| 1. |
- Albers, GW, et al.
(author)
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Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation - A Randomized trial
- 2005
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In: JAMA: The Journal of the American Medical Association. - 1538-3598. ; 293:6, s. 690-698
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Journal article (peer-reviewed)abstract
- Context Inpatients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. Objective To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. Design, Setting, and Participants Double-blind, randomized, multicenter trial (20002001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors. Interventions Adjusted-dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. Main Outcome Measures The primary end point was all strokes (ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0% per year according to the intention-to-treat model. Results During 6405 patient-years (mean 20 months) of follow-up, 88 patients experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was within target during 68% of the treatment period. The primary event rate with ximelagatran was 1.6% per year and with warfarin was 1.2% per year (absolute difference, 0.45% per year; 95% confidence interval, -0.13% to 1.03% per year; P<.001 for the pre-defined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10% per year (95% confidence interval, -0.97% to 1.2% per year; P=.86). There was no difference between treatment groups in rates of major bleeding, but total bleeding (major and minor) was lower with ximelagatran (37% vs 47% per year; 95% confidence interval for the difference, -14% to -6.0% per year; P<.001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0% of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred. Conclusions The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.
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| 2. |
- Carlson, Jonas, et al.
(author)
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Can Orthogonal Lead Indicators of Propensity to Atrial Fibrillation be Accurately Assessed from the 12-Lead ECG?
- 2005
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In: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 7:Suppl 2, s. 39-48
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Journal article (peer-reviewed)abstract
- Aims: When analyzing P-wave morphology, the vectorcardiogram(VCG) has been shown useful to identify indicators of propensity to atrial fibrillation (AF). Since VCG is rarely used in the clinical routine, we wanted to investigate if these indicators could be accurately determined in VCG derived from standard 12-lead ECG (dVCG).Methods: ECG and VCG recordings from 21 healthy subjects and 20 patients with a history of AF were studied. dVCG was calculated from ECG using the inverse Dower transform. Following signal averaging of P-waves, comparisons were madebetween VCG and dVCG, where three parameters characterizing signal shape and 15 parameters describing the P-wave morphology were used to assess the compatibility of the two recording techniques. The latter parameters were alsoused to compare the healthy and the AF groups.Results: After transformation, P-wave shape was convincingly preserved. P-wave morphology parameters were consistent within the respective groups when comparing VCG and dVCG, with better preservation observed in the healthy group.Conclusion VCG derived from routine 12-lead ECG may be a useful alternate method for studying orthogonal P-wave morphology.
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| 3. |
- Husser, D, et al.
(author)
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Determinants and prognostic significance of immediate atrial fibrillation recurrence following cardioversion in patients undergoing pulmonary vein isolation
- 2005
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In: PACE. - : Wiley. - 1540-8159. ; 28:2, s. 119-125
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Journal article (peer-reviewed)abstract
- Background: Immediate recurrence of atrial fibrillation (IRAF) occurs frequently after electrical cardioversion, its electrophysiological determinants and prognostic significance hove, however, not been studied in detail. This Study aimed to explore (1) the association of IRAF with clinical characteristics, pulmonary vein (PV) arrhythmogenicity as well as atrial electrophysiologic properties and (2) the prognostic significance of IRAF for outcome of PV isolation for atrial fibrillation (AF). Methods and Results: The subjects of this study were 41 consecutive patients (30 males, 11 females) who underwent PV isolation for drug-refroctory AF. Following successful initial cordioversion, 19 patients (46%) had IRAF within 2 minutes. Coupling intervals of AF reinitiating beats arising from PVs were shorter (386 +/- 39 vs 490 +/- 136 ms, P=0.008) and prematurity indices (0.38 +/- 0.06 vs 0.51 +/- 0.12, P=0.01) smaller than those of premature beats not initiating AF Patients with IRAF had more frequently AF duration <1 month, a longer P-wave duration, and a longer mid coronary sinus AF cycle length. Multivariate regression analysis revealed coronary sinus AF cycle length ( beta = 0.186, P=0.049), which was closely correlated with conduction time along the coronary sinus (R = 0.716, P = 0.003) to be independently associated with IRAF While early AF recurrence rate (within the first 5 days) following the procedure was higher in the IRAF group (53 vs 18%, P = 0.02), outcome was not different between the two groups thereafter. Conclusions: (1) IRAF is common in patients undergoing PV isolotion for AF, (2) is initiated by premature atrial beats with short coupling intervals, and (3) seems to be associated with conduction disturbances along the coronary sinus. It reflects susceptibility of arrhythmia recurrence within the first 5 days after the procedure, but not thereafter.
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| 4. |
- Husser, D, et al.
(author)
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Pilot study: Noninvasive monitoring of oral flecainide's effects on atrial electrophysiology during persistent human atrial fibrillation using the surface electrocardiogram
- 2005
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In: Annals of Noninvasive Electrocardiology. - 1082-720X. ; 10:2, s. 206-210
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Journal article (peer-reviewed)abstract
- Background: The relation between flecainide's plasma level and its influence on human atrial electrophysiology during acute and maintenance therapy of atrial fibrillation (AF) is unknown. Therefore, this study determined flecainide plasma levels and atrial fibrillatory rate obtained from the surface ECG during initiation and early maintenance of oral flecainice in patients with persistent lone AF and assessed their relationship. Methods and Results: In 10 patients (5 males, mean age 63 14 years, left atrial diameter 46 +/- 3 mm) with persistent lone AF, flecainide was administered as a single oral bolus (day 1) followed by 200-400 mg/day (days 2-5). The initial 300 mg flecainide bolus resulted in therapeutic plasma levels in all patients (range 288-629 ng/ml) with no side effects. Flecainide plasma levels increased on day 3 and remained stable thereafter. Day 5 plasma levels were lower (508 +/- 135 vs 974 :E 276 ng/ml, P = 0.009) in patients with daily mean flecainide doses of 200 mg compared to patients with higher maintenance doses. Fibrillatory rate obtained from the surface electrocardiogram measuring 378 +/- 17 fpm at baseline was reduced to 270 +/- 18 fpm (P < 0.001) after the flecainice bolus but remained stable thereafter. Fibrillatory rate reduction was independent of flecainide plasma levels or clinical variables. Conclusion: A 300 mg oral flecainide bolus is associated with electrophysio logic effects that are not increased during early maintenance therapy in persistent human lone AF In contrast to drug plasma levels, serial analysis of fibrillatory rate allows monitoring of individual drug effects on atrial electrophysiology.
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| 5. |
- Husser, D, et al.
(author)
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Time-frequency analysis of the surface electrocardiogram for monitoring antiarrhythmic drug effects in atrial fibrillation
- 2005
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In: American Journal of Cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 95:4, s. 526-528
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Journal article (peer-reviewed)abstract
- This study explored time-frequency analysis of surface electrocardiograms in patients with persistent atrial fibrillation for monitoring atrial drug action. Drug loading over 3 days with oral flecainide (n = 13) or amiodarone (n = 17) organized the fibrillatory process expressed by decreased atrial fibrillatory rate, increased rate stability, and decreased exponential decay. Effects were more pronounced with flecainide than with amiodarone.
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| 6. |
- Kongstad Rasmussen, Ole, et al.
(author)
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Epicardial and endocardial dispersion of ventricular repolarization. A study of monophasic action potential mapping in healthy pigs.
- 2005
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In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 39:6, s. 342-347
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Journal article (peer-reviewed)abstract
- Objectives. To investigate the total dispersion of ventricular repolarization of the epi- and endocardium. Design. Monophasic action potentials (MAP) were recorded from 211 +/- 54 (151-353) left and right ventricular epi- and endocardial sites during atrial pacing in 10 pigs using the CARTO system. The activation time (AT), MAP duration (MAPd) and end of repolarization time (EOR) were measured. Results. The total dispersion of AT, EOR and MAPd, defined as the maximal differences of these parameters over both the epi- and endocardium, were 57 +/- 10, 84 +/- 20, and 75 +/- 21 ms respectively and were significantly larger than the respective epi- and endocardial dispersions (p < 0.05). The epicardial dispersion of AT, EOR and MAPd of both the right and left ventricles were significantly larger than that of each ventricle alone (p < 0.02). Sternotomy did not affect these dispersion parameters. Conclusion. Detailed mapping of epicardial repolarization in vivo using the MAP mapping technique is feasible. Both the epi- and endocardium of the two ventricles contribute significantly to the total dispersion of repolarization.
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| 7. |
- Liang, YC, et al.
(author)
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QT dispersion failed to estimate the global dispersion of ventricular repolarization measured using monophasic action potential mapping technique in swine and patients
- 2005
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In: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 38:1, s. 19-27
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate whether the QT dispersion measured from 12-lead electrocardiogram (ECG) can estimate the global dispersion of ventricular repolarization (DVR) measured using a monophasic action potential (MAP) mapping technique. Monophasic action potentials were recorded from 75 +/- 12 left ventricular sites in 10 pigs and from 48 +/- 16 left or right ventricular sites in 15 patients using the CARTO mapping system. The maximum DVRs in both end-of-repolarization and MAP duration among all the mapped sites were calculated and termed as global DVR for each measurement. QT intervals, QT(peak) and QT(end), were measured from the 12-lead ECG, and QT dispersions; namely the differences between the maximum and the minimum of the QTpeak and QT(end) were calculated. We found that QT dispersions were significantly smaller than (P < .05) and poorly correlated with the global DVRs both in pigs and patients. Bland-Altman agreement analysis demonstrated a marked variation of the differences and an obvious lack of agreement between the results obtained using the ECG and the MAP methods. In our patients, the global DVR increased markedly during ventricular tachycardia as compared with that during sinus rhythm (P < .05), whereas there was no significant difference in QT dispersion between these 2 subgroups. In conclusion, QT dispersion on the surface ECG could not estimate the global DVR measured using the MAP mapping technique. These findings are not consistent with some previously reported observations, suggesting the need for reappraisal of the electrophysiological implications of QT dispersion.
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| 8. |
- Nieuwlaat, R, et al.
(author)
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Atrial fibrillation management: a prospective survey in ESC Member Countries - The Euro Heart Survey on Atrial Fibrillation
- 2005
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In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 26:22, s. 2422-2434
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Journal article (peer-reviewed)abstract
- Aims To describe atrial fibrillation (AF) management in member countries of the European Society of Cardiology (ESC) and to verify cardiology practices against guidelines. Methods and results Among 182 hospitals in 35 countries, 5333 ambulant and hospitalized AF patients were enrolled, in 2003 and 2004. AF was primary or secondary diagnosis, and was confirmed on ECG in the preceding 12 months. Clinical type of AF was reported to be first detected in 978, paroxysmal in 1517, persistent in 1167, and permanent in 1547 patients. Concomitant diseases were present in 90% of all patients, causing risk factors for stroke to be also highly prevalent (86%). As many as 69% of patients were symptomatic at the time of the survey; among asymptomatic patients, 54% were previously experienced symptoms. Oral anticoagulation was prescribed in 67 and 49% of eligible and ineligible patients, respectively. A rhythm control strategy was applied in 67% of currently symptomatic patients and in 44% of patients who never experienced symptoms. Conclusion This survey provides a unique snapshot of current AF management in ESC member countries. Discordance between guidelines and practice was found regarding several issues on stroke prevention and antiarrhythmic therapy.
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| 9. |
- Olivecrona, Göran, et al.
(author)
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Can pulsed ultrasound increase tissue damage during ischemia? A study of the effects of ultrasound on infarcted and non-infarcted myocardium in anesthetized pigs
- 2005
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In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 5:8
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Journal article (peer-reviewed)abstract
- BACKGROUND: The same mechanisms by which ultrasound enhances thrombolysis are described in connection with non-beneficial effects of ultrasound. The present safety study was therefore designed to explore effects of beneficial ultrasound characteristics on the infarcted and non-infarcted myocardium. METHODS: In an open chest porcine model (n = 17), myocardial infarction was induced by ligating a coronary diagonal branch. Pulsed ultrasound of frequency 1 MHz and intensity 0.1 W/cm2 (ISATA) was applied during one hour to both infarcted and non-infarcted myocardial tissue. These ultrasound characteristics are similar to those used in studies of ultrasound enhanced thrombolysis. Using blinded assessment technique, myocardial damage was rated according to histopathological criteria. RESULTS: Infarcted myocardium exhibited a significant increase in damage score compared to non-infarcted myocardium: 6.2 +/- 2.0 vs. 4.3 +/- 1.5 (mean +/- standard deviation), (p = 0.004). In the infarcted myocardium, ultrasound exposure yielded a further significant increase of damage scores: 8.1 +/- 1.7 vs. 6.2 +/- 2.0 (p = 0.027). CONCLUSION: Our results suggest an instantaneous additive effect on the ischemic damage in myocardial tissue when exposed to ultrasound of stated characteristics. The ultimate damage degree remains to be clarified.
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| 10. |
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