF) who might benefit from advanced therapies is crucial. The present study investigates the performance of the available risk scores aimed at predicting the risk of mortality in patients with severe HF., Methods and Results: The risk of 1-year mortality was estimated in patients with severe HF enrolled in the HELP-HF cohort according to the MAGGIC, 3-CHF, ADHF/NT-proBNP, and GWTG-HF risk scores, the number of criteria of the 2018 HFA-ESC definition of advanced HF, I NEED HELP markers, domains fulfilled of the 2019 HFA-ESC definition of frailty, the frailty index, and the INTERMACS profile. In addition, we tested the performance of different machine learning (ML)-based models to predict 1-year mortality. At 1-year follow-up, 265 patients (23.1%) died. The prognostic accuracy, tested in the subgroup of patients with completeness of all data regarding the variables included in the scores (497/1149 patients), resulted moderate for MAGGIC, GWTG-HF, and ADHF/NT-proBNP scores (area under the curve [AUC] ≥0.70) and only poor for the other tools. All the scores lost accuracy in estimating the rate of 1-year mortality in patients at the highest risk. Support vector machine-based model had the best AUC among ML-based models, slightly outperforming most of the tested risk scores., Conclusion: Most of the scores used to predict the risk of mortality in HF performed poorly in real-world patients with severe HF and provided inaccurate estimate of the risk of 1-year mortality in patients at the highest risk. ML-based models did not significantly outperform the currently available risk scores and their use must be validated in large cohort of patients., (© 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: To evaluate the prognostic impact of pre-procedural right ventricular longitudinal strain (RVLS) in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge repair (TEER) in comparison with conventional echocardiographic parameters of RV function., Methods and Results: This is a retrospective study including 142 patients with SMR undergoing TEER at two Italian centres. At 1-year follow-up 45 patients reached the composite endpoint of all-cause death or heart failure hospitalization. The best cut-off value of RV free-wall longitudinal strain (RVFWLS) to predict outcome was -18% [sensitivity 72%, specificity of 71%, area under curve (AUC) 0.78, P < 0.001], whereas the best cut-off value of RV global longitudinal strain (RVGLS) was -15% (sensitivity 56%, specificity 76%, AUC 0.69, P < 0.001). Prognostic performance was suboptimal for tricuspid annular plane systolic excursion, Doppler tissue imaging-derived tricuspid lateral annular systolic velocity and fractional area change (FAC). Cumulative survival free from events was lower in patients with RVFWLS ≥ -18% vs. RVFWLS < -18% (44.0% vs. 85.4%; < 0.001) as well as in patients with RVGLS ≥ -15% vs. RVGLS < -15% (54.9% vs. 81.7%; P < 0.001). At multivariable analysis FAC, RVGLS and RVFWLS were independent predictors of events. The identified cut-off of RVFWLS and RVGLS both resulted independently associated with outcomes., Conclusion: RVLS is a useful and reliable tool to identify patients with SMR undergoing TEER at high risk of mortality and HF hospitalization, on top of other clinical and echocardiographic parameters, with RVFWLS offering the best prognostic performance., Competing Interests: Conflict of interest: M.A. and M.M. received speakers fees from Abbott outside of the present work., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To investigate the prognostic value of the right ventricle-to-pulmonary artery (RV-PA) coupling in patients with either transthyretin (ATTR) or immunoglobulin light-chain (AL) cardiac amyloidosis (CA)., Methods and Results: Overall, 283 patients with CA from 3 Italian high-volume centres were included (median age 76 years; 63% males; 53% with ATTR-CA, 47% with AL-CA). The RV-PA coupling was evaluated by using the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. The median value of TAPSE/PASP was 0.45 (0.33-0.63) mm/mmHg. Patients with a TAPSE/PASP ratio <0.45 were older, had lower systolic blood pressure, more severe symptoms, higher cardiac troponin and N-terminal pro-B-type natriuretic peptide levels, greater left ventricular (LV) thickness, and worse LV systolic and diastolic function. A TAPSE/PASP ratio <0.45 was independently associated with a higher risk of all-cause death or heart failure (HF) hospitalization [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.32-2.96; P = 0.001] and all-cause death (HR 2.18, 95% CI 1.31-3.62; P = 0.003). The TAPSE/PASP ratio reclassified the risk of both endpoints [net reclassification index 0.46 (95% CI 0.18-0.74) P = 0.001 and 0.49 (0.22-0.77) P < 0.001, respectively], while TAPSE or PASP alone did not (all P > 0.05). The prognostic impact of the TAPSE/PASP ratio was significant both in AL-CA patients (HR for the composite endpoint 2.47, 95% CI 1.58-3.85; P < 0.001) and in ATTR-CA (HR 1.81, 95% CI 1.11-2.95; P = 0.017). The receiver operating characteristic curve showed that the optimal cut-off for predicting prognosis was 0.47 mm/mmHg., Conclusion: In patients with CA, RV-PA coupling predicted the risk of mortality or HF hospitalization. The TAPSE/PASP ratio was more effective than TAPSE or PASP in predicting prognosis., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)