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In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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: Few data are available regarding the role of tricuspid annulus plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP), a measurement of right ventricular to pulmonary artery coupling, in patients with chronic heart failure and left ventricular systolic dysfunction., Methods and Results: This retrospective single-centre study included outpatients with left ventricular systolic dysfunction (ejection fraction ≤ 50%) evaluated between January 2022 and December 2022. TAPSE/PASP was evaluated as a continuous variable and as tertiles according to its value on the first visit. The primary outcome of the study was a composite of all-cause mortality or heart failure (HF) events at the last available follow-up., Results: A total of 642 patients were included (mean age 71 ± 13 years, 78% male, mean left ventricular ejection fraction 40% [interquatile range 35-46]). Patients with lower TAPSE/PASP had more co-morbidities (i.e., atrial fibrillation, chronic kidney disease or previous cardiovascular implantable electronic device), an higher New York Heart Association class (P < 0.001), more signs of congestion (P = 0.007), and had more probability to receive intravenous furosemide during the visit (P < 0.001). After a median follow-up of 474 days [interquartile range 392-507 days], a total of 51 patients (8.0%) died (with 24 patients [3.8%] experiencing cardiovascular-related deaths), a total of 179 patients (28.1%) experienced a composite outcome, and 158 patients (24.8%) had HF events. Kaplan-Meier analysis showed that the estimated 1-year rate of the primary outcome was higher in the lowest tertile (38.0%), as compared with the intermediate (19.6%) and highest tertiles (14.9%; P-value log-rank <0.001). TAPSE/PASP ratio as a continuous variable was independently associated with the primary outcome (adjusted hazard ratio for 0.1 mm/mmHg increase 0.91, 95% CI 0.84-0.98, P = 0.009), predominantly driven by a higher risk of HF events during follow-up. Analysing the impact of TAPSE/PASP tertiles on the primary outcome, an independent associated was confirmed at multivariate analisys for the highest versus lowest tertile (adjusted hazard ratio 0.61, 95% CI 0.38-0.99, P = 0.044)., Conclusions: TAPSE/PASP was independently associated with mortality or HF events among ambulatory patients with left ventricular systolic dysfunction., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Endocarditis, a serious infectious disease, remains a diagnostic challenge in contemporary clinical practice. The advent of advanced imaging modalities has contributed significantly to the improved understanding and management of this complex disease. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging has shown remarkable potential in improving the diagnostic accuracy of endocarditis. In the update of the Modified Duke Criteria, in 2023, The International Society for Cardiovascular Infectious Diseases (ISCVID) Working Group recognized specific 18F-FDG PET/CT findings as a major diagnostic criterion, particularly in patient with prosthetic valve endocarditis. The ability of PET to visualize metabolic activity allows for the identification of infective foci and could differentiate between infective and non-infective processes. This review examines the clinical utility of PET in differentiating infective endocarditis from other cardiovascular pathologies, highlighting its sensitivity and specificity in detecting native and prosthetic valve infections, including patients with transcatheter aortic valve implantation (TAVI), cardiac implantable devices (CIEDs), and left ventricular assistance devices (LVAD). Also, practical aspects and indications are illustrated to optimize the quality of imaging and reduce potential false positive results. In conclusion, the current use of PET in endocarditis has become a valuable diagnostic tool; as technological advances continue, PET will play an increasingly important role in the multidisciplinary approach to the management of endocarditis.

Aim: The role of malnutrition among patients with severe heart failure (HF) is not well established. We evaluated the incidence, predictors, and prognostic impact of malnutrition in patients with severe HF., Methods and Results: Nutritional status was measured using the geriatric nutritional risk index (GNRI), based on body weight, height and serum albumin concentration, with malnutrition defined as GNRI ≤98. It was assessed in consecutive patients with severe HF, defined by at least one high-risk 'I NEED HELP' marker, enrolled at four Italian centres between January 2020 and November 2021. The primary endpoint was all-cause mortality. A total of 510 patients with data regarding nutritional status were included in the study (mean age 74 ± 12 years, 66.5% male). Among them, 179 (35.1%) had GNRI ≤98 (malnutrition). At multivariable logistic regression, lower body mass index (BMI) and higher levels of natriuretic peptides (B-type natriuretic peptide [BNP] > median value [685 pg/ml] or N-terminal proBNP > median value [5775 pg/ml]) were independently associated with a higher likelihood of malnutrition. Estimated rates of all-cause death at 1 year were 22.4% and 41.1% in patients without and with malnutrition, respectively (log-rank p < 0.001). The impact of malnutrition on all-cause mortality was confirmed after multivariable adjustment for relevant covariates (adjusted hazard ratio 2.03, 95% confidence interval 1.43-2.89, p < 0.001)., Conclusion: In a contemporary, real-world, multicentre cohort of patients with severe HF, malnutrition (defined as GNRI ≤98) was common and independently associated with an increased risk of mortality. Lower BMI and higher natriuretic peptides were identified as predictors of malnutrition in these patients., (© 2024 European Society of Cardiology.)

Aims: Frailty is highly prevalent in patients with heart failure (HF), but a concordant definition of this condition is lacking. The Heart Failure Association of the European Society of Cardiology (HFA-ESC) proposed in 2019 a new multi-domain definition of frailty, but it has never been validated., Methods and Results: Patients from the HELP-HF registry were stratified according to the number of HFA-ESC frailty domains fulfilled and to the cumulative deficits frailty index (FI) quintiles. Prevalence of frailty and of each domain was reported, as well as the rate of the composite of all-cause death and HF hospitalization, its single components, and cardiovascular death in each group and quintile. Among 854 included patients, 37 (4.3%), 206 (24.1%), 365 (42.8%), 217 (25.4%), and 29 (3.4%) patients fulfilled zero, one, two, three, or four domains, respectively, while 179 patients had a FI < 0.21 and were considered not frail. The 1-year risk of adverse events increased proportionally to the number of domains fulfilled (for each criterion increase, all-cause death or HF hospitalization: hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.27-1.62; all-cause death: HR 1.72, 95% CI 1.46-2.02, HF hospitalizations: subHR 1.21, 95% CI 1.04-1.31; cardiovascular death: HR 1.77, 95% CI 1.45-2.15). Consistent results were found stratifying the cohort for FI quintiles. The FI as a continuous variable demonstrated higher discriminative ability than the number of domains fulfilled (area under the curve = 0.68 vs. 0.64, p = 0.004)., Conclusion: Frailty in patients at risk for advanced HF, assessed via a multi-domain approach and the FI, is highly prevalent and identifies those at increased risk of adverse events. The FI was found to be slightly more effective in identifying patients at increased risk of mortality., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Hospitalization is associated with poor outcomes in patients with heart failure, but its prognostic role in advanced heart failure is still unsettled. We evaluated the prognostic role of heart failure hospitalization in patients with advanced heart failure., Methods: The multicenter HELP-HF registry enrolled consecutive patients with heart failure and at least one high-risk 'I NEED HELP' marker. Characteristics and outcomes were compared between patients who were hospitalized for decompensated heart failure (inpatients) or not (outpatients) at the time of enrolment. The primary endpoint was the composite of all-cause mortality or first heart failure hospitalization., Results: Among the 1149 patients included [mean age 75.1 ± 11.5 years, 67.3% men, median left ventricular ejection fraction (LVEF) 35% (IQR 25-50%)], 777 (67.6%) were inpatients at the time of enrolment. As compared with outpatients, inpatients had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 50.9% in inpatients versus 36.8% in outpatients [crude hazard ratio 1.70, 95% confidence interval (CI) 1.39-2.07, P < 0.001]. At multivariable analysis, inpatient status was independently associated with a higher risk of the primary endpoint (adjusted hazard ratio 1.54, 95% CI 1.23-1.93, P < 0.001). Among inpatients, the independent predictors of the primary endpoint were older age, lower SBP, heart failure association criteria for advanced heart failure and glomerular filtration rate 30 ml/min/1.73 m2 or less., Conclusion: Hospitalization for heart failure in patients with at least one high-risk 'I NEED HELP' marker is associated with an extremely poor prognosis supporting the need for specific interventions, such as mechanical circulatory support or heart transplantation., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

In patients with advanced heart failure (HF), defined according to the presence of at least one I-NEED-HELP criterium, the updated 2018 Heart Failure Association of the European Society of Cardiology (HFA-ESC) criteria for advanced HF identify a subgroup of patients with HF with worse prognosis, but whether ischemic etiology has a relevant prognostic impact in this very high-risk cohort is unknown. Patients from the HELP-HF registry were stratified according to ischemic etiology and presence of advanced HF based on 2018 HFA-ESC criteria. The primary end point was a composite of all-cause death and HF hospitalization at 1 year. Secondary end points were all-cause death, HF hospitalization, and cardiovascular death at 1 year. Ischemic etiology was a leading cause of HF, in both patients with advanced and nonadvanced HF (46.1% and 42.4%, respectively, p = 0.337). The risk of the primary end point (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.58) and all-cause mortality (HR 1.37, 95% CI 1.06 to 1.76) was increased in ischemic as compared with nonischemic patients. The risk of the primary end point was consistently higher in ischemic patients in both patients with advanced and nonadvanced HF (advanced HF, HR 1.50 95% CI 1.04 to 2.16; nonadvanced HF, HR 1.25 95% CI 1.01 to 1.56, p interaction  = 0.333), driven by an increased risk of mortality, mainly because of cardiovascular causes. In conclusion, ischemic etiology is the most common cause of HF in patients with at least one I-NEED-HELP marker and with or without advanced HF as defined by the 2018 HFA-ESC definition. In both patients with advanced and not-advanced HF, ischemic etiology carried an increased risk of worse prognosis., Competing Interests: Declaration of Competing Interest Dr. Stolfo reports personal fees from Novartis, Merck, GSK, and Acceleron outside of the submitted work. Dr. Merlo reports personal fees from Pfizer, Novartis, Novo Nordisk, and Vifor Pharma outside of the present work. Dr. Sinagra reports consulting fees from Novartis, Impulse Dynamics, and Biotronik, and speaker and honoraria from Novartis, Bayer, AstraZeneca, Boston Scientific, Vifor Pharma, Menarini, and Akcea Therapeutics outside of the submitted work. Dr. Metra received personal consulting honoraria of minimal amount from Abbott, Amgen, Bayer, Edwards Therapeutics, LivaNova, and Vifor Pharma for participation in advisory board meetings and executive committees of clinical trials. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Heart failure (HF) with preserved ejection fraction (HFpEF) causes a progressive limitation of functional capacity, poor quality of life (QoL) and increased mortality, yet unlike HF with reduced ejection fraction (HFrEF) there are no effective device-based therapies. Both HFrEF and HFpEF are associated with dysregulations in myocardial cellular calcium homeostasis and modifications in calcium-handling proteins, leading to abnormal myocardial contractility and pathological remodelling. Cardiac contractility modulation (CCM) therapy, based on a pacemaker-like implanted device, applies extracellular electrical stimulation to myocytes during the absolute refractory period of the action potential, which leads to an increase in cytosolic peak calcium concentrations and thereby the force of isometric contraction promoting positive inotropism. Subgroup analysis of CCM trials in HFrEF has demonstrated particular benefits in patients with LVEF between 35% and 45%, suggesting its potential effectiveness also in patients with higher LVEF values. Available evidence on CCM in HFpEF is still preliminary, but improvements in terms of symptoms and QoL have been observed. Future large, dedicated, prospective studies are needed to evaluate the safety and efficacy of this therapy in patients with HFpEF., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Permanent His bundle pacing (HBP) is the most physiological pacing modality, and new implantation systems are now available. The aim of the present study was to describe and compare four different techniques to perform HBP., Methods and Results: We included all consecutive patients who underwent a HBP attempt in our initial experience between June 2020 and May 2022. The success and characteristics of the procedure were compared among four implantation techniques: the Biotronik Selectra 3D sheath with Solia S60 lead (Selectra 3D), the Boston Scientific Site Selective Pacing Catheter with Ingevity lead (SSPC), the Abbott steerable stylet locator with Tendril lead (Locator), and the use of a standard stylet manually pre-shaped with a conventional pacing lead (Curved stylet). Ninety-eight patients (median age 79 years [interquartile range, 73-83], 83% men) were identified. The Selectra 3D technique was used in 43 procedures, SSPC in 26, Locator in 18 and Curved stylet in 11. The groups had similar clinical characteristics. Overall, procedural success was achieved in 91 patients (93%) with similar proportions among groups (p = .986). Fluoroscopy and procedural times were 6.0 (4.4-8.5) and 60 (45-75) min, respectively, without significant differences (p = .333 and p = .790). The rate of selective capture, the pacing threshold, and the paced QRS duration were also comparable. There was one pre-discharge HBP lead dislodgment (1%) that required implant revision., Conclusion: In our experience, four techniques for HBP achieved comparable results in terms of safety and effectiveness. The availability of different systems may lead to widespread use of physiological pacing., (© 2023 Wiley Periodicals LLC.)

Inflammation characterizes all stages of atherothrombosis and provides a critical pathophysiological link between plaque formation and its acute rupture, leading to coronary occlusion and heart attack. In the last 20 years the possibility of quantifying the degree of inflammation of atherosclerotic plaques and, therefore, also of vascular inflammation aroused much interest. 18 Fluoro-deoxy-glucose photon-emissions-tomography ( 18 F-FDG-PET) is widely used in oncology for staging and searching metastases; in cardiology, the absorption of 18 F-FDG into the arterial wall was observed for the first time incidentally in the aorta of patients undergoing PET imaging for cancer staging. PET/CT imaging with 18 F-FDG and 18 F-sodium fluoride ( 18 F-NaF) has been shown to assess atherosclerotic disease in its molecular phase, when the process may still be reversible. This approach has several limitations in the clinical practice, due to lack of prospective data to justify their use routinely, but it's desirable to develop further scientific evidence to confirm this technique to detect high-risk patients for cardiovascular events., (© 2022. The Author(s).)

Leadless pacemaker implantation (LPI) has fewer device complications and reduced chance of infection compared to conventional pacemakers. Dextrocardia with situs viscerum inversus (DC+SVI) is a rare condition, which seldom leads to cardiac complications. However, its presence poses a challenge to operators in cardiac procedures. LPI reports in DC patients are scarce. We report a case of LPI in a DC+SVI patient, followed by a brief but comprehensive literature review., (© 2022 Wiley Periodicals LLC.)

In the last years, major progress occurred in heart failure (HF) management. Quadruple therapy is now mandatory for all the patients with HF with reduced ejection fraction. Whilst verciguat is becoming available across several countries, omecamtiv mecarbil is waiting to be released for clinical use. Concurrent use of potassium-lowering agents may counteract hyperkalaemia and facilitate renin-angiotensin-aldosterone system inhibitor implementations. The results of the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trial were confirmed by the Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER) trial, and we now have, for the first time, evidence for treatment of also patients with HF with preserved ejection fraction. In a pre-specified meta-analysis of major randomized controlled trials, sodium-glucose co-transporter-2 inhibitors reduced all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in the patients with HF regardless of left ventricular ejection fraction. Other steps forward have occurred in the treatment of decompensated HF. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload (ADVOR) trial showed that the addition of intravenous acetazolamide to loop diuretics leads to greater decongestion vs. placebo. The addition of hydrochlorothiazide to loop diuretics was evaluated in the CLOROTIC trial. Torasemide did not change outcomes, compared with furosemide, in TRANSFORM-HF. Ferric derisomaltose had an effect on the primary outcome of CV mortality or HF rehospitalizations in IRONMAN (rate ratio 0.82; 95% confidence interval 0.66-1.02; P = 0.070). Further options for the treatment of HF, including device therapies, cardiac contractility modulation, and percutaneous treatment of valvulopathies, are summarized in this article., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)