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In an era with the increasing use of various imaging modalities including echocardiography, ventriculography and cardiac magnetic resonance (CMR) imaging, one must be aware of the limitations of each discipline. We report a case of an individual who presented with both a partial dehiscence of a mitral valve annuloplasty ring and an aorta-left atrium fistula following surgical management of infective endocarditis that was correctly identified using transesophageal echocardiographic imaging. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are associated with an increased risk of major adverse cardiovascular events (MACE). Glucagon-like peptide-1 agonists (GLP1a), initially developed for type 2 diabetes mellitus (T2DM), have shown promising results in reducing cardiovascular events. We aimed to investigate the effect of GLP1a on cardiovascular events in patients receiving ICIs., Methods: We conducted a retrospective, propensity score-matched cohort study using the TriNetX database. We identified adults with cancer and T2DM who received ICIs between April 2013 and May 2023. The primary efficacy outcome was incident MACE, defined as a composite of myocardial infarction, need for coronary revascularization, heart failure, ischemic stroke, and cardiac arrest. The secondary efficacy outcomes were the individual components of MACE as well as myocarditis and pericarditis. Safety outcomes included the occurrence of immune-related adverse events, serious adverse events related to GLP1a use, and all-cause mortality., Results: We identified 7651 patients eligible for inclusion, among which 479 received GLP1a and 7172 received non-GLP1a diabetes medications. After matching (469 patients each), baseline characteristics were well-balanced. Over a median 12-month follow-up, the GLP1a cohort had a significantly lower MACE incidence than the non-GLP1a cohort (9.0 vs. 17.1 events per 100 patient-years) with a 54 % lower risk of MACE (Hazard ratio (HR),0.46 [95 % CI: 0.32-0.67]). There were reductions in myocardial infarction or need for coronary revascularization, heart failure, and all-cause mortality, with no differences in other cardiovascular events. GLP1a use did not increase risk of adverse events, including pancreatitis, biliary disease, bowel obstruction, gastroparesis, and immune-related adverse events., Conclusion: GLP1a use in cancer patients with T2DM receiving ICIs was associated with reduced MACE and all-cause mortality without an increased risk in serious adverse events., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Neilan reported receipt of personal fees for consulting from Bristol Myers Squibb, Genentech, Roivant, Roche, and Sanofi, and receipt of grants from Bristol Myers Squibb, Abbott, and AstraZeneca. Dr Neilan is supported by a gift from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, and a Hassenfeld Scholar Award and has additional grant funding from the National Institutes of Health/NHLBI (R01HL137562, K24HL150238). Dr. Reynolds is on the Advisory Board of Regeneron and SAGA Diagnostics. Dr. Reynolds has received educational fees from MedScape and CME Outfitters and research support from Bristol Myers Squibb. The remaining authors have nothing to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The development of novel treatments has improved cancer outcomes but may result in cardiovascular toxicities. Traditional approaches to clinical trial safety evaluation have limitations in their ability to detect signals of cardiovascular risk. Mechanisms to increase power and specificity to clarify cardiovascular safety are required. However, implications include increased costs and slower development. The Cardiovascular Safety Research Consortium facilitated stakeholder discussions with representation from academia, industry, and regulators. A think tank was assembled with the aim of providing recommendations for improved collection and reporting of cardiovascular safety signals in oncology trials. Two working groups were formed. The first focuses on incorporation of consensus definitions of cardiovascular disease into the Common Terminology Criteria for Adverse Events used in oncology trial reporting. The second group considers methods for ascertainment and adjudication of cardiovascular events in cancer trials. The overarching aim of this primer is to improve understanding of the potential cardiovascular toxicities of cancer therapies., Competing Interests: Funding Support and Author Disclosures Dr Bonaca has received support from the American Heart Association SFRN under award numbers 18SFRN3390085 (BWH-DH SFRN Center) and 18SFRN33960262 (BWH-DH Clinical Project). Dr Lang is supported by British Heart Foundation Centre of Research Excellence Award RE/18/6/34217. Dr Deswal is supported in part by the Ting Tsung and Wei Fong Chao Distinguished Chair. Dr Moslehi is supported by National Institutes of Health grants R01HL141466, R01HL155990, R01HL156021, R01HL160688, and R01HL170038. Dr Bonaca is the executive director of CPC Clinical Research, a nonprofit academic research organization affiliated with the University of Colorado; has received research grant/consulting funding between August 2021 and present from: Abbott Laboratories, Agios Pharmaceuticals, Inc, Alexion Pharma, Alnylam Pharmaceuticals, Inc, Amgen Inc, Angionetics, Inc, Anthos Therapeutics, ARCA Biopharma, Inc, Array BioPharma, Inc, AstraZeneca and Affiliates, Atentiv LLC, Audentes Therapeutics, Inc, Bayer and Affiliates, Beth Israel Deaconess Medical Center, Better Therapeutics, Inc, Boston Clinical Research Institute, Bristol-Meyers Squibb Company, Cambrian Biopharma, Inc, Cardiol Therapeutics Inc, CellResearch Corp, Cleerly Inc, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc, EP Trading Co Ltd, EPG Communication Holdings Ltd, Epizon Pharma, Inc, Esperion Therapeutics, Inc, Everly Well, Inc, Exicon Consulting Pvt Ltd, Faraday Pharmaceuticals, Inc, Foresee Pharmaceuticals Co Ltd, Fortress Biotech, Inc, HDL Therapeutics Inc, HeartFlow Inc, Hummingbird Bioscience, Insmed Inc, Ionis Pharmaceuticals, IQVIA Inc, Janssen and Affiliates, Kowa Research Institute, Inc, Kyushu University, Lexicon Pharmaceuticals, Inc, Medimmune Ltd, Medpace, Merck & Affiliates, Nectero Medical Inc, Novartis Pharmaceuticals Corp, Novo Nordisk, Inc, Osiris Therapeutics Inc, Pfizer Inc, PhaseBio Pharmaceuticals, Inc, PPD Development, LP, Prairie Education and Research Cooperative, Prothena Biosciences Limited, Regeneron Pharmaceuticals, Inc, Regio Biosciences, Inc, Saint Luke’s Hospital of Kansas City, Sanifit Therapeutics S.A., Sanofi-Aventis Groupe, Silence Therapeutics PLC, Silence, Smith & Nephew plc, Stanford Center for Clinical Research, Stealth BioTherapeutics Inc, State of Colorado CCPD Grant, The Brigham & Women's Hospital, Inc, The Feinstein Institutes for Medical Research, Thrombosis Research Institute, University of Colorado, University of Pittsburgh, VarmX, Virta Health Corporation, Worldwide Clinical Trials Inc, WraSer, LLC, and Yale Cardiovascular Research Group. Dr Lang has received research grants from Roche Diagnostics, AstraZeneca, and Boehringer Ingelheim; and consultancy/speaker fees from Roche Diagnostics, Myokardia, Pharmacosmos, Akero Therapeutics, CV6 Therapeutics, Jazz Pharma, and Novartis outside the submitted work. Dr Chen reports that the National Cancer Institute has Cooperative Research and Development Agreements with Genentech and AstraZeneca for trials in which she is the principal investigator. Dr Lipka is an employee of Merck & Co; and owns stock in Merck & Co. Dr Janicijevic is employee of F. Hoffmann-La Roche Ltd, Basel, Switzerland; and has nonvoting shares in F. Hoffmann-La Roche. Dr Herrmann has served on advisory boards for AstraZeneca, Astellas, and Pfizer. Dr de Boer has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Novo Nordisk, and Roche; and has had speaker engagements with and/or received fees from Abbott, AstraZeneca, Bristol Myers Squibb, Cardior Pharmaceuticals GmbH, Novartis, and Roche. Dr Deswal has received research support from the NIH and CPRIT; and consultancy fees from Bayer. Dr Ky is the editor-in-chief of JACC: CardioOncology; has received research funding from Pfizer; has received honoraria from UpToDate and Medscape; and has been a consultant to AstraZeneca. Dr Dent has been a consultant to AstraZeneca, Novartis, Pfizer, Race Oncology, Myocardial Solutions, Bristol Myers Squibb, and Gilead Sciences. Dr Fernandez has received honoraria or consultation fees from Philips, Myocardial Solutions, Bayer, Daiichi Sankyo, AstraZeneca, Beigene, Janssen, and Pfizer outside the submitted work. Dr Cornell is employed at AbbVie; and owns stock in AbbVie. Dr Flaig has a leadership role and owns stock in Aurora Oncology; has been a consultant to Seagen and Janssen Oncology; has received research support from Novartis, Bavarian Nordic, Dendreon, GTx, Janssen Oncology, Medivation, Sanofi, Pfizer, Bristol Myers Squibb, Roche/Genentech, Exelixis, Aragon Pharmaceuticals, Sotio, Tokai Pharmaceuticals, AstraZeneca/MedImmune, Eli Lilly, Astellas Pharma, Agensys, Seagen, La Roche-Posay, Merck, Myovant Sciences, and Criterium; and is the inventor on patents filed by the University of Colorado. Dr de Azambuja has received honoraria from and/or served on advisory boards for Roche/GNE, Novartis, SeaGen, Zodiac, Libbs, Pierre Fabre, Eli Lilly, AstraZeneca, MSD, and Gilead Sciences; has received travel grants from Roche/GNE and AstraZeneca; has received institutional research grants from Roche/GNE, AstraZeneca, GSK/Novartis, and Gilead Sciences. Dr Seltzer has served on safety committee for AstraZeneca, Minoryx, Moderna, Vivoryon Therapeutics, Pathalys Pharma, Takeda, and Crinetics. Dr Neilan has been a consultant to and received fees from Parexel Imaging, Bristol Myers Squibb, Roivant, Intrinsic Imaging, H3-Biomedicine, Amgen, Sanofi, Genentech, Roche, and AbbVie; and has received research grant funding from Bristol Myers Squibb, Abbott, and AstraZeneca. Dr Moleshi has served on advisory boards for Bristol Myers Squibb, Takeda, AstraZeneca, Myovant, Kurome Therapeutics, Kiniksa Pharmaceuticals, Daiichi Sankyo, CRC Oncology, BeiGene, Prelude Therapeutics, TransThera Sciences, and Cytokinetics. Dr Januzzi is a trustee of the American College of Cardiology; is a director at Imbria Pharmaceuticals; is an advisor at Jana Care; has received grant support from Abbott, Applied Therapeutics, AstraZeneca, HeartFlow Inc, Innolife, and Roche Diagnostics; has received consulting income from Abbott, Beckman-Coulter, Boehringer Ingelheim, Janssen, Novartis, Merck, Roche Diagnostics, Siemens, Quidel-Ortho; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Intercept, Pfizer, and Takeda. Dr Petrie has received research funding from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; and has been a consultant and/or served on trial committees for Akero, Applied Therapeutics, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, AnaCardio, and Teikuko. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025. Published by Elsevier Inc.)

Background: In the STOP-CA (Statins to Prevent the Cardiotoxicity From Anthracyclines) trial, atorvastatin preserved the left ventricular ejection fraction among patients with lymphoma treated with anthracyclines. The protective mechanisms are currently unclear., Objectives: The aim of this study was to test the effect of atorvastatin on the anthracycline-associated increase in myocardial extracellular volume (ECV) using cardiac magnetic resonance imaging (MRI)., Methods: Cardiac MRI with mapping was performed at baseline and at 12-month follow-up. ECV was calculated, and the primary endpoint was a ≥3% increase. Increases of ≥1 SD in native T1 and T2 times and ECV were secondary endpoints., Results: The subgroup included 171 participants with paired cardiac MRI scans, and 127 had contrast scans of appropriate quality (median age 52 years, 47% women). The proportion of participants with ≥3% increases in ECV was lower in the atorvastatin compared with the placebo group (8% vs 29%; P = 0.002; OR: 0.20; 95% CI: 0.06 to 0.59). A ≥3% increase in ECV was associated with an 8.4% decrease in left ventricular ejection fraction at follow-up (95% CI: -6.31 to -10.38; P < 0.001). The proportion of participants with ≥1-SD increases in T1 and T2 times was statistically similar between groups at 12 months. At 24 months, there were fewer heart failure events among those without ≥3% increases in ECV (8% vs 24%; P = 0.054), though not statistically significantly., Conclusions: Compared with placebo, atorvastatin limited ECV expansion among participants with lymphoma undergoing anthracycline chemotherapy. This study is the first to provide mechanistic insight into statins' cardioprotective effects with anthracyclines. (Statins to Prevent the Cardiotoxicity From Anthracyclines [STOP-CA]; NCT02943590)., Competing Interests: Funding Support and Author Disclosures This study was supported by a grant from the National Heart, Lung, and Blood Institute (NHLBI) (R01HL130539) to Drs Neilan and Scherrer-Crosbie. Dr Neilan is supported by a gift from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, and a Hassenfeld Scholar Award and has received additional grant funding from the NHLBI (grants R01HL137562 and K24HL150238). Dr Januzzi was supported in part by the Adolph Hutter Professorship. Dr Drobni was supported by the ÚNKP-23-4-II-SE New National Excellence Program of the Ministry for Innovation and Technology from the National Research, Development, and Innovation Fund, Hungary. Dr Scherrer-Crosbie was supported by the NHLBI (grant R01131613) and has received additional grant funding from the American Society of Echocardiography. Dr Juhasz has received a scholarship from the Rosztoczy Foundation. Dr Ky is supported by grants R01HL148272, R01HL152707, R21HL157886, and K24HL167127. Dr Neilan has received personal fees for consulting from Bristol Myers Squibb; has received personal fees from Genentech, Roche, Sanofi, C4 Therapeutics, CardiolRx, and CRC Oncology; and has received grants from Bristol Myers Squibb and AstraZeneca. Dr Januzzi has served as a board member for Imbria Pharmaceuticals; has received grant support from Abbott, Applied Therapeutics, HeartFlow, Innolife, and Roche Diagnostics; has received consulting income from Abbott, Beckman, Bristol Myers Squibb, Boehringer Ingelheim, JanaCare, Janssen, Novartis, Pfizer, Merck, Roche Diagnostics, and Siemens; and has participated in clinical endpoint committees and data and safety monitoring boards for Abbott, AbbVie, CVRx, Intercept, and Takeda. Dr Neuberg owns stock in Madrigal Pharmaceuticals. Dr Asnani serves as the principal investigator for a sponsored research agreement with Genentech; has received royalties from U.S. patent US20210163495A1 (Mass General Brigham); and sits on the Board of Directors for Corventum. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Current approaches to accurately identify immune-related adverse events (irAEs) in large retrospective studies are limited. Large language models (LLMs) offer a potential solution to this challenge, given their high performance in natural language comprehension tasks. Therefore, we investigated the use of an LLM to identify irAEs among hospitalized patients, comparing its performance with manual adjudication and International Classification of Disease (ICD) codes., Methods: Hospital admissions of patients receiving immune checkpoint inhibitor (ICI) therapy at a single institution from February 5, 2011, to September 5, 2023, were individually reviewed and adjudicated for the presence of irAEs. ICD codes and an LLM with retrieval-augmented generation were applied to detect frequent irAEs (ICI-induced colitis, hepatitis, and pneumonitis) and the most fatal irAE (ICI-myocarditis) from electronic health records. The performance between ICD codes and LLM was compared via sensitivity and specificity with an α = .05, relative to the gold standard of manual adjudication. External validation was performed using a data set of hospital admissions from June 1, 2018, to May 31, 2019, from a second institution., Results: Of the 7,555 admissions for patients on ICI therapy in the initial cohort, 2.0% were adjudicated to be due to ICI-colitis, 1.1% ICI-hepatitis, 0.7% ICI-pneumonitis, and 0.8% ICI-myocarditis. The LLM demonstrated higher sensitivity than ICD codes (94.7% v 68.7%), achieving significance for ICI-hepatitis ( P < .001), myocarditis ( P < .001), and pneumonitis ( P = .003) while yielding similar specificities (93.7% v 92.4%). The LLM spent an average of 9.53 seconds/chart in comparison with an estimated 15 minutes for adjudication. In the validation cohort (N = 1,270), the mean LLM sensitivity and specificity were 98.1% and 95.7%, respectively., Conclusion: LLMs are a useful tool for the detection of irAEs, outperforming ICD codes in sensitivity and adjudication in efficiency.

Immune checkpoint inhibitors are widely used anticancer therapies 1 that can cause morbid and potentially fatal immune-related adverse events such as immune-related myocarditis (irMyocarditis) 2-5 . The pathogenesis of irMyocarditis and its relationship to antitumour immunity remain poorly understood. Here we sought to define immune responses in heart, tumour and blood in patients with irMyocarditis by leveraging single-cell RNA sequencing coupled with T cell receptor (TCR) sequencing, microscopy and proteomics analyses of samples from 28 patients with irMyocarditis and 41 unaffected individuals. Analyses of 84,576 cardiac cells by single-cell RNA sequencing combined with multiplexed microscopy demonstrated increased frequencies and co-localization of cytotoxic T cells, conventional dendritic cells and inflammatory fibroblasts in irMyocarditis heart tissue. Analyses of 366,066 blood cells revealed decreased frequencies of plasmacytoid dendritic cells, conventional dendritic cells and B lineage cells but an increased frequency of other mononuclear phagocytes in irMyocarditis. Fifty-two heart-expanded TCR clones from eight patients did not recognize the putative cardiac autoantigens α-myosin, troponin I or troponin T. Additionally, TCRs enriched in heart tissue were largely nonoverlapping with those enriched in paired tumour tissue. The presence of heart-expanded TCRs in a cycling blood CD8 T cell population was associated with fatal irMyocarditis case status. Collectively, these findings highlight crucial biology driving irMyocarditis and identify putative biomarkers., Competing Interests: Competing interests: S.M.B.: consultant to Two River Consulting and Third Rock Ventures; and equity in Candid Therapeutics, Kronos Bio, 76Bio and Allogene Therapeutics. D.A.Z.: consultant to Bristol Myers Squibb, Freeline Therapeutics and Intrinsic Imaging; and research funding from Abbott Laboratories. N.P.S.: consultant to Hera Biotech. L.Z.: consultant to Bristol Myers Squibb and Merck. J.F.G.: consultant to Amgen, Arcus Biosciences, AI Proteins, AstraZeneca, Beigene, Blueprint Medicines, Bristol Myers Squibb, Genentech/Roche, EMD Serono, InterVenn Biosciences, Gilead Sciences, iTeos Therapeutics, Jounce Therapeutics, Karyopharm Therapeutics, Lilly, Loxo, Merus, Mirati Therapeutics, Pfizer, Sanofi, Silverback Therapeutics, Merck, Moderna Therapeutics, Mariana Oncology and Takeda; honorarium from Merck, Pfizer, Novartis, Pfizer and Takeda; research funding from Adaptimmune, Alexo Therapeutics, Array BioPharma, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Genentech, Jounce Therapeutics, Merck, Moderna Therapeutics, Novartis and Tesaro; has an immediate family member who is an employee with stock and other ownership interests in Ironwood Pharmaceuticals; and equity in AI Proteins. C.J.W.: equity in BionTech; research funding from Pharmacyclics; and is on the scientific advisory board of Repertoire, Adventris and Aethon Therapeutics. D.J.: grants and personal fees from Novartis, Genentech, Syros and Eisai; personal fees from Vibliome, PIC Therapeutics, Mapkure and Relay Therapeutics; and grants from Pfizer, Amgen, InventisBio, Arvinas, Takeda, Blueprint Medicines, AstraZeneca, Ribon Therapeutics and Infinity that are outside the submitted work. M.M.-K.: consultant to AstraZeneca, Pfizer, Repare, Boehringer Ingelheim, Sanofi, AbbVie and Daiichi-Sankyo; and royalties from Elsevier. G.O.: consultant to Bicycle Therapeutics. R.J.S.: consultant to Bristol Myers Squibb, Merck, Pfizer, Marengo Therapeutics, Novartis, Eisai, Iovance, OncoSec and AstraZeneca; and research funding from Merck. G.M.B.: sponsored research agreements through her institution with Olink Proteomics, Teiko Bio, InterVenn Biosciences and Palleon Pharmaceuticals; is on advisory boards for Iovance, Merck, Nektar Therapeutics, Novartis and Ankyra Therapeutics; is a consultant for Merck, InterVenn Biosciences, Iovance and Ankyra Therapeutics; and has equity in Ankyra Therapeutics. T.G.N.: consultant to Bristol Myers Squibb, Genentech, CRC Oncology, Roche, Sanofi and Parexel Imaging Pharmaceuticals; and grant funding from Astra Zeneca, Bristol Myers Squibb related to the cardiac effects of ICIs. K.L.R.: on the advisory board to SAGA Diagnostics; speaker’s fees from CMEOutfitters and Medscape; and research funding from Bristol Myers Squibb. A.-C.V.: consultant to Bristol Myers Squibb; and financial interest in 10x Genomics. 10x Genomics designs and manufactures gene sequencing technology for use in research, and such technology is being used in this research; these interests were reviewed by the Massachusetts General Hospital and Mass General Brigham in accordance with their institutional policies. All other authors (I.J.K., S.R., J.C., N.S., S.M., M.W., A.T., Y.S., K.H.X., J.B., P.S., K.S., J.T., K.M., B.Y.A., M.N., C.J.P., D.M., M.J., P.C., A.L., W.A.M., T.S., L.T.N., J.R.S. and M.F.T.) declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Competing Interests: None.

The administration of certain cancer therapies can be associated with the development of cardiovascular toxicity or complications. This spectrum of toxicities is broad and requires nuanced approaches for prevention, identification, and management. This expert panel summarizes the consensus of opinions of diverse health care professionals in several key areas: 1) cardioprotection involves strategies aimed at the primary prevention of cancer therapy-related cardiovascular toxicity; 2) surveillance entails monitoring for cancer therapy-related cardiovascular toxicity during cancer therapy; 3) permissive cardiotoxicity is the informed continuation of cancer therapy in the presence of cardiovascular toxicity, along with the implementation of mitigating cardiovascular treatments; and 4) special considerations include the invasive management of severe cardiovascular disease in patients receiving treatments for advanced cancer and the exploration of drug-drug interactions in cardio-oncology. In this expert panel, we also highlight gaps in evidence in an effort to continue to advance science in the cardiovascular care of our patients undergoing cancer therapy., Competing Interests: Dr Leong has received consulting fees or honoraria from AbbVie, Ferring, Ipsen, Jazz, Myovant Sciences, Novartis, Pfizer, Sanofi, Tolmar, Antev, AstraZeneca, and Boston Scientific; and has received research grants from Novartis and Tolmar. Dr Waliany has received consulting fees from AstraZeneca. Dr Abdel-Qadir has received speaker honoraria from Jazz Pharmaceuticals and AstraZeneca. Dr Atkins has received honoraria from OncLive. Dr Neilan has received consulting fees from Bristol Myers Squibb, RACE Oncology, Roche, Genentech, Roivant, and Sanofi; and has received grant fees from Bristol Myers Squibb, AstraZeneca, and Abbott. Dr Lang has received research grants from Roche Diagnostics, Astra Zeneca, and Boehringer Ingelheim; and has received consulting fees and honoraria from Roche Diagnostics, Myokardia, Pharmacosmos, Akero Therapeutics, CV6 Therapeutics, Jazz Pharmaceuticals, and Novartis. Dr Moore has received consulting fees from AstraZeneca, Daiichi-Sankyo, Eli Lilly, Novartis, RACE Oncology, and Pfizer. Dr Mian has received research support from Janssen; and has received honoraria and consulting fees from Janssen, Pfizer, Sanofi, Bristol Myers Squibb, Takeda, Amgen, and FORUS. Dr Morgans has received consulting fees from Astellas, AstraZeneca, AAA, Bayer, Janssen, Exelixis, Lantheus, Myovant Sciences, Merck, Pfizer, Novartis, Sanofi, and Telix. Dr Ellis has received honoraria from AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Jazz Pharmaceuticals, Merck, Novartis, Roche, Sanofi, and Pfizer. Dr Dent has received honoraria from Pfizer, AstraZeneca, Gilead Sciences, Novartis, Bristol Myers Squibb, and Myocardial Solutions. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Purpose: Medical reports, governed by HIPAA regulations, contain personal health information (PHI), restricting secondary data use. Utilizing natural language processing (NLP) and large language models (LLM), we sought to employ publicly available methods to automatically anonymize PHI in free-text radiology reports., Materials and Methods: We compared two publicly available rule-based NLP models (spaCy; NLP ac , accuracy-optimized; NLP sp , speed-optimized; iteratively improved on 400 free-text CT-reports (test set)) and one offline LLM approach (LLM-model, LLaMa-2, Meta-AI) for PHI-anonymization. The three models were tested on 100 randomly selected chest CT reports. Two investigators assessed the anonymization of occurring PHI entities and whether clinical information was removed. Subsequently, precision, recall, and F1 scores were calculated., Results: NLP ac and NLP sp successfully removed all instances of dates (n = 333), medical record numbers (MRN) (n = 6), and accession numbers (ACC) (n = 92). The LLM model removed all MRNs, 96% of ACCs, and 32% of dates. NLP ac was most consistent with a perfect F1-score of 1.00, followed by NLP sp with lower precision (0.86) and F1-score (0.92) for dates. The LLM model had perfect precision for MRNs, ACCs, and dates but the lowest recall for ACC (0.96) and dates (0.52), corresponding F1 scores of 0.98 and 0.68, respectively. Names were removed completely or majorly (i.e., one first or family name non-anonymized) in 100% (NLP ac ), 72% (NLP sp ), and 90% (LLM-model). Importantly, NLP ac and NLP sp did not remove medical information, while the LLM model did in 10% (n = 10)., Conclusion: Pre-trained NLP models can effectively anonymize free-text radiology reports, while anonymization with the LLM model is more prone to deleting medical information., Key Points: Question This study compares NLP and locally hosted LLM techniques to ensure PHI anonymization without losing clinical information. Findings Pre-trained NLP models effectively anonymized radiology reports without removing clinical data, while a locally hosted LLM was less reliable, risking the loss of important information. Clinical relevance Fast, reliable, automated anonymization of PHI from radiology reports enables HIPAA-compliant secondary use, facilitating advanced applications like LLM-driven radiology analysis while ensuring ethical handling of sensitive patient data., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus., (© 2024 European Society of Cardiology.)

Background: Specific cancer treatments can lead to cancer therapy-related cardiac dysfunction (CTRCD). Sodium glucose cotransporter-2 inhibitors (SGLT2is) can potentially prevent these cardiotoxic effects., Objectives: This study sought to determine whether SGLT2i use is associated with a lower incidence of CTRCD in patients with type 2 diabetes mellitus (T2DM) and cancer, exposed to potentially cardiotoxic antineoplastic agents, and without a prior documented history of cardiomyopathy or heart failure., Methods: We conducted a retrospective analysis of patients aged ≥18 years within the TriNetX database with T2DM, cancer, exposure to cardiotoxic therapies, and no prior documented history of cardiomyopathy or heart failure. Patients were categorized by SGLT2i use. After propensity score matching, outcomes were compared over 12 months using Cox proportional HRs. Subgroup analyses focusing on different cancer therapy classes were performed., Results: The study included 8,675 propensity-matched patients in each cohort (mean age = ∼65 years, 42% females, 71% White, ∼19% gastrointestinal malignancy, and ∼25% anthracyclines). Patients prescribed SGLT2is had a lower risk of developing CTRCD (HR: 0.76: 95% CI: 0.69-0.84). SGLT2is also reduced heart failure exacerbations (HR: 0.81; 95% CI: 0.72-0.90), all-cause mortality (HR: 0.67; 95% CI: 0.61-0.74), and all-cause hospitalizations/emergency department visits (HR: 0.93; 95% CI: 0.89-0.97). Subgroup analyses also demonstrated reduced CTRCD risk across various classes of cancer therapies in patients prescribed SGLT2is., Conclusions: SGLT2i administration was associated with a significantly decreased risk of developing CTRCD in patients with T2DM and cancer., Competing Interests: Dr Yang has received research funding from CSL Behring (nonrelevant), Boehringer Ingelheim and Eli and Lilly, Amgen (nonrelevant), and Bristol Meyers Squibb (nonrelevant); and has received consulting fees from Xencor (nonrelevant). Dr Deswal has received consulting fees from Bayer. Dr Herrmann has received consulting fees from Pfizer, Astellas, and AstraZeneca; and has received grant funding from the National Institutes of Health (RO1 CA233610) and the Miami Heart Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Evidence regarding the effect of long-term exposure to particulate matter (PM) 2.5 and comorbid cancer and cardiovascular disease (CVD) mortality is limited., Objectives: In this study, the author report the association between long-term exposure to PM 2.5 and CVD mortality, cancer mortality and comorbid cancer and CVD mortality in the U.S. population., Methods: The Centers for Disease Control and Prevention (CDC) WONDER (Wide-Ranging Online Data for Epidemiologic Research) multiple-cause-of-death database was used to obtain U.S. county-level mortality and population estimates from 2016 to 2020. Data on average daily density of PM 2.5 were abstracted from the 2018 CDC's National Environmental Public Health Tracking system. Counties were divided into quartiles with Q1 representing counties with least average daily density and Q4 representing counties with maximum average daily density of PM 2.5. Age-adjusted mortality rates were abstracted for each quartile, for the overall population and subgroups of population., Results: The age-adjusted mortality rates for CVD, cancer, and comorbid cancer and CVD mortality were 505.3 (range: 505.0-505.7), 210.7 (range: 210.5-210.9), and 62.0 (range: 61.8-62.1) per 100,000 person-years, respectively. CVD mortality had the highest percentage excess mortality in Q4 compared with Q1, followed by comorbid cancer and CVD. Cancer had the least percentage excess mortality. A disproportionate effect of PM 2.5 exposure was noted on vulnerable and minority groups, based on Social Vulnerability Index and race stratification, respectively., Conclusions: Higher levels of long-term PM 2.5 exposure reported increased CVD mortality, cancer mortality and comorbid cancer and CVD disease mortality, with a pronounced detrimental effect in vulnerable and minority population., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Immune checkpoint molecules are physiological regulators of the adaptive immune response. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies targeting programmed cell death protein 1 or cytotoxic T lymphocyte-associated protein 4, have revolutionized cancer treatment and their clinical use is increasing. However, ICIs can cause various immune-related adverse events, including acute and chronic cardiotoxicity. Of these cardiovascular complications, ICI-induced acute fulminant myocarditis is the most studied, although emerging clinical and preclinical data are uncovering the importance of other ICI-related chronic cardiovascular complications, such as accelerated atherosclerosis and non-myocarditis-related heart failure. These complications could be more difficult to diagnose, given that they might only be present alongside other comorbidities. The occurrence of these complications suggests a potential role of immune checkpoint molecules in maintaining cardiovascular homeostasis, and disruption of physiological immune checkpoint signalling might thus lead to cardiac pathologies, including heart failure. Although inflammation is a long-known contributor to the development of heart failure, the therapeutic targeting of pro-inflammatory pathways has not been successful thus far. The increasingly recognized role of immune checkpoint molecules in the failing heart highlights their potential use as immunotherapeutic targets for heart failure. In this Review, we summarize the available data on ICI-induced cardiac dysfunction and heart failure, and discuss how immune checkpoint signalling is altered in the failing heart. Furthermore, we describe how pharmacological targeting of immune checkpoints could be used to treat heart failure., (© 2024. Springer Nature Limited.)

STOP-CA was a multicenter, double-blind, randomized, placebo-controlled trial comparing atorvastatin to placebo in treatment-naïve lymphoma patients receiving anthracycline-based chemotherapy. We performed a preplanned subgroup to analyze the impact of atorvastatin on efficacy in patients with diffuse large B-cell lymphoma (DLBCL). Patients received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at standard doses for six 21-day cycles and were randomly assigned to receive atorvastatin 40 mg daily ( n  = 55) or placebo ( n  = 47) for 12 months. The complete response (CR) rate was numerically higher in the atorvastatin arm (95% [52/55] vs. 85% [40/47], p  = .18), but this was not statistically significant. Adverse event rates were similar between the atorvastatin and placebo arms. In summary, atorvastatin did not result in a statistically significant improvement in the CR rate or progression-free survival, but both were numerically improved in the atorvastatin arm. These data warrant further investigation into the potential therapeutic role of atorvastatin added to anthracycline-based chemotherapies.

Background and Aim: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer., Methods: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i., Results: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P = 0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events., Conclusion: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Abstract: Immune checkpoint inhibitors (ICIs) are a form immunotherapy where the negative regulators of host immunity are targeted, thereby leveraging the own immune system. ICIs have significantly improved cancer survival in several advanced malignancies, and there are currently more than 90 different cancer indications for ICIs. Most patients develop immune-related adverse events during ICI therapy. Most are mild, but a small subset of patients will develop severe and potentially fatal immune-related adverse events. A serious cardiovascular complication of ICI therapy is myocarditis. Although the incidence of myocarditis is low, mortality rates of up to 50% have been reported. The mainstay of ICI-associated myocarditis treatment is high-dose corticosteroids. Unfortunately, half of patients with myocarditis do not show clinical improvement after corticosteroid treatment. Also, high doses of corticosteroids may adversely impact cancer outcomes. There is an evidence gap in the optimal second-line treatment strategy. Currently, there is a paradigm shift in second-line treatment taking place from empirical corticosteroid-only strategies to either intensified initial immunosuppression where corticosteroids are combined with another immunosuppressant or targeted therapies directed at the pathophysiology of ICI myocarditis. However, the available evidence to support these novel strategies is limited to observational studies and case reports. The aim of this review is to summarize the literature, guidelines, and future directions on the pharmacological treatment of ICI myocarditis., Competing Interests: The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF  ≥  45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling., Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system)., Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r =  - 0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r =  - 0.29, p = 0.04) and intracellular water lifetime ( τ ic ) (r =  - 0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r =  - 0.63, p < 0.01)., Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Otavio R Coelho-Filho reports financial support was provided by State of Sao Paulo Research Foundation. Otavio R Coelho-Filho reports was provided by. Otavio R Coelho-Filho reports a relationship with 10.13039/100004325AstraZeneca Pharmaceuticals LP that includes: funding grants and speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100002429Amgen Inc that includes: funding grants. Otavio R Coelho-Filho reports a relationship with 10.13039/100004319Pfizer Inc that includes: funding grants and speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100004336Novartis AG that includes: speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100004326Bayer AG that includes: speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100001003Boehringer Ingelheim Ltd that includes: speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100007723Takeda Pharmaceutical Company Limited that includes: funding grants and speaking and lecture fees. Tomas G Neilan reports a relationship with H3 Biomedicine Inc that includes: funding grants. Tomas G Neilan reports a relationship with 10.13039/100002429Amgen Inc that includes: funding grants. Tomas G Neilan reports a relationship with 10.13039/100006483AbbVie Inc that includes: funding grants. Tomas G Neilan reports a relationship with 10.13039/100004325AstraZeneca that includes: funding grants. T.G.N. has received support from 10.13039/100004325AstraZeneca, Bristol Myer Squibb, 10.13039/100006483AbbVie, 10.13039/100002429Amgen, and H3 Biomedicine. O.R.C.F. has received research grants and/or speaking honoraria from 10.13039/100002429Amgen, 10.13039/100004325AstraZeneca, 10.13039/100004326Bayer, 10.13039/100001003Boehringer Ingelheim, 10.13039/100004336Novartis, 10.13039/100007723Takeda, and 10.13039/100004319Pfizer. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Background: Immunotherapies such as immune checkpoint inhibitors (ICI) are effective in multiple tumor entities but induce a plethora of side effects. Comprehensive real-world analyses are essential to identify new signals, characterize diagnostic features, enable risk assessment, determine pathomechanisms, assess effectiveness of side effect management and compare tumor outcomes., Methods: The international online `Side-Effect Registry Immuno-Oncology´ (SERIO; www.serio-registry.org) collects rare, complex, and severe immunotherapy-induced side effects across all tumor entities with a strong focus on ICI-induced immune-related adverse events (irAE). The relational database management system (RDMS) contains structured data on patient and tumor characteristics, type of immunotherapy, treatment of side effects, and outcome of tumor and irAE. Data are captured within 25 organ modules including new modules for immune effector cell-associated neurotoxicity syndrome (ICANS) for CAR-T-cell therapies and cytokine release syndrome (CRS) for bispecific antibodies. Information on biological samples is gathered., Results: A total of 1398 irAE cases have been documented by 58 centers from 13 countries in patients with 17 tumor types. IrAEs were induced by nine different immunotherapies including tebentafusp and CAR-T cell therapies, and resulted, among others, in neurological (7.6%), pulmonary (4.0%), and cardiac toxicities (2.9%). 50.0% of all irAEs were graded severe or life-threatening and 23.0% of patients received second-line therapy for steroid-refractory or steroid-dependent irAE. SERIO has contributed to 44 original publications on topics ranging from irMyocarditis to irEncephalitis to long-term persistent sequelae of immunotherapy., Conclusions: A reliable evidence base is crucial for decision-making in rare, complex or therapy-refractory irAE. SERIO can help optimize side effect management and thereby reduce morbidity and mortality induced by immunotherapy., Competing Interests: Declaration of Competing Interest LH received speaker and consultancy fees from BiomeDx, BMS, Kyowa Kirin, Merck, MSD, Myoncare, Novartis, Pierre-Fabre, Roche, Sanofi, SUN and Therakos. The LMU received research grants or clinical study grants from Agenus, AstraZeneca Inc., BMS, Hoffmann-La Roche AG, Huya Bioscience, Immunocore, IO Biotech, Merck, Merck Sharp & Dome GmbH, Miltenyi Biomedicine GmbH, Novartis, Pfizer, Pierre Fabre, Regeneron, Replimune, and Sanofi Aventis. AF received honoraria for presentations and travel support from: BMS, Novartis, Pierre-Fabre. AF reports on participation on Advisory Boards of MSD, BMS, Novartis, Pierre-Fabre, Immunocore and institutional research grants from BMS Stiftung Immunonkologie for other financial or non-financial interests. AH reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, grants and personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Novartis Pharma, grants and personal fees from Eisai, personal fees from Immunocore, grants and personal fees from Replimune, personal fees from Seagen, personal fees from IO Biotech, personal fees from Dermagnostix, personal fees from Incyte, grants and personal fees from NeraCare, personal fees from Highlight Therapeutics, grants from Huya Biosciences, personal fees from Kyowa Kirin, personal fees from Iovance, outside the submitted work. CL received honoraria (lectures, presentations, speakers bureaus, manuscript writing or educational events) and travel support from: BMS, MSD Merck, Pierre-Fabre, Biontech, Almirall Hermal, Sun Pharma, KyowaKirin, Immunocore, Sanofi, Novartis. CP received honoraria (speaker honoraria or honoraria as a consultant) and travel support from: Novartis, BMS, MSD, Merck Serono, MSD, Celgene, AbbVie, Sunpharma, Pierre Fabre, UCB, Nutricia Milupa, Janssen and LEO outside the submitted work. CR reports personal consulting fees from BMS, Roche, MSD, Sanofi, Pierre Fabre, Sunpharma, Pfizer, Regeneron. CR received honoraria (lectures, presentations, speakers bureaus, manuscript writing or educational events) from Pierre Fabre, Sanofi, BMS. CR reports personal fees (participation on a Data Safety Monitoring Board or Advisory Board) from Ultimovacs and Regeneron. CR reports stocks/stock options: Ribonexus. DS reports grants, personal fees, non-financial support and other from Novartis, BMS, Amgen, MSD & Array/Pfizer; personal fees and from 4SC, Agenus, Array BioPharma, Astra Zeneca, BioAlta, CureVac, Daiichi Sanyko, Erasma, Haystack, Immatics, Immunocore, InFlarX, Merck Serono, Pierre Fabre, PamGene, Philogen, Neracare NoviGenix, Ultimovacs, Sandoz/Hexal, Sanofi, Seagen, Sun Pharma, Regeneron, and Replimune. GMcA reports on grants or contracts from BMS, Genentech-Roche, Merck to his institution. DT reports consultancy, speaker fees or travel grants: BMS, Roche, Novartis, Sanofi, Recordati, Kyowa Kirin, Sun Pharma and Pierre Fabre. GMcA reports on participation on Data Safety Monitoring or Advisory Board from Pierre Fabre and Pfizer (no payments) and on National Breast Cancer Foundation Board (Australia) (no payments). GVL is consultant advisor for Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA, Merck Sharpe & Dohme, Novartis, OncoSec, PHMR Ltd, Pierre Fabre, Provectus, Qbiotics, Regeneron. HG reports on grants or contracts from BMS, Roche, MSD Oncology, Amgen, Novartis, Iovance Biotherapeutics to her institution. HG received consulting fees from BMS, MSD Oncology, Pierre Fabre, Sanofi/ Regeneron. HG received speakers honoraria from BMS, MSD Oncology, Pierre-Fabre, Sanofi/ Regeneron. HG received travel support from MSD, Amgen, Pfizer. JH received scientific grants from BMS, Sanofi, Sunpharma and consulting fees (for advisory boards) from GSK, MSD, Pierre Fabre, Onkowiessen, Sunpharma. JH received honoraria (talks) from Amgen, BMS, GSK, Immunocore, MSD, Novartis, Pierre Fabre, Sanofi, Sunpharma. JH received meeting/travel support from BMS, Iovance, Sunpharma. JH reports on participation on a Data Safety Monitoring Board from Nekvax. LZ declares speakers and advisory board honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, Sunpharma, research support from Novartis and travel support from Merck Sharp & Dohme, Bristol-Myers Squibb, Pierre Fabre, Sanofi, Sunpharma and Novartis; outside the submitted work. MS reports on research support from Amgen, BMS/Celgene, Gilead/Kite, Janssen, Miltenyi, Novartis, Roche, Seattle Genetics, Takeda. MS reports on participation on Advisory Boards of Astra Zeneca, Avencell, Ichnos, Incyte, Janssen, Molecular Partners. MS received honoraria (speaker’s bureau) from: Amgen, BMS/Celgene, Janssen, Gilead/Kite, Novartis, Pfizer, Takeda. PA reports on grants and contracts from BMS, Roche-Genentech, Pfizer, Sanofi. PA received consulting fees from Bristol Myers Squibb, Roche-Genentech, Merck, Sharp & Dohme, Novartis, Merck Serono, PierreFabre, Sun Pharma, Sanofi, Sandoz, Italfarmaco, Nektar, Pfizer, Lunaphore, Medicenna. Bio-Al Health, ValoTx, Replimmune, Bayer. PA received travel support from Pfizer, BIO-AI Health, Replimmune. PA reports on participation on a Data Safety Monitoring or Advisory Board from BMS, Roche-Genentech, Merck, Sharp & Dohme, Novartis, AstraZeneca, BoehringerIngelheim, Eisai, Regeneron, Daiichi Sankyo, Oncosec, Nouscom, Seagen, iTeos, Erasca. RD has intermittent, project focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, Pfizer, Simcere and touchIME outside the submitted work. RG received honoraria for advice and lectures from BristolMyers Squibb, Roche Pharma, MerckSharpDohme, Novartis, Merck-Serono, Amgen, Almirall Hermal, Pierre-Fabre, Sun Pharma, Immunocore, 4SC, Delcath, Sanofi/Regeneron. Ralf Gutzmer received travel support from SUN Pharma, Boehringer Ingelheim and PierreFabre. Ralf Gutzmer received research grants from Novartis, Sanofi/Regeneron, Merck Serono, Amgen, SUN Pharma, KyowaKirin, Admiral Hermal. RK received meeting and travel support from SunPharma, Novartis, Pierre-Fabre. SG reports on clinical trials honoraria to institution from MSD, BMS, Sanofi, Pfizer, BioNTech, EORTC, I-O Biotech, Astra Zeneca, and Regeneron. SG received consulting fees from MSD and BMS and an Online Ticket for ASCO from BMS. TE received speaker and consultancy fees from BMS, Curevac, Merck, MSD, Novartis, Pierre-Fabre, Sanofi, Almiral Hermal, and SUN. TN reports on grants or contracts from NIH, BMS, Astra Zeneca to his institution. TN received consulting fees from Genentech, BMS, Roche, Sanofi, Roivant, Race Oncology. TN participated on Data Safety Monitoring Board/ Advisory Board from Genentech. TR declared speaker’s honoraria and travel grants from Therakos and SUN. AR, CE, MK, VM have declared no conflicts of interest. BR received support from BMS, Merck and Astrazeneca. BR received honoraria (for lectures, presentations, speakers bureaus, manuscript writing or educational events) from BMS, Merck and Astrazeneca. BR reports on participation on a Data Safety Monitoring Board or Advisory Board from BMS, Merck and Astrazeneca. All remaining authors have declared no conflicts of interest., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Purpose: Giredestrant is an investigational next-generation, oral, selective estrogen receptor antagonist and degrader for the treatment of estrogen receptor-positive (ER+) breast cancer. We present the primary analysis results of the phase Ia/b GO39932 study (NCT03332797)., Patients and Methods: Patients with ER+, HER2-negative locally advanced/metastatic breast cancer previously treated with endocrine therapy received single-agent giredestrant (10, 30, 90, or 250 mg), or giredestrant (100 mg) ± palbociclib 125 mg ± luteinizing hormone-releasing hormone (LHRH) agonist. Detailed cardiovascular assessment was conducted with giredestrant 100 mg. Endpoints included safety (primary), pharmacokinetics, pharmacodynamics, and efficacy., Results: As of January 28, 2021, with 175 patients enrolled, no dose-limiting toxicity was observed, and the MTD was not reached. Adverse events (AE) related to giredestrant occurred in 64.9% and 59.4% of patients in the single-agent ± LHRH agonist and giredestrant + palbociclib ± LHRH agonist cohorts, respectively (giredestrant-only-related grade 3/4 AEs were reported in 4.5% of patients across the single-agent cohorts and 3.1% of those with giredestrant + palbociclib). Dose-dependent asymptomatic bradycardia was observed, but no clinically significant changes in cardiac-related outcomes: heart rate, blood pressure, or exercise duration. Clinical benefit was observed in all cohorts (48.6% of patients in the single-agent cohort and 81.3% in the giredestrant + palbociclib ± LHRH agonist cohort), with no clear dose relationship, including in patients with ESR1-mutated tumors., Conclusions: Giredestrant was well tolerated and clinically active in patients who progressed on prior endocrine therapy. Results warrant further evaluation of giredestrant in randomized trials in early- and late-stage ER+ breast cancer., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes., Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs)., Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022. The patients were treated with ICI-based regimens. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates were determined according to Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events version 5.0., Results: Among 24 patients with CSTS, 17 (70.8%) were White, and 13 (54.2%) were male. Eight patients (33.3%) had angiosarcoma. At the time of ICI treatment, 18 patients (75.0%) had metastatic CSTS, and 4 (16.7%) had locally advanced disease. ICIs were administered as the first-line therapy in 6 patients (25.0%) and as the second-line therapy or beyond in 18 patients (75.0%). For the 18 patients with available response data, objective response rate was 11.1% (n = 2 of 18). The median PFS and median OS in advanced and metastatic CSTS (n = 22) were 5.7 months (95% CI: 2.8-13.3 months) and 14.9 months (95% CI: 5.7-23.7 months), respectively. The median PFS and OS were significantly shorter in patients with cardiac angiosarcomas than in those with nonangiosarcoma CSTS: median PFS was 1.7 vs 11 months, respectively ( P  < 0.0001), and median OS was 3.0 vs 24.0 months, respectively ( P  = 0.008). Any grade treatment-related adverse events occurred exclusively in the 15 patients with nonangiosarcoma CSTS (n = 7 [46.7%]), of which 6 (40.0%) were grade ≥3., Conclusions: Although ICIs demonstrate modest activity in CSTS, durable benefit was observed in a subset of patients with nonangiosarcoma, albeit with higher toxicity., Competing Interests: Dr Abdel-Wahab is supported by a K01 Mentored Research Scientist Development Award from the National Institute of Allergy and Infectious Diseases (grant K01AI163412) and has received the University of Texas MD Anderson Cancer Center Institutional Research Grant, Division of Internal Medicine Development Award, Survivorship Seed Money Award, Prioritizing Research Innovation and Mentoring Excellence Award, and Melanoma SPORE Career Enhancement Program Award. Dr Nassar has received honoraria from OncLive, TEMPUS, and the Korean Society for Medical Oncology; and has received consulting fees from Guidepoint Global. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Certain antineoplastic therapies are associated with an increased risk of cardiomyopathy and heart failure (HF). Sodium glucose co-transporter 2 (SGLT2) inhibitors improve outcomes in patients with HF., Objectives: This study aims to examine the efficacy of SGLT2 inhibitors in patients with cancer therapy-related cardiac dysfunction (CTRCD) or HF., Methods: The authors conducted a retrospective cohort analysis of deidentified, aggregate patient data from the TriNetX research network. Patients aged ≥18 years with a history of type 2 diabetes mellitus, cancer, and exposure to potentially cardiotoxic antineoplastic therapies, with a subsequent diagnosis of cardiomyopathy or HF between January 1, 2013, and April 30, 2020, were identified. Patients with ischemic heart disease were excluded. Patients receiving guideline-directed medical therapy were divided into 2 groups based on SGLT2 inhibitor use. After propensity score matching, odds ratios (ORs) and Cox proportional HRs were used to compare outcomes over a 2-year follow-up period., Results: The study cohort included 1,280 patients with CTRCD/HF (n = 640 per group; mean age: 67.6 years; 41.6% female; 68% White). Patients on SGLT2 inhibitors in addition to conventional guideline-directed medical therapy had a lower risk of acute HF exacerbation (OR: 0.483 [95% CI: 0.36-0.65]; P < 0.001) and all-cause mortality (OR: 0.296 [95% CI: 0.22-0.40]; P = 0.001). All-cause hospitalizations or emergency department visits (OR: 0.479; 95% CI: 0.383-0.599; P < 0.001), atrial fibrillation/flutter (OR: 0.397 [95% CI: 0.213-0.737]; P = 0.003), acute kidney injury (OR: 0.486 [95% CI: 0.382-0.619]; P < 0.001), and need for renal replacement therapy (OR: 0.398 [95% CI: 0.189-0.839]; P = 0.012) were also less frequent in patients on SGLT2 inhibitors., Conclusions: SGLT2 inhibitor use is associated with improved outcomes in patients with CTRCD/HF., Competing Interests: Funding Support and Author Disclosures Dr Deswal is supported in part by the Ting Tsung and Wei Fung Chao Distinguished Chair. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The association between human immunodeficiency virus (HIV) status and readmissions and death outcomes in patients with established heart failure (HF) remains unclear. We conducted a systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science up to March 1st, 2023, for cohort studies of adult patients (≥18 years) diagnosed with HF and recorded HIV status at baseline. Our analysis included 7 studies with 10,328 HF patients living with HIV and 48,757 HF patients without HIV. Compared to HF patients without HIV, those with HIV had a higher risk of all-cause deaths (HR: 1.20, 95% CI: 1.15-1.25). HIV infection was also associated with increased risks of HF-associated readmission (HR: 1.34, 95% CI: 1.03-1.75) and all-cause readmission (HR: 1.27, 95% CI: 1.10-1.46). Our study highlights the independent association between HIV and poor HF outcomes, emphasizing the need for improved management in individuals living with HIV., Competing Interests: Declaration of Competing Interest Dr. Neilan has been a consultant to and received fees from Bristol Myers Squibb, Genentech, CRC Oncology, Roche, Sanofi and Parexel Imaging Pharmaceuticals. Dr. Neilan also reports grant funding from Astra Zeneca and Bristol Myers Squibb related to the cardiac effects of immune checkpoint inhibitors, all outside of the current work. Dr. Zanni is Principal Investigator on an investigator-initiated research grant from Gilead to her institution, which is unrelated to this work. Other authors have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitors (ICIs) are widely used anti-cancer therapies that can cause morbid and potentially fatal immune-related adverse events (irAEs). ICI-related myocarditis (irMyocarditis) is uncommon but has the highest mortality of any irAE. The pathogenesis of irMyocarditis and its relationship to anti-tumor immunity remain poorly understood. We sought to define immune responses in heart, tumor, and blood during irMyocarditis and identify biomarkers of clinical severity by leveraging single-cell (sc)RNA-seq coupled with T cell receptor (TCR) sequencing, microscopy, and proteomics analysis of 28 irMyocarditis patients and 23 controls. Our analysis of 284,360 cells from heart and blood specimens identified cytotoxic T cells, inflammatory macrophages, conventional dendritic cells (cDCs), and fibroblasts enriched in irMyocarditis heart tissue. Additionally, potentially targetable, pro-inflammatory transcriptional programs were upregulated across multiple cell types. TCR clones enriched in heart and paired tumor tissue were largely non-overlapping, suggesting distinct T cell responses within these tissues. We also identify the presence of cardiac-expanded TCRs in a circulating, cycling CD8 T cell population as a novel peripheral biomarker of fatality. Collectively, these findings highlight critical biology driving irMyocarditis and putative biomarkers for therapeutic intervention., Competing Interests: Conflict of Interest S.M.B has been a paid consultant to Two River Consulting and Third Rock Ventures. He has equity positions in Kronos Bio, 76Bio, and Allogene Therapeutics. D.A.Z. has been a paid consultant to Bristol Myers Squibb, Freeline Therapeutics, and Intrinsic Imaging. L.Z. has received consulting fees from Bristol Myers Squibb and Merck. R.J.S has been a paid consultant to Bristol Myers Squibb, Merck, Pfizer, Marengo Therapeutics, Novartis, Eisai, Iovance, OncoSec, and AstraZeneca and has received research funding from Merck. T.G.N has been a paid consultant to Bristol Myers Squibb, Genentech, CRC Oncology, Roche, Sanofi and Parexel Imaging Pharmaceuticals and has received grant funding from Astra Zeneca and Bristol Myers Squibb related to the cardiac effects of immune checkpoint inhibitors. K.L.R has served as an advisory board to SAGA Diagnostics and received speaker’s fees from CMEOutfitters and Medscape as well as research funding from Bristol Myers Squibb. A.C.V. has been a paid consultant to Bristol Myers Squibb.

Cardiotoxicity is a growing concern in the oncology population. Transthoracic echocardiography and multigated acquisition scans have been used for surveillance but are relatively insensitive and resource intensive. Innovative imaging techniques are constrained by cost and availability. More sensitive, cost-effective cardiotoxicity surveillance strategies are needed. Circulating cardiovascular biomarkers could provide a sensitive, low-cost solution. Biomarkers such as troponins, natriuretic peptides (NPs), novel upstream signals of oxidative stress, inflammation, and fibrosis as well as panomic technologies have shown substantial promise, and guidelines recommend baseline measurement of troponins and NPs in all patients receiving potential cardiotoxins. Nonetheless, supporting evidence has been hampered by several limitations. Previous reviews have provided valuable perspectives on biomarkers in cancer populations, but important analytic aspects remain to be examined in depth. This review provides comprehensive assessment of critical challenges and solutions in this field, with focus on analytical issues relating to biomarker measurement and interpretation. Examination of evidence pertaining to common and serious forms of cardiotoxicity reveals that improved study designs incorporating larger, more diverse populations, registry-based approaches, and refinement of current definitions are key. Further efforts to harmonize biomarker methodologies including centralized biobanking and analyses, novel decision limits, and head-to-head comparisons are needed. Multimarker algorithms incorporating machine learning may allow rapid, personalized risk assessment. These improvements will not only augment the predictive value of circulating biomarkers in cardiotoxicity but may elucidate both direct and indirect relationships between cardiovascular disease and cancer, allowing biomarkers a greater role in the development and success of novel anticancer therapies.

Advances in cancer therapeutics have led to dramatic improvements in survival, now inclusive of nearly 20 million patients and rising. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Advances in cardiovascular imaging have solidified the critical role for robust methods for detecting, monitoring, and prognosticating cardiac risk among patients with cancer. However, decentralized evaluations have led to a lack of consensus on the optimal uses of imaging in contemporary cancer treatment (eg, immunotherapy, targeted, or biological therapy) settings. Similarly, available isolated preclinical and clinical studies have provided incomplete insights into the effectiveness of multiple modalities for cardiovascular imaging in cancer care. The aims of this scientific statement are to define the current state of evidence for cardiovascular imaging in the cancer treatment and survivorship settings and to propose novel methodological approaches to inform the optimal application of cardiovascular imaging in future clinical trials and registries. We also propose an evidence-based integrated approach to the use of cardiovascular imaging in routine clinical settings. This scientific statement summarizes and clarifies available evidence while providing guidance on the optimal uses of multimodality cardiovascular imaging in the era of emerging anticancer therapies.

Background: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) on recurrent atrial fibrillation (AF) among patients undergoing catheter ablation is not well described., Objectives: This study sought to assess the impact of SGLT2-Is on the recurrence of AF among patients with type 2 diabetes mellitus (DM) after catheter ablation., Methods: Using the TriNetX research network, we identified, by means of Current Procedural Terminology codes, patients ≥18 years of age with type 2 diabetes mellitus (DM) who had undergone AF ablation from April 1, 2014, to November 30, 2021. Patients were stratified based on the baseline SGLT2-I use. Propensity-score matching resulted in 2,225 patients in each cohort. The primary outcome was a composite of cardioversion, new antiarrhythmic drug (AAD) therapy, or re-do AF ablation after a blanking period after the index ablation. Additional outcomes included heart failure exacerbations, ischemic stroke, all-cause hospitalization, and death during 12 months of follow-up., Results: SGLT2-I use in patients with type 2 DM undergoing AF ablation was associated with a significantly lower risk of cardioversion, new AAD therapy, and re-do AF ablation (adjusted OR: 0.68; 95% CI: 0.602-0.776; P < 0.0001). At 12 months, patients on SGLT2-Is had a higher probability of event-free survival (HR: 0.85, 95% CI: 0.77-0.95; log-rank test chi-square = 8.7; P = 0.003). All secondary outcomes were lower in the SGLT2I group; however, the ischemic stroke did not differ between groups., Conclusions: Use of SGLT2-Is in patients with type 2 DM is associated with a lower risk of arrhythmia recurrence after AF ablation and thence a reduced need for cardioversion, AAD therapy, or re-do AF ablation., Competing Interests: Funding Support and Author Disclosures Dr Januzzi is a trustee of the American College of Cardiology and a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer-Ingelheim, Jana Care, Janssen, Novartis, Prevencio, Roche Diagnostics; and participates in clinical endpoint committees an data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Anthracycline chemotherapy causes cardiotoxicity, and the evidence regarding the benefit of concomitant statin use in reducing it remains uncertain. We conducted a meta-analysis of studies using statins and anthracyclines by searching PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until April 10, 2023. Our analysis included 3 observational studies and 4 RCTs, including the STOP-CA trial released in ACC23. Statin prescription significantly reduced cardiotoxicity in cancer patients receiving anthracycline chemotherapy (OR 0.46, 95% CI: 0.33-0.63; I2: 0%). However, no significant difference was observed in the decline of left ventricular ejection fraction (LVEF) from baseline (MD 4.15, 95% CI: -0.69 to 8.99, I2: 97%). These findings demonstrate the protective effect of concomitant statin prescription., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry., Methods: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative., Results: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment., Conclusions: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated., Competing Interests: Disclosures Dr Teske has received speaker fees from Philips and Abbott; consulting from Nordic Pharma. Dr Neilan reports consulting from BMS, Abbvie, Sanofi, Genentech, Roche, and C4-Therapeutics; grant funding from BMS and AZ. Dr López-Fernández has received speaker fees from Philips, Janssen, and Incyte. Dr Szmit has received speaker fees from Amgen, Angelini, Astra Zeneca, Bayer, Bristol-Myers Squibb, Gilead, and Pfizer. Dr Guha is supported by American Heart Association-Strategically Focused Research Network Grant in Disparities in Cardio-Oncology (847740 and 863620). Dr Iakobishvili has received speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Novo-Nordisk, and Bayer. Dr Sverdlov is supported by the National Heart Foundation of Australia Future Leader Fellowship (Award ID 106025) and reports research grants from the Medical Research Future Fund (Australia), NSW Health (Australia), Cancer Institute NSW (Australia), Hunter Medical Research Institute (Australia), Biotronik, RACE Oncology, Bristol Myer Squibb, Roche Diagnostics, and Vifor; and personal speaker fees from Novartis, Bayer, Bristol Myer Squibb, AstraZeneca, and Boehringer Ingelheim. The other authors report no conflicts.

Despite improvements in cancer survival, cancer therapy-related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of the burgeoning field of cardio-oncology, which aims to advance the cardiovascular health of cancer patients and survivors, through actionable and translatable science. In these Global Cardio-Oncology Symposium 2023 scientific symposium proceedings, we present a focused review on the mechanisms that contribute to common cardiovascular toxicities discussed at this meeting, the ongoing international collaborative efforts to improve patient outcomes, and the bidirectional challenges of translating basic research to clinical care. We acknowledge that there are many additional therapies that are of significance but were not topics of discussion at this symposium. We hope that through this symposium-based review we can highlight the knowledge gaps and clinical priorities to inform the design of future studies that aim to prevent and mitigate cardiovascular disease in cancer patients and survivors., Competing Interests: Dr Salloum is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Numbers R35HL155651 and R44HL164314, and the American Heart Association Strategically Focused Research Network Award Number 23SFRNPCS1063855. Dr Tocchetti is supported by grants from the Italian Ministry of Health (PNRR-MAD-2022-12376632 and RF-2016-02362988). Dr Ameri is supported by the European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 “Enhancement and strengthening of biomedical research in the NHS” (Italian Ministry of Health PNRR-MAD-2022-12376632). Dr Ardehali is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Numbers HL127646, HL140973, HL138982, and HL140927. Dr Asnani is supported by R01HL163172, R01HL166541, R01HL157530, and K08HL145019 from the National Institutes of Health/National Heart, Lung, and Blood Institute and by a sponsored research agreement with Genentech. Dr de Boer is supported by the Netherlands Heart Foundation (grants 2017-21, 2017-11, 2018-30, and 2020B005), the Leducq Foundation (Cure-PLaN), and the European Research Council (ERC CoG 818715). Dr Fernández-Velasco is supported by the Carlos III Health Institute (ISCIII) (PI20-01482 and PMP22/00098). Dr Fradley is funded by Medtronic and AstraZeneca. Dr Fuster is supported by grant RYC-2016-20026 from the Spanish Ministerio de Ciencia e Innovación (MICIN/AEI/10.13039/501100011033 and “ESF Investing in your future”) and the European Research Area Network on Cardiovascular Diseases CHEMICAL (grant AC19/00133, funded by ISCIII and co-funded by the European Union, ERDF, “A way to make Europe”). Drs Galán-Arriola, García-Lunar, Ibáñez, and Martin and the Centro Nacional de Investigaciones Cardiovasculares (CNIC) are supported by the ISCIII, the Ministry of Science and Innovation, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). Dr Ibáñez is supported by a European Research Council grant (ERC-CoG 819775). The RESILIENCE project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 945118. Dr Kitsis is supported by the national Heart, Lung, and Blood Institute of the National Institutes of Health under Award Numbers R01HL159062, R01HL157319, R01HL164772, and DOD PR191593. Dr Martin is supported by MCIN-ISCIII-Fondo de Investigación Sanitaria (PI22/01759; PMPTA22/00090-BIOCARDIOTOX) and the Comunidad de Madrid (P2022/BMD-7209-INTEGRAMUNE-CM). Dr Mauro is supported by T32HL149645. Dr Mazo Vega is supported by European Union’s H2020 Program under grant agreement No 874827 (BRAV∃) and the Ministerio de Ciencia e Innovación CARDIOPRINT (PLEC2021-008127). Dr Neilan is supported by a gift from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, and a Hassenfeld Scholar Award, and is supported by additional grant funding from the National Institutes of Health/National Heart, Lung, and Blood Institute under Award Numbers R01HL137562 and K24HL150238. Dr Rassaf is supported by the German Research Foundation Lower Saxony (DFG RA969/12-1), Ministry of Science and Culture REBIRTH I/II (ZN3440), and Stiftung Gerdes. Dr Ricke-Hoch is supported by the Lower Saxony Ministry of Science and Culture REBIRTH I/II (ZN3440) and Stiftung Gerdes. Dr van der Meer is supported by a grant from the European Research Council (ERC CoG 101045236, DISSECT-HF). Dr Thavendiranathan is supported by a Tier II Canada Research Chair in Cardiooncology (950-232646). Dr Ky is supported by National Institutes of Health grants R01 HL148272, R01 HL152707, R34 HL146927, R21 HL152148, R21HL157886, and K24 HL167127 and American Heart Association Strategically Focused Research Network Awards 849569 and 869105. Dr Sepulveda is supported by ISCIII (PMPTA2022/00011). Drs Ghigo, Lyon, Ibáñez, Hirsch, Ricke-Hoch, and Rassaf are supported by the Leducq Foundation Transatlantic Networks of Excellence (19CVD02). Dr Salloum has received consulting fees from Ring Therapeutics and funding from Novartis Pharmaceuticals, not related to this work; and served on the advisory board for NovoMedix, LLC, in cardio-oncology but not directly related to this work. Dr Tocchetti has received honoraria or consultation fees from VivaLyfe, Univers Formazione, Solaris, Summeet, AstraZeneca, and Myocardial Solutions; has received funding from Amgen and MSD, outside the submitted work; and is listed as an inventor of 2 patents related to heart failure. Dr Ameri has received speaker and/or advisor fees from AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, Daiichi Sankyo, Janssen, and MSD, all outside the submitted work. Dr Asnani has served as a consultant or advisory board member for Sanofi, AstraZeneca, Cytokinetics, and OncLive; served as the principal investigator of a sponsored research agreement with Genentech; and received honoraria from UpToDate. Dr de Boer has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Ionis Pharmaceuticals, Novo Nordisk, and Roche; and served as a speaker for Abbott, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, and Roche. Dr Fradley has served as a consultant for AbbVie, AstraZeneca, Johnson and Johnson, Pfizer/Myovant, and Zoll. Drs Ghigo and Hirsch are co-founders and shareholders of Kither Biotech, a pharmaceutical company focused on the development of PI3K inhibitors for airway diseases not in conflict with the content of this paper. Dr Kitsis is a founder of ASPIDA Therapeutics Inc. Dr Lyon has received speaker, advisory board, or consulting fees and/or research grants from Pfizer, Novartis, Servier, AstraZeneca, Bristol Myers Squibb, GSK, Amgen, Takeda, Roche, Janssen-Cilag Ltd, Astellas Pharma, Clinigen Group, Eli Lilly, Eisai Ltd, Ferring Pharmaceuticals, Boehringer Ingelheim, Akcea Therapeutics, Myocardial Solutions, iOWNA Health, and Heartfelt Technologies Ltd. Dr Neilan has served as a consultant for and received fees from Bristol Myers Squibb, Genentech, CRC Oncology, Roche, Sanofi, and Parexel Imaging Pharmaceuticals; and received grant funding from AstraZeneca and Bristol Myers Squibb related to immune therapies. Dr Rassaf has received honoraria, lecture fees, and grant support from Edwards Lifesciences, AstraZeneca, Bayer, Novartis, Berlin Chemie, Daiichi Sankyo, Boehringer Ingelheim, Novo Nordisk, Cardiac Dimensions, and Pfizer, all unrelated to this work. Dr Thavendiranathan’s institution has received speaker honoraria or consultation fees from Amgen, Novartis, Boehringer Ingelheim, and Takeda. Dr van der Meer has received consulting fees and/or grants from Novartis, Pharmacosmos, Vifor Pharma, AstraZeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Boehringer Ingelheim, and Ionis. Dr Ky has received honoraria or grants from Pfizer; and honoraria from Roche, Bristol Myers Squibb, and AstraZeneca. Dr López-Fernández has received speaker fees from Philips, Janssen, Daichi Sankyo, Myocardial Solutions, AstraZeneca, Beigene, and Bayer, not related to the current work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Aims: This study aimed to characterize the influence of a cancer diagnosis on the use of preventive cardiovascular measures in patients with and without cardiovascular disease (CVD)., Methods and Results: Data from the Behavioural Risk Factor Surveillance System Survey (spanning 2011-22) were used. Multivariable logistic regression models adjusted for potential confounders were applied to calculate average marginal effects (AME), the average difference in the probability of using a given therapy between patients with and without cancer. Outcomes of interest included the use of pharmacological therapies, physical activity, smoking cessation, and post-CVD rehabilitation. Among 5 012 721 respondents, 579 114 reported a history of CVD (coronary disease or stroke), and 842 221 reported a diagnosis of cancer. The association between cancer and the use of pharmacological therapies varied between those with vs. without CVD (P-value for interaction: <0.001). Among patients with CVD, a cancer diagnosis was associated with a lower use of blood pressure-lowering medications {AME: -1.46% [95% confidence interval (CI): -2.19% to -0.73%]}, lipid-lowering medications [AME: -2.34% (95% CI: -4.03% to -0.66%)], and aspirin [AME: -6.05% (95% CI: -8.88% to -3.23%)]. Among patients without CVD, there were no statistically significant differences between patients with and without cancer regarding pharmacological therapies. Additionally, cancer was associated with a significantly lower likelihood of engaging in physical activity in the overall cohort and in using post-CVD rehabilitation regimens, particularly post-stroke rehabilitation., Conclusion: Preventive pharmacological agents are underutilized in those with cancer and concomitant CVD, and physical activity is underutilized in patients with cancer in those with or without CVD., Lay Summary: •This paper compared the use of preventive cardiovascular measures, both pharmaceutical and non-pharmaceutical, in patients with and without cancer.•In patients with cardiovascular disease and cancer, there is a lower use of preventive cardiovascular medications compared with those with cardiovascular disease but without cancer. This includes a lower utilization of blood pressure-lowering medications, cholesterol-lowering medications, and aspirin.•Patients with cancer reported lower levels of exercise but higher levels of smoking cessation compared with those without cancer., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The broad application of immune checkpoint inhibitors (ICIs) has led to significant gains in cancer outcomes. By abrogating inhibitory signals, ICIs promote T cell targeting of cancer cells but can frequently trigger autoimmune manifestations, termed immune-related adverse events (irAEs), affecting essentially any organ system. Among cardiovascular irAEs, immune-related myocarditis (irMyocarditis) is the most described and carries the highest morbidity. The currently recommended treatment for irMyocarditis is potent immunosuppression with corticosteroids and other agents, but this has limited evidence basis. The cellular pathophysiology of irMyocarditis remains poorly understood, though mouse models and human data have both implicated effector CD8 + T cells, some of which are specific for the cardiomyocyte protein α-myosin. While the driving molecular signals and transcriptional programs are not well defined, the involvement of chemokine receptors such as CCR5 and CXCR3 has been proposed. Fundamental questions regarding why only approximately 1% of ICI recipients develop irMyocarditis and why irMyocarditis carries a much worse prognosis than other forms of lymphocytic myocarditis remain unanswered. Further work in both murine systems and with human samples are needed to identify better tools for diagnosis, risk-stratification, and treatment., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Sodium-glucose transporter 2 (SGLT2) inhibitors have been approved for treatment of diabetes mellitus (DM), chronic kidney disease, and heart failure, but little is known about prescription levels and safety profiles among people with HIV (PWH)., Methods: We leveraged data from the US Mass General Brigham electronic healthcare database to determine the use/uptake of SGLT2 inhibitors among PWH with type II diabetes (DM2) (with or without chronic kidney disease, proteinuria, or heart failure) and to assess rates of adverse events among PWH with DM2 taking SGLT2 inhibitors., Results: Among eligible PWH with DM2 receiving care at US Mass General Brigham (N = 907), SGLT2 inhibitors were prescribed to 8.8%. SGLT2 inhibitors were prescribed to a fraction of eligible PWH with DM2 and a concomitant diagnosis of chronic kidney disease (3.8%), proteinuria (13.2%), or heart failure (8.2%). PWH with DM2 on SGLT2 inhibitors experienced side effects (urinary tract infection, diabetic ketoacidosis, and acute kidney injury) at rates comparable with PWH with DM2 prescribed glucagon-like peptide-1 agonists. Rates of mycotic genitourinary infections were higher among those prescribed SGLT2 inhibitors (5% vs. 1%, P = 0.17), but no cases of necrotizing fasciitis ensued., Conclusions: Additional studies are needed to characterize population-specific salutary and adverse effects of SGLT2 inhibitors among PWH and potentially augment prescription rates when guideline indicated., Competing Interests: M.E. Sise reported grant support through her institution from NIH/NIDDK and from Angion, Gilead Sciences, Merck, AbbVie, and EMD/Serono, outside the submitted work. M.E. Sise also reported having served as a Scientific Advisory Board Member for Novartis, Travere, Gilead, and Mallinkcrodt. N. Katz-Agranov, I.A. Strohbehn, D. Harden, D. Moreno, C. Durbin have no funding or conflicts of interest to disclose. M. Toribio reported grant support through her institution from NIH/NHLBI, American Heart Association, and Robert Wood Johnson Foundation, outside the submitted work. T.G. Neilan reported having served as a consultant to and received fees from Amgen, Genentech, Roche, Sanofi, H3-Biomedicine, CRC Oncology, and AbbVie outside of the current work. He also reported receiving grant funding from AstraZeneca and Bristol Myers Squibb, outside the submitted work. T.G. Neilan holds the Michael and Kathryn Park Endowed Chair in Cardiology and was also supported, in part, through a kind gift from A. Curtis Greer and Pamela Kohlberg, Christina and Paul Kazilionis and a Hassenfeld Scholar Award, as well as NIH/NHLBI Grants R01HL130539, R01HL159187, R01HL137562, K24HL150238. M.V. Zanni reported Grant support through her institution from NIH/NHLBI (1R01HL146267 and R01HL137562), from NIH/NIAID (K24AI157882) and from Gilead Sciences, Inc. The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use., Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction., Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022., Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months., Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months., Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups., Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use., Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.

Importance: The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood., Objective: To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival., Design: Retrospective cohort study., Setting: Academic Medical Center (Massachusetts General Hospital, Boston)., Participants: 240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging., Measurements: 18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV)., Results: Among individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7-5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07-1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progression-free survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24-2.68], P = 0.001)., Conclusions and Relevance: AmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hassan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer., Methods: In this case-control (2:1 matched by age and gender) study, total, non-calcified, and calcified plaque volumes were measured in the thoracic aorta using sequential contrast-enhanced chest CT scans. Univariate and multivariate rank-based estimation regression models were developed to estimate the effect of ICI therapy on plaque progression in 40 cases (ICI) and 20 controls (non-ICI)., Results: The patients had a median age of 66 years (IQR: 58-69), with 50% of them being women. At baseline, there were no significant differences in plaque volumes between the groups, and their cardiovascular risk profiles were similar. However, the annual progression rate for non-calcified plaque volume was 7 times higher in the ICI group compared with the controls (11.2% vs 1.6% per year, p=0.001). Conversely, the controls showed a greater progression in calcified plaque volume compared with the ICI group (25% vs 2% per year, p=0.017). In a multivariate model that considered cardiovascular risk factors, the use of an ICI was associated with a more substantial progression of non-calcified plaque volume. Additionally, individuals treated with combination ICI therapy exhibited greater plaque progression., Conclusions: ICI therapy was associated with more non-calcified plaque progression. These findings underscore the importance of conducting studies aimed at identifying the underlying mechanisms responsible for plaque advancement in patients undergoing ICI treatment., Trial Registration Number: NCT04430712., Competing Interests: Competing interests: TGN has been a consultant to and received fees from Parexel Imaging, Intrinsic Imaging, Amgen, Sanofi, Genentech, Roche, and AbbVie, outside of the current work. TGN also reports consultant fees from Bristol Myers Squibb for a Scientific Advisory Board focused on myocarditis related to immune checkpoint inhibitors. The study was funded directly by an unrestricted grant from AstraZeneca. TGN also reports research grant funding from Bristol Myers Squibb for work related to immune checkpoint inhibitors. BF reports unrelated grant support from MedImmune/AstraZeneca and MedTrace, as well as grants from NIH/NHLBI outside the submitted work. JT reports speaker’s bureau Siemens Healthcare GmbH and speakers bureau Bayer AG, reviewer Universimed Cross Media Content GmbH, and consultant Core Lab Black Forrest GmbH, all unrelated to this work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient's immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality., Methods and Results: From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104-647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan-Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6-4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade ≥ 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4-8.8) after adjusting for cancer burden., Conclusion: Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin., Competing Interests: Conflict of interest S.S.M. has received consulting fees from Nektar Therapeutics, Health & Wellness Partners, Medicure. P.A.R. has received consulting fees from AbbVie, BMS, Janssen, Novartis, BeiGene, Kite/Gilead, Intellia Therapeutics, Sana Biotechnology, CVS Caremark, Genmab, Pharmacyclics, Takeda, Karyopharm, Nektar Therapeutics, Nurix Therapeutics, and ADC Therapeutics. M.A.P. reports consulting fees from Adicet, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Syncopation, VectivBio AG, and Vor Biopharma, is participating in DSMB of Cidara Therapeutics, Medigene, and Sellas Life Sciences, and is on the scientific advisory board of NexImmune and Omeros. M.B.G. has received institutional grant funding from Sanofi, Amgen, and Actinium and consulting fees from Sanofi, Novartis, and Allogene. M.L.P. has received royalties from Juno and Sers and consulting fees from Novartis, Cellectar, Synthekine, Kite, Seres, Magenta, WindMIL, Rheos, Nektar, Notch, Priothera, Ceramedix, Lygenesis, and Pluto. R.S. has received consulting fees from Mudexus and MyBiotics. G.S. has received research funding from Janssen, Amgen, Beyond Spring, and BMS and is on DSMB of ArcellX. E.H.Y. has received institutional grand funding from CSL Behring, Boehringer Ingelheim, BMS and Eli and Lilly and consulting fees from Pfizer. J.P.L. has received institutional grants from Genentech, Janssen, and Epizyme and consulting fees from Abbvie, Astellas, AstraZeneca, Bayer, Beigene, BMS, Calithera, Constellation, Caribou Biosciences, Eisai, Lilly, Epizyme, Genmab, Grail, Incyte, Jansssen, MEI Pharma, Merck, Mustang Bio, Novartis, Pfizer, Roche/Genentech, Seagen, Second Genome, Sutro, ADC Therapeutics, Miltenyi, and Karyopharm. T.G.N. has received consulting fees from BMS, Genentech, Abbvie, Roche, CRO Oncology, and Sanofi and participates in DSMB of Genentech and received research grant funding from AstraZeneca and BMS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chimeric antigen receptor (CAR) T cells have transformed the care for patients with hematologic malignancies. Patients treated with CAR T cells may experience cardiovascular and pulmonary complications, which primarily occur in the setting of cytokine release syndrome. In addition, many patients considered for CAR T-cell therapy have preexisting cardiac and pulmonary comorbidities. Among patients with good functional status, these conditions should not prevent patients from being offered these lifesaving therapies. In this article, we use a case-based approach to discuss how we evaluate and optimize conditions for patients with cardiac and pulmonary risk factors before CAR T-cell therapy and manage cardiac and pulmonary complications that may arise with treatment., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) are hypothesized to reduce the risk of anthracycline-associated cardiotoxicity., Objectives: This study sought to determine the association between SGLT2is and cardiovascular disease (CVD) after anthracycline-containing chemotherapy., Methods: Using administrative data sets, we conducted a population-based cohort study of people >65 years of age with treated diabetes and no prior heart failure (HF) who received anthracyclines between January 1, 2016, and December 31, 2019. After estimating propensity scores for SGLT2i use, the average treatment effects for the treated weights were used to reduce baseline differences between SGLT2i-exposed and -unexposed controls. The outcomes were hospitalization for HF, incident HF diagnoses (in- or out-of-hospital), and documentation of any CVD in future hospitalizations. Death was treated as a competing risk. Cause-specific HRs for each outcome were determined for SGLT2i-treated people relative to unexposed controls., Results: We studied 933 patients (median age 71.0 years, 62.2% female), 99 of whom were SGLT2i treated. During a median follow-up of 1.6 years, there were 31 hospitalizations for HF (0 in the SGLT2i group), 93 new HF diagnoses, and 74 hospitalizations with documented CVD. Relative to controls, SGLT2i exposure was associated with HR of 0 for HF hospitalization ( P < 0.001) but no significant difference in incident HF diagnosis (HR: 0.55; 95% CI: 0.23-1.31; P = 0.18) or CVD diagnosis (HR: 0.39; 95% CI: 0.12-1.28; P = 0.12). There was no significant difference in mortality (HR: 0.63; 95% CI: 0.36-1.11; P = 0.11)., Conclusions: SGLT2is may reduce the rate of HF hospitalization after anthracycline-containing chemotherapy. This hypothesis warrants further testing in randomized controlled trials., Competing Interests: Analysis of this study was funded by the Ted Rogers Centre for Heart Research (to Dr Thavendiranathan). Dr Abdel-Qadir is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada. Dr Thavendiranathan is supported by a Tier II Canada Research Chair in CardioOncology. The funding sources had no role in the conduct of the study, the decision to publish or the preparation of the manuscript. Dr Abdel-Qadir has received honoraria from Amgen, AstraZeneca, and Jazz Pharmaceuticals. Dr Thavendiranathan has received speaker honoraria from Amgen, Boehringer Ingelheim, and Takeda. This study was supported by ICES, an independent, nonprofit research institute funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). Parts of this material are based on data and/or information compiled and provided by Ontario Health, the Ontario Ministry of Health, and the Canadian Institute of Health Information (CIHI). Parts of this report are based on Ontario Registrar General information on deaths, the original source of which is Service Ontario. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources (ICES, CIHI, Ontario Health, ORG, or the Ontario MOH/ MLTC); no endorsement is intended or should be inferred. Dr Neilan has been a consultant to and received fees from Bristol Myers Squibb, Genentech, CRC Oncology, Roche, Sanofi and Parexel Imaging Pharmaceuticals, outside of the current work. Dr Neilan also reports grant funding from Astra Zeneca and Bristol Myers Squibb outside of the current work. Dr Neilan is supported by a gift from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, a Hassenfeld Scholar Award, and has additional grant funding from the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL137562, K24HL150238). All other authors have reported that they have no relationships to the contents of this paper to disclose., (© 2023 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background: Though the incidence of atrial fibrillation (AF) is increased in patients with cancer, the effectiveness of catheter ablation (CA) for AF in patients with cancer is not well studied., Methods: We conducted a retrospective cohort study of patients who underwent CA for AF. Patients with a history of cancer within 5-years prior to, or those with an exposure to anthracyclines and/or thoracic radiation at any time prior to the index ablation were compared to patients without a history of cancer who underwent AF ablation. The primary outcome was freedom from AF [with or without anti-arrhythmic drugs (AADs), or need for repeat CA at 12-months post-ablation]. Secondary endpoints included freedom from AF at 12 months post-ablation with AADs and without AADs. Safety endpoints included bleeding, pulmonary vein stenosis, stroke, and cardiac tamponade. Multivariable regression analysis was performed to identify independent risk predictors of the primary outcome., Results: Among 502 patients included in the study, 251 (50%) had a history of cancer. Freedom from AF at 12 months did not differ between patients with and without cancer (83.3% vs 72.5%, p 0.28). The need for repeat ablation was also similar between groups (20.7% vs 27.5%, p 0.29). Multivariable regression analysis did not identify a history of cancer or cancer-related therapy as independent predictors of recurrent AF after ablation. There was no difference in safety endpoints between groups., Conclusion: CA is a safe and effective treatment for AF in patients with a history of cancer and those with exposure to potentially cardiotoxic therapy., (© 2023. The Author(s).)

Background: The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association between abnormal MVP-related mechanics and myocardial fibrosis, and their association with arrhythmia., Methods: We studied 113 patients with MVP with both echocardiogram and gadolinium cardiac magnetic resonance imaging for myocardial fibrosis. Two-dimensional and speckle-tracking echocardiography evaluated mitral regurgitation, superior leaflet and papillary muscle displacement with associated exaggerated basal myocardial systolic curling, and myocardial longitudinal strain. Follow-up assessed arrhythmic events (nonsustained or sustained ventricular tachycardia or ventricular fibrillation)., Results: Myocardial fibrosis was observed in 43 patients with MVP, predominantly in the basal-midventricular inferior-lateral wall and papillary muscles. Patients with MVP with fibrosis had greater mitral regurgitation, prolapse, and superior papillary muscle displacement with basal curling and more impaired inferior-posterior basal strain than those without fibrosis ( P <0.001). An abnormal strain pattern with distinct peaks pre-end-systole and post-end-systole in inferior-lateral wall was frequent in patients with fibrosis (81 versus 26%, P <0.001) but absent in patients without MVP with basal inferior-lateral wall fibrosis (n=20). During median follow-up of 1008 days, 36 of 87 patients with MVP with >6-month follow-up developed ventricular arrhythmias associated (univariable) with fibrosis, greater prolapse, mitral annular disjunction, and double-peak strain. In multivariable analysis, double-peak strain showed incremental risk of arrhythmia over fibrosis., Conclusions: Basal inferior-posterior myocardial fibrosis in MVP is associated with abnormal MVP-related myocardial mechanics, which are potentially associated with ventricular arrhythmia. These associations suggest pathophysiological links between MVP-related mechanical abnormalities and myocardial fibrosis, which also may relate to ventricular arrhythmia and offer potential imaging markers of increased arrhythmic risk.