Background: Cardiac resynchronization therapy (CRT) is usually performed with biventricular pacing (BiVP), but recently, conduction system pacing (CSP) has been proposed as an alternative in case of BiVP failure. The aim of this study is to define an algorithm to choose between BiVP and CSP resynchronization using the interventricular conduction delays (IVCD) as a guide. Methods: Consecutive patients from January 2018 to December 2020 with an indication for CRT were prospectively enrolled in the study group (delays-guided resynchronization group, DRG). A treatment algorithm based on IVCD was used to decide whether to leave the left ventricular (LV) lead to perform BiVP or pull it out and perform CSP. Outcomes from the DRG group were compared to a historical cohort of CRT patients who underwent CRT procedures between January 2016 and December 2017 (resynchronization standard guide group, SRG). The primary endpoint was a composite of cardiovascular mortality, heart failure (HF) hospitalization, or HF event at 1 year after the date of intervention. Results: The study population consisted of 292 patients, of which 160 (54.8%) were in the DRG and 132 (45.2%) in the SRG. In the DRG, 41 of 160 patients underwent CSP based on the treatment algorithm (25.6%). The primary endpoint was significantly higher in the SRG (48/132, 36.4%) compared to the DRG (35/160, 21.8%) (hazard ratio (HR): 1.72; 95% confidence interval (CI): 1.12–2.65; p = 0.013). Conclusions: A treatment algorithm based on IVCD shifted one patient out of every four from BiVP to CSP, with consequent reduction in the primary endpoint after implantation. Therefore, its application could be useful to determine whether to perform BiVP or CSP.

Accurate prognostic stratification in patients with chronic heart failure and reduced ejection fraction (HFrEF) remains a significant clinical challenge. Many different parameters, including left ventricular (LV) and right ventricular (RV) function and cardiopulmonary exercise testing (CPET) parameters, are available in the literature. LV ejection fraction (LVEF) is the most used parameter in clinical practice. This study aimed to analyze CPET and echocardiographic data in patients under evaluation for heart transplantation (HTx) to identify the parameter that best correlates with cardiac events. Methods and Results. Echocardiography and CPET were performed in patients with HFrEF under evaluation for HTx. The population comprised 170 patients (mean age: 55 ± 9 years; 88% male; non-ischemic etiology: 63%). LVEF was 30.4 ± 7.6%, peak oxygen uptake (Vo_2peak) was 17.08 ± 4.6 mL/Kg/min; minute ventilation (VE)/carbon dioxide production (Vco₂) slope was 34.8 ± 8.7. During a follow-up of 4 ± 1 years, 37 hospitalizations, 4 deaths, 14 HTx, and 5 LV assist device implantation occurred. Patients who experienced major events had a lower Vo_2peak (p < 0.005), higher VE/Vco₂ slope (p < 0.005), greater LV end-systolic diameter (p < 0.005), and RV end-diastolic diameter (p < 0.005) than patients without events. Conversely, LVEF did not differ between these two groups. VE/Vco₂ slope and RV dimensions significantly correlated with hard cardiac events (p = 0.019 and p = 0.008, respectively). Conclusions. In patients with HFrEF, parameters quantifying the system reserve (i.e., Vo_2peak and VE/Vco₂ slope) and those demonstrating advanced biventricular remodeling may help stratify the risk of cardiac events. Conversely, LVEF showed a limited prognostic value in this setting.

Background: Loop diuretics are used to solve congestion in acute heart failure. However, a clear indication about the best infusion modality, dose, and duration of the treatment has not yet been established. In this analysis of the DIUR‐AHF (Different Loop Diuretic Dosing and Administration in Acute Heart Failure) study, we aimed to investigate the effects of different diuretic administration modalities (ie, intermittent versus continuous furosemide infusion) and dose (high dose [HD] versus low dose) on congestion, renal function, and outcome. Methods: Patients received intermittent or continuous intravenous loop diuretics infusion combined as a 1:1 ratio for a period of 72 to 120 hours. HD was defined as a high loop diuretic dose >120 mg/d. Clinical outcome was evaluated in terms of death or heart failure rehospitalization over a 6‐month follow‐up period. Results: A total of 370 patients with AHF were included in this analysis, 189 treated with continuous intravenous loop diuretics infusion and 181 with intermittent intravenous loop diuretics infusion. At baseline, the continuous intravenous loop diuretic infusion group showed increased median values of blood urea ( P =0.010) and creatinine ( P =0.017). Dividing our sample according to loop diuretic dosage, the HD group revealed similar congestion and weight loss compared with the low‐dose group; however, the HD group showed a reduced diuretic efficiency (−0.13 [−0.22 to −0.07] versus −0.32 [−0.59 to −0.20] kg/d; P <0.001) and an increased rate of adverse event occurrence (55% versus 20%; P <0.001). Multivariable analysis showed the association between HD treatment and poor postdischarge outcome (hazard ratio, 1.95 [95% CI, 1.23–3.10]; P =0.005). Conclusions: An HD of loop diuretics infusion revealed an increased risk for adverse events together with reduced diuretic response. Our results extend previous findings revealing the association between HD diuretics and prognosis in patients with chronic HF. Additional studies may confer loop diuretic response in relation to the other decongestive treatments.

Background: Left ventricular myocardial work (MW) derived from non-invasive pressure–strain loops has emerged as a load-adjusted index of contractile performance. Its value for risk stratification in advanced heart failure (HF) remains uncertain. Methods: We retrospectively studied 151 consecutive patients with advanced HF undergoing comprehensive evaluation at our tertiary centre between January 2016 and December 2022. MW parameters—left ventricular global work index (LVGWI), global constructive work (LVGCW), global wasted work (LVGWW) and global work efficiency (LVGWE)—were derived from speckle-tracking echocardiography integrated with brachial blood pressure. Cardiopulmonary exercise testing (CPET), right heart catheterisation (RHC) and biochemical markers were obtained. Patients were stratified according to an LVGWI threshold of 600 mmHg%, identified by receiver operating characteristic (ROC) analysis for predicting the combined end point of cardiovascular mortality or HF hospitalisation. Correlations between MW and traditional indices were assessed, and event-free survival was analysed by Kaplan–Meier curves. Results: LVGWI correlated modestly with pVO₂ (r = 0.35, p = 0.01) and left ventricular ejection fraction (r = 0.42, p < 0.001) and inversely with NT-proBNP (r = −0.30, p = 0.03). LVGWI displayed the largest area under the curve (AUC 0.76 [95% confidence interval 0.65–0.85]) for predicting the combined end point compared with pVO₂ (AUC 0.73) and LVEF (AUC 0.67). Dichotomisation by LVGWI ≤ 600 mmHg% identified a high-risk group (Group A) with worse NYHA class, lower systolic blood pressure and reduced exercise capacity. After a median follow-up of 24 months, Group A exhibited significantly lower event-free survival (log-rank p = 0.02). Multivariable analysis was not performed owing to the limited sample size; therefore, findings should be interpreted with caution. Conclusions: In patients with advanced HF, left ventricular myocardial work, particularly LVGWI, provides incremental prognostic information beyond conventional markers. An LVGWI cut-off of 600 mmHg% derived from ROC analysis identified patients at increased risk of cardiovascular events and may inform timely referral for mechanical circulatory support or transplantation. Larger prospective studies are warranted to confirm these observations and to establish standardised thresholds across vendors.

Background/Objectives: Cardiopulmonary exercise testing (CPET) is a well-established tool for risk stratification in patients with heart failure (HF); however, its utility is limited in routine clinical practice due to the associated cost and technical demands. The hemodynamic gain index (HGI), a non-metabolic parameter derived from systolic blood pressure and heart rate changes during exercise, has been demonstrated to play a promising role in HF populations. In this study, we aimed both to validate the prognostic value of the HGI and to evaluate a novel metric, heart hemodynamic reserve (HHR), in patients with HF and left ventricular ejection fraction (LVEF) below 50%. Methods: We retrospectively enrolled 479 consecutive patients with HF and reduced or mildly reduced LVEF who underwent maximal, symptom-limited CPET at three Italian university hospitals between 2012 and 2024. The HGI and HHR were computed using resting and peak exercise hemodynamic data. HHR is defined as the product of systolic blood pressure and heart rate reserve with exercise, normalized for the age-predicted maximum heart rate. The primary endpoint was a composite of cardiovascular death, urgent heart transplantation (HTx), or left ventricular assist device (LVAD) implantation. Prognostic associations were assessed using multivariable Cox regression and area under the receiver operating characteristic curves (AUCs). Results: During a median follow-up of 3.25 years, the composite outcome occurred in 56 patients (11.5%). Both the HGI and HHR were independently associated with the prespecified endpoint (HGI HR: 0.41, 95% CI: 0.20–0.83, p = 0.013; HHR HR: 0.89, 95% CI: 0.83–0.96, p = 0.004), with HHR showing a slightly higher prognostic accuracy than the HGI (AUC 0.78 vs. 0.74; p = 0.033). Conclusions: Both the HGI and HHR are independent prognostic markers in HF patients with LVEF < 50%. Their non-metabolic derivation makes them valuable tools for risk stratification in settings where CPET is unavailable.