ANMCO-SICPED consensus document on cardio-oncological transition in childhood cancer survivors Elena Bennati, Maria Laura Canale, Alice Pozza, Stefano Oliva, Andrea Tedeschi, Alessandra Greco, Gabriele Egidy Assenza, Anna Balducci, Maria Elena Derchi, Rachele Adorisio, Marcello Chinali, Massimo Chessa, Domenico Gabrielli, Silvia Favilli, Furio Colivicchi, Federico Nardi, Massimo Grimaldi, Fabrizio Oliva, Gabriele Rinelli Giornale Italiano Di Cardiologia, 2026 Nelle ultime decadi la sopravvivenza dei pazienti trattati per tumore pediatrico è notevolmente migliorata, ma tra i lungosopravviventi la malattia cardiovascolare rappresenta la prima causa non oncologica di morbilità e mortalità. La popolazione dei bambini, adolescenti e giovani adulti (childhood, adolescent, and young adult, CAYA) sopravvissuti al cancro è in aumento e presenta un maggior rischio cardiovascolare, per cui necessita di una sorveglianza cardiovascolare a lungo termine per identificare precocemente una cardiotossicità tardiva e iniziare un trattamento tempestivo. Per evitare la dispersione al follow-up e attuare strategie preventive personalizzate, è fondamentale assicurare il processo di transizione e il trasferimento delle cure dall’ospedale pediatrico a quello dell’adulto. Questo documento nasce dalla collaborazione tra ANMCO e SICPED per garantire la continuità di cure dei CAYA e promuovere percorsi di transizione, ancora poco strutturati nel nostro Paese, nonostante le linee guida internazionali.
SGLT2 Inhibitor Dapagliflozin Attenuates Cardiomyocyte Injury and Inflammation Induced by PI3Kα-Selective Inhibitor Alpelisib and Fulvestrant Under Hyperglycemia Vincenzo Quagliariello, Massimiliano Berretta, Matteo Barbato, Fabrizio Maurea, Maria Laura Canale, Andrea Paccone, Irma Bisceglia, Andrea Tedeschi, Marino Scherillo, Jacopo Santagata, Stefano Oliva, Christian Cadeddu Dessalvi, Pietro Forte, Cristiana D’Ambrosio, Tiziana Di Matola, Regina Parmentola, Domenico Gabrielli, Nicola Maurea International Journal of Molecular Sciences, 2026 Activating PIK3CA mutations occur in approximately 40% of hormone receptor-positive (HR+)/HER2-negative breast cancers and represent a major driver of endocrine resistance. The PI3Kα-selective inhibitor alpelisib, in combination with fulvestrant, significantly improves progression-free survival in patients with PIK3CA-mutant disease, as demonstrated in the SOLAR-1 trial. However, this therapeutic strategy is frequently complicated by treatment-induced hyperglycemia, a metabolic disturbance that promotes oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby increasing cardiovascular vulnerability. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as cardiometabolic modulators with benefits extending beyond glucose lowering. In this study, we used a human cardiomyocyte in vitro model designed to recapitulate the hyperglycemic metabolic milieu observed in breast cancer patients receiving PI3Kα-targeted therapy, to investigate whether the SGLT2 inhibitor dapagliflozin directly protects cardiomyocytes from alpelisib- and fulvestrant-induced injury. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured under hyperglycemic conditions (25 mM glucose) to mimic the metabolic environment associated with PI3Kα inhibitor-induced dysglycemia. Cells were exposed to alpelisib (100 nM) and fulvestrant (100 nM), alone or in combination, in the absence or presence of dapagliflozin (1 μM). Cardiomyocyte viability was assessed using the MTS assay, mitochondrial function by TMRM-based mitochondrial membrane potential (ΔΨm) measurements, and apoptosis by caspase-3 quantification. Cardiomyocyte injury was evaluated by release of cardiac troponin I and heart-type fatty acid binding protein (H-FABP). Lipid peroxidation markers (MDA and 4-HNE) were measured to assess oxidative membrane damage. Intracellular inflammasome-related signaling (NLRP3 and MyD88) and secreted inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2) were quantified by ELISA. Exposure to alpelisib, particularly in combination with fulvestrant, significantly reduced cardiomyocyte viability, induced mitochondrial depolarization, and increased caspase-3-mediated apoptotic signaling. These alterations were accompanied by elevated lipid peroxidation (MDA and 4-HNE) and increased release of cardiac injury biomarkers (troponin I and H-FABP). Alpelisib-based treatments also activated inflammasome-related signaling, as indicated by increased intracellular NLRP3 and MyD88 levels and enhanced secretion of pro-inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2). Co-treatment with dapagliflozin significantly attenuated these alterations, preserving mitochondrial membrane potential, reducing apoptotic signaling, limiting oxidative membrane damage, and suppressing inflammatory cytokine release. This study provides evidence that alpelisib-based therapy under hyperglycemic conditions is associated with oxidative, mitochondrial, and inflammatory stress responses in human cardiomyocytes, recapitulating key features of cardiometabolic stress relevant to PI3Kα-targeted therapy. Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy.
Cardiogenetics in Piacenza: Integrated care and telemedicine for precision medicine Francesco Di Spigno, Francesca Gualandi, Alessandro Arata, Miryam Rosa Stella Foti, Andrea Tedeschi, Federico Breviario, Luigi Gerra, Benedetta Annamaria Matrone, Paola Novara, Daniela Aschieri Giornale Italiano Di Cardiologia, 2026 Razionale. La cardiogenetica consente l’identificazione delle cause genetiche delle malattie cardiache ereditarie, con implicazioni rilevanti per la diagnosi precoce, la gestione clinica e la prevenzione della morte cardiaca improvvisa nei pazienti e nei loro familiari. In Italia, tuttavia, l’accesso a percorsi strutturati è disomogeneo e spesso limitato ai centri di terzo livello, con ostacoli legati anche alla sostenibilità economica del sistema.Materiali e metodi. È stato sviluppato un modello ambulatoriale di secondo livello che integra la telemedicina per favorire l’accesso alle indagini genetiche. Il percorso si articola in counseling genetico pre-test condotto dal cardiologo sulla base del fenotipo clinico, analisi molecolare con invio del campione biologico alla U.O.C. di Genetica Medica di Ferrara e counseling post-test realizzato come teleconsulto, con la partecipazione remota del genetista tramite piattaforma dedicata (c4C Dedalus). In caso di risultato positivo è prevista una valutazione in presenza presso la U.O. di Cardiologia di Piacenza, mentre in caso di test negativo o presenza di varianti di significato incerto il paziente viene rivalutato per eventuali approfondimenti fenotipici o familiari.Risultati. Nel primo anno di attività sono stati sottoposti ad analisi genetica 78 probandi e 20 familiari di primo grado. I tassi di positività, comprensivi dei casi con varianti rilevanti di significato incerto, sono risultati pari a 44% per la cardiomiopatia ipertrofica, 75% per la cardiomiopatia non dilatativa del ventricolo sinistro, 20% per la cardiomiopatia dilatativa, 100% per la cardiomiopatia aritmogena del ventricolo destro, 100% per la sindrome del QT lungo e 50% per la sindrome di Brugada.Conclusioni. Il modello proposto dimostra come la telemedicina possa rappresentare uno strumento efficace e sostenibile per estendere l’accesso alla consulenza genetica specialistica anche in contesti periferici, migliorando l’equità dell’assistenza e ottimizzando le risorse dedicate alla gestione delle cardiomiopatie ereditarie.
Cardiopulmonary Exercise Testing and HFpEF: Diagnostic and Therapeutic Perspectives Francesco Di Spigno, Valeria Dall’Ospedale, Luigi Gerra, Federico Breviario, Andrea Tedeschi, Giancarlo Trimarchi, Daniela Aschieri Healthcare Switzerland, 2025 Background: Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome that represents an increasing global health challenge due to its high rates of morbidity, hospitalization, and mortality. In this context, cardiopulmonary exercise testing (CPET) has emerged as a valuable diagnostic modality, particularly in patients presenting with unexplained exertional dyspnea and inconclusive resting imaging results. Objectives and Clinical Implications: This narrative review examines current evidence on the clinical relevance and prognostic value of CPET parameters in HFpEF. Peak VO2, a marker of aerobic capacity and cardiovascular fitness, has established prognostic value in heart failure with reduced ejection fraction (HFrEF). However, its prognostic significance in HFpEF remains less well defined. Oxygen pulse has emerged as another important measure for evaluating functional capacity and predicting response to exercise-based interventions, offering potential prognostic insight into adverse outcomes in HFpEF. Finally, the VE/VCO2 slope, an index of ventilatory efficiency during exercise, also holds clinical relevance in HFpEF, particularly with concomitant pulmonary hypertension, though evidence remains heterogeneous. Conclusions: CPET-derived variables are valuable parameters for HFpEF assessment. Their systematic integration into clinical evaluation of HFpEF patients could guide individualized management strategies and inform clinicians for improving outcomes in this challenging condition.
SGLT2i Dapagliflozin in primary prevention of chemotherapy induced cardiotoxicity in breast cancer patients treated with neo-adjuvant anthracycline-based chemotherapy +/- trastuzumab: rationale and design of the multicenter PROTECT trial A. Greco, V. Quagliariello, G. Rizzo, A. Tedeschi, S. Schirinzi, A. Turco, M. Galiazzo, M. Acquaro, M. De Amicis, C. Klersy, S. Ghio, L. Perrone, A. Paccone, G. Uccello, M. L. Canale, S. Oliva, F. Guerra, L. De Luca, N. Maurea, L. Scelsi Cardio Oncology, 2025 BACKGROUND: SGLT2i exerts several cardiometabolic benefits in heart failure with reduced and preserved ejection fraction through the systemic reduction of insulin, visceral fat, chemokines and growth factors involved in cardiovascular diseases. Anthracyclines are considered the principal culprit drugs behind chemotherapy-induced cardiotoxicity. The pathognomonic manifestation of anthracycline-induced cardiotoxicity is a hypokinetic cardiomyopathy progressively leading to heart failure. Anthracycline-induced cardiotoxicity is still a significant problem that compromises the quality of life and overall survival of breast cancer (BC) patients. Sequential therapy regimen of anthracyclines and HER-2 blocking agents is associated to higher risk of cardiotoxicity compared to monotherapy regimen. Recent studies in preclinical models of anthracycline-induced cardiotoxicity concluded that SGLT2i are able to prevent ejection fraction reduction and myocardial inflammation and fibrosis. A very recent retrospective study indicates that SGLT2i were associated with lower rate of cardiac events among patients with cancer and T2DM who were treated with anthracyclines. These data support the conducting of a randomized clinical trial testing Dapagliflozin in patients with breast cancer treated with anthracyclines+/- trastuzumab. OBJECTIVE: To evaluate the cardioprotective effects of the SGLT2 inhibitor Dapagliflozin in chemotherapy-naive patients with stage I-III breast cancer undergoing anthracycline-based treatment with or without trastuzumab, by assessing its ability to reduce the incidence of cardiotoxicity and improve systemic cardiometabolic markers. METHODS: Chemotherapy-naive patients (18-70 years) scheduled for antracycline +/- trastuzumab treatment in the [neo-]adjuvant setting for stage I-III breast cancer, will be randomized using a web-based system stratified by the use of trastuzumab to follow a chemotherapy regimen plus Dapagliflozin [10 mg/die] [active group] or chemotherapy regimen plus standard of care [control group]. During follow up period, if a patient develops asymptomatic or symptomatic systolic disfunction will be treated according to good clinical practice. From randomization, to the third, sixth, twelfth and eighteenth months, echocardiographic and cardiological visits will be performed associated to blood analysis for quantification of cardiotoxicity biomarkers (NT-pro-BNP, hsTNI), CKD-EPI eGFR and systemic inflammation (hsCRP, chemokines, cytokines and growth factors). RESULTS: The study is ongoing. Results will be published when the study is completed. CONCLUSION: The PROTECT trial is the first randomized clinical study designed to evaluate whether Dapagliflozin can reduce anthracycline- and/or trastuzumab-associated cardiotoxicity in patients with early-stage breast cancer. Beyond its established cardiometabolic effects, this trial will also provide insight into the systemic anti-inflammatory and metabolic benefits of SGLT2 inhibition in the oncology setting. Findings from this study may pave the way for novel cardio-oncology strategies aimed at improving both cardiac outcomes and quality of life in cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT06341842 [EudraCT Number 2022-003377-28]. Registered on 19 March 2024.
Advancing Heart Failure Care: Breakthroughs and Emerging Strategies Andrea Tedeschi, Federico Barocelli, Luigi Gerra, Federico Breviario, Matteo Palazzini, Nicolina Conti, Stefano Ferraro, Maria Giulia Bolognesi, Francesco Di Spigno, Piero Gentile, Andrea Garascia, Enrico Ammirati, Giulia Magnani, Giampaolo Niccoli, Nuccia Morici, Daniela Aschieri Journal of Clinical Medicine, 2025 Heart failure represents a complex clinical syndrome characterized by progressive ventricular dysfunction, systemic congestion, and high mortality despite significant advances in pharmacological and device-based therapy. This review explores recent developments across the heart failure continuum, with a focus on therapeutic advances across the continuum of care, with emphasis on both established and emerging strategies. In patients with reduced ejection fraction, early initiation of the four pillars markedly lowers cardiovascular events, yet real-world implementation remains limited by therapeutic inertia and underdosing. Novel agents such as finerenone provide cardiorenal benefits in patients with diabetes and chronic kidney disease, while glucagon-like peptide-1 receptor agonists show promise in preserved or mildly reduced ejection fraction, particularly with obesity. Tricuspid regurgitation, once considered a secondary phenomenon, is now recognized as a modifiable contributor to disease progression, with transcatheter interventions offering new therapeutic avenues. In advanced disease, innovations including donation after circulatory death and the development of total artificial heart systems offer promising solutions to overcome organ shortages and improve access to transplantation. Together, these advances highlight a shift toward precision-guided, multidisciplinary heart failure care.
Long-Term Cardiovascular Toxicity of Immunotherapy: Too Important to Ignore Andrea Camerini, Alessandro Inno, Maria Laura Canale, Stefano Oliva, Andrea Tedeschi, Alessandra Greco, Marzia De Biasio, Nicola Maurea, Irma Bisceglia, Luigi Tarantini, Giuseppina Gallucci, Carmine Riccio, Giovanna Geraci, Claudio Bilato, Alessandro Navazio, Attilio Iacovoni, Furio Colivicchi, Massimo Grimaldi, Fabrizio Oliva International Journal of Molecular Sciences, 2025 Immunotherapy improved survival in a significant number of cancer patients as never before. Its benefits spread across cancer types and stages, and new drugs, new combination, and new indications are on the way. Both atherosclerosis and cancer are associated with the same risk factors, molecular processes, and a persistent inflammatory state that is attributed to immune system dysregulation. Clinicians are now facing a new category of patients that are long survivors/cured by immunotherapy. While short-to-medium-term side effects of immunotherapy are well characterized, long-term exposure to immune checkpoint inhibitors could be associated with new and unpredicted toxicity with a potential impact on survival, reducing the clear advantage of immunotherapy. Because of this, it is clear that the worsening of atherosclerosis emerges as the most relevant long-term side effect, translating into an increased incidence of atherosclerosis-related cardiovascular events, such as myocardial infarction, ischemic stroke, and peripheral artery disease. We review the available evidence of this relevant association, providing an overview for all clinicians involved in the multidisciplinary cancer care process.
How to facilitate smoking cessation Furio Colivicchi, Stefania Angela Di Fusco, Vered Gil Ad, Silvia Castelletti, Luigi Pollarolo, Maria Laura Canale, Simona Giubilato, Roberta Rossini, Stefano Oliva, Andrea Tedeschi, Alessandra Greco, Myriam Rita Intravaia, Francesco Antonio Veneziano, Piero Clavario, Claudio Bilato, Marco Corda, Giovanna Geraci, Attilio Iacovoni, Alessandro Navazio, Federico Nardi, Domenico Gabrielli, Massimo Grimaldi, Fabrizio Oliva Progress in Cardiovascular Diseases, 2025
The first data of the TeleCuore project A. Tedeschi, P. Novara, B. Matrone, Evelina Cattadori, G. Lisè, F. Di Spigno, F. Breviario, Luigi Gerra, C. Sticozzi, M. Pisati, N. Ballerio, Daniela Aschieri Giornale Italiano Di Cardiologia, 2025 BACKGROUND Telemedicine is an innovative and impactful resource in the management of heart failure. At the Cardiology Department of the Piacenza Hospital, a pilot telemedicine project called "TeleCuore" has been launched, aimed at patients with heart failure. This article describes the organizational model adopted and the initial results of TeleCuore regarding its clinical impact and patient satisfaction. METHODS The project involved patients with de novo heart failure or those in outpatient follow-up with recent episodes of clinical instability and adequate digital skills. A multidisciplinary team, coordinated by a case manager nurse, managed patient monitoring and education. Using the AdiLife platform and multiparametric devices, vital and clinical parameters were monitored over time, with alert analysis by nurses and technicians in cardiocirculatory pathophysiology and cardiovascular perfusion, with continuous support from the cardiology medical staff. In addition to being monitored to detect potential instabilities early and optimize therapies, patients were subjected to questionnaires to measure the project's impact on satisfaction, disease awareness, and difficulties in using the equipment. RESULTS Overall, 257 patients completed at least 6 months of follow-up. Of these, 32 (12.5%) showed signs of heart failure. In 18 cases (56.2%), TeleCuore allowed for the early detection of instability, enabling outpatient management. A total of 14 patients (43.8%) were sent to the emergency department, 10 of whom were referred following parametric anomalies associated with symptoms identified during telephone interviews. Only 5 patients (15.6%) required hospitalization. During the follow-up, an increase in the use of guideline-recommended therapies was observed. The questionnaires highlighted a positive impact of TeleCuore on monitoring, therapy management, and the doctor-patient relationship. CONCLUSIONS TeleCuore has demonstrated the feasibility, appreciation, and effectiveness of managing heart failure through telemedicine, with benefits in reducing hospitalizations, optimizing therapies, and increasing disease awareness.
SGLT2 Inhibitors in Cancer Patients: A Comprehensive Review of Clinical, Biochemical, and Therapeutic Implications in Cardio-Oncology Alessandra Greco, Maria Laura Canale, Vincenzo Quagliariello, Stefano Oliva, Andrea Tedeschi, Alessandro Inno, Marzia De Biasio, Irma Bisceglia, Luigi Tarantini, Nicola Maurea, Alessandro Navazio, Marco Corda, Attilio Iacovoni, Furio Colivicchi, Massimo Grimaldi, Fabrizio Oliva International Journal of Molecular Sciences, 2025 Patients with active cancer and cancer survivors are at a markedly increased risk for developing cardiovascular comorbidities, including heart failure, coronary artery disease, and renal dysfunction, which are often compounded by the cardiotoxic effects of cancer therapies. This heightened cardiovascular vulnerability underscores the urgent need for effective, safe, and evidence-based cardioprotective strategies to reduce both cardiovascular morbidity and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), a class of drugs originally developed for the treatment of type 2 diabetes, have demonstrated significant cardiovascular and renal benefits in high-risk populations, independent of glycemic control. Among the currently available SGLT2i, such as empagliflozin, canagliflozin, dapagliflozin, and sotagliflozin, there is growing evidence supporting their role in reducing major adverse cardiovascular events (MACEs), hospitalization for heart failure, and the progression of chronic kidney disease. Recent preclinical and clinical data suggest that SGLT2is exert cardioprotective effects through multiple mechanisms, including the modulation of inflammasome activity, specifically by reducing NLRP3 inflammasome activation and MyD88-dependent signaling, which are critical drivers of cardiac inflammation and fibrosis. Moreover, SGLT2is have been shown to enhance mitochondrial viability in cardiac cells, promoting improved cellular energy metabolism and function, thus mitigating cardiotoxicity. This narrative review critically evaluates the emerging evidence on the cardiorenal protective mechanisms of SGLT2is, with a particular focus on their potential role in cardio-oncology. We explore the common pathophysiological pathways between cardiovascular dysfunction and cancer, the molecular rationale for the use of SGLT2is in cancer patients, and the potential benefits in both primary and secondary prevention of cardiovascular toxicity related to oncological treatments. The aim is to propose a therapeutic paradigm utilizing SGLT2is to reduce cardiovascular mortality, MACE, and the burden of cardiotoxicity in high-risk oncology patients, fostering an integrated approach to cardio-oncology care.
Impact of biological sex on heart transplant patients admitted to cardiac rehabilitation: A 10-year retrospective cohort study Andrea Tedeschi, Ignazio Cusmano, Francesca Di Salvo, Letizia Oreni, Anastasia Toccafondi, Monica Tavanelli, Paola Grati, Luca Mapelli, Luisa Arrondini, Gianmarco Cannadoro, Matteo Gonella, Chiara Barcella, Leone Stilo, Alessandro Verde, Gabriella Masciocco, Giacomo Ruzzenenti, Marco Biolcati, Andrea Garascia, Nuccia Morici International Journal of Cardiology Cardiovascular Risk and Prevention, 2024
Atherosclerosis, cancer, and immune checkpoint inhibitors M. Canale, Alessandra Greco, A. Inno, Andrea Tedeschi, M. De Biasio, Stefano Oliva, I. Bisceglia, N. Maurea, Luigi Tarantini, G. Gallucci, M. Gulizia, F. Turazza, Fabiana Lucà, S. D. Di Fusco, C. Riccio, A. Navazio, Leonardo De Luca, D. Gabrielli, F. Colivicchi, Massimo Grimaldi, Fabrizio Oliva Giornale Italiano Di Cardiologia, 2024
Pheochromocytoma-induced cardiogenic shock: A multicentre analysis of clinical profiles, management and outcomes Elena De Angelis, Thomas Bochaton, Enrico Ammirati, Andrea Tedeschi, Maria Vincenza Polito, Maurizio Pieroni, Marco Merlo, Piero Gentile, Caroline M. Van De Heyning, Thalia Bekelaar, Alberto Cipriani, Massimiliano Camilli, Tommaso Sanna, Martina Perazzolo Marra, Aderville Cabassi, Massimo F. Piepoli, Gianfranco Sinagra, Nathan Mewton, Eric Bonnefoy-Cudraz, Amelia Ravera, Ahmad Hayek International Journal of Cardiology, 2023