Continuous warfarin therapy is safe and feasible in catheter ablation of atrial fibrillation.

OBJECTIVES: In the context of catheter ablation of atrial fibrillation, oral anticoagulant therapy has been traditionally replaced by bridging with heparin during the periprocedural period. We wanted to study the feasibility and safety of continuous warfarin therapy compared to traditional bridging therapy. DESIGN: The complication rates were compared retrospectively in a consecutive patient series. In the bridging group, warfarin was discontinued three days and low molecular weight heparin started one day prior to the procedure. Warfarin was reinitiated one day after and low molecular weight heparin was continued until the therapeutic INR target was reached. Patients on continuous therapy received warfarin throughout the periprocedural period. All patients received unfractionated heparin during the procedure. RESULTS: Three thromboembolic cerebrovascular events (1.9%) occurred in the bridging group (n = 157) and seven (0.82%) in the warfarin group (n = 850) (p = 0.142). The number of cardiac tamponades was one (0.64%) and four (0.47%), respectively (p = 0.786). Total number of severe bleeding and thromboembolic complications was more common in the bridging group: 9 (5.7%) versus 22 (2.6%); p = 0.036. In multivariate analysis, female gender, advanced age, and bridging therapy predicted complications. CONCLUSIONS: Continuous oral anticoagulant therapy is a safe and feasible alternative for bridging therapy in patients undergoing catheter ablation of atrial fibrillation.

Preferential conduction patterns along the coronary sinus during atrial fibrillation in humans and their modification by pulmonary vein isolation.

INTRODUCTION: Correlation function analysis applied to endocardial electrograms has earlier been used for analysis of agreement between signals and direction of activation during atrial fibrillation (AF). This study was aimed at evaluating whether preferential activation patterns along the coronary sinus (CS) exist in patients with AF. METHODS: Twenty-seven patients (57 ± 10 years old) admitted for electrophysiological (EP) study (10 patients) and/or AF ablation (17 patients) were studied, 8 with permanent and 19 with persistent AF. Unipolar signals were recorded during 60 seconds from a 10-pole CS catheter during AF at baseline (BL) and after isolation of left and right pulmonary veins and after additional lines in the left atrium (LA) (End). Correlation function analysis was applied to signals from each pair of adjacent electrodes, and graphs of cumulated time delay were made to enable interpretation of direction of activation. RESULTS: Correlation between paired signals was highest in the distal and middle parts of CS and lowest in the proximal CS. In 21 patients, correlation values greater than 0.8 between closely spaced electrodes suggested uniform propagation of the fibrillatory waves. In 18 of 21 patients, preferential conduction pattern along CS was seen. Of those, 15 patients had left-to-right conduction, and 3 had right-to-left conduction. During ablation, atrial fibrillation cycle length increased from 184 ± 32 milliseconds at BL to 193 ± 39 milliseconds after pulmonary vein isolation and 215 ± 39 milliseconds at the end of ablation (P = .03, BL vs End). Because of ablation, preferential conduction along CS changed in 4 patients from left to right at BL to simultaneous CS activation or right to left. In 1 of 3 patients with simultaneous activation at BL, the direction changed to right to left. No direction change was observed in any of the 3 patients with right-to-left activation at BL. CONCLUSIONS: Atrial activation during AF exhibits a high degree of organization in distal and middle CS. Preferential conduction patterns observed in most patients may indicate either relatively dominant stable reentry circuits in the LA or activation spread from a focal source. The changes in preferential conduction during ablation of AF may reflect modification of AF substrate and indicate persistent right atrial sources not affected by ablation in the LA only.

Association of the beta-1 adrenergic receptor carboxyl terminal variants with left ventricular hypertrophy among diabetic and non-diabetic survivors of acute myocardial infarction.

BACKGROUND: The beta-1 adrenergic receptor (beta1AR) plays a fundamental role in the regulation of cardiovascular functions. It carries a nonsynonymous single nucleotide polymorphism in its carboxyl terminal tail (Arg389Gly), which has been shown to associate with various echocardiographic parameters linked to left ventricular hypertrophy (LVH). Diabetes mellitus (DM), on the other hand, represents a risk factor for LVH. We investigated the possible association between the Arg389Gly polymorphism and LVH among non-diabetic and diabetic acute myocardial infarction (AMI) survivors. METHODS: The study population consisted of 452 AMI survivors, 20.6% of whom had diagnosed DM. Left ventricular parameters were measured with two-dimensional guided M-mode echocardiography 2-7 days after AMI, and the Arg389Gly polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The Arg389 homozygotes in the whole study population had a significantly increased left ventricular mass index (LVMI) when compared to the Gly389 carriers (either Gly389 homozygotes or Arg389/Gly389 heterozygotes) [62.7 vs. 58.4, respectively (p = 0.023)]. In particular, the Arg389 homozygotes displayed thicker diastolic interventricular septal (IVSd) measures when compared to the Gly389 carriers [13.2 vs. 12.3 mm, respectively (p = 0.004)]. When the euglycemic and diabetic patients were analyzed separately, the latter had significantly increased LVMI and diastolic left ventricular posterior wall (LVPWd) values compared to the euglycemic patients [LVMI = 69.1 vs. 58.8 (p = 0.001) and LVPWd = 14.2 vs. 12.3 mm (p < 0.001), respectively]. Furthermore, among the euglycemic patients, the Arg389 homozygotes displayed increased LVMI and IVSd values compared to the Gly389 carriers [LVMI = 60.6 vs. 56.3, respectively (p = 0.028) and IVSd = 13.1 vs. 12.0 mm, respectively (p = 0.001)]. There was no difference in the LVMI and IVSd values between the diabetic Arg389 homozygotes and Gly389 carriers. CONCLUSIONS: The data suggest an association between the beta1AR Arg389Gly polymorphism and LVH, particularly the septal hypertrophy. The Arg389 variant appears to confer a higher risk of developing LVH than the corresponding Gly389 variant among patients who have suffered AMI. This association cannot be considered to be universal, however, since it does not appear to exist among diabetic AMI survivors.

Interatrial conduction in patients with paroxysmal atrial fibrillation and in healthy subjects.

BACKGROUND: Altered atrial conduction is linked to susceptibility to atrial fibrillation (AF). Whether signal propagation to left atrium (LA) during sinus rhythm differs between patients with paroxysmal lone AF and healthy subjects is not known. METHODS: In 107 patients with lone paroxysmal AF (age 45±12 years) and 94 controls 99-channel magnetocardiography (MCG) was recorded over anterior chest. The duration of the atrial wave (Pd) and the MCG maps over time intervals corresponding to early and later LA activations were determined. Based on magnetic field orientations in LA maps, MCG atrial waves were classified into 3 types which are related to distinct interatrial conduction routes: Type 1 to Bachmann bundle, Type 2 to margin of fossa ovalis or multisite, and Type 3 to coronary sinus ostial connections. RESULTS: Pd was longer in AF patients than in controls (112±13 vs. 104±13; p<0.001), which was most obvious in Type 1 wave (109±12 vs. 102±11 ms, p=0.003). The distribution of the atrial wave types differed between AF patients and controls: Type 1 occurred in 67% and Type 2 in 20% of controls whereas Type 1 occurred in 54% and Type 2 in 42% of AF patients, p<0.01 for difference. CONCLUSIONS: Susceptibility to paroxysmal lone AF is associated with propagation of atrial signal to LA via margin of fossa ovalis or multiple pathways. When conduction occurs via Bachmann bundle, it is related with prolonged atrial activation. Thus altered and alternative conduction pathways may contribute to pathogenesis of lone AF.

Interatrial right-to-left conduction in patients with paroxysmal atrial fibrillation.

PURPOSE: We wanted to illustrate the right-to-left impulse propagation routes during sinus in patients with paroxysmal atrial fibrillation (PAF), as alterations in conduction patterns have been linked to the pathogenesis of PAF, and as no large patient materials have been published. METHODS: Patients underwent 3-D electroanatomical contact mapping prior to catheter ablation. The site of the earliest left atrial (LA) activation was determined. RESULTS: Three different interatrial routes were identified, either as solitary pathways (36/50 patients, 72%) or in their combinations (14/50). Bachmann's bundle (BB) was involved in the majority of the cases with solitary routes (25/36). More seldom, impulse propagation occurred near the oval fossa (FO) (7/36) or the coronary sinus ostium (4/36). In patients with combined routes, both the BB (10/14) and FO routes (11/14) were included in most cases. CONCLUSIONS: In PAF patients, LA can be activated during sinus rhythm through three distinct connections, either encompassing a single route or via any combination of these connections. In one third, the earliest LA activation occurs outside BB. The knowledge of the propagation patterns may give insight into the pathophysiology of PAF and into refining ablation therapy.

Variation in the vascular endothelial growth factor gene, carotid intima-media thickness and the risk of acute myocardial infarction.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor, but its role in atherogenesis is still unclear. Our goal was to study whether three variants of the VEGF gene, previously associated with VEGF production, are linked to atherosclerosis defined as carotid intima-media thickness (IMT) and as the risk of acute myocardial infarction (AMI). MATERIAL AND METHODS: Three VEGF gene single nucleotide polymorphisms (SNPs) (-2578A>C rs699947, -634C>G rs2010963 and +936C>T rs3025039) were genotyped in 516 control subjects of the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort and in 251 survivors of AMI. In the OPERA cohort, the genotyped SNPs were analysed for their association with IMT. The SNPs were also analysed for their association with the risk of AMI, a complication of advanced atherosclerosis. In addition, haplotype frequencies and their associated effects on IMT and on the risk of AMI were estimated. RESULTS: None of the single genotyped polymorphisms was significantly associated with overall IMT or with the risk of AMI. However, the haplotype CCC was associated with higher overall IMT without plaques in women (p = 0.01, haplotypic effect +0.03 mm), the haplotype CCT with higher IMT without plaques in the internal carotid artery in men (p = 0.001, +0.11), while the haplotype AGT was associated with reduced AMI risk (p = 0.015, OR = 0.46). CONCLUSIONS: Variation in the VEGF gene is weakly associated with IMT and the risk of AMI, but the effect can only be observed when the information of the SNPs is combined by constructing haplotypes.

Non-invasive detection of conduction pathways to left atrium using magnetocardiography: validation by intra-cardiac electroanatomic mapping.

AIMS: Alteration in conduction from right to left atrium (LA) is linked to susceptibility to atrial fibrillation (AF). We examined whether different inter-atrial conduction pathways can be identified non-invasively by magnetocardiographic mapping (MCG). METHODS AND RESULTS: In 27 patients undergoing catheter ablation of paroxysmal AF, LA activation sequence was determined during sinus rhythm using invasive electroanatomic mapping. Before this, 99-channel magnetocardiography was recorded over anterior chest. The orientation of the magnetic fields during the early (40-70 ms from P onset) and later part (last 50%) of LA depolarization was determined using pseudocurrent conversion. Breakthrough of electrical activation to LA occurred through Bachmann bundle (BB) in 14, margin of fossa ovalis (FO) in 3, coronary sinus ostial region (CS) in 2, and their combinations in 10 cases by invasive reference in total of 29 different P-waves. Based on the combination of pseudocurrent angles over early and late parts of LA activation, the MCG maps were divided to three types. These types correctly identified the LA breakthrough sites to BB, CS, FO, or their combinations in 27 of 29 (93%) cases. CONCLUSION: Magnetocardiographic mapping seems capable of distinguishing inter-atrial conduction pathways. Recognizing the inter-atrial conduction pattern may assist in understanding the pathogenesis of AF and identifying the subgroups for patient-tailored therapy.

Interatrial conduction can be accurately determined using standard 12-lead electrocardiography: validation of P-wave morphology using electroanatomic mapping in man.

BACKGROUND: Different P-wave morphologies during sinus rhythm as displayed on standard ECGs have been postulated to correspond to differences in interatrial conduction. OBJECTIVE: The purpose of this study was to evaluate the hypothesis by comparing P-wave morphologies using left atrial activation maps. METHODS: Twenty-eight patients (mean age 49 +/- 9 years) admitted for ablation of paroxysmal atrial fibrillation were studied. Electroanatomic mapping of left atrial activation was performed at baseline during sinus rhythm with simultaneous recording of standard 12-lead ECG. Unfiltered signal-averaged P waves were analyzed to determine orthogonal P-wave morphology. The morphology was subsequently classified into one of three predefined types. All analyses were blinded. RESULTS: The primary left atrial breakthrough site was the fossa ovalis in 8 patients, Bachmann bundle in 18, and coronary sinus in 2. Type 1 P-wave morphology was observed in 9 patients, type 2 in 17, and type 3 in 2. Seven of eight patients with fossa ovalis breakthrough had type 1 P-wave morphology, 16 of 18 patients with Bachmann bundle breakthrough had type 2 morphology, and both patients with coronary sinus breakthrough had type 3 P-wave morphology. Overall, P-wave morphology criteria correctly identified the site of left atrial breakthrough in 25 (89%) of 28 patients. CONCLUSION: In the vast majority of patients, P-wave morphology derived from standard 12-lead ECG can be used to correctly identify the left atrial breakthrough site and the corresponding route of interatrial conduction.

Frequency of sudden cardiac death among acute myocardial infarction survivors with optimized medical and revascularization therapy.

The epidemiologic pattern of sudden cardiac death (SCD) may have changed in the modern treatment era of patients after an acute myocardial infarction (AMI). We evaluated the effect of optimized medical and revascularization therapy on the incidence of SCD after an AMI. A total of 2,130 consecutive patients (mean age 59 +/- 10 years) with an AMI from 2 European centers (Germany and Finland) was included in the study. In this population, 1,004 patients (47%) were treated with an optimized medical and revascularization strategy (defined as treatment with revascularization, beta blockers, aspirin, statins, and angiotensin-converting enzyme inhibitors). Nonoptimized treatment, defined as a lack of any optimized treatment, was received by 1,126 patients (53%). During the mean follow-up of 2.9 +/- 1.3 years, the incidence of SCD was very low among patients who received optimized treatment (1.2%, annual incidence 0.4%) compared with those who did not (3.6%, annual incidence 1.4%, p <0.01). The treatment strategy that had the greatest effect on differences in the SCD rate was revascularization therapy, with the hazard ratio of SCD being 2.1 (95% confidence interval 1.2 to 3.7, p <0.01) for SCD among nonrevascularized patients. Nonoptimized treatment was more often received by older patients, women, diabetic patients, and those with depressed left ventricular function. In conclusion, the incidence of SCD is low in the modern treatment era of patients after an AMI. Coronary revascularization seems to have a great effect on altered the epidemiologic pattern of SCD.

Prediction of sudden cardiac death after acute myocardial infarction: role of Holter monitoring in the modern treatment era.

AIMS: Current treatment may have changed the risk profiles of survivors of acute myocardial infarction (AMI). We evaluated the utility of Holter-based risk variables in the prediction of sudden cardiac death (SCD) among survivors of AMI treated with modern therapy. METHODS AND RESULTS: A total of 2130 AMI patients (mean age 59 +/- 10 years) were included. The patients were treated with modern therapeutic strategies, for example, 94% were on beta-blocking therapy and 70% underwent coronary revascularization. Various risk parameters from Holter monitoring were analysed. During a median follow-up of 1012 days (interquartile range: 750-1416 days), cardiac mortality was 113/2130, including 52 SCDs. All Holter variables predicted the occurrence of SCD (P<0.01), but only reduced post-ectopic turbulence slope (TS) (P<0.001) and non-sustained ventricular tachycardia (P<0.01) remained as marked SCD predictors after adjustment for age, diabetes, and ejection fraction (EF). In a subgroup analysis, none of the Holter variables predicted SCD among those with an EF < or = 0.35, but many variables predicted SCD among those with an EF >0.35, particularly TS (hazard ratio 5.9; 95% CI 2.9-11.7, P<0.001). CONCLUSION: Among the post-AMI patients treated according to the current guidelines, the incidence of SCD is low. Various Holter variables still predict the occurrence of SCD, particularly among the patients with preserved left ventricular function.

Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era.

OBJECTIVES: This prospective study tested whether the natriuretic peptides predict cardiac death among patients using beta-blocking therapy after an acute myocardial infarction (AMI). BACKGROUND: Natriuretic peptides have provided prognostic information after AMI, but their predictive value has not been well established in the era of beta-blocker use. METHODS: A series of 521 patients (mean age 61 +/- 10 years) with AMI was included in the study. The end points were total mortality and non-sudden and sudden cardiac death (SCD). Plasma concentrations of atrial natriuretic peptide (ANP), N-terminal atrial natriuretic propeptide (N-ANP), brain natriuretic peptide (BNP), and ejection fraction (EF) were analyzed before hospital discharge. The cardiac medication was optimized (e.g., adherence to beta-blocking therapy was 97% at discharge and 95% at one year after AMI). RESULTS: During a mean follow-up of 43 +/- 13 months, total mortality was 11.5% (60/521), cardiac mortality was 6.3% (33/521), and 3.1% (16/521) experienced SCD. On univariate analysis, high levels of all measured peptides and low EF predicted the occurrence of non-SCD (p < 0.001 for all). Peptides and EF also predicted the occurrence of SCD (p < 0.05), with elevated BNP (>23.0 pmol/l) being the most powerful predictor (hazard ratio [HR] 4.4, 95% confidence interval [CI] 1.4 to 13.8; p = 0.01). After adjusting for clinical variables, only elevated BNP (HR 3.9, 95% CI 1.2 to 12.3, p = 0.02) and low EF (<40%) (p = 0.03) remained as significant predictors of SCD. CONCLUSIONS: Natriuretic peptides retain their prognostic value in the beta-blocking era among survivors of AMI. Elevated BNP provides information on the risk of subsequent SCD, independent of clinical variables and left ventricular EF.

Temporal changes and prognostic significance of measures of heart rate dynamics after acute myocardial infarction in the beta-blocking era.

Previous studies have shown that indexes describing heart rate (HR) dynamics may predict subsequent deaths of patients after an acute myocardial infarction (AMI). Because beta-blocking (BB) drugs affect both mortality and HR dynamics, the prognostic power of measurements of HR dynamics may have changed in the current era of BB therapy. This study assessed the temporal changes and prognostic significance of time-domain, spectral, and fractal indexes of HR variability along with HR turbulence after an AMI among patients with optimized BB medication. SD of NN intervals, spectral indexes, the short-term fractal scaling exponent (alpha(1)), power-law slope (beta), and turbulence onset and slope were measured in 600 patients at 5 to 7 days after AMI and in 416 patients at 12 months after AMI. In the multivariate analysis, after adjusting for clinical variables, only reduced fractal HR indexes, alpha1 and beta (p <0.01 for both), turbulence onset, and slope (p <0.05 for both), measured at the convalescent phase after AMI, predicted subsequent cardiac death. All time-domain and spectral HR variability indexes and turbulence onset increased significantly during the 12-month period after AMI (p <0.001 for all), whereas the fractal indexes and turbulence slope remained unchanged. Late after AMI, reduced beta (p <0.05) and turbulence slope (p <0.01) were the only independent predictors of cardiac mortality. Traditional time-domain and spectral measurements of HR variability and turbulence onset improved significantly after AMI, whereas the fractal HR dynamics and turbulence slope remained stable. Fractal HR variability and HR turbulence retain their prognostic power in the BB era, when measured either at the convalescent or late phase after AMI.

Prediction of sudden cardiac death after myocardial infarction in the beta-blocking era.

OBJECTIVES: This study assessed the predictive power of arrhythmia risk markers after an acute myocardial infarction (AMI). BACKGROUND: Several risk variables have been suggested to predict the occurrence of sudden cardiac death (SCD), but the utility of these variables has not been well established among patients using medical therapy according to contemporary guidelines. METHODS: A consecutive series of 700 patients with AMI was studied. The end points were total mortality, SCD, and nonsudden cardiac death (non-SCD). Nonsustained ventricular tachycardia (nsVT), ejection fraction (EF), heart rate variability, baroreflex sensitivity, signal-averaged electrocardiogram (SAECG), QT dispersion, and QRS duration were analyzed (n = 675). Beta-blocking therapy was used by 97% of the patients at discharge and by 95% at one and two years after AMI. RESULTS: During a mean (+/-SD) follow-up of 43 +/- 15 months, 37 non-SCDs (5.5%) and 22 SCDs (3.2%) occurred. All arrhythmia risk variables differed between the survivors and those with non-SCD (e.g., the standard deviation of N-N intervals was 98 +/- 32 vs. 74 +/- 21 ms [p < 0.001] and the QRS duration was 103 +/- 22 vs.89 +/- 16 ms [p < 0.001]). Sudden cardiac death was weakly predicted only by reduced EF (<0.40; p < 0.05), nsVT (p < 0.05), and abnormal SAECG (p < 0.05), but not by autonomic markers or standard ECG variables. The positive predictive accuracy of EF, nsVT, and abnormal SAECG as predictors of SCD was relatively low (8%, 12%, and 13%, respectively). CONCLUSIONS: The common arrhythmia risk variables, particularly the autonomic and standard ECG markers, have limited predictive power in identifying patients at risk of SCD after AMI in the beta-blocking era.

Fractal analysis of heart rate variability and mortality after an acute myocardial infarction.

The recently developed fractal analysis of heart rate (HR) variability has been suggested to provide prognostic information about patients with heart failure. This prospective multicenter study was designed to assess the prognostic significance of fractal and traditional HR variability parameters in a large, consecutive series of survivors of an acute myocardial infarction (AMI). A consecutive series of 697 patients were recruited to participate 2 to 7 days after an AMI in 3 Nordic university hospitals. The conventional time-domain and spectral parameters and the newer fractal scaling indexes of HR variability were analyzed from 24-hour RR interval recordings. During the mean follow-up of 18.4 +/- 6.5 months, 49 patients (7.0%) died. Of all the risk variables, a reduced short-term fractal scaling exponent (alpha(1) <0.65), measured by detrended fluctuation analysis, was the most powerful predictor of mortality (univariate relative risk 5.05, 95% confidence intervals [CI] 2.87 to 8.89, p <0.001). A low scaling exponent alpha(1) predicted death in the patients with and without depressed left ventricular function (p <0.001 and p <0.01, respectively). Several other HR variability parameters also predicted mortality in univariate analyses, but in a multivariate analysis after adjustments for clinical variables and left ventricular ejection fraction, alpha(1) was the most significant independent HR variability index that predicted subsequent mortality (relative risk 3.90, 95% CI 2.03 to 7.49, p <0.001). Short-term fractal scaling analysis of HR variability is a powerful predictor of mortality among patients surviving an acute myocardial infarction.

Clinical applicability of heart rate variability analysis by methods based on nonlinear dynamics.

Analysis of heart rate (HR) variability has become an important widely used method for assessing cardiac autonomic regulation. Conventionally, HR variability has been analyzed with time and frequency domain methods. Analysis of HR dynamics by methods based on nonlinear systems theory has opened a novel approach for studying the abnormalities in HR behavior. Recent studies have shown that these measures, particularly scaling analysis methods of HR dynamics, are altered among various patients populations with cardiovascular diseases, and they provide prognostic information. Altered long-term scaling properties of HR dynamics and more random short-term HR fluctuation has been observed, e.g., among patients with previous myocardial infarction, and these alterations have been shown to be associated with increased mortality rate. A relatively large body of data indicate that altered scaling properties of R-R intervals are physiologically deleterious. These findings support the notion that some nonlinear methods, such as scaling and complexity measures, give clinically valuable information for risk stratification among various patient populations. This article provides a review of our current knowledge of the usefulness of dynamical measures of HR fluctuation.