Strain-derived myocardial work indices in adult cancer survivors: results from an observational study and comparison with available reference ranges Massimiliano Camilli, Federico Ballacci, Priscilla Lamendola, Marcello Viscovo, Giulia Tamburrini, Lorenzo Tinti, Ilaria Torre, Ludovica Amore, Stefan Hohaus, Filippo Crea, Gaetano Antonio Lanza, Francesco Burzotta, Giorgio Minotti, Antonella Lombardo Cardio Oncology, 2025 Adult survivors of haematological malignancies are at increased risk of long-term cardiovascular sequelae. Several echocardiographic metrics have been tested to detect subclinical myocardial dysfunction before it progresses toward cardiac events. Myocardial work (MW) is a load-independent echocardiographic index that conjugates non-invasive arterial blood pressure and global longitudinal strain (GLS). Sixty-three disease-free survivors of Hodgkin Lymphoma (HL) [49% male, median age 42 (33,0–50,5) years], without known cardiovascular disease or reported cardiological symptoms, were included in this observational study. Myocardial work data from cancer survivors were compared with those from healthy subjects recruited in the EACVI NORRE Study. Mean left ventricular ejection fraction and GLS were, respectively, 57,0% (55,0–60,0) and − 18,0% (-19,2–17,1). Global work efficiency [GWE, 96% (94–97)], global work index (GWI, 1732 ± 340 mmHg%) and global wasted work [GWW, 78 (55–131) mmHg%] did not differ between male and female survivors; however, global constructive work (GCW, 2116 ± 386 mmHg%) was lower in males. Of importance, GWI and GCW were lower in cancer survivors compared to healthy subjects from the EACVI NORRE study (p = 0,0008 and p = 0,0324, respectively). When evaluating associations of MW indices with patients’ characteristics, only systolic blood pressure and ejection fraction were independently associated with both GWI and GCW at multivariable analysis. For the first time, this report provides values of MW indices in asymptomatic HL survivors without cardiovascular disease. GWI and GCW were significantly lower in HL survivors compared to healthy subjects. MW metrics might serve as valuable markers of subclinical cardiac dysfunction in this population. Enrollment strategy and main results of the study. This report provides ranges of MW in a homogeneous population of asymptomatic cancer survivors without cardiovascular disease. Moreover, GWI and GCW were significantly lower from those previously reported in healthy volunteers. Legends. CV, cardiovascular; GCW, global constructive work; GLS, global longitudinal strain; GWE, global work efficiency; GWI, global work index; GWW, global wasted work; HL, Hodgkin Lymphoma; KCCQ, Kansas City Cardiomyopathy Questionnaire; LVEF, left ventricular ejection fraction; MW, myocardial work; NT-proBNP, N-terminal pro B-type natriuretic peptide
The effects of race on anti-PD-(L)1 monoclonal antibodies in non-small cell lung cancer: A systematic literature review and meta-analysis Carlo Genova, Federico Cappuzzo, Giorgio Minotti, Nicola Normanno, Barry Rodgers-Gray, Nicola Waghorne, Silvia Novello, Marcello Tiseo Critical Reviews in Oncology Hematology, 2025 INTRODUCTION: Non-small cell lung cancer (NSCLC) represents approximately 85 % of lung cancers, with five-year survival only 4.5 % for metastatic disease. Programmed death (ligand)-1 (PD-[L]1) inhibitors have advanced NSCLC treatment, but patient demographics can potentially affect clinical outcomes. This systematic literature review and meta-analysis were undertaken to determine if the benefits of anti-PD-(L)1 therapies in NSCLC are independent of race (bio-geographic background). METHODS: PubMed, Embase, Cochrane Library and World Health Organization Global Index Medicus were systematically searched (inception-to-Aug-2024). Primary analysis focused on studies with subgroup analysis (White vs Asian, White vs Non-White, Asian vs Non-Asian) of anti-PD-(L)1 efficacy in both resectable/localized and unresectable/advanced NSCLC. Subgroup analysis included stratification by PD-L1 expression, treatment line, and treatment regimen. Bayesian inferential meta-analysis was performed for outcomes with ≥ 1 study. RESULTS: From 4406 records, 22 randomized controlled trials, 3 pooled analyses, and 2 pharmacokinetic studies were included. In unresectable/advanced NSCLC, anti-PD-(L)1 therapy significantly improved overall survival and progression-free survival (PFS) for White (hazard ratio [HR] 0.80; 95 % credible interval [95 % CrI] 0.74-0.87, p < 0.001 and HR 0.68; 95 % CrI 0.61-0.77, p < 0.001, respectively) and Asian (HR 0.81; 95 % CrI 0.69-0.96, p = 0.027 and HR 0.63; 95 % CrI 0.50-0.80, p = 0.002) patients. The significant improvements in PFS were maintained for both groups within all sub-analyses. Limited data prohibited conduction of meta-analysis for resectable/localized NSCLC. CONCLUSIONS: The benefits of anti-PD-(L)1 therapy in unresectable/advanced NSCLC appear similar for White and Asian patients. Increased quality and quantity of data is required to draw definitive conclusions for resectable/localized NSCLC and with respect to treatment line/regimen and PD-L1 expression.
Effects of sodium-glucose cotransporter 2 inhibitors in patients with cancer and diabetes mellitus: a systematic review and meta-analysis Giuseppina Novo, Cristina Madaudo, Antonio Cannatà, Pietro Ameri, Daniela Di Lisi, Daniel I Bromage, Alfredo Ruggero Galassi, Giorgio Minotti, Alexander R Lyon European Heart Journal Cardiovascular Pharmacotherapy, 2025 Aims Cardiovascular disease and cancer represent significant global health challenges. An overlap between oncology and cardiology is compounded by cancer therapies, which are known to have cardiotoxic effects. Sodium–glucose cotransporter 2 inhibitors (SGLT2i), initially developed for treating diabetes, have shown promising cardiovascular benefits in non-cancer populations, particularly in preventing heart failure (HF) and reducing HF-related hospitalization and mortality in large randomized controlled trials (RCTs) across the spectrum of left ventricular ejection fraction. However, their potential cardioprotective role in cancer patients remains unclear. This systematic review and meta-analysis evaluated cardiovascular outcomes in cancer patients with type 2 diabetes undergoing chemotherapy with concomitant use of SGLT2i compared with those not using SGLT2i. Subgroup analyses were performed to explore patients without baseline HF and patients treated exclusively with anthracyclines. Methods and results A systematic review identified 11 observational retrospective studies (n = 104 327 patients). Based on the National Institutes of Health Quality Assessment Tool checklist, two studies were at moderate risk of bias, while all other included studies had a low risk of bias. Meta-analysis indicated that the use of SGLT2i was associated with a significant reduction in all-cause mortality [0.47, 95% confidence interval (CI) 0.33–0.67, P &lt; 0.0001] and risk of HF hospitalization (0.44, 95% CI 0.27–0.72, P = 0.001). Conclusion The use of SGLT2i may be associated with a significant reduction in all-cause mortality and risk of HF hospitalization in actively treated cancer patients with Type 2 diabetes. Our study highlights the need for further investigation through prospective RCTs to confirm the efficacy and safety of SGLT2i in attenuating cardiotoxicity and supporting cardiovascular health in oncology settings.
Advances in Bruton tyrosine kinase (Btk) inhibition are steered by Bruton tyrosine kinase phylogeny Giorgio Minotti, Massimiliano Camilli, Emanuela Salvatorelli, Pierantonio Menna British Journal of Pharmacology, 2025 Bruton tyrosine kinase (Btk) has long been known to play a key role in chronic lymphatic leukaemia, Waldenström macroglobulinaemia and other B‐cell proliferative disorders. An impressive programme of drug discovery and clinical development led to the approval of covalent and non‐covalent Btk inhibitors that became pillars of treatment of such malignancies. However, both a risk of cardiovascular events and the emergence of an elusive mutational landscape seem to complicate the clinical use of each Btk inhibitor. In this plain language mini‐review, we show that the search for better Btk inhibitors is challenged by the ancestral origin of Btk, its homology with innocent kinases in cardiovascular system and unique phylogenetic‐like modalities with which Btk can mutate upon exposure to one inhibitor or another. Whereas basic and clinical pharmacology is already at work to explore new avenues of Btk inhibition, phylogeny remains behind the curtain to steer achievements and failures in this field.
Sodium–glucose cotransporter 2 inhibitors and the cancer patient: from diabetes to cardioprotection and beyond Massimiliano Camilli, Marcello Viscovo, Luca Maggio, Alice Bonanni, Ilaria Torre, Claudio Pellegrino, Priscilla Lamendola, Lorenzo Tinti, Luciana Teofili, Stefan Hohaus, Gaetano Antonio Lanza, Peter Ferdinandy, Zoltan Varga, Filippo Crea, Antonella Lombardo, Giorgio Minotti Basic Research in Cardiology, 2025 Sodium–glucose cotransporter 2 inhibitors (SGLT2i), a new drug class initially designed and approved for treatment of diabetes mellitus, have been shown to exert pleiotropic metabolic and direct cardioprotective and nephroprotective effects that extend beyond their glucose-lowering action. These properties prompted their use in two frequently intertwined conditions, heart failure and chronic kidney disease. Their unique mechanism of action makes SGLT2i an attractive option also to lower the rate of cardiac events and improve overall survival of oncological patients with preexisting cardiovascular risk and/or candidate to receive cardiotoxic therapies. This review will cover biological foundations and clinical evidence for SGLT2i modulating myocardial function and metabolism, with a focus on their possible use as cardioprotective agents in the cardio-oncology settings. Furthermore, we will explore recently emerged SGLT2i effects on hematopoiesis and immune system, carrying the potential of attenuating tumor growth and chemotherapy-induced cytopenias.
Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence Nabil V Sayour, Ágnes M Paál, Pietro Ameri, Wouter C Meijers, Giorgio Minotti, Ioanna Andreadou, Antonella Lombardo, Massimiliano Camilli, Heinz Drexel, Erik Lerkevang Grove, Gheorghe Andrei Dan, Andreea Ivanescu, Anne Grete Semb, Gianluigi Savarese, Dobromir Dobrev, Filippo Crea, Juan-Carlos Kaski, Rudolf A de Boer, Péter Ferdinandy, Zoltán V Varga European Heart Journal, 2024
Cardiac Imaging in Childhood Cancer Survivors: A State-of-the-Art Review Massimiliano Camilli, Roderick Skinner, Giulia Iannaccone, Giulia La Vecchia, Rocco Antonio Montone, Gaetano Antonio Lanza, Luigi Natale, Filippo Crea, Matteo Cameli, Marco Giuseppe Del Buono, Antonella Lombardo, Giorgio Minotti Current Problems in Cardiology, 2023
Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement Joerg Herrmann, Daniel Lenihan, Saro Armenian, Ana Barac, Anne Blaes, Daniela Cardinale, Joseph Carver, Susan Dent, Bonnie Ky, Alexander R Lyon, Teresa López-Fernández, Michael G Fradley, Sarju Ganatra, Giuseppe Curigliano, Joshua D Mitchell, Giorgio Minotti, Ninian N Lang, Jennifer E Liu, Tomas G Neilan, Anju Nohria, Rupal O'Quinn, Iskra Pusic, Charles Porter, Kerry L Reynolds, Kathryn J Ruddy, Paaladinesh Thavendiranathan, Peter Valent European Heart Journal, 2022
In ®Entresto we trust Massimiliano Camilli, Marco Giuseppe Del Buono, Pierantonio Menna, Giorgio Minotti Cardio Oncology, 2020
The cancer patient and cardiology José Luis Zamorano, Christer Gottfridsson, Riccardo Asteggiano, Dan Atar, Lina Badimon, Jeroen J. Bax, Daniela Cardinale, Antonella Cardone, Elizabeth A.M. Feijen, Péter Ferdinandy, Teresa López‐Fernández, Chris P. Gale, John H. Maduro, Javid Moslehi, Torbjørn Omland, Juan Carlos Plana Gomez, Jessica Scott, Thomas M. Suter, Giorgio Minotti European Journal of Heart Failure, 2020
Cardio-oncology care in the era of the coronavirus disease 2019 (COVID-19) pandemic: An International Cardio-Oncology Society (ICOS) statement Daniel Lenihan, Joseph Carver, Charles Porter, Jennifer E. Liu, Susan Dent, Paaladinesh Thavendiranathan, Joshua D. Mitchell, Anju Nohria, Michael G. Fradley, Iskra Pusic, Keith Stockerl‐Goldstein, Anne Blaes, Alexander R. Lyon, Sarju Ganatra, Teresa López‐Fernández, Rupal O'Quinn, Giorgio Minotti, Sebastian Szmit, Daniela Cardinale, Jose Alvarez‐Cardona, Giuseppe Curigliano, Tomas G. Neilan, Joerg Herrmann CA Cancer Journal for Clinicians, 2020
Cardio-oncological management of patients Daniela M. Cardinale, Ana Barac, Adam Torbicki, Bijoy K. Khandheria, Daniel Lenihan, Giorgio Minotti Seminars in Oncology, 2019
Cardiovascular events in cancer survivors Emily Howard, Richard M. Steingart, Gregory T. Armstrong, Alexander R. Lyon, Saro H. Armenian, Maria Teresa Voso, Laura Cicconi, Francesco Lo Coco, Giorgio Minotti Seminars in Oncology, 2019
Practical management of ibrutinib in the real life: Focus on atrial fibrillation and bleeding Giuseppe Boriani, Paolo Corradini, Antonio Cuneo, Anna Falanga, Robin Foà, Gianluca Gaidano, Paolo Prospero Ghia, Maurizio Martelli, Roberto Marasca, Massimo Massaia, Francesca Romana Mauro, Giorgio Minotti, Stefano Molica, Marco Montillo, Antonio Pinto, Alessandra Tedeschi, Umberto Vitolo, Pier Luigi Zinzani Hematological Oncology, 2018
Early diagnosis of acute coronary syndrome Hugo Katus, André Ziegler, Okan Ekinci, Evangelos Giannitsis, Wendy Gattis Stough, Stephan Achenbach, Stefan Blankenberg, Martina Brueckmann, Paul Collinson, Dorin Comaniciu, Filippo Crea, Wilfried Dinh, Grégory Ducrocq, Frank A. Flachskampf, Keith A. A. Fox, Matthias G. Friedrich, Kathy A. Hebert, Anders Himmelmann, Mark Hlatky, Dominik Lautsch, Bertil Lindahl, Daniel Lindholm, Nicholas L. Mills, Giorgio Minotti, Martin Möckel, Torbjørn Omland, Véronique Semjonow European Heart Journal, 2017
2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC) Jose Luis Zamorano, Patrizio Lancellotti, Daniel Rodriguez Muñoz, Victor Aboyans, Riccardo Asteggiano, Maurizio Galderisi, Gilbert Habib, Daniel J. Lenihan, Gregory Y. H. Lip, Alexander R. Lyon, Teresa Lopez Fernandez, Dania Mohty, Massimo F. Piepoli, Juan Tamargo, Adam Torbicki, Thomas M. Suter, Jose Luis Zamorano, Victor Aboyans, Stephan Achenbach, Stefan Agewall, Lina Badimon, Gonzalo Barón-Esquivias, Helmut Baumgartner, Jeroen J. Bax, Héctor Bueno, Scipione Carerj, Veronica Dean, Çetin Erol, Donna Fitzsimons, Oliver Gaemperli, Paulus Kirchhof, Philippe Kolh, Patrizio Lancellotti, Gregory Y. H. Lip, Petros Nihoyannopoulos, Massimo F. Piepoli, Piotr Ponikowski, Marco Roffi, Adam Torbicki, António Vaz Carneiro, Stephan Windecker European Journal of Heart Failure, 2017
Anthracyclines. Luca Gianni, Giacomo Grasselli, Sara Cresta, Alberta Locatelli, Lucia Viganò, Giorgio Minotti Cancer Chemotherapy and Biological Response Modifiers, 2003
Anthracyclines. Cancer Chemotherapy and Biological Response Modifiers, 2002
Doxorubicin irreversibly inactivates iron regulatory proteins 1 and 2 in cardiomyocytes: Evidence for distinct metabolic pathways and implications for iron-mediated cardiotoxicity of antitumor therapy Cancer Research, 2001
γ-Glutamyl transpeptidase-dependent iron reduction and LDL oxidation - A potential mechanism in atherosclerosis Journal of Investigative Medicine, 1999
Erratum: The secondary alcohol metabolite of doxorubicin irreversibly inactivates aconitase/iron regulatory protein-1 in cytosolic fractions from human myocardium (The FASEB Journal 12 (541-552)) FASEB Journal, 1998
Superoxide and hydrogen peroxide dependent inhibition of iron regulatory protein activity: A protective stratagem against oxidative injury Journal of Investigative Medicine, 1996
Novel mechanisms for the inhibition of low density lipoprotein oxidation by ascorbic acid Journal of Investigative Medicine, 1996
Vitamin e inhibits enhanced f2-isoprostane biosynthesis in type iia hypercholesterolemia Journal of Investigative Medicine, 1996
Secondary alcohol metabolites mediate iron delocalization in cytosolic fractions of myocardial biopsies exposed to anticancer anthracyclines: Novel linkage between anthracycline metabolism and iron-induced cardiotoxicity Journal of Clinical Investigation, 1995
Fe(II) oxidation and Fe(III) incorporation by the Mr 66,000 microsomal iron protein that stimulates NADPH oxidation Journal of Biological Chemistry, 1992
