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Background Women with atrial fibrillation (AF) may be treated less actively with oral anticoagulation (OAC) than men. Patients and methods We assessed sex differences in the implementation of stroke risk stratification with CHADS2 and CHA2DS2-VASc scores and reasons not to use OAC in 1747 AF patients suffering their first cerebrovascular event after the AF diagnosis. Results Women were older and had more often a high stroke risk (CHADS2/CHA2DS2-VASc ≥2) than men (p

Aims Rhythm control using electrical cardioversion (CV) is a common treatment strategy for patients with symptomatic atrial fibrillation (AF). To guide clinical decision making, we sought to assess if electrocardiographic interatrial blocks could predict CV failure or AF recurrence as the phenomenon is strongly associated with atrial arrhythmias. Methods This study included 715 patients who underwent a CV for persistent AF lasting >48 h. P-wave duration and morphology were analyzed in post-procedure or the most recent sinus rhythm electrocardiograms and compared with rates of CV failure and AF recurrence within 30 days after CV as well as their combination (ineffective CV). Results CV was unsuccessful in 63 out of 715 patients (8.8%) and AF recurred in 209 out of 652 (29.2%) patients within 30 days after CV. Overall, 272 (38.0%) CVs turned out ineffective. Advanced interatrial block (AIAB) defined as P-wave duration ≥120 ms and biphasic morphology in inferior leads (II, III and aVF) was diagnosed in 72 (10.1%) cases. AIAB was an independent predictor for CV failure (OR 4.51, 95%CI 1.76–11.56, p = .002), AF recurrence (OR 2.93, 95%CI 1.43–5.99, p = .003) and ineffective CV (OR 3.87, 95%CI 2.04–7.36, p

BACKGROUND There are limited data on the association of minor troponin elevation in unselected patients with atrial fibrillation (AF) presenting to the emergency department (ED) with adverse events. In this study, we sought to assess the early and mid-term mortality of these patients. METHODS In this observational study, 2911 patients with AF were admitted to the ED. They were divided into 3 groups based on peak high-sensitivity troponin (TnT) levels: normal (

Introduction Patients with atrial fibrillation (AF) are selected for oral anticoagulation (OAC) therapy based on individual clinical characteristics collected in CHA2DS2-VASc -score. The characteristics of AF itself, however, are currently not included in stroke risk stratification schemes. Accumulating scientific evidence suggest that AF burden can be considered as an independent risk factor for cardiogenic stroke. So far, there are no studies evaluating the influence of AF burden measured by the frequency of symptomatic AF episodes on ischemic stroke risk. Purpose We sought to explore influence of symptomatic AF burden as determined by the frequency of acute cardioversions (CV) to the long-term ischemic stroke rate in AF patients. Methods This interim analysis of the multicenter, observational FinCV 4-study included 3867 CVs in 1521 non-anticoagulated patients. Clinical and laboratory data were collected manually through electronic patient records. Study follow-up started from the 1st CV of each patient and continued until one of the following events occurred: initiation of permanent OAC, non-CV related ischemic stroke, or death. Patients were divided in to three groups according to the individual frequency of CVs: high frequency (mean interval between CVs 18 months). Results A total of 113 (7.43% of patients) non-CV related (>30 days after CV) ischemic strokes occurred during the follow-up period (median 3.7 years [interquartile range 9.1 years]). The ischemic stroke rate per 100 patient-years was 7.5 in the high CV frequency group, 1.9 in the medium frequency group and 0.6 in the low frequency group. The mean CHA2DS2-VASc scores were 2.63±1.64, 2.46±1.63 and 2.20±1.68 in the three groups respectively. After adjusting for the CHA2DS2-VASc score, Cox regression analysis revealed CV frequency as an independent predictor for ischemic stroke (p Conclusions Determining the burden of AF based solely on the frequency of acute CVs seems to stratify the risk of ischemic stroke beyond CHA2DS2-VASc score. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): State clinical research fund (EVO) of Turku University Hospital

Background Rhythm control using electrical cardioversion (CV) is a common treatment strategy for patients with symptomatic atrial fibrillation (AF). However, little is known about electrocardiographic (ECG) markers predicting CV failure and AF recurrence. Methods This study included 726 patients who underwent a CV for AF lasting >48h in a referral hospital. We analysed markers of atrial cardiomyopathy in post-CV sinus rhythm ECGs and compared them with CV failure and AF recurrence rates within 30 days after CV as well as their combination (ineffective CV). Of those with failed CV the most recent sinus rhythm ECG was used. Results CV was unsuccessful in 66 out of 726 patients (9.09%). Advanced interatrial block (IAB) defined as P-wave duration ≥120ms and biphasic morphology in inferior (II, III and aVF) leads (OR 3.96, 95%-CI 2.09–7.52, p Conclusions Advanced IAB predicts CV inefficacy. This study identified ECG markers of atrial cardiomyopathy for clinical use in CV patient selection. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): This study research was funded by grants from the Finnish Medical Foundation, the Finnish Foundation for Cardiovascular Research, State Clinical Research Fund of Turku University Hospital, Turku, Finland, Finnish Cardiac Society, the Emil Aaltonen Foundation, and the Maud Kuistila Foundation.

Cardioversion (CV) for acute (

CHA2DS2-VASc and HAS-BLED scores stratify the risk of thromboembolic and bleeding events respectively in patients with atrial fibrillation. There is only little information on how they differentiate which of the 2 clinically most important complications (ischemic stroke [IS] or an intracranial bleeding [IB]) the patient is more prone to suffer. We evaluated both scores in patients with either of these major complications. The FibStroke Study collected data on all patients with atrial fibrillation with either an IS or an IB event between 2003 and 2012 in 4 Finnish hospital districts. Individual electronic patient records were manually reviewed to collect the study data. To assess the relative risk of IS and IB, an IS/IB-ratio was calculated by dividing the absolute number of ISs with the absolute number of IBs within each score category. A total of 3,816 (82.7%) ISs and 798 (17.3%) IBs were detected in 3,909 patients. In general, ISs occurred more often than IBs in patients on oral anticoagulation in each score category (ratio 1.6 to 5.1). The ratio decreased below 1, however, only with very high HAS-BLED scores (>4). Moreover, 221 ISs and 53 IBs occurred in patients with HAS-BLED > CHA2DS2-VASc, of whom only 19.7% were on anticoagulation. In conclusion, IS was the predominant intracranial event irrespective of CHA2DS2-VASc score, HAS-BLED score ≤4, or use of oral anticoagulation, also in patients with low estimated thromboembolic risk (CHA2DS2-VASc 0 to 1). Furthermore, the HAS-BLED score predicted the excess of IBs over ISs only at very high-risk levels.

Background and purpose Atrial fibrillation (AF) and significant carotid artery stenosis (CAS) often coexist in patients with acute stroke but whether CAS affects the stroke recurrence rate in anticoagulated AF patients is largely unknown. The effect of concomitant CAS on both short- and long-term prognosis after stroke in patients with AF was evaluated. Methods The multicentre, retrospective FibStroke registry included AF patients with an ischaemic stroke or transient ischaemic attack (TIA) during 2003–2012. In this sub-study, 165 AF patients with ischaemic stroke or TIA with significant (>50%) CAS (CAS group) and 734 AF patients without CAS (non-CAS group) were identified. The median follow-up time after an index event was 3.5 (interquartile range 3.9) years. Long-term stroke recurrence rate, 30-day mortality, CHA2DS2-VASc score, other risk factors and the use and intensity of anticoagulation were assessed. Results The recurrence rate of ischaemic stroke (21.2% vs. 12.7%, P = 0.005, 8.1 vs. 3.6 events per100 follow-up years) was significantly higher in CAS patients compared to the non-CAS group despite similar anticoagulation/antithrombotic therapy. CAS patients had higher mean CHA2DS2-VASc scores than non-CAS patients (4.3 vs. 3.3, P < 0.001). However, in a multivariate analysis CAS was shown to be an independent risk factor for stroke recurrence (hazard ratio 2.02, 95% confidence interval 1.37–3.01, P = 0.001). The 30-day all-cause mortality was significantly higher in CAS patients (7.9% vs. 1.9%, P < 0.001) and CAS was an independent risk factor also for 30-day mortality (odds ratio 3.34, 95% confidence interval 1.51–7.38, P = 0.003). Conclusions In patients with AF, concomitant CAS was an independent risk factor for both long-term stroke recurrence and 30-day mortality.

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 Patients with atrial fibrillation (AF) frequently undergo invasive procedures. Optimal perioperative use of oral anticoagulation (OAC) and heparin bridging is not well defined. Hypothesis Discontinuation of OAC for minor procedures/operations places AF patients at risk for thromboembolism. Methods In this study, we assessed perioperative antithrombotic treatment in patients with AF who suffered a postoperative stroke or intracranial bleeding. The FibStroke Study includes AF patients with an ischemic stroke or intracranial bleed identified from the discharge registries of 4 Finnish hospitals. In total, 3632 consecutive patients developed 3252 ischemic strokes and 794 intracranial bleeds. All invasive procedures during the 30 days preceding the stroke or intracranial bleed were identified. Results A total of 194/3252 (6.0%) ischemic strokes and 23/794 (2.9%) intracranial bleeds were preceded by a procedure. Altogether, 69% of the patients were on OAC prior to index procedure, OAC was interrupted in 81.2% of the procedures preceding a stroke, and heparin bridging was used in 27.8% of interruptions. Of the procedures leading to stroke, 42.3% were low-bleeding-risk procedures, and OAC was interrupted in 84.7% of these procedures. The median time from procedure to stroke was 4 days. Heparin bridging was used in 54.5% of OAC interruptions preceding intracranial bleeding and combination of anticoagulation with antiplatelet therapy by 43.5% of patients with postoperative intracranial bleeding. Conclusions Perioperative interruption of OAC is common in patients who suffer a postoperative stroke, even in patients with low-bleeding-risk procedures. Postoperative intracranial bleeding is frequently preceded by perioperative heparin bridging.

This cohort study investigates heart rate and cardiac troponin levels in patients admitted to the emergency department with symptomatic atrial fibrillation.

BACKGROUND: Electrical cardioversion (CV) is essential in rhythm management of atrial fibrillation (AF). However, optimal timing of CV remains unknown. HYPOTHESIS: Timing of CV in AF is associated with risk of adverse events. METHODS: We analyzed the effect of AF episode duration on safety and efficacy of electrical CV in a multicenter, multicohort study exploring 4356 CVs in 2530 patients on oral anticoagulation. The composite adverse outcome included unsuccessful CV, acute arrhythmic complications, thromboembolic events, mortality, and AF recurrence within 30‐day follow‐up. RESULTS: Study groups were stratified according to duration of index AF episode ( 30d), consisting of 1767, 516, 632, and 1441 CVs, respectively. CVs were unsuccessful in 8.5% (30d), respectively (P 5 seconds (0.7%) within 30‐day follow‐up was infrequent and comparable in the study groups. AF recurrence within 30 days after initially successful CVs was 29.8% (30d), respectively (P 48 hours was an independent predictor for the composite endpoint (OR: 1.49, 95% CI: 1.28–1.74, P < 0.01) in multivariate analysis. CONCLUSIONS: Optimal timing of CV for AF showed a J‐shaped curve, with fewest adverse outcomes in patients with CV performed 24 to 48 hours after onset of AF. In patients with rhythm‐control strategy, delaying CV >48 hours is associated with increased risk for adverse outcomes.

BackgroundIntracranial hemorrhage is the most devastating complication in patients with atrial fibrillation (AF) receiving oral anticoagulation (OAC). It can be either spontaneous or caused by head trauma. We sought to address the prevalence, clinical characteristics, and prognosis of traumatic and spontaneous intracranial hemorrhages in AF patients on OAC.MethodsMulticenter FibStroke registry of 5,629 patients identified 592 intracranial hemorrhages during warfarin treatment between 2003 and 2012.ResultsA large proportion (40%) of intracranial hemorrhages were traumatic. Of these, 64% were subdural hemorrhages (SDHs) and 20% intracerebral hemorrhages (ICHs). With respect to the spontaneous hemorrhages, 25% were SDHs and 67% ICHs. Patients with traumatic hemorrhage were older (81 vs 78 years, p = 0.01) and more often had congestive heart failure (30% vs 16%, p < 0.01) and anemia (7% vs 3%, p = 0.03) compared to patients with spontaneous hemorrhage. Admission international normalized ratio (INR) values (2.7 vs 2.7, p = 0.79), as well as CHA2DS2-VASc (median 4 vs 4, p = 0.08) and HAS-BLED (median 2 vs 2, p = 0.05) scores, were similar between the groups. The 30-day mortality after traumatic hemorrhage was significantly lower than after spontaneous hemorrhage (25% vs 36%, p < 0.01).ConclusionsA significant proportion of intracranial hemorrhages in anticoagulated AF patients were traumatic. Traumatic hemorrhages were predominantly SDHs and less often fatal when compared to spontaneous hemorrhages, which were mainly ICHs. Admission INR values as well as CHA2DS2-VASc and HAS-BLED scores were similar in patients with spontaneous and traumatic intracranial hemorrhage.Clinicaltrials.gov identifierNCT02146040.

The impact of ventricular rate (VR) on the outcome of electrical cardioversion (ECV) of acute atrial fibrillation (AF) is currently unknown. We aimed to determine the effect of VR during acute AF on the success of ECV, recurrence of AF, and occurrence of post-cardioversion complications in 30 days of follow-up.A total of 6,624 ECVs were performed in 2,821 consecutive patients with AF lasting48 hours. VR ≤ 60 bpm was defined low, and VR ≥ 160 bpm high.The median VR before ECV was 109 bpm. The success rate of ECV was 94.2%. Bradycardia occurred in 62 (0.9%) and thromboembolic complications in 39 (0.6%) ECVs. Low VR was observed before 75 (1.1%) ECVs, and male sex was its only independent predictor. High VR was observed in 165 (2.5%) ECVs. The independent predictors of high VR were younger age,12 h episode duration, no previous history of AF, and alcohol abuse. Low or high VR were not related to the success of ECV, incidence of thromboembolic or bradycardic complications, or recurrence of AF, although VR was significantly (P0.001) lower in the patients in whom AF recurred.VR during acute AF does not affect the efficacy or safety of ECV.

Background Atrial fibrillation (AF) increases risk of ischemic stroke, and oral anticoagulation (OAC) increases risk of intracerebral hemorrhage (ICH). This study aimed to compare OAC-treated AF patients with an ischemic stroke/transient ischemic attack (TIA) or spontaneous ICH as their first lifetime cerebrovascular event, especially focusing on patients with therapeutic international normalized ratio (INR). Hypothesis We assumed that in AF patients suffering ischemic stroke/TIA or ICH, patient characteristics could be different in patients with therapeutic INR than in patients with warfarin. Methods FibStroke is a multicenter, retrospective registry collating details of AF patients with ischemic stroke/TIA or intracranial hemorrhage in 2003-2012. This substudy included AF patients on OAC with first lifetime ischemic stroke/TIA or spontaneous ICH. Results A total of 1457 patients with 1290 ischemic strokes/TIAs and 167 ICHs were identified. Of these, 553 (42.9%) strokes/TIAs and 96 (57.5%) ICHs occurred in patients with INR within therapeutic range. During OAC with therapeutic INR, congestive heart failure (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.18-4.58) and hypercholesterolemia (OR: 2.52, 95% CI: 1.51-4.19) were more common in patients with ischemic stroke/TIA, whereas a history of bleeding (OR: 0.30, 95% CI: 0.11-0.82) was less common when compared with patients with ICH. In the whole cohort, renal impairment (OR: 1.86, 95% CI: 1.23-2.80) and mechanical valve prosthesis (OR: 4.41, 95% CI: 1.32-14.7) were overrepresented in patients with stroke/TIA, whereas aspirin use (OR: 0.52, 95% CI: 0.30-0.91) and high INR (OR: 0.40, 95% CI: 0.33-0.48) were overrepresented in patients with ICH. Conclusions In anticoagulated AF patients with therapeutic INR and first lifetime cerebrovascular event, congestive heart failure and hypercholesterolemia were associated with ischemic stroke/TIA and history of bleeding with ICH.

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Female sex, old age, and time to cardioversion increase the risk of thromboembolic complications (TEC) after cardioversion of atrial fibrillation (AF) 48 h. The interaction of these variables is not known. We investigated the interaction of sex, age, and time to electrical cardioversion (ECV) on TEC in anticoagulant-naive patients with acute AF.The primary outcome was a TEC within 30 days following ECV. Patients were divided into three age groups and time to cardioversion into12 h and ≥12 h in 4715 ECVs. TEC occurred in 40 (0.8%) patients. In multivariate analysis, female sex, time to ECV, and vascular disease were independent predictors of TEC. For patients ≤75 cardioverted within 12 h, the incidence of TEC was low. In patients75 TEC increased in both sexes and particularly in women (1.4% vs. 0.9%, p = 0.03). When ECVs exceeded 12 h, the risk of TEC was two- to four-fold higher in women in all age groups.The risk of TEC increases substantially in patients75 and ECVs ≥12 h, particularly in women. Time to cardioversion should be added to risk-stratification of ECVs of acute AF. Key messages The ideal timing of cardioversion is still unknown and not based on solid evidence. Delay to cardioversion ≥12 h should be added to the risk stratification of atrial fibrillation cardioversion. Female sex increases the risk of complications and failure of cardioversion after electrical cardioversion of atrial fibrillation 48 h, especially with age 75 years and time to cardioversion exceeding 12 h.

Introduction: Severe warfarin overanticoagulation is a risk factor for bleeding, but there is little information on its manifestations, prognosis and factors affecting the outcome. We describe the manifestations and clinical outcomes of severe warfarin overanticoagulation in a large group of patients with atrial fibrillation (AF). Material and methods: All international normalized ratio (INR) samples (n = 961,431) in the Turku University Hospital region between 2003 and 2015 were screened. A total of 412 AF patients with INR ≥9 were compared to 405 patients with stable warfarin anticoagulation for AF. Electronic patient records were manually reviewed to collect comprehensive data. Results: Of the 412 patients with INR ≥9, bleeding was the primary manifestation in 105 (25.5%). Non-bleeding symptoms were recorded in 165 (40.0%) patients and 142 (34.5%) had no symptoms. A total of 17 (16.2%) patients with a bleed and 67 (21.8%) without bleeding died within 30 days after the event. Intracranial haemorrhage strongly predicted death within 30 days. Other significant predictors were non-bleeding symptoms, active malignancies, recent bleed, history of myocardial infarction, older age, renal dysfunction and a recent treatment episode. Conclusions: Bleeds are not the major determinant of the poor prognosis in severe overanticoagulation, as coincidental INR ≥9 findings also associate with high mortality.KEY MESSAGESOnly a quarter of AF patients with INR ≥9 suffered a bleeding event and the clinical manifestation of INR ≥9 had a significant impact on patient outcome.The 30-day mortality rate in patients with INR ≥9 was high ranging from 9.2 to 32.7%.Several significant predictors of 30-day mortality after INR ≥9 were identified. Only a quarter of AF patients with INR ≥9 suffered a bleeding event and the clinical manifestation of INR ≥9 had a significant impact on patient outcome. The 30-day mortality rate in patients with INR ≥9 was high ranging from 9.2 to 32.7%. Several significant predictors of 30-day mortality after INR ≥9 were identified.

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

Background Data on predictors of failure of electrical cardioversion of acute atrial fibrillation are scarce. Methods We explored 6,906 electrical cardioversions of acute (

Patients with atrial fibrillation (AF) presenting to the emergency department (ED) often have elevated cardiac troponin T (TnT) levels without evidence of type 1 myocardial infarction. We sought to explore the causes and significance of minor TnT elevations in patients with AF at the ED. All patients with AF admitted to the ED of Turku University Hospital between 1 March, 2013 and 11 April, 2016, and at least two TnT measurements, were screened. Overall, 2911 patients with a maximum TnT of 100 ng/L during hospitalization were analyzed. TnT was between 15 and 100 ng/L in 2116 patients. The most common primary discharge diagnoses in this group were AF (18.1%), infection (18.3%), ischemic stroke/transient ischemic attack (10.7%), and heart failure (5.0%). Acute coronary syndrome (ACS) was equally uncommon both in patients with normal TnT and elevated TnT (4.4% vs. 4.5%). Age &ge, 75 years, low estimated glomerular filtration rate (eGFR), high C-reactive protein (CRP), and hemoglobin &lt, 10.0 g/dL, were the most important predictors of elevated TnT. Importantly, TnT elevation was a very frequent (&gt, 93%) finding in elderly (&ge, 75 years) AF patients with either low eGFR or high CRP. In conclusion, minor TnT elevations carry limited diagnostic value in elderly AF patients with comorbidities.

Objectives This study sought to explore the incidence and risk factors of thromboembolic complications after cardioversion of acute atrial fibrillation. Background Anticoagulation therapy is currently recommended after cardioversion of acute atrial fibrillation in patients with risk factors for stroke, but the implementation of these new consensus-based guidelines has been slow. Methods A total of 7,660 cardioversions were performed in 3,143 consecutive patients with atrial fibrillation lasting Results There were 38 (0.7%; 95% confidence interval [CI]: 0.5% to 1.0%) definite thromboembolic events (31 strokes) within 30 days (median 2 days, mean 4.6 days) after cardioversion. In addition, 4 patients suffered transient ischemic attack after cardioversion. Age (odds ratio [OR]: 1.05; 95% CI: 1.02 to 1.08), female sex (OR: 2.1; 95% CI: 1.1 to 4.0), heart failure (OR: 2.9; 95% CI: 1.1 to 7.2), and diabetes (OR: 2.3; 95% CI: 1.1 to 4.9) were the independent predictors of definite embolic events. Classification tree analysis showed that the highest risk of thromboembolism (9.8%) was observed among patients with heart failure and diabetes, whereas patients with no heart failure and age Conclusions The incidence of post-cardioversion thromboembolic complications is high in certain subgroups of patients when no anticoagulation is used after cardioversion of acute atrial fibrillation. (Safety of Cardioversion of Acute Atrial Fibrillation [FinCV]; NCT01380574 )

To determine the incidence and risk factors of arrhythmic complications after electrical cardioversion of acute atrial fibrillation (AF).Our retrospective multicentre study collected data from 7660 cardioversions of acute (48 h) AF in 3143 consecutive patients. Immediate arrhythmic complications were evaluated after 6906 (90.2%) electrical cardioversions performed in 2868 patients. We also assessed the predictors of arrhythmic complications and whether post-cardioversion bradycardia or asystole led to later a permanent pacemaker implantation. Altogether, 63 (0.9%) electrical cardioversions resulted in bradyarrhythmia in 54 patients. Asystole (5 s) occurred immediately after 51 cardioversions leading to a short resuscitation in seven cases and two patients needed extrinsic pacing after the cardioversion. In nine cases, asystole was followed by bradycardia. Bradycardic ventricular rate (40 b.p.m.) alone was seen after 12 procedures. No ventricular arrhythmias needing intervention were detected. Old age [odds ratio (OR) 1.1; 95% confidence interval (CI) 1.05-1.10, P0.0001], female sex (OR 2.5; 95% CI 1.4-4.8, P = 0.004), and unsuccessful cardioversion (OR 2.2; 95% CI 1.1-4.6, P = 0.03) were the independent predictors of bradycardic complications. Slow ventricular rate, use of digoxin, beta blocker, or antiarrhythmic medication did not increase the risk of bradycardic complications. Pacemaker was implanted in 24 (44.4%) patients after a median delay of 66 days.Bradycardic complications are rare and usually benign after cardioversion of acute AF. They seem to reflect sinus node dysfunction and often result in later implantation of a permanent pacemaker.

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.

Recent studies have reported that patients with paroxysmal atrial fibrillation (AF) have lower risk of thromboembolism and better prognosis than patients with chronic AF. We sought to address the differences in ischaemic events in patients with paroxysmal AF and chronic AF.The FibStroke study is a cross-sectional observational multicenter registry that included AF patients with an ischaemic stroke, TIA (transient ischaemic attack) or intracranial bleed during 2003-2012 identified from discharge registries of four Finnish hospitals. Altogether 1448 patients with paroxysmal and 1808 patients with chronic atrial fibrillation suffered a total of 707 TIA-episodes and 2549 ischaemic strokes.Mortality within 30days after the index event was significantly lower in patients with paroxysmal AF than with chronic AF (7.6% vs 16.9%, p0.01). At the onset of event, 62.8% of the patients with paroxysmal AF were in sinus rhythm, and these patients had better prognosis after the event compared to patients with other rhythm than sinus rhythm (mortality 5.2% vs 15.7%, p0.01). In the propensity score matched analysis mortality after stroke was significantly lower in patients with paroxysmal AF than in patients with chronic AF (11.6% vs 17.8%, p0.01), while mortality after TIA was also lower, but did not reach statistical significance (0.4% vs 1.7%, p=0.31).A significant proportion of strokes in AF patients occur in patients with paroxysmal AF, but they have better prognosis than patients with chronic AF. The prognosis is also significantly better in patients who are in sinus rhythm at the onset of event.

BACKGROUND: Patients with atrial fibrillation (AF) frequently undergo invasive procedures. Optimal perioperative use of oral anticoagulation (OAC) and heparin bridging is not well defined. HYPOTHESIS: Discontinuation of OAC for minor procedures/operations places AF patients at risk for thromboembolism. METHODS: In this study, we assessed perioperative antithrombotic treatment in patients with AF who suffered a postoperative stroke or intracranial bleeding. The FibStroke Study includes AF patients with an ischemic stroke or intracranial bleed identified from the discharge registries of 4 Finnish hospitals. In total, 3632 consecutive patients developed 3252 ischemic strokes and 794 intracranial bleeds. All invasive procedures during the 30 days preceding the stroke or intracranial bleed were identified. RESULTS: A total of 194/3252 (6.0%) ischemic strokes and 23/794 (2.9%) intracranial bleeds were preceded by a procedure. Altogether, 69% of the patients were on OAC prior to index procedure, OAC was interrupted in 81.2% of the procedures preceding a stroke, and heparin bridging was used in 27.8% of interruptions. Of the procedures leading to stroke, 42.3% were low‐bleeding‐risk procedures, and OAC was interrupted in 84.7% of these procedures. The median time from procedure to stroke was 4 days. Heparin bridging was used in 54.5% of OAC interruptions preceding intracranial bleeding and combination of anticoagulation with antiplatelet therapy by 43.5% of patients with postoperative intracranial bleeding. CONCLUSIONS: Perioperative interruption of OAC is common in patients who suffer a postoperative stroke, even in patients with low‐bleeding‐risk procedures. Postoperative intracranial bleeding is frequently preceded by perioperative heparin bridging.

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 (

CHA2DS2-VASc and HAS-BLED scores stratify the risk of thromboembolic- and bleeding events respectively in patients with atrial fibrillation (AF). There is only little information on how the risk scores differentiate which of the two clinically most important complications (an ischemic stroke or an

The efficacy of the anticoagulation in preventing thromboembolic complications (TEC) and the usefulness of the CHA2DS2VASc score for assessing stroke risk during cardioversion of acute atrial fibrillation (AF) are unclear. Thus, our objectives were to assess the ability of the CHA2DS2VASc score to predict TEC and to evaluate the efficacy of anticoagulation in the prevention of TEC in Finnish CardioVersion (FinCV) study. The FinCV is a retrospective, multicenter study of 3,143 patients, who underwent 7,660 cardioversions for acute AF. The value of the CHA2DS2VASc score in predicting TEC was analyzed separately in cardioversions performed without and with anticoagulation. A total of 40 definite TEC (0.6%) occurred after 7,237 successful cardioversions and 1 stroke (0.2%) after 423 unsuccessful procedures. In 5,362 cardioversions performed without anticoagulation, the risk of definite TEC increased significantly from 0.4% in patients with a CHA2DS2VASc score of 0 to 1 to 2.3% in those with score of ≥5 (p0.001 for trend). The C-statistic of the CHA2DS2VASc score was 0.72 (0.61 to 0.83) in predicting definite TEC in non-anticoagulated patients with first cardioversion. The incidence of definite TEC was significantly lower in 2,298 cardioversions performed during anticoagulation (0.1% vs 0.7%, p = 0.001), and the preventive effect of anticoagulation was significant in patients with a score of ≥2 (0.2% vs 1.1%, p = 0.001). In conclusion, CHA2DS2VASc score is a strong predictor of TEC in cardioversion of acute AF performed without anticoagulation. Importantly, periprocedural anticoagulation reduced the risk of TEC by 82%. The overall risk of these complications was low after failed cardioversion.

Cardioversion of atrial fibrillation (AF) is associated with an increased risk for stroke. We identified all cardioversions during the 30 days preceding stroke or transient ischemic attack (TIA) in patients with a previously diagnosed AF, and sought to assess the characteristics of cardioversions leading to stroke or TIA.FibStroke is a cross-sectional observational multicenter registry that included AF patients with an ischemic stroke or intracranial bleed identified from a discharge registry of four Finnish hospitals. In total 3677 consecutive AF patients suffered 3252 strokes and 956 TIA episodes during 2003–2012. This pre-specified analysis focused on the 1644 events that occurred to patients with paroxysmal or persistent AF at the time of stroke/TIA.A total of 78 strokes and 22 TIA episodes were preceded by a cardioversion. Post-cardioversion strokes accounted for 6.4% of strokes in patients with paroxysmal/persistent AF. Of the 100 cardioversions leading to an ischemic event, 77 were acute and 23 were elective, 63 events occurred in patients not using anticoagulation, and 5 patients had periprocedural INR2. Importantly, 21 patients were in low risk of stroke, i.e. CHA2DS2-VASc score2. The median delay from cardioversion to event was 2 days. All nine patients who after an unsuccessful cardioversion developed a stroke had a spontaneous cardioversion prior to stroke.Every sixteenth stroke of patients with paroxysmal/persistent AF is preceded by a cardioversion. Most post-cardioversion strokes occur in patients not using oral anticoagulation before cardioversion of acute AF.

Background and purpose Current guidelines recommend oral anticoagulation (OAC) for patients with atrial fibrillation (AF) and increased risk of thromboembolic events. The reasons for not using OAC in AF patients suffering stroke or transient ischaemic attack (TIA) were assessed. Methods This retrospective registry included 3404 patients with previously diagnosed AF who suffered a total of 2955 ischaemic strokes and 895 TIAs during 2003–2012. Results A CHA2DS2-VASc score ≥2 and a CHADS2 score ≥2 was observed in 3590 (93.2%) and in 2784 (72.3%) of the events, respectively. Of the high-risk patients (CHADS2 ≥2) only 55.1% were on OAC before the onset of stroke or TIA. The most frequently documented reasons for withholding OAC were infrequent paroxysms of AF (14%), previous bleeding episodes (13%) and the patient's decline/independent discontinuation of treatment (9%). Moreover, patients with paroxysmal AF (40% using OAC), previous bleeding (26% using OAC) and alcohol abuse (30% using OAC) were using OAC significantly less often than patients without these characteristics. A significant increase in the proportion of high-risk patients using OAC from 49% in 2003 to 65% in 2012 was seen. Conclusions Underuse of anticoagulation is a common contributor to ischaemic strokes and TIA episodes in patients with AF. Infrequent AF episodes, previous bleeds, patient preference and alcohol abuse were the most common reasons for not using OAC.

Statins are known to cause short-term reduction in serum lipid-soluble antioxidant concentrations, but their long-term effects are not known.We randomised 104 subjects with CHD and hypercholesterolaemia to receive either atorvastatin or simvastatin treatment for 52 weeks and measured the antioxidant potential of LDL and serum antioxidant vitamin concentrations.Initial daily dose for both statins was 20 mg.LDL antioxidant capacity and serum alpha-tocopherol, gamma-tocopherol and beta-carotene concentrations decreased by 22%-35% with both statins during the first 12 weeks' therapy (P0.01 for all). After 52 weeks' therapy, the concentrations of serum gamma-tocopherol in the simvastatin group and serum beta-carotene in both treatment groups returned to baseline levels, while the concentrations of serum gamma-tocopherol in the atorvastatin group and LDL anti-oxidant capacity and serum alpha-tocopherol in both treatment groups remained reduced (P0.001 for all). The LDL antioxidant capacity:LDL-cholesterol and the serum alpha-tocopherol:LDL-cholesterol ratios were significantly elevated with both statins after 12 and 52 weeks (P0.001 for all). Statistically significant increases were also observed for corresponding ratios of the less abundant vitamins gamma-tocopherol and beta-carotene.Some of the decreases in serum lipid soluble antioxidant vitamins reported in short-term statin interventions may become attenuated when therapy continues longer. The relative antioxidant capacity of LDL particles increased during the 52-week treatment, suggesting that the oxidation resistance of LDL particles did not become impaired and that their atherogenicity did not increase.

Background: Little is known about the effect of vitamin D status on bone gain in adolescents. Objective: The objective was to examine whether vitamin D status is associated with accrual of bone mineral density (BMD) and bone mineral apparent density (BMAD). Design: This 3-y prospective study examined the association between changes in BMD or BMAD and serum 25-hydroxyvitamin D [25(OH)D] in 171 healthy Finnish girls aged 9-15 y. Lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry. Results: Baseline 25(OH)D correlated significantly with the unadjusted 3-y change in BMD at the lumbar spine (r = 0.35, P < 0.001) and femoral neck (r = 0.32, P < 0.001) in all participants. The difference from baseline in adjusted 3-y BMD accumulation between those with severe hypovitaminosis D [25(OH)D < 20 nmol/L] and those with a normal vitamin D status [25(OH)D ≥ 37.5 nmol/L] was 4% (12.7%, 13.1%, and 16.7% for the lowest, middle, and highest tertiles of 25(OH)D, respectively; P for trend = 0.01) at the lumbar spine in the girls with advanced sexual maturation at baseline (n = 129). Moreover, the adjusted change in lumbar spine BMD was 27% greater in the highest vitamin D intake tertile than in the lowest tertile in the same girls (P for trend = 0.016). Conclusions: Pubertal girls with hypovitaminosis D seem to be at risk of not reaching maximum peak bone mass, particularly at the lumbar spine. Dietary enrichment or supplementation with vitamin D should be considered to ensure an adequate vitamin D status.

The nature of the genetic and environmental factors influencing low density lipoprotein (LDL) particle size in patients with familial combined hyperlipidaemia (FCHL) is under debate. We measured LDL peak particle size in 553 subjects belonging to 48 Finnish FCHL families. Individuals with high triglyceride (TG) concentrations (phenotype IV) or combined hyperlipidaemia (phenotype IIB) had significantly smaller LDL particles than those with hypercholesterolaemia (phenotype IIA) or unaffected subjects (P0.001). In stepwise regression analyses, serum TGs (r(2)=43%, P0.001) and high density lipoprotein cholesterol (HDL-C) (r(2)=4.5%, P0.001) were the only significant predictors of LDL peak particle size. Familial correlations support the conclusion that LDL peak particle size is familial, and most probably influenced by genes in these families. Segregation analysis of LDL peak particle size, a quantitative trait, was performed to model this genetic influence. Our results suggest a polygenic background for LDL size with a recessive major gene that may contribute to large LDL peak particle size in women. Serum TG and HDL-C concentrations predict the majority of variations in LDL particle size.

This study aimed to assess the role of complement C3, hormone-sensitive lipase (HSL), and peroxisome proliferator-activated receptor gamma (PPARgamma) gene expression in familial combined hyperlipidemia (FCHL). mRNA expression of these 3 determinants of adipose tissue fatty acid (FA) metabolism was quantified in subcutaneous adipose tissue of 41 Finnish FCHL patients and 14 normolipidemic control subjects. No difference in steady-state mRNA expression level of C3, HSL, or PPARgamma mRNA was detected between the FCHL patients and the control subjects. Adipose tissue C3 mRNA expression level correlated with the area under the curve (AUC) for glucose and for insulin in FCHL patients and control subjects. HSL mRNA level was positively correlated with waist-to-hip ratio in patients, whereas the correlation was negative in control subjects. A significant correlation was observed for PPARgamma with free FA (FFA)-AUC in the FCHL group, and an inverse correlation with serum triglycerides (TG) in the control subjects. Although no difference in adipose tissue gene expression of C3, HSL, or PPARgamma was observed between the FCHL patients and the control subjects, several significant correlations were observed between the mRNA levels and FCHL-related metabolic parameters. Thus, the genes of C3, HSL, and PPARgamma may exert a modifying effect on lipid and glucose metabolism in FCHL. However, defects in adipose tissue expression of these genes are not likely to play a primarily role in the pathogenesis of FCHL in Finnish FCHL families.

Small, dense LDL particles are typical for FCHL. Intravascular lipid exchange and net transfer among HDL, LDL, and triglyceride-rich lipoproteins as well as lipolysis in the VLDL-IDL-LDL cascade regulate properties of LDL. We investigated postheparin plasma activities of hepatic lipase (HL) and LPL, and plasma activities of CETP and phospho- lipid transfer protein (PLTP) in 191 individuals from 37 Finnish FCHL families. LDL peak particle diameter (LDL size) was measured with 2-10% gradient polyacrylamide gel electrophoresis. LDL size was significantly smaller in af- fected FCHL family members (n � 68) as compared with nonaffected FCHL family members (n � 78) or spouses (n � 45) (25.3 � 1.5 nm, 26.8 � 1.2 nm, and 26.6 � 1.2 nm, re- spectively, P � 0.001 for both). In affected FCHL family members, serum triglycerides were the strongest correlate for LDL size ( r � � 0.71, P � 0.001). In univariate correla- tion analysis LDL size was not associated with HL, LPL, CETP, and PLTP activities. In multivariate stepwise regres- sion analysis, however, serum triglycerides, CETP activity, HL activity, and HDL cholesterol were significant predictors of LDL size in affected FCHL subjects (adjusted r 2 � 0.642). We conclude that serum triglyceride concentra- tion is strongly correlated with LDL size in affected FCHL subjects. After adjustment for serum triglycerides, HL and CETP activities are associated with LDL size in FCHL. — Vakkilainen, J., M. Jauhiainen, K. Ylitalo, I. O. Nuotio, J. S. A. Viikari, C. Ehnholm, and M-R. Taskinen. LDL particle size in familial combined hyperlipidemia: effects of serum lipids, lipoprotein-modifying enzymes, and lipid transfer proteins. J. Lipid Res. 2002. 43: 598-603.

Adult dyslipidemias may reveal familial and, therefore, offspring dyslipidemias. We evaluated the prevalences of the adult-offspring dyslipidemias in 441 general population families composed of both parents and one 5-year-old child. Family members were classified using the 90th or 10th percentiles for hypercholesterolemia (IIA), hypertriglyceridemia (IV), combined hyperlipidemia (IIB), and low high density lipoprotein cholesterol concentration without hyperlipidemia (hypoHDL). In familial combined hyperlipidemia (FCHL), the IIB-phenotype was in one generation and one of the three hyperlipidemias in the other generation. Finally, the parental dyslipidemia phenotypes and elevated lipids (>80th percentile) that reveal offspring dyslipidemia were selected by stepwise logistic regression. Either the IIA-, IV- or hypoHDL phenotype was found in both generations in 2.8, 2.0 and 1.4% of the families, respectively. FCHL was seen in 1.8% of the families, which confirms the earlier views. The predictive values of the elevated parental cholesterol, type IV or hypoHDL parents to find type IIA, IV and hypoHDL children were low for systematic screening: 16, 13 and 15%, respectively. However, 44% of the children of IIB parents expressed hyperlipidemia (odds ratio 4.7, P=0.006). The IIB phenotype of the parent is a good predictor of the child's hyperlipidemia, and when encountered, it indicates that the lipids of the child should be studied. This would be as important as selective screening of familial hypercholesterolemia.