Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death.

BACKGROUND: Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death. METHODS AND RESULTS: Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca(v)1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours. Three probands displaying ST-segment elevation and corrected QT intervals < or = 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Ca(v)1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca(v beta2b)-subunits. CONCLUSIONS: This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.

Chylopericardium presenting as cardiac tamponade secondary to an anterior mediastinal cystic teratoma.

Cardiac tamponade, the accumulation of fluid in the pericardial space, leads to impaired venous return, loss of left ventricular preload, and hemodynamic collapse. The many causes of tamponade include malignancy, infection, inflammation, connective tissue disorders, and uremia. Herein, we report the case of a young woman who presented with syncope. She was found to have cardiac tamponade secondary to a chylous pericardial effusion that was due to a mature and benign anterior mediastinal cystic teratoma. Numerous reports have described pericardial effusions secondary to an anterior mediastinal cystic teratoma; however, to our knowledge, this is the 1st case of a teratoma causing chylopericardium that presented as tamponade.

Hemodynamic instability after receiving intravenous Perflutren for contrast echocardiography in an elderly female.

Myocardial contrast echocardiography (MCE) has been used with increasing frequency and is considered a safe way to improve left ventricular border opacification. Studies have consistently documented that MCE can improve the ability to assess both global and regional left ventricular function by echocardiography. We report the case of an 83-year-old female who developed immediate and sustained hemodynamic instability after the injection of Perflutren for a contrast echocardiogram. We reviewed the literature and found no such previous reactions with Perflutren. Based on the temporal sequence of hypotension following Perflutren injection along with other clinical data, we concluded that our patient's hemodynamic instability was most likely secondary to an anaphylactic reaction.