Gadolinium is a silvery-white metal when oxidation is removed, and gadolinium salts are used in magnetic resonance imaging. The gadolinium-based contrast mediums are the most commonly used agents in magnetic resonance angiography and for brain tumor enhancement due to their association with the degradation of the blood-brain barrier. However, nephrogenic systemic fibrosis and acute kidney injury due to primary excretion of gadolinium from the kidneys and various cardiac arrhythmias including QTc electrocardiographic prolongation and hypersensitivity reactions are occasionally encountered with use of such contrast mediums.1
In the very interesting report published in Baylor University Medical Center Proceedings,2 a 53-year-old woman suffering from renal cell carcinoma and recent right nephrectomy with secondaries of the left lower lung lobe developed type I Kounis syndrome with chest pain and shortness of breath following gadolinium administration for magnetic resonance imaging of the brain for headaches. The patient became edematous, unconscious, and unresponsive, with an oxygen saturation of 50% and a heart rate of 40 beats/min. This report raises issues concerning gadolinium-induced anaphylaxis and gadolinium-induced bradycardia and electrocardiographic manifestations related to Kounis syndrome.
Whereas gadolinium has been placed in the lowest-list category for acute kidney injury and the development of nephrogenic systemic fibrosis in patients with renal impairment, several mild to severe adverse drug reactions have been noted, including mild or severe immediate hypersensitivity reactions with cardiovascular and respiratory impairment. The most common immediate hypersensitivity symptoms are mild pruritus and urticaria occurring a few minutes after intravenous administration. However, in the US Food and Drug Administration’s Adverse Event Reporting System for the period of 1998 to 2012, 614 cases were reported of adverse drug reactions to gadolinium-based contrast agents, of which 7.2% had a fatal outcome.3 One fatality was a 42-year-old man who had undergone a previous successful contrast-enhanced computed tomography and underwent elective magnetic resonance imaging with gadolinium for diagnostic clarification of a suspicious finding in the abdomen.4 At autopsy, this patient was found to have massive brain edema (1450 g). The role of an immunoglobulin E–mediated mechanism has been advocated in such reactions, and there is an increased risk for more severe reactions, up to 8 times more severe, at the second administration of gadolinium-based contrast agents in patients with a history of hypersensitivity.5 The described patient2 had been subjected to previous magnetic resonance imaging without contrast and experienced no adverse effects, but she had a history of renal cell carcinoma and recent right nephrectomy, and therefore renal impairment could not be excluded.
This patient presented with ST elevations in leads II, III, aVF, V3, and V4; ST segment depression in lead I; increased troponin levels from 0.015 to 1.12 ng/mL; and left heart catheterization with no evidence of obstruction or pulmonary embolism—which were compatible with a diagnosis of Kounis syndrome type I variant. Indeed, electrocardiographic abnormalities ranging from cardiac arrhythmias of any kind to those resembling digitalis intoxication and the ST segment elevation or depression to any degree of heart block can be associated with the cardiac symptoms and signs of Kounis syndrome.
Recently, a unique electrocardiographic sign of ST elevation in lead aVR, with reciprocal ST depression in the majority of other leads, has been described in Kounis syndrome.6 The lead aVR, until recent years, was regarded as the “neglected lead.” However, ST segment elevation in lead aVR associated with widespread ST segment depression in inferolateral leads best identifies severe left main or three-vessel disease and denotes high-risk non–ST segment elevation acute coronary syndrome that requires urgent revascularization in addition to medical treatment that includes antiplatelets, aspirin, and heparin.7 The same electrocardiographic findings, however, can be present in a type A dissecting aneurysm affecting the ascending aorta that expands and presses the left main artery and the coronary ostia. Whereas the clinical picture is of acute myocardial infarction, the treatment is completely different and includes emergency surgery and avoidance of antiplatelets, aspirin, and heparin.8
Gadolinium-based contrast mediums are generally benign but on some occasions can lead to life-threatening conditions and Kounis syndrome.9–11 Physicians, therefore, should be aware of clinical and electrocardiographic manifestations of Kounis syndrome as potential serious complications of agents and drugs given for diagnostic and therapeutic purposes.
—Nicholas G. Kounis, MD, PhD
Department of Cardiology, University of Patras Medical School, Patras, Greece ngkounis@otenet.gr
—Ioanna Koniari, MD, PhD
Electrophysiology and Device Department, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK
—GEORGED.SOUFRAS, MD, PhD
Department of Cardiology, Saint Andrews State General Hospital, Patras, Greece
—GRIGORIOS TSIGKAS, MD, PhD, Panagiotis Plotas, MD, PhD, Periklis Davlouros, MD, PhD, and George Hahalis, MD, PhD
Department of Cardiology, University of Patras Medical School, Patras, Greece
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