CoChat
Sign Up
Cited by 747Chemotherapy-induced cardiotoxicity and mitigationCardiac tumors and thrombiCancer Treatment and Pharmacology

Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia

Open access
Herrmann, Joerg·2020·Nature Reviews Cardiology
DOI 10.1038/s41569-020-0348-1PMC PMC8782611
Open this paper in CoChat — free account

Abstract

Remarkable progress has been made in the development of new therapies for cancer, dramatically changing the landscape of treatment approaches for several malignancies and continuing to increase patient survival. Accordingly, adverse effects of cancer therapies that interfere with the continuation of best-possible care, induce life-threatening risks or lead to long-term morbidity are gaining increasing importance. Cardiovascular toxic effects of cancer therapeutics and radiation therapy are the epitome of such concerns, and proper knowledge, interpretation and management are needed and have to be placed within the context of the overall care of individual patients with cancer. Furthermore, the cardiotoxicity spectrum has broadened to include myocarditis with immune checkpoint inhibitors and cardiac dysfunction in the setting of cytokine release syndrome with chimeric antigen receptor T cell therapy. An increase in the incidence of arrhythmias related to inflammation such as atrial fibrillation can also be expected, in addition to the broadening set of cancer therapeutics that can induce prolongation of the corrected QT interval. Therefore, cardiologists of today have to be familiar not only with the cardiotoxicity associated with traditional cancer therapies, such as anthracycline, trastuzumab or radiation therapy, but even more so with an ever-increasing repertoire of therapeutics. This Review provides this information, summarizing the latest developments at the juncture of cardiology, oncology and haematology.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41569-020-0348-1

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • ICI myocarditis occurs in less than 1% of patients.

    “Despite occurring in <1% of patients”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [176]

    The Type III cardiomyopathy section says currently reported rates of ICI-induced myocarditis are up to 1%, which supports the claim's approximate frequency. It also says incidence estimates are evolving and expected to rise beyond those rates, so an unqualified statement that it occurs in less than 1% of patients is stronger than the source supports. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • ICI myocarditis has a fatality rate of up to 50%.

    “ICI myocarditis has a high fatality rate of up to 50%.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [176]

    The Type III cardiomyopathy section describes ICI myocarditis as having high mortality, citing 40% in a systematic review and meta-analysis. It does not report a fatality rate of up to 50%; the nearly 50% figure in a separate 35-patient study refers to major adverse cardiac events, with mortality of 17%. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • ICI myocarditis is an infrequent but potentially fatal condition associated with ICI therapies, especially when used in combination.

    “ICI myocarditis emerges as an infrequent but potentially fatal condition associated with ICI therapies, especially when used in combination”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [176]

    The Type III cardiomyopathy section reports ICI-induced myocarditis at rates of up to 1% and a mortality of 40% in a systematic review, supporting its description as infrequent but potentially fatal. It says immune-related adverse events overall are most frequent with combined CTLA4 and PDL1 inhibition, but does not establish that myocarditis specifically is more frequent with combination therapy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 261

  1. [1]Global Burden of Disease Cancer Collaboration. The global burden of cancer 2013. JAMA Oncol. 1, 505– 527 (2015). 26181261 PMC4500822
  2. [3]Ewer MS & Ewer SM Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat. Rev. Cardiol 7, 564– 575 (2010). 20842180
  3. [4]Ewer MS & Ewer SM Cardiotoxicity of anticancer treatments. Nat. Rev. Cardiol 12, 547– 558 (2015). 25962976
  4. [5]Herrmann J Vascular toxic effects of cancer therapies. Nat. Rev. Cardiol 10.1038/s41569-020-0347-2 (2020). PMC8782612 32218531 · DOI
  5. [6]Gianni L Anthracycline cardiotoxicity: from bench to bedside. J. Clin. Oncol 26, 3777– 3784 (2008). 18669466 PMC3018290
  6. [7]Herrmann J Evaluation and management of patients with heart disease and cancer: cardio-oncology. Mayo Clin. Proc 89, 1287– 1306 (2014). 25192616 PMC4258909
  7. [8]Bristow MR Early anthracycline cardiotoxicity. Am. J. Med 65, 823– 832 (1978). 707541
  8. [9]Bristow MR, Billingham ME, Mason JW & Daniels JR Clinical spectrum of anthracycline antibiotic cardiotoxicity. Cancer Treat. Rep 62, 873– 879 (1978). 667861
  9. [10]Ferrans VJ Overview of cardiac pathology in relation to anthracycline cardiotoxicity. Cancer Treat. Rep 62, 955– 961 (1978). 352510
  10. [11]Berry GJ & Jorden M Pathology of radiation and anthracycline cardiotoxicity. Pediatr. Blood Cancer 44, 630– 637 (2005). 15825155
  11. [12]Ewer MS A comparison of cardiac biopsy grades and ejection fraction estimations in patients receiving Adriamycin. J. Clin. Oncol 2, 112– 117 (1984). 6699662
  12. [13]Nousiainen T, Jantunen E, Vanninen E & Hartikainen J Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients. Br. J. Cancer 86, 1697– 1700 (2002). 12087452 PMC2375393
  13. [14]Felker GM Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N. Engl. J. Med 342, 1077– 1084 (2000). 10760308
  14. [15]Mazur M Burden of cardiac arrhythmias in patients with anthracycline-related cardiomyopathy. JACC Clin. Electrophysiol 3, 139– 150 (2017). 29759386
  15. [16]Kremer LC, van der Pal HJ, Offringa M, van Dalen EC & Voute PA Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann. Oncol 13, 819– 829 (2002). 12123328
  16. [17]Zhang S Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat. Med 18, 1639– 1642 (2012). 23104132
  17. [18]Chen B, Peng X, Pentassuglia L, Lim CC & Sawyer DB Molecular and cellular mechanisms of anthracycline cardiotoxicity. Cardiovasc. Toxicol 7, 114– 121 (2007). 17652815
  18. [19]Varga ZV, Ferdinandy P, Liaudet L & Pacher P Drug-induced mitochondrial dysfunction and cardiotoxicity. Am. J. Physiol. Heart Circ. Physiol 309, H1453– H1467 (2015). 26386112 PMC4666974
  19. [20]Ichikawa Y Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J. Clin. Invest 124, 617– 630 (2014). 24382354 PMC3904631
  20. [21]Lebrecht D, Setzer B, Ketelsen UP, Haberstroh J & Walker UA Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain defects in chronic doxorubicin cardiomyopathy. Circulation 108, 2423– 2429 (2003). 14568902
  21. [22]De Angelis A Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function. Circulation 121, 276– 292 (2010). 20038740 PMC2810713
  22. [23]Piegari E Doxorubicin induces senescence and impairs function of human cardiac progenitor cells. Basic Res. Cardiol 108, 334 (2013). 23411815
  23. [24]Ali MK, Ewer MS, Gibbs HR, Swafford J & Graff KL Late doxorubicin-associated cardiotoxicity in children. The possible role of intercurrent viral infection. Cancer 74, 182– 188 (1994). 8004574
  24. [25]Carter P Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl Acad. Sci. USA 89, 4285– 4289 (1992). 1350088 PMC49066
  25. [26]Moasser MM The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 26, 6469– 6487 (2007). 17471238 PMC3021475
  26. [27]Moasser MM & Krop IE The evolving landscape of HER2 targeting in breast cancer. JAMA Oncol. 1, 1154– 1161 (2015). 26204261
  27. [28]Slamon DJ Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med 344, 783– 792 (2001). 11248153
  28. [29]Farolfi A Trastuzumab-induced cardiotoxicity in early breast cancer patients: a retrospective study of possible risk and protective factors. Heart 99, 634– 639 (2013). 23349345
  29. [30]Nowsheen S Trastuzumab in female breast cancer patients with reduced left ventricular ejection fraction. J. Am. Heart Assoc 7, e008637 (2018). 30371238 PMC6201446
  30. [31]Ewer MS & Lippman SM Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J. Clin. Oncol 23, 2900– 2902 (2005). 15860848
  31. [32]Ewer MS Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J. Clin. Oncol 23, 7820– 7826 (2005). 16258084
  32. [33]Tan TC Time trends of left ventricular ejection fraction and myocardial deformation indices in a cohort of women with breast cancer treated with anthracyclines, taxanes, and trastuzumab. J. Am. Soc. Echocardiogr 28, 509– 514 (2015). 25772019
  33. [34]Yu AF Trastuzumab interruption and treatment-induced cardiotoxicity in early HER2-positive breast cancer. Breast Cancer Res. Treat 149, 489– 495 (2015). 25552363 PMC4970316
  34. [35]Guarneri V Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J. Clin. Oncol 24, 4107– 4115 (2006). 16908934
  35. [36]Cardinale D Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J. Clin. Oncol 28, 3910– 3916 (2010). 20679614
  36. [37]ElZarrad MK Trastuzumab alters the expression of genes essential for cardiac function and induces ultrastructural changes of cardiomyocytes in mice. PLoS One 8, e79543 (2013). 24255707 PMC3821852
  37. [38]de Azambuja E Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1–01). J. Clin. Oncol 32, 2159– 2165 (2014). 24912899
  38. [39]Chen J Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J. Am. Coll. Cardiol 60, 2504– 2512 (2012). 23158536
  39. [40]Bowles EJ Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J. Natl Cancer Inst 104, 1293– 1305 (2012). 22949432 PMC3433392
  40. [41]Baselga J Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N. Engl. J. Med 366, 109– 119 (2012). 22149875 PMC5705202
  41. [43]Piccart-Gebhart M Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J. Clin. Oncol 34, 1034– 1042 (2016). 26598744 PMC4872016
  42. [44]Watanabe H Congestive heart failure during osimertinib treatment for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Intern. Med 56, 2195– 2197 (2017). 28781309 PMC5596283
  43. [45]Bhullar KS Kinase-targeted cancer therapies: progress, challenges and future directions. Mol. Cancer 17, 48 (2018). 29455673 PMC5817855
  44. [46]Thompson PA, Kantarjian HM & Cortes JE Diagnosis and treatment of chronic myeloid leukemia in 2015. Mayo Clin. Proc 90, 1440– 1454 (2015). 26434969 PMC5656269
  45. [47]Kerkela R Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat. Med 12, 908– 916 (2006). 16862153
  46. [48]Herman EH A multifaceted evaluation of imatinib-induced cardiotoxicity in the rat. Toxicol. Pathol 39, 1091– 1106 (2011). 21937741
  47. [49]Wolf A Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies. Leuk. Res 34, 1180– 1188 (2010). 20122731
  48. [50]Ribeiro AL An evaluation of the cardiotoxicity of imatinib mesylate. Leuk. Res 32, 1809– 1814 (2008). 18495246
  49. [51]Estabragh ZR A prospective evaluation of cardiac function in patients with chronic myeloid leukaemia treated with imatinib. Leuk. Res 35, 49– 51 (2011). 21030079
  50. [52]Force T, Krause DS & Van Etten RA Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat. Rev. Cancer 7, 332– 344 (2007). 17457301
  51. [53]Greineder CF, Kohnstamm S & Ky B Heart failure associated with sunitinib: lessons learned from animal models. Curr. Hypertens. Rep 13, 436– 441 (2011). 21826469
  52. [54]Hasinoff BB, Patel D & O’Hara KA Mechanisms of myocyte cytotoxicity induced by the multiple receptor tyrosine kinase inhibitor sunitinib. Mol. Pharmacol 74, 1722– 1728 (2008). 18815214
  53. [55]Hasinoff BB & Patel D The lack of target specificity of small molecule anticancer kinase inhibitors is correlated with their ability to damage myocytes in vitro. Toxicol. Appl. Pharmacol 249, 132– 139 (2010). 20832415
  54. [56]Hasinoff BB The cardiotoxicity and myocyte damage caused by small molecule anticancer tyrosine kinase inhibitors is correlated with lack of target specificity. Toxicol. Appl. Pharmacol 244, 190– 195 (2010). 20045709
  55. [57]Will Y Effect of the multitargeted tyrosine kinase inhibitors imatinib, dasatinib, sunitinib, and sorafenib on mitochondrial function in isolated rat heart mitochondria and H9c2 cells. Toxicol. Sci 106, 153– 161 (2008). 18664550
  56. [58]Jacob F Analysis of tyrosine kinase inhibitor-mediated decline in contractile force in rat engineered heart tissue. PLoS One 11, e0145937 (2016). 26840448 PMC4740402
  57. [59]Lamore SD Deconvoluting kinase inhibitor induced cardiotoxicity. Toxicol. Sci 158, 213– 226 (2017). 28453775 PMC5837613
  58. [60]Stuhlmiller TJ Kinome and transcriptome profiling reveal broad and distinct activities of erlotinib, sunitinib, and sorafenib in the mouse heart and suggest cardiotoxicity from combined signal transducer and activator of transcription and epidermal growth factor receptor inhibition. J. Am. Heart Assoc 6, e006635 (2017). 29051215 PMC5721866
  59. [61]Sharma A High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells. Sci. Transl Med 9, eaaf2584 (2017). 28202772 PMC5409837
  60. [62]Shim JV Mechanistic systems modeling to improve understanding and prediction of cardiotoxicity caused by targeted cancer therapeutics. Front. Physiol 8, 651 (2017). 28951721 PMC5599787
  61. [63]Brown SA, Sandhu N & Herrmann J Systems biology approaches to adverse drug effects: the example of cardio-oncology. Nat. Rev. Clin. Oncol 12, 718– 731 (2015). 26462128
  62. [64]Brown SA, Nhola L & Herrmann J Cardiovascular toxicities of small molecule tyrosine kinase inhibitors: an opportunity for systems-based approaches. Clin. Pharmacol. Ther 101, 65– 80 (2017). 27806435
  63. [65]Plana JC Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J. Am. Soc. Echocardiogr 27, 911– 939 (2014). 25172399
  64. [66]Cardinale D Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 109, 2749– 2754 (2004). 15148277
  65. [67]Negishi T, Thavendiranathan P, Negishi K & Marwick TH Rationale and design of the strain surveillance of chemotherapy for improving cardiovascular outcomes: the SUCCOUR trial. JACC Cardiovasc. Imaging 11, 1098– 1105 (2018). 29909105
  66. [68]US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03879629 (2019) 28792816
  67. [69]Yancy CW 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J. Am. Coll. Cardiol 70, 776– 803 (2017). 28461007
  68. [71]Curigliano G Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines. Ann. Oncol 23, vii155– vii166 (2012). 22997448
  69. [72]Russell RR The role and clinical effectiveness of multimodality imaging in the management of cardiac complications of cancer and cancer therapy. J. Nucl. Cardiol 23, 856– 884 (2016). 27251147
  70. [73]Chang HM, Okwuosa TM, Scarabelli T, Moudgil R & Yeh ETH Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management: part 2. J. Am. Coll. Cardiol 70, 2552– 2565 (2017). 29145955 PMC5825188
  71. [74]Alexander J Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography. N. Engl. J. Med 300, 278– 283 (1979). 759880
  72. [75]Avila MS Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial. J. Am. Coll. Cardiol 71, 2281– 2290 (2018). 29540327
  73. [76]Urbanek K Cardioprotection by targeting the pool of resident and extracardiac progenitors. Curr. Drug Targets 16, 884– 894 (2015). 25619752
  74. [77]Hamed S Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy. Eur. Heart J 27, 1876– 1883 (2006). 16731534
  75. [78]Hoch M Erythropoietin preserves the endothelial differentiation capacity of cardiac progenitor cells and reduces heart failure during anticancer therapies. Cell Stem Cell 9, 131– 143 (2011). 21816364
  76. [79]Burridge PW Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity. Nat. Med 22, 547– 556 (2016). 27089514 PMC5086256
  77. [80]Chen IY, Matsa E & Wu JC Induced pluripotent stem cells: at the heart of cardiovascular precision medicine. Nat. Rev. Cardiol 13, 333– 349 (2016). 27009425 PMC5917945
  78. [81]Pituskin E Multidisciplinary approach to novel therapies in cardio-oncology research (MANTICORE 101-Breast): a randomized trial for the prevention of trastuzumab-associated cardiotoxicity. J. Clin. Oncol 35, 870– 877 (2017). 27893331
  79. [82]Boekhout AH Angiotensin II-receptor inhibition with candesartan to prevent trastuzumab-related cardiotoxic effects in patients with early breast cancer: a randomized clinical trial. JAMA Oncol. 2, 1030– 1037 (2016). 27348762
  80. [83]Nowsheen S Trastuzumab in female breast cancer patients with reduced left ventricular ejection fraction. J. Am. Heart Assoc 7, e008637 (2018). 30371238 PMC6201446
  81. [84]Crone SA ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat. Med 8, 459– 465 (2002). 11984589
  82. [85]Herrmann J, Herrmann SM & Haddad TC New-onset heart failure in association with severe hypertension during trastuzumab therapy. Mayo Clin. Proc 89, 1734– 1739 (2014). 25441402
  83. [86]Gilchrist SC Cardio-oncology rehabilitation to manage cardiovascular outcomes in cancer patients and survivors: a scientific statement from the American Heart Association. Circulation 139, e997– e1012 (2019). 30955352 PMC7603804
  84. [87]Squires RW, Shultz AM & Herrmann J Exercise training and cardiovascular health in cancer patients. Curr. Oncol. Rep 20, 27 (2018). 29525828
  85. [88]Cerny J, Hassan A, Smith C & Piperdi B Coronary vasospasm with myocardial stunning in a patient with colon cancer receiving adjuvant chemotherapy with FOLFOX regimen. Clin. Colorectal Cancer 8, 55– 58 (2009). 19203898
  86. [89]Basselin C 5-Fluorouracil-induced Tako-Tsubo-like syndrome. Pharmacotherapy 31, 226 (2011). 21275498
  87. [90]Gianni M, Dentali F & Lonn E 5 flourouracil-induced apical ballooning syndrome: a case report. Blood Coagul. Fibrinolysis 20, 306– 308 (2009). 19300240
  88. [91]Grunwald MR, Howie L & Diaz LA Jr. Takotsubo cardiomyopathy and fluorouracil: case report and review of the literature. J. Clin. Oncol 30, e11– e14 (2012). 22147738
  89. [92]Kobayashi N A case of takotsubo cardiomyopathy during 5-fluorouracil treatment for rectal adenocarcinoma. J. Nippon Med. Sch 76, 27– 33 (2009). 19305108
  90. [93]Ozturk MA, Ozveren O, Cinar V, Erdik B & Oyan B Takotsubo syndrome: an underdiagnosed complication of 5-fluorouracil mimicking acute myocardial infarction. Blood Coagul. Fibrinolysis 24, 90– 94 (2013). 23249567
  91. [94]S YH, Tornvall P, Tornerud M & Henareh L Capecitabine caused cardiogenic shock through induction of global takotsubo syndrome. Cardiovasc. Revasc. Med 14, 57– 61 (2013). 23218901
  92. [95]Stewart T, Pavlakis N & Ward M Cardiotoxicity with 5-fluorouracil and capecitabine: more than just vasospastic angina. Intern. Med. J 40, 303– 307 (2010). 20529041
  93. [96]Dechant C Acute reversible heart failure caused by coronary vasoconstriction due to continuous 5-fluorouracil combination chemotherapy. Case Rep. Oncol 5, 296– 301 (2012). 22740819 PMC3383295
  94. [97]Tsibiribi P Cardiac lesions induced by 5-fluorouracil in the rabbit. Hum. Exp. Toxicol 25, 305– 309 (2006). 16866187
  95. [98]Martin M Lethal cardiac toxicity after cisplatin and 5-fluorouracil chemotherapy. Report of a case with necropsy study. Am. J. Clin. Oncol 12, 229– 234 (1989). 2729179
  96. [99]Eskandari MR, Moghaddam F, Shahraki J & Pourahmad J A comparison of cardiomyocyte cytotoxic mechanisms for 5-fluorouracil and its pro-drug capecitabine. Xenobiotica 45, 79– 87 (2015). 25034007
  97. [100]Focaccetti C Effects of 5-fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ROS production in endothelial cells and cardiomyocytes. PLoS One 10, e0115686 (2015). 25671635 PMC4324934
  98. [101]Lamberti M A mechanistic study on the cardiotoxicity of 5-fluorouracil in vitro and clinical and occupational perspectives. Toxicol. Lett 227, 151– 156 (2014). 24704391
  99. [102]Lischke J, Lang C, Sawodny O & Feuer R Impairment of energy metabolism in cardiomyocytes caused by 5-FU catabolites can be compensated by administration of amino acids. Conf. Proc. IEEE Eng. Med. Biol. Soc 2015, 5363– 5366 (2015). 26737503
  100. [103]Polk A, Vistisen K, Vaage-Nilsen M & Nielsen DL A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. BMC Pharmacol. Toxicol 15, 47 (2014). 25186061 PMC4170068
  101. [104]Sara JD 5-fluorouracil and cardiotoxicity: a review. Ther. Adv. Med. Oncol 10, 1758835918780140 (2018). PMC6024329 29977352
  102. [105]Arellano M, Malet-Martino M, Martino R & Gires P The anti-cancer drug 5-fluorouracil is metabolized by the isolated perfused rat liver and in rats into highly toxic fluoroacetate. Br. J. Cancer 77, 79– 86 (1998). 9459149 PMC2151255
  103. [106]Matsubara I, Kamiya J & Imai S Cardiotoxic effects of 5-fluorouracil in the guinea pig. Jpn. J. Pharmacol 30, 871– 879 (1980). 7241861
  104. [107]Diasio RB The role of dihydropyrimidine dehydrogenase (DPD) modulation in 5-FU pharmacology. Oncology 12, 23– 27 (1998). 9830621
  105. [108]Papanastasopoulos P & Stebbing J Molecular basis of 5-fluorouracil-related toxicity: lessons from clinical practice. Anticancer Res. 34, 1531– 1535 (2014). 24692679
  106. [109]Franco TH, Khan A, Joshi V & Thomas B Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer. Ther. Clin. Risk Manag 4, 1367– 1370 (2008). 19337443 PMC2643117
  107. [110]Numico G Takotsubo syndrome in a patient treated with sunitinib for renal cancer. J. Clin. Oncol 30, e218– e220 (2012). 22802320
  108. [111]Touyz RM & Herrmann J Cardiotoxicity with vascular endothelial growth factor inhibitor therapy. NPJ Precis. Oncol 2, 13 (2018). 30202791 PMC5988734
  109. [112]Baffert F Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am. J. Physiol. Heart Circ. Physiol 290, H547– H559 (2006). 16172161
  110. [113]Kamba T VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am. J. Physiol. Heart Circ. Physiol 290, H560– H576 (2006). 16172168
  111. [114]Lazarus A & Keshet E Vascular endothelial growth factor and vascular homeostasis. Proc. Am. Thorac. Soc 8, 508– 511 (2011). 22052928
  112. [115]Maharaj AS & D’Amore PA Roles for VEGF in the adult. Microvasc. Res 74, 100– 113 (2007). 17532010 PMC2128714
  113. [116]June CH & Sadelain M Chimeric antigen receptor therapy. N. Engl. J. Med 379, 64– 73 (2018). 29972754 PMC7433347
  114. [117]Brudno JN & Kochenderfer JN Chimeric antigen receptor T-cell therapies for lymphoma. Nat. Rev. Clin. Oncol 15, 31– 46 (2018). 28857075 PMC12145160
  115. [118]Brichard VG & Godechal Q MAGE-A3-specific anticancer immunotherapy in the clinical practice. Oncoimmunology 2, e25995 (2013). 24244898 PMC3827067
  116. [119]Linette GP Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122, 863– 871 (2013). 23770775 PMC3743463
  117. [120]Cameron BJ Identification of a titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci. Transl Med 5, 197ra103 (2013). PMC6002776 23926201
  118. [121]Morgan RA Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther 18, 843– 851 (2010). 20179677 PMC2862534
  119. [122]Ahmed N Human epidermal growth factor receptor 2 (HER2) -specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J. Clin. Oncol 33, 1688– 1696 (2015). 25800760 PMC4429176
  120. [123]Brudno JN & Kochenderfer JN Toxicities of chimeric antigen receptor T cells: recognition and management. Blood 127, 3321– 3330 (2016). 27207799 PMC4929924
  121. [124]Bonifant CL, Jackson HJ, Brentjens RJ & Curran KJ Toxicity and management in CAR T-cell therapy. Mol. Ther. Oncolytics 3, 16011 (2016). 27626062 PMC5008265
  122. [125]Neelapu SS Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat. Rev. Clin. Oncol 15, 47– 62 (2018). 28925994 PMC6733403
  123. [126]Sato R & Nasu M A review of sepsis-induced cardiomyopathy. J. Intensive Care 3, 48 (2015). 26566443 PMC4642671
  124. [127]Krishnagopalan S, Kumar A, Parrillo JE & Kumar A Myocardial dysfunction in the patient with sepsis. Curr. Opin. Crit. Care 8, 376– 388 (2002). 12357104
  125. [128]Vallabhajosyula S New-onset heart failure and mortality in hospital survivors of sepsis-related left ventricular dysfunction. Shock 49, 144– 149 (2018). 28727607 PMC5766383
  126. [129]Court O, Kumar A, Parrillo JE & Kumar A Clinical review: myocardial depression in sepsis and septic shock. Crit. Care 6, 500– 508 (2002). 12493071 PMC153435
  127. [130]Morelli A Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 310, 1683– 1691 (2013). 24108526
  128. [131]Kumar A Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock. Crit. Care 12, R35 (2008). 18318900 PMC2447556
  129. [132]Przepiorka D FDA approval: blinatumomab. Clin. Cancer Res 21, 4035– 4039 (2015). 26374073
  130. [133]Slaney CY, Wang P, Darcy PK & Kershaw MH CARs versus BiTEs: a comparison between T cell-redirection strategies for cancer treatment. Cancer Discov. 8, 924– 934 (2018). 30012854
  131. [135]Boutros C Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat. Rev. Clin. Oncol 13, 473– 486 (2016). 27141885
  132. [136]Sury K, Perazella MA & Shirali AC Cardiorenal complications of immune checkpoint inhibitors. Nat. Rev. Nephrol 14, 571– 588 (2018). 30013100
  133. [137]Yang S & Asnani A Cardiotoxicities associated with immune checkpoint inhibitors. Curr. Probl. Cancer 42, 422– 432 (2018). 30173878
  134. [138]Ederhy S Takotsubo-like syndrome in cancer patients treated with immune checkpoint inhibitors. JACC Cardiovasc. Imaging 11, 1187– 1190 (2018). 29550317
  135. [139]Giza DE Stress-induced cardiomyopathy in cancer patients. Am. J. Cardiol 120, 2284– 2288 (2017). 29096885
  136. [140]Ogawa Y Paradigm shift in radiation biology/radiation oncology-exploitation of the “H2O2 effect” for radiotherapy using low-LET (linear energy transfer) radiation such as X-rays and high-energy electrons. Cancers 8, 28 (2016). PMC4810112 26927177
  137. [141]Saiki H Risk of heart failure with preserved ejection fraction in older women after contemporary radiotherapy for breast cancer. Circulation 135, 1388– 1396 (2017). 28132957 PMC5388583
  138. [142]Heselich A High LET radiation shows no major cellular and functional effects on primary cardiomyocytes in vitro. Life Sci. Space Res 16, 93– 100 (2018). 29475525
  139. [144]Fajardo LF & Stewart JR Experimental radiation-induced heart disease. I. Light microscopic studies. Am. J. Pathol 59, 299– 316 (1970). 5443637 PMC2032869
  140. [145]Khan MY Radiation-induced cardiomyopathy. I. An electron microscopic study of cardiac muscle cells. Am. J. Pathol 73, 131– 146 (1973). 4749211 PMC1904046
  141. [146]Fajardo LF & Stewart JR Capillary injury preceding radiation-induced myocardial fibrosis. Radiology 101, 429– 433 (1971). 5114783
  142. [147]Stewart FA, Seemann I, Hoving S & Russell NS Understanding radiation-induced cardiovascular damage and strategies for intervention. Clin. Oncol 25, 617– 624 (2013). 23876528
  143. [148]Cuomo JR How to prevent and manage radiation-induced coronary artery disease. Heart 104, 1647– 1653 (2018). 29764968 PMC6381836
  144. [149]Taunk NK, Haffty BG, Kostis JB & Goyal S Radiation-induced heart disease: pathologic abnormalities and putative mechanisms. Front. Oncol 5, 39 (2015). 25741474 PMC4332338
  145. [150]Cosset JM Pericarditis and myocardial infarctions after Hodgkin’s disease therapy. Int. J. Radiat. Oncol. Biol. Phys 21, 447– 449 (1991). 1905691
  146. [151]Jensen SA & Sorensen JB Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine. Cancer Chemother. Pharmacol 58, 487– 493 (2006). 16418875
  147. [152]Meyer CC, Calis KA, Burke LB, Walawander CA & Grasela TH Symptomatic cardiotoxicity associated with 5-fluorouracil. Pharmacotherapy 17, 729– 736 (1997). 9250550
  148. [153]Clasen SC Fluoropyrimidine-induced cardiac toxicity: challenging the current paradigm. J. Gastrointest. Oncol 8, 970– 979 (2017). 29299356 PMC5750187
  149. [154]Ma WW Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity. Cancer 123, 345– 356 (2017). 27622829 PMC5248610
  150. [155]Truitt R Increased afterload augments sunitinib-induced cardiotoxicity in an engineered cardiac microtissue model. JACC Basic Transl Sci. 3, 265– 276 (2018). 30062212 PMC6059907
  151. [156]Touyz RM, Herrmann SMS & Herrmann J Vascular toxicities with VEGF inhibitor therapies-focus on hypertension and arterial thrombotic events. J. Am. Soc. Hypertens 12, 409– 425 (2018). 29703600 PMC6168784
  152. [157]Chu TF Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370, 2011– 2019 (2007). 18083403 PMC2643085
  153. [158]Di Lorenzo G Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis. Ann. Oncol 20, 1535– 1542 (2009). 19474115
  154. [159]Abdel-Qadir H, Ethier JL, Lee DS, Thavendiranathan P & Amir E Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: a systematic review and meta-analysis. Cancer Treat. Rev 53, 120– 127 (2017). 28104567
  155. [160]Annane D A global perspective on vasoactive agents in shock. Intensive Care Med. 44, 833– 846 (2018). 29868972
  156. [161]Donis N, Oury C, Moonen M & Lancellotti P Treating cardiovascular complications of radiotherapy: a role for new pharmacotherapies. Expert Opin. Pharmacother 19, 431– 442 (2018). 29494295
  157. [162]Lancellotti P Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J. Am. Soc. Echocardiogr 26, 1013– 1032 (2013). 23998694
  158. [163]Iliescu CA SCAI expert consensus statement: evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (endorsed by the Cardiological Society of India, and Sociedad Latino Americana de Cardiologia Intervencionista). Catheter. Cardiovasc. Interv 87, E202– E223 (2016). 26756277
  159. [164]Appelbaum F Acute lethal carditis caused by high-dose combination chemotherapy. A unique clinical and pathological entity. Lancet 1, 58– 62 (1976). 54581
  160. [165]O’Connell TX & Berenbaum MC Cardiac and pulmonary effects of high doses of cyclophosphamide and isophosphamide. Cancer Res. 34, 1586– 1591 (1974). 4833912
  161. [166]Dhesi S Cyclophosphamide-induced cardiomyopathy: a case report, review, and recommendations for management. J. Investig. Med. High Impact Case Rep 1, 2324709613480346 (2013). PMC4528786 26425570
  162. [167]Bianchini G & Gianni L The immune system and response to HER2-targeted treatment in breast cancer. Lancet Oncol. 15, e58– e68 (2014). 24480556
  163. [168]Yousif NG & Al-Amran FG Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice. BMC Cardiovasc. Disord 11, 62 (2011). 21999911 PMC3209438
  164. [169]Asawaeer M, Barton D, Radio S & Chatzizisis YS Tyrosine kinase inhibitor-induced acute myocarditis, myositis, and cardiogenic shock. Methodist Debakey Cardiovasc. J 14, e5– e6 (2018). PMC6217568 30410662
  165. [170]Palmieri DJ & Carlino MS Immune checkpoint inhibitor toxicity. Curr. Oncol. Rep 20, 72 (2018). 30066230
  166. [171]Puzanov I Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J. Immunother. Cancer 5, 95 (2017). 29162153 PMC5697162
  167. [172]Spain L, Diem S & Larkin J Management of toxicities of immune checkpoint inhibitors. Cancer Treat. Rev 44, 51– 60 (2016). 26874776
  168. [173]Eigentler TK Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat. Rev 45, 7– 18 (2016). 26922661
  169. [174]Wang DY Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 4, 1721– 1728 (2018). 30242316 PMC6440712
  170. [175]Lyon AR, Yousaf N, Battisti NML, Moslehi J & Larkin J Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol. 19, e447– e458 (2018). 30191849
  171. [176]Mir H Cardiac complications associated with checkpoint inhibition: a systematic review of the literature in an important emerging area. Can. J. Cardiol 34, 1059– 1068 (2018). 29980467
  172. [177]Escudier M Clinical features, management, and outcomes of immune checkpoint inhibitor-related cardiotoxicity. Circulation 136, 2085– 2087 (2017). 29158217
  173. [178]Johnson DB Fulminant myocarditis with combination immune checkpoint blockade. N. Engl. J. Med 375, 1749– 1755 (2016). 27806233 PMC5247797
  174. [179]Nishimura H Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291, 319– 322 (2001). 11209085
  175. [180]Okazaki T Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat. Med 9, 1477– 1483 (2003). 14595408
  176. [181]Grabie N Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8+ T-cell mediated injury in the heart. Circulation 116, 2062– 2071 (2007). 17938288
  177. [182]Lichtman AH The heart of the matter: protection of the myocardium from T cells. J. Autoimmun 45, 90– 96 (2013). 23810579 PMC3783609
  178. [183]Rodig N Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis. Eur. J. Immunol 33, 3117– 3126 (2003). 14579280
  179. [185]Baban B, Liu JY, Qin X, Weintraub NL & Mozaffari MS Upregulation of programmed death-1 and Its ligand in cardiac injury models: interaction with GADD153. PLoS One 10, e0124059 (2015). 25902191 PMC4406739
  180. [186]Varricchi G, Galdiero MR & Tocchetti CG Cardiac toxicity of immune checkpoint inhibitors: cardio-oncology meets immunology. Circulation 136, 1989– 1992 (2017). 29158212
  181. [187]Freilich M Recovery from anthracycline cardiomyopathy after long-term support with a continuous flow left ventricular assist device. J. Heart Lung Transpl 28, 101– 103 (2009). 19134539
  182. [188]Arangalage D Survival after fulminant myocarditis induced by immune-checkpoint inhibitors. Ann. Intern. Med 167, 683– 684 (2017). 28869988
  183. [189]Mahajan VS & Jarolim P How to interpret elevated cardiac troponin levels. Circulation 124, 2350– 2354 (2011). 22105197
  184. [190]Mahmood SS Myocarditis in patients treated with immune checkpoint inhibitors. J. Am. Coll. Cardiol 71, 1755– 1764 (2018). 29567210 PMC6196725
  185. [191]O’Regan DP & Cook SA Myocarditis or myocardial infarction? MRI can help. Heart 97, 1283 (2011). 21487125
  186. [192]Miller EJ & Culver DA Establishing an evidence-based method to diagnose cardiac sarcoidosis: the complementary use of cardiac magnetic resonance imaging and FDG-PET. Circ. Cardiovasc. Imaging 11, e007408 (2018). 29335273
  187. [193]Wang DY, Okoye GD, Neilan TG, Johnson DB & Moslehi JJ Cardiovascular toxicities associated with cancer immunotherapies. Curr. Cardiol. Rep 19, 21 (2017). 28220466 PMC10176498
  188. [194]Salem JE Abatacept for severe immune checkpoint inhibitor-associated myocarditis. N. Engl. J. Med 380, 2377– 2379 (2019). 31189043
  189. [195]Arbuck SG A reassessment of cardiac toxicity associated with Taxol. J. Natl Cancer Inst. Monogr 15, 117– 130 (1993). 7912518
  190. [196]Pai VB & Nahata MC Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. Drug Saf 22, 263– 302 (2000). 10789823
  191. [197]Tamargo J, Caballero R & Delpon E Cancer chemotherapy and cardiac arrhythmias: a review. Drug Saf. 38, 129– 152 (2015). 25577497
  192. [198]Ghiaseddin A Phase II study of bevacizumab and vorinostat for patients with recurrent World Health Organization grade 4 malignant glioma. Oncologist 23, 157– e121 (2018). 29133513 PMC5813746
  193. [199]Lele AV, Clutter S, Price E & De Ruyter ML Severe hypothyroidism presenting as myxedema coma in the postoperative period in a patient taking sunitinib: case report and review of literature. J. Clin. Anesth 25, 47– 51 (2013). 23246982
  194. [200]Herrmann J Tyrosine kinase inhibitors and vascular toxicity: impetus for a classification system? Curr. Oncol. Rep 18, 33 (2016). 27099141
  195. [201]Mathur K, Saini A, Ellenbogen KA & Shepard RK Profound sinoatrial arrest associated with Ibrutinib. Case Rep. Oncol. Med 2017, 7304021 (2017). PMC5742500 29375920
  196. [202]Cooper LT Jr. Myocarditis. N. Engl. J. Med 360, 1526– 1538 (2009). 19357408 PMC5814110
  197. [203]Kaplan BM, Miller AJ, Bharati S, Lev M & Martin Grais I Complete AV block following mediastinal radiation therapy: electrocardiographic and pathologic correlation and review of the world literature. J. Interv. Card. Electrophysiol 1, 175– 188 (1997). 9869969
  198. [204]Orzan F Associated cardiac lesions in patients with radiation-induced complete heart block. Int. J. Cardiol 39, 151– 156 (1993). 8314649
  199. [205]Tzivoni D, Ratzkowski E, Biran S, Brook JG & Stern S Complete heart block following therapeutic irradiation of the left side of the chest. Chest 71, 231– 234 (1977). 832502
  200. [206]Cohen SI, Bharati S, Glass J & Lev M Radiotherapy as a cause of complete atrioventricular block in Hodgkin’s disease. An electrophysiological-pathological correlation. Arch. Intern. Med 141, 676– 679 (1981). 7224752

200 of 261 shown

Cited by

Sorted by citations

Authors
Herrmann, J.
Affiliations
Mayo Clinic (US)
Corresponding author
Herrmann, Joerg
ORCID
Herrmann, Joerg
Venue
Nature Reviews Cardiology
Publisher
Springer Science and Business Media LLC
Published
2020-03-30
Volume
17
Issue
8
Pages
474-502
ISSN
  • 1759-5002 (ISSN-L)
  • 1759-5010
DOI
10.1038/s41569-020-0348-1
PMC
PMC8782611
OpenAlex
W3013813739
Cited by
747
References
8
Citations by year
2026: 108 · 2025: 155 · 2024: 152 · 2023: 129 · 2022: 82 · 2021: 83 · 2020: 38
FWCI
14.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Cardiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (K08HL116952)
  • National Cancer Institute (R01CA233610)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac tumors and thrombi
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
cardiotoxicity, cardiac arrhythmias, cardio-oncology, cancer treatment side effects, radiation-induced cardiotoxicity, anthracyclines, trastuzumab, immune checkpoint inhibitors, myocarditis, cytokine release syndrome, CAR T-cell therapy, atrial fibrillation, QT prolongation, cardiac dysfunction
MeSH terms
Animals, Antineoplastic Agents, Arrhythmias, Cardiac, Humans, Neoplasms, Radiotherapy, Mice, Cardiotoxicity

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review