Differences in continuous spectra of fractionated electrograms in paroxysmal versus persistent atrial fibrillation.

INTRODUCTION: Quantitative measurements are helpful to discern fractionated electrograms in paroxysmal and persistent atrial fibrillation (AF), and may be useful to detect optimal ablation sites. However, electrical activation events can be transient, leading to erroneous estimates of electrogram properties. Measurement of continuous changes in electrogram frequency content may improve analysis. METHOD: Fractionated local electrograms from 10 paroxysmal and 10 persistent AF patients were acquired from outside the pulmonary vein ostia and left atrial free wall using the distal bipolar ablation catheter electrode, and analyzed over continuous 16 second intervals. A New Spectral Estimator (NSE) updated the frequency spectrum and spectral parameters once per millisecond. The tallest spectral peak (dominant frequency or DF) was determined. Statistical tests of variability were used to determine significant differences between paroxysmal and persistent AF. RESULTS: Changes in the value of the DF over 16 seconds were caused by transient drifts in the frequency of the dominant peak, or by changes in which peak had the highest amplitude. The continuous DF and the spectral profile parameters were more highly variable in paroxysmal as compared with persistent AF patients (p<0.001). There was found to be a gradient from high to low variability of DF in paroxysmal AF, from the left superior pulmonary vein antrum to the left atrial free wall. CONCLUSIONS: The results suggest that atrial electrical activation becomes more stable and focused at a narrow frequency range in persistent as compared to paroxysmal AF. The NSE implemented for continuous update of spectral parameters, enables a rapid characterization of fractionated electrograms with high time-frequency resolution and low computational cost.

Dietary Fat Intake Is Differentially Associated with Risk of Paroxysmal Compared with Sustained Atrial Fibrillation in Women.

BACKGROUND: Dietary fats have effects on biological pathways that may influence the development and maintenance of atrial fibrillation (AF). However, associations between n-3 (ω-3) polyunsaturated fatty acids and AF are inconsistent, and data on other dietary fats and AF risk are sparse. OBJECTIVES: We examined the association between dietary fatty acid (FA) subclasses and risk of incident AF and explored whether these associations differed for sustained and paroxysmal AF. METHODS: We conducted a prospective cohort study in 33,665 women ≥45 y old without cardiovascular disease (CVD) and AF at baseline in 1993. Fat intake was estimated from food frequency questionnaires at baseline and in 2004. Incident AF was confirmed by medical records through October 2013. AF patterns were classified according to the most sustained form of AF within 2 y of diagnosis. Cox proportional hazards models with the use of a competing risk model approach estimated the RR. RESULTS: Over 19.2 y, 1441 cases of incident AF (929 paroxysmal and 467 persistent/chronic) were confirmed. Intakes of total fat and FA subclasses were not associated with risk of AF. Saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) were differentially associated with AF patterns. The RR for a 5% increment of energy from SFAs was 1.47 (95% CI: 1.04, 2.09) for persistent/chronic and 0.85 (95% CI: 0.66, 1.08) for paroxysmal AF (P-difference = 0.01). For MUFAs, the RR for a 5% increment was 0.67 (95% CI: 0.46, 0.98) for persistent/chronic and 1.03 (95% CI: 0.78, 1.34) for paroxysmal AF, although the difference between patterns was not significant (P-difference = 0.07). CONCLUSIONS: Dietary fat was not associated with risk of incident AF in women without established CVD or AF. High SFA and low MUFA intakes were associated with greater risk of persistent or chronic, but not paroxysmal, AF. Improving dietary fat quality may play a role in the prevention of sustained forms of AF. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479.

Systematic comparison of non-invasive measures for the assessment of atrial fibrillation complexity: a step forward towards standardization of atrial fibrillation electrogram analysis.

AIMS: To present a comparison of electrocardiogram-based non-invasive measures of atrial fibrillation (AF) substrate complexity computed on invasive animal recordings to discriminate between short-term and long-term AF. The final objective is the selection of an optimal sub-set of measures for AF complexity assessment. METHODS AND RESULTS: High-density epicardial direct contact mapping recordings (234 leads) were acquired from the right and the left atria of 17 goats in which AF was induced for 3 weeks (short-term AF group, N = 10) and 6 months (long-term AF group, N = 7). Several non-invasive measures of AF organization proposed in the literature in the last decade were investigated to assess their power in discriminating between the short-term and long-term group. The best performing measures were identified, which when combined attained a correct classification rate of 100%. Their ability to predict standard invasive AF complexity measures was also tested, showing an average R(2) of 0.73 ± 0.04. CONCLUSION: An optimal set of measures of the AF substrate complexity was identified out of the set of non-invasive measures analysed in this study. These measures may contribute to improve patient-tailored diagnosis and therapy of sustained AF.

Surgical treatment of atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, resulting in significant morbidity and mortality, and enormous socio-economic consequences. Though many surgical procedures exist for the treatment ofAF, the Cox-Maze IV procedure developed at Washington University has shown excellent long-term results in diverse patient populations. Furthermore, advances in preoperative diagnostic technology currently under investigation at our institution may allow for further refinement and individualization of the surgical treatment ofAF in the future.

Vitamin D deficiency is unrelated to type of atrial fibrillation and its complications.

INTRODUCTION: Vitamin D plays an important role in a broad range of organ functions, including the cardiovascular system. Only one study has tested the association between vitamin D deficiency and arrhythmia and it found no association. The aim of the present study was to evaluate the association between vitamin D deficiency and the type of atrial fibrillation (AF) and complications to AF. MATERIAL AND METHODS: In total, 258 patients were consecutively included from March 2009 to February 2011. All in- and out-patients in the Department of Cardiology at Hvidovre Hospital were invited to participate, provided they had electrocardiographically documented AF. Patients with dementia or terminal illness were excluded. 25 hydroxyvitamin D (25 OHD) was measured with a chemiluminescence assay (Liaison from DiaSorin, Stillwater, Minnesota, USA). RESULTS: No association between vitamin D level and type of AF was found. Furthermore, no association between vitamin D deficiency and ischaemic heart disease, stroke or acute myocardial infarction was found. Vitamin D deficiency was significantly associated with low age (p = 0.02) and gender with a higher proportion of females having the optimal level of 25 OHD (p = 0.0005). CONCLUSION: Other studies have found a beneficial effect of vitamin D on cardiovascular diseases, but we found no association between vitamin D deficiency and the type of AF or complications to AF. Further investigation is necessary to determine whether vitamin D supplementation improves cardiovascular outcomes in patients with AF. FUNDING: The study has received financial support from several private and one public fund. TRIAL REGISTRATION: The study was approved by the National Ethics Committee (Project-ID: H-C-2009-014).

Does location of epicardial adipose tissue correspond to endocardial high dominant frequency or complex fractionated atrial electrogram sites during atrial fibrillation?

BACKGROUND: Although increased epicardial adipose tissue (EAT) volume is known to be associated with increased prevalence of atrial fibrillation (AF), the exact mechanisms are unclear. Therefore, we investigated whether EAT locations were associated with high dominant frequency (DF) sites or complicated fractionated atrial electrogram sites during AF. METHODS AND RESULTS: Three-dimensional reconstruction computed tomography images depicting EAT volumes (obtained by 320-detector-row multislice computed tomography) were merged with NavX-based DF and complicated fractionated atrial electrogram maps obtained during AF for 16 patients with paroxysmal AF and for 18 patients with persistent AF. Agreement between locations of the EAT, especially EAT surrounding the left atrium, and of high DF or complicated fractionated atrial electrogram sites was quantified. In addition, serum biomarker levels were determined. EAT surrounding the left atrium volumes was significantly greater in patients with persistent AF than in patients with paroxysmal AF (52.9 cm(3) [95% CI, 44.2-61.5] versus 34.8 cm(3) [95% CI, 26.6-43.0]; P=0.007). Serum high-sensitivity C-reactive protein and interleukin-6 levels were significantly higher in persistent AF patients than in paroxysmal AF patients (median high-sensitivity C-reactive protein, 969 ng/mL [interquartile range, 307-1678] versus 320 ng/mL [interquartile range, 120-660]; P=0.008; median interleukin-6, 2.4 pg/mL [interquartile range, 1.7-3.2] versus 1.3 [interquartile range, 0.8-2.4] pg/mL; P=0.017). EAT locations were in excellent agreement with high DF sites (κ=0.77 [95% CI, 0.71-0.82]) but in poor agreement with complicated fractionated atrial electrogram sites (κ=0.22 [95% CI, 0.13-0.31]). CONCLUSIONS: Increased EAT volume and elevation of inflammatory biomarkers are noted in persistent AF rather than paroxysmal AF patients. High DF sites are located adjacent to EAT sites. Thus, EAT may be involved in the maintenance of AF.

Spatiotemporal behavior of high dominant frequency during paroxysmal and persistent atrial fibrillation in the human left atrium.

BACKGROUND: Sites of high dominant frequency (DF(peak)) are thought to indicate the location of drivers of atrial fibrillation (AF), but characterization of their spatiotemporal distribution and stability, critical to their relevance as targets for catheter ablation, requires simultaneous global mapping of the left atrium. METHODS AND RESULTS: Noncontact electrograms recorded simultaneously from 256 left atrial sites during spontaneous AF were analyzed. After subtraction of the ventricular component, fast Fourier transform identified the DF at each site. Focal areas of DF(peak) were defined as those having a DF >20% above all neighboring sites. Twenty-four patients with spontaneous AF (11 paroxysmal and 13 persistent) were studied. In paroxysmal AF, sites of DF(peak) (mean DF, 11.6±2.9 Hz) were observed in 100% of patients (present during 65% of the mapping period). In contrast, DF(peak) was detected in only 31% of patients with persistent AF (P<0.001) and for only 5% of the mapping period (P<0.001). In both groups, locations of DF(peak) varied widely in both consecutive and separated segments of AF (κ coefficient range, -0.07-0.22). Activation sequences around sites of DF(peak) did not demonstrate centrifugal activation that would be expected from focal drivers. CONCLUSIONS: Focal areas of high DF are more frequent in paroxysmal than persistent AF, are spatiotemporally unstable, are not the source of centrifugal activation, and are not, therefore, indicative of fixed drivers of AF. In the absence of spatiotemporal stability, the success of ablation at sites of DF(peak) cannot be explained by elimination of fixed drivers.

Differences in repeating patterns of complex fractionated left atrial electrograms in longstanding persistent atrial fibrillation as compared with paroxysmal atrial fibrillation.

BACKGROUND: Complex fractionated atrial electrograms (CFAE) are morphologically more uniform in persistent longstanding as compared with paroxysmal atrial fibrillation (AF). It was hypothesized that this may result from a greater degree of repetitiveness in CFAE patterns at disparate left atrial (LA) sites in longstanding AF. METHODS AND RESULTS: CFAEs were obtained from recording sites outside the 4 pulmonary vein (PV) ostia and at a posterior and an anterior LA site during paroxysmal and longstanding persistent AF (10 patients each, 120 sequences total). To quantify repetitiveness in CFAE, the dominant frequency was measured from ensemble spectra using 8.4-second sequences, and repetitiveness was calculated by 2 novel techniques: linear prediction and Fourier reconstruction methods. Lower prediction and reconstruction errors were considered indicative of increasing repetitiveness and decreasing randomness. In patients with paroxysmal AF, CFAE pattern repetitiveness was significantly lower (randomness higher) at antral sites outside PV ostia as compared with LA free wall sites (P < 0.001). In longstanding AF, repetitiveness increased outside the PV ostia, especially outside the left superior PV ostium, and diminished at the LA free wall sites. The result was that in persistent AF, there were no significant site-specific differences in CFAE repetitiveness at the selected LA locations used in this study. Average dominant frequency magnitude was 5.32 ± 0.29 Hz in paroxysmal AF and higher in longstanding AF, at 6.27 ± 0.13 Hz (P < 0.001), with the frequency of local activation approaching a common upper bound for all sites. CONCLUSIONS: In paroxysmal AF, CFAE repetitiveness is low and randomness high outside the PVs, particularly the left superior PV. As evolution to persistent longstanding AF occurs, CFAE repetitiveness becomes more uniformly distributed at disparate sites, possibly signifying an increasing number of drivers from remote PVs.

Current status and outcomes of catheter ablation for atrial fibrillation.

Catheter ablation has evolved as an effective treatment modality in patients with AF. In this review, the rationale and outcomes of ablation strategies targeting various mechanisms of AF based on our current understanding are discussed. Likely mechanisms responsible for the therapeutic effects of these approaches are reviewed.

The surgical treatment of atrial fibrillation.

Atrial fibrillation is a complex disease affecting a significant portion of the general population. Although medical therapy is the mainstay of treatment, intervention plays an important role in selected patients. The Cox-Maze procedure is the gold standard for the surgical treatment of atrial fibrillation and has more than 90% success in eliminating atrial fibrillation. Ablation technologies have played a key role in simplifying this technically demanding procedure and making it available to more patients. A myriad of new lesion sets and approaches were introduced over the last decade which has made the operative treatment of atrial fibrillation less invasive and more confusing.

Role of the right atrial substrate in different types of atrial arrhythmias.

BACKGROUND: The regional distribution of the low-voltage zones (LVZs) may relate to the maintenance of atrial arrhythmias in the right atrium (RA). OBJECTIVES: The purpose of this study was to investigate the RA substrate characteristics in different types of atrial arrhythmias originating from RA and left atrium (LA). METHODS: Forty-five patients (35 men, age = 62 +/- 15 years) with RA atypical atrial flutter (n = 15, group 1), RA atrial fibrillation (AF; n = 15, no PV initiating foci, group 2), and LA AF (n = 1 5, no RA arrhythmias, group 3) referred for three-dimensional EnSite mapping were included. Voltage and activation maps were visualized. RESULTS: The mean voltage of the RA was lower in group 2, and compared with group 3, a voltage reduction during atrial pacing was evident in groups 1 and 2. The fixed LVZs (independent of the rhythm) were mostly located along the lower crista terminalis (CT). A functional extension of the LVZ was located on the CT in 84% of patients, sinus venosa in 18%, and free-wall region in 27%, forming the borders of the slow conduction isthmus for the reentrant circuits. The number of slow conduction isthmuses was 1.3 +/- 0.9, 2.2 +/- 1.0, and 0.87 +/- 0.74, for the groups 1-3 patients, respectively (P <.05). Radiofrequency ablation connecting the LVZs successfully eliminated those isthmuses. The long-term follow-up revealed that 66% of the patients remained in sinus rhythm. CONCLUSIONS: Single and multiple slow conduction isthmuses bordered by the fixed and functional LVZs were critical for the reentrant circuits in the RA. The conduction isthmuses could be identified by their substrate characteristics and ablated successfully.

[Application of spectral frequency analysis in atrial fibrillation mechanism assessment]. / Zastosowanie spektralnej analizy czestotliwosciowej do oceny podloza napadowego migotania przedsionków.

Recent studies have demonstrated spatio-temporal organisation in atrial fibrillation (AF), with a highest dominant frequencies (DF) at pulmonary veins ostia (PVo). We present a case of 58-year-old woman with AF evaluated by spectral frequency analysis. Simultaneous recordings at each veno-atrial junction and coronary sinus were obtained. Sequential fast Fourier transforms (FFT) of digitalized signals were performed. FFT profiles were analysed to determine DF. Low DF recorded at right inferior PVo suggested no contribution to AF process. Ablation of high DF PVo and low DF SVC with nonuniform anisotropic conduction resulted in AF termination and good clinical outcome in 1-year follow-up.

Frequency analysis in different types of paroxysmal atrial fibrillation.

OBJECTIVES: This study sought to investigate the regional frequency distribution from multiple bi-atrial sites in different types of paroxysmal atrial fibrillation (AF). BACKGROUND: A previous study showed a left atrium (LA) to right atrium (RA) frequency gradient in patients with paroxysmal AF. METHODS: Forty-four patients (age = 60 +/- 16, male patients = 27) with paroxysmal AF originating from the pulmonary veins (PVs) (n = 31) or superior vena cava (SVC) (n = 13) were included. Frequency analysis was performed on the intracardiac electrograms (7 s, 1 kHz/channel) recorded from PV, posterior LA, coronary sinus (CS), posterolateral RA, and SVC. The largest peak frequency was identified as the dominant frequency (DF). RESULTS: In the PV-AF patients, there was a frequency gradient from the PV ostium to the LA, RA, and SVC (8.5 +/- 3.3 Hz vs. 5.9 +/- 1.1 Hz vs. 5.2 +/- 0.85 Hz vs. 5.5 +/- 0.48 Hz, respectively, p < 0.001). The highest DFs were mostly located at the arrhythmogenic PV ostium (58%). The DFs of the arrhythmogenic PV and PV ostium were significantly higher than those of the non-arrhythmogenic PVs and PV ostia (p < 0.05). In the SVC-AF patients, there was a frequency gradient from the SVC to the RA, LA, and PV (8.0 +/- 2.4 Hz vs. 5.9 +/- 1.1 Hz vs. 5.9 +/- 0.7 Hz vs. 5.8 +/- 0.7 Hz, respectively, p = 0.001). The highest DFs were mostly located inside the SVC (77%) instead of the SVC ostium (as compared with PV-AF patients, p = 0.035). CONCLUSIONS: The location of the highest DF depended on the arrhythmogenic PV or SVC. A frequency gradient was present between the arrhythmogenic thoracic vein and atrium in all patients.

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.

Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation.

OBJECTIVES: The purpose of this study was to evaluate the role of autonomic reflexes in the genesis of syncope associated with the onset of paroxysmal atrial fibrillation. BACKGROUND: Syncope associated with paroxysmal atrial fibrillation has been interpreted as an ominous finding predictive of rapid ventricular rates. However, various mechanisms may be involved when heart rate is not particularly high. METHODS: Forty patients (age 60 +/- 14 years, 20 men, 20 women) with syncope and atrial fibrillation were compared with atrial fibrillation without syncope. Carotid sinus massage and head-up tilt testing (at 60 degrees for 60 min at baseline and during isoproterenol infusion) were performed during sinus rhythm. A positive response was defined as the induction of syncope. Atrial fibrillation was also induced on a tilt table at 60 degrees by means of short bursts of atrial pacing. RESULTS: Results of carotid sinus massage were positive in 15 (37%) of 40 patients but in no control subjects (p = 0.002). Head-up tilt test findings were positive in 25 (66%) of 38 patients and in 2 (12%) of 16 control subjects (p = 0.0004). The induction of atrial fibrillation in the upright position elicited syncope in 16 (42%) of 38 patients but in none of 16 control subjects (p = 0.001). At the beginning of atrial fibrillation, systolic blood pressure was lower in patients than in control subjects (88 +/- 32 vs. 127 +/- 32 mm Hg), whereas mean heart rate was similar (142 +/- 35 vs. 134 +/- 25 beats/min). The correlation between heart rate and systolic blood pressure was weak (r = 0.35), and in five patients syncope occurred at a heart rate < or = 130 beats/min. At the time of syncope, heart rate decreased (-12 +/- 21 beats/min) in patients with induced syncope, whereas it remained unchanged in patients without induced syncope (+1 +/- 17 beats/min, p = 0.04) or slightly increased in control subjects (+9 +/- 21 beats/min, p = 0.009). CONCLUSIONS: Patients with syncope associated with paroxysmal atrial fibrillation are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. In some patients the onset of atrial fibrillation triggers vasovagal syncope.