The anticoagulation choices of internal medicine residents for stroke prevention in non-valvular atrial fibrillation.

PURPOSE OF THE STUDY: To explore the oral anticoagulation (OAC) prescribing choices of Canadian internal medicine residents, at different training levels, in comparison with the Canadian Cardiovascular Society (CCS) guidelines for non-valvular atrial fibrillation (NVAF). STUDY DESIGN: Cross-sectional, web-based survey, involving clinical scenarios designed to favour the use of non-vitamin K antagonists (NOACs) as per the 2014 CCS NVAF guidelines. Additional questions were also designed to determine resident attitudes towards OAC prescribing. RESULTS: A total of 518 internal medicine responses were analysed, with 196 postgraduate year (PGY)-1s, 169 PGY-2s and 153 PGY-3s. The majority of residents (81%) reported feeling comfortable choosing OAC, with 95% having started OAC in the past 3 months. In the initial clinical scenario involving an uncomplicated patient with a CHADS2 score of 3, warfarin was favoured over any of the NOACs by PGY-1s (81.6% vs 73.9%), but NOACs were favoured by PGY-3s (88.3% vs 83.7%). This was the only scenario where OAC choices varied by PGY year, as each of the subsequent clinical scenarios residents generally favoured warfarin over NOACs irrespective of level of training. The majority of residents stated that they would no longer prescribe warfarin once NOAC reversal agents are available, and residents felt risk of adverse events was the most important factor when choosing OAC. CONCLUSIONS: Canadian internal medicine residents favoured warfarin over NOACs for patients with NVAF, which is in discordance with the evidence-based CCS guidelines. This finding persisted throughout the 3 years of core internal medicine training.

Synthesis and preliminary evaluation of [(18)F]-fluoro-(2S)-Exaprolol for imaging cerebral beta-adrenergic receptors with PET.

Cerebral beta-adrenergic receptors (beta-ARs) are of interest in several disorders including Parkinson's disease, Alzheimer's disease and in particular major depressive disorder. Development of a positron emission tomography (PET) ligand for imaging beta-ARs would allow the quantification of these receptors in the living human brain so as to better understand both the pathophysiology of depression and how to improve treatment. Currently there are no radioligands suitable for this purpose. In an attempt to achieve this goal, we prepared [(18)F]-labeled (2S)-1-(1-fluoropropan-2-ylamino)-3-(2-cyclohexylphenoxy)propan-2-ol (fluoro-Exaprolol; (2S)-1). Radiolabeling with fluorine-18 was accomplished via preparation of a precursor containing a tosyl leaving group (10), and utilizes the 2-oxazolidinone group to simultaneously protect both the amine and hydroxy groups. The oxazolidinone was readily removed with lithium aluminum hydride following a nucleophilic [(18)F]-fluoride for tosyl displacement to prepare [(18)F]-(2S)-1 in 31% radiochemical yield (uncorrected for decay), with >98% radiochemical purity in <1h. The specific activity of the formulated product was 927 mCi/micromol and the log P (pH 7.4) was 2.97. Preliminary biological evaluations in conscious rats indicated that [(18)F]-(2S)-1 had good brain uptake for imaging (0.8-1.3% injected dose/gram (% ID/g) of wet tissue, 5 min post-injection of the radiotracer) with a slow washout (>0.5% ID/g at 60 min post-injection) in all brain regions. Pharmacological challenges indicate that the binding is largely non-specific, as administration of Propranolol, authentic (2S)-1, or WAY 100635 prior to injection of [(18)F]-(2S)-1 did not block uptake of the radiotracer. These results indicate that [(18)F]-(2S)-1 is not a suitable candidate for PET imaging of cerebral beta-ARs.

N-Isopropyl-benzamide.

In the title compound, C(10)H(13)NO, the dihedral angle between the amide group and the phenyl ring is 30.0 (3)°. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds link mol-ecules into one-dimensional chains along the a axis.

Resident Physicians Choices of Anticoagulation for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation.

Atrial fibrillation (AF) is a common cardiac arrhythmia and is associated with an increased risk of ischemic stroke. The aim of this study was to identify practice patterns of Canadian resident physicians pertaining to stroke prevention in nonvalvular AF according to the Canadian Cardiovascular Society guidelines. A Web-based survey consisting of 16 multiple-choice questions was distributed to 11 academic centres. Questions involved identification of risks of stroke, bleeding, and selection of appropriate therapy in clinical scenarios that involve a patient with AF with a Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS2) score of 3 and no absolute contraindications to anticoagulation. There were 1014 total respondents, of whom 570 were internal, 247 family, 137 emergency medicine, and 60 adult cardiology residents. For a patient with a new diagnosis of AF, warfarin was chosen by 80.3%, novel oral anticoagulants (NOACs) by 60.3%, and acetylsalicylic acid (ASA) by 7.2% of residents. To a patient with a history of gastrointestinal bleed during ASA treatment, warfarin was recommended by 75.1%, NOACs by 36.1%, ASA by 12.1%, and 4% were unsure. For a patient with a history of an intracranial bleed, warfarin was recommended by 38.8%, NOACs by 23%, ASA by 24.8%, and 18.2% were unsure. For a patient taking warfarin who had a labile international normalized ratio, 89% would switch to a NOAC and 29.5% would continue warfarin. This study revealed that, across a wide sampling of disciplines and centres, resident physician choices of anticoagulation in nonvalvular AF differ significantly from contemporary Canadian Cardiovascular Society guidelines.

The histology of human right atrial tissue in patients with high-risk Obstructive Sleep Apnea and underlying cardiovascular disease: A pilot study.

BACKGROUND: Obstructive Sleep Apnea (OSA) results in intermittent hypoxia leading to atrial remodeling, which, among other things, facilitates development of atrial fibrillation. While much data exists on the macrostructural changes in cardiac physiology induced by OSA, there is a lack of studies looking for histologic changes in human atrial tissue induced by OSA which might lead to the observed macrostructural changes. METHODS: A case control study was performed. Patients undergoing coronary artery bypass grafting (CABG) were evaluated for OSA and categorized as high-risk or low-risk. The right atrial tissue samples were obtained during CABG and both microscopic histological analysis and Sirius Red staining were performed. RESULTS: 18 patients undergoing CABG were included; 10 high-risk OSA and 8 low-risk OSA in evenly matched populations. No statistically significant difference between the two groups was observed in amount of myocytolysis (p = 0.181), nuclear hypertrophy (p = 0.671), myocardial inflammation (p = n/a), amyloid deposition (p = n/a), or presence of thrombi (p = n/a), as measured through routine H&E staining. As well, no statistically significant difference in interstitial and epicardial collagen was observed, as measured by Sirius Red staining (for total tissue: p = 0.619: for myocardium: p = 0.776). CONCLUSIONS: In this pilot study there were no observable histological differences in human right atrial tissue from individuals at high- and low-risk for OSA. Further investigation would be required for more definitive results.

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.

Effect of preoperative obstructive sleep apnea on the frequency of atrial fibrillation after coronary artery bypass grafting.

Patients with obstructive sleep apnea (OSA) have intermittent hypoxia leading to atrial remodeling and this has been associated with the development of atrial fibrillation (AF). Postoperative AF is a common complication of coronary artery bypass grafting (CABG). The aim of this prospective study was to determine whether the presence of OSA predicts the occurrence of post-CABG AF (PCAF). This was a prospective single-center study. Patients undergoing elective CABG were evaluated and categorized as confirmed, high-risk, or low-risk OSA according to a modified Berlin questionnaire. PCAF was evaluated by 24-hour cardiac monitoring strip or 12-lead electrocardiography during the postoperative period, and validated by an electrophysiologist. We included 277 patients. OSA prevalence was 47.7%, with body mass index (31.0 vs 26.9 kg/m(2), p ≤0.001), advanced age (63.7 vs 66.4 years, p = 0.031), hypertension (78.0% vs 64.8%, p = 0.015), and diabetes (45.5% vs 28.3%, p = 0.003) more prevalent in the OSA group. PCAF was found to occur in 37.2% of all patients and OSA was found to be a strong predictor of PCAF (45.5% vs 29.7%, p = 0.007). PCAF was also associated with continuous positive airway pressure use (12.6% vs 5.2%, p = 0.027). Increased length of stay was associated with PCAF (6.5 vs 5.3 days, p = 0.006), as was longer time from surgery to occurrence of PCAF (p = 0.001). In conclusion, OSA was found to be a strong predictor of PCAF, which in turn was found to be associated with increased length of stay.

Sleep apnea does not predict atrial flutter recurrence after atrial flutter ablation.

PURPOSE: Sleep apnea (SA) has been associated with atrial fibrillation (AF) and has been found to be a predictor of AF recurrence after successful pulmonary vein isolation. No investigations have been carried out to determine the prevalence of SA in patients with typical atrial flutter (AFL) and the impact of SA on AFL recurrence after AFL ablation. Our aim is to determine if SA is a predictor of recurrence of AFL and/or atrial arrhythmias in patients who have undergone AFL ablation. METHODS: This study used a retrospective electronic chart review analysis of consecutive right-sided isthmus-dependent AFL referred for ablation over a 2-year period. Recurrent atrial arrhythmias were classified as AFL, AF, or other arrhythmias. SA prevalence was determined. RESULTS: We included 122 consecutive patients undergoing AFL ablation between January 2008 and December 2009. Mean follow-up was 28.3 ± 6.4 months. Males were 75.4%, had a mean age of 68.3 ± 10.4 years, hypertension 65%, and structural heart disease 42%. Prevalence of SA was 27%. Recurrence of AFL was observed in 9.8%, recurrence of AF was observed in 22.1%, and other arrhythmias 4.9%. SA was not a predictor of AFL recurrence (6.1% vs. 11.2%; p = 0.39). SA was neither a predictor of AF nor of other arrhythmia recurrences. Variables associated with AFL recurrence were: no history of preablation antiarrhythmic drugs (18.8% vs. 6.7%; p = 0.04) and lower BMI (27.07 kg/m(2) vs. 30.87 kg/m(2); p = 0.04). CONCLUSIONS: Prevalence of SA in patients with AFL was 27%. SA was not found to be a predictor of AFL recurrence after successful AFL ablation.

Synthesis and preliminary biological evaluations of [18F]-1-deoxy-1-fluoro-scyllo-inositol.

A novel PET radiotracer, [18F]-1-deoxy-1-fluoro-scyllo-inositol, was synthesized via a one-pot reaction in 16 +/- 3% uncorrected radiochemical yield within 80 minutes; although this compound revealed low brain penetration it shows promise in rodent tumour models for breast cancer imaging.

An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18F]FP-TZTP.

The radioligand 3-(4-(3-[(18)F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5,6-tetrahydropyridine ([(18)F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2) receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [(18)F]FP-TZTP, automated using a GE TRACERlab FX(FN) radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio)propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [(18)F]fluoride (K[(18)F]/K(222)) in CH(3)CN at 80 degrees C for 5 min, and purified by HPLC. Formulated [(18)F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29+/-4%, with a specific activity of 138+/-41 GBq/micromol (3732+/-1109 mCi/micromol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported.