{"title":"DNA Methylation–Based Epigenetic Clocks and Cardiovascular Disease","authors":"Yi Li MA , Jiantao Ma PhD","doi":"10.1016/j.jaccao.2025.07.010","DOIUrl":"10.1016/j.jaccao.2025.07.010","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 705-707"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paolo Milani MD, PhD , Giuseppe Damiano Sanna MD, PhD , Claudia Bellofiore MD , Mario Nuvolone MD, PhD , Marco Basset MD, PhD , Roberta Mussinelli MD, PhD , Giulia Mazzini BS , Martina Nanci MD , Martina Ciardo MD , Serena Caminito BS , Matin Ghazi Esfahani MS , Mohammadjavad Sadrzadeh MS , Alessandro Fogliani MD , Francesca Benigna MD , Gianluigi Guida MD , Francesco Salinaro MD, PhD , Tiziana Bosoni BS , Alessandra Barassi MD , Andrea Foli MD , Riccardo Albertini MD , Giovanni Palladini MD, PhD
{"title":"Diagnostic Performance of the New Free Light Chain Ratio in Systemic Amyloidosis","authors":"Paolo Milani MD, PhD , Giuseppe Damiano Sanna MD, PhD , Claudia Bellofiore MD , Mario Nuvolone MD, PhD , Marco Basset MD, PhD , Roberta Mussinelli MD, PhD , Giulia Mazzini BS , Martina Nanci MD , Martina Ciardo MD , Serena Caminito BS , Matin Ghazi Esfahani MS , Mohammadjavad Sadrzadeh MS , Alessandro Fogliani MD , Francesca Benigna MD , Gianluigi Guida MD , Francesco Salinaro MD, PhD , Tiziana Bosoni BS , Alessandra Barassi MD , Andrea Foli MD , Riccardo Albertini MD , Giovanni Palladini MD, PhD","doi":"10.1016/j.jaccao.2025.07.012","DOIUrl":"10.1016/j.jaccao.2025.07.012","url":null,"abstract":"<div><h3>Background</h3><div>Detection of monoclonal components (MCs) using serum and urine immunofixation (IFE) and free light chain measurement is a critical early step in diagnosing cardiac amyloidosis. Patients with MCs are referred for biopsy-based diagnostic work-up. New reference ranges for the free light chain ratio (FLCR), adjusted for age and estimated glomerular filtration rate, have been proposed.</div></div><div><h3>Objectives</h3><div>The aim of this study was to compare the diagnostic performance of the new vs the conventional FLCR in patients with light chain (AL) amyloidosis and wild-type transthyretin (ATTRwt) amyloidosis.</div></div><div><h3>Methods</h3><div>The analysis included 1,705 patients with AL amyloidosis and 675 with ATTRwt amyloidosis.</div></div><div><h3>Results</h3><div>In the AL cohort, 44 patients (3%) had negative results on serum and urine IFE at diagnosis. Among these, 13 patients had normal conventional FLCRs and 15 had normal new FLCRs, with no significant difference in diagnostic sensitivity (70.4% [95% CI: 55.8%-82.5%] vs 65.9% [95% CI: 50.0%-79.5%]; <em>P</em> = 0.82). Overall diagnostic sensitivity for MC detection was similar between the new and conventional FLCRs (99.2% vs 99.1%). Among patients with ATTRwt amyloidosis and negative serum and urine IFE results, 156 (26.5%) had abnormal FLCRs using the conventional cutoff, compared with only 12 (2%) using the new FLCR. At hematologic response assessment in AL amyloidosis, concordance in the definition of complete response between the 2 FLCR methods was 94.9% (95% CI: 93.4%-95.9%).</div></div><div><h3>Conclusions</h3><div>The new FLCR demonstrates equivalent diagnostic sensitivity in AL amyloidosis and can be integrated into complete response criteria. In patients with suspected ATTRwt amyloidosis, it significantly reduces the proportion of FLCR-only abnormalities, thereby limiting the need for biopsy confirmation.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 751-759"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoxi Meng PhD , Tiffany Eulalio PhD , Yoonji Kim PhD , John Easton PhD , Heather L. Mulder BSc , Emily Walker BSc , Geoffrey Neale PhD , Nan Song PhD , Kyla Shelton MPH , Rebecca M. Howell PhD , Mengqi Xing MR , Sedigheh Mirzaei PhD , Deo Kumar Srivastava PhD , Bonnie Ky MD , Stephanie B. Dixon MD , Melissa M. Hudson MD , Kirsten K. Ness PhD , Gregory T. Armstrong MD , Zhaoming Wang PhD
{"title":"Epigenetic Age Acceleration Mediates Treatment Effects on Cardiometabolic and Cardiovascular Risk in Childhood Cancer Survivors","authors":"Xiaoxi Meng PhD , Tiffany Eulalio PhD , Yoonji Kim PhD , John Easton PhD , Heather L. Mulder BSc , Emily Walker BSc , Geoffrey Neale PhD , Nan Song PhD , Kyla Shelton MPH , Rebecca M. Howell PhD , Mengqi Xing MR , Sedigheh Mirzaei PhD , Deo Kumar Srivastava PhD , Bonnie Ky MD , Stephanie B. Dixon MD , Melissa M. Hudson MD , Kirsten K. Ness PhD , Gregory T. Armstrong MD , Zhaoming Wang PhD","doi":"10.1016/j.jaccao.2025.06.001","DOIUrl":"10.1016/j.jaccao.2025.06.001","url":null,"abstract":"<div><h3>Background</h3><div>Childhood cancer survivors are at increased risk for epigenetic age acceleration (EAA) and subsequent morbidities, including cardiometabolic risk factors (CMRFs) and cardiovascular diseases, because of prior genotoxic treatments.</div></div><div><h3>Objectives</h3><div>The aim of this study was to evaluate the mediating role of EAA in the relationship between cancer treatment exposures and risk for CMRFs and cardiovascular diseases.</div></div><div><h3>Methods</h3><div>This study included 2,939 5-year survivors from SJLIFE (St. Jude Lifetime Cohort) who underwent DNA methylation profiling using peripheral blood mononuclear cells. EAA was calculated using 3 established epigenetic clocks: DunedinPACE, PCPhenoAge, and GrimAge2. Treatment data, including body region–specific radiotherapy (RT) and chemotherapeutic agents such as anthracyclines and corticosteroids, were abstracted from medical records. Outcomes included 3 CMRFs (abnormal glucose metabolism, hypertension, and obesity) and 2 cardiovascular diseases (cardiomyopathy and myocardial infarction). Mediation analysis was conducted to quantify the extent to which EAA mediated the association between each treatment exposure and each clinical outcome.</div></div><div><h3>Results</h3><div>EAA partially mediated the associations between abdominal RT and abnormal glucose metabolism (DunedinPACE 35.4%, GrimAge2 16.2%), between abdominal RT (DunedinPACE 25.9%) or anthracyclines (DunedinPACE 12.5%) and hypertension, and between corticosteroids and obesity (DunedinPACE 8.6%). EAA also mediated the associations between heart RT and cardiomyopathy (PCPhenoAge 30.3%, DunedinPACE 19.9%, GrimAge2 14.4%) and myocardial infarction (PCPhenoAge 24.1%, DunedinPACE 15.5%, GrimAge2 13.2%), and anthracyclines and cardiomyopathy (GrimAge2 6.0%, PCPhenoAge 5.2%, DunedinPACE 3.9%).</div></div><div><h3>Conclusions</h3><div>EAA accounted for a substantial proportion of the association between cancer treatment exposures and risk for CMRFs and cardiovascular diseases. These findings provide insight into biological aging as a potential mechanistic pathway and support the development of interventions targeting accelerated aging to mitigate long-term treatment-related toxicities and reduce premature mortality in this high-risk population.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 691-704"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evaline Cheng MD , Maja Ivanovic MD , Antonia Chan MD , Sidra Xu , Miguel Franquiz PharmD, MD , Carissa Lee BS , Jonathan You MD , Muhammad Fazal MD , Yann Le Guen PhD , Ryan Batchelder PA-C , Sunil A. Reddy MD , Tamiko Katsumoto MD , Kavitha Ramchandran MD , A. Dimitrios Colevas MD , Saad Kahn MD , Alice Fan MD , Heather Wakelee MD , Paul Cheng MD, PhD , Eldrin F. Lewis MD, MPH , Sean M. Wu MD, PhD , Han Zhu MD
{"title":"Cardiac Troponin Screening and Clinical Outcomes in Patients Receiving Immunotherapy","authors":"Evaline Cheng MD , Maja Ivanovic MD , Antonia Chan MD , Sidra Xu , Miguel Franquiz PharmD, MD , Carissa Lee BS , Jonathan You MD , Muhammad Fazal MD , Yann Le Guen PhD , Ryan Batchelder PA-C , Sunil A. Reddy MD , Tamiko Katsumoto MD , Kavitha Ramchandran MD , A. Dimitrios Colevas MD , Saad Kahn MD , Alice Fan MD , Heather Wakelee MD , Paul Cheng MD, PhD , Eldrin F. Lewis MD, MPH , Sean M. Wu MD, PhD , Han Zhu MD","doi":"10.1016/j.jaccao.2025.06.009","DOIUrl":"10.1016/j.jaccao.2025.06.009","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs) are associated with cardiotoxicities such as myocarditis. However, data on the implementation and outcomes of cardiac biomarker screening remain limited.</div></div><div><h3>Objectives</h3><div>The aim of this study was to examine the impact of cardiac troponin I (cTnI) surveillance integrated with symptom-based triaging in patients receiving immunotherapy.</div></div><div><h3>Methods</h3><div>A single-center retrospective cohort study was conducted among adults who underwent routine serial cTnI monitoring during immunotherapy between January 2019 and October 2021. For patients with elevated cTnI, clinical presentation, management, and outcomes were analyzed. Major adverse cardiac events included arrhythmia, myocarditis, heart failure, acute coronary syndrome, stroke, and pericardial effusion. Patients were followed for 24 months from their first ICI dose.</div></div><div><h3>Results</h3><div>Among 428 patients (mean age 67.1 ± 13.9 years, 60.3% men), 42 (9.8%) had elevated cTnI detected through monitoring. Compared with symptomatic patients, asymptomatic patients more often underwent outpatient evaluation (88.0% vs 17.6%; <em>P</em> < 0.001) and continued immunotherapy (68.0% vs 35.3%; <em>P</em> < 0.001), whereas symptomatic patients more often underwent myocarditis-specific diagnostics such as cardiac magnetic resonance imaging (58.8% vs 8.0%; <em>P</em> = 0.001) and received immunosuppression (47.1% vs 8.0%; <em>P</em> = 0.008). The cumulative incidence of major adverse cardiac events at 1.5 years following cTnI elevation was 19.0% (95% CI: 7.0%-31.1%) and was significantly higher in symptomatic vs asymptomatic patients (subdistribution HR: 18.9; 95% CI: 2.2-162.5; <em>P</em> = 0.008). Symptomatic patients had a significantly higher risk for all-cause mortality at 2-year follow-up (HR: 3.24; 95% CI: 1.06-9.94; <em>P</em> = 0.04). In total, 6 patients were diagnosed with myocarditis, with no cardiac-related deaths.</div></div><div><h3>Conclusions</h3><div>cTnI surveillance integrated with symptom-based triaging can facilitate early intervention and treatment of cardiotoxicities such as myocarditis.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 708-721"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recognizing and Responding to Cardiac Risk With Osimertinib","authors":"Eun Kyoung Kim MD, PhD , Se-Hoon Lee MD, PhD","doi":"10.1016/j.jaccao.2025.08.002","DOIUrl":"10.1016/j.jaccao.2025.08.002","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 749-750"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Krithika Loganath MBBS ∗ , Kuan Ken Lee PhD ∗ , Olga Oikonomidou MD, BSc, MSc, MRes, PhD , Peter Hall PhD , Nicholas L. Mills BSc Hons, MBChB, PhD , Shruti Joshi PhD , Trisha Singh PhD , Tom McGillivray PhD , Scott Semple PhD , Ninian N. Lang BSc (Hons), MB ChB, PhD , Marc R. Dweck BSc (Hons), MBChB, PhD , Peter A. Henriksen BSc, MB ChB, PhD
{"title":"Anthracycline Dose, Myocardial Injury, and Change in Left Ventricular Function in the Cardiac CARE Trial","authors":"Krithika Loganath MBBS ∗ , Kuan Ken Lee PhD ∗ , Olga Oikonomidou MD, BSc, MSc, MRes, PhD , Peter Hall PhD , Nicholas L. Mills BSc Hons, MBChB, PhD , Shruti Joshi PhD , Trisha Singh PhD , Tom McGillivray PhD , Scott Semple PhD , Ninian N. Lang BSc (Hons), MB ChB, PhD , Marc R. Dweck BSc (Hons), MBChB, PhD , Peter A. Henriksen BSc, MB ChB, PhD","doi":"10.1016/j.jaccao.2025.06.003","DOIUrl":"10.1016/j.jaccao.2025.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Anthracycline-induced toxicity contributes to long-term cardiovascular morbidity in cancer survivors. Cardiac troponin is recommended for risk stratification and diagnosis, but the relationship between troponin concentrations—particularly those measured using high-sensitivity assays—and subsequent cardiac dysfunction remains unclear.</div></div><div><h3>Objectives</h3><div>The authors sought to examine associations between high-sensitivity cardiac troponin I (hs-cTnI), cumulative anthracycline dose, number of treatment cycles, and changes in left ventricular (LV) function.</div></div><div><h3>Methods</h3><div>The Cardiac CARE trial was a prospective, multicenter, randomized, open-label, blinded-endpoint study of cardioprotective therapy in patients with elevated baseline hs-cTnI undergoing high-dose anthracycline chemotherapy. Hs-cTnI was measured before each chemotherapy cycle and at 2, 4, and 6 months after treatment. LV function was assessed by cardiac magnetic resonance at baseline and 6 months post-chemotherapy.</div></div><div><h3>Results</h3><div>Of the 175 participants (mean age 52 ± 11 years; 86.5% women), 171 received ≥3 anthracycline cycles. The median cumulative epirubicin-equivalent dose was 600 mg/m<sup>2</sup> (Q1-Q3: 513-660 mg/m<sup>2</sup>). Peak hs-cTnI concentrations were observed 2 months after chemotherapy (median 14.0 ng/L [Q1-Q3: 9.0-30.5 ng/L]) and statistically correlated with the number of treatment cycles, but not with cumulative dose. No participants developed an LV ejection fraction (LVEF) <50%, although 24 of 171 patients (14.0%) experienced a decline in LVEF >10%. Hs-cTnI showed a weak correlation with LVEF change and was not predictive of global longitudinal strain by cardiac magnetic resonance.</div></div><div><h3>Conclusions</h3><div>Hs-cTnI levels were not associated with cumulative anthracycline dose and were only weakly associated with LVEF decline at 6 months. These findings suggest that mild myocardial injury, as reflected by hs-cTnI elevation, may not reliably predict subsequent cardiac dysfunction following anthracycline chemotherapy.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 725-735"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}