Ventricular arrhythmias ablated successfully in the subvalvular interleaflet triangle between the right and left coronary cusps: Electrophysiological characteristics and catheter ablation.

BACKGROUND: Ventricular arrhythmias (VAs) ablated successfully at the right-left subvalvular interleaflet triangle (R-L ILT) between right and left coronary cusps have not been fully characterized. OBJECTIVE: The purpose of this study was to investigate the electrophysiological characteristics of these VAs and their relationships with the left ventricular (LV) summit. METHODS: Twenty-eight VAs ablated successfully at the R-L ILT were studied. RESULTS: Ninety-six percent of VAs had an early precordial electrocardiographic transition. R-wave amplitude in lead V1 was relatively high (RS morphology, R-wave amplitude 0.35 ± 0.09 mV; R/S ratio 0.35 ± 0.27), whereas the morphology of lead I was R-shaped in 71% and M-shaped in 50% of VAs. Earliest potential was recorded at the R-L ILT in 13 of 28 patients and the left pulmonary sinus cusp (LC) in 6 of 28 patients. Mapping the summit communicating vein (summit-CV) failed because of anatomic or instrumental limitations in these 19 patients. In the other 9 patients, earliest potential was successfully recorded at the summit-CV, while perfect pacemapping was achieved. Poor pace mapping was achieved at the R-L ILT or LC in most patients (27/28). Target site was located at the top of the R-L ILT in all cases. A presystolic potential was present at the target site in 18 of 28 patients. A U-curve via the retrograde method was conventionally used to reach the top of the R-L ILT. CONCLUSION: VAs ablated successfully at the R-L ILT have unique electrophysiological characteristics, and R-L ILT may be an endocardial anatomic ablation target for VAs originating from the base of the LV summit.

The isthmus characteristics of scar-related macroreentrant atrial tachycardia in patients with and without cardiac surgery.

INTRODUCTION: Identifying the critical isthmus (CI) in scar-related macroreentrant atrial tachycardia (AT) is challenging, especially for patients with cardiac surgery. We aimed to investigate the electrophysiological characteristics of scar-related macroreentrant ATs in patients with and without cardiac surgery. METHODS: A prospective study of 31 patients (mean age 59.4 ± 9.81 years old) with scar-related macroreentrant ATs were enrolled for investigation of substrate properties. Patients were categorized into the nonsurgery (n = 18) and surgery group (n = 13). The CIs were defined by concealed entrainment, conduction velocity less than 0.3 m/s, and the presence of local fractionated electrograms. RESULTS: Among the 31 patients, a total of 65 reentrant circuits and 76 CIs were identified on the coherent map. The scar in the surgical group is larger than the nonsurgical group (18.81 ± 9.22 vs. 10.23 ± 5.34%, p = .016). The CIs in surgical group have longer CI length (15.27 ± 4.89 vs. 11.20 ± 2.96 mm, p = .004), slower conduction velocity (0.46 ± 0.19 vs. 0.69 ± 0.14 m/s, p < .001), and longer total activation time (45.34 ± 9.04 vs. 38.24 ± 8.41%, p = .016) than those in the nonsurgical group. After ablation, 93.54% of patients remained in sinus rhythm during a follow-up of 182 ± 19 days. CONCLUSION: The characteristics of the isthmus in macroreentrant AT are diverse, especially for surgical scar-related AT. The identification of CIs can facilitate the successful ablation of scar-related ATs.

Left atrial imaging and registration of fibrosis with conduction voltages using LGE-MRI and electroanatomical mapping.

BACKGROUND AND PURPOSE: Abnormal electrical conduction and excitability associated with fibrosis in the left atrium (LA) may serve as a substrate for atrial fibrillation (AF). Electroanatomical voltage mapping systems (EAMs) have become a dominant facilitator to treat AF with catheter ablation assisted by additional diagnostic imaging modalities. Importantly, AF has been associated with structural changes to the extracellular matrix of the myocardium, including increased collagen deposition-a process known as fibrosis. Late gadolinium enhancement-magnetic resonance imaging (LGE-MRI) may aid in guiding AF cardiac ablation therapy by determination of location of fibrosis in the LA. To locate fibrosis for cardiac ablation, however, accurate registration between EAMs and LGE-MRI data is crucial. The purpose of this work was to develop a method for registering EAMs with late gadolinium enhancement-magnetic resonance (LGE-MR) images of fibrosis. METHODS: Twenty patients with persistent AF, who underwent magnetic resonance imaging scanning and EAMs prior to first-time catheter ablation, participated in the study. In our registration pipeline, LGE-MR images were registered to the left atrial surface on EAMs using manual alignment followed by iterative closest point (ICP), and non-rigid ICP (NICP) algorithm. RESULTS AND CONCLUSIONS: The results demonstrate that NICP provided a substantial reduction in registration error when compared to the use of affine ICP alone. Regions of fibrosis on LGE-MR images identified using the signal threshold to reference mean threshold demonstrated the most regional overlap with low bipolar voltage points on EAMs. Successful co-registration of LGE-MR images to EAMs may assist electro-physiologists in selecting candidate targets for ablation and ultimately, reduce the rate of AF recurrence for patients.

2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias.

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias.

MG53, A Novel Regulator of KChIP2 and Ito,f, Plays a Critical Role in Electrophysiological Remodeling in Cardiac Hypertrophy.

BACKGROUND: KChIP2 (K+ channel interacting protein) is the auxiliary subunit of the fast transient outward K+ current ( Ito,f) in the heart, and insufficient KChIP2 expression induces Ito,f downregulation and arrhythmogenesis in cardiac hypertrophy. Studies have shown muscle-specific mitsugumin 53 (MG53) has promiscuity of function in the context of normal and diseased heart. This study investigates the possible roles of cardiac MG53 in regulation of KChIP2 expression and Ito,f, and the arrhythmogenic potential in hypertrophy. METHODS: MG53 expression is manipulated by genetic ablation of MG53 in mice and adenoviral overexpression or knockdown of MG53 by RNA interference in cultured neonatal rat ventricular myocytes. Cardiomyocyte hypertrophy is produced by phenylephrine stimulation in neonatal rat ventricular myocytes, and pressure overload-induced mouse cardiac hypertrophy is produced by transverse aortic constriction. RESULTS: KChIP2 expression and Ito,f density are downregulated in hearts from MG53-knockout mice and MG53-knockdown neonatal rat ventricular myocytes, but upregulated in MG53-overexpressing cells. In phenylephrine-induced cardiomyocyte hypertrophy, MG53 expression is reduced with concomitant downregulation of KChIP2 and Ito,f, which can be reversed by MG53 overexpression, but exaggerated by MG53 knockdown. MG53 knockout enhances Ito,f remodeling and action potential duration prolongation and increases susceptibility to ventricular arrhythmia in mouse cardiac hypertrophy. Mechanistically, MG53 regulates NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity and subsequently controls KChIP2 transcription. Chromatin immunoprecipitation demonstrates NF-κB protein has interaction with KChIP2 gene. MG53 overexpression decreases, whereas MG53 knockdown increases NF-κB enrichment at the 5' regulatory region of KChIP2 gene. Normalizing NF-κB activity reverses the alterations in KChIP2 in MG53-overexpressing or knockdown cells. Coimmunoprecipitation and Western blotting assays demonstrate MG53 has physical interaction with TAK1 (transforming growth factor-b [TGFb]-activated kinase 1) and IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), critical components of the NF-κB pathway. CONCLUSIONS: These findings establish MG53 as a novel regulator of KChIP2 and Ito,f by modulating NF-κB activity and reveal its critical role in electrophysiological remodeling in cardiac hypertrophy.

The relationship between the P wave and local atrial electrogram in predicting conduction block during catheter ablation of cavo-tricuspid isthmus-dependent atrial flutter.

PURPOSE: The endpoint for radiofrequency catheter ablation (RFA) of cavo-tricuspid isthmus (CTI)-dependent atrial flutter (AFL) is complete conduction block along the CTI. The purpose of this study is to evaluate the utility of the temporal relationship between the P wave and the local atrial electrograms in determining complete CTI block. METHODS: RFA of CTI was performed in 125 patients (age 63 ± 11 years). During pacing from the coronary sinus (CS), the intervals from the peak of the P wave (Ppeak) in lead V1 to the second component of the local atrial electrogram (A2) along the ablation line (Ppeak-A2) and from the end of the P wave (Pend) to A2 (Pend-A2) were investigated before and after complete block in the first 100 patients (training set). In the next 25 patients (validation set), Ppeak-A2 and Pend-A2 intervals were prospectively assessed to determine CTI block. RESULTS: The mean Ppeak-A2 and Pend-A2 immediately before complete block were - 15±24 and - 39±23 ms compared to 49 ± 17 and 21 ± 16 ms after CTI block (P < 0.0001). Ppeak-A2 ≥ 20 ms and Pend-A2 ≥ 0 ms predicted CTI block with 98% sensitivity and 95% specificity and 96% sensitivity and 100% specificity, respectively. In the validation set, the positive and negative predictive values of Ppeak-A2 ≥ 20 ms or Pend-A2 ≥ 0 ms were 100 and 96%, respectively. The diagnostic accuracy was 98%. CONCLUSIONS: During pacing from the CS, the temporal relationship between the P wave in lead V1 and A2 is a simple and reliable indicator of complete block during RFA of CTI-AFL.

Insights from Novel Noninvasive CT and ECG Imaging Modalities on Electromechanical Myocardial Activation in a Canine Model of Ischemic Dyssynchronous Heart Failure.

INTRODUCTION: The interplay between electrical activation and mechanical contraction patterns is hypothesized to be central to reduced effectiveness of cardiac resynchronization therapy (CRT). Furthermore, complex scar substrates render CRT less effective. We used novel cardiac computed tomography (CT) and noninvasive electrocardiographic imaging (ECGI) techniques in an ischemic dyssynchronous heart failure (DHF) animal model to evaluate electrical and mechanical coupling of cardiac function, tissue viability, and venous accessibility of target pacing regions. METHODS AND RESULTS: Ischemic DHF was induced in 6 dogs using coronary occlusion, left bundle ablation and tachy RV pacing. Full body ECG was recorded during native rhythm followed by volumetric first-pass and delayed enhancement CT. Regional electrical activation were computed and overlaid with segmented venous anatomy and scar regions. Reconstructed electrical activation maps show consistency with LBBB starting on the RV and spreading in a "U-shaped" pattern to the LV. Previously reported lines of slow conduction are seen parallel to anterior or inferior interventricular grooves. Mechanical contraction showed large septal to lateral wall delay (80 ± 38 milliseconds vs. 123 ± 31 milliseconds, P = 0.0001). All animals showed electromechanical correlation except dog 5 with largest scar burden. Electromechanical decoupling was largest in basal lateral LV segments. CONCLUSION: We demonstrated a promising application of CT in combination with ECGI to gain insight into electromechanical function in ischemic dyssynchronous heart failure that can provide useful information to study regional substrate of CRT candidates.

Evaluation of a novel high-resolution mapping technology for ablation of recurrent scar-related atrial tachycardias.

BACKGROUND: Rhythmia is a new technology capable of rapid and high-resolution mapping. However, its potential advantage over existing technologies in mapping complex scar-related atrial tachycardias (ATs) has not yet been evaluated. OBJECTIVE: The purpose of this study was to examine the utility of Rhythmia for mapping scar-related ATs in patients who had failed previous ablation procedure(s). METHODS: This multicenter study included 20 patients with recurrent ATs within 2 years after a previous ablation procedure (1.8 ± 0.7 per patient). In all cases, the ATs could not be adequately mapped during the index procedure because of scar with fractionated electrograms, precluding accurate time annotation, frequent change in the tachycardia in response to pacing, and/or degeneration into atrial fibrillation. These patients underwent repeat mapping and ablation procedure with Rhythmia. RESULTS: From a total of 28 inducible ATs, 24 were successfully mapped. Eighteen ATs (75%) terminated during radiofrequency ablation and 4 (16.6%) with catheter pressure or entrainment from the site of origin or isthmus. Two ATs that were mapped to the interatrial septum slowed but did not terminate with ablation. In 21 of 24 ATs the mechanism was macroreentry, while in 3 of 24 the mechanism was focal. Interestingly, in 5 patients with previously failed ablation of an allegedly "focal" tachycardia, high-resolution mapping demonstrated macroreentrant arrhythmia. The mean mapping time was 28.6 ± 17 minutes, and the mean radiofrequency ablation time to arrhythmia termination was 3.2 ± 2.6 minutes. During a mean follow-up of 7.5 ± 3.1 months, 15 of 20 patients (75%) were free of AT recurrences. CONCLUSION: The Rhythmia mapping system may be advantageous for mapping complex scar-related ATs.

Biophysical Modeling Predicts Ventricular Tachycardia Inducibility and Circuit Morphology: A Combined Clinical Validation and Computer Modeling Approach.

INTRODUCTION: Computational modeling of cardiac arrhythmogenesis and arrhythmia maintenance has made a significant contribution to the understanding of the underlying mechanisms of arrhythmia. We hypothesized that a cardiac model using personalized electro-anatomical parameters could define the underlying ventricular tachycardia (VT) substrate and predict reentrant VT circuits. We used a combined modeling and clinical approach in order to validate the concept. METHODS AND RESULTS: Non-contact electroanatomic mapping studies were performed in 7 patients (5 ischemics, 2 non-ischemics). Three ischemic cardiomyopathy patients underwent a clinical VT stimulation study. Anatomical information was obtained from cardiac magnetic resonance imaging (CMR) including high-resolution scar imaging. A simplified biophysical mono-domain action potential model personalized with the patients' anatomical and electrical information was used to perform in silico VT stimulation studies for comparison. The personalized in silico VT stimulations were able to predict VT inducibility as well as the macroscopic characteristics of the VT circuits in patients who had clinical VT stimulation studies. The patients with positive clinical VT stimulation studies had wider distribution of action potential duration restitution curve (APD-RC) slopes and APDs than the patient with a negative VT stimulation study. The exit points of reentrant VT circuits encompassed a higher percentage of the maximum APD-RC slope compared to the scar and non-scar areas, 32%, 4%, and 0.2%, respectively. CONCLUSIONS: VT stimulation studies can be simulated in silico using a personalized biophysical cardiac model. Myocardial spatial heterogeneity of APD restitution properties and conductivity may help predict the location of crucial entry/exit points of reentrant VT circuits.

Percolation as a mechanism to explain atrial fractionated electrograms and reentry in a fibrosis model based on imaging data.

BACKGROUND: Complex fractionated atrial electrograms (CFAEs) have long been associated with proarrhythmic alterations in atrial structure or electrophysiology. Structural alterations disrupt and slow smoothly propagating wavefronts, leading to wavebreaks and electrogram (EGM) fractionation, but the exact nature and characteristics for arrhythmia remain unknown. Clinically, in atrial fibrillation (AF) patients, increases in frequency, whether by pacing or fibrillation, increase EGM fractionation and duration, and reentry can occur in relation with the conduction disturbance. Recently, percolation has been proposed as an arrhythmogenic mechanism, but its role in AF has not been investigated. OBJECTIVE: We sought to determine if percolation can explain reentry formation and EGM behavior observed in AF patients. METHODS: Computer models of fibrotic tissue with different densities were generated based on late gadolinium-enhanced magnetic resonance images, using pixel intensity as a fibrosis probability to avoid an arbitrary binary threshold. Clinical pacing protocols were followed to induce AF, and EGMs were computed. RESULTS: Reentry could be elicited, with a biphasic behavior dependent on fibrotic density. CFAEs were recorded above fibrotic regions, and consistent with clinical data, EGM duration and fractionation increased with more rapid pacing. CONCLUSION: These findings confirm percolation as a potential mechanism to explain AF in humans and give new insights into dynamics underlying conduction distortions and fractionated signals in excitable media, which correlate well with the experimental findings in fibrotic regions. The greater understanding of the different patterns of conduction changes and related EGMs could lead to more individualized and effective approaches to AF ablation therapy.

Ablation of Persistent Atrial Fibrillation Targeting Low-Voltage Areas With Selective Activation Characteristics.

BACKGROUND: Complex-fractionated atrial electrograms and atrial fibrosis are associated with maintenance of persistent atrial fibrillation (AF). We hypothesized that pulmonary vein isolation (PVI) plus ablation of selective atrial low-voltage sites may be more successful than PVI only. METHODS AND RESULTS: A total of 85 consecutive patients with persistent AF underwent high-density atrial voltage mapping, PVI, and ablation at low-voltage areas (LVA < 0.5 mV in AF) associated with electric activity lasting > 70% of AF cycle length on a single electrode (fractionated activity) or multiple electrodes around the circumferential mapping catheter (rotational activity) or discrete rapid local activity (group I). The procedural end point was AF termination. Arrhythmia freedom was compared with a control group (66 patients) undergoing PVI only (group II). PVI alone was performed in 23 of 85 (27%) patients of group I with low amount (< 10% of left atrial surface area) of atrial low voltage. Selective atrial ablation in addition to PVI was performed in 62 patients with termination of AF in 45 (73%) after 11 ± 9 minutes radiofrequency delivery. AF-termination sites colocalized within LVA in 80% and at border zones in 20%. Single-procedural arrhythmia freedom at 13 months median follow-up was achieved in 59 of 85 (69%) patients in group I, which was significantly higher than the matched control group (31/66 [47%], P < 0.001). There was no significant difference in the success rate of patients in group I with a low amount of low voltage undergoing PVI only and patients requiring PVI+selective low-voltage ablation (P = 0.42). CONCLUSIONS: Ablation of sites with distinct activation characteristics within/at borderzones of LVA in addition to PVI is more effective than conventional PVI-only strategy for persistent AF. PVI only seems to be sufficient to treat patients with left atrial low voltage < 10%.

Association of Left Atrial Local Conduction Velocity With Late Gadolinium Enhancement on Cardiac Magnetic Resonance in Patients With Atrial Fibrillation.

BACKGROUND: Prior studies have demonstrated regional left atrial late gadolinium enhancement (LGE) heterogeneity on magnetic resonance imaging. Heterogeneity in regional conduction velocities is a critical substrate for functional reentry. We sought to examine the association between left atrial conduction velocity and LGE in patients with atrial fibrillation. METHODS AND RESULTS: LGE imaging and left atrial activation mapping were performed during sinus rhythm in 22 patients before pulmonary vein isolation. The locations of 1468 electroanatomic map points were registered to the corresponding anatomic sites on 469 axial LGE image planes. The local conduction velocity at each point was calculated using previously established methods. The myocardial wall thickness and image intensity ratio defined as left atrial myocardial LGE signal intensity divided by the mean left atrial blood pool intensity was calculated for each mapping site. The local conduction velocity and image intensity ratio in the left atrium (mean ± SD) were 0.98 ± 0.46 and 0.95 ± 0.26 m/s, respectively. In multivariable regression analysis, clustered by patient, and adjusting for left atrial wall thickness, conduction velocity was associated with the local image intensity ratio (0.20 m/s decrease in conduction velocity per increase in unit image intensity ratio, P<0.001). CONCLUSIONS: In this clinical in vivo study, we demonstrate that left atrial myocardium with increased gadolinium uptake has lower local conduction velocity. Identification of such regions may facilitate the targeting of the substrate for reentrant arrhythmias.

Spatial Relationship of Focal Impulses, Rotors and Low Voltage Zones in Patients With Persistent Atrial Fibrillation.

INTRODUCTION: Focal impulses (FI) and rotors are sources associated with the initiation and maintenance of atrial fibrillation (AF). Their ablation results in a lower recurrence rate. The aim of this study was to characterize for the first time the spatial relationship between such sources and atrial low voltage zones (LVZ) representing fibrosis. METHODS: Twenty-five consecutive patients undergoing their first ablation for persistent AF were included. Voltage mapping of both atria was done during AF. Endocardial mapping of FI and rotors (sources) was performed using a basket catheter and displayed using RhythmView(TM) (Topera Inc.) before ablation. Spatial relationship of LVZ and sources was analyzed. RESULTS: LVZs covered 13 ± 12% of right atrial (RA) endocardial surface and 33 ± 25% of left atrial (LA) endocardial surface. The median number of sources was 1 [1-3] in RA and 3 [1-4] in LA. Of LA sources, 18 (30%) were definitely not associated with LVZs or pulmonary vein (PV) antra. Of RA sources, 32 (84%) were remote from LVZ. During ablation of such sources substantial cycle length (CL) prolongation or AF conversion occurred in 11/23 patients (48%). Altogether, 8/11 (73%) of these pertinent sources were located remotely from LVZ and PV antra. CONCLUSIONS: There is a wide discrepancy in distribution of LVZ areas and sites of identified rotors. Site and incidence of FIRM sources appear to be unpredictable with atrial substrate mapping. Further prospective, randomized studies are necessary to elucidate the impact of additional ablation of such sources in patients with persistent or longstanding persistent AF.

Catheter ablation for atrioventricular nodal reentrant tachycardia in patients with congenital heart disease.

BACKGROUND: Variability in atrioventricular (AV) node location in congenital heart disease (CHD) can make catheter ablation for atrioventricular nodal reentrant tachycardia (AVNRT) challenging. OBJECTIVE: The purpose of this study was to describe institutional technique and outcomes for slow pathway modification in a cohort with CHD. METHODS: The study consisted of a retrospective review of CHD patients who underwent study from 2001 to 2013 with a diagnosis of AVNRT. Outcomes for slow pathway modification were recorded. In cases in which ablation was deferred, the reasons for this choice were examined. RESULTS: Forty-nine patients (median age 19 years) were included. CHD anatomy involved d-transposition of the great arteries (n = 6), "congenitally corrected" transposition of the great arteries (n = 4), Ebstein anomaly (n = 4), tetralogy of Fallot (n = 5), venous anomalies (n = 8), single ventricle (n = 16), and miscellaneous (n = 6). Ablation was attempted in 39 patients, using radiofrequency energy in 24, cryoablation in 8, and both in 7. Acute success rate was 92% (36/39). One patient had first-degree block in response to cryoablation, but no other complications occurred. At median follow-up 32 months, 1 patient had AVNRT recurrence. Most of the 10 patients in whom ablation was deferred had single-ventricle anatomy with uncertain AV node location. CONCLUSION: Ablation for AVNRT in CHD can be accomplished successfully with attention to underlying anatomy and prior surgery. Patients with single ventricle are a difficult subgroup, and a pharmacologic approach may be indicated in some cases if node localization is ambiguous.

Impact of Voltage Mapping to Guide Whether to Perform Ablation of the Posterior Wall in Patients With Persistent Atrial Fibrillation.

BACKGROUND: Fibrosis as a substrate for atrial fibrillation (AF) has been shown in numerous preclinical models. Voltage mapping enables in vivo assessment of scar in the left atrium (LA), which can be targeted with catheter ablation. OBJECTIVE: We hypothesized that using the presence or absence of low voltage to guide ablation beyond pulmonary vein antral isolation (PVAI) will improve atrial arrhythmia (AF/AT)-free survival in persistent AF. METHODS AND RESULTS: Single-center retrospective analysis of 2 AF ablation strategies: (1) standard ablation (SA) versus (2) voltage-guided ablation (VGA). PVAI was performed in both groups. With SA, additional lesions beyond PVAI were performed at the discretion of the operator. With VGA, additional lesions to isolate the LA posterior wall were performed if voltage mapping of this region in sinus rhythm showed scar (LA voltage < 0.5 mV). AF-/AT-free endpoint was defined as no sustained AF/AT seen off antiarrhythmic medications after a 2-month postablation blanking period. Seventy-six patients underwent SA and 65 underwent VGA. Patients were well matched for comorbidities, LVEF, and left atrial size. Posterior wall ablation was performed in 57% of patient with SA compared to 42% with VGA. VGA ablation increased 1-year AF-/AT-free survival in patients when compared to SA (80% vs. 57%; P = 0.005). In a multivariate analysis, VGA was the only independent predictor of AF-/AT-free survival (hazard ratio of 0.30; P = 0.002). CONCLUSIONS: The presence of LA posterior wall scar may be an important ablation target in persistent AF. A prospective randomized trial is needed to confirm these data.

VT Recurrence After Ablation: Incomplete Ablation or Disease Progression? A Multicentric European Study.

AIM: To determine whether ventricular tachycardia (VT) recurrences in arrhythmogenic RV cardiomyopathy (ARVC) and nonischemic cardiomyopathy (NICM) are related to incomplete ablation or disease progression. METHODS: ARVC and NICM patients with two substrate maps of the same diseased ventricle with an interprocedural delay of ≥12 months were included. Disease progression was defined as ≥1 factor: scar area progression (PROG, +5%), ventricular remodeling (dilatation [+25 mL] or decreased ejection fraction [-5%EF]). Incomplete ablation was defined as index VT recurrence or ablation in previously unablated regions inside index scar without PROG. RESULTS: Twenty patients from nine centers were included (80% male 55 ± 16 years, 7 ARVC and 13 NICM, LVEF 43 ± 14%). Mean delay was 28 ± 18 months. Disease progression occurred in 75% with ventricular remodeling in 70%: ventricular dilation in 45% (ARVC [71%]; NICM [38%]), decreased EF in 60% [RVEF in ARVC (71%); LVEF in NICM (54%)], and scar progression in 50% (in ARVC [57%] and NICM [46%]). Index VT recurrence was observed in 40%. Redo ablation sites were located in previously unablated regions inside the index scar in 70% of patients. VT recurrence following the second procedure was seen in 25%. Fifteen percent died during a follow-up of 17 ± 17 months. CONCLUSION: Disease progression is the rule in ARVC and NICM while scar progression occurs in half. However, even if disease progression is frequently observed, incomplete index ablation is the most common finding, strongly suggesting the need for more extensive ablation.

Antiarrhythmic effects and potential mechanism of WenXin KeLi in cardiac Purkinje cells.

BACKGROUND: Previous studies have demonstrated that WenXin KeLi (WXKL), a traditional Chinese medicine, can exert antiarrhythmic properties through complex multichannel inhibition, but its pharmacologic effect remains to be elucidated, especially in the cardiac conductive system. OBJECTIVE: To explore the antiarrhythmic property of WXKL in cardiac Purkinje cells (PCs). METHODS: PCs were isolated from rabbit hearts and action potentials (APs) and ion currents were recorded by whole-cell patch clamp technique. Anemonia toxin II (ATX-II) and isoproterenol (ISO) were used to induce early or delayed afterdepolarizations (EADs, DADs) or triggered activities (TAs). RESULTS: WXKL (1 g/L and 5 g/L) significantly abbreviated the action potential duration (APD) of PCs in a dose- and rate-dependent manner. Treatment of PCs with ATX-II (2 nM) prolonged APD and induced EADs, which were significantly suppressed by WXKL. WXKL (1, 5 g/L) also inhibited ISO-induced EADs, DADs, and TAs. To reveal the ionic mechanisms, we studied the effects of WXKL on late sodium current (I(NaL)), peak sodium current (I(NaP)), and L-type calcium currents (ICaL) in PCs. WXKL-attenuated ATX-II (5 nM) induced I(NaL) augmentation and blocked I(NaL) with an IC50 of 4.3 ± 0.5 g/L, which is 3- to 4-fold more selective than that of I(NaP) (13.3 ± 0.9 g/L) and ICaL (17.6 ± 1.4 g/L). Moreover, WXKL exerted significantly less use-dependent block of I(NaP) than that of flecainide, indicating its lower proarrhythmic effect. CONCLUSIONS: WXKL exhibits antiarrhythmic properties in cardiac PCs via selective inhibition of I(NaL).

Box Isolation of Fibrotic Areas (BIFA): A Patient-Tailored Substrate Modification Approach for Ablation of Atrial Fibrillation.

BACKGROUND: Catheter ablation strategies beyond pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF) are less well defined. Increasing clinical data indicate that atrial fibrosis is a critical common left atrial (LA) substrate in AF patients (pts). OBJECTIVE: We applied a new substrate modification concept according to the individual fibrotic substrate as estimated from electroanatomic voltage mapping (EAVM) in 41 pts undergoing catheter ablation of AF. RESULTS: First, EAVM during sinus rhythm was done in redo cases of 10 pts with paroxysmal AF despite durable PVI. Confluent low-voltage areas (LVA) were found in all pts and were targeted with circumferential isolation, so-called box isolation of fibrotic areas (BIFA). This strategy led to stable sinus rhythm in 9/10 pts and was transferred prospectively to first procedures of 31 pts with nonparoxysmal AF. In 13 pts (42%), no LVA (<0.5 mV) were identified, and only PVI was performed. In 18 pts (58%), additional BIFA strategies were applied (posterior box in 5, anterior box in 7, posterior plus anterior box in 5, no box in 1 due to diffuse fibrosis). Mean follow-up was 12.5 ± 2.4 months. Single-procedure freedom from AF/atrial tachycardia was achieved in 72.2% of pts and in 83.3% of pts with 1.17 procedures/patient. CONCLUSIONS: In approximately 40% of pts with nonparoxysmal AF, no substantial LVA were identified, and PVI alone showed high success rate. In pts with paroxysmal AF despite durable PVI and in approximately 60% of pts with nonparoxysmal AF, individually localized LVA were identified and could be targeted successfully with the BIFA strategy.

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.