Capecitabine-Induced Takotsubo Cardiomyopathy: A Case Report



 

Prarthna V Bhardwaj, MD1; Vinod Kumar Chaubey, MD2; Ashequl M Islam, MD2

Perm J 2019;23:18.245 [Full Citation]

https://doi.org/10.7812/TPP/18.245
E-pub: 09/12/2019

Abstract

Introduction: The medication 5-fluorouracil is known to cause cardiotoxic effects (with an incidence ranging from 5% to 18%), such as rhythm abnormalities and cardiomyopathies, including takotsubo cardiomyopathy. Capecitabine, an oral prodrug of 5-fluorouracil, has rarely been reported to cause cardiotoxic effects compared with its parent drug.
Case Presentation: An 80-year-old woman presented to the hospital with chest pain after recent initiation of capecitabine use for anal cancer. Results of cardiac catheterization revealed moderate nonobstructive coronary disease. Overall, the findings were highly consistent with a clinical diagnosis of takotsubo cardiomyopathy.
Discussion: With the current increasing use of capecitabine, recognizing this agent as a potential risk factor for cardiac-related events is important.

INTRODUCTION

Capecitabine is an oral prodrug of 5-fluorouracil that has been used in different types of cancers, especially colorectal cancers, because of the convenience of administration and comparable efficacy with 5-fluorouracil. Capecitabine metabolizes to 5-fluorouracil at the tumor site, resulting in fewer cardiotoxic effects than are associated with 5-fluorouracil. Common cardiotoxic effects of 5-fluorouracil reported in the literature include angina, rarely rhythm abnormalities, myopericarditis, and well-documented takotsubo cardiomyopathy. However, capecitabine-induced cardiotoxicity is presumed to be more infrequent and less documented. This condition often presents a diagnostic and therapeutic dilemma, mostly because oral capecitabine is preferred over 5-fluorouracil in elderly patients, especially those with colorectal cancers, because 5-fluorouracil causes significantly more toxic effects and is an infusional chemotherapy, whereas capecitabine is in pill form, which is convenient. We present the case of a woman undergoing oral capecitabine therapy who presented with chest pain and dynamic electrocardiographic changes and was found to have takotsubo cardiomyopathy.

CASE PRESENTATION

An 80-year-old white woman of German descent with a medical history of long-standing anxiety who had been taking benzodiazepines long-term and had hypertension and hyperlipidemia presented to the hospital with chest pain. She experienced chest pain 4 hours before admission (midsternal, 8/10 in severity), which she described as a tightness in her chest associated with shortness of breath but without nausea, diaphoresis, or palpitations. she initially thought her pain was related to her anxiety; however, the pain did not subside with her regular medications, which prompted her to seek medical attention. The results of a review of systems were otherwise negative.

The patient had been diagnosed with anal cancer approximately 2 months previously, for which she was prescribed capecitabine 4 days before admission. She denied any other recent stressors. Her current medications also included clonazepam (0.25 mg twice a day), atorvastatin (10 mg once daily), and meclizine as needed. She is a nonsmoker and denied alcohol and recreational drug use. She was independent and lived with one of her children. Her family history was significant for a father with coronary artery disease after the age of 50 years.

On examination, her vital signs were significant for a pulse of 58 beats/min, blood pressure of 132/78 mmHg, and respiratory rate of 24 breaths/min. She was afebrile. She was 160 cm in height and weighed 47.6 kg. Significant cardiorespiratory examination included no jugular venous distension, normal heart sounds without murmurs, and clear lungs to auscultation.

She was noted to have hyperacute T waves in the anterior precordial leads on an electrocardiogram taken at the time of chest pain (Figure 1). There was no prior electrocardiogram for comparison. She was prescribed aspirin and given a heparin drip. Initial cardiac enzyme levels were within normal limits. Her other laboratory test results were significant for mild normocytic anemia with a hemoglobin level of 10.9 mg/dl. Her renal function was within normal limits for her age. Further workup revealed a hemoglobin A1c level of 5.3, and a fasting lipid panel revealed a low-density lipoprotein level of 49 mg/dl and a high-density lipoprotein level of 58 mg/dl.

Results of cardiac catheterization revealed nonobstructive coronary disease with no more than moderate disease. She had 40% stenosis in the middle left anterior descending artery territory, with 50% stenosis in the right coronary artery and 45% stenosis in the proximal left circumflex artery (Figures 2 and 3). Ventriculography results revealed apical ballooning with a hyperdynamic base (Figure 4). Results of echocardiography performed a day later showed a hyperdynamic base with apical akinesis with an ejection fraction of 55% to 60%. Overall, the findings were highly consistent with a clinical diagnosis of takotsubo cardiomyopathy.

The patient was given aspirin, statin, and b-blockers for cardiac remodeling. She remained free of chest pain at the time of her discharge after 3 days. Results of an electrocardiogram performed on discharge showed an upright T wave without any ischemic findings (Figure 5). She was advised to discontinue use of capecitabine and undergo follow-up echocardiography in 6 to 8 weeks. She was also advised to attend cardiac rehabilitation. At 6-week follow-up, a subsequent echocardiogram revealed that her wall motion abnormality had completely recovered. Table 1 provides a timeline of the case.

18.245

DISCUSSION

we present a case of capecitabine-induced stress cardiomyopathy that manifested as an acute ischemic event in a patient with moderate coronary artery disease on the basis of the findings of apical ballooning and akinesis on cardiac imaging. Although rare, cardiotoxicity may occur during therapy with several cytotoxic agents. The spectrum of cardiotoxicity with chemotherapeutic agents includes hypertension, QT-interval prolongation, acute cardiomyopathy, vasospasm, and bradyarrhythmia. cardiotoxicity induced by 5-fluorouracil usually occurs during continuous intravenous infusion, and estimates of its incidence vary from 1% to 5% to as much as 18%.1 Although a prodrug of 5-fluorouracil, capecitabine is less cardiotoxic than 5-fluorouracil, some scattered incidents have been documented in the literature, including angina-like chest pain, myocardial infarction, cardiogenic shock, and sudden cardiac death.2-6 The preferential delivery of 5-fluorouracil to tumor tissue is thought to result in a lower risk of cardiovascular adverse events with the use of capecitabine compared with other fluoropyrimidines.

Interestingly, only 1 of 6 reported cases of possible capecitabine-induced cardiomyopathy described the classic apical ballooning characteristic of cardiomyopathy.7 Our case is the second report of apical ballooning with capecitabine use consistent with cardiomyopathy.

The pathogenesis of capecitabine-induced cardiac toxic effects is largely unknown, but the proposed mechanisms include effects on coronary vasculature and direct toxic effect on myocytes. Coronary vasospasm has also been suggested on the basis of the characteristic electrocardiographic and clinical features that are similar to those of reversible ischemic heart disease.

We could not identify other predisposing factors, such as previous chest radiotherapy and concurrent treatment with other cardiotoxic agents, in our patient. Although she has a long-standing history of anxiety while taking benzodiazepines long-term, she had no inciting events that potentially triggered this event, and we assume that it was merely a confounder in this case. Hence, she was presumed to have chemotherapy-induced takotsubo cardiomyopathy in the setting of recent initiation of chemotherapy. Reviewing the literature, cardiotoxic effects are completely reversible with cessation of capecitabine therapy.6

As general internists who encounter symptoms of chest pain routinely in clinical practice, it is important to consider medication adverse effects as a source for this pain. Takotsubo cardiomyopathy remains a diagnosis of exclusion in patients who present with ischemic changes on electrocardiography. Also noteworthy is that takotsubo cardiomyopathy is usually reversible with time.

CONCLUSION

In the near future, the incidence of fluoropyrimidine-induced cardiovascular adverse effects is expected to increase worldwide because of the increasing use of these drugs in patients with breast or gastrointestinal cancers, especially common in our aging population. Although the incidence of cardiotoxic effects caused by capecitabine is estimated at 5%, which is lower than the parent drug, we suspect these effects may be underreported. Further studies and clinical experience are needed to determine which patients are at higher risk for cardiotoxic effects. For now, potential cardiotoxic effects and other risk factors vs benefits should be weighed carefully before prescribing capecitabine to any patient. In addition, these adverse effects need to be discussed with patients before use.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

Acknowledgments

Laura King, ELS, performed a primary copy edit.

How to Cite this Article

Bhardwaj PV, Chaubey VK, Islam AM. Capecitabine-induced takotsubo cardiomyopathy: A case report. Perm J 2019;23:18.245. DOI: https://doi.org/10.7812/TPP/18.245

Author Affiliations

1 Department of Internal Medicine, Baystate Medical Center, Springfield, MA

2 Department of Cardiology, Baystate Medical Center, Springfield, MA

Corresponding Author

Prarthna V Bhardwaj, MD (prarthnabhardwaj@gmail.com)

References
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Keywords: 5-fluorouracil, capecitabine, cardiac toxic effects, chemotherapy-induced takotsubo cardiomyopathy, oral capecitabine therapy, takotsubo cardiomyopathy

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