Percolation and tortuosity in heart-like cells.

In the last several years, quite a few papers on the joint question of transport, tortuosity and percolation have appeared in the literature, dealing with passage of miscellaneous liquids or electrical currents in different media. However, these methods have not been applied to the passage of action potential in heart fibrosis (HF), which is crucial for problems of heart arrhythmia, especially of atrial tachycardia and fibrillation. In this work we address the HF problem from these aspects. A cellular automaton model is used to analyze percolation and transport of a distributed-fibrosis inflicted heart-like tissue. Although based on a rather simple mathematical model, it leads to several important outcomes: (1) It is shown that, for a single wave front (as the one emanated by the heart's sinus node), the percolation of heart-like matrices is exactly similar to the forest fire case. (2) It is shown that, on the average, the shape of the transport (a question not dealt with in relation to forest fire, and deals with the delay of action potential when passing a fibrotic tissue) behaves like a Gaussian. (3) Moreover, it is shown that close to the percolation threshold the parameters of this Gaussian behave in a critical way. From the physical point of view, these three results are an important contribution to the general percolation investigation. The relevance of our results to cardiological issues, specifically to the question of reentry initiation, are discussed and it is shown that: (A) Without an ectopic source and under a mere sinus node operation, no arrhythmia is generated, and (B) A sufficiently high refractory period could prevent some reentry mechanisms, even in partially fibrotic heart tissue.

Differentiating atrial tachycardias with centrifugal activation: Lessons from high-resolution mapping.

BACKGROUND: Centrifugal activation is not always the origin of a focal atrial tachycardia (AT) ("true-focal"), but passive activation from the other structures ("pseudo-focal"). OBJECTIVE: We aimed to establish a method to differentiate true-focal from pseudo-focal. METHODS: In 49 centrifugal activations in 35 patients with AT, 12-lead electrocardiogram, activation map, atrial global activation histogram (GAH), and local electrograms were analyzed. GAH demonstrates the relation between the activation area and timing through the cycle length, displayed with a normalized value, ranging from 0 (smallest activation area) to 1.0 (largest activation area). RESULTS: Of 30 centrifugal activations observed in the septal region, 6/30 (20.0%) were true-focal. The remaining 24/60 (80.0%) were pseudo-focal, of which 23 (95.8%) were from the opposite chamber. P-wave/flutter-wave duration < 200 ms discriminated true-focal from pseudo-focal (sensitivity 100%; specificity 54.5%; positive predictive value 33.3%; negative predictive value 100%). Multiple breakthrough ruled out the possibility of a true-focal AT. Other differentiating factors were an activation area within the initial 20 ms of <5 mm2 and a typical QS pattern electrogram at the origin. Of 19 centrifugal activations observed outside the septal regions, 7 were true-focal and 12 were pseudo-focal exited from an epicardial structure: 10 of 12 (83.3%) were located around the left atrial appendage and ridge. Flutter wave, GAH score ≤ 0.05, and GAH score < 0.1 for >110 ms of cycle length differentiated true-focal from pseudo-focal with a sensitivity/negative predictive value of 100%. GAH score < 0.1 for >40% of the cycle length simply discriminated true-focal from pseudo-focal with 100% accuracy. CONCLUSION: Centrifugal activation is not necessarily due to a focal AT but passive activation. The activation map with GAH in addition to the 12-lead electrocardiogram and local electrograms enables an accurate differentiation.

Associations of Left Atrial Function and Structure With Supraventricular Ectopy: The Multi-Ethnic Study of Atherosclerosis.

Background High levels of supraventricular ectopy are associated with greater risk of atrial fibrillation, stroke, and death. Little information is available about differences by race/ethnicity in the extent of supraventricular ectopy, or about whether high levels of supraventricular ectopy are associated with impaired left atrial (LA) function and LA enlargement. Methods and Results In the MESA (Multi-Ethnic Study of Atherosclerosis), 1148 participants (47% men; mean age, 67 years) had cardiovascular magnetic resonance imaging in 2010 to 2012, followed by 14-day ambulatory electrocardiographic monitoring in 2016 to 2018. We analyzed participant characteristics and cardiovascular magnetic resonance measures of LA function and structure in relation to average count of premature atrial contractions (PACs) per hour and average number of runs per day of supraventricular tachycardia. In adjusted regression analyses, older age, male sex, White race, elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide), and a history of clinically detected atrial fibrillation were associated with more PACs/hour. Chinese and Hispanic participants had on average fewer PACs/hour than White participants (Chinese participants, 31% less [95% CI, 8%-49%]; Hispanic participants, 38% less [95% CI, 19%-52%]). Greater LA total emptying fraction was associated with fewer PACs/hour (per SD, 16% fewer PACs/hour [95% CI, 7%-25% fewer PACs/hour]). Larger LA minimum volume was associated with more PACs/hour (per SD, 7% more PACs/hour [95% CI, 2%-13% more PACs/hour]). Associations of LA volumes with runs of supraventricular tachycardia/day were similar in direction but were weaker. Conclusions Impaired LA function and LA enlargement were associated with more PACs/hour on extended ambulatory electrocardiographic monitoring. Measurement of supraventricular ectopy may provide information about the extent of atrial myopathy.

Biophysical properties, efficacy, and lesion characteristics of a new linear cryoablation catheter in a canine model.

BACKGROUND: The cryoballoon (CB) catheter is an established tool for pulmonary vein isolation (PVI), but its use is limited for that purpose. OBJECTIVE: The purpose of this study was to investigate the biophysical properties of a newly developed linear cryoablation catheter for creation of linear ablation lesions in an in vivo model. METHODS: Twenty-nine dogs (14 acutely ablated, 15 chronically followed) underwent cryoablation using the linear cryoablation catheter. Regions of interest included the cavotricuspid isthmus (CTI), mitral isthmus (MI), left atrial (LA) roof, and LA posterior wall in an acute study. Cryoablations for CTI and MI were performed in 14 atrial fibrillation animals after PVI and followed over 1 month in the chronic study. Tissue temperature during cryoablation was monitored using implanted thermocouples in the regions of interest. Gross and microscopic pathologic characteristics of the lesions were assessed. RESULTS: In acute animals, lesion length (transmurality) was CTI 34 ± 4 mm (89% ± 11%); MI 29 ± 4 mm (90% ± 13%); LA roof 19 ± 3 mm (90% ± 8%); and LA posterior wall 19 ± 2 mm (81% ± 13%), with 1 or 2 freezes. Chronic bidirectional block was achieved in 13 of 14 CTI (93%) and 10 of 14 MI (71%) ablations after 1-month follow-up and was consistent with lesion continuity and transmurality upon pathology. The lowest tissue temperature correlated well with the closest distance to the linear cryocatheter (r = 0.688; P <.001). CONCLUSION: This linear cryocatheter created continuous and transmural linear lesions with "single-shot" cryoenergy application and has the potential for clinical use in the setting of various arrhythmias.

Centrifugal wave-front propagation speed for localizing the atrial tachycardia origin.

BACKGROUND: The earliest activation site (EAS) on a centrifugally-propagated atrial tachycardia (AT) map may represent the true AT origin (true-focal pattern), or the earliest site resulting from passive activation of AT originating from neighboring tissue (pseudo-focal pattern). We assessed the benefits of using the wave-front propagation speed to distinguish between the true- and the pseudo-focal pattern. METHODS: AT mapping was performed using a novel ultra-high resolution mapping system with a 64-electrode mini-basket catheter. The true AT origin was defined as the site where radiofrequency application eliminated AT. The wave-front propagation speed was estimated from the area surrounded by the centrifugally-propagated wave front over a specific time interval. RESULTS: Total of 46 centrifugally propagated AT maps from 34 patients were analyzed, including 18 true-focal and 28 pseudo-focal pattern. The area surrounded by the propagated wave front was significantly smaller for the true-focal pattern than for the pseudo-focal pattern, 1-20 msec after the earliest activation. The true-focal pattern was identified by the area 13 msec after the earliest activation, with the best cut-off area value of <4.5 cm2. CONCLUSION: The presence or absence of a true origin of AT at the EAS on centrifugally-propagated AT maps can be distinguished using a wave-front propagation speed.

Characteristics, Mechanism and Long-Term Ablation Outcome of Atrial Tachycardias After Mitral Valvular Surgery and Concomitant Cox-MAZE IV Procedure.

The incidence of atrial tachycardia (AT) after rheumatic mitral valvular (RMV) surgery has been well described. However, there have been few reports on the characteristics, mechanism, and long-term ablation outcome of ATs after RMV surgery and concomitant Cox-MAZE IV procedure.The present study reviewed consecutive patients who underwent AT ablation between May 2008 and July 2013. All patients were refractory to antiarrhythmic drugs (AADs) and had a history of RMV surgery and Cox-MAZE IV procedure. A total of 34 patients underwent AT ablation after RMV surgery and concomitant Cox-MAZE IV procedure, and presented 57 mappable and 2 unmappable ATs. The 57 mappable ATs included 14 focal-ATs and 43 reentry-ATs. Ten of the 14 focal-like ATs were located at the pulmonary vein (PV) antrum and border of a box lesion. Of the 43 reentry-ATs, 16 were marco-reentrant around the mitral annulus (MA) and 16 around the tricuspid annulus. There were 41 atypical ATs (non-cavotricuspid isthmus related) including 16 ATs related to the box lesion and 21 ATs related to other Cox-MAZE IV lesions. The AT were successfully terminated in 33 (97.1%) patients. After mean follow-up of 46.9 ± 15.7 months, 25 (73.5%) patients maintained sinus rhythm without AADs after a single procedure and 28 (82.4%) patients after repeated procedures.The recurrent ATs after RMV surgery and concomitant Cox-MAZE IV were mainly reentry mechanism, and largely related to LA. An incomplete lesion or re-conductive gaps in a prior lesion might be the predominant mechanisms for these ATs. Catheter-based mapping and ablation of these ATs seems to be effective and safe during a long-term follow-up.

Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients.

Multifocal atrial tachycardia (MAT) has a well-known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Nonreentrant atrial tachycardias may cause cardiac compromise if sinus rhythm is not restored expeditiously. Typical first-line supraventricular tachycardia anti-arrhythmics (propranolol and digoxin) were generally not effective in restoring or maintaining sinus rhythm in this cohort, while flecainide or amiodarone alone or in concert with propranolol were effective anti-arrhythmic agents for acute and chronic use. Atrial tachycardia resolved in all patients. However, a 4-month-old boy from the cohort was found asystolic (with concurrent cellulitis) and a second patient underwent cardiac transplant for heart failure complicated by recalcitrant atrial arrhythmia. While propranolol alone frequently failed to convert or maintain sinus rhythm, fleccainide or amiodarone, occasionally in combination with propranolol, was effective for RASopathy patient treatment for nonreentrant atrial arrhythmia. Our analysis shows that RASopathy patients may have nonreentrant atrial tachycardia with and without associated cardiac hypertrophy. While nonreentrant arrhythmia has been traditionally associated with Costello syndrome, this work provides an expanded view of RASopathy cardiac arrhythmia phenotype as we demonstrate mutant proteins throughout this signaling pathway can also give rise to ectopic and/or MAT.

Role of surface electrocardiogram precordial leads in localizing different anatomic sites of ectopic atrial tachycardia arising from lower right atrium in pediatric population.

BACKGROUND: The study was designed to examine P wave morphology (PWM) in precordial leads (V1 -V6 ) during ectopic atrial tachycardia (EAT) originating from low right atrium (RA) to identify the anatomic sites of these foci in children. METHODS: Twenty-three consecutive pediatric patients (56% females, mean age 8.5 ± 2.5) with EAT originating from the low RA underwent detailed atrial endocardial activation mapping and radiofrequency ablation. PWM during EAT was analyzed using standard 12-lead ECG in relation to successful ablation sites in RA. RESULTS: Ectopic atrial tachycardia originated from coronary sinus ostium (CSo) in 12 patients, nonseptal tricuspid annulus (TA) in five, lower crista terminalis (CT) in three and lower free wall in three. In lead V1 , PWM showed a positive pattern during EAT originating from CSo (8/12) [91.7% sensitivity, 100% specificity, 100% positive predictive value (PPV), 100% negative predictive value (NPV)]. A negative pattern was observed in EAT originating from lower free wall (1/3) and nonseptal TA (5/5) [50% sensitivity, 100% specificity, 100% PPV, 75% NPV], while isoelectric pattern was in EAT originating from lower CT (3/3) [100% sensitivity, 100% specificity, 100% PPV, 100% NPV]. In leads V3 -V6 , PWM showed a negative pattern in at least two consecutive leads during EAT from CSo (12/12), nonseptal TA (5/5) and lower free wall (3/3) while it was positive in EAT originating from lower CT (3/3) [100% sensitivity, 95% specificity, 75% PPV and 100% NPV]. CONCLUSIONS: P wave morphology in precordial leads can help differentiate the anatomic sites of EAT from lower RA with high PPVs and NPVs.

Catheter Ablation of Focal Atrial Tachycardia Using Remote Magnetic Navigation.

OBJECTIVES: The outcomes of catheter ablation in focal atrial tachycardia (AT) using remote magnetic navigation (RMN) are still controversial. The objectives of this study were to assess the acute and long-term outcomes of catheter ablation in focal AT using RMN. BACKGROUND: A total of 53 patients with focal AT who underwent catheter ablation using RMN were included. Thirty-six patients had structural heart disease, including previous atrial fibrillation ablation and heart surgery (abnormal group), and the remaining 17 patients had no structural heart disease (normal group). METHODS: In 53 patients, a total of 56 atrial foci were found. Acute success of the primary ablation was obtained in 52 patients (98%). Mean procedure duration was 109 ± 35 min, ablation duration was 401 sec (interquartile range [IQR], 332 sec), and fluoroscopy time was 5.0 min (IQR, 3.0 min). After a mean follow-up of 31 ± 18 months, 47 patients (89%) were free from focal AT. No major complications were observed. In the abnormal group, age and target atrium volume were higher and the left ventricular ejection fraction was lower when compared to the normal group. However, there were no significant differences in procedure duration (normal group 106 ± 31 min vs abnormal group 111 ± 37 min); ablation duration (normal group 457 sec [IQR, 412 sec] vs abnormal group 378 sec [IQR, 217 sec]); fluoroscopy time (normal group 4.2 min [IQR, 3.0 min] vs abnormal group 5.4 min [IQR, 3.3 min]); acute success rate (normal group 100% vs abnormal group 97%); and long-term success rate (normal group 88% vs abnormal group 89%) between the two groups (P>.05). CONCLUSION: Our study has demonstrated that catheter ablation of focal AT using RMN is safe and effective, with low fluoroscopy exposure.

Non-invasive localization of atrial ectopic beats by using simulated body surface P-wave integral maps.

Non-invasive localization of continuous atrial ectopic beats remains a cornerstone for the treatment of atrial arrhythmias. The lack of accurate tools to guide electrophysiologists leads to an increase in the recurrence rate of ablation procedures. Existing approaches are based on the analysis of the P-waves main characteristics and the forward body surface potential maps (BSPMs) or on the inverse estimation of the electric activity of the heart from those BSPMs. These methods have not provided an efficient and systematic tool to localize ectopic triggers. In this work, we propose the use of machine learning techniques to spatially cluster and classify ectopic atrial foci into clearly differentiated atrial regions by using the body surface P-wave integral map (BSPiM) as a biomarker. Our simulated results show that ectopic foci with similar BSPiM naturally cluster into differentiated non-intersected atrial regions and that new patterns could be correctly classified with an accuracy of 97% when considering 2 clusters and 96% for 4 clusters. Our results also suggest that an increase in the number of clusters is feasible at the cost of decreasing accuracy.

Electrophysiological relation between the superior vena cava and right superior pulmonary vein in patients with paroxysmal atrial fibrillation.

INTRODUCTION: The superior vena cava (SVC) is a main source of nonpulmonary vein (PV) ectopies initiating atrial fibrillation (AF). Empiric SVC isolation may improve rhythm outcomes after catheter ablation of AF. Because the SVC passes immediately adjacent to the right superior PV (RSPV), an electrophysiological relation could be present between the two structures. The present study aimed to estimate the interrelation between the SVC and RSPV by evaluating arrhythmogenic activities observed during catheter ablation of AF. METHODS AND RESULTS: Study subjects comprised 121 consecutive patients referred for catheter ablation of paroxysmal AF. Isoproterenol infusion was used to induce ectopies and AF. Patients were divided into two groups depending on the presence of arrhythmogenic SVC: arrhythmogenic-SVC (A-SVC) and nonarrhythmogenic SVC (Non-A-SVC) groups. The prevalence of females was higher and body surface area was smaller in the A-SVC group (N = 22) than Non-A-SVC group (N = 99). Arrhythmogenic activities were observed in 60 (49%) RSPVs, 24 (20%) right inferior PVs, 72 (59%) left superior PVs, and 31 (25%) left inferior PVs. Arrhythmogenic RSPVs were more prevalent in the A-SVC group than Non-A-SVC group (86% vs. 41%, P = 0.0001), whereas these prevalences in the other three PVs were not different between groups (P >0.3). In multivariable analysis, arrhythmogenic RSPV was the only independent predictor of arrhythmogenicity of the SVC (OR, 8.53; 95% CI 2.31-31.46; P = 0.001). CONCLUSIONS: An electrophysiological interrelation may be present between the SVC and RSPV in patients with paroxysmal AF. Semiempiric SVC isolation limited to patients with an arrhythmogenic RSPV may be a more efficient treatment strategy.

Comparison of strategies for catheter ablation of focal atrial tachycardia originating near the His bundle region.

BACKGROUND: Recent studies have suggested that para-Hisian atrial tachycardia (AT) can be successfully ablated from the right atrium (RA), left atrium (LA), or noncoronary cusp (NCC) in the aorta; however, the best approach remains unclear. OBJECTIVE: This study aimed to compare different approaches to radiofrequency catheter ablation (RFCA) of para-Hisian AT. METHODS: We retrospectively analyzed 68 consecutive patients (49[72%] women; mean age 61 ± 13 years) treated with RFCA for this type of AT. Mapping of the RA (n = 68), LA (n = 21), and NCC (n = 52) was performed during AT to identify the earliest activation site and to apply RFCA. RESULTS: RFCA successfully terminated AT in the RA in 13 of 28 patients (46.4%), in the LA in 4 of 16 patients (25.0%), and in the NCC in 46 of 52 patients (88.5%) after 1 procedure (P < .05). Atrioventricular block occurred only during RFCA in the RA in 4 of 28 patients (14.3%). After a mean follow-up of 33.5 ± 25.4 months, AT recurrence was observed in 5 of 13 patients (38.5%) ablated in the RA, 1 of 4 (25.0%) ablated in the LA, and 2 of 46 (4.4%) ablated in the NCC (P < .05). RFCA in the LA was effective only if the local activation time (LAT) was earlier than that in the RA. RFCA in the NCC was successful regardless of the LAT (P < .05). CONCLUSION: Mapping and ablation in the NCC should be always considered in cases of AT originating from the His bundle region, regardless of the LAT.

Clinical Features and Sites of Ablation for Patients With Incessant Supraventricular Tachycardia From Concealed Nodofascicular and Nodoventricular Tachycardias.

OBJECTIVES: This study sought to describe the clinical features and sites of successful ablation for incessant nodofascicular (NF) and nodoventricular (NV) tachycardias. BACKGROUND: Incessant supraventricular tachycardias have been associated with tachycardia-induced cardiomyopathies and have been previously attributed to permanent junctional reciprocating tachycardias, atrial tachycardias, and atrioventricular nodal re-entrant tachycardias. Incessant concealed NF and NV tachycardias have not been described previously. METHODS: Three cases of incessant concealed NF and NV re-entrant tachycardias were identified from 2 centers. RESULTS: The authors describe 3 cases with incessant supraventricular tachycardia resulting from NV (2 cases) and NF (1 case) pathways. Atrioventricular nodal re-entrant tachycardia was excluded by His synchronous premature ventricular complexes that either delayed or terminated the tachycardia. Ventricular pacing showed constant and progressive fusion in cases 1 and 3. In 2 cases, there was spontaneous initiation with a 1:2 response (cases 1 and 3); the presence of retrograde longitudinal dissociation or marked decremental pathway conduction in cases 1 and 3 sustains these tachycardias. The NV pathway was successfully ablated in the slow pathway region in case 3 and at the right bundle branch in case 1. The NF pathway was successfully ablated within the proximal coronary sinus in case 2. CONCLUSIONS: This is the first report of incessant supraventricular tachycardia using concealed NF or NV pathways. These tachycardias demonstrated spontaneous initiation from sinus rhythm with a 1:2 response and retrograde longitudinal dissociation or marked decremental pathway conduction. Successful ablation was achieved at either right-sided sites or within the coronary sinus.

Unifying Algorithm for Mechanistic Diagnosis of Atrial Tachycardia.

BACKGROUND: No existing criteria unequivocally differentiate focal atrial tachycardia (AT) caused by microreentry, triggered activity, or enhanced automaticity. Although macroreentrant AT is readily diagnosed based on entrainment criteria, the smaller circuit dimension associated with microreentrant AT makes it challenging to validate the presence of reset with fusion. An algorithm was, therefore, developed that is independent of entrainment but which reliably identifies specific mechanisms of focal AT. METHODS AND RESULTS: Fifty-nine patients with AT underwent adenosine testing after mapping of tacycardia. Ten ATs had nonfocal activation, with ≥90% of tachycardia cycle length identified with electroanatomical mapping, findings consistent with macroreenty. All ATs were insensitive to adenosine. Forty-nine patients had focal AT with centrifugal activation. In 32/49 (67%) ATs, electrograms were nonfractionated, and <50% of tachycardia cycle length could be mapped. Based on programmed stimulation, 26/32 (81%) of these ATs were classified as due to triggered activity and 6/32 (19%) as due to enhanced automaticity. Adenosine terminated 100% of triggered ATs and transiently slowed or suppressed 100% of automatic ATs. The remaining 17 focal ATs had localized fractionated electrograms (≥35% of tachycardia cycle length) at the site of successful ablation and were classified as microreentrant. Adenosine had no effect in these ATs. The response to adenosine accurately differentiated all subtypes of focal AT, P<0.05. CONCLUSIONS: Adenosine-sensitivity (termination or transient slowing/suppression) in response to adenosine was 100% sensitive and specific for identifying focal AT mechanisms due to triggered activity or automaticity, respectively. Absence of adenosine effect on focal AT identifies tachycardia due to microreentry.