BACKGROUNDS:Extracorporeal photopheresis (ECP) is a promising immunomodulatory strategy for complex rejection in heart transplant (HTx) recipients. By combining leukapheresis, 8-methoxypsoralen photoactivation, and UVA irradiation, ECP induces leukocyte apoptosis and promotes immune tolerance through dendritic-cell modulation, regulatory T-cell expansion, and cytokine reprogramming. Clinical evidence supports its use in steroid-refractory acute cellular rejection (ACR) and selected antibody-mediated rejection (AMR). This study reviews the mechanistic rationale and clinical evidence for ECP and reports the real-world experience of the Azienda Ospedaliera Universitaria Senese (AOU Senese). METHODS:We retrospectively analyzed a single-centre cohort of 19 heart transplant recipients treated with extracorporeal photopheresis at AOU Senese between March 2010 and November 2024. Clinical, histological, immunological, echocardiographic, biomarker, immunosuppressive-treatment, and safety data were extracted at baseline and at dataset-defined 3-, 6-, 12-, and 24-month assessments. Analyses were descriptive and used variable-specific denominators because follow-up and laboratory data were incomplete at later time points. RESULTS:Biopsy data for cellular-mediated rejection (CMR) were available in 19 patients through 12 months and in 11 patients at 24 months. The proportion with ≥ 1R CMR decreased from 11/19 (57.9%) at baseline to 4/19 (21.1%) at 3 months, 3/19 (15.8%) at 6 months, 2/19 (10.5%) at 12 months, and 0/11 at 24 months. pAMR1 was present in 6/18 (33.3%) patients with available baseline AMR data, absent at 3 months, present in 1/19 (5.3%) at 6 months, and absent among patients with available biopsies at 12 and 24 months. In contrast, Class II DSA positivity did not show a consistent decline (12/19 [63.2%] at baseline and 8/10 [80.0%] at 24 months). Left ventricular systolic function remained broadly preserved among available observations, and corticosteroid dose decreased over time. Seven deaths occurred during the available overall follow-up, four of which were recorded as reasons for ECP discontinuation. CONCLUSIONS:In this small, retrospective, uncontrolled, and clinically heterogeneous cohort, ECP use was temporally associated with a lower biopsy-documented rejection burden and reduced corticosteroid exposure. The study does not establish a causal effect of ECP on rejection, antibody burden, or safety, and the antibody data do not support a uniform reduction in DSA. Prospective multicentre studies with standardized treatment protocols, assay definitions, and complete longitudinal follow-up are required.

BACKGROUND:Cardiogenic shock (CS) is a life-threatening syndrome with persistently high mortality rates despite therapeutic advances. Structured regional networks may offer improved outcomes through standardized care and early advanced support.This study evaluates the impact of a structured regional cardiogenic shock network on in-hospital mortality and clinical outcomes. METHODS:We conducted a prospective observational study at the University Siena Hospital, enrolling CS patients (SCAI stage C-D-E) between September 2020 and November 2024. The study population was divided into patients directly admitted to the shock center (hub group) and those initially admitted to a referring network hospital (spoke group). RESULTS:We enrolled 145 consecutive patients with CS (mean age 61.0 ± 14.2 years; 81.4% male), predominantly due to acute coronary syndrome (46.9%) or acute on chronic heart failure (32.4%). The majority (61.4%) were transferred from referring network regional hospitals. Despite a high-risk profile (SCAI stage D + E in 48.3%, phenotype II + III in 62.1%), 73.5% of patients achieved a successful outcome, defined as hospital discharge or cardiac replacement therapy (23 heart transplants, 9 LVADs). The overall in-hospital mortality was 26.5%. Mortality increased with SCAI stage (p = 0.001) according to literature data. A vaso-inotropic score (VIS score) major than 21 at 48 h after admission was predictive of mortality (AUC = 0.722). CONCLUSIONS:In this observational study CS population presented low in-hospital mortality rate without any difference in hub and spoke group. It may be determined by the benefits of a structured regional network for CS and multidisciplinary approach management with early MCS implantation.

Solid organ transplant recipients (SOT) have shown impaired immune responses to infection and vaccination. Here, serological data collected in heart and lung transplant recipients after vaccination against SARS-CoV-2 were analyzed using dimensionality reduction, clustering algorithms and statistical methods to define factors associated with immune responsiveness. Transplanted organ type, bivalent Omicron-adapted vaccine administration, and immunosuppressive regimen were associated with distinct serological profiles. These factors were associated with significant differences in the RBD-specific memory B cell (MBC) responses. Indeed, a lower frequency of MBC recognizing both wild-type and Omicron BA.2 RBD was detected in lung versus heart transplant recipients. Administration of the bivalent Omicron-adapted fifth dose was associated with the modulation of RBD-specific MBC phenotypes, and the mycophenolate mofetil (MMF) treatment was associated with significantly lower humoral and MBC responses in heart transplant recipients. This work identifies factors associated with vaccine-induced immune responses in SOT recipients, useful to inform tailored vaccination strategies.

(1) Background: Left ventricular assist device (LVAD) implantation is a valuable alternative as a bridge to transplant but also as a destination therapy in ineligible patients. Right ventricular failure (RVF) is a major cause of short- and long-term mortality post-LVAD. We aimed to validate echocardiographic and hemodynamic parameters predictive of RVF and adverse outcomes post-LVAD; (2) Methods: We screened a population of patients with end-stage heart failure selected for LVAD implantation according to SIENA protocol and standard international indications, including right heart catheterization (RHC). Individuals were followed up for 1 year with different time points for the development of RVF (primary endpoint) or mortality and hospitalization (secondary endpoint); (3) Results: The population included 29 patients with a mean age of 63 ± 7 years with a mean ejection fraction of 23 ± 4%, mostly due to ischemic etiology. All the patients had a SIENA protocol score of 0–1 before LVAD, and none met the primary endpoint. Regarding the secondary endpoint, among all the tested clinical, laboratory, echo, and RHC indices, only a central venous pressure/wedge pressure (CVP/PCWP) ratio > 0.63 was significantly associated with adverse outcomes (ß = 2.99, p = 0.026); (4) Conclusions: Excluding a pre-implantation RV dysfunction according to SIENA protocol significantly reduces the risk of post-LVAD RVF. The CVP/PCWP ratio may be an additional prognostic marker for mortality and rehospitalization in LVAD patients.

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 (Vo2peak) 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 Vo2peak (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., Vo2peak 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 Individuals with primary and secondary immunodeficiencies, being more susceptible to infections, are a priority for vaccination. Here, we determined and compared in a longitudinal study the immune response elicited by SARS-CoV-2 vaccination across different groups of individuals who are immunocompromised. Methods In the PatoVac_COV longitudinal prospective single-centre study, the spike-specific B cell and antibody responses to SARS-CoV-2 mRNA vaccination were compared across 5 different groups of individuals with haematological malignancies, hematopoietic stem cell (HCT) or solid organ transplantation (SOT), undergoing haemodialysis, and people living with HIV (PLWH), for a total of 585 participants. Data from participants who were immunocompromised were compared to a group of 123 participants who were immunocompetent. Blood samples were collected before and after each vaccine administration, up to 2 years. Findings A different immune responsiveness was observed after the first two vaccine doses, with haematological, haemodialysis, and SOT participants showing reduced responsiveness compared to HCT and PLWH, and relative to the comparison group. Spike-specific B cell response was both slower and lower in all groups except in PLWH when compared to participants who were immunocompetent. However, the first booster dose enhanced both the B and the antibody responses in all groups, that persisted up to 2 years after the first vaccine administration. The administration of Omicron-adapted booster vaccines promoted a primary BA.2 RBD-specific B cell response, especially in participants who were immunocompromised. Despite repeated vaccinations, a subset of persistent low-responders, especially among SOT, was identified. Interpretation Our study highlights the heterogeneous immune response across individuals with different pathologies, the pivotal role of the first booster dose, the primary activation of Omicron-specific B cells elicited by updated variant-adapted vaccines and the persistence of low-responders despite multiple vaccine administrations. These aspects have a clinical relevance for planning vaccination schedules tailored for individuals with different immunocompromising conditions. Copyright (c) 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

Abstract Introduction The transplanted heart (HTX) has pathophysiological differences compared to standard hearts, partially understood. Early detection of abnormal grafts function (e.g. cellular or immune-mediated rejection, coronary artery vasculopathy) by advanced echocardiography can significantly improve management and prognosis of HTX patients. Speckle tracking-derived global longitudinal strain (GLS) and myocardial work (MW) have lower values in healthy HTX patients compared to controls. How much these abnormalities can be dependent on the surgical procedure itself is not known yet. Aim to compare MW values in stable patients after HTX and other cardiac surgical procedures to evaluate possible different impact of surgery on heart function. Methods in a monocentric study, we screened stable post-operative patients with a preserved left ventricular (LV) ejection fraction who underwent surgery at our hospital for HTX (group 1), aortic valve replacement, AVR, for severe aortic stenosis (group 2), mitral valve replacement, MVR, for severe primary regurgitation (group 3) and elective coronary artery bypass graft (CABG) (group 4). We excluded patients with other previous cardiac surgery, active pacemakers, BMI > 30, abnormal LV global function, more than mild regurgitation and/or stenosis, major post-operative complications absent informed consent. None of the HTX patients had previous history of rejection or coronary artery disease. All the surgical procedures required a median sternotomy and on-pump approach. All echocardiograms were performed between the 5th and the 12th postoperative day or within 2-3 months after HTX. For all patients, data regarding standard echo, GLS and MW parameters were collected and compared. One-way analysis of variance (ANOVA) and Bonferroni post-hoc tests were used to compare the variables among groups. Any independent predictor was tested to MW values reduction. Results Final population included 202 patients (137 males, 67%) with median age of 62 [50-86] years: 82 HTX, 40 AVR, 42 MVR and 40 CABG. MW-derived global work index (GWI), global constructive work (GCW) and global work efficiency (GWE) were significantly lower in group 2, 3 and 4 compared to HTX patients while having comparable global wasted work (GWW) (Table 1). Multivariate regression analysis showed significant relationship between all MW indices and GLS and blood pressure, as expected. GWI was also related to E/e’ ratio (b=0,131 p=0,033), GCW and GWW with LV end-diastolic volume, EDV (b=-0,177 p=0,012 and b=-0,261 p=0,030 respectively), GWE with EF (b=0,245 p=0,009) and EDV (b=0,210 p=0,027). Conclusions GLS and MW indices are lower after HTX than healthy general population. However, the transplanted heart has better MW indices compared to other post-operative patients. These preliminary results can suggest that the impact of surgical procedure on transplanted hearts might be only partially related to abnormal deformation and needs further characterization.

The prevalence of advanced heart failure (AdHF) is increasing globally, driven by population aging and improved survival rates in chronic heart failure (CHF). Durable Mechanical Circulatory Support (DMCS), particularly Left Ventricular Assist Devices (LVADs), has become a cornerstone in AdHF management. However, its successful implantation requires a comprehensive preoperative evaluation integrating cardiac, hemodynamic, and systemic assessments. Echocardiography and cardiac magnetic resonance (CMR) provide critical data for risk stratification—e.g., LV ejection fraction < 25%, LV end-diastolic diameter < 60 mm, or free wall RV longitudinal strain (fwRVLS) > −14% predict poorer outcomes. Right heart catheterization (RHC) identifies hemodynamic contraindications (PVR > 6 WU, PAPi < 1.5, cardiac index < 2 L/min/m2), while cardiopulmonary exercise testing (CPET) remains pivotal for assessing functional reserve (peak VO2 < 12 mL/kg/min or <50% predicted). Systemic assessment must address renal, hepatic, oncologic, and psychiatric comorbidities that influence surgical risk. Integrating these multimodal data within a multidisciplinary framework—spanning cardiologists, cardiac surgeons, anesthesiologists, and psychologists—optimizes selection and outcomes for DMCS candidates.

Cardiogenic shock (CS) is a heterogenous, life-threatening condition burdened by high mortality rate. The clinical presentation and the pathophysiological mechanisms underlying CS in acute decompensated cardiogenic shock (ADHF-CS) in comparison with other acute etiology are completely different. Aim of this study was to assess the differences between ADHF-CS and other acute etiology of CS, based on clinical features, echocardiographic and laboratory variables, type of support, outcomes. We prospectively analyzed a cohort of CS patients consecutively admitted in an intensive cardiac care unit (ICCU) of a tertiary center in the period October 2020 to August 2024. This ICCU has a program for cardiac replacement therapy and it is inserted in a regional network for CS and advanced heart failure. A total of 109 patients (pts) with CS consecutively admitted in our ICCU were included in our analysis. ADHF-CS group was composed by 59 pts (male 84.7%, media age 60.4 years), with a significant less number of diabetic patients (25.4% respect of 44.0%, p 0.041). ADHF pts had no significative differences in severity of shock, they have similar SCAI stage, similar value of central venous pressure and lactate ad the admission but a significative lower value of central venous saturation (svcO2 54.8% vs 61.3%, p=0.026). Echocardiographic variables are very different in two groups: in ADHF-CS group the pts have major value of end diastolic diameter at the admission (left ventricle EDD admission 51.6 mm vs 64.4 mm, p< 0.001), lower left ventricular ejection fraction (EF 19.0% vs 23.2%, p=0.016), lower value of RVFAC (32.4% vs 38.1%) and a significative higher value of pulmonary pressure (44.8 mHg vs 35.5 mmHg, p= 0.001), no significative differences in left and right strain value. In ADHF group pts were supported with a major dose of vaso-inotropic drugs and dobutamine were used in 30% of patients in comparison with 14% of other group. The use of microaxial pump and VA-ECMO was no significative different, whereas IABP was used less frequent (41% in ADHF-CS vs 68%, p= 0.004), also ADHF-CS patients had less need of continuous renal replacement therapy (7.0% vs 28.0 p=0.04). ADHF CS patients had a significant liver disfunction (higher bilirubine and INR). ICCU- mortality was inferior in ADHF-CS without a significative value (16.9% vs 32.0%, p=0.065), a similar number of patient were implanted with LVAD but a significative higher number of pts were treated with heart transplantation (22.0% vs 5.0%, p=0.018). In our cohort ADHF-CS population had similar baseline feature population, worse echocardiographic variables, major liver disfunction in comparison with other etiology of CS. ADHF-CS patients needed of higher dose of vaso-inotropic drug, similar mechanical circulatory support, excepted for a less use of IABP, they have a better survival rate in ICCU and they more often treated with successful heart transplantation.

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.

Cardiogenic shock (CS) management is challenging due to the heterogeneity of clinical presentations, complex hemodynamic perturbations and several complications. Therefore a multidisciplinary shock team and dedicated intensive cardiac care unit (ICCU) are necessary to treat these patients (pts). To assess clinical features and outcome of CS pts treated in a ICCU of a single tertiary center,inserted in a regional network for CS. We prospectively analyzed a cohort of CS pts admitted in an ICCU of a tertiary center from October 2020 to October 2024. This ICCU provides cardiac replacement therapy and operates as part of a regional system for advanced heart failure and CS. Early referrals, collaborative multidisciplinary discussions for pts transfers, and shared protocols are common to all network’s centers. We enrolled 145 pts with CS admitted in our ICCU.Mean age of the population was 60.9 years,80.6% were males. CS etiology was ACS in 46.2% of pts, acute decompensated heart failure in 47.6%,other etiologies in 6.2%. Ninty–one pts (62.7%) were transferred from other ICU/ICCU of the regional network for CS. These pts were supported by mechanical circulatory support (58.6% IABP, 13.7% microaxial pump, 20.0% VA–ECMO). The mechanical supports were selected and re–assessed by a multidisciplinary team, considering data from a multiparametric monitoring, and according to an escalation and de–escalation strategy. Sixty–eight pts needed mechanical ventilation, 29 continuous replacement therapy. Despite including a high–risk population, with a significant proportion of pts in SCAI stages D (36.5%) and E (12.4%) and phenotypes of the cardiogenic shock working group type II (40.0%) and type III (22.1%), the overall outcomes were favorable.The successful outcome, comprehensive of pts discharged from hospital or treated with a cardiac replacement therapy, were obtained in 80.6% of the cohort: 23 pts were treated with heart transplantation and 9 with LVAD implantation. The in–hospital mortality rate was 26.2%. [Table 1, Figure 1]. Despite the severity of CS population this study showed lower mortality rate than that reported in literature. A structured network for CS with early referral to ICCU and a multidisciplinary team for evaluation of escalation and de–escalation of mechanical circulatory support may play a role on outcome.Table 1 Figure 1

Background: Patients with primary and secondary immunodeficiencies, being more susceptible to infections, are a priority for vaccination. Here, we determined and compared the immune response elicited by SARS-CoV-2 vaccination across different cohorts of immunocompromised patients in a longitudinal study.Methods: In the PatoVac longitudinal prospective single-center study, the spike-specific B cell and antibody responses to SARS-CoV-2 mRNA vaccination were compared across haematological and haemodialysis patients, hematopoietic stem cell and solid organ transplant recipients (SOT), and people living with HIV (PLWH), for a total of 598 subjects. Blood samples were collected before and after each vaccine administration, and followed up for 2 years.Findings: A different immune responsiveness was observed after the first two doses, with hematological, hemodialysis and solid organ transplanted subjects less responsive than stem-cell transplanted patients and PLHW. Spike-specific B cell response was slower and lower in all cohorts except in PLWH compared to HC, but the first booster dose raised both the B and the antibody responses that persisted up to 2 years after the first vaccine administration. Persisting low-responder subjects, especially among SOT, were detected.Interpretation: Our study highlights the heterogeneous immune response across different pathologies, the pivotal role of the third dose, and the persistence of low-responders despite multiple vaccine administrations. These aspects have a clinical relevance for planning vaccination schedules tailored for patients with different immunocompromising conditions.Funding: This work was supported by funds from the Department of Medical Biotechnology of the University of Siena, and from EU within the NextGenerationEU-MUR PNRR Tuscany Health Ecosystem (Project no ECS00000017-THE). Declaration of Interest: MB has received honoraria and support for attending meetings from NOVARTIS, ABVVIE, INCYTE. The authors: Annalisa Ciabattini, Elena Pettini, Fabio Fiorino, Jacopo Polvere, Simone Lucchesi, Chiara Coppola, Simone Costagli, Gabiria Pastore, Anna Sicuranza, Monica Tozzi, Arianna Lippi, Francesca Panza, Alessandro Bucalossi, Guido Garosi, David Bennett, Sonia Bernazzali, Massimiliano Fabbiani, Francesca Montagnani and Donata Medaglini declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Ethical Approval: The studies were performed in compliance with all relevant ethical regulations and the protocol were approved by local Ethical Committee for Clinical experimentation (CEAVSE; protocol code n.19479, approved on 3rd March 2021 for PatoVac, and n. 18869 v1.0 approved on the 21st December 2020 for IMMUNO_COV).

AIMS:Advanced heart failure (AdHF) is characterized by variable degrees of left ventricular (LV) dysfunction, myocardial fibrosis, and raised filling pressures which lead to left atrial (LA) dilatation and cavity dysfunction. This study investigated the relationship between LA peak atrial longitudinal strain (PALS), assessed by speckle-tracking echocardiography (STE), and invasive measures of LV filling pressures and fibrosis in a group of AdHF patients undergoing heart transplantation (HTX). METHODS AND RESULTS:We consecutively enrolled patients with AdHF who underwent HTX at our Department. Demographic and basic echocardiographic data were registered, then invasive intracardiac pressures were obtained from right heart catheterization, and STE was also performed. After HTX, biopsy specimens from explanted hearts were collected to quantify the degree of LV myocardial fibrosis. Sixty-four patients were included in the study (mean age 62.5 ± 11 years, 42% female). The mean LV ejection fraction (LVEF) was 26.7 ± 6.1%, global PALS was 9.65 ± 4.5%, and mean pulmonary capillary wedge pressure (PCWP) was 18.8 ± 4.8 mmHg. Seventy-three % of patients proved to have severe LV fibrosis. Global PALS was inversely correlated with PCWP (R = -0.83; P < 0.0001) and with LV fibrosis severity (R = -0.78; P < 0.0001) but did not correlate with LVEF (R = 0.15; P = 0.2). Among echocardiographic indices of LV filling pressures, global PALS proved the strongest [area under the curve 0.955 (95% confidence interval 0.87-0.99)] predictor of raised (>18 mmHg) PCWP. CONCLUSION:In patients with AdHF, reduced global PALS strongly correlated with the invasively assessed LV filling pressure and degree of LV fibrosis. Such relationship could be used as non-invasive indicator for optimum patient stratification for therapeutic strategies.

Abstract Introduction The use of left ventricular assist devices (LVAD) is increasing both as bridge-to-transplantation or destination therapy, considering the lack of heart donors for transplantation in advanced heart failure (AHF) population. Right ventricular post-implantation failure, major bleedings and infective events remain the principal adverse events in LVAD carriers, thus an accurate selection of candidates is needed. Purpose To identify between clinical, laboratory, standard and advanced (Speckle Tracking, STE) echocardiography, and right heart catheterization (RHC) indices, the best predictors of outcome after LVAD implantation. Materials and Methods We screened in our third-level center 30 patients with AHF, followed up from May 2013 to February 2022, for the assessment of LVAD implantation suitability. They all underwent a complete cardiological history collection, electrocardiography, standard and STE left ventricular (LV) and left atrial (LA) size and function assessment. Regarding the right ventricle, SIENA score parameters, including RV sphericity index, RV free wall longitudinal strain (LS), right ventricular fractional area change (RVFAC), and 3D ejection fraction were used for exclude RV disfunction. RHC was performed on the same day of echocardiography. Follow-up was conducted at 1, 3, 6, 9 and 12 months repeating all the assessments, for the occurrence of RV failure, all-causes mortality, hemorrhagic events and re-hospitalization for heart failure. With a univariate and multivariate statistical analysis, we went to test among all the parameters the possible predictors of outcome. Results The final population consists of 29 patients (93% male, mean age of 63±11 years), in NYHA class III or IV and a severe reduction of left ventricular (LV) ejection fraction (EF), in whom arterial hypertension and smoking, present or previous, were present in 58% and 65% of cases, respectively. The population was divided into two groups according to the occurrence of at least one cardiovascular event. 11 major events were recorded: including 4 hemorrhagic events, 3 all-causes mortality and 4 hospital admission for HF. No RV failure occurred in the first 12 months of follow-up. No differences were identified between the two groups in terms of echocardiographic indices and RV function, including RVFAC or RV-FWLS. At univariate analysis (see Table 1), the only parameter able to predict major CV events was central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio, obtained by RHC, an index of balance between right and left heart filling pressure. Conclusions A careful application of SIENA score indices before LVAD implantation can significantly reduce the incidence of post-operative RV failure, as in our small population. Our results also confirmed the paramount role of RHC in the diagnostic work up of AHF.

Aims:Myocardial work (MW) is a relatively novel non-invasive echocardiographic method with increasing fields of application. Normal reference ranges of MW indices in patients who have undergone a heart transplant (HTx) have not been determined yet. The aim of this study was to obtain the reference ranges for 2D echocardiographic indices of MW for adult HTx patients and to compare them with the results of the European Association of Cardiovascular Imaging (EACVI) Normal Reference Ranges for Echocardiography (NORRE) study. Methods and results:All consecutive HTx patients admitted at our institution (University Hospital of Siena, Italy) between September 2019 and May 2022 who underwent endomyocardial biopsy (EMB) were considered. Patients with a history of rejection, a history of coronary artery vasculopathy, either acute cellular rejection or acute antibody-mediated rejection at EMB, and donor-specific antibodies were excluded. MW retrospectively performed for the included patients was retrieved, and the results were compared with those from the EACVI NORRE study. Out of 176 HTx patients who underwent EMB, 94 patients were excluded. The study population consisted of 82 HTx patients [68.3% male, median age 53 (46-62) years]. The median duration from HTx was 5 (2-22) months. The main MW indices such as global work efficiency (GWE, 84 ± 8%), global work index (GWI, 1447 ± 409 mmHg%), global constructive work (GCW, 2067 ± 423 mmHg%), and global wasted work [GWW, 310 (217-499) mmHg%] did not differ according to gender. Each of these indices significantly differed from those reported in the EACVI NORRE study (P-value <0.001), with lower GWI, GCW, and GWE and higher GWW values in the HTx population. Conclusion:This study provides reference ranges for MW indices in an adult HTx population free from transplant-related complications which proved to be different from those previously reported in healthy volunteers.

Background: An increasing proportion of heart failure (HF) patients progress to the advanced stage (AdHF) with high event rates and limited treatment options. Echocardiography, particularly Speckle Tracking-derived myocardial work (MW), is useful for HF diagnosis and prognosis. We aimed to assess MW’s feasibility in the prognostic stratification of AdHF. Methods: We retrospectively screened patients with AdHF who accessed our hospital in 2018–2022. We excluded subjects with inadequate acoustic windows; unavailable brachial artery cuff pressure at the time of the echocardiography; atrial fibrillation; and mitral or aortic regurgitation. We measured standard parameters and left ventricular (LV) strain (LS) and MW. The population was followed up to determine the composite outcomes of all-cause mortality, left ventricular assist device implantation and heart transplantation (primary endpoint), as well as unplanned HF hospitalization (secondary endpoint). Results: We enrolled 138 patients, prevalently males (79.7%), with a median age of 58 years (IQR 50–62). AdHF etiology was predominantly non-ischemic (65.9%). Thirty-five patients developed a composite event during a median follow-up of 636 days (IQR 323–868). Diastolic function, pulmonary pressures, and LV GLS and LV MW indices were not associated with major events. Contrarily, for the secondary endpoint, the hazard ratio for each increase in global work index (GWI) by 50 mmHg% was 0.90 (p = 0.025) and for each increase in global constructive work (GCW) by 50 mmHg% was 0.90 (p = 0.022). Kaplan–Meier demonstrated better endpoint-free survival, with an LV GWI ≥ 369 mmHg%. Conclusions: GWI and GCW, with good feasibility, can help in the better characterization of patients with AdHF at higher risk of HF hospitalization and adverse events, identifying the need for closer follow-up or additional HF therapy.

Abstract Background Extra–Circulatory Life Support (ECLS) is a vital therapeutic option in patients (pts) with refractory cardiogenic shock (CS). Few centers can assure optimal assistance to these delicate pts and early centralization in the context of regional networks is essential. Methods We enrolled all consecutive pts with ECLS for refractory CS admitted to our Intensive Cardiac Care Unit (ICCU) from January 2021 to November 2023. The primary endpoints evaluated were weaning from ECLS and in–hospital mortality. The secondary endpoints included neurological outcomes and major complications. Results We enrolled 21 consecutive pts (90% male, 55y median age) with refractory CS and indication for peripheral Veno–Arterial Extracorporeal Membrane Oxygenation (VA–ECMO), percutaneously or surgically positioned, with antegrade perfusion to avoid limb ischemia. Fourteen pts (67%) came from other hospitals, 8 (38%) of which already had been implanted with ECLS. Concerning the CS etiology, we observed 8 (38%) heart failure, 12 (57%) post–myocardial infarction, 1 (5%) adrenergic storm and 10 (48%) cardiac arrests. Six pts (28%) were deemed eligible for heart transplant (HT) list before the CS episode. In all pts we assured left ventricle unloading with IABP (9), Impella CP (3), Impella 5.5 (1). Five pts underwent apical left ventricular venting and escalation of mechanical support. The median duration of ECLS support was 10.1 days. Eleven pts (52%) were successfully weaned from VA–ECMO due to myocardial recovery (n=6; 29%) or HT (n=5; 24%); of the latter, 1 died due to peri–operative complication. Overall in–hospital mortality rate was 52%. Ten pts were discharged: 7 without neurological deficit (CPC 1), 2 with mildly impaired neurological function (CPC 2–3) and 1 with severe disability (CPC 4). During ECLS we observed the following complications: bleeding (28%), AKI (28%), infections (28%), neurological complications as acute ischemic stroke or intracerebral hemorrhage (19%); no limb ischemia occurred. Conclusions ECLS provides cardiac and respiratory support and serves as a bridge to recovery or heart replacement therapies (LVAD, HT). Tertiary Shock Centers in a Regional Network assure optimal assistance for this vital support.

Advanced heart failure (AdvHF) can only be treated definitively by heart transplantation (HTx), yet problems such right ventricle dysfunction (RVD), rejection, cardiac allograft vasculopathy (CAV), and primary graft dysfunction (PGD) are linked to a poor prognosis. As a result, numerous biomarkers have been investigated in an effort to identify and prevent certain diseases sooner. We looked at both established biomarkers, such as NT-proBNP, hs-troponins, and pro-inflammatory cytokines, and newer ones, such as extracellular vesicles (EVs), donor specific antibodies (DSA), gene expression profile (GEP), donor-derived cell free DNA (dd-cfDNA), microRNA (miRNA), and soluble suppression of tumorigenicity 2 (sST2). These biomarkers are typically linked to complications from HTX. We also highlight the relationships between each biomarker and one or more problems, as well as their applicability in routine clinical practice.

The implantation of left ventricular assist devices (LVADs) has been increasing, with good long-term results, in parallel with a growing population with advanced heart failure (HF). However, in some European countries, LVADs are still underused, with one of the main issues being the patient's late referral. On the contrary, the use of transcatheter edge-to-edge mitral valve repair (TEER) has exponentially increased over the past decade, expanding its potential use even in patients on the heart transplantation waiting list. Even though the study populations of the main trials that investigated the prognostic impact of LVAD and TEER are different, in clinical practice a clear distinction might not be so clear. Therefore, patients with refractory HF symptoms and significant mitral regurgitation should be thoroughly evaluated through a multidisciplinary Heart Team meeting with both an advanced HF specialist and interventional cardiologist, to avoid futile procedures and to define the optimal timing for advanced HF therapies, when they are indicated. We analyzed the main available studies and registries on both TEERs and LVADs and we compared their populations and outcomes, to provide the current evidence on the use of LVAD and TEER in the HF population, especially in the light of the recently released 5-year follow-up results, giving some insights on the Italian situation, and finally to stress the importance of a solid HF network between hospitals, aiming for advanced HF patients’ timely referral for LVAD or heart transplants.