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Requests for reprints should be addressed to Emil Missov, MD, PhD, Division of Cardiology, University of Minnesota Medical Center, 420 Delaware Street SE, Minneapolis, MN 55455.
A 47-year-old previously healthy woman presented with witnessed out-of-hospital cardiac arrest after being treated with the macrolide antibiotic azithromycin. The initial electrocardiogram had no acute ischemic changes and only a marginally prolonged QT interval of 495 ms. Coronary angiography was normal. Echocardiography showed myxomatous mitral valve disease with flail posterior leaflet resulting in severe eccentric mitral regurgitation. The left ventricular ejection fraction was mildly reduced at 45%. Following therapeutic hypothermia, prolonged rehabilitation, and tracheostomy for long-term ventilatory management followed by weaning and decannulation, the patient underwent minimally invasive mitral valve repair 3 months after the initial event. While coming off cardiopulmonary bypass, she experienced several episodes of ventricular fibrillation requiring multiple external defibrillatory shocks. The electrocardiogram obtained in the postanesthesia care unit shows sinus rhythm and an extremely prolonged corrected QT interval of 641 ms (Figure). The patient underwent placement of an implantable cardioverter-defibrillator for secondary prevention of sudden cardiac death and has since made a full recovery.
FigureThe electrocardiogram shows normal sinus rhythm with a ventricular rate of 86 beats per minute. The QT interval is 536 ms. The corrected QT interval is extremely prolonged and measures 641 ms. A corrected QT interval exceeding 450 ms in men and 470 ms in women is considered abnormal.
Genetic testing revealed a novel sodium voltage-gated channel type V-a gene mutation (SCN5A c.3404 G>T) and a variant of unknown significance in the desmoplakin gene (DSP c.852 G>A). Neither of these variants has been reported before. The association of myxomatous mitral valve disease and sudden cardiac death has long been suggested, but the mechanisms remain unclear.
We describe sudden cardiac death due to a novel disease causing mutation in the SCN5A gene encoding the cardiac sodium channel in a patient with myxomatous mitral valve disease and flail posterior leaflet treated with the macrolide antibiotic azithromycin. Of the known genetic variants of the long QT syndrome, the long QT3 variant results from mutations in the SCN5A gene and accounts for 5% to 10% of clinical cases.
Desmoplakin is a desmosomal protein responsible for mechanical coupling of adjacent cardiac myocytes. Desmoplakin gene mutations are among the most common cardiomyopathy mutations and are known to overlap with channelopathies.
Genetic analysis of the desmoplakin gene mutation (DSP c.852 G>A) was inconclusive, thus resulting in the genetic classification of variant of unknown significance.
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