Extended Cardiac Monitoring in Patients With Severe Sleep Apnea and No History of Atrial Fibrillation (The Reveal XT-SA Study).

Atrial fibrillation (AF) is a risk factor for ischemic stroke and reported to be associated with severe obstructive sleep apnea (OSA). The aim of this study was to determine the occurrence of newly detected AF in patients with severe OSA and no previous history of AF. Prospective observational study included patients with severe OSA (Apnea-Hypopnea Index [AHI] ≥ 30) and no history of AF. Primary outcome was detection of AF lasting ≥10 seconds. Patients were subjected to 2 24-hour Holter monitors, and if no AF was detected, implanted with a Medtronic Reveal XT implantable loop recorder. Follow-up was done every 6 months for a total of 3years. Implantable loop recorder was explanted if the primary outcome was detected (AF) or the battery was exhausted. Of the 31 patients enrolled, 6 withdrew participation in the study before implantation. Mean age was 57 ± 10years, mean body mass index was 35 ± 6; 52% male patients. Hypertension 56% and coronary artery disease 24%. Mean AHI was 55 ± 18. AF was detected in 5 patients (20%). AF mean duration was 4.8hours (range 20 seconds to 15.3 hours). Mean time to diagnosis was 11 ± 7 months. Male gender was predictive for AF detection (p = 0.04). Continuous positive airway pressure therapy was used by 96% of patients with 68% total adherence. Mean follow-up was 27 months. In conclusion, extended cardiac monitoring of patients with severe OSA may facilitate the identification of newly detected AF.

Implantable loop recorders in the real world: a study of two Canadian centers.

PURPOSE: Implantable loop recorders (ILRs) are increasingly being used for ambulatory electrocardiography. We sought to evaluate ILR indications, diagnostic yield, ILR-guided interventions, and complications in two Canadian centers. METHODS: This was a retrospective study using electronic medical records to identify ILR implants at Queen's University and the University of Manitoba. Information was collected on patient characteristics, medications, indication for implant, results of prior investigations, diagnostic outcome, and subsequent management. RESULTS: A total of 540 patients were identified; 386 had completed monitoring at time of analysis. Forty patients were lost to follow-up. Indications were unexplained syncope 84.8%, palpitations 12.8%, and suspected atrial fibrillation 11.7%. For syncope, ILRs documented arrhythmia or conduction disorder in 46%. Most common conditions were asystole/sinus pause (22%), complete heart block (10.4%), and atrial fibrillation (AF) (6.9%). After ILR diagnosis, 39.9% of implanted patients received pacemaker/ICD and 2.7% underwent catheter ablation. For palpitations, ILRs documented arrhythmia or conduction disorder in 60.4%. Most common conditions were AVNRT, AF, complete heart block, and ventricular tachycardia. After diagnosis, 25% underwent catheter ablation and 22.9% received pacemaker/ICD. For suspected AF, AF was diagnosed in 40%. Complications were observed in 3.3% of implanted patients: implant site infection 1.5%, non-infectious implant site pain requiring device removal or pocket revision 1.5%, 0.2% hypertrophic scar, and 0.2% device malfunction. CONCLUSIONS: An ILR has excellent diagnostic yield for syncope, palpitations, and suspected AF, and a considerable proportion of patients undergo ILR-directed interventions following monitoring. ILR implantation is a low-risk procedure.

The impact of fever on corrected QT interval.

AIMS: We were interested in the impact of fever on the QT interval as information on this subject is limited. METHODS: We performed a retrospective, single centre study over a two year period, ending December 31st, 2013. Participants were identified using an electronic chart review of emergency department records linked to an ECG data base. Study subjects were drawn from patients presenting with fever to an academic emergency department in Canada. Our study identified febrile (T>38.0°C) patients aged >18years presenting to our centre. Included participants must have had an ED based ECG at the time of presentation with fever and a comparison ECG performed within 30days and without fever. Actively paced patients were excluded. QT values were corrected using Bazett's, Fridericia's and The Framingham Formula. QT values for febrile and afebrile cohorts were compared using Related-Samples Wilcoxon Signed Rank Test. RESULTS: 181 patients satisfied our inclusion/exclusion criteria, 54.1% were female and mean age was 68.9years old. Mean duration between febrile and afebrile ECGs was 6.1days. The median corrected QT interval (QTc) was significantly shorter in patients during their febrile presentation, as compared to their afebrile presentation when correcting for QT using both Framingham [QTc=466.1ms (445.8-499.5) vs. 507.6 (476.0-539.0); p<0.001] and Fridericia's formula [QTc=388.7ms, (371.5-407.5) vs. 406.7ms, (386.1-434.4); p<0.001]. This difference was independent of gender. CONCLUSION: We found fever to shorten the QTc independently of sex in a general emergency department population.

Obstructive sleep apnea as a predictor of atrial fibrillation after coronary artery bypass grafting: a systematic review and meta-analysis.

BACKGROUND: Post-coronary artery bypass grafting atrial fibrillation (PCAF) is associated with increased morbidity, mortality, and system costs. Few studies have explored obstructive sleep apnea (OSA) as a risk factor for PCAF. We aimed to systematically review and synthesize the evidence associating OSA with PCAF. METHODS: We conducted a search of MEDLINE, EMBASE, Google Scholar, and Web of Science, as well as abstracts, conference proceedings, and reference lists until June 2014. Eligible studies were in English, were conducted in humans, and assessed OSA with polysomnography (PSG) or a validated questionnaire. Two reviewers independently selected studies, with disagreement resolved by consensus. Piloted forms were used to extract data and assess risk of bias. RESULTS: Five prospective cohort studies were included (n = 642). There was agreement in study selection (κ statistic, 0.89; 95% confidence interval [CI], 0.75-1.00). OSA was associated with a higher risk of PCAF (odds ratio [OR], 1.86; 95% CI 1.24-2.80; P = 0.003; I(2) = 35%). We conducted 3 subgroup analyses. The associations increased for data that used PSG to assess OSA (OR, 2.34; 95% CI, 1.48-3.70), when severe OSA was included from 1 study (OR, 2.59; 95% CI, 1.63-4.11), and when adjusted analyses were pooled (OR, 2.38; 95% CI, 1.57-3.62; P < 0.001 in all), with no heterogeneity detected in any subgroup analysis (I(2) < 0.01% in all). CONCLUSIONS: OSA was shown to be a strong predictor of PCAF.

The relationship between obstructive sleep apnea and atrial fibrillation in special patient populations.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder associated with both cardiovascular morbidity and mortality. Studies have shown a strong relationship between OSA and the most common cardiac arrhythmia - atrial fibrillation (AF). In this review, the authors intend to analyze AF in the context of OSA in populations of special medical interest; specifically investigating OSA in post-cardioversion, post-pulmonary isolation and post-coronary artery bypass graft patients as well as those afflicted by congestive heart failure, hypertrophic cardiomyopathy, coronary artery disease, erectile dysfunction and stroke. Moreover, the authors will highlight the importance of OSA severity, our current understanding of its mechanistic link to AF pathophysiology and treatment options.

Kar3Vik1 mechanochemistry is inhibited by mutation or deletion of the C terminus of the Vik1 subunit.

Force production by kinesins has been linked to structural rearrangements of the N and C termini of their motor domain upon nucleotide binding. In recent crystal structures, the Kar3-associated protein Vik1 shows unexpected homology to these conformational states even though it lacks a nucleotide-binding site. This conservation infers a degree of commonality in the function of the N- and C-terminal regions during the mechanochemical cycle of all kinesins and kinesin-related proteins. We tested this inference by examining the functional effects on Kar3Vik1 of mutating or deleting residues in Vik1 that are involved in stabilizing the C terminus against the core and N terminus of the Vik1 motor homology domain (MHD). Point mutations at two moderately conserved residues near the Vik1 C terminus impaired microtubule gliding and microtubule-stimulated ATP turnover by Kar3Vik1. Deletion of the seven C-terminal residues inhibited Kar3Vik1 motility much more drastically. Interestingly, none of the point mutants seemed to perturb the ability of Kar3Vik1 to bind microtubules, whereas the C-terminal truncation mutant did. Molecular dynamics simulations of these C-terminal mutants showed distinct root mean square fluctuations in the N-terminal region of the Vik1 MHD that connects it to Kar3. Here, the degree of motion in the N-terminal portion of Vik1 highly correlated with that in the C terminus. These observations suggest that the N and C termini of the Vik1 MHD form a discrete folding motif that is part of a communication pathway to the nucleotide-binding site of Kar3.

Neck rotation and neck mimic docking in the noncatalytic Kar3-associated protein Vik1.

BACKGROUND: Kar3Vik1 is a heterodimeric kinesin with one catalytic subunit (Kar3) and one noncatalytic subunit (Vik1). RESULTS: Vik1 experiences conformational changes in regions analogous to the force-producing elements in catalytic kinesins. CONCLUSION: A molecular mechanism by which Kar3 could trigger Vik1's release from microtubules was revealed. SIGNIFICANCE: These findings will serve as the prototype for understanding the motile mechanism of kinesin-14 motors in general. It is widely accepted that movement of kinesin motor proteins is accomplished by coupling ATP binding, hydrolysis, and product release to conformational changes in the microtubule-binding and force-generating elements of their motor domain. Therefore, understanding how the Saccharomyces cerevisiae proteins Cik1 and Vik1 are able to function as direct participants in movement of Kar3Cik1 and Kar3Vik1 kinesin complexes presents an interesting challenge given that their motor homology domain (MHD) cannot bind ATP. Our crystal structures of the Vik1 ortholog from Candida glabrata may provide insight into this mechanism by showing that its neck and neck mimic-like element can adopt several different conformations reminiscent of those observed in catalytic kinesins. We found that when the neck is α-helical and interacting with the MHD core, the C terminus of CgVik1 docks onto the central ß-sheet similarly to the ATP-bound form of Ncd. Alternatively, when neck-core interactions are broken, the C terminus is disordered. Mutations designed to impair neck rotation, or some of the neck-MHD interactions, decreased microtubule gliding velocity and steady state ATPase rate of CgKar3Vik1 complexes significantly. These results strongly suggest that neck rotation and neck mimic docking in Vik1 and Cik1 may be a structural mechanism for communication with Kar3.