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. 2009 Dec 14;32(12):E80–E84. doi: 10.1002/clc.20685

Myocardial Stunning Following Combined Modality Combretastatin‐Based Chemotherapy: Two Case Reports and Review of the Literature

Shyam Bhakta 1, Susan M Flick 1, Matthey M Cooney 1, John F Greskovich 2, Robert C Gilkeson 1, Scot C Remick 3, Jose Ortiz 1,✉
PMCID: PMC6653067  PMID: 20014213

Abstract

Myocardial stunning, known as stress cardiomyopathy, broken‐heart syndrome, transient left ventricular apical ballooning, and Takotsubo cardiomyopathy, has been reported after many extracardiac stressors, but not following chemotherapy. We report 2 cases with characteristic electrocardiographic and echocardiographic features following combined modality therapy with combretastatin, a vascular‐disrupting agent being studied for treatment of anaplastic thyroid cancer. In 1 patient, an ECG performed per protocol 18 hours after drug initiation showed deep, symmetric T‐wave inversions in limb leads I and aVL and precordial leads V2 through V6. Echocardiography showed mildly reduced overall left ventricular systolic function with akinesis of the entire apex. The patient had mild elevations of troponin I. Coronary angiography revealed no epicardial coronary artery disease. The electrocardiographic and echocardiographic abnormalities resolved after several weeks. The patient remains stable from a cardiovascular standpoint and has not had a recurrence during follow‐up. An electrocardiogram performed per protocol in a second patient showed deep, symmetric T‐wave inversions throughout the precordial leads and a prolonged QT interval. Echocardiography showed mildly reduced left ventricular function with hypokinesis of the apical‐septal wall. Acute coronary syndrome was ruled out, and both the electrocardiographic and echocardiographic changes resolved at follow‐up. Although the patient remained pain‐free without recurrence of anginal symptoms during long‐term follow‐up, the patient developed progressive malignancy and died. Copyright © 2009 Wiley Periodicals, Inc.

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References

  • 1. Dowlati A, Robertson K, Cooney M, et al. A phase I pharmacokinetic and translational study of the novel vascular targeting agent combretastatin A‐4 phosphate on a single‐dose intravenous schedule in patients with advanced cancer. Cancer Res 2002; 62: 3408–3416. [PubMed] [Google Scholar]
  • 2. Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral Features of Myocardial Stunning Due to Sudden Emotional Stress. N Engl J Med 2005; 352: 539–548. [DOI] [PubMed] [Google Scholar]
  • 3. Mayer SA, Lin J, Homma S, et al. Myocardial injury and left ventricular performance after subarachnoid hemorrhage. Stroke 1999; 30: 780–786. [DOI] [PubMed] [Google Scholar]
  • 4. Bybee KA, Prasad A, Barsness GW, et al. Clinical Characteristics and Thrombolysis in Myocardial Infarction Frame Counts in Women With Transient Left Ventricular Apical Ballooning Syndrome. Am J Cardiol 2004; 94: 343–346. [DOI] [PubMed] [Google Scholar]
  • 5. Tsuchihashi K, Ueshima K, Uchida T, et al. Transient Left Ventricular Apical Ballooning Without Coronary Artery Stenosis: A Novel Heart Syndrome Mimicking Acute Myocardial Infarction. J Am Coll Cardiol 2001; 38: 11–18. [DOI] [PubMed] [Google Scholar]
  • 6. Mann DL, Kent RL, Parsons B, et al. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 1992; 85: 790–804. [DOI] [PubMed] [Google Scholar]
  • 7. Ako J. Transient left ventricular apical ballooning without coronary artery stenosis: a form of stunning‐like phenomenon? J Am Coll Cardiol 2002; 39: 4. [DOI] [PubMed] [Google Scholar]
  • 8. Rustin GJ, Galbraith SM, Anderson H, et al. Phase I clinical trial of weekly combretastatin A4 phosphate: clinical and pharmacokinetic results. J Clin Oncol 2003; 21: 2815–2822. [DOI] [PubMed] [Google Scholar]
  • 9. Dark GG, Hill SA, Prise VE, et al. Combretastatin A4. An agent that displays potent and selective toxicity towards tumour vasculature. Cancer Res 1997; 57: 1829–1834. [PubMed] [Google Scholar]
  • 10. Cooney MM, Radivoyevitch T, Dowlati A, et al. Cardiovascular safety profile of combretastatin A4 phosphate in a single‐dose phase I study in patients with advanced cancer. Clin Cancer Res 2004; 10: 96–100. [DOI] [PubMed] [Google Scholar]
  • 11. Anderson HL, Yap JT, Miller MP, et al. Assessment of pharmacodynamic vascular response in a phase I trial of combretastatin A4 phosphate. J Clin Oncol 2003; 21: 2823–2830. [DOI] [PubMed] [Google Scholar]
  • 12. Iyer S, Chaplin DJ, Rosenthal DS, et al. Induction of apoptosis in proliferating human endothelial cells by the tumor‐specific antiangiogenesis agent, combretastatin A‐4. Cancer Res 1998; 58: 4510–4514. [PubMed] [Google Scholar]
  • 13. Grosios K, Loadman PM, Swaine DJ, et al. Combination chemotherapy with combretastatin A‐4 phosphate and 5‐fluorouracil in an experimental murine colon adenocarcinoma. Anticancer Res 2000; 20: 229–234. [PubMed] [Google Scholar]
  • 14. Murata R, Siemann DW, Overgaard J, et al. Interaction between combretastatin A‐4 disodium phosphate and radiation in murine tumors. Radiother and Oncol 2001; 60: 155–161. [DOI] [PubMed] [Google Scholar]
  • 15. Takemura G, Fujiwara H. Doxorubicin‐induced cardiomyopathy from the cardiotoxic mechanisms to management. Prog Cardiovasc Dis 2007; 49(5): 330–352. [DOI] [PubMed] [Google Scholar]
  • 16. Robert J. Preclinical assessment of anthracycline cardiotoxicity in laboratory animals: predictiveness and pitfalls. Cell Biol Toxicol 2007; 23(1): 27–37. [DOI] [PubMed] [Google Scholar]
  • 17. Outomuro D, Grana DR, Azzato F, et al. Adriamycin‐induced myocardial toxicity: new solutions for an old problem? Int J Cardiol 2007; 117(1): 6–15. [DOI] [PubMed] [Google Scholar]

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