Heart Rhythm (2004) 1, 126 –127
ASSOCIATE EDITOR: PENG-SHENG CHEN
Peng-Sheng Chen, MD Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and David Geffen School of Medicine, UCLA, Los Angeles, California.
Genetic basis of short QT syndrome There is an association between sudden death and short-QT intervals in the electrocardiogram. To determine the genetic basis of this syndrome, Brugada et al (Circulation. 2004; 109:30) studied three families with hereditary short-QT syndrome and a high incidence of ventricular arrhythmias and sudden cardiac death. In two of them, the authors identified two different missense mutations resulting in the same amino acid change (N588K) in the S5-P loop region of the cardiac IKr channel HERG (KCNH2). The mutations dramatically increase IKr, leading to heterogeneous abbreviation of action potential duration and refractoriness, and reduce the affinity of the channels to IKr blockers. The authors conclude that mutations in KCNH2 constitute a genetic and biophysical mechanism responsible for sudden death. KCNH2 is the binding target for a wide spectrum of cardiac and noncardiac pharmacological compounds. The authors suggested that these findings may provide better understanding of drug interaction with KCNH2 and have implications for diagnosis and therapy of this and other arrhythmogenic diseases.
A biological pacemaker HCN2 is an isoform of the gene encoding the pacemaker current If. Overexpression of this gene in canine left atrium provided pacemaker function when sinus rhythm was suppressed (Qu, Circulation. 2003;107:1106). Plotnikov et al (Circulation. 2004;109:506) hypothesized that administration of HCN2 gene to the left bundle-branch system in dogs would provide pacemaker function in the physiological range of heart rate. They injected an adenoviral construct
Address correspondence: Dr. Peng-Sheng Chen, Rm 5342, CedarsSinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048. E-mail address: [email protected]
via catheter under fluoroscopic control into the posterior division of the left bundle branch. During vagal stimulation, HCN2-injected dogs showed rhythms originating from the left ventricle. The rate was significantly more rapid than in dogs that received no HCN2 gene transfer. Isolated tissues from the injected dogs showed immunohistochemical and biophysical evidence of overexpressed HCN2. The authors concluded that a gene-therapy approach for induction of biological pacemaker activity within the left bundle-branch system provides ventricular escape rhythms that have physiologically acceptable rates.
Comparison of vasopressin and epinephrine in cardiopulmonary resuscitation Wenzel et al (N Engl J Med. 2004;350:105) performed a study to compare vasopressin and epinephrine during cardiopulmonary resuscitation. The authors randomly assigned 1186 adults who had had an out-of-hospital cardiac arrest to receive two injections of either 40 IU of vasopressin (N ⫽ 589) or 1 mg of epinephrine (N ⫽ 597). There were no significant differences in the rates of hospital admission between the vasopressin group and the epinephrine group either among patients with ventricular fibrillation or among those with pulseless electrical activity. Among patients with asystole, however, vasopressin use was associated with significantly higher rates of hospital admission and hospital discharge. Among 732 patients in whom spontaneous circulation was not restored with the two injections of the study drug, additional treatment with epinephrine resulted in significant improvement in the vasopressin group, but not in the epinephrine group. Cerebral performance was similar in the two groups. The authors concluded that the effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity, but vasopressin was superior
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to epinephrine in patients with asystole. Vasopressin followed by epinephrine may be more effective than epinephrine alone in the treatment of refractory cardiac arrest.
Function of connexin subtypes Gap junction channels in the heart are composed of several different types of connexins (Cx): Cx43, Cx40, and Cx45. It is unclear if these connexins are interchangeable. Alcole´ a et al (Circ Res. 2004;94:100) generated Cx40 knock-in Cx45 mice to explore the ability of Cx45 to replace Cx40, and to assess the functional equivalence of these two connexins. Electrocardiograms revealed an increased duration of the P wave most likely due to slowed conduction in the left atrium. The conduction velocities in the right atrium and the ventricular myocardium, as well as conduction through the atrioventricular node, were unaffected. There is a prolonged and fractionated QRS complex as a result of slow conduction measured in the right branch. The conduction velocity in the left branch was unchanged. The authors concluded that, in the absence of Cx40, the upregulation of Cx45 in the heart results in normal impulse propagation in the right atrium, the atrioventricular node, and the left His bundle branch only.
Pulmonary vein denervation and atrial fibrillation ablation Pappone et al (Circulation. 2004;109:327) performed a study to evaluate the relationship between autonomic nerve function modification and recurrent atrial fibrillation after circumferential pulmonary vein ablation. The authors collected data from 297 patients undergoing circumferential pulmonary vein ablation for paroxysmal atrial fibrillation. Vagal reflexes were defined as sinus bradycardia (⬍40 beats/min), asystole, atrioventricular block, or hypotension that occurred within a few seconds of the onset of radiofrequency energy application. If a reflex was elicited, radiofrequency energy was delivered until such reflexes were abolished. The roof junction of the left superior pulmonary vein and the posteroinferior junction of the left and right inferior pulmonary veins are the optimal sites for eliciting and eliminating vagal reflexes. During follow-up, patients free of recurrent atrial fibrillation were characterized by marked and prolonged heart rate variability changes consistent with vagal withdrawal. Only the percentage area of left atrial isolation and complete vagal denervation were predictors of atrial fibrillation recurrence after circumferential pulmonary vein ablation (P ⬍ .001 and P ⫽ .025, respectively). The authors concluded that adjunctive complete vagal denervation during circumferential pulmonary vein ablation significantly reduces recurrence of atrial fibrillation at 12 months.