IMPORTANCE Atrial fibrillation (AF) is a major cause of preventable strokes. Screening asymptomatic individuals for AF may increase anticoagulant use for stroke prevention. OBJECTIVE To evaluate 2 home-based AF screening interventions. DESIGN, SETTING, AND PARTICIPANTS This multicenter randomized clinical trial recruited individuals from primary care practices aged 75 years or older with hypertension and without known AF. From April 5, 2015, to March 26, 2019, 856 participants were enrolled from 48 practices. INTERVENTIONSThe control group received standard care (routine clinical follow-up plus a pulse check and heart auscultation at baseline and 6 months). The screening group received a 2-week continuous electrocardiographic (cECG) patch monitor to wear at baseline and at 3 months, in addition to standard care. The screening group also received automated home blood pressure (BP) machines with oscillometric AF screening capability to use twice-daily during the cECG monitoring periods. MAIN OUTCOMES AND MEASURESWith intention-to-screen analysis, the primary outcome was AF detected by cECG monitoring or clinically within 6 months. Secondary outcomes included anticoagulant use, device adherence, and AF detection by BP monitors. RESULTSOf the 856 participants, 487 were women (56.9%); mean (SD) age was 80.0 (4.0) years. Median cECG wear time was 27.4 of 28 days (interquartile range [IQR], 18.4-28.0 days). In the primary analysis, AF was detected in 23 of 434 participants (5.3%) in the screening group vs 2 of 422 (0.5%) in the control group (relative risk, 11.2; 95% CI, 2.7-47.1; P = .001; absolute difference, 4.8%; 95% CI, 2.6%-7.0%; P < .001; number needed to screen, 21). Of those with cECG-detected AF, median total time spent in AF was 6.3 hours (IQR, 4.2-14.0 hours; range 1.3 hours-28 days), and median duration of the longest AF episode was 5.7 hours (IQR, 2.9-12.9 hours). Anticoagulation was initiated in 15 of 20 patients (75.0%) with cECG-detected AF. By 6 months, anticoagulant therapy had been prescribed for 18 of 434 participants (4.1%) in the screening group vs 4 of 422 (0.9%) in the control group (relative risk, 4.4; 95% CI, 1.5-12.8; P = .007; absolute difference, 3.2%; 95% CI, 1.1%-5.3%; P = .003). Twice-daily AF screening using the home BP monitor had a sensitivity of 35.0% (95% CI, 15.4%-59.2%), specificity of 81.0% (95% CI, 76.7%-84.8%), positive predictive value of 8.9% (95% CI, 4.9%-15.5%), and negative predictive value of 95.9% (95% CI, 94.5%-97.0%). Adverse skin reactions requiring premature discontinuation of cECG monitoring occurred in 5 of 434 participants (1.2%). CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, among older community-dwelling individuals with hypertension, AF screening with a wearable cECG monitor was well tolerated, increased AF detection 10-fold, and prompted initiation of anticoagulant therapy in most cases. Compared with continuous ECG, intermittent oscillometric screening with a BP monitor was an inferior strategy for detecting paroxysmal AF. Large trials with hard...

The relative rates of detection of atrial fibrillation (AF) or atrial flutter from evaluating patients with prolonged electrocardiographic monitoring with an external loop recorder or implantable loop recorder after an ischemic stroke are unknown.OBJECTIVE To determine, in patients with a recent ischemic stroke, whether 12 months of implantable loop recorder monitoring detects more occurrences of AF compared with conventional external loop recorder monitoring for 30 days. Investigator-initiated, open-label, randomized clinical trial conducted at 2 university hospitals and 1 community hospital in Alberta, Canada, including 300 patients within 6 months of ischemic stroke and without known AF from May 2015 through November 2017; final follow-up was in December 2018. DESIGN, SETTING, AND PARTICIPANTSINTERVENTIONS Participants were randomly assigned 1:1 to prolonged electrocardiographic monitoring with either an implantable loop recorder (n = 150) or an external loop recorder (n = 150) with follow-up visits at 30 days, 6 months, and 12 months. MAIN OUTCOMES AND MEASURESThe primary outcome was the development of definite AF or highly probable AF (adjudicated new AF lasting Ն2 minutes within 12 months of randomization). There were 8 prespecified secondary outcomes including time to event analysis of new AF, recurrent ischemic stroke, intracerebral hemorrhage, death, and device-related serious adverse events within 12 months. RESULTS Among the 300 patients who were randomized (median age, 64.1 years [interquartile range, 56.1 to 73.7 years]; 121 were women [40.3%]; and 66.3% had a stroke of undetermined etiology with a median CHA 2 DS 2 -VASc [congestive heart failure, hypertension, age Ն75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score of 4 [interquartile range, 3 to 5]), 273 (91.0%) completed cardiac monitoring lasting 24 hours or longer and 259 (86.3%) completed both the assigned monitoring and 12-month follow-up visit. The primary outcome was observed in 15.3% (23/150) of patients in the implantable loop recorder group and 4.7% (7/150) of patients in the external loop recorder group (between-group difference, 10.7% [95% CI, 4.0% to 17.3%]; risk ratio, 3.29 [95% CI, 1.45 to 7.42]; P = .003). Of the 8 specified secondary outcomes, 6 were not significantly different. There were 5 patients (3.3%) in the implantable loop recorder group who had recurrent ischemic stroke vs 8 patients (5.3%) in the external loop recorder group (between-group difference, −2.0% [95% CI, −6.6% to 2.6%]), 1 (0.7%) vs 1 (0.7%), respectively, who had intracerebral hemorrhage (between-group difference, 0% [95% CI, −1.8% to 1.8%]), 3 (2.0%) vs 3 (2.0%) who died (between-group difference, 0% [95% CI, −3.2% to 3.2%]), and 1 (0.7%) vs 0 (0%) who had device-related serious adverse events.CONCLUSIONS AND RELEVANCE Among patients with ischemic stroke and no prior evidence of AF, implantable electrocardiographic monitoring for 12 months, compared with prolonged external monitoring for 30 da...

BackgroundThe precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata.Methods and findingsA systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%–1.82%) and 0.41% (95% CI, 0.31%–0.53%) for <65-year-olds. New AF detection rate increased progressively with age from 0.34% (<60 years) to 2.73% (≥85 years). Neither the choice of screening methodology or device, the geographical region, nor the screening setting influenced the detection rate of AF. Mean CHA2DS2-VASc scores (n = 1,369) increased with age from 1.1 (<60 years) to 3.9 (≥85 years); 72% of ≥65 years had ≥1 additional stroke risk factor other than age/sex. All new AF ≥75 years and 66% between 65 and 74 years had a Class-1 OAC recommendation. The NNS-Rx is 83 for ≥65 years, 926 for 60–64 years; and 1,089 for <60 years. The main limitation of this study is there are insufficient data on sociodemographic variables of the populations and possible ascertainment biases to explain the variance in the samples.ConclusionsPeople with screen-detected AF are at elevated calculated stroke risk: above age 65, the majority have a Class-1 OAC recommendation for stroke prevention, and >70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and str...

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Journal of Physiologyventricle in rabbit heart 8-9 weeks after an experimentally induced apical infarct, and compares these values with equivalent measurements from sham-operated (sham) hearts.

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This two-part manuscript reviews diagnostic pacing maneuvers for supraventricular tachycardia (SVT). Part one will involve a detailed consideration of ventricular overdrive pacing (VOP), since this pacing maneuver provides the diagnosis in the majority of cases. This will include a review of the post-VOP response, fusion during entrainment, the importance of the VOP site, quantitative results of entrainment such as the postpacing interval, differential entrainment, and new criteria derived from features found at the beginning of the VOP train. There is a considerable literature on this topic, and this review is by no means meant to be all-encompassing. Rather, we hope to clearly explain and illustrate the physiology, strengths, and weaknesses of what we consider to be the most important and commonly employed diagnostic pacing maneuvers, that is, those that trainees in cardiac electrophysiology should be well familiar with at a minimum. \

Abstract-Loss-of-function mutations in the human ERG1 potassium channel (hERG1) frequently underlie the long QT2 (LQT2) syndrome. The role of the ERG potassium channel in cardiac development was elaborated in an in vivo model of a homozygous, loss-of-function LQT2 syndrome mutation. The hERG N629D mutation was introduced into the orthologous mouse gene, mERG, by homologous recombination in mouse embryonic stem cells. Intact homozygous embryos showed abrupt cessation of the heart beat. N629D/N629D embryos die in utero by embryonic day 11.5. Their developmental defects include altered looping architecture, poorly developed bulbus cordis, and distorted aortic sac and branchial arches. N629D/N629D myocytes from embryonic day 9.5 embryos manifested complete loss of I Kr function, depolarized resting potential, prolonged action potential duration (LQT), failure to repolarize, and propensity to oscillatory arrhythmias. N629D/N629D myocytes manifest calcium oscillations and increased sarcoplasmic reticulum Ca ϩ2 content. Although the N629D/N629D protein is synthesized, it is mainly located intracellularly, whereas ϩ/ϩ mERG protein is mainly in plasmalemma. N629D/N629D embryos show robust apoptosis in craniofacial regions, particularly in the first branchial arch and, to a lesser extent, in the cardiac outflow tract. Because deletion of Hand2 produces apoptosis, in similar regions and with a similar final developmental phenotype, Hand2 expression was evaluated. Robust decrease in Hand2 expression was observed in the secondary heart field in N629D/N629D embryos. In conclusion, loss of I Kr function in N629D/N629D cardiovascular system leads to defects in cardiac ontogeny in the first branchial arch, outflow tract, and the right ventricle. Key Words: KCNH2 (hERG) Ⅲ knock-in mouse Ⅲ embryo developmental defect T he human ERG gene (hERG/KCNH2) encodes a potassium channel that is important in the late stage of action potential repolarization in heart. Mutations in this gene, which generally reduce plasmalemmal expression of hERG, lead to the long QT2 (LQT2) syndrome in humans. [1][2] Patients with the LQT2 syndrome have a delay in cardiac repolarization that predisposes them to cardiac arrhythmias that can be lethal. 1,2 Mutations in hERG are associated with embryonic lethality and the sudden infant death syndrome. [3][4] Although the LQT2 syndrome generally occurs in individuals heterozygous for the mutant allele, individuals homozygous for the exon 4 duplication manifest embryonic lethality or are rescued in the neonatal period by pacing. 5 Although not widely recognized, mutations of' hERG appear to be associated with structural congenital cardiovascular anomalies including: tetralogy of Fallot, atrial-septal defects, ventricularseptal defects, and patent ductus arteriosus. 6 -9 Mouse ERG (mERG) is the dominant repolarizing current in the mouse embryonic heart. 10 A channel analogous to hERG is expressed in differentiating quail neural crest cells 11 early in development. These data imply a potential role of the ERG potass...