A diagnostic algorithm to optimize data collection and interpretation of Ripple Maps in atrial tachycardias.

BACKGROUND: Ripple Mapping (RM) is designed to overcome the limitations of existing isochronal 3D mapping systems by representing the intracardiac electrogram as a dynamic bar on a surface bipolar voltage map that changes in height according to the electrogram voltage-time relationship, relative to a fiduciary point. OBJECTIVE: We tested the hypothesis that standard approaches to atrial tachycardia CARTO™ activation maps were inadequate for RM creation and interpretation. From the results, we aimed to develop an algorithm to optimize RMs for future prospective testing on a clinical RM platform. METHODS: CARTO-XP™ activation maps from atrial tachycardia ablations were reviewed by two blinded assessors on an off-line RM workstation. Ripple Maps were graded according to a diagnostic confidence scale (Grade I - high confidence with clear pattern of activation through to Grade IV - non-diagnostic). The RM-based diagnoses were corroborated against the clinical diagnoses. RESULTS: 43 RMs from 14 patients were classified as Grade I (5 [11.5%]); Grade II (17 [39.5%]); Grade III (9 [21%]) and Grade IV (12 [28%]). Causes of low gradings/errors included the following: insufficient chamber point density; window-of-interest<100% of cycle length (CL); <95% tachycardia CL mapped; variability of CL and/or unstable fiducial reference marker; and suboptimal bar height and scar settings. CONCLUSIONS: A data collection and map interpretation algorithm has been developed to optimize Ripple Maps in atrial tachycardias. This algorithm requires prospective testing on a real-time clinical platform.

Long-term Prognosis of Paroxysmal Atrial Fibrillation and Predictors for Progression to Persistnt or Chronic Atrial Fibrillation in the Korean Population.

Little is known about the long-term prognosis of or predictors for the different clinical types of atrial fibrillation (AF) in Korean populations. The aim of this study was to validate a risk stratification to assess the probability of AF progression from paroxysmal AF (PAF) to persistent AF (PeAF) or permanent AF. A total of 434 patients with PAF were consecutively enrolled (mean age; 71.7 ± 10.7 yr, 60.6% male). PeAF was defined as episodes that are sustained > 7 days and not self-terminating, while permanent AF was defined as an ongoing long-term episode. Atrial arrhythmia during follow-up was defined as atrial premature complex, atrial tachycardia, and atrial flutter. During a mean follow-up of 72.7 ± 58.3 months, 168 patients (38.7%) with PAF progressed to PeAF or permanent AF. The mean annual AF progression was 10.7% per year. In univariate analysis, age at diagnosis, body mass index, atrial arrhythmia during follow-up, left ventricular ejection fraction, concentric left ventricular hypertrophy, left atrial diameter (LAD), and severe mitral regurgitation (MR) were significantly associated with AF progression. In multivariate analysis, age at diagnosis (P = 0.009), atrial arrhythmia during follow-up (P = 0.015), LAD (P = 0.002) and MR grade (P = 0.026) were independent risk factors for AF progression. Patients with younger age at diagnosis, atrial arrhythmia during follow-up, larger left atrial chamber size, and severe MR grade are more likely to progress to PeAF or permanent AF, suggesting more intensive medical therapy with close clinical follow-up would be required in those patients.

Rosuvastatin suppresses atrial tachycardia-induced cellular remodeling via Akt/Nrf2/heme oxygenase-1 pathway.

Atrial fibrillation (AF) is associated with structural remodeling in atrial myocytes. Emerging evidence suggests that statin has a protective effect on AF through cholesterol-independent mechanisms. The aim of this study is to investigate whether heme oxygenase-1 (HO-1), a potent antioxidant system, mediates the suppressive effect of statin on atrial tachycardia-induced structural remodeling. Treatment of cultured atrium-derived myocytes (HL-1 cell line) with rosuvastatin enhanced HO-1 expression/activity and attenuated tachypacing-induced oxidative stress and myofibril degradation. Heme oxygenase-1 inhibitors and small-interfering RNA for HO-1 blocked the inhibitory effect of rosuvastatin on tachypacing-stimulated changes, suggesting the crucial role of HO-1 in mediating the effect of rosuvastatin. Time-dependent experiments and loss-of-function study demonstrated that Akt/Nrf2 pathways lay to the up-stream of HO-1 in this signaling cascade. Furthermore, the involvement of Akt/Nrf2/HO-1 pathway in the antioxidant effect of rosuvastatin was documented in an ex vivo tachypacing model. The suppressive effect of statin on atrial tachypacing-induced cellular remodeling is mediated via the activation of Akt/Nrf2/HO-1 signaling, which provides a possible explanation for the protective effect of statin on AF.

[Catheter ablation of focal atrial tachycardia:the topographic distribution and long-term outcome].

OBJECTIVE: To explore the topographic distribution and long-term outcome of catheter ablation for focal atrial tachycardia (AT). METHOD: The data of 207 patients who underwent electrophysiologic study for AT were retrospectively analyzed. RESULTS: A total of 200 AT were identified in 185 patients. The most common site for AT was ostium of the coronary sinus (23.8%), followed by crista terminalis (20.5%), perinodal area (20.0%), cava vena (17.8%), annulus (13.0%), and appendage (10.3%). Eighty percent AT originated from the right atrium, 17.8% originated from the left atrium. AT originated from the left atrium was more common in male than in female (25.0% vs. 13.3%, P = 0.042), while AT originated from the right atrium was more common in female than in male (69.4% vs. 86.7%, P = 0.004). Among the 185 patients, acute success ablation rate was 93.5% (n = 173). The acute success rate in the conventional mapping group was lower than that in the three-dimensional mapping group (79.3% vs. 96.5%, P < 0.01). During a median of 36 months follow up, the AT recurred in 20 patients (success ablation rate 88.4%). Success ablation rate was similar between the conventional mapping group and the three-dimensional mapping group (P > 0.05). CONCLUSIONS: Focal AT commonly originates from ostium of coronary sinus, crystal terminalis, perinodal area, and cava veins. There is a gender related difference in the distribution of focal AT. The radiofrequency catheter ablation yields a satisfying success rate and very low complication rate and could be the first line choice for treating ATs in experienced electrophysiological center.

Atrial fibrillation ablation strategies for paroxysmal patients: randomized comparison between different techniques.

BACKGROUND: Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) long-term freedom from AF/atrial tachyarrhythmia is unclear. We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF. METHODS AND RESULTS: One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study. Patients were randomized to pulmonary vein antrum isolation (PVAI; n=35) versus biatrial ablation of the complex fractionated atrial electrograms (CFAEs; n=34) versus PVAI followed by CFAEs (n=34). Patients were given event recorders and followed up at 3, 6, 9, 12, and 15 months postablation. There was no statistical significant difference between the groups in term of sex, age, AF duration, left atrial size, and ejection fraction. At 1 year follow-up, freedom from AF/atrial tachyarrhythmia was documented in 89% of patients in the PVAI group, 91% in the PVAI plus CFAEs group, and 23% in the CFAEs group (P<0.001) after a single procedure and with antiarrhythmic drugs. CONCLUSIONS: No difference in terms of success rate was seen between PVAI alone and PVAI associated with defragmentation. CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up. These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF.

Electrophysiological characteristics of the Marshall potential in dogs.

BACKGROUND: The electrophysiological characteristics of the Marshall potential is important in ligament of Marshall (LOM) ablation. METHODS AND RESULTS: Marshall potential was recorded under sinus rhythm and left atrial appendage (LAA) pacing and in the first randomly selected 5 dogs (Group 1), LOM ablation was performed. Histological examination was performed in the remaining 10 dogs, which were subdivided according to the results (Groups 2, 3). During LAA pacing in Group 2, the AM interval was prolonged or shortened, whereas in Group 3 it was prolonged (125+/-9 vs 80+/-6 ms, P=0.043, when the pacing rate =350) (126+/-9 vs 80+/-6 ms, P=0.0442, when the pacing rate =450). The Marshall potential was separated from the atrial electrogram by LAA pacing in Groups 2 and 3. There was no significant difference in the AM interval during sinus rhythm and right atrial appendage pacing. CONCLUSIONS: Marshall potential has different forms on electrograms, including a prolonged AM interval, which presents with LAA pacing. This finding might be useful in LOM ablation.

An unusual diagnosis of atrial shunt defect by magnetic resonance imaging.

Paroxysmal atrial arrhythmias especially atrial fibrillation are frequently encountered in adult patients with atrial septal defect. However, the diagnosis of atrial defect can be difficult. Thransthoracic echocardiography, the mostly utilized cardiac technique, has shown a limited ability to identify small atrial defects. Transesophageal echocardiography has shown high accuracy to identify but it isn't well tolerated of the patients. Recently, the utility of multislice computed tomography in the evaluation of direction, location, and size of shunt flow in congenital heart disease has been demonstrated. Cardiac magnetic resonance imaging (MRI) is a recent imaging technique that permits with high spatial resolution and without ionising radiation an accurate identification of many cardiovascular diseases. We report an unusual detection of an atrial defect by phase-contrast cine MRI in a patient clinically suspected of arrhitmogenic right ventricular displasia.

The association of atrial tachyarrhythmias with isolated atrial amyloid disease: preliminary observations in autopsied heart specimens.

OBJECTIVE: Isolated atrial amyloidosis (IAA) is associated with atrial tachyarrhythmias. However, only a few studies have appraised atrial tachyarrhythmias and atrial depolarization abnormalities in connection with high-grade IAA. We conducted a collaborative retrospective study to assess this association. METHODS: One hundred consecutive autopsied hearts were studied histologically for IAA. To increase the specificity for atrial depolarization abnormalities in this preliminary study, we excluded those specimens with intermediate amyloid involvement, i.e. IAA grades 1 and 2 (grade 0 = absent or trivial deposits; grade 1 = small deposits; grade 2 = moderate deposits; grade 3 = dense, large deposits). We then screened for baseline, premortem electrocardiograms (ECGs) to assess rhythm. In those with sinus rhythm, the P wave axis, duration, dispersion and terminal force in V1 were determined under magnification. RESULTS: Of the 27 premortem ECGs corresponding to the autopsy specimens with grades 3 (sample) or 0 (controls) IAA, 9 showed sinus rhythm, 13 showed atrial fibrillation, 1 showed atrial flutter and 4 were uninterpretable. Fourteen autopsied hearts (52%) were positive for grade 3 IAA. Ten of those had atrial tachyarrhythmias (9 atrial fibrillation and 1 atrial flutter) compared to 4 of the 13 hearts with grade 0 IAA (72 vs. 31%, respectively; p = 0.03). Although there was excellent interobserver agreement using intraclass correlation coefficients, there were no significant differences in P wave measurements among the small number of patients with sinus rhythm for grade 3 versus grade 0 IAA. CONCLUSION: In a collaborative, preliminary, pilot assessment of autopsied hearts for which premortem ECGs were necessarily screened retrospectively, significantly more hearts with high-grade IAA were associated with atrial tachyarrhythmias compared to those with low-grade IAA. A larger study with an appropriately matched autopsy control group is needed to confirm these and previous observations.

Ectopic atrial arrhythmias arising from canine thoracic veins during in vivo stellate ganglia stimulation.

The purpose of the present study was to determine whether thoracic veins may act as ectopic pacemakers and whether nodelike cells and rich sympathetic innervation are present at the ectopic sites. We used a 1,792-electrode mapping system with 1-mm resolution to map ectopic atrial arrhythmias in eight normal dogs during in vivo right and left stellate ganglia (SG) stimulation before and after sinus node crushing. SG stimulation triggered significant elevations of transcardiac norepinephrine levels, sinus tachycardia in all dogs, and atrial tachycardia in two of eight dogs. Sinus node crushing resulted in a slow junctional rhythm (51 +/- 6 beats/min). Subsequent SG stimulation induced 20 episodes of ectopic beats in seven dogs and seven episodes of pulmonary vein tachycardia in three dogs (cycle length 273 +/- 35 ms, duration 16 +/- 4 s). The ectopic beats arose from the pulmonary vein (n = 11), right atrium (n = 5), left atrium (n = 2), and the vein of Marshall (n = 2). There was no difference in arrhythmogenic effects of left vs. right SG stimulation (13/29 vs. 16/29 episodes, P = nonsignificant). There was a greater density of periodic acid Schiff-positive cells (P < 0.05) and sympathetic nerves (P < 0.05) at the ectopic sites compared with other nonectopic atrial sites. We conclude that, in the absence of a sinus node, thoracic veins may function as subsidiary pacemakers under heightened sympathetic tone, becoming the dominant sites of initiation of focal atrial arrhythmias that arise from sites with abundant sympathetic nerves and periodic acid Schiff-positive cells.

Reversal of global apoptosis and regional stress kinase activation by cardiac resynchronization.

BACKGROUND: Cardiac dyssynchrony in the failing heart worsens global function and efficiency and generates regional loading disparities that may exacerbate stress-response molecular signaling and worsen cell survival. We hypothesized that cardiac resynchronization (CRT) from biventricular stimulation reverses such molecular abnormalities at the regional and global levels. METHODS AND RESULTS: Adult dogs (n=27) underwent left bundle-branch radiofrequency ablation, prolonging the QRS by 100%. Dogs were first subjected to 3 weeks of atrial tachypacing (200 bpm) to induce dyssynchronous heart failure (DHF) and then randomized to either 3 weeks of additional atrial tachypacing (DHF) or biventricular tachypacing (CRT). At 6 weeks, ejection fraction improved in CRT (2.8+/-1.8%) compared with DHF (-4.4+/-2.7; P=0.02 versus CRT) dogs, although both groups remained in failure with similarly elevated diastolic pressures and reduced dP/dtmax. In DHF, mitogen-activated kinase p38 and calcium-calmodulin-dependent kinase were disproportionally expressed/activated (50% to 150%), and tumor necrosis factor-alpha increased in the late-contracting (higher-stress) lateral versus septal wall. These disparities were absent with CRT. Apoptosis assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining, caspase-3 activity, and nuclear poly ADP-ribose polymerase cleavage was less in CRT than DHF hearts and was accompanied by increased Akt phosphorylation/activity. Bcl-2 and BAD protein diminished with DHF but were restored by CRT, accompanied by marked BAD phosphorylation, enhanced BAD-14-3-3 interaction, and reduced phosphatase PP1alpha, consistent with antiapoptotic effects. Other Akt-coupled modulators of apoptosis (FOXO-3alpha and GSK3beta) were more phosphorylated in DHF than CRT and thus less involved. CONCLUSIONS: CRT reverses regional and global molecular remodeling, generating more homogeneous activation of stress kinases and reducing apoptosis. Such changes are important benefits from CRT that likely improve cardiac performance and outcome.

Multiple focal atrial tachycardias in a healthy adult population: characterization and description of successful radiofrequency ablation.

BACKGROUND: The electrophysiologic (EP) characteristics and ablation outcomes of focal atrial tachycardia (AT) have been extensively characterized over recent years. However, there are limited published data describing patients who at EP study have more than one sustained focal tachycardia. OBJECTIVE: To characterize the demographics, tachycardia data, and outcome of patients with successful ablation of more than one focal AT. METHODS: A retrospective review of our supraventricular tachycardia database from 2000 to 2006 identified 258 patients who had undergone radiofrequency ablation of focal AT. Ten patients were identified who had more than one sustained focal tachycardia at EP study, including seven patients with two ATs and three patients with three ATs. The patients were all women with a mean age of 54.2 +/- 10.3 years. AT locations included the crista terminalis, coronary sinus ostium, tricuspid and mitral annuli, and pulmonary vein ostium. Successful ablation was performed for 22 (95.7%) of 23 tachycardias. RESULTS: During long-term follow-up of 32.7 +/- 22.2 months, there were no recurrences of AT in those patients with successful ablation. No patients developed new AT foci, and only one developed late AF. CONCLUSIONS: We have described a series of patients with multiple focal ATs with typical anatomic distribution. These patients do not have significant cardiac or respiratory disease, and in this series, all were women. This report demonstrates that up to three focal ATs can be successfully ablated at a single procedure without recurrence or development of other atrial arrhythmias in long-term follow-up.

Entrainment mapping for rapid distinction of left and right atrial tachycardias.

BACKGROUND: Distinguishing left from right atrial tachycardia is a critical step for guiding ablation. OBJECTIVES: The purpose of this study was to develop and validate a simple algorithm predicting the location of macroreentrant atrial tachycardia (AT) circuits from limited entrainment mapping in right atrium (RA) and coronary sinus (CS). METHODS: In 180 patients with organized reentrant AT, entrainment was performed at the high RA, proximal CS, and distal CS. The difference between the postpacing interval (PPI) and tachycardia cycle length (TCL) was calculated at each site. The location of the AT reentrant circuit was determined by mapping and ablation. An algorithm predicting AT regions was developed from 104 ATs in the first 90 patients (group I) and prospectively evaluated in a validation cohort of 106 ATs in the second 90 patients (group II). RESULTS: In group I, PPI-TCL difference <50 or >50 ms at the high RA distinguished RA from LA reentrant circuits. For RA tachycardias, PPI-TCL difference at the proximal CS distinguished common flutter from lateral RA circuits. For LA circuits, PPI-TCL difference at the proximal and distal CS distinguished perimitral reentry from reentry involving the right pulmonary veins and septum. In group II, an algorithm based on PPI-TCL difference >50 or <50 ms at the high RA, proximal CS, or distal CS had sensitivity of 94%, specificity of 88%, and predictive accuracy of 93% for predicting the successful ablation region. CONCLUSION: Limited entrainment from sites accessible from the RA can expeditiously suggest the AT location to guide more detailed mapping and potentially avoid unnecessary transseptal punctures in some patients.

Reconstruction of the patterns of gene expression in the developing mouse heart reveals an architectural arrangement that facilitates the understanding of atrial malformations and arrhythmias.

Firm knowledge about the formation of the atrial components and of the variations seen in congenital cardiac malformations and abnormal atrial rhythms is fundamental to our understanding of the normal structure of the definitive atrial chambers. The atrial region is relatively inaccessible and has continued to be the source of disagreement. Seeking to resolve these controversies, we made three-dimensional reconstructions of the myocardial components of the developing atrium, identifying domains on the basis of differential expression of myocardial markers, connexin40, and natriuretic precursor peptide A. These reconstructions, made from serial sections of mouse embryos, show that from the outset of atrial development, the systemic and pulmonary veins are directly connected to the atrium. Relative to the systemic junctions, however, the pulmonary venous junction appears later. Our experience shows that three-dimensional reconstructions have three advantages. First, they provide clear access to the combined morphological and molecular data, allowing clarification and verification of morphogenetic concepts for nonmorphological experts and setting the scene for further discussion. Second, they demonstrate that, from the outset, the myocardium surrounding the pulmonary veins is distinct from that clothing the systemic venoatrial junctions. Third, they reveal an anatomical and molecular continuity between the entrance of the systemic venous tributaries, the internodal atrial myocardium, and the atrioventricular region. All these regions are derived from primary myocardium, providing a molecular basis for the observed nonrandom distribution of focal right atrial tachycardias.

Atrial ultrastructural changes during experimental atrial tachycardia depend on high ventricular rate.

INTRODUCTION: Atrial structural and electrophysiologic changes occur during atrial tachycardia. The role of high ventricular rate in these processes remains to be established. METHODS AND RESULTS: Six goats were subjected to 4 weeks of rapid atrioventricular (AV) pacing at an atrial and ventricular rate of 240 beats/min, resulting in development of congestive heart failure. In another five goats, AV block was created. These goats then were subjected to 4 weeks of atrial pacing, also at 240 beats/min while the ventricular rate was kept low and regular at 80 beats/min (A-paced). Pacing was interrupted only for measurement of atrial effective refractory period and right atrial diameter. The ultrastructure of both atria was examined by light and electron microscopy, including quantification of the percentage of atrial extracellular matrix (%ECM). A group of six goats served as controls. In the AV-paced group, severe structural remodeling occurred in the atria, including severe loss of sarcomeres, glycogen accumulation, disruption of sarcoplasmic reticulum, and appearance of numerous small mitochondria and nuclei with homogeneously distributed chromatin. In contrast, structural changes were virtually absent in the atria of A-paced goats. Only a redistribution of nuclear chromatin and the appearance of numerous mitochondria were observed. The ultrastructure was normal in control animals. The%ECM was increased in AV-paced goats (29%) compared to A-paced animals (18%) and controls (17%) (P < 0.05). Finally, right atrial diameter increased by 51% in AV-paced goats but was unchanged in A-paced goats (P < 0.05). In both experimental groups, atrial effective refractory period shortened during pacing. CONCLUSION: Structural remodeling during chronic atrial tachycardia is related to the concomitant presence of a high ventricular rate and hence the occurrence of congestive heart failure rather than a high atrial rate. Electrical remodeling can occur in the absence of significant structural changes.