American Journal of Therapeutics 0, 1–5 (2014)
Capecitabine-Induced Takotsubo Cardiomyopathy: A Case Report and Literature Review Abdulraheem Qasem, MD,1,2* Aref A. Bin Abdulhak, MD,1 Abdelrahman Aly, MD,1 and Jill Moormeier, MD, MPH1,2
Capecitabine is an orally administered chemotherapeutic agent that is metabolized at the tumor site to 5-fluorouracil and thought to be without significant cardiac toxicity. We report a rare case of takotsubo cardiomyopathy that is thought to be related to capecitabine where the patient presented with chest pain, and ST elevation within 48 hours of capecitabine therapy. Workup included cardiac catheterization and coronary angiogram that showed nonobstructive coronary artery disease and anteroapical left ventricular wall motion abnormality with left ventricular ejection fraction of 35%. The drug was stopped, and the patient was treated with beta-blocker and angiotensin-converting enzymes inhibitor. Six weeks later, she had a repeat echocardiogram that was normal. Capecitabinerelated cardiomyopathy seems to be very rare because only 5 cases have been reported in the literature (including our case). The condition has to be anticipated and treated to prevent the serious consequence of cardiac dysfunction. All reported cases have eventually recovered after stopping capecitabine. Keywords: takotsubo, cardiomyopathy, capecitabine
INTRODUCTION Takotsubo cardiomyopathy (TC) is a unique form of reversible cardiomyopathy that is characterized by transient apical and mid-ventricular wall motion abnormality in the absence of an obstructive coronary artery disease (CAD).1,2 However, other patterns of the left ventricular regional wall motion abnormality have been described in TC including mid-apical, basal, and even global.3–5 TC was initially named after the Japanese octopus traps because of similar appearance
1 Department of Medicine, School of Medicine, University of Missouri-Kansas City, Kansas City, MO; and 2Richard and Annette Bloch Cancer Center, Truman Medical Center-Hospital Hill, Kansas City, MO. The authors have no conflicts of interest to declare. A. Qasem and A. A. Bin Abdulhak have contributed equally to this work. *Address for correspondence: Assistant professor of Medicine, Department of medicine, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108. E-mail: [email protected]
of left ventriculogram.6 Subsequently, it has been referred to as stress cardiomyopathy, apical ballooning syndrome, and broken heart syndrome.2 The syndrome is usually associated with emotional stress, acute medical, and surgical illnesses.7,8 Nonetheless, chemotherapeutic agents have held responsible for several cases of TC. Capecitabine is a target-specific oral fluoropyrimidine chemotherapeutic agent that is metabolized at the tissue level to 5-fluorouracil (5-FU).9 However, capecitabine is thought to be associated with less systemic toxicity compared with 5-FU. We report a case of TC thought to be related to capecitabine and provide a literature review on capecitabine-induced cardiomyopathy.
CASE DESCRIPTION A –47-year-old white female patient was diagnosed with invasive ductal breast carcinoma with metastases to bone, ovary, and peritoneum. Pathological examination revealed that tumor cells were estrogen receptor positive, progesterone receptor negative, and human
1075–2765 Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. www.americantherapeutics.com
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
2
FIGURE 1. Electrocardiogram shows ST segment elevations in leads I, II, aVL, V6, and ST depression and T-wave inversion in V1 and V2.
epidermal growth factor receptor 2 (HER2/neu) negative. Over the course of 4 years, the patient had received treatment with doxorubicin, Paclitaxel, vinorelbine, tamoxifen, and anastrazole. Unfortunately, she continued to have progression of her disease and was subsequently started on capecitabine. Two days after capecitabine was started, she presented with retrosternal chest pain that was heavy in nature and radiating to both arms. The pain was associated with shortness of breath, nausea, and vomiting. She denied any unusual stressors. Her vital signs were normal and physical examination was unremarkable. Electrocardiogram (ECG) showed nonspecific ST-T wave changes. On admission, serum troponin I level was slightly elevated at 0.19 ng/mL (normal: 0–0.75 ng/mL). Patient was admitted to the CCU and was started on aspirin, simvastatin, carvedilol, and intravenous heparin as a part of acute coronary syndrome initial management. Capecitabine was stopped on admission. The patient continued to have intermittent chest pain that was not relieved with intravenous morphine or sublingual nitroglycerine. Repeat ECG 10
Qasem et al
hours after presentation revealed new ST segment elevations in the inferolateral leads I, II, aVL, and V6, along with ST depression and T-wave inversion in leads V1 and V2 (Figure 1). Patient, subsequently, was given a loading dose of clopidogrel and taken emergently to cardiac catheterization laboratory. Coronary angiogram revealed no occlusive CAD, but left ventriculogram showed anteroapical wall motion abnormality with the left ventricular ejection fraction (LVEF) 35% (Figure 2). Patient’s chest pain resolved 2 hours after the cardiac catheterization. Echocardiogram was performed 2 days later and showed severely depressed LV systolic function LVEF 30% and global hypokinesia. She continued to be clinically stable and was discharged after 3 days of hospital stay with anti-heart failure treatment. Repeat 2D echocardiogram 6 weeks later showed normal left ventricular function with LVEF 55%, with no wall motion abnormalities. Taken all together, the clinical presentation, coronary angiogram, and left ventriculogram findings along with the resolution of her wall motion abnormality/depressed LV function, were consistent with TC most likely because of capecitabine.
DISCUSSION The findings in our case are consistent with TC with some nonclassic features, in particular, absence of apical ballooning on left ventriculogram. However, chest pain, ST segment elevation on ECG, absence of obstructive CAD, and the regional wall motion abnormalities on left ventriculogram that do not match with a specific territorial arterial supply, depressed LVEF, and rapid and complete recovery are in favor of stress cardiomyopathy. However, the echocardiogram that was performed 2 days after the cardiac catheterization has shown global hypokinesia that favors global
FIGURE 2. Left ventriculogram during systole (A) and diastole (B) shows anteroapical wall motion abnormality with EF of 35%. American Journal of Therapeutics (2014) 0(0)
www.americantherapeutics.com
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Reference
Time of onset, Type of h Age Gender malignancy
Presentation
83
Female Colon cancer
48
Chest pain
Y-Hassan et al11
55
Male
Colon cancer
28
Chest pain, cardiogenic shock
Endo et al12
62
Male
Colon cancer
72
Cardiogenic shock
Molteni et al13
39
Female Breast cancer
72
Cardiogenic shock
Qasem et al (current case)
47
Female Breast cancer
48
Chest pain
Cardiac catheterization
Nonobstructive T-wave inversion coronary disease. in the Akinesis of anteroseptal, the distal half of the inferior, anterior and inferior and lateral leads walls. LVEF 30% Atheromatous ST-elevations in changes with leads a markedly V2–6, and aVR, II, sluggish blood flow, and aVF especially LAD ST-elevations in Nonocclusive precordial leads coronary artery. Extensive anterior wall hyperkinesia. LVEF 35% NR Sinus tachycardia with T-wave inversion in anterolateral leads Nonocclusive ST elevation I, II, coronary artery. aVLV6, and ST Anteroapical depression wall motion and T-wave abnormality with inversion LVEF 35% in V1, and V2
Echo NR
Outcome Normal LVEF 1 week later
Normal LVEF 1 Global week later hypokinesia LVEF, 15%–20%
Anteroseptal wall Normal LVEF motion, LVEF within 12 days 35% of presentation
Global akinesia with LVEF 28%
Normal LVEF 1 week later
Global hypokinesia, LVEF 35%
Normal LVEF 6 weeks later
EKG, electrocardiogram; LAD, left anterior descending coronary artery; NR, not reported.
3
American Journal of Therapeutics (2014) 0(0)
Stewart et al10
EKG
Capecitabine-Induced Cardiomyopathy
www.americantherapeutics.com
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Table 1. General characteristics of the reported cases of capecitabine-induced cardiomyopathy.
4
takotsubo syndrome in contrary to the ventriculogram findings. It is not clear why would left ventriculogram and echocardiographic findings differ in regard to wall motion abnormalities, but there are several explanation including that both readings are operator dependent, or the disease process might be dynamic and could have started as regional and then progressed to global hypokinesia. Interestingly, all reported cases of what was thought to be capecitabine-induced takostsubo cardiomyopathy were also lacking the classic apical ballooning characteristic of TC. Hence, it is uncertain if such cases represent a spectrum of TC or rather a specific entity related to direct capecitabine cardiotoxicity. Table 1 summarizes the general characteristics of the reported cases of capecitabine-induced cardiomyopathy including our case. Importantly, all patients had symptoms that start within 72 hours of drug initiation and completely recovered within 6 weeks of drug cessation. Capecitabine is a chemotherapeutic agent that is used for the treatment of metastatic breast, colorectal, gastric, and pancreatic cancers.9,14,15 Cardiovascular adverse effects related to capecitabine are not common and include angina-like chest pain, myocardial infarction, cardiogenic shock, and sudden cardiac death.15 The preferential delivery of 5-FU to tumor tissue is thought to result in a lower risk of cardiovascular adverse events with the use of capecitabine compared with other fluoropyrimidines. 5-FU therapy is reported to cause ischemia in 4.5% and 1.1% of patients with or without underlying CAD, respectively.15 The exact incidence of cardiovascular adverse effects of capecitabine is still not well known, although it might be smaller compared with the incidence due to 5-FU.15 The pathogenesis of capecitabine-induced cardiac toxicity is largely unknown, but proposed mechanisms include effects on coronary vasculature and direct toxic effect on myocytes.15 Coronary vasospasm has also been suggested based on the characteristic electrocardiographic and clinical features that are similar to those of reversible ischemic heart disease. Several lines of evidence suggest a direct drug-mediated or drug metabolite–mediated toxic action on the myocytes as opposed to a vasospastic event. Vasospasm has not been seen on coronary angiography during attacks of chest pain that develop in patients treated with capecitabine. In addition, significant atherosclerosis, which is common in patients with coronary vasospasm, is not commonly seen in capecitabine-induced chest pain patients.15 Moreover, during attacks, echocardiography demonstrates reduced ejection fraction and significant apical, mid-ventricular, or global akinesia that does not correspond to the segmental distribution of the major coronary arteries.15 American Journal of Therapeutics (2014) 0(0)
Qasem et al
CONCLUSIONS Capecitapine is not entirely without cardiovascular risks. Cardiomyopathy due to capecitapine is extremely rare but important to be anticipated and treated promptly to prevent the serious consequence of cardiac dysfunction. Capecitapine-induced cardiomyopathy typically manifests within 72 hours of drug administration, and complete recovery is expected on stopping the medication.
REFERENCES 1. Maron BJ, Towbin JA, Thiene G, et al; American Heart Association. Contemporary definitions and classification of the cardiomyopathies: American Heart Association scientific statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006;113:1807–1816. 2. Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes. Circulation. 2008;118:397–409. 3. Song BG, Hahn JY, Cho SJ, et al. Clinical characteristics, ballooning pattern, and long-term prognosis of transient left ventricular ballooning syndrome. Heart Lung. 2010; 39:188–195. 4. Singh NK, Rumman S, Mikell FL, et al. Stress cardiomyopathy: clinical and ventriculographic characteristics in 107 North American subjects. Int J Cardiol. 2010;141: 297–303. 5. Win CM, Pathak A, Guglin M. Not takotsubo: a different form of stress-induced cardiomyopathy—a case series. Congest Heart Fail. 2011;17:38–41. 6. 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. Angina PectorisMyocardial Infarction Investigations in Japan. J Am Coll Cardiol. 2001;38:11–18. 7. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med. 2004;141:858–865. 8. Kawai S, Suzuki H, Yamaguchi H, et al. Ampulla cardiomyopathy Takotsubo cardiomyopathy—reversible left ventricular dysfunction: with ST segment elevation. Jpn Circ J. 2000;64:156–159. 9. Wagstaff AJ, Ibbotson T, Goa KL. Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. Drugs. 2003;63: 217–236. 10. Stewart T, Pavlakis N, Ward M. Cardiotoxicity with 5fluorouracil and capecitabine: more than just vasospastic angina. Intern Med J. 2010;40:303–307. www.americantherapeutics.com
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Capecitabine-Induced Cardiomyopathy 11. Y-Hassan S, Tornvall P, Tornerud M, et al. Capecitabine caused cardiogenic shock through induction of global Takotsubo syndrome. Cardiovasc Revasc Med. 2013;14:57–61. 12. Endo A, Yoshida Y, Nakashima R, et al. Capecitabine induces both cardiomyopathy and multifocal cerebral leukoencephalopathy. Int Heart J. 2013;54:417–420. 13. Molteni LP, Rampinelli I, Cergnul M, et al. Capecitabine in breast cancer: the issue of cardiotoxicity during
www.americantherapeutics.com
5 fluoropyrimidine treatment. Breast J. 2010;16(Suppl 1): S45–S48. 14. Alter P, Herzum M, Soufi M, et al. Cardiotoxicity of 5fluorouracil. Cardiovasc Hematol Agents Med Chem. 2006; 4:1–5. 15. Jensen SA, Sørensen JB. Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine. Cancer Chemother Pharmacol. 2006;58:487–493.
American Journal of Therapeutics (2014) 0(0)
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Capecitabine-Induced Takotsubo Cardiomyopathy: A Case Report and Literature Review Abdulraheem Qasem, MD,1,2* Aref A. Bin Abdulhak, MD,1 Abdelrahman Aly, MD,1 and Jill Moormeier, MD, MPH1,2
Capecitabine is an orally administered chemotherapeutic agent that is metabolized at the tumor site to 5-fluorouracil and thought to be without significant cardiac toxicity. We report a rare case of takotsubo cardiomyopathy that is thought to be related to capecitabine where the patient presented with chest pain, and ST elevation within 48 hours of capecitabine therapy. Workup included cardiac catheterization and coronary angiogram that showed nonobstructive coronary artery disease and anteroapical left ventricular wall motion abnormality with left ventricular ejection fraction of 35%. The drug was stopped, and the patient was treated with beta-blocker and angiotensin-converting enzymes inhibitor. Six weeks later, she had a repeat echocardiogram that was normal. Capecitabinerelated cardiomyopathy seems to be very rare because only 5 cases have been reported in the literature (including our case). The condition has to be anticipated and treated to prevent the serious consequence of cardiac dysfunction. All reported cases have eventually recovered after stopping capecitabine. Keywords: takotsubo, cardiomyopathy, capecitabine
INTRODUCTION Takotsubo cardiomyopathy (TC) is a unique form of reversible cardiomyopathy that is characterized by transient apical and mid-ventricular wall motion abnormality in the absence of an obstructive coronary artery disease (CAD).1,2 However, other patterns of the left ventricular regional wall motion abnormality have been described in TC including mid-apical, basal, and even global.3–5 TC was initially named after the Japanese octopus traps because of similar appearance
1 Department of Medicine, School of Medicine, University of Missouri-Kansas City, Kansas City, MO; and 2Richard and Annette Bloch Cancer Center, Truman Medical Center-Hospital Hill, Kansas City, MO. The authors have no conflicts of interest to declare. A. Qasem and A. A. Bin Abdulhak have contributed equally to this work. *Address for correspondence: Assistant professor of Medicine, Department of medicine, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108. E-mail: [email protected]
of left ventriculogram.6 Subsequently, it has been referred to as stress cardiomyopathy, apical ballooning syndrome, and broken heart syndrome.2 The syndrome is usually associated with emotional stress, acute medical, and surgical illnesses.7,8 Nonetheless, chemotherapeutic agents have held responsible for several cases of TC. Capecitabine is a target-specific oral fluoropyrimidine chemotherapeutic agent that is metabolized at the tissue level to 5-fluorouracil (5-FU).9 However, capecitabine is thought to be associated with less systemic toxicity compared with 5-FU. We report a case of TC thought to be related to capecitabine and provide a literature review on capecitabine-induced cardiomyopathy.
CASE DESCRIPTION A –47-year-old white female patient was diagnosed with invasive ductal breast carcinoma with metastases to bone, ovary, and peritoneum. Pathological examination revealed that tumor cells were estrogen receptor positive, progesterone receptor negative, and human
1075–2765 Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. www.americantherapeutics.com
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
2
FIGURE 1. Electrocardiogram shows ST segment elevations in leads I, II, aVL, V6, and ST depression and T-wave inversion in V1 and V2.
epidermal growth factor receptor 2 (HER2/neu) negative. Over the course of 4 years, the patient had received treatment with doxorubicin, Paclitaxel, vinorelbine, tamoxifen, and anastrazole. Unfortunately, she continued to have progression of her disease and was subsequently started on capecitabine. Two days after capecitabine was started, she presented with retrosternal chest pain that was heavy in nature and radiating to both arms. The pain was associated with shortness of breath, nausea, and vomiting. She denied any unusual stressors. Her vital signs were normal and physical examination was unremarkable. Electrocardiogram (ECG) showed nonspecific ST-T wave changes. On admission, serum troponin I level was slightly elevated at 0.19 ng/mL (normal: 0–0.75 ng/mL). Patient was admitted to the CCU and was started on aspirin, simvastatin, carvedilol, and intravenous heparin as a part of acute coronary syndrome initial management. Capecitabine was stopped on admission. The patient continued to have intermittent chest pain that was not relieved with intravenous morphine or sublingual nitroglycerine. Repeat ECG 10
Qasem et al
hours after presentation revealed new ST segment elevations in the inferolateral leads I, II, aVL, and V6, along with ST depression and T-wave inversion in leads V1 and V2 (Figure 1). Patient, subsequently, was given a loading dose of clopidogrel and taken emergently to cardiac catheterization laboratory. Coronary angiogram revealed no occlusive CAD, but left ventriculogram showed anteroapical wall motion abnormality with the left ventricular ejection fraction (LVEF) 35% (Figure 2). Patient’s chest pain resolved 2 hours after the cardiac catheterization. Echocardiogram was performed 2 days later and showed severely depressed LV systolic function LVEF 30% and global hypokinesia. She continued to be clinically stable and was discharged after 3 days of hospital stay with anti-heart failure treatment. Repeat 2D echocardiogram 6 weeks later showed normal left ventricular function with LVEF 55%, with no wall motion abnormalities. Taken all together, the clinical presentation, coronary angiogram, and left ventriculogram findings along with the resolution of her wall motion abnormality/depressed LV function, were consistent with TC most likely because of capecitabine.
DISCUSSION The findings in our case are consistent with TC with some nonclassic features, in particular, absence of apical ballooning on left ventriculogram. However, chest pain, ST segment elevation on ECG, absence of obstructive CAD, and the regional wall motion abnormalities on left ventriculogram that do not match with a specific territorial arterial supply, depressed LVEF, and rapid and complete recovery are in favor of stress cardiomyopathy. However, the echocardiogram that was performed 2 days after the cardiac catheterization has shown global hypokinesia that favors global
FIGURE 2. Left ventriculogram during systole (A) and diastole (B) shows anteroapical wall motion abnormality with EF of 35%. American Journal of Therapeutics (2014) 0(0)
www.americantherapeutics.com
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Reference
Time of onset, Type of h Age Gender malignancy
Presentation
83
Female Colon cancer
48
Chest pain
Y-Hassan et al11
55
Male
Colon cancer
28
Chest pain, cardiogenic shock
Endo et al12
62
Male
Colon cancer
72
Cardiogenic shock
Molteni et al13
39
Female Breast cancer
72
Cardiogenic shock
Qasem et al (current case)
47
Female Breast cancer
48
Chest pain
Cardiac catheterization
Nonobstructive T-wave inversion coronary disease. in the Akinesis of anteroseptal, the distal half of the inferior, anterior and inferior and lateral leads walls. LVEF 30% Atheromatous ST-elevations in changes with leads a markedly V2–6, and aVR, II, sluggish blood flow, and aVF especially LAD ST-elevations in Nonocclusive precordial leads coronary artery. Extensive anterior wall hyperkinesia. LVEF 35% NR Sinus tachycardia with T-wave inversion in anterolateral leads Nonocclusive ST elevation I, II, coronary artery. aVLV6, and ST Anteroapical depression wall motion and T-wave abnormality with inversion LVEF 35% in V1, and V2
Echo NR
Outcome Normal LVEF 1 week later
Normal LVEF 1 Global week later hypokinesia LVEF, 15%–20%
Anteroseptal wall Normal LVEF motion, LVEF within 12 days 35% of presentation
Global akinesia with LVEF 28%
Normal LVEF 1 week later
Global hypokinesia, LVEF 35%
Normal LVEF 6 weeks later
EKG, electrocardiogram; LAD, left anterior descending coronary artery; NR, not reported.
3
American Journal of Therapeutics (2014) 0(0)
Stewart et al10
EKG
Capecitabine-Induced Cardiomyopathy
www.americantherapeutics.com
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Table 1. General characteristics of the reported cases of capecitabine-induced cardiomyopathy.
4
takotsubo syndrome in contrary to the ventriculogram findings. It is not clear why would left ventriculogram and echocardiographic findings differ in regard to wall motion abnormalities, but there are several explanation including that both readings are operator dependent, or the disease process might be dynamic and could have started as regional and then progressed to global hypokinesia. Interestingly, all reported cases of what was thought to be capecitabine-induced takostsubo cardiomyopathy were also lacking the classic apical ballooning characteristic of TC. Hence, it is uncertain if such cases represent a spectrum of TC or rather a specific entity related to direct capecitabine cardiotoxicity. Table 1 summarizes the general characteristics of the reported cases of capecitabine-induced cardiomyopathy including our case. Importantly, all patients had symptoms that start within 72 hours of drug initiation and completely recovered within 6 weeks of drug cessation. Capecitabine is a chemotherapeutic agent that is used for the treatment of metastatic breast, colorectal, gastric, and pancreatic cancers.9,14,15 Cardiovascular adverse effects related to capecitabine are not common and include angina-like chest pain, myocardial infarction, cardiogenic shock, and sudden cardiac death.15 The preferential delivery of 5-FU to tumor tissue is thought to result in a lower risk of cardiovascular adverse events with the use of capecitabine compared with other fluoropyrimidines. 5-FU therapy is reported to cause ischemia in 4.5% and 1.1% of patients with or without underlying CAD, respectively.15 The exact incidence of cardiovascular adverse effects of capecitabine is still not well known, although it might be smaller compared with the incidence due to 5-FU.15 The pathogenesis of capecitabine-induced cardiac toxicity is largely unknown, but proposed mechanisms include effects on coronary vasculature and direct toxic effect on myocytes.15 Coronary vasospasm has also been suggested based on the characteristic electrocardiographic and clinical features that are similar to those of reversible ischemic heart disease. Several lines of evidence suggest a direct drug-mediated or drug metabolite–mediated toxic action on the myocytes as opposed to a vasospastic event. Vasospasm has not been seen on coronary angiography during attacks of chest pain that develop in patients treated with capecitabine. In addition, significant atherosclerosis, which is common in patients with coronary vasospasm, is not commonly seen in capecitabine-induced chest pain patients.15 Moreover, during attacks, echocardiography demonstrates reduced ejection fraction and significant apical, mid-ventricular, or global akinesia that does not correspond to the segmental distribution of the major coronary arteries.15 American Journal of Therapeutics (2014) 0(0)
Qasem et al
CONCLUSIONS Capecitapine is not entirely without cardiovascular risks. Cardiomyopathy due to capecitapine is extremely rare but important to be anticipated and treated promptly to prevent the serious consequence of cardiac dysfunction. Capecitapine-induced cardiomyopathy typically manifests within 72 hours of drug administration, and complete recovery is expected on stopping the medication.
REFERENCES 1. Maron BJ, Towbin JA, Thiene G, et al; American Heart Association. Contemporary definitions and classification of the cardiomyopathies: American Heart Association scientific statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006;113:1807–1816. 2. Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes. Circulation. 2008;118:397–409. 3. Song BG, Hahn JY, Cho SJ, et al. Clinical characteristics, ballooning pattern, and long-term prognosis of transient left ventricular ballooning syndrome. Heart Lung. 2010; 39:188–195. 4. Singh NK, Rumman S, Mikell FL, et al. Stress cardiomyopathy: clinical and ventriculographic characteristics in 107 North American subjects. Int J Cardiol. 2010;141: 297–303. 5. Win CM, Pathak A, Guglin M. Not takotsubo: a different form of stress-induced cardiomyopathy—a case series. Congest Heart Fail. 2011;17:38–41. 6. 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. Angina PectorisMyocardial Infarction Investigations in Japan. J Am Coll Cardiol. 2001;38:11–18. 7. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med. 2004;141:858–865. 8. Kawai S, Suzuki H, Yamaguchi H, et al. Ampulla cardiomyopathy Takotsubo cardiomyopathy—reversible left ventricular dysfunction: with ST segment elevation. Jpn Circ J. 2000;64:156–159. 9. Wagstaff AJ, Ibbotson T, Goa KL. Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. Drugs. 2003;63: 217–236. 10. Stewart T, Pavlakis N, Ward M. Cardiotoxicity with 5fluorouracil and capecitabine: more than just vasospastic angina. Intern Med J. 2010;40:303–307. www.americantherapeutics.com
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Capecitabine-Induced Cardiomyopathy 11. Y-Hassan S, Tornvall P, Tornerud M, et al. Capecitabine caused cardiogenic shock through induction of global Takotsubo syndrome. Cardiovasc Revasc Med. 2013;14:57–61. 12. Endo A, Yoshida Y, Nakashima R, et al. Capecitabine induces both cardiomyopathy and multifocal cerebral leukoencephalopathy. Int Heart J. 2013;54:417–420. 13. Molteni LP, Rampinelli I, Cergnul M, et al. Capecitabine in breast cancer: the issue of cardiotoxicity during
www.americantherapeutics.com
5 fluoropyrimidine treatment. Breast J. 2010;16(Suppl 1): S45–S48. 14. Alter P, Herzum M, Soufi M, et al. Cardiotoxicity of 5fluorouracil. Cardiovasc Hematol Agents Med Chem. 2006; 4:1–5. 15. Jensen SA, Sørensen JB. Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine. Cancer Chemother Pharmacol. 2006;58:487–493.
American Journal of Therapeutics (2014) 0(0)
Copyright ª 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
