Atrial fibrillation in sub-saharan Africa: epidemiology, unmet needs, and treatment options

Health care in Sub-Saharan Africa is being challenged by a double burden of disease as lifestyle diseases common in the developed world, such as stroke and atrial fibrillation (AF), increase, while, simultaneously, health issues of the developing world in terms of communicable disease persist. The prevalence of AF is lower in Africa than in the developed world but is expected to increase significantly over the next few decades. Patients with AF in Africa tend to be younger and have a higher prevalence of rheumatic valvular heart disease than patients with AF in other regions. Permanent AF is the most prevalent type of AF in Africa, possibly due to the lower use of rhythm control strategies than in the developed world. Mortality rates of patients with AF in Africa are high, due largely to poor health care access and suboptimal therapy. The risk of stroke in AF, which is moderate to high in Africans as in the developed world, contributes to the high mortality rate. Patients with AF in Africa are often undertreated with antithrombotics, as cost and access to monitoring are major barriers. Vitamin K antagonists, including warfarin, are the most commonly available oral anticoagulants, but regular monitoring can be challenging, especially for patients in remote areas. Several non-vitamin K antagonist oral anticoagulants (NOACs) have been approved for use in countries across Sub-Saharan Africa and have the potential to reduce stroke burden. The higher cost of newer agents may be offset by the reduced need for regular monitoring, fixed dosing, and lower risk of intracranial bleeding; NOACs could provide a treatment option for patients in remote areas with limited access to regular monitoring. However, NOACs are not indicated in valvular AF. More work is needed to increase understanding of the epidemiology of AF and stroke, as well as to improve management strategies to reduce the burden of cardiovascular disease predicted for Africa

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

Ground-Laboratory to In-Space Atomic Oxygen Correlation for the Polymer Erosion and Contamination Experiment (PEACE) Polymers

The Materials International Space Station Experiment 2 (MISSE 2) Polymer Erosion and Contamination Experiment (PEACE) polymers were exposed to the environment of low Earth orbit (LEO) for 3.95 years from 2001 to 2005. There were 41 different PEACE polymers, which were flown on the exterior of the International Space Station (ISS) in order to determine their atomic oxygen erosion yields. In LEO, atomic oxygen is an environmental durability threat, particularly for long duration mission exposures. Although spaceflight experiments, such as the MISSE 2 PEACE experiment, are ideal for determining LEO environmental durability of spacecraft materials, ground-laboratory testing is often relied upon for durability evaluation and prediction. Unfortunately, significant differences exist between LEO atomic oxygen exposure and atomic oxygen exposure in ground-laboratory facilities. These differences include variations in species, energies, thermal exposures and radiation exposures, all of which may result in different reactions and erosion rates. In an effort to improve the accuracy of ground-based durability testing, ground-laboratory to in-space atomic oxygen correlation experiments have been conducted. In these tests, the atomic oxygen erosion yields of the PEACE polymers were determined relative to Kapton H using a radio-frequency (RF) plasma asher (operated on air). The asher erosion yields were compared to the MISSE 2 PEACE erosion yields to determine the correlation between erosion rates in the two environments. This paper provides a summary of the MISSE 2 PEACE experiment; it reviews the specific polymers tested as well as the techniques used to determine erosion yield in the asher, and it provides a correlation between the space and ground laboratory erosion yield values. Using the PEACE polymers asher to in-space erosion yield ratios will allow more accurate in-space materials performance predictions to be made based on plasma asher durability evaluation

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

Targeting stroke risk and improving outcomes in patients with atrial fibrillation in Latin America

ABSTRACT CONTEXT AND OBJECTIVE: To examine stroke risk factors, including atrial fibrillation, management and prevention, and stroke outcomes across Latin America. DESIGN AND SETTING: Narrative review conducted at Piedmont Heart Institute, United States. METHODS: The PubMed, Embase and Cochrane databases were searched for stroke AND "Latin America" AND epidemiology (between January 2009 and March 2015). Further studies in the SciELO, World Health Organization and Pan-American Health Organization databases were used to address specific points. RESULTS: Countries categorized as low or middle-income nations by the World Bank, which includes most of Latin America, account for two-thirds of all strokes. Globally, fewer than half of patients (median treatment level: 43.9%) with atrial fibrillation receive adequate anticoagulation to reduce stroke risk, which correlates with data from Latin America, where 46% of outpatients did not receive guideline-compliant anticoagulation, ranging from 41.8% in Brazil to 54.8% in Colombia. CONCLUSIONS: Atrial fibrillation-related stroke carries a heavy burden. Non-vitamin K antagonist oral anti-coagulants provide options for reducing the risk of atrial fibrillation-related stroke. However, cost-effectiveness comparisons with warfarin are warranted before observational health-economics study results can be applied clinically. Initiatives to remedy inequalities and improve access to care across Latin America should accompany risk factor modification and guideline-based prevention