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

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 V 2 through V 6 . 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. IntroductionMyocardial stunning, known as stress cardiomyopathy, broken heart syndrome, left ventricular apical ballooning, and Takotsubocardiomyopathyis defined as: left ventricular apical ballooning on echocardiography or ventriculography; no angiographic stenoses > 50%; and no history of known cardiomyopathy. While the patient in the first of our 2 case reports fulfills these criteria, the second patient had a positive stress test following the incident but did not undergo coronary angiography, so ischemic heart disease was not excluded.Combretastatin may precipitate acute coronary syndrome. 1 A 57-year-old male with pancreatic cancer developed chest pain 80 minutes after combretastatin, and ECG showed acute myocardial infarction. Coronary angiography demonstrated an occluded distal left anterior descending artery. A 77-year-old male developed ECG changes and elevated troponin I following combretastatin. Coronary angiography revealed 2-vessel coronary artery disease.

A dose‐escalation study of combretastatin A4‐phosphate in healthy dogs

“…The increase in cTnI did not seem to correlate to significant structural nor functional echocardiographic changes in this study. Although cases of myocardial stunning have been described, reports of echocardiographic myocardial dysfunction after CA4P administration are rare in humans …”

Takotsubo cardiomyopathy in cancer patients

“…Combretastatin-related TCM has been reported in two postmenopausal women between 71 and 78 years of age without any known history of CAD [68]. Both patients had anaplastic thyroid carcinoma where combretastatin was used as part of primary chemotherapy regimen with cisplatin and doxorubicin.…”

Takotsubo Cardiomyopathy Following Initial Chemotherapy Presenting with Syncope and Cardiogenic Shock – a Case Report and Literature Review

“…The literature reported five cases of TC after exposure to other types of chemotherapy, i.e. bevacizumab [18], cetuximab, oxaliplatin/ capecitabine combination [19], 5-flurouracil [20,21] and combretastatin [22]. There were also other sporadic cases of drug-induced TC such as with nortriptyline [23] and epinephrine [24].…”