Predictors of recurrence after catheter ablation and electrical cardioversion of atrial fibrillation: an umbrella review of meta-analyses.

AIMS: The recurrence rates after catheter ablation (CA) and direct current (DC) cardioversion remain high, although they have been established treatments of rhythm control of atrial fibrillation (AF). This umbrella review systematically appraises published meta-analyses of both observational and randomized controlled trials (RCTs) for the association of risk and protective factors for arrhythmia recurrence after CA and DC cardioversion of AF. METHODS AND RESULTS: Three bibliographic databases were searched up to June 2021. Evidence of association was rated as convincing, highly suggestive, suggestive, weak, or not significant with respect to observational studies and as high, moderate, low, or very low with respect to RCTs, according to established criteria. Thirty-one meta-analyses were included. Of the 28 associations between CA and the risk of arrhythmia recurrence, none presented convincing evidence, and only the time from diagnosis to ablation over 1 year provided highly suggestive evidence. The association between hypertension and metabolic profile provided suggestive evidence. The associations of Class IC and III antiarrhythmic drugs use with the recurrence after DC cardioversion were supported by an intermediate level of evidence. CONCLUSION: Although AF is a major health issue, few risk- and protective factors for AF recurrence have been identified. None of these factors examined were supported by convincing evidence, whereas established factors such as female gender and left atrial volume showed only weak association. An early CA strategy combined with treatment of metabolic syndrome and hypertension prior to CA may reduce the risk of arrhythmia recurrence. The use of antiarrhythmics can increase the success rate of DC cardioversion. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registry number: CRD42021270613.

Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias.

BACKGROUND: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis. METHODS: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy. RESULTS: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P<0.01), more frequently men (96% vs 82% vs 55%; P<0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P<0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P<0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (P<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (P<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (P<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P<0.01). CONCLUSIONS: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.

Comparing efficacy and safety in catheter ablation strategies for atrial fibrillation: a network meta-analysis.

BACKGROUND: There is no consensus on the most efficient catheter ablation (CA) strategy for patients with atrial fibrillation (AF). The objective of this study was to compare the efficacy and safety of different CA strategies for AF ablation through network meta-analysis (NMA). METHODS: A systematic search of PubMed, Web of Science, and CENTRAL was performed up to October 5th, 2020. Randomized controlled trials (RCT) comparing different CA approaches were included. Efficacy was defined as arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of 6 months. RESULTS: In total, 67 RCTs (n = 9871) comparing 19 different CA strategies were included. The risk of recurrence was significantly decreased compared to pulmonary vein isolation (PVI) alone for PVI with renal denervation (RR: 0.60, CI: 0.38-0.94), PVI with ganglia-plexi ablation (RR: 0.62, CI: 0.41-0.94), PVI with additional ablation lines (RR: 0.8, CI: 0.68-0.95) and PVI in combination with bi-atrial modification (RR: 0.32, CI: 0.11-0.88). Strategies including PVI appeared superior to non-PVI strategies such as electrogram-based approaches. No significant differences in safety were observed. CONCLUSIONS: This NMA showed that PVI in combination with additional CA strategies, such as autonomic modulation and additional lines, seem to increase the efficacy of PVI alone. These strategies can be considered in treating patients with AF, since, additionally, no differences in safety were observed. This study provides decision-makers with comprehensive and comparative evidence about the efficacy and safety of different CA strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registry number: CRD42020169494 .

Collateral injury of the conduction system during catheter ablation of septal substrate in nonischemic cardiomyopathy.

INTRODUCTION: In patients with nonischemic cardiomyopathy (NICM) little is known about the clinical impact of catheter ablation (CA) of septal ventricular tachycardia (VT) resulting in the collateral injury of the conduction system (CICS). METHODS AND RESULTS: Ninety-five consecutive patients with NICM underwent CA of septal VT. Outcomes in patients with no baseline conduction abnormalities who developed CICS (group 1, n = 28 [29%]) were compared to patients with no CICS (group 2, n = 17 [18%]) and to patients with preexisting conduction abnormalities or biventricular pacing (group 3, n = 50 [53%]). Group-1 patients were younger, had a higher left ventricular ejection fraction and a lower prevalence of New York Heart Association III/IV class compared to group 3 while no significant differences were observed with group 2. After a median follow-up of 15 months, VT recurred in 14% of patients in group 1, 12% in group 2 (P = .94) and 32% in group 3 (P = .08) while death/transplant occurred in 14% of patients in group 1, 18% in group 2 (P = .69) and 28% in group 3 (P = .15). A worsening of left ventricular ejection fraction (LVEF) (median LVEF variation, -5%) was observed in group 1 compared to group 2 (median LVEF variation, 0%; P < .01) but not group-3 patients (median LVEF variation, -4%; P = .08) with a consequent higher need for new biventricular pacing in group 1 (43%) compared to group 2 (12%; P = .03) and group 3 (16%; P < .01). CONCLUSIONS: In patients with NICM and septal substrate, sparing the abnormal substrate harboring the conduction system provides acceptable VT control while preventing a worsening of the systolic function.

Gender and age differences in symptoms and health-related quality of life in patients with atrial fibrillation referred for catheter ablation.

BACKGROUND: Primary indication for catheter ablation of atrial fibrillation (AF) is to reduce symptoms and improve health-related quality of life (HRQoL). There are data showing differences between the genders and between younger and older patients. To evaluate this, we studied a large Scandinavian cohort of patients referred for catheter ablation of AF. METHODS: Consecutive patients filled out the ASTA questionnaire, assessing symptoms, HRQoL, and perception of arrhythmia, prior to ablation. Patients were recruited from four Swedish and one Danish tertiary center. RESULTS: A total of 2493 patients (72% men) filled out the ASTA questionnaire. Women experienced eight of the nine ASTA scale symptoms more often than men. Patients <65 years reported four symptoms more often, only tiredness was more frequent in those ≥65 years (P = .007). Women and patients <65 years experienced more often palpitations and regarding close to fainting and this was more common among women, no age differences were seen. Women and men scored differently in 10 of the 13 HRQoL items. Only negative impact on sexual life was more common in men (P < .001). Older patients reported more negative influence in four of the HRQoL items and the younger in one; ability to concentrate. CONCLUSIONS: Women experienced a more pronounced symptom burden and were more negatively affected in all HRQoL concerns, except for the negative impact on sexual life, where men reported more influence of AF. Differences between age groups were less pronounced. Disease-specific patient-reported outcomes measures (PROMs) add important information where gender differences should be considered in the care.

Loss of local capture of the pulmonary vein myocardium after antral isolation: prevalence and clinical significance.

INTRODUCTION: Capture of the myocardial sleeves of the pulmonary veins (PV) during PV pacing is mandatory for assessing exit block after PV isolation (PVI). However, previous studies reported that a significant proportion of PVs failed to demonstrate local capture after PVI. We designed this study to evaluate the prevalence and the clinical significance of loss of PV capture after PVI. METHODS AND RESULTS: Thirty patients (14 redo) undergoing antral PVI were included. Before and after PVI, local PV capture was assessed during circumferential pacing (10 mA/2 milliseconds) with a circular multipolar catheter (CMC), using EGM analysis from each dipole of the CMC and from the ablation catheter placed in ipsilateral PV. Pacing output was varied to optimize identification of sleeve capture. All PVs demonstrated sleeve capture before PVI, but only 81% and 40% after first time and redo PVI, respectively (P < 0.001 vs. before PVI). In multivariate analysis, absence of spontaneous PV depolarizations after PVI and previous PVI procedures were associated with less PV sleeve capture after PVI (40% sleeve capture, P < 0.001 for both). Loss of PV local capture by design was coincident with the development of PV entrance block and importantly predicted absence of acute reconnection during adenosine challenge with 96% positive predictive value (23% negative predictive value). CONCLUSION: Loss of PV local capture is common after antral PVI resulting in entrance block, and may be used as a specific alternate endpoint for PV electrical isolation. Additionally, loss of PV local capture may identify PVs at very low risk of acute reconnection during adenosine challenge.

The substrate and ablation of ventricular tachycardia in patients with nonischemic cardiomyopathy.

The term "nonischemic cardiomyopathy" (NICM) designates a myocardial disease characterized by mechanical and/or electrical dysfunction in the absence of significant coronary artery disease, valvular heart disease, hypertension, or congenital heart disease. Although sustained ventricular tachycardia (VT) occurs in only 5% of patients with NICM, it is an important cause of sudden cardiac death. In this review we summarize the current understanding of the anatomic and electrophysiologic substrates of VT in the different types of NICM. In addition, we discuss recent progress and experience with catheter ablation of VT in these patients.

Symptoms and health-related quality of life 5 years after catheter ablation of atrial fibrillation.

OBJECTIVES: To investigate the effect of catheter ablation (CA) on symptoms and health-related quality of life (HRQoL) after 5 years, and analyze predictors of recurrence of symptoms. BACKGROUND: The primary indication for CA of atrial fibrillation (AF) is to reduce symptoms and improve HRQoL where long-term follow-up are sparse. METHODS: In this observational, long-term, single-center study, patients were recruited from Linköping University Hospital, Sweden. They were aged ≥18 years and had been referred for CA from November 2011 until June 2019. Arrhythmia-specific symptoms and HRQoL were assessed by patient-reported outcome measures (PROMs) with the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA). RESULTS: In the study were 1521 patients, 69% men, mean age 62 years. At baseline, 87% of the patients and at the 5-year follow-up 80% of those eligible filled out the ASTA questionnaire. At follow-up, 50% reported freedom from symptoms, 18% had >50% symptom reduction, 14% had a minor reduction, while 18% reported no effect or a worsening of symptoms. Factors predicting symptoms were female gender (hazard ratio [HR]: 1.8; 1.2-2.8), body mass index ≥ 35 (HR: 3.9; 1.6-9.8), and ischemic heart disease (IHD) (HR: 2.6; 1.2-5.9). After 5 years, breathlessness during activity, weakness/fatigue, and tiredness were still the most common symptoms; regarding HRQoL they were impaired physical ability and deteriorated life situation. CONCLUSIONS AND CLINICAL IMPLICATIONS: This clinical cohort of patients with AF evaluated through PROMs showed that CA had long-lasting effects on symptoms and HRQoL and that the use of PROMs in clinical routines was feasible. Factors predicting symptoms after CA were female gender, IHD, and obesity, an important reminder to encourage lifestyle management.

Comparing Efficacy and Safety in Catheter Ablation Strategies for Paroxysmal Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

Although catheter ablation (CA) is an established treatment for paroxysmal atrial fibrillation (PAF), there is no consensus regarding the most efficient CA strategy. The objective of this network meta-analysis (NMA) was to compare the efficacy and safety of different CA strategies for PAF. A systematic search was performed in PubMed, Web of Science, and CENTRAL until the final search date, 5 October 2020. Randomised controlled trials (RCT) comparing different CA strategies and methods for pulmonary vein isolation (PVI) were included. Efficacy was defined as lack of arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of six months. In total, 43 RCTs comparing 11 different CA strategies involving 6701 patients were included. The risk of recurrence was significantly decreased in comparison with PVI with radiofrequency only for the following treatments: PVI with adjuvant ablation (RR: 0.79, CI: 0.65-0.97) and PVI with sympathetic modulation (RR: 0.64, CI: 0.46-0.88). However, PVI with radiofrequency was superior to non-PVI strategies (RR: 1.65, CI: 1.2-2.26). No statistically significant difference was found in safety between different CA strategies. Concerning different PVI strategies, no difference was observed either in efficacy or in safety between tested strategies. This NMA suggests that different PVI strategies are generally similar in terms of efficacy, while PVI with additional ablation or sympathetic modulation may be more effective than PVI alone. This study provides decision-makers with insights into the efficacy and safety of different CA strategies.

Sinus rhythm QRS amplitude and fractionation in patients with nonischemic cardiomyopathy to identify ventricular tachycardia substrate and location.

BACKGROUND: Ventricular tachycardia (VT) substrate in left ventricular (LV) nonischemic cardiomyopathy (NICM) consists of fibrosis with surviving myocardium. OBJECTIVE: The purpose of this study was to determine whether, in patients with LV NICM and sustained VT, reduced QRS amplitude and QRSf during sinus rhythm can identify the presence and location of abnormal septal (S-NICM) and/or free-wall (FW-NICM) VT substrate. METHODS: We compared patients with NICM and VT (group 1) with electroanatomic mapping septal (S-NICM; n = 21) or free-wall (FW-NICM; n = 20) VT substrate to a 38-patient reference cohort (group 2) with cardiac magnetic resonance imaging (cMRI) and NICM but no VT referred for primary prevention implantable cardioverter-defibrillator (26 [68.4%] with late gadolinium enhancement). RESULTS: Group 1 had lower QRS amplitude in leads II (0.60 ± 0.22 vs 0.86 ± 0.35, P <.001), aVR (0.60 ± 0.24 vs 0.75 ± 0.31, P = .002), aVF (0.48 ± 0.20 vs 0.70 ± 0.28, P <.001), and V2 (1.09 ± 0.52 vs 1.38 ± 0.55, P = .001) than group 2. QRS <0.55 mV in lead aVF identified VT and accompanying substrate with sensitivity 70% and specificity 71%. Most group 1 and group 2 patients had 12-lead ECG QRS fractionation (QRSf) in ≥2 contiguous leads (78% vs 63.2%, P = .14). Sensitivity and specificity for ≥2 QRSf leads identifying respective regional electroanatomic or cMRI abnormalities were 76% and 50% for inferior, 44% and 87% for lateral, and 21% and 89% for anterior leads. CONCLUSION: In LV NICM, low frontal plane QRS (<0.55 mV in aVF) is associated with VT substrate. Although multilead QRS fractionation is associated with the presence and location of VT substrate, it is frequently identified in patients without VT with cMRI abnormalities.

Endocrine and Mechanical Cardiacfunction Four Months after Radiofrequency Ablation of Atrialfibrillation.

BACKGROUND: Radiofrequency ablation (RFA)is an important treatment option for patients with atrial fibrillation (AF). During RFA, a significant amount of energy is delivered into the left atrium (LA), resulting in considerable LA-injury. The impact of this damage on mechanical and endocrine LA-function, however, is often disregarded.We therefore aimed to evaluate the endocrine- and mechanical function of the heart 4-months after RFA of AF. METHODS: In total 189 patients eligible for RFA of AF were studied. The levels of the N-terminal pro-B-natriuretic peptide (NT-proBNP) and the mid-regional fragment of the N-terminal pro-atrial natriuretic peptide (MR-proANP)were measured. The maximum LAvolume (LAVmax),the LAejection fraction (LAEF) and the LA peak longitudinal strain (PALS), were measured usingtransthoracic echocardiography. The measurements were performed before and 4-months after the intervention. RESULTS: 87 patients had a recurrence during a mean follow-up of 143±36 days.NT-proBNPand MR-proANPdecreased significantly at follow-up. This reduction was greater in patients who did not suffer any recurrence after RFA.The LAVmax decreased significantly, whereasthe PALS only improved in patients who did not suffer from any recurrence. On the other hand, LAEF did not change significantly after RFA of AF. CONCLUSIONS: Despite extensiveablation during RFA of AF, the endocrine function of the heart improved 4-months after the index procedure. Patients with no arrhythmia recurrence showed a more pronounced improvement in their endocrinal function. Mechanically, the LAVmax was reduced, and the LA strain improved significantly.

Substrate Characterization and Outcome of Catheter Ablation of Ventricular Tachycardia in Patients With Nonischemic Cardiomyopathy and Isolated Epicardial Scar.

BACKGROUND: The substrate for ventricular tachycardia (VT) in left ventricular (LV) nonischemic cardiomyopathy may be epicardial. We assessed the prevalence, location, endocardial electrograms, and VT ablation outcomes in LV nonischemic cardiomyopathy with isolated epicardial substrate. METHODS: Forty-seven of 531 (9%) patients with LV nonischemic cardiomyopathy and VT demonstrated normal endocardial (>1.5 mV)/abnormal epicardial bipolar low-voltage area (LVA, <1.0 mV and signal abnormality). Abnormal endocardial unipolar LVA (≤8.3 mV) and endocardial bipolar split electrograms and predictors of ablation success were assessed. RESULTS: Epicardial bipolar LVA (27.3 cm2 [interquartile range, 15.8-50.0]) localized to basal (40), mid (8), and apical (3) LV with basal inferolateral LV most common (28/47, 60%). Of 44 endocardial maps available, 40 (91%) had endocardial unipolar LVA (24.5 cm2 [interquartile range, 9.4-68.5]) and 29 (67%) had characteristic normal amplitude endocardial split electrograms opposite the epicardial LVA. At mean of 34 months, the VT-free survival was 55% after one and 72% after multiple procedures. Greater endocardial unipolar LVA than epicardial bipolar LVA (hazard ratio, 10.66 [CI, 2.63-43.12], P=0.001) and number of inducible VTs (hazard ratio, 1.96 [CI, 1.27-3.00], P=0.002) were associated with VT recurrence. CONCLUSIONS: In patients with LV nonischemic cardiomyopathy and VT, the substrate may be confined to epicardial and commonly basal inferolateral. LV endocardial unipolar LVA and normal amplitude bipolar split electrograms identify epicardial LVA. Ablation targeting epicardial VT and substrate achieves good long-term VT-free survival. Greater endocardial unipolar than epicardial bipolar LVA and more inducible VTs predict VT recurrence.

[Evaluation and treatment of PVC's]. / Utredning och behandling av ventrikulära extraslag.

Premature ventricular complex (PVC) is common in the general population. Symptoms vary from none to pronounced. The prognostic significance of PVC's depends on the presence of underlying structural heart disease. The clinical evaluation in patients with PVC aims at excluding structural heart disease and usually involves transthoracic echocardiogram and Holter. Patients without structural heart disease usually have a good prognosis. Frequent PVC's may cause impaired left ventricular function, which usually is reversible after treatment with drugs or ablation. A 12-lead ECG provides important information about PVC localization, however anatomical factors such as the heart's localization in the thorax as well as electrode placement and pharmacological treatment may affect the ECG appearance. In symptomatic patients with or without left ventricular impairment, pharmacological treatment or catheter ablation is indicated. However, in most cases the main goal is to reasure the patient of the good prognosis. To summarize, treatment of choice depends on symptoms, comorbidities, left ventricular function and patient's choice.

Risk Stratification of Patients With Apparently Idiopathic Premature Ventricular Contractions: A Multicenter International CMR Registry.

OBJECTIVES: This study investigated the prevalence and prognostic significance of concealed myocardial abnormalities identified by cardiac magnetic resonance (CMR) imaging in patients with apparently idiopathic premature ventricular contractions (PVCs). BACKGROUND: The role of CMR imaging in patients with frequent PVCs and otherwise negative diagnostic workup is uncertain. METHODS: This was a multicenter, international study that included 518 patients (age 44 ± 15 years; 57% men) with frequent (>1,000/24 h) PVCs and negative routine diagnostic workup. Patients underwent a comprehensive CMR protocol including late gadolinium enhancement imaging for detection of necrosis and/or fibrosis. The study endpoint was a composite of sudden cardiac death, resuscitated cardiac arrest, and nonfatal episodes of ventricular fibrillation or sustained ventricular tachycardia that required appropriate implantable cardioverter-defibrillator therapy. RESULTS: Myocardial abnormalities were found in 85 (16%) patients. Male gender (odds ratio [OR]: 4.28; 95% confidence interval [CI]: 2.06 to 8.93; p = 0.01), family history of sudden cardiac death and/or cardiomyopathy (OR: 3.61; 95% CI: 1.33 to 9.82; p = 0.01), multifocal PVCs (OR: 11.12; 95% CI: 4.35 to 28.46; p < 0.01), and non-left bundle branch block inferior axis morphology (OR: 14.11; 95% CI: 7.35 to 27.07; p < 0.01) were all significantly related to the presence of myocardial abnormalities. After a median follow-up of 67 months, the composite endpoint occurred in 26 (5%) patients. Subjects with myocardial abnormalities on CMR had a higher incidence of the composite outcome (n = 25; 29%) compared with those without abnormalities (n = 1; 0.2%; p < 0.01). CONCLUSIONS: CMR can identify concealed myocardial abnormalities in 16% of patients with apparently idiopathic frequent PVCs. Presence of myocardial abnormalities on CMR predict worse clinical outcomes.

Focal atrial tachycardia: increased electrogram fractionation in the vicinity of the earliest activation site.

AIMS: Fractionated electrograms are often noted during mapping of focal atrial tachycardia (FAT). This finding suggests poor cell-to-cell coupling, which is thought to be an important prerequisite in the process of ectopic impulse initiation and propagation. The purpose of the present study was to assess the electrogram fractionation in the vicinity of the earliest activation site and in the remaining atrium in these patients. METHODS AND RESULTS: Thirteen patients with FAT (age 48 +/- 17 years) who underwent catheter ablation were investigated. Mapping was performed with the CARTO system. Electrogram fractionation was assessed on the basis of the number of negative deflections, both in the region surrounding the earliest activation site and in the remaining atrium. Unipolar and bipolar peak-to-peak voltage and bipolar electrogram duration were also studied. All patients underwent successful radiofrequency ablation. A higher degree of electrogram fractionation existed in the region surrounding the earliest activation site and activated within the first 15 ms when compared with the remaining atrium (incidence of bipolar electrograms with multiple negative deflections: 88 vs. 79%, P < 0.0001; incidence of unipolar electrograms with multiple negative deflections: 56 vs. 43%, P = 0.0001). The peak-to-peak voltage in the region activated within the first 15 ms was less than that in the remaining atrium (bipolar voltage: 1.33 +/- 0.99 vs. 1.61 +/- 1.11 mV, P < 0.001; unipolar voltage: 1.75 +/- 0.92 vs. 1.95 +/- 1.11 mV, P = 0.0188). There were no significant differences in bipolar electrogram duration. Within the region activated during the first 15 ms, from the periphery to the earliest activation site, there was a gradual increase in electrogram fractionation (incidence of bipolar electrograms with multiple negative deflections gradually increasing from 82 to 100% and incidence of unipolar electrograms with multiple negative deflections increasing from 56 to 90%), as well as a gradual decrease in peak-to-peak voltage (bipolar voltage gradually decreasing from 1.47 +/- 1.06 to 0.89 +/- 0.54 mV, P < 0.0001; unipolar voltage gradually decreasing from 1.89 +/- 0.94 to 1.30 +/- 0.63 mV, P < 0.0001). Irregular, closely spaced isochrones were also noted in the region activated during the first 15 ms. The area of this region was 4.88 +/- 3.59 cm(2). CONCLUSION: Increased electrogram fractionation exists within a relatively wide region around the tachycardia origin when compared with the remaining atrium. Moreover, this region is electrically heterogeneous, as suggested by the fact that the degree of electrogram fractionation increases gradually whereas the electrogram voltage decreases gradually towards the earliest activation site. These findings suggest that a non-discrete atrial region with gradually changing electrophysiological properties may underlie the substrate of FAT.

Source of inflammatory markers in patients with atrial fibrillation.

AIMS: Elevated levels of C-reactive protein and other inflammatory markers have been reported in some patients with atrial fibrillation (AF). Whether this finding is related to AF per se or to other conditions remains unclear. In addition, the source of inflammatory markers is unknown. Therefore, in the present study, we sought to assess the extent and the source of inflammation in patients with AF and no other concomitant heart or inflammatory conditions. METHODS AND RESULTS: The study group consisted of 29 patients referred for radiofrequency catheter ablation: 10 patients with paroxysmal AF, 8 patients with permanent AF, and 10 control patients with Wolf-Parkinson-White (WPW) syndrome and no evidence of AF (mean age 54 +/- 11 vs. 57 +/- 13 vs. 43 +/- 16). No patient had structural heart diseases or inflammatory conditions. High-sensitive C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were assessed in blood samples from the femoral vein, right atrium, coronary sinus, and the left and right upper pulmonary veins. All samples were collected before ablation. Compared with controls and patients with paroxysmal AF, patients with permanent AF had higher plasma levels of IL-8 in the samples from the femoral vein, right atrium, and coronary sinus, but not in the samples from the pulmonary veins (median values in the femoral vein: 2.58 vs. 2.97 vs. 4.66 pg/mL, P = 0.003; right atrium: 2.30 vs. 3.06 vs. 3.93 pg/mL, P = 0.013; coronary sinus: 2.85 vs. 3.15 vs. 4.07, P = 0.016). A high-degree correlation existed between the IL-8 levels in these samples (correlation coefficient between 0.929 and 0.976, P < 0.05). No differences in the C-reactive protein and IL-6 levels were noted between the three groups of patients. CONCLUSION: The normal levels of C-reactive protein and IL-6, along with the elevated levels of IL-8 in patients with permanent AF but not in those with paroxysmal AF, suggest a link between a low-grade inflammatory reaction and long-lasting AF. The elevated IL-8 levels in the peripheral blood, right atrium, and coronary sinus but not in the pulmonary veins suggest a possible source of inflammation in the systemic circulation.