Methods and Results— In 484 patients with documented AF (62.2±12.5 years of age, 67% men; 62% paroxysmal and 38% persistent/permanent), the SAF class was assessed and 2 validated quality-of-life questionnaires were administered: the SF-36 generic scale and the disease-specific AFSS (University of Toronto Atrial Fibrillation Severity Scale). There is a significant linear graded correlation between the SAF class and measures of symptom severity, physical and emotional components of quality of life, general well-being, and health care consumption related to AF. Patients with SAF class 0 had age- and sex-standardized SF-36 scores of 0.15±0.16 and –0.04±0.31 (SD units), that is, units away from the mean population score for the mental and physical summary scores, respectively. For each unit increase in SAF class, there is a 0.36 and 0.40 SD unit decrease in the SF-36 score for the physical and mental components. As the SAF class increases from 0 to 4, the symptom severity score (range, 0 to 35) increases from 4.2±5.0 to 18.4±7.8 (P<0.0001).

Conclusions— The CCS-SAF scale is a simple semiquantitative scale that closely approximates patient-reported subjective measures of quality of life in AF and may be practical for clinical use.

Methods and Results— One hundred consecutive patients with drug-resistant atrial fibrillation (63 paroxysmal, 37 persistent) were enrolled. The isolation of the PVs was performed by wedging the balloon at each PV antrum to create circumferential lesions in each case. Contiguous linear lesions were also created at the roof between the superior PVs and at the bottom of the posterior LA between the inferior PVs by dragging the balloon along the endocardium. Complete elimination of the posterior LA and PV potentials was achieved in all 100 cases, confirmed by either conventional or electro-anatomic mapping system. The total procedure time was 129±26 minutes, inclusive of 29.9±7.3 minutes of fluoroscopy time. Follow-up during 11.0±4.8 months confirmed that 92 patients (60 paroxysmal, 32 persistent) were free from atrial fibrillation without antiarrhythmic drugs, and in the remaining patients except for 2 with LA tachycardia, sinus rhythm was maintained with antiarrhythmic drugs. With precautions of esophageal cooling by irrigation dictated by temperature monitoring and monitoring phrenic nerve pacing, no LA-esophageal fistula or permanent phrenic nerve injury occurred.

Conclusion— This feasibility study supports the safety and efficacy of radiofrequency hot balloon catheter for complete isolation of the posterior LA and PVs.

Methods and Results— Seventy-two AF patients (age, 53±11 years) underwent mapping and catheter ablation using an NavX system. The biatrial characteristics such as the complex fractionated atrial electrograms (CFEs; based on fractionated intervals) and frequency analysis (based on dominant frequencies) were mapped before and after PVI. PVI with electric isolation was performed in all patients. In the 45 patients who did not respond to PVI, the continuous CFEs (>8 seconds, 18±18% and 12±17% of the LA sites, before and after PVI, respectively, P=0.02), degree of LA fractionation (mean fractionated interval: 75.6±14.3 msec versus 87.3±16.7 msec, P=0.001), and mean LA dominant frequencies (6.92±0.88 Hz versus 6.58±0.91 Hz, P=0.001) decreased after PVI. Complete PVI altered the distribution of the CFEs toward the LA anteroseptum, mitral annulus, and LA appendage regions. A persistent presence of continuous CFEs in the vicinity of the dominant frequencies sites (observed in 53% patients) correlated with a higher procedural AF termination rate for the CFE ablation (63% versus 23%, P<0.05).

Conclusions— Complete PVI eliminated some CFEs in the LA and altered the distribution of the CFEs. The persistent presence of CFEs before and after PVI in the vicinity of the high frequency sites is important for AF maintenance after PVI.

Methods and Results— Patients with univentricular heart (n=19, 11 male; age, 29±9 years) referred for ablation of SVT were studied. Ablation was guided by 3D electroanatomic mapping in all but 2 procedures. A total of 41 SVT were diagnosed as intra-atrial reentrant tachycardia (n=30; cycle length, 310±68 ms), typical atrial flutter (n=4; cycle length, 288±42 ms), focal atrial tachycardia (n=6; cycle length, 400±60 ms), and atrial fibrillation (n=1). Ablation was successful in 73% of intra-atrial reentrant tachycardia, 75% of atrial flutter, and all focal atrial tachycardia and focal atrial fibrillation. During the follow-up period of 53±34 months, 2 patients were lost to follow-up, 3 died of heart failure, 2 underwent heart transplantation, and 1 underwent conduit replacement. Of the remaining group, 8 had sinus rhythm and 3 had SVT.

Conclusions— Focal and reentrant mechanisms underlie postoperative SVT in patients with univentricular heart. Successive SVT developing over time may be caused by different mechanisms. Ablative therapy is potentially curative, with a procedural success rate of 78%. In patients who had multiple ablation procedures, the SVT originated from different atrial sites, suggesting that these new SVT were caused by progressive atrial disease. Despite recurrent SVT, sinus rhythm at the end of the follow-up period was achieved in 72%.

Methods and Results— In 78 patients undergoing catheter ablation for AF, speckle tracking strain imaging was performed to assess LV strain in 3 directions (radial, circumferential, and longitudinal) at baseline and after 12-month follow-up. The study population was divided into 2 groups, according to the maintenance of sinus rhythm (SR) during follow-up. After 13.8±4.7 months of follow-up, 54 patients (69%) were in SR (SR group), whereas 24 patients (31%) had recurrence of AF (AF group). No significant changes in LV ejection fraction from baseline to follow-up were noted (60±7% versus 59±7%, P=NS). Circumferential strain improved significantly in the SR group (–18.3±3.2% versus –20.4±3.8%, P<0.001), whereas it remained unchanged in the AF group (–18.9±3.5% versus –17.9±3.1%, P=NS). In the SR group, significant improvements in LV longitudinal strain and strain rate were noted, whereas in the AF group, LV longitudinal strain and strain rate deteriorated significantly at long-term follow-up.

Conclusions— After successful catheter ablation, LV circumferential and longitudinal strain and strain rate improve significantly in patients who maintain SR. In contrast, a decrease in LV longitudinal strain and strain rate is observed in patients with recurrence of AF.

Methods and Results— The setup, including a steerable carbon catheter, was tested for safety, image distortion, and feasibility of diagnostic EP studies and radiofrequency ablation at 1.5 T. MRI was performed in 3 different 1.5-T whole-body scanners using various receive coils and pulse sequences. To assess unintentional heating of the catheters by radiofrequency pulses of the MR scanner in vitro, a fluoroptic thermometry system was used to record heating at the catheter tip. Programmed stimulation and ablation therapy was performed in 8 pigs. There was no significant heating of the carbon catheters while using short, repetitive radiofrequency pulses from the MR system. Because there was no image distortion when using the carbon catheters, exact targeting of the lesion sites was possible. Both atrial and ventricular radiofrequency ablation procedures including atrioventricular node modulation were performed successfully in the scanner. Potential complications such as pericardial effusion after intentional perforation of the right ventricular free wall during ablation could be monitored in real time as well.

Conclusion— We describe a newly developed EP technology for interventional electrophysiology based on carbon catheters. The feasibility of this approach was demonstrated by safety testing and performing EP studies and ablation therapy with carbon catheters in the MRI environment.

Methods and Results— Screening for mutations in the 4 β-subunit genes was performed in 480 patients with AF (118 patients with lone AF and 362 patients with AF and cardiovascular disease) and 548 control subjects (188 ethnically defined anonymized subjects and 360 subjects without AF). The effects of mutant β-subunits on SCN5A mediated currents were studied using electrophysiological studies. We identified 2 nonsynonymous variants in SCN1B (resulting in R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with AF. These occur at residues highly conserved across mammals and were absent in control subjects. In 3 of 4 mutation carriers, the ECGs showed saddleback-type ST-segment elevation in the right precordial leads. Transcripts encoding both SCN1B and SCN2B were detected in human atrium and ventricle. In heterologous expression studies using Chinese hamster ovary cells, the mutant β1- or β2-subunits reduced SCN5A-mediated current and altered channel gating compared with coexpression of wild-type subunits.

Conclusions— Loss of function mutations in sodium channel β-subunits were identified in patients with AF and were associated with a distinctive ECG phenotype. These findings further support the hypothesis that decreased sodium current enhances AF susceptibility.

Methods and Results— Surface ECG and FF and NF intracardiac EGMs were simultaneously recorded at rest (mean heart rate, 74±15 bpm) for 4.5±1.3 minutes in 298 patients (mean age, 59±14; 216 male [73%]) with structural heart disease and an implanted Medtronic ICD for primary (231 patients, 78%) or secondary (67 patients, 22%) prevention of SCD. During mean follow-up of 16±8 months, 52 (13.1% per person-year of follow-up) patients sustained VT/VF and received appropriate ICD therapies, but only 19 (4.8% per person-year of follow-up) patients sustained FVT/VF with cycle length ≤240 ms. The Kaplan–Meier survival analysis showed that the highest QT variability index (QTVI) quartile from all cardiac sources (surface ECG; NF and FF EGMs) is associated with event-free survival (P=0.038 for ECG; P=0.024 for FF EGM; P=0.012 for NF EGM). QTVI was a predictor of all VT/VF events and FVT/VF in the multivariate Cox model (including ischemic or nonischemic cardiomyopathy, history of revascularization procedures, LVEF, New York Heart Association class). Strong significant correlation among QTVI determined from all 3 sources was found.

Conclusion— Repolarization lability is present throughout the ventricular myocardium. Increased intracardiac QT variability predicts VT/VF events in patients with structural heart disease.

Methods and Results— We examine the influence of overexpressing cytoplasmic CaMKII_C, both acutely in rabbit ventricular myocytes (24-hour adenoviral gene transfer) and chronically in CaMKII_C-transgenic mice, on transient outward potassium current (I_to), and inward rectifying current (I_K1). Acute and chronic CaMKII overexpression increases I_to,slow amplitude and expression of the underlying channel protein K_V1.4. Chronic but not acute CaMKII overexpression causes downregulation of I_to,fast, as well as K_V4.2 and KChIP2, suggesting that K_V1.4 expression responds faster and oppositely to K_V4.2 on CaMKII activation. These amplitude changes were not reversed by CaMKII inhibition, consistent with CaMKII-dependent regulation of channel expression and/or trafficking. CaMKII (acute and chronic) greatly accelerated recovery from inactivation for both I_to components, but these effects were acutely reversed by AIP (CaMKII inhibitor), suggesting that CaMKII activity directly accelerates I_to recovery. Expression levels of I_K1 and Kir2.1 mRNA were downregulated by CaMKII overexpression. CaMKII acutely increased I_K1, based on inhibition by AIP (in both models). CaMKII overexpression in mouse prolonged APD (consistent with reduced I_to,fast and I_K1), whereas CaMKII overexpression in rabbit shortened APD (consistent with enhanced I_K1 and I_to,slow and faster I_to recovery). Computational models allowed discrimination of contributions of different channel effects on APD.

Conclusion— CaMKII has both acute regulatory effects and chronic expression level effects on I_to and I_K1 with complex consequences on APD.

Methods and Results— We measured ventricular cardiomyocyte [Ca²⁺]_i (Indo1-AM), L-type Ca²⁺-current (I_CaL) and APs (whole-cell perforated-patch), and Ca²⁺-handling protein expression (immunoblot). CAVB increased AP duration, cell shortening, systolic [Ca²⁺]_i transients, and caffeine-induced [Ca²⁺]_i release, and CAVB cells showed spontaneous early afterdepolarizations (EADs). I_CaL density was unaffected by CAVB, but inactivation was shifted to more positive voltages, increasing the activation-inactivation overlap zone for I_CaL window current. Ca²⁺-calmodulin–dependent protein kinase-II (CaMKII) autophosphorylation was enhanced in CAVB, indicating CaMKII activation. CAVB also enhanced CaMKII-dependent phospholamban-phosphorylation and accelerated [Ca²⁺]_i-transient decay, consistent with phosphorylation-induced reductions in phospholamban inhibition of sarcoplasmic reticulum (SR) Ca²⁺-ATPase as a contributor to enhanced SR Ca²⁺ loading. The CaMKII-inhibitor KN93 reversed CAVB-induced changes in caffeine-releasable [Ca²⁺]_i and I_CaL inactivation voltage and suppressed CAVB-induced EADs. Similarly, the calmodulin inhibitor W7 suppressed CAVB-induced I_CaL inactivation voltage shifts and EADs, and a specific CaMKII inhibitory peptide prevented I_CaL inactivation voltage shifts. The SR Ca²⁺-uptake inhibitor thapsigargin and the SR Ca²⁺ release inhibitor ryanodine also suppressed CAVB-induced EADs, consistent with an important role for SR Ca²⁺ loading and release in arrhythmogenesis. AP-duration changes reached a maximum after 1 week of bradypacing, but peak alterations in CaMKII and [Ca²⁺]_i required 2 weeks, paralleling the EAD time course.

Conclusions— CAVB-induced remodeling enhances [Ca²⁺]_i load and activates the Ca²⁺-calmodulin-CaMKII system, producing [Ca²⁺]_i-handling abnormalities that contribute importantly to CAVB-induced arrhythmogenic afterdepolarizations.

Methods and Results— The abundance of 30 transcripts for markers, gap junctions, ion channels, and Ca²⁺-handling proteins in different regions of the rabbit atrioventricular node (nodal extension and proximal and distal penetrating bundle of His as well as atrial and ventricular muscle) was measured using a novel quantitative polymerase chain reaction technique and in situ hybridization. The expression profile of the nodal extension (slow pathway into penetrating bundle) was similar to that of the sinoatrial node. For example, in the nodal extension, in contrast to the atrial muscle and as expected for a slowly conducting tissue with pacemaker activity, there was no or reduced expression of Cx43, Na_v1.5, Ca_v1.2, K_v1.4, KChIP2, and RYR3 and high expression of Ca_v1.3 and HCN4. The expression profile of the penetrating bundle was less specialized. In situ hybridization revealed a transitional zone with reduced expression of Cx43, Na_v1.5, and KChIP2 that may form the fast pathway into the penetrating bundle.

Conclusions— At the atrioventricular node, the expression of gap junctions and ion channels in the nodal extension (slow pathway) and a transitional zone (putative fast pathway) as well as the penetrating bundle (output pathway) is specialized and heterogeneous and roughly matches the electrophysiology of the different regions.