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.
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.
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.
A 31-year-old parturient delivered twins at 35 weeks’ gestation by cesarean section with spinal anesthesia. Following anesthesia induction, hypotension and bradycardia occurred, and were immediately ...treated with theodrenaline plus cafedrin (Akrinor) and atropine. Blood pressure and heart rate increased to 180/100 mmHg and 140 beats per minute, respectively. Several minutes later, the patient developed a myocardial infarction (MI) that she survived after intensive care treatment without sequelae. Although the coronary angiography showed normal coronary vessels, an intravascular ultrasound study demonstrated an atheroma in the left main coronary artery with ruptured fibrous cap. Laboratory screening for risk factors of coronary artery disease (CAD) showed hypercholesterinemia, increased factor VII activity, and hyperfibrogenemia. Angiographically normal coronary vessels are frequently found in pregnant patients who suffered MI. In these patients, coronary spasms have been discussed as the major mechanism of disease. Our case demonstrates that a significant CAD may be present despite angiographically normal findings. Plaque rupture was triggered by hypertension and led to MI as the first symptom of disease. On the basis of these findings, we believe that MI during pregnancy is more often caused by plaque rupture than may be expected, according to the current literature.
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