Background. The Cardiac Arrhythmia Suppression Trial (CAST) tested the hypothesis that the suppression of asymptomatic or mildly symptomatic ventricular premature depolarizations in survivors of myocardial infarction would decrease the number of deaths from ventricular arrhythmias and improve overall survival. The second CAST study (CAST-II) tested this hypothesis with a comparison of moricizine and placebo.Methods. CAST-II was divided into two blinded, randomized phases: an early, 14-day exposure phase that evaluated the risk of starting treatment with moricizine after myocardial infarction (1325 patients), and a long-term phase that evaluated the effect of moricizine on survival after myocardial infarction in patients whose ventricular premature depolarizations were either adequately suppressed by moricizine (1155 patients) or only partially suppressed (219 patients).Results. CAST-II was stopped early because the first 14-day period of treatment with moricizine after a myocardial infarction was associated with excess mortality (17 of 665 patients died or had cardiac arrests), as compared with no treatment or placebo (3 of 660 patients died or had cardiac arrests); and estimates of conditional power indicated that it was highly unlikely (<8 percent chance) that a survival benefit from moricizine could be observed if the trial were completed. At the completion of the long-term phase, there were 49 deaths or cardiac arrests due to arrhythmias in patients assigned to moricizine, and 42 in patients assigned to placebo (adjusted P = 0.40).Conclusions. As with the antiarrhythmic agents used in CAST-I (flecainide and encainide), the use of moricizine in CAST-II to suppress asymptomatic or mildly symptomatic ventricular premature depolarizations to try to reduce mortality after myocardial infarction is not only ineffective but also harmful.

Journal of Cardiovascular ElectrophysiologyVolume 1, Issue 4 p. 313-334 The Evolution of Low Threshold Leads GERALD C. TIMMIS M.D., Corresponding Author GERALD C. TIMMIS M.D. From the Division of Cardiovascular Diseases, Royal Oak, MichiganAddress for reprints: Gerald C. Timmis, M.D., Division of Cardiovascular Diseases, William Beaumont Hospital, 3601 West Thirteen Mile Road, Royal Oak, Michigan 48072Search for more papers by this authorJOHN HELLAND B.M.E., JOHN HELLAND B.M.E. Medtronic, Inc., Minneapolis, MinnesotaSearch for more papers by this authorDOUGLAS C. WESTVEER M.D., DOUGLAS C. WESTVEER M.D. Electrophysiology Laboratory, William Beaumont Hospital, Royal Oak, MichiganSearch for more papers by this authorJAMES STEWART M.D., JAMES STEWART M.D. Electrophysiology Laboratory, William Beaumont Hospital, Royal Oak, MichiganSearch for more papers by this authorSEYMOUR GORDON M.D., SEYMOUR GORDON M.D. From the Division of Cardiovascular Diseases, Royal Oak, MichiganSearch for more papers by this author GERALD C. TIMMIS M.D., Corresponding Author GERALD C. TIMMIS M.D. From the Division of Cardiovascular Diseases, Royal Oak, MichiganAddress for reprints: Gerald C. Timmis, M.D., Division of Cardiovascular Diseases, William Beaumont Hospital, 3601 West Thirteen Mile Road, Royal Oak, Michigan 48072Search for more papers by this authorJOHN HELLAND B.M.E., JOHN HELLAND B.M.E. Medtronic, Inc., Minneapolis, MinnesotaSearch for more papers by this authorDOUGLAS C. WESTVEER M.D., DOUGLAS C. WESTVEER M.D. Electrophysiology Laboratory, William Beaumont Hospital, Royal Oak, MichiganSearch for more papers by this authorJAMES STEWART M.D., JAMES STEWART M.D. Electrophysiology Laboratory, William Beaumont Hospital, Royal Oak, MichiganSearch for more papers by this authorSEYMOUR GORDON M.D., SEYMOUR GORDON M.D. From the Division of Cardiovascular Diseases, Royal Oak, MichiganSearch for more papers by this author First published: August 1990 https://doi.org/10.1111/j.1540-8167.1983.tb01632.xCitations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume1, Issue4August 1990Pages 313-334 RelatedInformation

Fully automatic pacing systems rely on accurate identification of spontaneous atrial signals for physiologically responsive pacing. These signals must be discriminated from far-field ventricular activity, which might otherwise be sensed in the atrium. To amplify on the previously reported superiority of bipolar signals and high-impedance circuitry for atrial sensing, we studied the effects of various intraatrial electrode positions on the atrial and ventricular contribution to electrograms recorded in this chamber. Compared with other intraatrial endocardial sites, right atrial signals were greatest in amplitude and slew rate in the appendage (RAA), averaging 3.3 +/- 0.41 mV and 1.15 +/- 0.16 V/sec (mean +/- SEM), respectively. These values were substantially higher than in the low atrium (p less than 0.001 and 0.0005 for amplitude and slew rate, respectively) and the high lateral atrium (p less than 0.05 for slew rate). Appendage atrial electrograms also had significantly higher amplitude and slew rate than far-field R waves recorded here (p less than 0.0001 for both). Additionally, the greatest difference in spectral content between atrial and far-field ventricular signals was also observed in the RAA. Thus, parameters in the domain of both time and frequency identified the RAA as the superior location for atrial sensing. Except for phrenic nerve problems with pacing, the HRA also appears to be a suitable electrode location for sensing. These considerations are germane in light of a growing number of atrial active and passive fixation leads now being employed for physiologic pacing.