Biatrial multisite mapping of atrial premature complexes triggering onset of atrial fibrillation

Pulmonary veins are considered to be the most common origin of the focal activity that triggers the onset of atrial fibrillation (AF). However, little is known about the importance of ectopic activity located outside the pulmonary veins. This study included 45 patients (8 women and 37 men, mean age 55 ± 12 years) with paroxysmal (n = 25) and persistent (n = 20) AF in whom multisite mapping of the right and left atria was performed using a 64-electrode basket catheter (n = 21) or a noncontact mapping system (n = 24). Spontaneous or orciprenaline-induced atrial premature complexes (APCs) were mapped. In all, 94 AF onsets from 38 distinct foci in 30 patients were observed and analyzed. Of these foci, 20 (53%) were located in pulmonary veins and 18 (47%) were located outside the pulmonary veins in other parts of the atria. In 22 patients (73%), AF was reproducibly induced by APCs from a single focus (59 episodes). In 8 patients (27%), AF originated from 2 distinct foci (35 episodes). Additionally, 20 of 30 patients (67%) who developed AF had APCs in different locations not inducing AF. APCs inducing AF had shorter coupling intervals than APCs not inducing AF (307 ± 54 vs 409 ± 76 ms, p <0.001). This study showed that 47% of ectopic foci triggering the onset of AF were located outside the pulmonary veins in extravenous parts of the left atrium and the right atrium, and 27% of patients had AF onsets of bifocal origin. These data challenge the current opinion that extrapulmonary foci play a minor role in inducing AF.     

Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B12 levels and the extent of coronary artery disease

The question of whether mild hyperhomocysteinemia is a risk factor for coronary artery disease (CAD) has long been debated and is still unclear. We investigated whether there is a link between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms or plasma homocysteine and CAD. This is a case-control study that included 2,121 consecutive patients (cases) with angiographically proved CAD and 617 patients without CAD (controls). MTHFR gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B(12) concentrations were determined and coronary angiography was performed in all subjects. The distribution of MTHFR gene C677T genotypes in patients (or controls) was: CC-genotype in 915 cases, 43.1% (266 controls, 43.1%); CT-genotype in 955 cases, 45.0%, (283 controls, 45.9%); and TT-genotype in 251 cases, 11.9% (68 controls, 11.0%) (p = 0.84). The distribution of MTHFR gene A1298C genotypes in patients (or controls) was: AA-genotype in 973 cases, 45.9% (281 controls, 45.5%); AC-genotype in 905 cases, 42.7% (284 controls, 46.0%); and CC-genotype in 243 cases, 11.4% (52 controls, 8.5%) (p = 0.07). Patients with CAD had higher levels of plasma homocysteine (12.9 +/- 5.1 vs 11.9 +/- 4.5 micromol/L, p <0.001) and lower levels of folate (9.5 +/- 3.1 vs 9.9 +/- 3.8 ng/ml, p = 0.008) than controls. After adjustment for other risk factors for CAD, plasma homocysteine (p = 0.89), MTHFR gene C677T (p = 0.38), or A1298C polymorphisms (p = 0.13) were not independent correlates of CAD. This study demonstrated that MTHFR gene C677T or A1298C polymorphisms are not associated with the presence of angiographic CAD. Although there is an apparent association between elevated levels of homocysteine and CAD, this association is not independent of conventional cardiovascular risk factors.     

Characterization of paroxysmal and persistent atrial fibrillation in the human left atrium during initiation and sustained episodes

INTRODUCTION: Atrial fibrillation (AF) in the left atrium (LA) is poorly defined in terms of regional differences in the degree of organization, characteristics of paroxysmal and persistent variants, and electrophysiologic events that develop at the onset of episodes. METHODS AND RESULTS: The study population consisted of 21 patients (15 men and 6 women; mean age 58+/-9.4 years) with paroxysmal (10 patients) or persistent (11 patients) AF. Mapping of the LA during sustained episodes and the onset of AF was performed with a 64-electrode basket catheter. At the onset of AF, repetitive beats starting with atrial premature complexes and ending with generation of the earliest fibrillatory activity were defined as intermediary rhythm. Patients with paroxysmal AF had longer AF cycle lengths and more pronounced regional differences than patients with persistent AF. In total, AF cycle lengths in the LA in patients with persistent AF were 20% shorter than in patients with paroxysmal AF. Initiation of AF was preceded by an intermediary rhythm of 5.5+/-2.5 cycles (6.3+/-2.7 cycles in paroxysmal AF vs 4.2+/-1.0 cycles in persistent AF; P = 0.026). At the onset of AF, the earliest generators of fibrillatory activity were located more frequently in the posterior wall of the LA. CONCLUSION: AF in the LA displays substantial regional differences in terms of AF cycle lengths and degree of organization. Patients with persistent AF have shorter cycle lengths and a higher degree of disorganized activity than patients with paroxysmal AF. Intermediary rhythms play an important role in initiation of AF via activation of generator regions in the LA.     

Characterization of onset mechanism and waveform analysis in patients with atrial fibrillation using a high-resolution noncontact mapping system

INTRODUCTION: Information on the spatiotemporal organization of atrial activity at the onset of atrial fibrillation (AF) is limited. METHODS AND RESULTS: The study consisted of 26 consecutive patients (22 men and 4 women; mean age 56 +/- 9 years) with AF in whom the left atrium (LA) was mapped using a noncontact mapping system. At the onset of AF, the AF cycle lengths and wavefronts were analyzed at the site of origin of the triggering atrial premature complex (APC) and five predefined sites within the LA (superior, anterior, posterior, lateral, and septal walls). If repetitive activity was observed at the site of origin of APCs, triggered AF episodes were considered as focally driven. APCs that induced AF had shorter coupling intervals than APCs that did not induce AF (300 +/- 41 msec vs 392 +/- 64 msec, P < 0.001). Immediately after AF onset, repetitive firing was crucial for maintenance of arrhythmia in 52 (80%) of 65 AF episodes. In 13 AF onset episodes (20%), AF was maintained by other mechanisms. The number of LA wavefronts after AF onset was lower in focally driven AF episodes compared with episodes in which no focally driven activity was observed (1.9 +/- 0.6 v. 2.3 +/- 2.3 wavefronts, P < 0.05). After the onset of AF, the posterior wall of the LA showed the earliest disorganized activity (after 5.2 +/- 3.1 cycles). CONCLUSION: In the majority of AF episodes (80%), repetitive firing from the triggering foci may play an important role in maintaining AF immediately after arrhythmia onset. In 20% of the episodes, AF at early stages seems to be maintained by other mechanisms. The capability of APCs to induce AF depends on the coupling interval and the focus localization. The posterior wall of the LA shows the earliest disorganization of wavefronts at the onset of AF.     

Acute effects and long-term outcome of pulmonary vein isolation in combination with electrogram-guided substrate ablation for persistent atrial fibrillation

Complex fractionated atrial electrographic (CFAE) catheter ablation is a new approach for the treatment of atrial fibrillation (AF). It is unclear if acute results of this approach correspond to long-term outcome. The purpose of this study was to prospectively assess acute and long-term successes of an ablation approach combining pulmonary vein isolation (PVI) and ablation of CFAE areas for treatment of persistent AF. PVI and ablation of CFAE areas were performed in 35 patients with persistent AF (30 men, 57+/-9 years of age). At the end of the ablation procedure AF had terminated in 23 of 35 patients (66%) by conversion to sinus rhythm (8 of 23 patients, 35%) or organization to atrial tachycardia (15 of 23 patients, 65%). AF persisted in 12 of 35 patients (34%). At the end of the follow-up period (19+/-12 months), sinus rhythm was present in 26 of 35 patients (74%), including 9 patients with a repeat procedure. This group of 26 patients consisted of 7 of 8 patients (88%) with acute sinus rhythm after the first ablation, 11 of 15 patients (73%) with organization, and 8 of 12 patients (66%) with ongoing AF (p=0.32). In conclusion, a combined approach of PVI and CFAE ablation in persistent AF leads to acute AF termination in 66% and long-term maintenance of sinus rhythm in 74% of cases. However, long-term outcome was not predictable by acute results of the ablation procedure.     

Association of uric acid with mortality in patients with stable coronary artery disease

ObjectiveThe association between uric acid and cardiovascular disease is poorly studied. We undertook this study to assess whether uric acid level predicts clinical outcome in patients with stable coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI).Materials/MethodsThis study included 8149 patients with stable CAD who underwent PCI. Uric acid was measured before angiography. The primary end point was 1-year mortality. Quartiles of quartiles of uric acid were: 1.49 to < 5.49 mg/dl (1st quartile; n=2032 patients), 5.49 to < 6.40 mg/dl (2nd quartile; n=1981 patients), 6.40 to < 7.50 mg/dl (3rd quartile; n=2093 patients) and 7.50 to 21.90 mg/dl (4th quartile; n=2043 patients).ResultsThere were 196 deaths during the 1-year follow-up. The numbers of deaths (Kaplan-Meier estimates) according to uric acid quartiles were: 35 deaths (1.8%) in the 1st quartile, 30 deaths (1.6%) in the 2nd quartile, 45 deaths (2.2%) in the 3rd quartile and 86 deaths (4.3%) in the 4th quartile (unadjusted hazard ratio [HR]=1.60, 95% confidence interval [CI] 1.38-1.86, P < 0.001 for each standard deviation [SD] increase in the logarithmic scale). After adjustment for traditional cardiovascular risk factors, renal function and inflammatory status, the association between uric acid and 1-year mortality remained significant (adjusted HR=1.26, 95% CI 1.07-1.48; P=0.005 for each standard deviation increase in the logarithmic scale). Uric acid improved predictivity of the multivariable model regarding mortality (P=0.040).ConclusionsElevated level of uric acid is an independent predictor of 1-year mortality in patients with stable CAD treated with PCI.