{"title":"Concomitant Administration of Dantrolene is Sufficient to Protect Against Doxorubicin-Induced Cardiomyopathy","authors":"Yoshihide Nakamura MD, PhD , Takeshi Yamamoto MD, PhD , Shigeki Kobayashi MD, PhD , Takeshi Suetomi MD, PhD , Hitoshi Uchinoumi MD, PhD , Tetsuro Oda MD, PhD , Motoaki Sano MD, PhD , Masafumi Yano MD, PhD","doi":"10.1016/j.jaccao.2024.10.011","DOIUrl":"10.1016/j.jaccao.2024.10.011","url":null,"abstract":"<div><h3>Background</h3><div>Doxorubicin (DOX), a commonly used anticancer agent, can result in cardiac dysfunction, presenting a significant clinical challenge. DOX has been shown to induces Ca<sup>2+</sup> leakage via the ryanodine receptor 2 (RYR2) of the sarcoplasmic reticulum, increasing Ca<sup>2+</sup> levels in the cytoplasm.</div></div><div><h3>Objectives</h3><div>This study investigated whether stabilizing RYR2 could suppress DOX-induced cardiomyopathy (DIC) and identified the optimal duration of dantrolene treatment as a pharmacological method.</div></div><div><h3>Methods</h3><div>We investigated the effects of RYR2 stabilization on DOX cardiotoxicity using in vivo and in vitro experiments.</div></div><div><h3>Results</h3><div>DOX administration caused calmodulin dissociation, marked Ca<sup>2+</sup> leakage from RYR2, and increased oxidative stress in isolated cardiomyocytes. Stabilizing the RYR2 tetramer—either pharmacologically with dantrolene or genetically via RYR2 V3599K mutation, which enhances calmodulin binding affinity—suppressed these effects. In DIC mice models, DOX impaired cardiac function, increased fibrosis and TUNEL-positive cells, reduced GRP78, and elevated lipid peroxide levels, leading to endoplasmic reticulum stress and ferroptosis. Both continuous dantrolene treatment and RYR2 V3599K mutation improved cardiac function. Interestingly, dantrolene administration provided myocardial protection even when terminated 7 days after DOX.</div></div><div><h3>Conclusions</h3><div>Short-term concomitant use of dantrolene offers a promising and clinically feasible strategy to prevent DIC. Given dantrolene’s established clinical safety as a treatment for malignant hyperthermia, these findings suggest potential for repositioning dantrolene in DIC prevention.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 1","pages":"Pages 38-52"},"PeriodicalIF":12.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura De Michieli MD , Omar F. AbouEzzeddine MDCM, MS , Muhannad A. Abbasi MD , Daniel R. Davies MD , Christopher G. Scott MS , Eli Muchtar MD , Angela Dispenzieri MD , Martha Grogan MD , Margaret M. Redfield MD , Allan S. Jaffe MD
{"title":"Biomarkers to Predict Abnormal Technetium-99m Pyrophosphate Scans in Patients With Suspected Transthyretin Amyloidosis","authors":"Laura De Michieli MD , Omar F. AbouEzzeddine MDCM, MS , Muhannad A. Abbasi MD , Daniel R. Davies MD , Christopher G. Scott MS , Eli Muchtar MD , Angela Dispenzieri MD , Martha Grogan MD , Margaret M. Redfield MD , Allan S. Jaffe MD","doi":"10.1016/j.jaccao.2024.10.013","DOIUrl":"10.1016/j.jaccao.2024.10.013","url":null,"abstract":"<div><h3>Background</h3><div>Technetium Tc 99m pyrophosphate scintigraphy (<sup>99m</sup>Tc PYP imaging) is a diagnostic tool for transthyretin amyloid cardiomyopathy (ATTR-CM). Cardiac biomarkers, particularly high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro–B-type natriuretic peptide (NT-proBNP), may help identify patients at low or high risk for ATTR-CM.</div></div><div><h3>Objectives</h3><div>The authors sought to evaluate the predictive value of hs-cTnT and NT-proBNP in patients undergoing <sup>99m</sup>Tc PYP imaging for suspected ATTR-CM in a large U.S. cohort.</div></div><div><h3>Methods</h3><div>This was a retrospective study of patients who underwent <sup>99m</sup>Tc PYP imaging between May 2013 and September 2022, including those with at least 1 hs-cTnT measurement within 6 months of the scan.</div></div><div><h3>Results</h3><div>ATTR-CM was diagnosed in 427 of 1,442 patients (29.6%). A hs-cTnT level <6 ng/L (n = 50, 3.5%) showed a negative predictive value of 100% (95% CI: 93%-100%) and sensitivity of 100% (95% CI: 99%-100%) for ruling out ATTR-CM. As the hs-cTnT threshold increased, the number of patients who could be ruled out also increased, but false negatives emerged. The positive predictive value for ruling in ATTR-CM remained low. NT-proBNP showed similar results (n = 1,378). The combination of hs-cTnT <14 ng/L and NT-proBNP <60 ng/L identified 45 patients (3.3%) without ATTR-CM.</div></div><div><h3>Conclusions</h3><div>In patients undergoing <sup>99m</sup>Tc PYP imaging for suspected ATTR-CM, very low hs-cTnT levels can effectively rule out the diagnosis, although in a small subset of patients. Higher thresholds increase the risk of false negatives. NT-proBNP and combined biomarker strategies showed similar trends, the utility of hs-cTnT and NT-proBNP for ruling in the disease is limited.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 1","pages":"Pages 70-78"},"PeriodicalIF":12.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne Blaes MD, MS , Anju Nohria MD , Saro Armenian DO, MPH , Carmen Bergom MD, PhD , Paaladinesh Thavendiranathan MD, SM , Ana Barac MD, PhD , Gabriela Sanchez-Petitto MD , Sanjal Desai MD , Leah L. Zullig PhD , Alicia K. Morgans MD, MPH , Joerg Herrmann MD, PhD
{"title":"Cardiovascular Considerations After Cancer Therapy","authors":"Anne Blaes MD, MS , Anju Nohria MD , Saro Armenian DO, MPH , Carmen Bergom MD, PhD , Paaladinesh Thavendiranathan MD, SM , Ana Barac MD, PhD , Gabriela Sanchez-Petitto MD , Sanjal Desai MD , Leah L. Zullig PhD , Alicia K. Morgans MD, MPH , Joerg Herrmann MD, PhD","doi":"10.1016/j.jaccao.2024.06.006","DOIUrl":"10.1016/j.jaccao.2024.06.006","url":null,"abstract":"<div><div>Cancer survivors, particularly those treated with anthracyclines and chest radiation, face an elevated risk of cancer therapy–related cardiovascular toxicity. These complications affect not only physical health, but also life expectancy. Risk factors for cancer therapy–related cardiovascular toxicity include age at which cancer treatment was received, the use of (potentially) cardiotoxic cancer therapies, and the presence of concomitant cardiovascular risk factors. Current guidelines provide recommendations for cardiovascular surveillance after cancer therapy, including type and frequency. All cancer survivors are advised to undergo annual clinical screenings and optimization of cardiovascular risk factors. Those at higher risk should undergo additional cardiovascular testing. This document aims to summarize the available evidence, present practical recommendations, and outline existent gaps in the current literature regarding cardiovascular care after cancer therapies.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 1","pages":"Pages 1-19"},"PeriodicalIF":12.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suresh Poudel PhD , Him Shrestha PhD , Yue Pan PhD , Qian Li PhD , Kendrick Li PhD , Cindy Im PhD , Stephanie B. Dixon MD , Matthew J. Ehrhardt MD , Daniel A. Mulrooney MD , Suiping Zhou PhD , Haiyan Tan PhD , Anthony A. High PhD , Paul W. Burridge PhD , Smita Bhatia MD , John L. Jefferies MD , Kirsten K. Ness PhD , Melissa M. Hudson MD , Leslie L. Robison PhD , Gregory T. Armstrong MD , Junmin Peng PhD , Yadav Sapkota PhD
{"title":"Serum Proteins Predict Treatment-Related Cardiomyopathy Among Survivors of Childhood Cancer","authors":"Suresh Poudel PhD , Him Shrestha PhD , Yue Pan PhD , Qian Li PhD , Kendrick Li PhD , Cindy Im PhD , Stephanie B. Dixon MD , Matthew J. Ehrhardt MD , Daniel A. Mulrooney MD , Suiping Zhou PhD , Haiyan Tan PhD , Anthony A. High PhD , Paul W. Burridge PhD , Smita Bhatia MD , John L. Jefferies MD , Kirsten K. Ness PhD , Melissa M. Hudson MD , Leslie L. Robison PhD , Gregory T. Armstrong MD , Junmin Peng PhD , Yadav Sapkota PhD","doi":"10.1016/j.jaccao.2024.10.004","DOIUrl":"10.1016/j.jaccao.2024.10.004","url":null,"abstract":"<div><h3>Background</h3><div>Anthracyclines, a highly effective chemotherapy for many pediatric malignancies, cause cardiomyopathy, a major late effect in adult survivors. Biomarkers are needed for early detection and targeted interventions for anthracycline-associated cardiomyopathy.</div></div><div><h3>Objectives</h3><div>The aim of this study was to determine if serum proteins and/or metabolites in asymptomatic childhood cancer survivors can discriminate symptomatic cardiomyopathy.</div></div><div><h3>Methods</h3><div>Using an untargeted mass spectrometry–based approach, 867 proteins and 218 metabolites were profiled in serum samples of 75 asymptomatic survivors with subclinical cardiomyopathy and 75 individually matched survivors without cardiomyopathy from SJLIFE (St. Jude Lifetime Cohort Study). Models were developed on the basis of the most influential differentially expressed proteins and metabolites, using conditional logistic regression with a least absolute shrinkage and selection operator penalty. The best performing model was evaluated in 23 independent survivors with severe or symptomatic cardiomyopathy and 23 individually matched cardiomyopathy-free survivors.</div></div><div><h3>Results</h3><div>A 27-protein model identified using conditional logistic regression with a least absolute shrinkage and selection operator penalty discriminated symptomatic or severe cardiomyopathy requiring heart failure medications in independent survivors; 19 of 23 individually matched survivors with and without cardiomyopathy were correctly discriminated with 82.6% (95% CI: 71.4%-93.8%) accuracy. Pathway enrichment analysis revealed that the 27 proteins were enriched in various biological processes, many of which have been linked to anthracycline-related cardiomyopathy.</div></div><div><h3>Conclusions</h3><div>A risk model was developed on the basis of the differential expression of serum proteins in subclinical cardiomyopathy, which accurately discriminated the risk for severe cardiomyopathy in an independent, matched sample. Further assessment of these proteins as biomarkers of cardiomyopathy risk should be conducted in external larger cohorts and through prospective studies.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 1","pages":"Pages 56-67"},"PeriodicalIF":12.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shanshan Gao MD, Jingjjing Mu MD, Beina Hui MD, Weibin Hu MD, Yongkai Lu PhD
{"title":"Enhancing Life’s Essential 8 for Cardiovascular Risk Assessment in Breast Cancer Survivors","authors":"Shanshan Gao MD, Jingjjing Mu MD, Beina Hui MD, Weibin Hu MD, Yongkai Lu PhD","doi":"10.1016/j.jaccao.2024.09.010","DOIUrl":"10.1016/j.jaccao.2024.09.010","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"6 6","pages":"Page 987"},"PeriodicalIF":12.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isabel G. Scalia MD , Mohamad Bassam Sonbol MD , Juan M. Farina MD , Milagros Pereyra MD , Yuxiang Wang MD , Tanios S. Bekaii-Saab MD , Ming Yang MD , Heidi M. Connolly MD , Patricia A. Pellikka MD , Joerg Herrmann MD , Thorvardur R. Halfdanarson MD , Jason S. Starr DO , Sushil Allen Luis MBBS, PhD , Reza Arsanjani MD , Chadi Ayoub MBBS, PhD
{"title":"Lutetium-177 DOTATATE Therapy and Cardiac Outcomes in Patients With Neuroendocrine Tumor and Cardiac Metastases","authors":"Isabel G. Scalia MD , Mohamad Bassam Sonbol MD , Juan M. Farina MD , Milagros Pereyra MD , Yuxiang Wang MD , Tanios S. Bekaii-Saab MD , Ming Yang MD , Heidi M. Connolly MD , Patricia A. Pellikka MD , Joerg Herrmann MD , Thorvardur R. Halfdanarson MD , Jason S. Starr DO , Sushil Allen Luis MBBS, PhD , Reza Arsanjani MD , Chadi Ayoub MBBS, PhD","doi":"10.1016/j.jaccao.2024.09.008","DOIUrl":"10.1016/j.jaccao.2024.09.008","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"6 6","pages":"Pages 982-984"},"PeriodicalIF":12.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}