Management of Long QT Syndrome in Women Before, During, and After Pregnancy

Congenital long QT syndrome (LQTS) is a primary genetic and electrical disorder that increases risk for torsades de pointes, syncope, and sudden death. Post-pubertal women with LQTS require specialized multidisciplinary management before, during, and after pregnancy involving cardiology and obstetrics to reduce risk for cardiac events in themselves and their fetuses and babies. The risk of potentially life-threatening events is lower during pregnancy but increases significantly during the 9-month postpartum period. Treatment of women with LQTS with a preferred β-blocker at optimal doses along with close monitoring are indicated throughout pregnancy and during the high-risk postpartum period

Conversion Efficacy and Safety of Intravenous Ibutilide Compared With Intravenous Procainamide in Patients With Atrial Flutter or Fibrillation 11This study was sponsored by Pharmacia & Upjohn, Kalamazoo, Michigan.22See Appendix Afor a complete list of investigators and study sites.

AbstractObjectives. This multicenter study compared the efficacy and safety of ibutilide versus procainamide for conversion of recent-onset atrial flutter or fibrillation.Background. Ibutilide fumarate is an intravenous (IV) class III antiarrhythmic agent that has been shown to be significantly more effective than placebo in the pharmacologic conversion of atrial flutter and fibrillation to sinus rhythm. Procainamide is commonly used for conversion of recent-onset atrial fibrillation to normal sinus rhythm.Methods. One hundred twenty-seven patients (age range 22 to 92 years) with atrial flutter or fibrillation of 3 h to 90 days’ (mean 21 days) duration were randomized to receive either two 10-min IV infusions of 1 mg of ibutilide fumarate, separated by a 10-min infusion of 5% dextrose in sterile water, or three successive 10-min IV infusions of 400 mg of procainamide hydrochloride.Results. Of the 127 patients, 120 were evaluated for efficacy: 35 (58.3%) of 60 in the ibutilide group compared with 11 (18.3%) of 60 in the procainamide group had successful termination within 1.5 h of treatment (p < 0.0001). Seven patients were found to have violated the protocol and were not included in the final evaluation. In the patients with atrial flutter, ibutilide had a significantly higher success rate than procainamide (76% [13 of 17] vs. 14% [3 of 22], p = 0.001). Similarly, in the atrial fibrillation group, ibutilide had a significantly higher success rate than procainamide (51% [22 of 43] vs. 21% [8 of 38], p = 0.005). One patient who received ibutilide, which was found to be a protocol violation, had sustained polymorphic ventricular tachycardia requiring direct current cardioversion. Seven patients who received procainamide became hypotensive.Conclusions. This study establishes the superior efficacy of ibutilide over procainamide when administered to patients to convert either atrial fibrillation or atrial flutter to sinus rhythm. Hypotension was the major adverse effect seen with procainamide. A low incidence of serious proarrhythmia was seen with the administration of ibutilide occurring at the end of infusion

Quality of Life and Clinical Outcomes in Elderly Patients Treated with Ventricular Pacing as Compared with Dual-Chamber Pacing

ABSTRACT Background Standard clinical practice permits the use of either single-chamber ventricular pacemakers or dual-chamber pacemakers for most patients who require cardiac pacing. Ventricular pacemakers are less expensive, but dual-chamber pacemakers are believed to be more physiologic. However, it is not known whether either type of pacemaker results in superior clinical outcomes. Methods The Pacemaker Selection in the Elderly study was a 30-month, single-blind, randomized, controlled comparison of ventricular pacing and dualchamber pacing in 407 patients 65 years of age or older in 29 centers. Patients received a dual-chamber pacemaker that had been randomly programmed to either ventricular pacing or dual-chamber pacing. The primary end point was health-related quality of life as measured by the 36-item Medical Outcomes Study Short-Form General Health Survey. Results The average age of the patients was 76 years (range, 65 to 96), and 60 percent were men. Quality of life improved significantly after pacemaker implantation (P0.001), but there were no differences between the two pacing modes in either the quality of life or prespecified clinical outcomes (including cardiovascular events or death). However, 53 patients assigned to ventricular pacing (26 percent) were crossed over to dual-chamber pacing because of symptoms related to the pacemaker syndrome. Patients with sinus-node dysfunction, but not those with atrioventricular block, had moderately better quality of life and cardiovascular functional status with dual-chamber pacing than with ventricular pacing. Trends of borderline statistical significance in clinical end points favoring dual-chamber pacing were observed in patients with sinus-node dysfunction, but not in those with atrioventricular block. Conclusions The implantation of a permanent pacemaker improves health-related quality of life. The quality-of-life benefits associated with dualchamber pacing as compared with ventricular pacing are observed principally in the subgroup of patients with sinus-node dysfunction. (N Engl J Med 1998;338:1097-104.

Self-Administered Intranasal Etripamil Using a Symptom-Prompted, Repeat-Dose Regimen for Atrioventricular-Nodal-Dependent Supraventricular Tachycardia (RAPID): A Multicentre, Randomised Trial

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min. METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes (≥20 min) as documented by electrocardiogram. Patients were administered two test doses of intranasal etripamil (each 70 mg, 10 min apart) during sinus rhythm; those who tolerated the test doses were randomly assigned (1:1) using an interactive response technology system to receive either etripamil or placebo. Prompted by symptoms of paroxysmal supraventricular tachycardia, patients self-administered a first dose of intranasal 70 mg etripamil or placebo and, if symptoms persisted beyond 10 min, a repeat dose. Continuously recorded electrocardiographic data were adjudicated, by individuals masked to patient assignment, for the primary endpoint of time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm for at least 30 s within 30 min after the first dose, which was measured in all patients who administered blinded study drug for a confirmed atrioventricular-nodal-dependent event. Safety outcomes were assessed in all patients who self-administered blinded study drug for an episode of perceived paroxysmal supraventricular tachycardia. This trial is registered at ClinicalTrials.gov, NCT03464019, and is complete. FINDINGS: Between Oct 13, 2020, and July 20, 2022, among 692 patients randomly assigned, 184 (99 from the etripamil group and 85 from the placebo group) self-administered study drug for atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia, with diagnosis and timing confirmed. Kaplan-Meier estimates of conversion rates by 30 min were 64% (63/99) with etripamil and 31% (26/85) with placebo (hazard ratio 2·62; 95% CI 1·66-4·15; p INTERPRETATION: Using a symptom-prompted, self-administered, initial and optional-repeat-dosing regimen, intranasal etripamil was well tolerated, safe, and superior to placebo for the rapid conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm. This approach could empower patients to treat paroxysmal supraventricular tachycardia themselves outside of a health-care setting, and has the potential to reduce the need for additional medical interventions, such as intravenous medications given in an acute-care setting. FUNDING: Milestone Pharmaceuticals

Podcast on Self-administered Intranasal Etripamil for Symptomatic Paroxysmal Supraventricular Tachycardia: The RAPID Trial

Abstract Paroxysmal supraventricular tachycardia (PSVT) is commonly seen in clinical practice and represents a significant burden to the healthcare system and to patients. First-line treatments include calcium channel blockers (CCB), although they are intravenous and require medical supervision. Etripamil is an investigational self-administered intranasal L-type CCB for unsupervised treatment of PSVT. In this podcast, we discuss the RAPID trial (NCT03464019), which was a phase 3 study that evaluated the safety and efficacy of etripamil in terminating PSVT episodes using a repeat-dosing regimen. RAPID was a multicenter, randomized trial that enrolled adults with electrocardiograph (ECG)-documented PSVT episodes lasting ≥ 20 min. Patients who tolerated test doses of etripamil were randomized 1:1 to receive either etripamil or placebo. Upon perceiving PSVT symptoms, patients began ECG monitoring and performed a vagal maneuver. If arrhythmia termination was unsuccessful, they self-administered 70 mg of etripamil or placebo, followed by an optional second dose after 10 min. The primary endpoint was time to conversion of PSVT to sinus rhythm within 30 min of the initial dose and sustained for ≥ 30 s. The safety group included all patients who self-administered the study treatment. Of 692 enrollees, 184 self-administered the study drug (99 etripamil, 85 placebo) for ECG-confirmed PSVT. Conversion of PSVT to sinus rhythm within 30 min was achieved in 64.3% of etripamil-treated subjects versus 31.2% of placebo-treated subjects. A significant threefold reduction in the median time to conversion of 17.2 min was observed in the etripamil group versus 53.5 min in the placebo group. Treatment-emergent adverse events were mild or moderate and primarily included transient nasal discomfort, nasal congestion, and rhinorrhea. If etripamil is approved by the US FDA, it can potentially address a significant unmet need for PSVT treatment outside a clinical setting, reducing the need for intravenous treatments that require medical supervision. Podcast available for this article

Search for the optimal right ventricular pacing site: Design and implementation of three randomized multicenter clinical trials

Background: The optimal site to permanently pace the right ventricle (RV) has yet to be determined. To address this issue, three randomized prospective multicenter clinical trials are in progress comparing the long-term effects of RV apical versus septal pacing on left ventricular (LV) function. The three trials are Optimize RV Selective Site Pacing Clinical Trial (Optimize RV), Right Ventricular Apical and High Septal Pacing to Preserve Left Ventricular Function (Protect Pace), and Right Ventricular Apical versus Septal Pacing (RASP). Methods: Patients that require frequent or continuous ventricular pacing are randomized to RV apical or septal pacing. Optimize RV excludes patients with LV ejection fractio