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BackgroundWe aimed to determine the relative frequency of affected cerebrovascular territories in patients with atrial fibrillation (AF) suffering an ischemic stroke.MethodsAltogether, 1,976 patients who suffered their first-ever ischemic stroke during 2003–2012 and were diagnosed with AF either before or within 30 days after the event were included in this retrospective multicenter cohort study. Strokes were classified radiographically to be located either within the anterior or the posterior cerebrovascular territory, and the effect of the CHA2DS2-VASc score, oral anticoagulant (OAC) use, and timing of AF diagnosis on lesion localization was determined.ResultsThe median age of the patients was 78.4 (interquartile range: 71.7–84.2) years, 1,137 (57.5%) of them were women, their mean CHA2DS2-VASc score was 3.5 (95% confidence interval: 3.4–3.5), 656 (33.2%) were receiving OAC drugs, and altogether, 1,450 (73%) had a previous AF diagnosis. The localization of ischemic lesions between the anterior and the posterior cerebrovascular territories was not affected by the timing of AF diagnosis (p = 0.46), use of OACs (p = 0.70), or the CHA2DS2-VASc score (p = 0.10). Within the anterior territory, altogether 774 strokes (53.2%) were located in the left hemisphere and 3 (0.2%) were bilateral. The timing of AF diagnosis (p = 0.84), use of OACs (p = 0.90), or the CHA2DS2-VASc score (p = 0.21) did not affect the location of the ischemic lesion between the hemispheres.ConclusionsThe timing of AF diagnosis, use of OAC drugs, or the CHA2DS2-VASc score did not affect the distribution of ischemic strokes. Anterior territory strokes were slightly more often located within the left hemisphere.

Background Elective cardioversion (ECV) for atrial fibrillation (AF) is associated with a relatively low risk of thromboembolic complications. However, the optimal intensity of anticoagulation for ECV is unknown. We sought to assess the risk of thromboembolism in low (INR 2.0–2.4) vs. high (INR ≥ 2.5) therapeutic range in a large retrospective cohort study. Methods This multi-centre “real world” study included 1424 ECVs in 1021 patients. The primary outcome was a stroke or a transient ischaemic attack (TIA) or a systemic embolus during the 30-day follow-up after ECV. Results Altogether 4 (0.3%) strokes, 2 (0.1%) TIAs and 2 (0.1%) bleeds were detected during the 30-day follow-up after ECV. No systemic emboli were detected. There were 2 deaths (0.1%), one associated with a stroke. Median time to stroke/TIA was 4 (IQR 9.5) days and the median CHA2DS2-VASc-score was 2 (IQR 1.25) among patients with thromboembolic events. Mean INR at ECV was 2.7 (SD 0.54) in the study cohort. Patients with INR 2.0–2.4 at ECV had more thromboembolic events compared with patients with INR ≥ 2.5 (5/529 (0.9%) vs. 1/895 (0.1%), p = 0.03). Comprehensive postprocedural INR data was available for 733 (71.8%) patients and 1007 cardioversions. At least one subtherapeutic (< 2.0) INR value was detected within 21 days after 230 (22.8%) ECVs and this drop in INR level was associated with a higher risk for thromboembolic events compared with continuous therapeutic post-cardioversion anticoagulation (1.7% vs 0.3%, p = 0.03). Conclusions Our results suggest that the intensity of periprocedural anticoagulation is associated with the risk of thromboembolic events after ECV., final draft, peerReviewed

Vitamin K antagonist warfarin is widely used in clinical practice and excessive anticoagulation is a well-known complication of this therapy. Little is known about permanent and temporary predictors for severe overanticoagulation. The aim of this study was to investigate the occurrence and predicting factors for episodes with very high (≥9) international normalized ratio (INR) values in warfarin treated patients with atrial fibrillation (AF). Excessive Warfarin Anticoagulation (EWA) study screened all patients (n = 13618) in the Turku University Hospital region with an INR ≥2 between years 2003-2015. Patients using warfarin anticoagulation for AF with very high (≥9) INR values (EWA Group) were identified (n = 412 patients) and their characteristics were compared to a control group (n = 405) of AF patients with stable INR during long-term follow-up. Over 20% (n = 92) of the EWA patients had more than one event of very high INR and in 105 (25.5%) patients EWA led to a bleeding event. Of the several temporary and permanent EWA risk factors observed, strongest were excessive alcohol consumption in 9.6% of patients (OR 24.4, 95% CI 9.9-50.4, p

Electrical cardioversion (ECV) is the standard treatment for acute atrial fibrillation (AF), but identification of patients with increased risk of ECV failure or early AF recurrence is of importance for rational clinical decision-making. The objective of this study was to derive and validate a clinical risk stratification tool for identifying patients at high risk for unsuccessful outcome after ECV for acute AF. Data on 2,868 patients undergoing 5,713 ECVs of acute AF in 3 Finnish hospitals from 2003 through 2010 (the FinCV study data) were included in the analysis. Patients from western (n = 3,716 cardioversions) and eastern (n = 1,997 cardioversions) hospital regions were used as derivation and validation datasets. The composite of cardioversion failure and recurrence of AF within 30 days after ECV was recorded. A clinical scoring system was created using logistic regression analyses with a repeated-measures model in the derivation data set. A multivariate analysis for prediction of the composite end point resulted in identification of 5 clinical variables for increased risk: Age (odds ratio [OR] 1.31, confidence interval [CI] 1.13 to 1.52), not the First AF (OR 1.55, CI 1.19 to 2.02), Cardiac failure (OR 1.52, CI 1.08 to 2.13), Vascular disease (OR 1.38, CI 1.11 to 1.71), and Short interval from previous AF episode (within 1 month before ECV, OR 2.31, CI 1.83 to 2.91) [hence, the acronym, AF-CVS]. The c-index for the AF-CVS score was 0.67 (95% CI 0.65 to 0.69) with Hosmer-Lemeshow p value 0.84. With high (>5) scores (i.e., 12% to 16% of the patients), the rate of composite end point was ∼40% in both cohorts, and among low-risk patients (score

Coronary heart disease (CHD) is a complex disorder constituting a major health problem in Western societies. To assess the genetic background of CHD, we performed a genomewide linkage scan in two study samples from the genetically isolated population of Finland. An initial study sample consisted of family material from the northeastern part of Finland, settled by a small number of founders approximately 300 years ago. A second study sample originated from the southwestern region of Finland, settled approximately 2,000 years ago. Families were ascertained through probands exhibiting premature CHD, defined as >50% stenosis of at least two coronary arteries at a young age, as verified by coronary angiography. Both study samples and the pooled data set provided evidence for linkage in two chromosomal regions. A region on chromosome 2q21.1-22 yielded two-point LOD scores of 3.2, 1.9, and 3.7, in the affected sib-pair (ASP) analyses of the northeastern, southwestern, and pooled study samples. The corresponding multipoint maximum-likelihood scores (MLSs) for these three study samples were 2.4, 1.3, and 3.0. In addition, a region on chromosome Xq23-26 resulted in two-point LOD scores of 1.9, 3.5, and 2.9 and in multipoint MLSs of 3.4, 3.1, and 2.5, respectively. In conclusion, this study identifies two loci likely to contribute to premature CHD: one on chromosome 2q21.1-22 and another on chromosome Xq23-26.

Atrial fibrillation may remain undiagnosed until an ischemic stroke occurs. In this retrospective cohort study we assessed the prevalence of ischemic stroke or transient ischemic attack as the first manifestation of atrial fibrillation in 3,623 patients treated for their first ever stroke or transient ischemic attack during 2003–2012. Two groups were formed: patients with a history of atrial fibrillation and patients with new atrial fibrillation diagnosed during hospitalization for stroke or transient ischemic attack. A control group of 781 patients with intracranial hemorrhage was compiled similarly to explore causality between new atrial fibrillation and stroke. The median age of the patients was 78.3 [13.0] years and 2,009 (55.5%) were women. New atrial fibrillation was diagnosed in 753 (20.8%) patients with stroke or transient ischemic attack, compared to 15 (1.9%) with intracranial hemorrhage. Younger age and no history of coronary artery disease or other vascular diseases, heart failure, or hypertension were the independent predictors of new atrial fibrillation detected concomitantly with an ischemic event. Thus, ischemic stroke was the first clinical manifestation of atrial fibrillation in 37% of younger (

Combined analysis of genome scans of dutch and finnish families reveals a susceptibility locus for high-density lipoprotein cholesterol on chromosome 16q.Pajukanta P, Allayee H, Krass KL, Kuraishy A, Soro A, Lilja HE, Mar R, Taskinen MR, Nuotio I, Laakso M, Rotter JI, de Bruin TW, Cantor RM, Lusis AJ, Peltonen L.Department of Human Genetics, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA 90095, USA. ppajukanta@mednet.ucla.eduSeveral genomewide screens have been performed to identify novel loci predisposing to unfavorable serum lipid levels and coronary heart disease (CHD). We hypothesized that the accumulating data of these screens in different study populations could be combined to verify which of the identified loci truly harbor susceptibility genes. The power of this strategy has recently been demonstrated with other complex diseases, such as inflammatory bowel disease and asthma. We assessed the largely unknown genetic background of CHD by investigating the most common dyslipidemia predisposing to CHD, familial combined hyperlipidemia (FCHL), affecting 1%-2% of Western populations and 10%-20% of families with premature CHD. To be able to perform a combined data analysis, we unified the diagnostic criteria for FCHL and its component traits and combined the data from two genomewide scans performed in two populations, the Finns and the Dutch. As a result of our pooled data analysis, we identified three chromosomal regions, on chromosomes 2p25.1, 9p23, and 16q24.1, exceeding the statistical significance level of a LOD score >2.0. The 2p25.1 region was detected for the FCHL trait, and the 9p23 and 16q24.1 regions were detected for the low high-density lipoprotein cholesterol (HDL-C) trait. In addition, the previously recognized 1q21 region also obtained additional support in the other study sample, when the triglyceride trait was used. Analysis of the 16q24.1 region resulted in a statistically significant LOD score of 3.6 when the data from Finnish families with low HDL-C were included in the analysis. To search for the underlying gene in the 16q24.1 region, we investigated a novel functional and positional candidate gene, helix/forkhead transcription factor (FOXC2), by sequencing and by genotyping of two single-nucleotide polymorphisms in the families

The pathogenetic mechanisms behind familial combined hyperlipidemia (FCHL) are unknown. However, exaggerated postprandial lipemia and excessive serum free fatty acid (FFA) concentrations have drawn attention to altered lipid storage and lipolysis in peripheral adipose tissue. Hormone-sensitive lipase (HSL) is the enzyme responsible for intracellular lipolysis in adipocytes and a decrease of adipocyte HSL activity has been demonstrated in Swedish FCHL subjects. The aim of the study was to investigate if adipose tissue HSL activity had any effect on lipid phenotype and if low HSL activity and FCHL were linked in Finnish FCHL families. A total of 48 family members from 13 well-characterized Finnish FCHL families and 12 unrelated spouses participated in the study. FCHL patients with different lipid phenotypes (IIA, IIB, IV) did not differ in adipose tissue HSL activity from each other or from the 12 normolipidemic spouses (P = 0.752). In parametric linkage analysis using an affecteds-only strategy the low adipose tissue HSL activity was not significantly linked with FCHL phenotype. However, we found a significant sibling-sibling correlation for the HSL trait (0.51, P < 0.01). Thus, a modifying or interacting role of HSL in the pathogenesis of FCHL could not be excluded.

Background Elective cardioversion (ECV) of atrial fibrillation (AF) is a standard procedure to restore sinus rhythm. However, predictors for ineffective ECV (failure of ECV or recurrence of AF within 30 days) are unknown. Methods We investigated 1998 ECVs performed for AF lasting >48 h in 1,342 patients in a retrospective multi-center study. Follow-up data were collected from 30 days after ECV. Results Median number of cardioversions was one per patient with a range of 1–10. Altogether 303/1998 (15.2%) ECVs failed. Long (>5 years) AF history and over 30 days duration of the index AF episode were independent predictors for ECV failure and low (60/min) ventricular rate, renal failure and antiarrhythmic agents at discharge were the independent predictors for recurrence. In total ECV was ineffective in 852 (42.6%) cases. Female gender (OR 1.44, CI95% 1.15–1.80, p 60/min (OR 1.92, CI95% 1.08–3.41, p = 0.03), antiarrhythmic medication at discharge (OR 1.48, CI95% 1.14–1.93, p, published version, peerReviewed