Sanjiv Narayan

All Publications

• Safety of transvenous cardiac defibrillator and magnetic titanium beads system for gastroesophageal reflux disease: a case report. Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing Vasireddi, S. K., Greif, S., Fazal, M., Wei, C., Gomez, S., Shah, S., Rogers, A. J., Narayan, S. M., Wang, P. J., Kapoor, R., Baykaner, T. 2023

  View details for DOI 10.1007/s10840-023-01604-x

  View details for PubMedID 37421563

  View details for PubMedCentralID 3667475

• Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors. Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing Wei, C., Fazal, M., Loh, A., Kapoor, R., Gomez, S. E., Shah, S., Rogers, A. J., Narayan, S. M., Wang, P. J., Witteles, R. M., Perino, A. C., Cheng, P., Rhee, J. W., Baykaner, T. 2023

  Abstract

  Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of hematologic malignancies. Limited studies have shown an association between treatment-limiting arrhythmias and TKI, particularly ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. We sought to comprehensively assess the arrhythmia burden in patients receiving ibrutinib vs non-BTK TKI vs non-TKI therapies.We performed a retrospective analysis of consecutive patients who received long-term cardiac event monitors while on ibrutinib, non-BTK TKIs, or non-TKI therapy for a hematologic malignancy between 2014 and 2022.One hundred ninety-three patients with hematologic malignancies were included (ibrutinib = 72, non-BTK TKI = 46, non-TKI therapy = 75). The average duration of TKI therapy was 32 months in the ibrutinib group vs 64 months in the non-BTK TKI group (p = 0.003). The ibrutinib group had a higher prevalence of atrial fibrillation (n = 32 [44%]) compared to the non-BTK TKI (n = 7 [15%], p = 0.001) and non-TKI (n = 15 [20%], p = 0.002) groups. Similarly, the prevalence of non-sustained ventricular tachycardia was higher in the ibrutinib group (n = 31, 43%) than the non-BTK TKI (n = 8 [17%], p = 0.004) and non-TKI groups (n = 20 [27%], p = 0.04). TKI therapy was held in 25% (n = 18) of patients on ibrutinib vs 4% (n = 2) on non-BTK TKIs (p = 0.005) secondary to arrhythmias.In this large retrospective analysis of patients with hematologic malignancies, patients receiving ibrutinib had a higher prevalence of atrial and ventricular arrhythmias compared to those receiving other TKI, with a higher rate of treatment interruption due to arrhythmias.

  View details for DOI 10.1007/s10840-023-01575-z

  View details for PubMedID 37256462

• Atrial Fibrillation Ablation Outcome Prediction with a Machine Learning Fusion Framework Incorporating Cardiac Computed Tomography. Journal of cardiovascular electrophysiology Razeghi, O., Kapoor, R., Alhusseini, M. I., Fazal, M., Tang, S., Roney, C. H., Rogers, A. J., Lee, A., Wang, P. J., Clopton, P., Rubin, D. L., Narayan, S. M., Niederer, S., Baykaner, T. 2023

  Abstract

  BACKGROUND: Structural changes in the left atrium (LA) modestly predict outcomes in patients undergoing catheter ablation for atrial fibrillation (AF). Machine learning (ML) is a promising approach to personalize AF management strategies and improve predictive risk models after catheter ablation by integrating atrial geometry from cardiac computed tomography (CT) scans and patient-specific clinical data. We hypothesized that ML approaches based on a patient's specific data can identify responders to AF ablation.METHODS: Consecutive patients undergoing AF ablation, who had preprocedural CT scans, demographics, and 1-year follow-up data, were included in the study for a retrospective analysis. The inputs of models were CT-derived morphological features from left atrial segmentation (including the shape, volume of the LA, LA appendage, and pulmonary vein ostia) along with deep features learned directly from raw CT images, and clinical data. These were merged intelligently in a framework to learn their individual importance and produce the optimal classification.RESULTS: 321 patients (64.2 + 10.6 years, 69% male, 40% paroxysmal AF) were analyzed. Post 10-fold nested cross-validation, the model trained to intelligently merge and learn appropriate weights for clinical, morphological, and imaging data (AUC 0.821) outperformed those trained solely on clinical data (AUC 0.626), morphological (AUC 0.659) or imaging data (AUC 0.764).CONCLUSION: Our machine learning approach provides an end-to-end automated technique to predict AF ablation outcomes using deep learning from CT images, derived structural properties of LA, augmented by incorporation of clinical data in a merged ML framework. This can help develop personalized strategies for patient selection in invasive management of AF. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/jce.15890

  View details for PubMedID 36934383

• Quantifying a spectrum of clinical response in atrial tachyarrhythmias using spatiotemporal synchronization of electrograms. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Ganesan, P., Deb, B., Feng, R., Rodrigo, M., Ruiperez-Campillo, S., Rogers, A. J., Clopton, P., Wang, P. J., Zeemering, S., Schotten, U., Rappel, W., Narayan, S. M. 2023

  Abstract

  AIMS: There is a clinical spectrum for atrial tachyarrhythmias wherein most patients with atrial tachycardia (AT) and some with atrial fibrillation (AF) respond to ablation, while others do not. It is undefined if this clinical spectrum has pathophysiological signatures. This study aims to test the hypothesis that the size of spatial regions showing repetitive synchronized electrogram (EGM) shapes over time reveals a spectrum from AT, to AF patients who respond acutely to ablation, to AF patients without acute response.METHODS AND RESULTS: We studied n = 160 patients (35% women, 65.0 ± 10.4 years) of whom (i) n = 75 had AF terminated by ablation propensity matched to (ii) n = 75 without AF termination and (iii) n = 10 with AT. All patients had mapping by 64-pole baskets to identify areas of repetitive activity (REACT) to correlate unipolar EGMs in shape over time. Synchronized regions (REACT) were largest in AT, smaller in AF termination, and smallest in non-termination cohorts (0.63 ± 0.15, 0.37 ± 0.22, and 0.22 ± 0.18, P < 0.001). Area under the curve for predicting AF termination in hold-out cohorts was 0.72 ± 0.03. Simulations showed that lower REACT represented greater variability in clinical EGM timing and shape. Unsupervised machine learning of REACT and extensive (50) clinical variables yielded four clusters of increasing risk for AF termination (P < 0.01, chi2), which were more predictive than clinical profiles alone (P < 0.001).CONCLUSION: The area of synchronized EGMs within the atrium reveals a spectrum of clinical response in atrial tachyarrhythmias. These fundamental EGM properties, which do not reflect any predetermined mechanism or mapping technology, predict outcome and offer a platform to compare mapping tools and mechanisms between AF patient groups.

  View details for DOI 10.1093/europace/euad055

  View details for PubMedID 36932716

• Can Machine Learning Disrupt the Prediction of Sudden Death? Journal of the American College of Cardiology Narayan, S. M., Rogers, A. J. 2023; 81 (10): 962-963

  View details for DOI 10.1016/j.jacc.2022.12.027

  View details for PubMedID 36889874

• OBSTRUCTIVE SLEEP APNEA PORTENDS STROKE IN YOUNG INDIVIDUALS WITHOUT ATRIAL FIBRILLATION: A LARGE REGISTRY STUDY Deb, B., Vasireddi, S., Bhatia, N. K., Rogers, A. J., Clopton, P., Baykaner, T., Ganesan, P., Feng, R., Azizi, Z., Narayan, S. M. ELSEVIER SCIENCE INC. 2023: 130

  View details for Web of Science ID 000990866100131

• Ambient Circulation Surrounding an Ablation Catheter Tip Affects Ablation Lesion Characteristics. Journal of cardiovascular electrophysiology Nussinovitch, U., Wang, P., Babakhanian, M., Narayan, S. M., Viswanathan, M., Badhwar, N., Zheng, L., Sauer, W. H., Nguyen, D. T. 2023

  Abstract

  The association between ambient circulating environments (CE) and ablation lesions has been largely underexplored.Viable bovine myocardium was placed in a saline bath in an ex vivo endocardial model. RF ablation was performed using 3 different ablation catheters: 3.5mm open irrigated (OI), 4 mm, and 8 mm. Variable flow rates of surrounding bath fluids were applied to simulate standard flow, high flow, and no flow. For in-vivo epicardial ablation, 24 rats underwent a single OI ablation and performed with circulating saline (30 ml/min; n=12), vs. those immersed in saline without circulation (n=12).High flow reduced ablation lesion volumes for all 3 catheters. In no flow endocardial CE, both 4 mm and OI catheters produced smaller lesions compared to standard flow. However, the 8 mm catheter produced the largest lesions in a no flow CE. Ablation performed in an in-vivo model with CE resulted in smaller lesions compared to ablation performed in a no-flow environment. No statistically significant differences in steam pops were found amongst the groups.A higher endocardial CE flow can decrease RF effectiveness. Cardiac tissue subjected to no endocardial CE flow may also limit RF for 4 mm catheters, but not for OI catheters; these findings may have implications for RF ablation safety and efficacy, especially, in the epicardial space without circulating fluid or in the endocardium under varying flow conditions. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/jce.15874

  View details for PubMedID 36852908

• Machine learning of electrophysiological signals for the prediction of ventricular arrhythmias: systematic review and examination of heterogeneity between studies. EBioMedicine Kolk, M. Z., Deb, B., Ruipérez-Campillo, S., Bhatia, N. K., Clopton, P., Wilde, A. A., Narayan, S. M., Knops, R. E., Tjong, F. V. 2023; 89: 104462

  Abstract

  Ventricular arrhythmia (VA) precipitating sudden cardiac arrest (SCD) is among the most frequent causes of death and pose a high burden on public health systems worldwide. The increasing availability of electrophysiological signals collected through conventional methods (e.g. electrocardiography (ECG)) and digital health technologies (e.g. wearable devices) in combination with novel predictive analytics using machine learning (ML) and deep learning (DL) hold potential for personalised predictions of arrhythmic events.This systematic review and exploratory meta-analysis assesses the state-of-the-art of ML/DL models of electrophysiological signals for personalised prediction of malignant VA or SCD, and studies potential causes of bias (PROSPERO, reference: CRD42021283464). Five electronic databases were searched to identify eligible studies. Pooled estimates of the diagnostic odds ratio (DOR) and summary area under the curve (AUROC) were calculated. Meta-analyses were performed separately for studies using publicly available, ad-hoc datasets, versus targeted clinical data acquisition. Studies were scored on risk of bias by the PROBAST tool.2194 studies were identified of which 46 were included in the systematic review and 32 in the meta-analysis. Pooling of individual models demonstrated a summary AUROC of 0.856 (95% CI 0.755-0.909) for short-term (time-to-event up to 72 h) prediction and AUROC of 0.876 (95% CI 0.642-0.980) for long-term prediction (time-to-event up to years). While models developed on ad-hoc sets had higher pooled performance (AUROC 0.919, 95% CI 0.867-0.952), they had a high risk of bias related to the re-use and overlap of small ad-hoc datasets, choices of ML tool and a lack of external model validation.ML and DL models appear to accurately predict malignant VA and SCD. However, wide heterogeneity between studies, in part due to small ad-hoc datasets and choice of ML model, may reduce the ability to generalise and should be addressed in future studies.This publication is part of the project DEEP RISK ICD (with project number 452019308) of the research programme Rubicon which is (partly) financed by the Dutch Research Council (NWO). This research is partly funded by the Amsterdam Cardiovascular Sciences (personal grant F.V.Y.T).

  View details for DOI 10.1016/j.ebiom.2023.104462

  View details for PubMedID 36773349

• Reduction in long-term mortality using remote device monitoring in a large real-world population of patients with implantable defibrillators. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Kolk, M. Z., Narayan, S. M., Clopton, P., Wilde, A. A., Knops, R. E., Tjong, F. V. 2023

  Abstract

  Remote monitoring (RM) for implantable cardioverter-defibrillators (ICDs) is advocated for the potential of early detection of disease progression and device dysfunction. While studies have examined the effect of RM on clinical outcomes in carefully selected populations of heart failure patients implanted with ICDs from a single vendor, there is a paucity of data in real-world patients. We aimed to assess the long-term effect of RM in a representative ICD population using real-world data.This is an observational retrospective longitudinal study of 1004 patients implanted with an ICD or cardiac resynchronization therapy device (CRT-D) from all device vendors between 2010 and 2021. Patients started on RM (N = 403) within 90 days following de novo device implantation and yearly in-office visits were compared with patients with only bi-yearly in-office follow-up (non-RM, N = 601). In a propensity score matched cohort of 430 patients (mean age 61.4 ± 14.3 years, 26.7% female), all-cause mortality at 4-year was 12.6% in the RM and 27.7% in the non-RM group [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.32-0.82; P = 0.005]. No difference in inappropriate ICD-therapy (HR 1.90, 95% CI 0.86-4.21; P = 0.122) was observed. The risk of appropriate ICD-therapy (HR 1.71, 95% CI 1.07-2.74; P = 0.026) was higher in the RM group.Remote monitoring was associated with a reduction in long-term all-cause and cardiac mortality compared with traditional office visits in a real-world ICD population.

  View details for DOI 10.1093/europace/euac280

  View details for PubMedID 36636951

• Predicting acute termination and non-termination during ablation of human atrial fibrillation using quantitative indices. Frontiers in physiology Kappel, C., Reiss, M., Rodrigo, M., Ganesan, P., Narayan, S. M., Rappel, W. J. 2022; 13: 939350

  Abstract

  Background: Termination of atrial fibrillation (AF), the most common arrhythmia in the United States, during catheter ablation is an attractive procedural endpoint, which has been associated with improved long-term outcome in some studies. It is not clear, however, whether it is possible to predict termination using clinical data. We developed and applied three quantitative indices in global multielectrode recordings of AF prior to ablation: average dominant frequency (ADF), spectral power index (SPI), and electrogram quality index (EQI). Methods: In N = 42 persistent AF patients (65 ± 9 years, 14% female) we collected unipolar electrograms from 64-pole baskets (Abbott, CA). We studied N = 17 patients in whom AF terminated during ablation ("Term") and N = 25 in whom it did not ("Non-term"). For each index, we determined its ability to predict ablation by computing receiver operating characteristic (ROC) and calculated the area under the curve (AUC). Results: The ADF did not differ for Term and Non-term patients at 5.28 ± 0.82 Hz and 5.51 ± 0.81 Hz, respectively (p = 0.34). Conversely, the SPI for these two groups was. 0.85 (0.80-0.92) and 0.97 (0.93-0.98) and the EQI was 0.61 (0.58-0.64) and 0.56 (0.55-0.59) (p < 0.0001). The AUC for predicting AF termination for the SPI was 0.85 ([0.68, 0.95] 95% CI), and for the EQI, 0.86 ([0.72, 0.95] 95% CI). Conclusion: Both the EQI and the SPI may provide a useful clinical tool to predict procedural ablation outcome in persistent AF patients. Future studies are required to identify which physiological features of AF are revealed by these indices and hence linked to AF termination or non-termination.

  View details for DOI 10.3389/fphys.2022.939350

  View details for PubMedID 36483297

  View details for PubMedCentralID PMC9725096

• Tyrosine kinase inhibitor-associated ventricular arrhythmias: a case series and review of literature. Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing Fazal, M., Wei, C., Chuy, K. L., Hussain, K., Gomez, S. E., Ba, S. S., Pietrasik, G., Yadav, N., Ghazizadeh, Z., Kapoor, R., Witteles, R. M., Blackmon, A., Wang, P. J., John, R. M., Narayan, S. M., Cheng, P., Rhee, J., Baykaner, T. 2022

  Abstract

  BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been increasingly used as first-line therapy in hematologic and solid-organ malignancies. Multiple TKIs have been linked with the development of cardiovascular complications, especially atrial arrhythmias, but data on ventricular arrhythmias (VAs) is scarce.METHODS: Herein we describe five detailed cases of VAs related to TKI use in patients with varied baseline cardiovascular risk factors between 2019 and 2022 at three centers. Individual chart review was conducted retrospectively.RESULTS: Patient ages ranged from 43 to 83years. Three patients were on Bruton's TKI (2 ibrutinib and 1 zanubrutinib) at the time of VAs; other TKIs involved were afatinib and dasatinib. Three patients had a high burden of non-sustained ventricular tachycardia (NSVT) requiring interventions, whereas two patients had sustained VAs. While all patients in our case series had significant improvement in VA burden after TKI cessation, two patients required new long-term antiarrhythmic drug therapy, and one had an implantable defibrillator cardioverter (ICD) placed due to persistent VAs after cessation of TKI therapy. One patient reinitiated TKI therapy after control of arrhythmia was achieved with antiarrhythmic drug therapy.CONCLUSIONS: Given the expanding long-term use of TKIs among a growing population of cancer patients, it is critical to acknowledge the association of TKIs with cardiovascular complications such as VAs, to characterize those at risk, and deploy preventive and therapeutic measures to avoid such complications and interference with oncologic therapy. Further efforts are warranted to develop monitoring protocols and optimal treatment strategies for TKI-induced VAs.

  View details for DOI 10.1007/s10840-022-01400-z

  View details for PubMedID 36411365

• Opportunities and challenges in heart rhythm research: Rationale and development of an electrophysiology collaboratory HEART RHYTHM Nguyen, D. T., Bilchick, K. C., Narayan, S. M., Chung, M. K., Thomas, K. L., Laurita, K. R., Vaseghi, M., Sandhu, R., Chelu, M. G., Kannankeril, P. J., Packer, D. L., McManus, D. D., Verma, A., Singleton, M., Tarakji, K., Al-Khatib, S. M., Kaltman, J. R., Balijepalli, R. C., Van Hare, G. F., Hurwitz, J. L., Russo, A. M., Kusumoto, F. M., Albert, C. M. 2022; 19 (11): 1927-1945

  View details for DOI 10.1016/j.hrthm.2022.08.004

  View details for Web of Science ID 000882631300034

• Needle-Tipped Catheter Ablation of Papillary Muscle Results in Deeper and Larger Ablation Lesions. Journal of cardiovascular translational research Nussinovitch, U., Wang, P., Babakhanian, M., Narayan, S. M., Viswanathan, M., Badhwar, N., Zheng, L., Sauer, W. H., Nguyen, D. T. 2022

  Abstract

  Ventricular tachycardia associated with papillary muscle (PM) is often refractory to standard radiofrequency ablation (RFA). The needle-tipped ablation catheter (NT-AC) has been used to treat deep intramyocardial substrates, but its use for PM has not been characterized. Using an ex vivo experimental platform, both 3mm and 6mm NT-AC created larger ablation lesion volumes and depths than open-irrigated ablation catheter did (OI-AC; e.g., 57.12±9.70mm3 and 2.42±0.22mm, respectively; p<0.01 for all comparisons). Longer NT-AC extension (6mm) resulted in greater ablation lesion volumes and maximum depths (e.g., 333.14±29.13mm3 and 6.46±0.29mm, respectively, compared to the shorter 3mm NT-AC extension, 143.33±12.77mm3, and 4.46±0.14mm; both p<0.001). There were no steam pops. In conclusion, for PM ablation, the NT-AC was able to achieve ablation lesions that were larger and deeper than with conventional OI-AC. Ablation of PM may be another application for needle-tip ablation. Further studies are warranted to establish long-term safety and efficacy in human studies.

  View details for DOI 10.1007/s12265-022-10331-z

  View details for PubMedID 36264437

• Racial, ethnic, and sex disparities in atrial fibrillation management: rate and rhythm control. Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing Gomez, S. E., Fazal, M., Nunes, J. C., Shah, S., Perino, A. C., Narayan, S. M., Tamirisa, K. P., Han, J. K., Rodriguez, F., Baykaner, T. 2022

  Abstract

  BACKGROUND: Atrial fibrillation (AF) affects around 6 million Americans. AF management involves pharmacologic therapy and/or interventional procedures to control rate and rhythm, as well as anticoagulation for stroke prevention. Different populations may respond differently to distinct management strategies. This review will describe disparities in rate and rhythm control and their impact on outcomes among women and historically underrepresented racial and/or ethnic groups.METHODS: This is a narrative review exploring the topic of sex and racial and/or ethnic disparities in rate and rhythm management of AF. We describe basic terminology, summarize AF epidemiology, discuss diversity in clinical research, and review landmark clinical trials.RESULTS: Despite having higher rates of traditional AF risk factors, Black and Hispanic adults have lower risk of AF than non-Hispanic White (NHW) patients, although those with AF experience more severe symptoms and report lower quality-of-life scores than NHW patients with AF. NHW patients receive antiarrhythmic drugs, cardioversions, and invasive therapies more frequently than Black and Hispanic patients. Women have lower rates of AF than men, but experience more severe symptoms, heart failure, stroke, and death after AF diagnosis. Women and people from diverse racial and ethnic backgrounds are inadequately represented in AF trials; prevalence findings may be a result of underdetection.CONCLUSION: Race, ethnicity, and gender are social determinants of health that may impact the prevalence, evolution, and management of AF. This impact reflects differences in biology as well as disparities in treatment and representation in clinical trials.

  View details for DOI 10.1007/s10840-022-01383-x

  View details for PubMedID 36224481

• Machine Learning of Adipose Tissue in Atrial Fibrillation. Heart rhythm Baykaner, T., Narayan, S. 2022

  View details for DOI 10.1016/j.hrthm.2022.08.027

  View details for PubMedID 36041687

• Machine Learning-Enabled Multimodal Fusion of Intra-Atrial and Body Surface Signals in Prediction of Atrial Fibrillation Ablation Outcomes. Circulation. Arrhythmia and electrophysiology Tang, S., Razeghi, O., Kapoor, R., Alhusseini, M. I., Fazal, M., Rogers, A. J., Rodrigo Bort, M., Clopton, P., Wang, P., Rubin, D., Narayan, S. M., Baykaner, T. 2022: 101161CIRCEP122010850

  Abstract

  BACKGROUND: Machine learning is a promising approach to personalize atrial fibrillation management strategies for patients after catheter ablation. Prior atrial fibrillation ablation outcome prediction studies applied classical machine learning methods to hand-crafted clinical scores, and none have leveraged intracardiac electrograms or 12-lead surface electrocardiograms for outcome prediction. We hypothesized that (1) machine learning models trained on electrograms or ECG signals can perform better at predicting patient outcomes after atrial fibrillation ablation than existing clinical scores and (2) multimodal fusion of electrogram, ECG, and clinical features can further improve the prediction of patient outcomes.METHODS: Consecutive patients who underwent catheter ablation between 2015 and 2017 with panoramic left atrial electrogram before ablation and clinical follow-up for at least 1 year following ablation were included. Convolutional neural network and a novel multimodal fusion framework were developed for predicting 1-year atrial fibrillation recurrence after catheter ablation from electrogram, ECG signals, and clinical features. The models were trained and validated using 10-fold cross-validation on patient-level splits.RESULTS: One hundred fifty-six patients (64.5±10.5 years, 74% male, 42% paroxysmal) were analyzed. Using electrogram signals alone, the convolutional neural network achieved an area under the receiver operating characteristics curve of 0.731, outperforming the existing APPLE scores (area under the receiver operating characteristics curve=0.644) and CHA2DS2-VASc scores (area under the receiver operating characteristics curve=0.650). Similarly using 12-lead ECG alone, the convolutional neural network achieved an AUROC of 0.767. Combining electrogram, ECG, and clinical features, the fusion model achieved an AUROC of 0.859, outperforming single and dual modality models.CONCLUSIONS: Deep neural networks trained on electrogram or ECG signals improved the prediction of catheter ablation outcome compared with existing clinical scores, and fusion of electrogram, ECG, and clinical features further improved the prediction. This suggests the promise of using machine learning to help treatment planning for patients after catheter ablation.

  View details for DOI 10.1161/CIRCEP.122.010850

  View details for PubMedID 35867397

• Mapping Atrial Fibrillation After Surgical Therapy to Guide Endocardial Ablation. Circulation. Arrhythmia and electrophysiology Bhatia, N. K., Shah, R. L., Deb, B., Pong, T., Kapoor, R., Rogers, A., Badhwar, N., Brodt, C., Wang, P. J., Narayan, S. M., Lee, A. M. 2022: 101161CIRCEP121010502

  Abstract

  Surgical ablation for atrial fibrillation (AF) can be effective, yet has mixed results. It is important to improve the success of AF surgery, yet unclear which endocardial lesions will best augment surgical lesion sets in individual patients. We addressed this question by systematically mapping AF endocardially after surgical ablation and relating findings to early recurrence.We studied 81 consecutive patients undergoing epicardial surgical ablation (stage 1 hybrid), of whom 64 proceeded to endocardial catheter mapping and ablation (stage 2). Stage 2 comprised high-density mapping of pulmonary vein (PV) or posterior wall (PW) reconnections, low-voltage zones (LVZs), and potential localized AF drivers. We related findings to postsurgical recurrence of AF.Mapping at stage 2 revealed PW isolation reconnection in 59.4%, PV isolation reconnection in 28.1%, and LVZ in 42.2% of patients. Postsurgical recurrence of AF occurred in 36 patients (56.3%), particularly those with long-standing persistent AF (P=0.017), but had no relationship to reconnection of PVs (P=0.53) or PW isolation (P=0.75) when compared with those without postsurgical recurrence of AF. LVZs were more common in patients with postsurgical recurrence of AF (P=0.002), long-standing persistent AF (P=0.002), advanced age (P=0.03), and elevated CHA2DS2-VASc (P=0.046). AF mapping revealed 4.4±2.7 localized focal/rotational sites near and also remote from PV or PW reconnection. After ablation at patient-specific targets, arrhythmia freedom at 1 year was 81.0% including and 73.0% excluding previously ineffective antiarrhythmic medications.After surgical ablation, AF may recur by several modes including recovery of PW or PV isolation, mechanisms related to localized LVZ, or other sustaining mechanisms. LVZs are more common in patients at high clinical risk for recurrence. Patient-specific targeting of these mechanisms yields excellent long-term outcomes from hybrid ablation.

  View details for DOI 10.1161/CIRCEP.121.010502

  View details for PubMedID 35622437

• Future Directions for Mapping Atrial Fibrillation ARRHYTHMIA & ELECTROPHYSIOLOGY REVIEW Zaman, J. B., Grace, A. A., Narayan, S. M. 2022; 11

  View details for DOI 10.15420/aer.2021.52

  View details for Web of Science ID 000799674300003

• What Cannot Be Missed: Important Publications on Electrophysiology in 2021 Foreword ARRHYTHMIA & ELECTROPHYSIOLOGY REVIEW Narayan, S. M., Calkins, H., Grace, A., Ellenbogen, K., Lip, G. H., Lambiase, P. D., Katritsis, D. G. 2022; 11 (1)

  View details for DOI 10.15420/aer.2022.04

  View details for Web of Science ID 000778853700002

• Future Directions for Mapping Atrial Fibrillation. Arrhythmia & electrophysiology review Zaman, J. A., Grace, A. A., Narayan, S. M. 2022; 11: e08

  Abstract

  Mapping for AF focuses on the identification of regions of interest that may guide management and - in particular - ablation therapy. Mapping may point to specific mechanisms associated with localised scar or fibrosis, or electrical features, such as localised repetitive, rotational or focal activation. In patients in whom AF is caused by disorganised waves with no spatial predilection, as proposed in the multiwavelet theory for AF, mapping would be of less benefit. The role of AF mapping is controversial at the current time in view of the debate over the underlying mechanisms. However, recent clinical expansions of mapping technologies confirm the importance of understanding the state of the art, including limitations of current approaches and potential areas of future development.

  View details for DOI 10.15420/aer.2021.52

  View details for PubMedID 35734143

  View details for PubMedCentralID PMC9194915

• What Cannot Be Missed: Important Publications on Electrophysiology in 2021. Arrhythmia & electrophysiology review Narayan, S. M., Calkins, H., Grace, A., Lip, G. Y., Ellenbogen, K., Lambiase, P. D., Katritsis, D. G. 2022; 11: e01

  View details for DOI 10.15420/aer.2022.04

  View details for PubMedID 35444809

  View details for PubMedCentralID PMC9014699

• Atrial fibrillation signatures on intracardiac electrograms identified by deep learning. Computers in biology and medicine Rodrigo, M., Alhusseini, M. I., Rogers, A. J., Krittanawong, C., Thakur, S., Feng, R., Ganesan, P., Narayan, S. M. 2022; 145: 105451

  Abstract

  BACKGROUND: Automatic detection of atrial fibrillation (AF) by cardiac devices is increasingly common yet suboptimally groups AF, flutter or tachycardia (AT) together as 'high rate events'. This may delay or misdirect therapy.OBJECTIVE: We hypothesized that deep learning (DL) can accurately classify AF from AT by revealing electrogram (EGM) signatures.METHODS: We studied 86 patients in whom the diagnosis of AF or AT was established at electrophysiological study (25 female, 65±11 years). Custom DL architectures were trained to identify AF using N=29,340 unipolar and N=23,760 bipolar EGM segments. We compared DL to traditional classifiers based on rate or regularity. We explained DL using computer models to assess the impact of controlled variations in shape, rate and timing on AF/AT classification in 246,067 EGMs reconstructed from clinical data.RESULTS: DL identified AF with AUC of 0.97±0.04 (unipolar) and 0.92±0.09 (bipolar). Rule-based classifiers misclassified 10-12% of cases. DL classification was explained by regularity in EGM shape (13%) or timing (26%), and rate (60%; p<0.001), and also by a set of unipolar EGM shapes that classified as AF independent of rate or regularity. Overall, the optimal AF 'fingerprint' comprised these specific EGM shapes, >15% timing variation, <0.48 correlation in beat-to-beat EGM shapes and CL<190ms (p<0.001).CONCLUSIONS: Deep learning of intracardiac EGMs can identify AF or AT via signatures of rate, regularity in timing or shape, and specific EGM shapes. Future work should examine if these signatures differ between different clinical subpopulations with AF.

  View details for DOI 10.1016/j.compbiomed.2022.105451

  View details for PubMedID 35429831

• TARGETING SYNCHRONIZED ELECTROGRAM ISLANDS WITHIN ATRIAL FIBRILLATION FOR ABLATION Ganesan, P., Deb, B., Feng, R., Rodrigo, M., Ruiperez-Campillo, S., Bhatia, N. K., Rogers, A. J., Clopton, P., Rappel, W., Narayan, S. M. ELSEVIER SCIENCE INC. 2022: 3

  View details for Web of Science ID 000781026600004

• A MORPHOLOGICAL OPERATION-BASED APPROACH TO AUTOMATICALLY SEPARATE AND LABEL LEFT ATRIUM BODY AND PULMONARY VEINS Feng, R., Ganesan, P., Deb, B., Rogers, A. J., Ruiperez-Campillo, S., Rodrigo, M., Zaharia, M., Clopton, P., Rappel, W., Narayan, S. M. ELSEVIER SCIENCE INC. 2022: 1244

  View details for Web of Science ID 000781026601343

• UNSUPERVISED MACHINE LEARNING IDENTIFIES PHENOTYPES FOR ATRIAL FIBRILLATION THAT PREDICT ACUTE ABLATION SUCCESS Deb, B., Ganesan, P., Feng, R., Bhatia, N. K., Rogers, A. J., Ruiperez-Campillo, S., Clopton, P., Narayan, S. M. ELSEVIER SCIENCE INC. 2022: 51

  View details for Web of Science ID 000781026600052

• Perpendicular Catheter Orientation During Papillary Muscle Ablation Results in Larger, Deeper Lesions. Journal of cardiovascular electrophysiology Nussinovitch, U., Wang, P., Narayan, S., Viswanathan, M., Badhwar, N., Zheng, L., Sauer, W. H., Nguyen, D. T. 2022

  Abstract

  INTRODUCTION: Ablation of papillary muscles (PM) for refractory ventricular arrhythmias can often be challenging. The catheter approach and orientation during ablation may affect optimal radiofrequency (RF) delivery. Yet, no previous study investigated the association between catheter orientation and PM lesion size. We evaluated ablation lesion characteristics with various catheter orientations relative to the PM tissue during open irrigated ablation, using a standardized, experimental setting.METHODS: Viable bovine PM was positioned on a load cell in a circulating saline bath. RF ablation was performed over PM tissue at 50W, with the open irrigated catheter positioned either perpendicular or parallel to the PM surface. Applied force was 10 grams. Ablation lesions were sectioned and underwent quantitative morphometric analysis.RESULTS: A catheter position oriented directly perpendicular to the PM tissue resulted in the largest ablation lesion volumes and depths compared to ablation with the catheter parallel to PM tissue (75.26±8.40 mm3 vs. 34.04±2.91 mm3 , p<0.001) and (3.33±0.18 mm vs. 2.24±0.10 mm, p<0.001), respectively. There were no significant differences in initial impedance, peak voltage, peak current, or overall decrease in impedance among groups. Parallel catheter orientation resulted in higher peak temperature (41.33±0.28°C vs. 40.28±0.24°C, p=0.003), yet, there were no steam pops in either group.CONCLUSION: For PM ablation, catheter orientation perpendicular to the PM tissue achieves more effective and larger ablation lesions, with greater lesion depth. This may have implications for the chosen ventricular access approach, the type of catheter used, consideration for remote navigation, and steerable sheaths. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/jce.15408

  View details for PubMedID 35133050

• Predicting Atrial Fibrillation Recurrence by Combining Population Data and Virtual Cohorts of Patient-Specific Left Atrial Models. Circulation. Arrhythmia and electrophysiology Roney, C. H., Sim, I., Yu, J., Beach, M., Mehta, A., Alonso Solis-Lemus, J., Kotadia, I., Whitaker, J., Corrado, C., Razeghi, O., Vigmond, E., Narayan, S. M., O'Neill, M., Williams, S. E., Niederer, S. A. 1800: CIRCEP121010253

  Abstract

  BACKGROUND: Current ablation therapy for atrial fibrillation is suboptimal, and long-term response is challenging to predict. Clinical trials identify bedside properties that provide only modest prediction of long-term response in populations, while patient-specific models in small cohorts primarily explain acute response to ablation. We aimed to predict long-term atrial fibrillation recurrence after ablation in large cohorts, by using machine learning to complement biophysical simulations by encoding more interindividual variability.METHODS: Patient-specific models were constructed for 100 atrial fibrillation patients (43 paroxysmal, 41 persistent, and 16 long-standing persistent), undergoing first ablation. Patients were followed for 1 year using ambulatory ECG monitoring. Each patient-specific biophysical model combined differing fibrosis patterns, fiber orientation maps, electrical properties, and ablation patterns to capture uncertainty in atrial properties and to test the ability of the tissue to sustain fibrillation. These simulation stress tests of different model variants were postprocessed to calculate atrial fibrillation simulation metrics. Machine learning classifiers were trained to predict atrial fibrillation recurrence using features from the patient history, imaging, and atrial fibrillation simulation metrics.RESULTS: We performed 1100 atrial fibrillation ablation simulations across 100 patient-specific models. Models based on simulation stress tests alone showed a maximum accuracy of 0.63 for predicting long-term fibrillation recurrence. Classifiers trained to history, imaging, and simulation stress tests (average 10-fold cross-validation area under the curve, 0.85±0.09; recall, 0.80±0.13; precision, 0.74±0.13) outperformed those trained to history and imaging (area under the curve, 0.66±0.17) or history alone (area under the curve, 0.61±0.14).CONCLUSION: A novel computational pipeline accurately predicted long-term atrial fibrillation recurrence in individual patients by combining outcome data with patient-specific acute simulation response. This technique could help to personalize selection for atrial fibrillation ablation.

  View details for DOI 10.1161/CIRCEP.121.010253

  View details for PubMedID 35089057

• Stochastic termination of spiral wave dynamics in cardiac tissue. Frontiers in network physiology Rappel, W., Krummen, D. E., Baykaner, T., Zaman, J., Donsky, A., Swarup, V., Miller, J. M., Narayan, S. M. 2022; 2

  Abstract

  Rotating spiral waves are self-organized features in spatially extended excitable media and may play an important role in cardiac arrhythmias including atrial fibrillation (AF). In homogeneous media, spiral wave dynamics are perpetuated through spiral wave breakup, leading to the continuous birth and death of spiral waves, but have a finite probability of termination. In non-homogeneous media, however, heterogeneities can act as anchoring sources that result in sustained spiral wave activity. It is thus unclear how and if AF may terminate following the removal of putative spiral wave sources in patients. Here, we address this question using computer simulations in which a stable spiral wave is trapped by an heterogeneity and is surrounded by spiral wave breakup. We show that, following ablation of spatial heterogeneity to render that region of the medium unexcitable, termination of spiral wave dynamics is stochastic and Poisson-distributed. Furthermore, we show that the dynamics can be accurately described by a master equation using birth and death rates. To validate these predictions in vivo, we mapped spiral wave activity in patients with AF and targeted the locations of spiral wave sources using radiofrequency ablation. Targeted ablation was indeed able to terminate AF, but only after a variable delay of up to several minutes. Furthermore, and consistent with numerical simulations, termination was not accompanied by gradual temporal or spatial organization. Our results suggest that spiral wave sources and tissue heterogeneities play a critical role in the maintenance of AF and that the removal of sources results in spiral wave dynamics with a finite termination time, which could have important clinical implications.

  View details for DOI 10.3389/fnetp.2022.809532

  View details for PubMedID 36187938

• Identifying Atrial Fibrillation Mechanisms for Personalized Medicine. Journal of clinical medicine Deb, B., Ganesan, P., Feng, R., Narayan, S. M. 2021; 10 (23)

  Abstract

  Atrial fibrillation (AF) is a major cause of heart failure and stroke. The early maintenance of sinus rhythm has been shown to reduce major cardiovascular endpoints, yet is difficult to achieve. For instance, it is unclear how discoveries at the genetic and cellular level can be used to tailor pharmacotherapy. For non-pharmacologic therapy, pulmonary vein isolation (PVI) remains the cornerstone of rhythm control, yet has suboptimal success. Improving these therapies will likely require a multifaceted approach that personalizes therapy based on mechanisms measured in individuals across biological scales. We review AF mechanisms from cell-to-organ-to-patient from this perspective of personalized medicine, linking them to potential clinical indices and biomarkers, and discuss how these data could influence therapy. We conclude by describing approaches to improve ablation, including the emergence of several mapping systems that are in use today.

  View details for DOI 10.3390/jcm10235679

  View details for PubMedID 34884381

• Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram. Mayo Clinic proceedings Attia, Z. I., Kapa, S., Dugan, J., Pereira, N., Noseworthy, P. A., Jimenez, F. L., Cruz, J., Carter, R. E., DeSimone, D. C., Signorino, J., Halamka, J., Chennaiah Gari, N. R., Madathala, R. S., Platonov, P. G., Gul, F., Janssens, S. P., Narayan, S., Upadhyay, G. A., Alenghat, F. J., Lahiri, M. K., Dujardin, K., Hermel, M., Dominic, P., Turk-Adawi, K., Asaad, N., Svensson, A., Fernandez-Aviles, F., Esakof, D. D., Bartunek, J., Noheria, A., Sridhar, A. R., Lanza, G. A., Cohoon, K., Padmanabhan, D., Pardo Gutierrez, J. A., Sinagra, G., Merlo, M., Zagari, D., Rodriguez Escenaro, B. D., Pahlajani, D. B., Loncar, G., Vukomanovic, V., Jensen, H. K., Farkouh, M. E., Luescher, T. F., Su Ping, C. L., Peters, N. S., Friedman, P. A., Discover Consortium (Digital and Noninvasive Screening for COVID-19 with AI ECG Repository) 2021; 96 (8): 2081-2094

  Abstract

  OBJECTIVE: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG).METHODS: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network wastrained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site.RESULTS: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%.CONCLUSION: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control.

  View details for DOI 10.1016/j.mayocp.2021.05.027

  View details for PubMedID 34353468

• Editorial: Electrical and Structural Remodelling in Atrial Fibrillation: Phenotyping for Personalized Therapy FRONTIERS IN PHYSIOLOGY Chauhan, V. S., Verma, A., Narayan, S. M. 2021; 12: 697536

  View details for DOI 10.3389/fphys.2021.697536

  View details for Web of Science ID 000659549900001

  View details for PubMedID 34122153

  View details for PubMedCentralID PMC8191843

• Immediate and Delayed Response of Simulated Human Atrial Myocytes to Clinically-Relevant Hypokalemia FRONTIERS IN PHYSIOLOGY Clerx, M., Mirams, G. R., Rogers, A. J., Narayan, S. M., Giles, W. R. 2021; 12: 651162

  Abstract

  Although plasma electrolyte levels are quickly and precisely regulated in the mammalian cardiovascular system, even small transient changes in K+, Na+, Ca2+, and/or Mg2+ can significantly alter physiological responses in the heart, blood vessels, and intrinsic (intracardiac) autonomic nervous system. We have used mathematical models of the human atrial action potential (AP) to explore the electrophysiological mechanisms that underlie changes in resting potential (Vr) and the AP following decreases in plasma K+, [K+]o, that were selected to mimic clinical hypokalemia. Such changes may be associated with arrhythmias and are commonly encountered in patients (i) in therapy for hypertension and heart failure; (ii) undergoing renal dialysis; (iii) with any disease with acid-base imbalance; or (iv) post-operatively. Our study emphasizes clinically-relevant hypokalemic conditions, corresponding to [K+]o reductions of approximately 1.5 mM from the normal value of 4 to 4.5 mM. We show how the resulting electrophysiological responses in human atrial myocytes progress within two distinct time frames: (i) Immediately after [K+]o is reduced, the K+-sensing mechanism of the background inward rectifier current (IK1) responds. Specifically, its highly non-linear current-voltage relationship changes significantly as judged by the voltage dependence of its region of outward current. This rapidly alters, and sometimes even depolarizes, Vr and can also markedly prolong the final repolarization phase of the AP, thus modulating excitability and refractoriness. (ii) A second much slower electrophysiological response (developing 5-10 minutes after [K+]o is reduced) results from alterations in the intracellular electrolyte balance. A progressive shift in intracellular [Na+]i causes a change in the outward electrogenic current generated by the Na+/K+ pump, thereby modifying Vr and AP repolarization and changing the human atrial electrophysiological substrate. In this study, these two effects were investigated quantitatively, using seven published models of the human atrial AP. This highlighted the important role of IK1 rectification when analyzing both the mechanisms by which [K+]o regulates Vr and how the AP waveform may contribute to "trigger" mechanisms within the proarrhythmic substrate. Our simulations complement and extend previous studies aimed at understanding key factors by which decreases in [K+]o can produce effects that are known to promote atrial arrhythmias in human hearts.

  View details for DOI 10.3389/fphys.2021.651162

  View details for Web of Science ID 000659214100001

  View details for PubMedID 34122128

  View details for PubMedCentralID PMC8188899

• CONSISTENT SPATIOTEMPORAL VECTORS IN ATRIAL FIBRILLATION PREDICT RESPONSE TO ABLATION Ganesan, P., Bhatia, N., Beck, T. C., Ravi, N., Rogers, A., Krummen, D., Wang, P., Rappel, W., Narayan, S. ELSEVIER SCIENCE INC. 2021: 334

  View details for Web of Science ID 000647487500334

• NON-INVASIVE TRACKING OF ATRIAL FIBRILLATION PREDICTS ACUTE TERMINATION BY ABLATION Rodrigo, M., Baykaner, T., Rappel, W., Narayan, S. ELSEVIER SCIENCE INC. 2021: 280

  View details for Web of Science ID 000647487500280

• CLASSIFICATION OF INDIVIDUAL ATRIAL INTRACARDIAC ELECTROGRAMS BY DEEP LEARNING Rodrigo, M., Rogers, A., Ganesan, P., Krittanawong, C., Alhusseini, M., Narayan, S. ELSEVIER SCIENCE INC. 2021: 3217

  View details for Web of Science ID 000647487503241

• PROBING MACHINE LEARNING TO SEPARATE ATRIAL FIBRILLATION FROM OTHER ARRHYTHMIAS Rodrigo, M., Rogers, A., Ganesan, P., Alhusseini, M., Krittanawong, C., Narayan, S. ELSEVIER SCIENCE INC. 2021: 3410

  View details for Web of Science ID 000647487503431

• MACHINE LEARNING CLASSIFIES INTRACARDIAC ELECTROGRAMS OF ATRIAL FIBRILLATION FROM OTHER ARRHYTHMIAS Rodrigo, M., Rogers, A., Ganesan, P., Krittanawong, C., Alhusseini, M., Narayan, S. ELSEVIER SCIENCE INC. 2021: 279

  View details for Web of Science ID 000647487500279

• VALIDATING NON-INVASIVE INDICES OF AF COMPLEXITY AGAINST INTRACARDIAC MEASUREMENTS Rodrigo, M., Alhusseini, M., Rogers, A., Narayan, S. ELSEVIER SCIENCE INC. 2021: 1354

  View details for Web of Science ID 000647487501362

• IDENTIFICATION OF AREAS OF ORGANIZED 1:1 ACTIVITY IN ATRIAL FIBRILLATION IN PATIENTS POST MAZE SURGERY Bhatia, N. K., Shah, R., Ganesan, P., Rogers, A., Pong, T., Purewal, S., Baykaner, T., Wang, P., Lee, A., Rappel, W., Narayan, S. ELSEVIER SCIENCE INC. 2021: 333

  View details for Web of Science ID 000647487500333

• Re-Interpreting Complex Atrial Tachycardia Maps Using Global Atrial Vectors. Journal of cardiovascular electrophysiology Rodrigo, M., Narayan, S. M. 2021

  Abstract

  The mapping and ablation of Atrial Tachycardias (AT) can be challenging, particularly in patients with prior ablation or structural atrial disease. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/jce.15073

  View details for PubMedID 33955113

• What Cannot Be Missed: Important Publications on Electrophysiology in 2020. Arrhythmia & electrophysiology review Narayan, S. M., Calkins, H., Grace, A., Ellenbogen, K., Lip, G. Y., Lambiase, P. D., Katritsis, D. G. 2021; 10 (1): 5–6

  View details for DOI 10.15420/aer.2021.02

  View details for PubMedID 33936736

• Prognostication for Sudden Cardiac Arrest Patients Achieving ROSC. Journal of the American College of Cardiology Daubert, J. P., Lee, J. S., Narayan, S. M. 2021; 77 (4): 372–74

  View details for DOI 10.1016/j.jacc.2020.11.052

  View details for PubMedID 33509393

• Non-invasive Spatial Mapping of Frequencies in Atrial Fibrillation: Correlation With Contact Mapping FRONTIERS IN PHYSIOLOGY Rodrigo, M., Waddell, K., Magee, S., Rogers, A. J., Alhusseini, M., Hernandez-Romero, I., Costoya-Sanchez, A., Liberos, A., Narayan, S. M. 2021; 11

  View details for DOI 10.3389/fphys.2020.611266

  View details for Web of Science ID 000608806200001

• Three Dimensional Transmural Mapping to Guide Ventricular Arrhythmia Ablation. Heart rhythm Narayan, S. M., Badhwar, N. n. 2021

  View details for DOI 10.1016/j.hrthm.2021.05.003

  View details for PubMedID 33964464

• Deep Neural Network Trained on Surface ECG Improves Diagnostic Accuracy of Prior Myocardial Infarction Over Q Wave Analysis Yildirim, O., Baloglu, U. B., Talo, M., Ganesan, P., Tung, J. S., Kang, G., Tooley, J., Alhusseini, M., Baykaner, T., Wang, P. J., Perez, M., Tereshchenko, L., Narayan, S. M., Rogers, A. J., IEEE IEEE. 2021

  View details for DOI 10.22489/CinC.2021.010

  View details for Web of Science ID 000821955000130

• Arrhythmia Patterns in Patients on Ibrutinib. Frontiers in cardiovascular medicine Fazal, M., Kapoor, R., Cheng, P., Rogers, A. J., Narayan, S. M., Wang, P., Witteles, R. M., Perino, A. C., Baykaner, T., Rhee, J. 1800; 8: 792310

  Abstract

  Introduction: Ibrutinib, a Bruton's tyrosine kinase inhibitor (TKI) used primarily in the treatment of hematologic malignancies, has been associated with increased incidence of atrial fibrillation (AF), with limited data on its association with other tachyarrhythmias. There are limited reports that comprehensively analyze atrial and ventricular arrhythmia (VA) burden in patients on ibrutinib. We hypothesized that long-term event monitors could reveal a high burden of atrial and VAs in patients on ibrutinib. Methods: A retrospective data analysis at a single center using electronic medical records database search tools and individual chart review was conducted to identify consecutive patients who had event monitors while on ibrutinib therapy. Results: Seventy-two patients were included in the analysis with a mean age of 76.9 ± 9.9 years and 13 patients (18%) had a diagnosis of AF prior to the ibrutinib therapy. During ibrutinib therapy, most common arrhythmias documented were non-AF supraventricular tachycardia (n = 32, 44.4%), AF (n = 32, 44%), and non-sustained ventricular tachycardia (n = 31, 43%). Thirteen (18%) patients had >1% premature atrial contraction burden; 16 (22.2%) patients had >1% premature ventricular contraction burden. In 25% of the patients, ibrutinib was held because of arrhythmias. Overall 8.3% of patients were started on antiarrhythmic drugs during ibrutinib therapy to manage these arrhythmias. Conclusions: In this large dataset of ambulatory cardiac monitors on patients treated with ibrutinib, we report a high prevalence of atrial and VAs, with a high incidence of treatment interruption secondary to arrhythmias and related symptoms. Further research is warranted to optimize strategies to diagnose, monitor, and manage ibrutinib-related arrhythmias.

  View details for DOI 10.3389/fcvm.2021.792310

  View details for PubMedID 35047578

• Three dimensional reconstruction to visualize atrial fibrillation activation patterns on curved atrial geometry. PloS one Abad, R., Collart, O., Ganesan, P., Rogers, A. J., Alhusseini, M. I., Rodrigo, M., Narayan, S. M., Rappel, W. 2021; 16 (4): e0249873

  Abstract

  BACKGROUND: The rotational activation created by spiral waves may be a mechanism for atrial fibrillation (AF), yet it is unclear how activation patterns obtained from endocardial baskets are influenced by the 3D geometric curvature of the atrium or 'unfolding' into 2D maps. We develop algorithms that can visualize spiral waves and their tip locations on curved atrial geometries. We use these algorithms to quantify differences in AF maps and spiral tip locations between 3D basket reconstructions, projection onto 3D anatomical shells and unfolded 2D surfaces.METHODS: We tested our algorithms in N = 20 patients in whom AF was recorded from 64-pole baskets (Abbott, CA). Phase maps were generated by non-proprietary software to identify the tips of spiral waves, indicated by phase singularities. The number and density of spiral tips were compared in patient-specific 3D shells constructed from the basket, as well as 3D maps from clinical electroanatomic mapping systems and 2D maps.RESULTS: Patients (59.4±12.7 yrs, 60% M) showed 1.7±0.8 phase singularities/patient, in whom ablation terminated AF in 11/20 patients (55%). There was no difference in the location of phase singularities, between 3D curved surfaces and 2D unfolded surfaces, with a median correlation coefficient between phase singularity density maps of 0.985 (0.978-0.990). No significant impact was noted by phase singularities location in more curved regions or relative to the basket location (p>0.1).CONCLUSIONS: AF maps and phase singularities mapped by endocardial baskets are qualitatively and quantitatively similar whether calculated by 3D phase maps on patient-specific curved atrial geometries or in 2D. Phase maps on patient-specific geometries may be easier to interpret relative to critical structures for ablation planning.

  View details for DOI 10.1371/journal.pone.0249873

  View details for PubMedID 33836026

• Electrical Substrate Ablation for Refractory Ventricular Fibrillation: Results of the AVATAR Study. Circulation. Arrhythmia and electrophysiology Krummen, D. E., Ho, G. n., Hoffmayer, K. S., Schweis, F. n., Baykaner, T. n., Rogers, A. J., Han, F. T., Hsu, J. C., Viswanathan, M. N., Wang, P. J., Rappel, W. J., Narayan, S. M. 2021

  Abstract

  Background - Refractory ventricular fibrillation (VF) is a challenging clinical entity, for which ablation of triggering premature ventricular complexes (PVCs) is described. When PVCs are infrequent and multifocal, the optimal treatment strategy is uncertain. Methods - We prospectively enrolled consecutive patients presenting with multiple ICD shocks for VF refractory to antiarrhythmic drug therapy, exhibiting infrequent (≤3%), multifocal PVCs (≥3 morphologies). Procedurally, VF was induced with rapid pacing and mapped, identifying sites of conduction slowing and rotation or rapid focal activation. VF electrical substrate ablation (VESA) was then performed. Outcomes were compared against reference patients with VF who were unable or unwilling to undergo catheter ablation. The primary outcome was a composite of ICD shock, electrical storm, or all-cause mortality. Results - VF was induced and mapped in 6 patients (60±10 y, LVEF 46±19%) with ischemic (n=3) and nonischemic cardiomyopathy. An average of 3.3±0.5 sites of localized reentry during VF were targeted for radiofrequency ablation (38.3±10.9 minutes) during sinus rhythm, rendering VF non-inducible with pacing. Freedom from the primary outcome was 83% in the VF ablation group versus 17% in 6 non-ablation reference patients at a median of 1.0 years (IQR 0.5-1.5 years, p=0.046) follow-up. Conclusions - VESA is associated with a reduction in the combined endpoint compared with the non-ablation reference group. Additional work is required to understand the precise pathophysiologic changes which promote VF in order to improve preventative and therapeutic strategies.

  View details for DOI 10.1161/CIRCEP.120.008868

  View details for PubMedID 33550811

• Competing Risks in Patients with Primary Prevention Implantable Cardioverter-Defibrillators: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) Study. Heart rhythm Waks, J. W., Haq, K. T., Tompkins, C. n., Rogers, A. J., Ehdaie, A. n., Bender, A. n., Minnier, J. n., Dalouk, K. n., Howell, S. n., Peiris, A. n., Raitt, M. n., Narayan, S. M., Chugh, S. S., Tereshchenko, L. G. 2021

  Abstract

  Global electrical heterogeneity (GEH) is associated with sudden cardiac death in the general population. Its utility in patients with systolic heart failure (HF) who are candidates for primary prevention (PP) implantable cardioverter-defibrillators (ICDs) is unclear.To investigate whether GEH is associated with sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) leading to appropriate ICD therapies in HF patients with PP ICDs.We conducted a multicenter retrospective cohort study. GEH was measured by spatial ventricular gradient (SVG) direction (azimuth and elevation) and magnitude, QRS-T angle, and sum absolute QRST integral (SAIQRST) on pre-implant 12-lead ECGs. Survival analysis using cause-specific hazard functions compared the strength of associations with two competing outcomes: sustained VT/VF leading to appropriate ICD therapies and all-cause death without appropriate ICD therapies.We analyzed 2,668 patients (age 63±12y; 23% female; 78% white; 43% nonischemic cardiomyopathy (NICM); left ventricular ejection fraction 28±11% from 6 academic medical centers). After adjustment for demographic, clinical, device, and traditional ECG characteristics, SVG elevation (Hazard Ratio (HR) per 1 standard deviation (SD) 1.14 (95% CI 1.04-1.25); P=0.004), SVG azimuth (HR per 1 SD 1.12(1.01-1.24); P=0.039); SVG magnitude (HR per 1 SD 0.75(0.66-0.85); P<0.0001), and QRS-T angle (HR per 1 SD 1.21 (95% CI 1.08-1.36); P=0.001) were associated with appropriate ICD therapies. SAIQRST had different associations in infarct-related [HR 1.29(1.04-1.60)] and NICM [HR 0.78(0.62-0.96); Pinteraction=0.022].In patients with PP ICDs, GEH is independently associated with appropriate ICD therapies. The SVG vector points in distinctly different directions in patients with two competing outcomes.

  View details for DOI 10.1016/j.hrthm.2021.03.006

  View details for PubMedID 33684549

• Machine Learned Cellular Phenotypes Predict Outcome in Ischemic Cardiomyopathy. Circulation research Rogers, A. J., Selvalingam, A., Alhusseini, M. I., Krummen, D. E., Corrado, C., Abuzaid, F., Baykaner, T., Meyer, C., Clopton, P., Giles, W. R., Bailis, P., Niederer, S. A., Wang, P. J., Rappel, W., Zaharia, M., Narayan, S. M. 2020

  Abstract

  RATIONALE: Susceptibility to ventricular arrhythmias (VT/VF) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside.OBJECTIVE: To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning (ML) of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes.METHODS AND RESULTS: We recorded 5706 ventricular MAPs in 42 patients with coronary disease (CAD) and left ventricular ejection fraction (LVEF) {less than or equal to}40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10 fold. Support vector machines (SVM) and convolutional neural networks (CNN) were trained to 2 endpoints: (i) sustained VT/VF or (ii) mortality at 3 years. SVM provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each endpoint. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI: 0.76-1.00) and 0.91 for mortality (95% CI: 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained SVM revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium calcium exchanger as predominant phenotypes for VT/VF.CONCLUSIONS: Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.

  View details for DOI 10.1161/CIRCRESAHA.120.317345

  View details for PubMedID 33167779

• Integration of novel monitoring devices with machine learning technology for scalable cardiovascular management. Nature reviews. Cardiology Krittanawong, C., Rogers, A. J., Johnson, K. W., Wang, Z., Turakhia, M. P., Halperin, J. L., Narayan, S. M. 2020

  Abstract

  Ambulatory monitoring is increasingly important for cardiovascular care but is often limited by the unpredictability of cardiovascular events, the intermittent nature of ambulatory monitors and the variable clinical significance of recorded data in patients. Technological advances in computing have led to the introduction of novel physiological biosignals that can increase the frequency at which abnormalities in cardiovascular parameters can be detected, making expert-level, automated diagnosis a reality. However, use of these biosignals for diagnosis also raises numerous concerns related to accuracy and actionability within clinical guidelines, in addition to medico-legal and ethical issues. Analytical methods such as machine learning can potentially increase the accuracy and improve the actionability of device-based diagnoses. Coupled with interoperability of data to widen access to all stakeholders, seamless connectivity (an internet of things) and maintenance of anonymity, this approach could ultimately facilitate near-real-time diagnosis and therapy. These tools are increasingly recognized by regulatory agencies and professional medical societies, but several technical and ethical issues remain. In this Review, we describe the current state of cardiovascular monitoring along the continuum from biosignal acquisition to the identification of novel biosensors and the development of analytical techniques and ultimately to regulatory and ethical issues. Furthermore, we outline new paradigms for cardiovascular monitoring.

  View details for DOI 10.1038/s41569-020-00445-9

  View details for PubMedID 33037325

• Populations of in silico myocytes and tissues reveal synergy of multi-atrial-predominant K+ -current block in atrial fibrillation. British journal of pharmacology Ni, H., Iseppe, A. F., Giles, W. R., Narayan, S. M., Zhang, H., Edwards, A. G., Morotti, S., Grandi, E. 2020

  Abstract

  BACKGROUND AND PURPOSE: Current pharmacological therapies for atrial fibrillation (AF), the most common cardiac arrhythmia, remain unsatisfactory due to low efficacy and safety concerns. New promising strategies for AF pharmacotherapy include targeting atrial-predominant ion-channels and multi-channel block (poly)therapy. Further, as AF is characterized by rapid and irregular atrial activations, compounds displaying potent antiarrhythmic effects at fast rates and minimal effects at slow rates are desirable. We present a novel Systems Pharmacology framework to quantitatively evaluate synergistic anti-AF effects of combined block of multiple atrial-predominant K+ currents (ultra-rapid delayed rectifier K+ current, IKur , small conductance Ca2+ -activated K+ current, IKCa , K2P 3.1 2-pore-domain K+ current, IK2P ) in AF.EXPERIMENTAL APPROACH: We constructed experimentally calibrated populations of virtual atrial myocyte models in both normal sinus rhythm (nSR) and AF-remodeled conditions using two distinct, well-established atrial models. Next, we conducted sensitivity analyses on our atrial populations to investigate the rate dependence of action potential duration (APD) changes due to blocking IKur , IK2P or IKCa , and uncover interactions among block of these three currents in modulating APD. Block was simulated in both single myocytes and one-dimensional tissue strands to confirm insights from the sensitivity analyses and examine anti-arrhythmic effects of multi-atrial-predominant K+ current block in single cells and coupled tissue.KEY RESULTS: In both virtual atrial myocytes and tissues, multiple atrial-predominant K+ -current block promoted favorable positive rate-dependent APD prolongation and displayed positive rate-dependent synergy, i.e., increasing synergistic antiarrhythmic effects at fast pacing vs slow rates.CONCLUSION AND IMPLICATIONS: Simultaneous block of multiple atrial-predominant K+ currents may be a valuable antiarrhythmic pharmacotherapeutic strategy for AF.

  View details for DOI 10.1111/bph.15198

  View details for PubMedID 32667679

• Artificial Intelligence and Machine Learning in Arrhythmias and Cardiac Electrophysiology. Circulation. Arrhythmia and electrophysiology Feeny, A. K., Chung, M. K., Madabhushi, A., Attia, Z. I., Cikes, M., Firouznia, M., Friedman, P. A., Kalscheur, M. M., Kapa, S., Narayan, S. M., Noseworthy, P. A., Passman, R. S., Perez, M. V., Peters, N. S., Piccini, J. P., Tarakji, K. G., Thomas, S. A., Trayanova, N. A., Turakhia, M. P., Wang, P. J. 2020

  Abstract

  Artificial intelligence (AI) and machine learning (ML) in medicine are currently areas of intense exploration, showing potential to automate human tasks and even perform tasks beyond human capabilities. Literacy and understanding of AI/ML methods are becoming increasingly important to researchers and clinicians. The first objective of this review is to provide the novice reader with literacy of AI/ML methods and provide a foundation for how one might conduct an ML study. We provide a technical overview of some of the most commonly used terms, techniques, and challenges in AI/ML studies, with reference to recent studies in cardiac electrophysiology to illustrate key points. The second objective of this review is to use examples from recent literature to discuss how AI and ML are changing clinical practice and research in cardiac electrophysiology, with emphasis on disease detection and diagnosis, prediction of patient outcomes, and novel characterization of disease. The final objective is to highlight important considerations and challenges for appropriate validation, adoption, and deployment of AI technologies into clinical practice.

  View details for DOI 10.1161/CIRCEP.119.007952

  View details for PubMedID 32628863

• Machine Learning to Classify Intracardiac Electrical Patterns during Atrial Fibrillation. Circulation. Arrhythmia and electrophysiology Alhusseini, M. I., Abuzaid, F., Rogers, A. J., Zaman, J. A., Baykaner, T., Clopton, P., Bailis, P., Zaharia, M., Wang, P. J., Rappel, W., Narayan, S. M. 2020

  Abstract

  Background - Advances in ablation for atrial fibrillation (AF) continue to be hindered by ambiguities in mapping, even between experts. We hypothesized that convolutional neural networks (CNN) may enable objective analysis of intracardiac activation in AF, which could be applied clinically if CNN classifications could also be explained. Methods - We performed panoramic recording of bi-atrial electrical signals in AF. We used the Hilbert-transform to produce 175,000 image grids in 35 patients, labeled for rotational activation by experts who showed consistency but with variability (kappa=0.79). In each patient, ablation terminated AF. A CNN was developed and trained on 100,000 AF image grids, validated on 25,000 grids, then tested on a separate 50,000 grids. Results - In the separate test cohort (50,000 grids), CNN reproducibly classified AF image grids into those with/without rotational sites with 95.0% accuracy (CI 94.8-95.2%). This accuracy exceeded that of support vector machines, traditional linear discriminant and k-nearest neighbor statistical analyses. To probe the CNN, we applied Gradient-weighted Class Activation Mapping which revealed that the decision logic closely mimicked rules used by experts (C-statistic 0.96). Conclusions - Convolutional neural networks improved the classification of intracardiac AF maps compared to other analyses, and agreed with expert evaluation. Novel explainability analyses revealed that the CNN operated using a decision logic similar to rules used by experts, even though these rules were not provided in training. We thus describe a scaleable platform for robust comparisons of complex AF data from multiple systems, which may provide immediate clinical utility to guide ablation.

  View details for DOI 10.1161/CIRCEP.119.008160

  View details for PubMedID 32631100

• What Cannot Be Missed: Important Publications on Electrophysiology in 2019. Arrhythmia & electrophysiology review Grace, A., Calkins, H., Ellenbogen, K., Lambiase, P. D., Lip, G. Y., Narayan, S. M., Katritsis, D. G. 2020; 9 (1): 4

  View details for DOI 10.15420/aer.2020.06

  View details for PubMedID 32637112

  View details for PubMedCentralID PMC7330725

• PREDICTING SUDDEN CARDIAC DEATH BY MACHINE LEARNING OF VENTRICULAR ACTION POTENTIALS Selvalingam, A., Alhusseini, M., Rogers, A. J., Krummen, D., Abuzaid, F. M., Baykaner, T., Clopton, P., Bailis, P., Zaharia, M., Wang, P., Narayan, S. ELSEVIER SCIENCE INC. 2020: 427

  View details for Web of Science ID 000522979100416

• LARGER ORGANIZED AREAS IN PERSISTENT ATRIAL FIBRILLATION PREDICTS TERMINATION DURING ABLATION Ravi, N., Rogers, A. J., Bhatia, N., Tung, J. S., Krummen, D., Sauer, W., Alhusseini, M., Baykaner, T., Wang, P., Rappel, W., Narayan, S. ELSEVIER SCIENCE INC. 2020: 279

  View details for Web of Science ID 000522979100273

• What Cannot Be Missed: Important Publications on Electrophysiology in 2019 Foreword ARRHYTHMIA & ELECTROPHYSIOLOGY REVIEW Grace, A., Calkins, H., Ellenbogen, K., Lambiase, P. D., Lip, G. H., Narayan, S. M., Katritsis, D. G. 2020; 9 (1): 4

  View details for DOI 10.15420/aer.2020.06

  View details for Web of Science ID 000539058200001

• Getting in Contact With AtrialFibrillationor Not. JACC. Clinical electrophysiology Verma, A., Narayan, S. M. 2020; 6 (2): 182–84

  View details for DOI 10.1016/j.jacep.2019.10.023

  View details for PubMedID 32081220

• Automatic quality electrogram assessment improves phase-based reentrant activity identification in atrial fibrillation. Computers in biology and medicine Costoya-Sanchez, A., Climent, A. M., Hernandez-Romero, I., Liberos, A., Fernandez-Aviles, F., Narayan, S. M., Atienza, F., Guillem, M. S., Rodrigo, M. 2020; 117: 103593

  Abstract

  Identification of reentrant activity driving atrial fibrillation (AF) is increasingly important to ablative therapies. The goal of this work is to study how the automatically-classified quality of the electrograms (EGMs) affects reentrant AF driver localization. EGMs from 259 AF episodes obtained from 29 AF patients were recorded using 64-poles basket catheters and were manually classified according to their quality. An algorithm capable of identifying signal quality was developed using time and spectral domain parameters. Electrical reentries were identified in 3D phase maps using phase transform and were compared with those obtained with a 2D activation-based method. Effect of EGM quality was studied by discarding 3D phase reentries detected in regions with low-quality EGMs. Removal of reentries identified by 3D phase analysis in regions with low-quality EGMs improved its performance, increasing the area under the ROC curve (AUC) from 0.69 to 0.80. The EGMs quality classification algorithm showed an accurate performance for EGM classification (AUC 0.94) and reentry detection (AUC 0.80). Automatic classification of EGM quality based on time and spectral signal parameters is feasible and accurate, avoiding the manual labelling. Discard of reentries identified in regions with automatically-detected poor-quality EGMs improved the specificity of the 3D phase-based method for AF driver identification.

  View details for DOI 10.1016/j.compbiomed.2019.103593

  View details for PubMedID 32072974

• Non-invasive Spatial Mapping of Frequencies in Atrial Fibrillation: Correlation With Contact Mapping. Frontiers in physiology Rodrigo, M., Waddell, K., Magee, S., Rogers, A. J., Alhusseini, M., Hernandez-Romero, I., Costoya-Sánchez, A., Liberos, A., Narayan, S. M. 2020; 11: 611266

  Abstract

  Introduction: Regional differences in activation rates may contribute to the electrical substrates that maintain atrial fibrillation (AF), and estimating them non-invasively may help guide ablation or select anti-arrhythmic medications. We tested whether non-invasive assessment of regional AF rate accurately represents intracardiac recordings. Methods: In 47 patients with AF (27 persistent, age 63 ± 13 years) we performed 57-lead non-invasive Electrocardiographic Imaging (ECGI) in AF, simultaneously with 64-pole intracardiac signals of both atria. ECGI was reconstructed by Tikhonov regularization. We constructed personalized 3D AF rate distribution maps by Dominant Frequency (DF) analysis from intracardiac and non-invasive recordings. Results: Raw intracardiac and non-invasive DF differed substantially, by 0.54 Hz [0.13 - 1.37] across bi-atrial regions (R2 = 0.11). Filtering by high spectral organization reduced this difference to 0.10 Hz (cycle length difference of 1 - 11 ms) [0.03 - 0.42] for patient-level comparisons (R2 = 0.62), and 0.19 Hz [0.03 - 0.59] and 0.20 Hz [0.04 - 0.61] for median and highest DF, respectively. Non-invasive and highest DF predicted acute ablation success (p = 0.04). Conclusion: Non-invasive estimation of atrial activation rates is feasible and, when filtered by high spectral organization, provide a moderate estimate of intracardiac recording rates in AF. Non-invasive technology could be an effective tool to identify patients who may respond to AF ablation for personalized therapy.

  View details for DOI 10.3389/fphys.2020.611266

  View details for PubMedID 33584334

  View details for PubMedCentralID PMC7873897

• Re-evaluating The Multiple Wavelet Hypothesis for Atrial Fibrillation. Heart rhythm Ganesan, P. n., Narayan, S. M. 2020

  View details for DOI 10.1016/j.hrthm.2020.07.009

  View details for PubMedID 32673795

• Continuous Ablation Improves Lesion Maturation Compared with Intermittent Ablation Strategies. Journal of cardiovascular electrophysiology Rogers, A. J., Borne, R. T., Ho, G. n., Sauer, W. H., Wang, P. J., Narayan, S. M., Zheng, L. n., Nguyen, D. T. 2020

  Abstract

  Interrupted ablation is increasingly proposed as part of high-power short duration radiofrequency ablation (RFA) strategies and may also result from loss of contact from respiratory patterns or cardiac motion.To study the extent that ablation interruption affects lesions.In ex vivo and in vivo experiments, lesion characteristics and tissue temperatures were compared between continuous (Group 1) and interrupted (Groups 2,3) RFA with equal total ablation duration and contact force. Extended duration ablation lesions were also characterized from 1 to 5 minutes.In the ex vivo study, continuous RFA (Group 1) produced larger total lesion volumes compared with each interrupted ablation lesion group (273.8±36.5 mm3 vs. 205.1±34.2 and vs. 174.3±32.3, all p<0.001). Peak temperatures for Group 1 were higher at 3mm and 5mm than Groups 2 and 3. In vivo, continuous ablation resulted in larger lesions, greater lesion depths, and higher tissue temperatures. Longer ablation durations created larger lesion volumes and increased lesion depths. However, after 3 min of ablation, the rate of lesion volume and depth formation decreased.Continuous RFA delivery resulted in larger and deeper lesions with higher tissue temperatures compared to interrupted ablation. This work may have implications for high-power short duration ablation strategies, motivates strategies to reduce variations in ablation delivery, and provides an upper limit for ablation duration beyond which power delivery has diminishing returns. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/jce.14510

  View details for PubMedID 32323395

• Non-Invasive Assessment of Complexity of Atrial Fibrillation: Correlation with Contact Mapping and Impact of Ablation. Circulation. Arrhythmia and electrophysiology Rodrigo, M. n., Climent, A. M., Hernández-Romero, I. n., Liberos, A. n., Baykaner, T. n., Rogers, A. J., Alhusseini, M. n., Wang, P. J., Fernández-Avilés, F. n., Guillem, M. S., Narayan, S. M., Atienza, F. n. 2020

  Abstract

  Background - It is difficult to non-invasively phenotype atrial fibrillation (AF) in a way that reflects clinical endpoints such as response to therapy. We set out to map electrical patterns of disorganization and regions of reentrant activity in AF from the body surface using electrocardiographic imaging (ECGI), calibrated to panoramic intracardiac recordings and referenced to AF termination by ablation. Methods - Bi-atrial intracardiac electrograms of 47 AF patients at ablation (30 persistent, 29 male, 63±9 years) were recorded with 64-pole basket catheters and simultaneous 57-lead body surface ECGs. Atrial epicardial electrical activity was reconstructed and organized sites were invasively and non-invasively tracked in 3D using phase singularity (PS). In a subset of 17 patients, sites of AF organization were targeted for ablation. Results - Body surface mapping showed greater AF organization near intracardially-detected drivers than elsewhere, both in PS density (2.3±2.1 vs 1.9±1.6, p=0.02) and number of drivers (3.2±2.3 vs 2.7±1.7, p=0.02). Complexity, defined as the number of stable AF reentrant sites, was concordant between non-invasive and invasive methods (r2 =0.5, CC=0.71). In the subset receiving targeted ablation, AF complexity showed lower values in those in whom AF terminated than those in whom AF did not terminate (p<0.01). Conclusions - AF complexity tracked non-invasively correlates well with organized and disorganized regions detected by panoramic intracardiac mapping, and correlates with the acute outcome by ablation. This approach may assist in bedside monitoring of therapy or in improving the efficacy of ongoing ablation procedures.

  View details for DOI 10.1161/CIRCEP.119.007700

  View details for PubMedID 32078374

• Termination of persistent atrial fibrillation by ablating sites that control large atrial areas. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Bhatia, N. K., Rogers, A. J., Krummen, D. E., Hossainy, S. n., Sauer, W. n., Miller, J. M., Alhusseini, M. I., Peszek, A. n., Armenia, E. n., Baykaner, T. n., Brachmann, J. n., Turakhia, M. P., Clopton, P. n., Wang, P. J., Rappel, W. J., Narayan, S. M. 2020

  Abstract

  Persistent atrial fibrillation (AF) has been explained by multiple mechanisms which, while they conflict, all agree that more disorganized AF is more difficult to treat than organized AF. We hypothesized that persistent AF consists of interacting organized areas which may enlarge, shrink or coalesce, and that patients whose AF areas enlarge by ablation are more likely to respond to therapy.We mapped vectorial propagation in persistent AF using wavefront fields (WFF), constructed from raw unipolar electrograms at 64-pole basket catheters, during ablation until termination (Group 1, N = 20 patients) or cardioversion (Group 2, N = 20 patients). Wavefront field mapping of patients (age 61.1 ± 13.2 years, left atrium 47.1 ± 6.9 mm) at baseline showed 4.6 ± 1.0 organized areas, each separated by disorganization. Ablation of sites that led to termination controlled larger organized area than competing sites (44.1 ± 11.1% vs. 22.4 ± 7.0%, P < 0.001). In Group 1, ablation progressively enlarged unablated areas (rising from 32.2 ± 15.7% to 44.1 ± 11.1% of mapped atrium, P < 0.0001). In Group 2, organized areas did not enlarge but contracted during ablation (23.6 ± 6.3% to 15.2 ± 5.6%, P < 0.0001).Mapping wavefront vectors in persistent AF revealed competing organized areas. Ablation that progressively enlarged remaining areas was acutely successful, and sites where ablation terminated AF were surrounded by large organized areas. Patients in whom large organized areas did not emerge during ablation did not exhibit AF termination. Further studies should define how fibrillatory activity is organized within such areas and whether this approach can guide ablation.

  View details for DOI 10.1093/europace/euaa018

  View details for PubMedID 32243508

• Action Potential Dynamics in Human Atrial Fibrillation CARDIAC REPOLARIZATION: BASIC SCIENCE AND CLINICAL MANAGEMENT Zaman, J., Narayan, S. M., Franz, M. R., ElSherif, N. 2020: 333–45

  View details for DOI 10.1007/978-3-030-22672-5_20

  View details for Web of Science ID 000544795500022

• The interconnected atrium: Acute impact of pulmonary vein isolation on remote atrial tissue. Journal of cardiovascular electrophysiology Rogers, A. J., Baykaner, T. n., Narayan, S. M. 2020

  View details for DOI 10.1111/jce.14389

  View details for PubMedID 32090385

• Novel Three-Dimensional Imaging Approach for Cryoballoon Navigation and Confirmation of Pulmonary Vein Occlusion. Pacing and clinical electrophysiology : PACE Kowalewski, C. A., Rodrigo, M., Brodt, C., Haddad, F., Wang, P. J., Narayan, S. M. 2019

  Abstract

  BACKGROUND: Cryoballoon apposition is crucial for durable pulmonary vein isolation (PVI) in atrial fibrillation, yet the balloon is difficult to visualize by conventional mapping systems, and pulmonary venography may miss small or out-of-plane leaks. We report a novel imaging system that offers real-time 3-D navigation of the cryoballoon within atrial anatomy that may circumvent these issues.METHODS AND RESULTS: A novel overlay guidance system(OGS) (Siemens Healthcare, Forchheim, Germany) registers already-acquired segmented atrial cardiac tomography (CT) with fluoroscopy, enabling real-time visualization of the cryoballoon within tomographic left atrial imaging during PVI. Phantom experiments in a patient-specific 3D printed left atrium showed feasibility for confirming PV apposition and leaks. We applied OGS prospectively to 68 PVs during PVI in 17 patients. The cryoballoon was successfully reconstructed in all cases, and its apposition was compared to concurrent PV venography. The OGS uncovered leaks undetected by venography in 9 veins (8 cases) which enabled repositioning, confirming apposition in remaining 68 veins. Concordance of OGS to venography was 83.8% (chi2 , p<0.01) CONCLUSIONS: We report a new system for real-time imaging of cryoballoon catheters to ensure PV apposition within the tomography of the left atrium. While providing high concordance with other imaging modalities for confirming balloon apposition or leak, the system also identified leaks missed by venography. Future studies should determine if this tool can provide a new reference for cryoballoon positioning. This article is protected by copyright. All rights reserved Cryoballoon ablation is increasingly used for pulmonary vein isolation (PVI), but it may be difficult to track cryoballoon position relative to the PV for complete occlusion. We describe a novel overlay guidance system (OGS) for real-time 3D visualization of the cryoballoon within atrial anatomy, by registering atrial computed tomography in 2 fluoroscopic planes. Phantom experiments with a custom 3D printed left atrium showed feasibility for visualizing balloon apposition within PVs. In 68 PVs in 17 patients, the OGS prospectively identified cryoballoon position relative to PVs, and uncovered leaks undetected by venography. Future studies should test if the OGS can serve as a new reference for cryoballoon positioning.

  View details for DOI 10.1111/pace.13858

  View details for PubMedID 31868241

• Mapping and Ablation of Rotational and Focal Drivers in Atrial Fibrillation. Cardiac electrophysiology clinics Zaman, J., Baykaner, T., Narayan, S. M. 2019; 11 (4): 583–95

  Abstract

  Drivers are increasingly studied ablation targets for atrial fibrillation (AF). However, results from ablation remain controversial. First, outcomes vary between centers and patients. Second, it is unclear how best to perform driver ablation. Third, there is a lack of practical guidance on how to identify critical from secondary sites using different AF mapping methods. This article addresses each of these issues.

  View details for DOI 10.1016/j.ccep.2019.08.010

  View details for PubMedID 31706467

• Atrial Fibrillation Burden Signature and Near-Term Prediction of Stroke: A Machine Learning Analysis. Circulation. Cardiovascular quality and outcomes Han, L., Askari, M., Altman, R. B., Schmitt, S. K., Fan, J., Bentley, J. P., Narayan, S. M., Turakhia, M. P. 2019; 12 (10): e005595

  Abstract

  BACKGROUND: Atrial fibrillation (AF) increases the risk of stroke 5-fold and there is rising interest to determine if AF severity or burden can further risk stratify these patients, particularly for near-term events. Using continuous remote monitoring data from cardiac implantable electronic devices, we sought to evaluate if machine learned signatures of AF burden could provide prognostic information on near-term risk of stroke when compared to conventional risk scores.METHODS AND RESULTS: We retrospectively identified Veterans Health Administration serviced patients with cardiac implantable electronic device remote monitoring data and at least one day of device-registered AF. The first 30 days of remote monitoring in nonstroke controls were compared against the past 30 days of remote monitoring before stroke in cases. We trained 3 types of models on our data: (1) convolutional neural networks, (2) random forest, and (3) L1 regularized logistic regression (LASSO). We calculated the CHA2DS2-VASc score for each patient and compared its performance against machine learned indices based on AF burden in separate test cohorts. Finally, we investigated the effect of combining our AF burden models with CHA2DS2-VASc. We identified 3114 nonstroke controls and 71 stroke cases, with no significant differences in baseline characteristics. Random forest performed the best in the test data set (area under the curve [AUC]=0.662) and convolutional neural network in the validation dataset (AUC=0.702), whereas CHA2DS2-VASc had an AUC of 0.5 or less in both data sets. Combining CHA2DS2-VASc with random forest and convolutional neural network yielded a validation AUC of 0.696 and test AUC of 0.634, yielding the highest average AUC on nontraining data.CONCLUSIONS: This proof-of-concept study found that machine learning and ensemble methods that incorporate daily AF burden signature provided incremental prognostic value for risk stratification beyond CHA2DS2-VASc for near-term risk of stroke.

  View details for DOI 10.1161/CIRCOUTCOMES.118.005595

  View details for PubMedID 31610712

• Electrographic flow mapping in persistent atrial fibrillation Baykaner, T., Alhusseini, M., Rogers, A., Sauer, W., Ruppersberg, P., Narayan, S. WILEY. 2019: 1745–46

  View details for Web of Science ID 000485280500073

• Wavefront Field Mapping Reveals a Physiologic Network Between Drivers Where Ablation Terminates Atrial Fibrillation. Circulation. Arrhythmia and electrophysiology Leef, G., Shenasa, F., Bhatia, N. K., Rogers, A. J., Sauer, W., Miller, J. M., Swerdlow, M., Tamboli, M., Alhusseini, M. I., Armenia, E., Baykaner, T., Brachmann, J., Turakhia, M. P., Atienza, F., Rappel, W., Wang, P. J., Narayan, S. M. 2019; 12 (8): e006835

  Abstract

  BACKGROUND: Localized drivers are proposed mechanisms for persistent atrial fibrillation (AF) from optical mapping of human atria and clinical studies of AF, yet are controversial because drivers fluctuate and ablating them may not terminate AF. We used wavefront field mapping to test the hypothesis that AF drivers, if concurrent, may interact to produce fluctuating areas of control to explain their appearance/disappearance and acute impact of ablation.METHODS: We recruited 54 patients from an international registry in whom persistent AF terminated by targeted ablation. Unipolar AF electrograms were analyzed from 64-pole baskets to reconstruct activation times, map propagation vectors each 20 ms, and create nonproprietary phase maps.RESULTS: Each patient (63.6±8.5 years, 29.6% women) showed 4.0±2.1 spatially anchored rotational or focal sites in AF in 3 patterns. First, a single (type I; n=7) or, second, paired chiral-antichiral (type II; n=5) rotational drivers controlled most of the atrial area. Ablation of 1 to 2 large drivers terminated all cases of types I or II AF. Third, interaction of 3 to 5 drivers (type III; n=42) with changing areas of control. Targeted ablation at driver centers terminated AF and required more ablation in types III versus I (P=0.02 in left atrium).CONCLUSIONS: Wavefront field mapping of persistent AF reveals a pathophysiologic network of a small number of spatially anchored rotational and focal sites, which interact, fluctuate, and control varying areas. Future work should define whether AF drivers that control larger atrial areas are attractive targets for ablation.

  View details for DOI 10.1161/CIRCEP.118.006835

  View details for PubMedID 31352796

• Propagation velocity at atrial fibrillation sources: Go with the flow INTERNATIONAL JOURNAL OF CARDIOLOGY Rogers, A. J., Bhatia, N. K., Brodt, C. R., Narayan, S. M. 2019; 286: 76–77

  View details for DOI 10.1016/j.ijcard.2019.04.007

  View details for Web of Science ID 000465271500018

• Deep learning for cardiovascular medicine: a practical primer EUROPEAN HEART JOURNAL Krittanawong, C., Johnson, K. W., Rosenson, R. S., Wang, Z., Aydar, M., Baber, U., Min, J. K., Tang, W., Halperin, J. L., Narayan, S. M. 2019; 40 (25): 2058-+

  View details for DOI 10.1093/eurheartj/ehz056

  View details for Web of Science ID 000490138100016

• Editorial: High density mapping of atrial fibrillation sources JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Rogers, A. J., Bhatia, N. K., Brodt, C., Narayan, S. M. 2019; 30 (6): 964–65

  View details for DOI 10.1111/jce.13949

  View details for Web of Science ID 000472680300020

• Propagation velocity at atrial fibrillation sources: Go with the flow. International journal of cardiology Rogers, A. J., Bhatia, N. K., Brodt, C. R., Narayan, S. M. 2019

  View details for PubMedID 30979605

• MACHINE LEARNING IDENTIFIES SITES WHERE ABLATION TERMINATES PERSISTENT ATRIAL FIBRILLATION Alhusseini, M., Abuzaid, F., Clopton, P., Rogers, A., Rodrigo, M., Baykaner, T., Wang, P., Rappel, W., Narayan, S. ELSEVIER SCIENCE INC. 2019: 301

  View details for Web of Science ID 000460565900301

• Deep learning for cardiovascular medicine: a practical primer. European heart journal Krittanawong, C., Johnson, K. W., Rosenson, R. S., Wang, Z., Aydar, M., Baber, U., Min, J. K., Tang, W. H., Halperin, J. L., Narayan, S. M. 2019

  Abstract

  Deep learning (DL) is a branch of machine learning (ML) showing increasing promise in medicine, to assist in data classification, novel disease phenotyping and complex decision making. Deep learning is a form of ML typically implemented via multi-layered neural networks. Deep learning has accelerated by recent advances in computer hardware and algorithms and is increasingly applied in e-commerce, finance, and voice and image recognition to learn and classify complex datasets. The current medical literature shows both strengths and limitations of DL. Strengths of DL include its ability to automate medical image interpretation, enhance clinical decision-making, identify novel phenotypes, and select better treatment pathways in complex diseases. Deep learning may be well-suited to cardiovascular medicine in which haemodynamic and electrophysiological indices are increasingly captured on a continuous basis by wearable devices as well as image segmentation in cardiac imaging. However, DL also has significant weaknesses including difficulties in interpreting its models (the 'black-box' criticism), its need for extensive adjudicated ('labelled') data in training, lack of standardization in design, lack of data-efficiency in training, limited applicability to clinical trials, and other factors. Thus, the optimal clinical application of DL requires careful formulation of solvable problems, selection of most appropriate DL algorithms and data, and balanced interpretation of results. This review synthesizes the current state of DL for cardiovascular clinicians and investigators, and provides technical context to appreciate the promise, pitfalls, near-term challenges, and opportunities for this exciting new area.

  View details for PubMedID 30815669

• New Concepts in Sudden Cardiac Arrest to Addressan Intractable Epidemic: JACC State-of-the-Art Review. Journal of the American College of Cardiology Narayan, S. M., Wang, P. J., Daubert, J. P. 2019; 73 (1): 70–88

  Abstract

  Sudden cardiac arrest (SCA) is one of the largest causes of mortality globally, with an out-of-hospital survival below 10% despite intense research. This document outlines challenges in addressing the epidemic of SCA, along the framework of respond, understand and predict, and prevent. Response could be improved by technology-assisted orchestration of community responder systems, access to automated external defibrillators, and innovations to match resuscitation resources to victims in place and time. Efforts to understand and predict SCA may be enhanced by refining taxonomy along phenotypical and pathophysiological "axes of risk," extending beyond cardiovascular pathology to identify less heterogeneous cohorts, facilitated by open-data platforms and analytics including machine learning to integrate discoveries across disciplines. Prevention of SCA must integrate these concepts, recognizing that all members of society are stakeholders. Ultimately, solutions to the public health challenge of SCA will require greater awareness, societal debate and focused public policy.

  View details for PubMedID 30621954

• Efficacy of Ablation Lesion Sets in Addition to Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation: Findings From the SMASH - AF Meta-Analysis Study Cohort. Journal of the American Heart Association Cluckey, A., Perino, A. C., Yunus, F. N., Leef, G. C., Askari, M., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2019; 8 (1): e009976

  Abstract

  Background The objective was to explore the efficacy of ablation lesion sets in addition to pulmonary vein isolation ( PVI ) for paroxysmal atrial fibrillation. The optimal strategy for catheter ablation of paroxysmal atrial fibrillation is debated. Methods and Results The SMASH-AF (Systematic Review and Meta-analysis of Ablation Strategy Heterogeneity in Atrial Fibrillation) study cohort includes trials and observational studies identified in PubMed, Scopus, and Cochrane databases from January 1 1990, to August 1, 2016. We included studies reporting single procedure paroxysmal atrial fibrillation ablation success rates. Exclusion criteria included insufficient reporting of outcomes, ablation strategies that were not prespecified and uniform, and a sample size of fewer than 40 patients. We analyzed lesion sets performed in addition to PVI ( PVI plus) using multivariable random-effects meta-regression to control for patient, study, and procedure characteristics. The analysis included 145 total studies with 23263 patients ( PVI- only cohort: 115 studies, 148 treatment arms, 16500 patients; PVI plus cohort: 39 studies; 46 treatment arms, 6763 patients). PVI plus studies, as compared with PVI -only studies, included younger patients (56.7years versus 58.8years, P=0.001), fewer women (27.2% versus 32.0% women, P=0.002), and were more methodologically rigorous with longer follow-up (29.5 versus 17.1months, P 0.004) and more randomization (19.4% versus 11.8%, P<0.001). In multivariable meta-regression, PVI plus studies were associated with improved success (7.6% absolute improvement [95% CI, 2.6-12.5%]; P<0.01, I2=88%), specifically superior vena cava isolation (4 studies, 4 treatment arms, 1392 patients; 15.1% absolute improvement [95%CI, 2.3-27.9%]; P 0.02, I2=87%). However, residual heterogeneity was large. Conclusions Across the paroxysmal atrial fibrillation ablation literature, PVI plus ablation strategies were associated with incremental improvements in success rate. However, large residual heterogeneity complicates evidence synthesis.

  View details for PubMedID 30587059

• Integrating blockchain technology with artificial intelligence for cardiovascular medicine. Nature reviews. Cardiology Krittanawong, C. n., Rogers, A. J., Aydar, M. n., Choi, E. n., Johnson, K. W., Wang, Z. n., Narayan, S. M. 2019

  View details for DOI 10.1038/s41569-019-0294-y

  View details for PubMedID 31605093

• Response by Bhatia et al to Letter Regarding Article, "Wavefront Field Mapping Reveals a Physiologic Network Between Drivers Where Ablation Terminates Atrial Fibrillation". Circulation. Arrhythmia and electrophysiology Bhatia, N. K., Rappel, W. J., Narayan, S. M. 2019; 12 (11): e008022

  View details for DOI 10.1161/CIRCEP.119.008022

  View details for PubMedID 31726861

• Editorial: High density mapping of atrial fibrillation sources. Journal of cardiovascular electrophysiology Rogers, A. J., Bhatia, N. K., Brodt, C. n., Narayan, S. M. 2019

  View details for PubMedID 31056801

• Urinary tract infection after catheter ablation of atrial fibrillation. Pacing and clinical electrophysiology : PACE Cluckey, A. n., Perino, A. C., Fan, J. n., Askari, M. n., Nasir, J. n., Marcus, G. M., Baykaner, T. n., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2019

  Abstract

  Urinary tract infection (UTI) is common after surgical procedures and a quality improvement target. For non-surgical procedures such as catheter ablation of atrial fibrillation (AF), UTI risk has not been characterized. We sought to determine incidence and risk factors of UTI after AF ablation and risk variation across sites.Using Marketscan commercial claims databases, we performed a retrospective cohort study of patients that underwent AF ablation from 2007 to 2011. The primary outcome was UTI diagnosis within 30 days after ablation. We performed multivariate analyses to determine risk factors for UTI and risk of sepsis within 30 days after ablation with UTI as the predictor variable. Median odds ratio was used to quantify UTI site variation.Among 21,091 patients (age 59.2±10.9; 29.1% female; CHA2 DS2 -VASc 2.0±1.6), 622 (2.9%) were diagnosed with UTI within 30 days. In multivariate analyses, UTI was independently associated with age, female sex, prior UTI, and general anesthesia (all p < 0.01). UTI diagnosis was associated with a substantial increased risk of sepsis within 30 days (5.0% vs. 0.3%; OR 17.5; 95% CI 10.8 - 28.2; p < 0.0001). Among 416 sites, 211 had at least one UTI. Among these 211 sites, the incidence of post-ablation UTI ranged from 0.7%-26.7% (median: 5.4%; IQR: 3.0%-7.1%; 95th percentile: 14.3%; median odds ratio: 1.45; 95% CI 1.41-1.50).UTI after AF ablation is not uncommon and varies substantially across sites. Consideration of UTI as a quality measure and interventions targeted at high-risk patients or sites warrant consideration. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pace.13738

  View details for PubMedID 31168821

• Online webinar training to analyse complex atrial fibrillation maps: A randomized trial. PloS one Mesquita, J. n., Maniar, N. n., Baykaner, T. n., Rogers, A. J., Swerdlow, M. n., Alhusseini, M. I., Shenasa, F. n., Brizido, C. n., Matos, D. n., Freitas, P. n., Santos, A. R., Rodrigues, G. n., Silva, C. n., Rodrigo, M. n., Dong, Y. n., Clopton, P. n., Ferreira, A. M., Narayan, S. M. 2019; 14 (7): e0217988

  Abstract

  Specific tools have been recently developed to map atrial fibrillation (AF) and help guide ablation. However, when used in clinical practice, panoramic AF maps generated from multipolar intracardiac electrograms have yielded conflicting results between centers, likely due to their complexity and steep learning curve, thus limiting the proper assessment of its clinical impact.The main purpose of this trial was to assess the impact of online training on the identification of AF driver sites where ablation terminated persistent AF, through a standardized training program. Extending this concept to mobile health was defined as a secondary objective.An online database of panoramic AF movies was generated from a multicenter registry of patients in whom targeted ablation terminated non-paroxysmal AF, using a freely available method (Kuklik et al-method A) and a commercial one (RhythmView-method B). Cardiology Fellows naive to AF mapping were enrolled and randomized to training vs no training (control). All participants evaluated an initial set of movies to identify sites of AF termination. Participants randomized to training evaluated a second set of movies in which they received feedback on their answers. Both groups re-evaluated the initial set to assess the impact of training. This concept was then migrated to a smartphone application (App).12 individuals (median age of 30 years (IQR 28-32), 6 females) read 480 AF maps. Baseline identification of AF termination sites by ablation was poor (40%±12% vs 42%±11%, P = 0.78), but similar for both mapping methods (P = 0.68). Training improved accuracy for both methods A (P = 0.001) and B (p = 0.012); whereas controls showed no change in accuracy (P = NS). The Smartphone App accessed AF maps from multiple systems on the cloud to recreate this training environment.Digital online training improved interpretation of panoramic AF maps in previously inexperienced clinicians. Combining online clinical data, smartphone apps and other digital resources provides a powerful, scalable approach for training in novel techniques in electrophysiology.

  View details for DOI 10.1371/journal.pone.0217988

  View details for PubMedID 31269029

• Moving the Needle: Tissue Characterization and Lesion Formation During Infusion-Needle Ablation. Heart rhythm Nguyen, D. T., Narayan, S. M. 2019

  View details for DOI 10.1016/j.hrthm.2019.10.018

  View details for PubMedID 31614225

• Electroporation: The End of the Thermal Ablation Era? Journal of the American College of Cardiology Narayan, S. M., Baykaner, T. n. 2019; 74 (3): 327–29

  View details for DOI 10.1016/j.jacc.2019.06.013

  View details for PubMedID 31319914

• Rapid Point-by-Point Pulmonary Vein Isolation. JACC. Clinical electrophysiology Michaud, G. F., Narayan, S. M. 2019; 5 (7): 787–88

  View details for DOI 10.1016/j.jacep.2019.05.007

  View details for PubMedID 31320007

• Dielectric-Based Imaging And Navigation Of The Heart. Heart rhythm Rogers, A. J., Narayan, S. M. 2019

  View details for DOI 10.1016/j.hrthm.2019.07.016

  View details for PubMedID 31323349

• Transparent Sharing of Digital Health Data: A Call to Action. Heart rhythm Slotwiner, D. J., Tarakji, K. G., Al-Khatib, S. M., Passman, R. S., Saxon, L. A., Peters, N. S., McCall, D. n., Turakhia, M. P., Schaeffer, J. n., Mendenhall, G. S., Hindricks, G. n., Narayan, S. M., Davenport, E. E., Marrouche, N. F. 2019

  View details for PubMedID 31077802

• Catheter ablation or surgery to eliminate longstanding persistent atrial fibrillation. International journal of cardiology Shah, R. L., Zaman, J. A., Narayan, S. M. 2019

  View details for DOI 10.1016/j.ijcard.2019.12.048

  View details for PubMedID 31924396

• Transient Outward K+ Current Can Strongly Modulate Action Potential Duration and Initiate Alternans in Human Atrium. American journal of physiology. Heart and circulatory physiology Ni, H., Zhang, H., Grandi, E., Narayan, S. M., Giles, W. 2018

  Abstract

  Efforts to identify the mechanisms that are responsible for the initiation and maintenance of human atrial fibrillation (AF) often focus on changes in one or more elements of the atrial 'substrate'. These correspond to the electrophysiological properties and/or structural elements. We have used experimentally validated mathematical models of the human atrial myocyte action potential, both at baseline in sinus rhythm (SR) and in the setting of chronic AF, to identify significant contributions of the Ca2+-independent transient outward K+ current, Ito, to electrophysiological instability and arrhythmia initiation. Specifically, our initial simulations explored whether changes in the recovery or restitution of the action potential duration (APD), and/or its dynamic stability (alternans) can be modulated by Ito. Recent reports have identified spatial differences in the expression levels of specific K+ channel alpha-subunits that underlie Ito in the left atrium. We observed that following replacement of 50% of the native Ito current, Kv4.3; and its replacement with Kv1.4, significant changes in the stability of human atrial action potential waveform arose. This isoform switch resulted in discontinuities in the initial slope of the APD restitution curve and APD alternans sometimes emerged. Important insights into cellular mechanisms for these changes are based on known biophysical properties (reactivation kinetics) of Kv1.4 versus those of Kv4.3. The emerging pattern of in silico results resemble some of the changes observed in high resolution MAP recordings during clinical electrophysiological studies. The resulting insights provide a basis for considering novel Kv1.4-based pharmacological treatment(s) in management of AF.

  View details for PubMedID 30576220

• Comparison of phase-mapping and electrogram-based driver mapping for catheter ablation in atrial fibrillation. Pacing and clinical electrophysiology : PACE Lin, C., Lin, Y., Narayan, S. M., Baykaner, T., Lo, M., Chung, F., Chen, Y., Chang, S., Lo, L., Hu, Y., Liao, J., Tuan, T., Chao, T., Te, A. L., Kuo, L., Vicera, J. J., Chang, T., Salim, S., Chien, K., Chen, S. 2018

  Abstract

  INTRODUCTION: Adjunctive driver-guided ablation in addition to pulmonary vein isolation has been proposed as a strategy to improve procedural success and outcomes for various populations with atrial fibrillation (AF). This study firstly aimed to evaluate the different mapping techniques for driver/rotor identification and secondly to evaluate the benefit of driver/rotor guided ablation in patients with paroxysmal and persistent AF.METHODS: We searched the electronic database in PubMed using the keywords "atrial fibrillation", "rotor", "rotational driver", "atrial fibrillation source", and "drivers" for both randomized controlled trials and observational controlled trials. Clinical studies reporting efficacy or safety outcomes of driver-guided ablation for paroxysmal AF (PAF) or PerAF were identified. We performed subgroup analyses comparing different driver mapping methods in patients with PerAF. The odds ratios (OR) with random-effects were analyzed.RESULTS: Out of 175 published articles, 7 met the inclusion criteria, of which 2 were randomized controlled trials, 1 quasi-experimental study, and four observational studies (three case-controlled studies and one cross-sectional study). Overall, adjunctive driver-guided ablation was associated with higher rates of acute AF termination (OR: 4.62, 95% confidence interval [CI]: 2.12-10.08; P<0.001), lower recurrence of any atrial arrhythmia (OR: 0.44, 95% CI: 0.30-0.065; P<0.001), and comparable complication incidence.CONCLUSIONS: Adjunctive driver-guided catheter ablation suggested increased freedom from AF/AT relative to conventional strategies, irrespective of the mapping technique. Furthermore, phase-mapping appears to be superior to electrogram-based driver mapping in PerAF ablation. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30536679

• Structurally-based electrical predictors of atrial arrhythmias. International journal of cardiology Rogers, A. J., Moosvi, N. F., Brodt, C. R., Narayan, S. M. 2018

  View details for PubMedID 30528625

• Predictability in Complex Atrial Arrhythmias: the N/N-1 Algorithm to Guide Ablation of Atrial Tachycardias. Heart rhythm Kaiser, D. W., Rogers, A. J., Narayan, S. M. 2018

  View details for PubMedID 30465903

• Secular trends in success rate of catheter ablation for atrial fibrillation: The SMASH-AF cohort. American heart journal Perino, A. C., Leef, G. C., Cluckey, A., Yunus, F. N., Askari, M., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2018

  Abstract

  BACKGROUND: Approaches, tools, and technologies for atrial fibrillation (AF) ablation have evolved significantly since its inception. We sought to characterize secular trends in AF ablation success rates.METHODS: We performed a systematic review and meta-analysis of AF ablation from January 1, 1990, to August 1, 2016, searching PubMed, Scopus, and Cochrane databases. Major exclusion criteria were insufficient outcome reporting and ablation strategies that were not prespecified and uniform. We stratified treatment arms by AF type (paroxysmal AF; nonparoxysmal AF) and analyzed single-procedure outcomes. Multivariate meta-regressions analyzed effects of study, patient, and procedure characteristics on success rate trends. Registered in PROSPERO (CRD42016036549).RESULTS: A total of 180 trials and observational studies with 28,118 patients met inclusion. For paroxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 73.1% in 2003 to 77.1% in 2016, increasing by 0.9%/year (95% CI 0.4%-1.4%; P = .001; I2 = 90%). After controlling for study design and patient demographics, rate of improvement in success rate summary estimate increased (1.6%/year; 95% CI 0.9%-2.2%; P = .001; I2 = 87%). For nonparoxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 70.0% in 2010 to 64.3% in 2016 (1.1%/year; 95% CI -1.3% to 3.5%; P = .37; I2 = 85%), with no improvement in multivariate analyses.CONCLUSIONS: Despite substantial research investment and health care expenditure, improvements in AF ablation success rates have been incremental. Meaningful improvements may require major paradigm or technology changes, and evaluation of clinical outcomes such as mortality and quality of life may prove to be important going forward.

  View details for PubMedID 30502925

• Characterizing Electrogram Signal Fidelity and the Effects of Signal Contamination on Mapping Human Persistent Atrial Fibrillation FRONTIERS IN PHYSIOLOGY Vidmar, D., Alhusseini, M., Narayan, S. M., Rappel, W. 2018; 9

  View details for DOI 10.3389/fphys.2018.01232

  View details for Web of Science ID 000443769500001

• Characterizing Electrogram Signal Fidelity and the Effects of Signal Contamination on Mapping Human Persistent Atrial Fibrillation. Frontiers in physiology Vidmar, D., Alhusseini, M. I., Narayan, S. M., Rappel, W. J. 2018; 9: 1232

  Abstract

  Objective: Determining accurate intracardiac maps of atrial fibrillation (AF) in humans can be difficult, owing primarily to various sources of contamination in electrogram signals. The goal of this study is to develop a measure for signal fidelity and to develop methods to quantify robustness of observed rotational activity in phase maps subject to signal contamination. Methods: We identified rotational activity in phase maps of human persistent AF using the Hilbert transform of sinusoidally recomposed signals, where localized ablation at rotational sites terminated fibrillation. A novel measure of signal fidelity was developed to quantify signal quality. Contamination is then introduced to the underlying electrograms by removing signals at random, adding noise to computations of cycle length, and adding realistic far-field signals. Mean tip number N and tip density δ, defined as the proportion of time a region contains a tip, at the termination site are computed to compare the effects of contamination. Results: Domains of low signal fidelity correspond to the location of rotational cores. Removing signals and altering cycle length accounted for minor changes in tip density, while targeted removal of low fidelity electrograms can result in a significant increase in tip density and stability. Far-field contamination was found to obscure rotation at the termination site. Conclusion: Rotational activity in clinical AF can produce domains of low fidelity electrogram recordings at rotational cores. Observed rotational patterns in phase maps appear most sensitive to far-field activation. These results may inform novel methods to map AF in humans which can be tested directly in patients at electrophysiological study and ablation.

  View details for DOI 10.3389/fphys.2018.01232

  View details for PubMedID 30237766

  View details for PubMedCentralID PMC6135945

• Integrating mapping methods for atrial fibrillation. Pacing and clinical electrophysiology : PACE Rogers, A. J., Tamboli, M., Narayan, S. M. 2018

  View details for DOI 10.1111/pace.13476

  View details for PubMedID 30144115

• Interaction of Localized Drivers and Disorganized Activation in Persistent Atrial Fibrillation: Reconciling Putative Mechanisms Using Multiple Mapping Techniques CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Kowalewski, C. B., Shenasa, F., Rodrigo, M., Clopton, P., Meckler, G., Alhusseini, M. I., Swerdlow, M. A., Joshi, V., Hossainy, S., Zaman, J. B., Baykaner, T., Rogers, A. J., Brachmann, J., Miller, J. M., Krummen, D. E., Sauer, W. H., Peters, N. S., Wang, P. J., Narayan, S. M. 2018; 11 (6): e005846

  Abstract

  Mechanisms for persistent atrial fibrillation (AF) are unclear. We hypothesized that putative AF drivers and disorganized zones may interact dynamically over short time scales. We studied this interaction over prolonged durations, focusing on regions where ablation terminates persistent AF using 2 mapping methods.We recruited 55 patients with persistent AF in whom ablation terminated AF prior to pulmonary vein isolation from a multicenter registry. AF was mapped globally using electrograms for 360±45 cycles using (1) a published phase method and (2) a commercial activation/phase method.Patients were 62.2±9.7 years, 76% male. Sites of AF termination showed rotational/focal patterns by methods 1 and 2 (51/55 vs 55/55; P=0.13) in spatially conserved regions, yet fluctuated over time. Time points with no AF driver showed competing drivers elsewhere or disordered waves. Organized regions were detected for 61.6±23.9% and 70.6±20.6% of 1 minute per method (P=nonsignificant), confirmed by automatic phase tracking (P<0.05). To detect AF drivers with >90% sensitivity, 8 to 32 s of AF recordings were required depending on driver definition.Sites at which persistent AF terminated by ablation show organized activation that fluctuate over time, because of collision from concurrent organized zones or fibrillatory waves, yet recur in conserved spatial regions. Results were similar by 2 mapping methods. This network of competing mechanisms should be reconciled with existing disorganized or driver mechanisms for AF, to improve clinical mapping and ablation of persistent AF.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02997254.

  View details for PubMedID 29884620

• Improving sudden cardiac death risk stratification by evaluating electrocardiographic measures of global electrical heterogeneity and clinical outcomes among patients with implantable cardioverter-defibrillators: rationale and design for a retrospective, multicenter, cohort study JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Waks, J. W., Hamilton, C., Das, S., Ehdaie, A., Minnier, J., Narayan, S., Niebauer, M., Raitt, M., Tompkins, C., Varma, N., Chugh, S., Tereshchenko, L. G. 2018; 52 (1): 77–89

  Abstract

  Implantable cardioverter-defibrillators (ICDs) improve survival of systolic heart failure (HF) patients who are at risk of sudden cardiac death (SCD). We recently showed that electrocardiographic (ECG) global electrical heterogeneity (GEH) is independently associated with SCD in the community-dwelling cohort and developed GEH SCD risk score. The Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study is a retrospective multicenter cohort designed with two goals: (1) validate an independent association of ECG GEH with sustained ventricular tachyarrhythmias and appropriate ICD therapies and (2) validate GEH ECG risk score for prediction of sustained ventricular tachyarrhythmias and appropriate ICD therapies in systolic HF patients with primary prevention ICD.All records of primary prevention ICD recipients with available data for analysis are eligible for inclusion. Records of ICD implantation in patients with inherited channelopathies and cardiomyopathies are excluded. Raw digital 12-lead pre-implant ECGs will be used to measure GEH (spatial QRST angle, spatial ventricular gradient magnitude, azimuth, and elevation, and sum absolute QRST integral). The primary endpoint is defined as a sustained ventricular tachyarrhythmia event with appropriate ICD therapy. All-cause death without preceding sustained ventricular tachyarrhythmia with appropriate ICD therapy will serve as a primary competing outcome. The study will draw data from the academic medical centers.We describe the study protocol of the first multicenter retrospective cohort of primary prevention ICD patients with recorded at baseline digital 12-lead ECG.Findings from this study will inform future trials to identify patients who are most likely to benefit from primary prevention ICD.URL: http://www.clinicaltrials.gov . Unique identifier: NCT03210883.

  View details for PubMedID 29541969

• Statistical guidance of VT ablation. Journal of cardiovascular electrophysiology Rodrigo, M., Narayan, S. M. 2018

  View details for PubMedID 29771455

• Interpreting Activation Mapping of Atrial Fibrillation: A Hybrid Computational/Physiological Study ANNALS OF BIOMEDICAL ENGINEERING Costabal, F., Zaman, J. B., Kuhl, E., Narayan, S. M. 2018; 46 (2): 257–69

  Abstract

  Atrial fibrillation is the most common rhythm disorder of the heart associated with a rapid and irregular beating of the upper chambers. Activation mapping remains the gold standard to diagnose and interpret atrial fibrillation. However, fibrillatory activation maps are highly sensitive to far-field effects, and often disagree with other optical mapping modalities. Here we show that computational modeling can identify spurious non-local components of atrial fibrillation electrograms and improve activation mapping. We motivate our approach with a cohort of patients with potential drivers of persistent atrial fibrillation. In a computational study using a monodomain Maleckar model, we demonstrate that in organized rhythms, electrograms successfully track local activation, whereas in atrial fibrillation, electrograms are sensitive to spiral wave distance and number, spiral tip trajectories, and effects of fibrosis. In a clinical study, we analyzed n = 15 patients with persistent atrial fibrillation that was terminated by limited ablation. In five cases, traditional activation maps revealed a spiral wave at sites of termination; in ten cases, electrogram timings were ambiguous and activation maps showed incomplete reentry. By adjusting electrogram timing through computational modeling, we found rotational activation, which was undetectable with conventional methods. Our results demonstrate that computational modeling can identify non-local deflections to improve activation mapping and explain how and where ablation can terminate persistent atrial fibrillation. Our hybrid computational/physiological approach has the potential to optimize map-guided ablation and improve ablation therapy in atrial fibrillation.

  View details for PubMedID 29214421

  View details for PubMedCentralID PMC5880222

• Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation. Journal of cardiovascular electrophysiology Navara, R., Leef, G., Shenasa, F., Kowalewski, C., Rogers, A. J., Meckler, G., Zaman, J. A., Baykaner, T., Park, S., Turakhia, M. P., Zei, P., Viswanathan, M., Wang, P. J., Narayan, S. M. 2018

  Abstract

  OBJECTIVE: To investigate mechanisms by which atrial fibrillation (AF) may terminate during ablation near the pulmonary veins before the veins are isolated (PVI).INTRODUCTION: It remains unstudied how AF may terminate during ablation before PVs are isolated, or how patients with PV reconnection can be arrhythmia-free. We studied patients in whom PV antral ablation terminated AF before PVI, using two independent mapping methods.METHODS: We studied patients with AF referred for ablation, in whom biatrial contact basket electrograms were studied by both an activation/phase mapping method and by a second validated mapping method reported not to create false rotational activity.RESULTS: In 22 patients (age 60.1 ± 10.4, 36% persistent AF), ablation at sites near the PVs terminated AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n=20) and focal (n=2) patterns at sites of termination by mapping method 1 and method 2. Both methods showed organized sites that were spatially concordant (P<0.001) with similar stability (P<0.001). Vagal slowing was not observed at sites of AF termination.DISCUSSION: PV antral regions where ablation terminated AF before PVI exhibited rotational and focal activation by two independent mapping methods. These data provide an alternative mechanism for the success of PVI, and may explain AF termination before PVI or lack of arrhythmias despite PV reconnection. Mapping such sites may enable targeted PV lesion sets and improved freedom from AF.

  View details for PubMedID 29377478

• Geographic and racial representation and reported success rates of studies of catheter ablation for atrial fibrillation: Findings from the SMASH-AF meta-analysis study cohort. Journal of cardiovascular electrophysiology Leef, G. C., Perino, A. C., Cluckey, A., Yunus, F. N., Askari, M., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2018

  Abstract

  INTRODUCTION: We performed a systematic review and meta-analysis of geographic and racial representation and reported success rates of studies of catheter ablation for atrial fibrillation (AF).METHODS AND RESULTS: We searched PubMed, Scopus, and Cochrane databases from 1/1/1990 to 8/1/2016 for trials and observational studies reporting AF ablation outcomes. Major exclusion criteria were insufficient reporting of outcomes, non-English language articles, and ablation strategies that were not prespecified and uniform. We described geographic and racial representation and single-procedure ablation success rates by country, controlling for patient demographics and study design characteristics. The analysis cohort included 306 studies (49,227 patients) from 28 countries. Over half of the paroxysmal (PAF) and nonparoxysmal AF (NPAF) treatment arms were conducted in 5 and 3 countries, respectively. Reporting of race or ethnicity demographics and outcomes were rare (1 study, 0.3%) and nonexistent, respectively. Unadjusted success rates by country ranged from 63.5% to 83.0% for PAF studies and 52.7% to 71.6% for NPAF studies, with substantial variation in patient demographics and study design. After controlling for covariates, South Korea and the United States had higher PAF ablation success rates, with large residual heterogeneity. NPAF ablation success rates were statistically similar by country.CONCLUSIONS: Studies of AF ablation have substantial variation in patient demographics, study design, and reported outcomes by country. There is limited geographic representation of trials and observational studies of AF ablation and a paucity of race- or ethnicity-stratified results. Future AF ablation studies and registries should aim to have broad representation by race, geography, and ethnicity to ensure generalizability.

  View details for PubMedID 29364570

• Clinical Implications of Ablation of Drivers for Atrial Fibrillation: A Systematic Review and Meta-Analysis. Circulation. Arrhythmia and electrophysiology Baykaner, T. n., Rogers, A. J., Meckler, G. L., Zaman, J. n., Navara, R. n., Rodrigo, M. n., Alhusseini, M. n., Kowalewski, C. A., Viswanathan, M. N., Narayan, S. M., Clopton, P. n., Wang, P. J., Heidenreich, P. A. 2018; 11 (5): e006119

  Abstract

  The outcomes from pulmonary vein isolation (PVI) for atrial fibrillation (AF) are suboptimal, but the benefits of additional lesion sets remain unproven. Recent studies propose ablation of AF drivers improves outcomes over PVI, yet with conflicting reports in the literature. We undertook a systematic literature review and meta-analysis to determine outcomes from ablation of AF drivers in addition to PVI or as a stand-alone procedure.Database search was done using the terms atrial fibrillation and ablation or catheter ablation and driver or rotor or focal impulse or FIRM (Focal Impulse and Rotor Modulation). We pooled data using random effects model and assessed heterogeneity with I2 statistic.Seventeen studies met inclusion criteria, in a cohort size of 3294 patients. Adding AF driver ablation to PVI reported freedom from AF of 72.5% (confidence interval [CI], 62.1%-81.8%; P<0.01) and from all arrhythmias of 57.8% (CI, 47.5%-67.7%; P<0.01). AF driver ablation when added to PVI or as stand-alone procedure compared with controls produced an odds ratio of 3.1 (CI, 1.3-7.7; P=0.02) for freedom from AF and an odds ratio of 1.8 (CI, 1.2-2.7; P<0.01) for freedom from all arrhythmias in 4 controlled studies. AF termination rate was 40.5% (CI, 30.6%-50.9%) and predicted favorable outcome from ablation(P<0.05).In controlled studies, the addition of AF driver ablation to PVI supports the possible benefit of a combined approach of AF driver ablation and PVI in improving single-procedure freedom from all arrhythmias. However, most studies are uncontrolled and are limited by substantial heterogeneity in outcomes. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to PVI.

  View details for PubMedID 29743170

• Patient and facility variation in costs of catheter ablation for atrial fibrillation. Journal of cardiovascular electrophysiology Perino, A. C., Fan, J. n., Schmitt, S. n., Kaiser, D. W., Heidenreich, P. A., Narayan, S. M., Wang, P. J., Chang, A. Y., Turakhia, M. P. 2018

  Abstract

  Cost-effectiveness or value of cardiovascular therapies may be undermined by unwarranted cost variation, particularly for heterogeneous procedures such as catheter ablation for atrial fibrillation (AF). We sought to characterize cost variation of AF ablation in the U.S. health care system and the relationship between cost and outcomes.We performed a retrospective cohort study using data from the MarketScan® commercial claims and Medicare supplemental databases including patients who received an AF ablation from 2007 through 2011. We aggregated encounter cost, reflecting total payments received for the encounter, to the facility level to calculate median facility cost. We classified procedures as outpatient or inpatient and assessed for association between cost and 30-day and one-year outcomes. The analysis cohort included 9,415 AF ablations (59±11 years; 28% female; 52% outpatient) occurring at 327 facilities, with large cost variation across facilities (median: $25,100; 25th percentile: $18,900, 75th percentile: $35,600, 95th percentile: $57,800). Among outpatient procedures, there was reduced health care utilization in higher cost quintiles with reductions in rehospitalization at 30-days (Quintile 1: 16.1%, Quintile 5: 8.8%, p < 0.001) and one-year (Quintile 1: 34.8%, Quintile 5: 25.6%, p < 0.001), which remained significant in multivariate analysis.Although median costs of AF ablation are below amounts used in prior cost-effectiveness studies that demonstrated good value, large facility variation in cost suggests opportunities for cost reduction. However, for outpatient encounters, association of cost to modestly improved outcomes suggests cost containment strategies could have variable effects. This article is protected by copyright. All rights reserved.

  View details for PubMedID 29864193

• Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Zaman, J. B., Sauer, W. H., Alhusseini, M. I., Baykaner, T., Borne, R. T., Kowalewski, C. B., Busch, S., Zei, P. C., Park, S., Viswanathan, M. N., Wang, P. J., Brachmann, J., Krummen, D. E., Miller, J. M., Rappel, W., Narayan, S. M., Peters, N. S. 2018; 11 (1): e005258

  Abstract

  The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation.We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. For each site, we performed an offline analysis of unprocessed unipolar electrograms collected during AF from multipolar basket catheters using the maximum -dV/dt assignment to construct isochronal activation maps for multiple cycles. Additional computational modeling and phase analysis were used to study mechanisms of map variability. At all sites of AF termination, localized repetitive activation patterns were observed. Partial rotational circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%), and complete rotational activity in 12 of 57 (21%) cases. In computer simulations, incomplete segments of partial rotations coincided with areas of slow conduction characterized by complex, multicomponent electrograms, and variations in assigning activation times at such sites substantially altered mapped mechanisms.Local activation mapping at sites of termination of persistent AF showed repetitive patterns of rotational or focal activity. In computer simulations, complete rotational activation sequence was observed but was sensitive to assignment of activation timing particularly in segments of slow conduction. The observed phenomena of repetitive localized activation and the mechanism by which local ablation terminates putative AF drivers require further investigation.

  View details for PubMedID 29330332

  View details for PubMedCentralID PMC5769709

• Spatiotemporal Progression of Early Human Ventricular Fibrillation. JACC. Clinical electrophysiology Vidmar, D., Krummen, D. E., Hayase, J., Narayan, S. M., Ho, G., Rappel, W. J. 2017; 3 (12): 1437-1446

  Abstract

  The objective of this study was to evaluate the spatio-temporal organization and progression of human ventricular fibrillation (VF) in the left (LV) and right (RV) ventricles.Studies suggest that localized sources contribute to VF maintenance, but the evolution of VF episodes has not been quantified.Synchrony between electrograms recorded from 25 patients with induced VF is computed and used to define the Asynchronous Index (ASI), indicating regions which are out-of-step with surrounding tissue. Computer simulations show that ASI can identify the location of VF-maintaining sources, where larger values of ASImax correlate with more stable sources.Automated synchrony analysis shows elevated values of ASI in a majority of self-terminating episodes (LV: 8/9, RV: 7/8) and sustained episodes (LV: 11/11, RV: 12/12). The locations of ASImax in sustained episodes co-localize with rotor cores when rotational activity is simultaneously present in phase maps (LV: 8/8, RV: 5/7, p<.05). The distribution of ASImax differentiates self-terminating from sustained episodes (mean ASImax = 0.60±0.14 and 0.70±0.16, respectively; p=0.01). Across sustained episodes the LV exhibits an increase in ASImax with time.Quantitative analysis identifies localized asynchronous regions that correlate with sources in VF, with sustained episodes evolving to exhibit more stable activation in the LV. This successive increase in stability indicates a stabilizing agent may be responsible for perpetuating fibrillation in a "migrate-and-capture" mechanism in the LV.

  View details for DOI 10.1016/j.jacep.2017.04.009

  View details for PubMedID 29238755

  View details for PubMedCentralID PMC5725953

• Ablation of Atrial Fibrillation Drivers ARRHYTHMIA & ELECTROPHYSIOLOGY REVIEW Baykaner, T., Zaman, J. B., Wang, P. J., Narayan, S. M. 2017; 6 (4): 195–201

  Abstract

  Pulmonary vein isolation (PVI) is central to ablation approaches for atrial fibrillation (AF), yet many patients still have arrhythmia recurrence after one or more procedures, despite evolving technologies for PVI. Ablation of localised AF drivers, which lie outside the pulmonary veins in many patients, is a practical approach that has been shown to improve success by many groups. Such localised drivers lie in atrial regions shown mechanistically to sustain AF in optical mapping and clinical studies of human AF, as well as computational and animal studies. Clinical studies now verify rotational activation by multiple mapping approaches in the same patients, at sites where ablation terminates persistent AF. This review article provides a mechanistic and clinical rationale to ablate localised drivers, and describes successful techniques for their ablation as well as pitfalls to avoid, which may explain discrepancies between results from some centres. We hope that this review will serve as a platform for future improvements in the patient-tailored ablation for complex arrhythmias.

  View details for PubMedID 29326835

  View details for PubMedCentralID PMC5739904

• Rotational Drivers in Atrial Fibrillation: Are Multiple Techniques Circling Similar Mechanisms? Circulation. Arrhythmia and electrophysiology Zaman, J. A., Rogers, A. J., Narayan, S. M. 2017; 10 (12)

  View details for PubMedID 29254949

• Synergistic Anti-arrhythmic Effects in Human Atria with Combined Use of Sodium Blockers and Acacetin FRONTIERS IN PHYSIOLOGY Ni, H., Whittaker, D. G., Wang, W., Giles, W. R., Narayan, S. M., Zhang, H. 2017; 8: 946

  Abstract

  Atrial fibrillation (AF) is the most common cardiac arrhythmia. Developing effective and safe anti-AF drugs remains an unmet challenge. Simultaneous block of both atrial-specific ultra-rapid delayed rectifier potassium (K+) current (IKur) and the Na+ current (INa) has been hypothesized to be anti-AF, without inducing significant QT prolongation and ventricular side effects. However, the antiarrhythmic advantage of simultaneously blocking these two channels vs. individual block in the setting of AF-induced electrical remodeling remains to be documented. Furthermore, many IKur blockers such as acacetin and AVE0118, partially inhibit other K+ currents in the atria. Whether this multi-K+-block produces greater anti-AF effects compared with selective IKur-block has not been fully understood. The aim of this study was to use computer models to (i) assess the impact of multi-K+-block as exhibited by many IKur blokers, and (ii) evaluate the antiarrhythmic effect of blocking IKur and INa, either alone or in combination, on atrial and ventricular electrical excitation and recovery in the setting of AF-induced electrical-remodeling. Contemporary mathematical models of human atrial and ventricular cells were modified to incorporate dose-dependent actions of acacetin (a multichannel blocker primarily inhibiting IKur while less potently blocking Ito, IKr, and IKs). Rate- and atrial-selective inhibition of INa was also incorporated into the models. These single myocyte models were then incorporated into multicellular two-dimensional (2D) and three-dimensional (3D) anatomical models of the human atria. As expected, application of IKur blocker produced pronounced action potential duration (APD) prolongation in atrial myocytes. Furthermore, combined multiple K+-channel block that mimicked the effects of acacetin exhibited synergistic APD prolongations. Synergistically anti-AF effects following inhibition of INa and combined IKur/K+-channels were also observed. The attainable maximal AF-selectivity of INa inhibition was greatly augmented by blocking IKur or multiple K+-currents in the atrial myocytes. This enhanced anti-arrhythmic effects of combined block of Na+- and K+-channels were also seen in 2D and 3D simulations; specially, there was an enhanced efficacy in terminating re-entrant excitation waves, exerting improved antiarrhythmic effects in the human atria as compared to a single-channel block. However, in the human ventricular myocytes and tissue, cellular repolarization and computed QT intervals were modestly affected in the presence of actions of acacetin and INa blockers (either alone or in combination). In conclusion, this study demonstrates synergistic antiarrhythmic benefits of combined block of IKur and INa, as well as those of INa and combined multi K+-current block of acacetin, without significant alterations of ventricular repolarization and QT intervals. This approach may be a valuable strategy for the treatment of AF.

  View details for PubMedID 29218016

• The continuous challenge of AF ablation: From foci to rotational activity. Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology Narayan, S. M., Vishwanathan, M. N., Kowalewski, C. A., Baykaner, T., Rodrigo, M., Zaman, J. A., Wang, P. J. 2017; 36 Suppl 1: 9–17

  Abstract

  Pulmonary vein isolation (PVI) is central to ablation approaches for atrial fibrillation (AF), yet many patients still have arrhythmia recurrence after one or more procedures despite the latest technology for PVI. Ablation of rotational or focal sources for AF, which lie outside the pulmonary veins in many patients, is a practical approach that has been shown to improve success by many groups. Localized sources lie in atrial regions shown mechanistically to sustain AF in optical mapping and clinical studies of human AF, as well as computational and animal studies. Because they arise in localized atrial regions, AF sources may explain central paradoxes in clinical practice - such as how limited ablation in patient specific sites can terminate persistent AF yet extensive anatomical ablation at stereotypical locations, which should extinguish disordered waves, does not improve success in clinical trials. Ongoing studies may help to resolve many controversies in the field of rotational sources for AF. Studies now verify rotational activation by multiple mapping approaches in the same patients, at sites where ablation terminates persistent AF. However, these studies also show that certain mapping methods are less effective for detecting AF sources than others. It is also recognized that the success of AF source ablation is technique dependent. This review article provides a mechanistic and clinical rationale to ablate localized sources (rotational and focal), and describes successful techniques for their ablation as well as pitfalls to avoid. We hope that this review will serve as a platform for future improvements in the patient-tailored ablation for complex arrhythmias.

  View details for PubMedID 29126896

• Treating Specialty and Outcomes in Newly Diagnosed Atrial Fibrillation From the TREAT-AF Study JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Perino, A. C., Fan, J., Schmitt, S. K., Askari, M., Kaiser, D. W., Deshmukh, A., Heidenreich, P. A., Swan, C., Narayan, S. M., Wang, P. J., Turakhia, M. P. 2017; 70 (1): 78–86

  Abstract

  Atrial fibrillation (AF) occurs in many clinical contexts and is diagnosed and treated by clinicians across many specialties. This approach has resulted in treatment variations.The goal of this study was to evaluate the association between treating specialty and AF outcomes among patients newly diagnosed with AF.Using data from the TREAT-AF (Retrospective Evaluation and Assessment of Therapies in AF) study from the Veterans Health Administration, patients with newly diagnosed, nonvalvular AF between 2004 and 2012 were identified who had at least 1 outpatient encounter with primary care or cardiology within 90 days of the AF diagnosis. Cox proportional hazards regression was used to evaluate the association between treating specialty and AF outcomes.Among 184,161 patients with newly diagnosed AF (age 70 ± 11 years; 1.7% women; CHA2DS2-VASc score 2.6 ± 1.7), 40% received cardiology care and 60% received primary care only. After adjustment for covariates, cardiology care was associated with reductions in stroke (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.86 to 0.96; p < 0.001) and death (HR: 0.89; 95% CI: 0.88 to 0.91; p < 0.0001) and increases in hospitalizations for AF/supraventricular tachycardia (HR: 1.38; 95% CI: 1.35 to 1.42; p < 0.0001) and myocardial infarction (HR: 1.03; 95% CI: 1.00 to 1.05; p < 0.04). The propensity-matched cohort had similar results. In mediation analysis, oral anticoagulation prescription within 90 days of diagnosis may have mediated reductions in stroke but did not mediate reductions in survival.In patients with newly diagnosed AF, cardiology care was associated with improved outcomes, potentially mediated by early prescription of oral anticoagulation therapy. Although hypothesis-generating, these data warrant serious consideration and study of health care system interventions at the time of new AF diagnosis.

  View details for PubMedID 28662810

• Multicentre safety of adding Focal Impulse and Rotor Modulation (FIRM) to conventional ablation for atrial fibrillation. Europace Krummen, D. E., Baykaner, T., Schricker, A. A., Kowalewski, C. A., Swarup, V., Miller, J. M., Tomassoni, G. F., Park, S., Viswanathan, M. N., Wang, P. J., Narayan, S. M. 2017; 19 (5): 769-774

  Abstract

  Focal Impulse and Rotor Modulation (FIRM) uses 64-electrode basket catheters to identify atrial fibrillation (AF)-sustaining sites for ablation, with promising results in many studies. Accordingly, new basket designs are being tested by several groups. We set out to determine the procedural safety of adding basket mapping and map-guided ablation to conventional pulmonary vein isolation (PVI).We collected 30 day procedural safety data in five US centres for consecutive patients undergoing FIRM plus PVI (FIRM-PVI) compared with contemporaneous controls undergoing PVI without FIRM. A total of 625 cases were included in this analysis: 325 FIRM-PVI and 300 PVI-controls. FIRM-PVI patients were more likely than PVI-controls to be male (83% vs. 66%, P < 0.001) and have long-standing persistent AF (26% vs. 13%, P < 0.001) reflecting patients referred for FIRM. Total ablation time was greater for FIRM-PVI (62 ± 22 min) vs. PVI-controls (52 ± 18 min, P = 0.03). The complication rate for FIRM-PVI procedures (4.3%) was similar to controls (4.0%, P = 1) for both major and minor complications; no deaths were reported. The rate of complications potentially attributable to the basket catheter was small and did not differ between basket types (Constellation 2.8% vs. FIRMap 1.8%, P = 0.7) or between cases in which basket catheters were and were not used (P = 0.5). Complication rates did not differ between centres (P = 0.6).Procedural complications from the use of the basket catheters for AF mapping are low, and thus procedural safety appears similar between FIRM-PVI and PVI-controls in a large multicentre cohort. Future studies are required to determine the optimal approach to maximize the efficacy of FIRM-guided ablation.

  View details for DOI 10.1093/europace/euw377

  View details for PubMedID 28339546

• Spatial relationship of organized rotational and focal sources in human atrial fibrillation to autonomic ganglionated plexi. International journal of cardiology Baykaner, T., Zografos, T. A., Zaman, J. A., Pantos, I., Alhusseini, M., Navara, R., Krummen, D. E., Narayan, S. M., Katritsis, D. G. 2017

  Abstract

  One approach to improve ablation for atrial fibrillation (AF) is to focus on physiological targets including focal or rotational sources or ganglionic plexi (GP). However, the spatial relationship between these potential mechanisms has never been studied. We tested the hypothesis that rotors and focal sources for AF may co-localize with ganglionated plexi (GP).We prospectively identified locations of AF rotors and focal sources, and correlated these to GP sites in 97 consecutive patients (age 59.9±11.4, 73% persistent AF). AF was recorded with 64-pole catheters with activation/phase mapping, and related to anatomic GP sites on electroanatomic maps.AF sources arose in 96/97 (99%) patients for 2.6±1.4 sources per patient (left atrium: 1.7±0.9 right atrium: 1.1±0.8), each with an area of 2-3cm(2). On area analyses, the probability of an AF source randomly overlapping a GP area was 26%. Left atrial sources were seen in 94 (97%) patients, in whom ≥1 source co-localized with GP in 75 patients (80%; p<0.05). AF sources were more likely to colocalize with left vs right GPs (p<0.05), and colocalization was more likely in patients with higher CHADS2VASc scores (age>65, diabetes; p<0.05).This is the first study to demonstrate that clinically detected AF focal and rotational sources in the left atrium often colocalize with regions of autonomic innervation. Studies should define if the role of AF sources differs by their anatomical location.

  View details for DOI 10.1016/j.ijcard.2017.02.152

  View details for PubMedID 28433558

• Mapping Ripples or Waves in Atrial Fibrillation? Journal of cardiovascular electrophysiology Zaman, J. A., Kowalewski, C. A., Narayan, S. M. 2017; 28 (4): 383-385

  View details for DOI 10.1111/jce.13181

  View details for PubMedID 28185356

  View details for PubMedCentralID PMC5398913

• Mechanistic targets for the ablation of atrial fibrillation. Global cardiology science & practice Zaman, J. A., Baykaner, T., Schricker, A. A., Krummen, D. E., Narayan, S. M. 2017; 2017 (1): e201707

  Abstract

  The mechanisms responsible for sustaining atrial fibrillation are a key debate in cardiovascular pathophysiology, and directly influence the approach to therapy including ablation Clinical and basic studies have split AF mechanisms into two basic camps: 'spatially distributed disorganization' and 'localized sources'. Recent data suggest that these mechanisms can also be separated by the method for mapping - with nearly all traditional electrogram analyses showing spatially distributed disorganization and nearly all optical mapping studies showing localized sources We will review this dichotomy in light of these recently identified differences in mapping, and in the context of recent clinical studies in which localized ablation has been shown to impact AF, also lending support to the localized source hypothesis. We will conclude with other concepts on mechanism-based ablation and areas of ongoing research that must be addressed to continue improving our knowledge and treatment of AF.

  View details for DOI 10.21542/gcsp.2017.7

  View details for PubMedID 28971106

  View details for PubMedCentralID PMC5621726

• Two Independent Mapping Techniques Identify Rotational Activity Patterns at Sites of Local Termination during Persistent Atrial Fibrillation. Journal of cardiovascular electrophysiology Alhusseini, M., Vidmar, D., Meckler, G. L., Kowalewski, C., Shenasa, F., Wang, P. J., Narayan, S. M., Rappel, W. 2017

  Abstract

  The mechanisms for atrial fibrillation (AF) are unclear in part because diverse mapping techniques yield diverse maps, ranging from stable organized sources to highly disordered waves. We hypothesized that AF mechanisms may be clarified if mapping techniques were compared in the same patients, and referenced to a clinical endpoint. We compared two independent AF mapping techniques in patients in whom ablation terminated persistent AF before pulmonary vein isolation (PVI).We identified 12 patients with persistent AF (61.2 ± 10.8 years, four female) in whom mapping with 64 pole baskets and technique 1 (activation/phase mapping, FIRM) identified rotational activation patterns during at least 50% of the 4-second mapping interval and targeted ablation at these rotational sites terminated AF to sinus rhythm (n = 10) or atrial tachycardia. We analyzed the unipolar electrograms of these patients to determine phase maps of activation by an independent technique 2 (Kuklik, Schotten et al., IEEE Trans Biomed Eng 2015). Compared to technique 1, technique 2 revealed a source in 12 of 12 (100%) cases with spatial concordance in all cases (P <0.05) and similar rotational characteristics.At sites where ablation terminated persistent AF, two independent mapping techniques identified stable rotational activation for multiple cycles that drove peripheral disorder. Future comparative studies referenced to a clinical endpoint may help reconcile if discrepancies between AF mapping studies reports represent techniques, patient populations or models of AF, and improve mapping to better guide ablation.

  View details for DOI 10.1111/jce.13177

  View details for PubMedID 28185348

• Electrocardiographic spatial loops indicate organization of atrial fibrillation minutes before ablation-related transitions to atrial tachycardia. Journal of electrocardiology Baykaner, T., Trikha, R., Zaman, J. A., Krummen, D. E., Wang, P. J., Narayan, S. M. 2017

  Abstract

  During ablation for atrial fibrillation (AF), it is challenging to anticipate transitions to organized tachycardia (AT). Defining indices of this transition may help to understand fibrillatory conduction and help track therapy.To determine the timescale over which atrial fibrillation (AF) organizes en route to atrial tachycardia (AT) using the ECG referenced to intracardiac electrograms.In 17 AF patients at ablation (58.7±9.6years; 53% persistent AF) we analyzed spatial loops of atrial activity on the ECG and intracardiac electrograms over successive timepoints. Loops were tracked at precisely 15, 10, 5, 3 and 1min prior to defined transitions of AF to AT.Organizational indices reliably quantified changes from AF to AT. Spatiotemporal AF organization on the ECG was identifiable at least 15min before AT was established (p=0.02).AF shows anticipatory global organization on the ECG minutes before AT is clinically evident. These results offer a foundation to establish when AF therapy is on an effective path, and for a quantitative classification separating AT from AF.

  View details for DOI 10.1016/j.jelectrocard.2017.01.007

  View details for PubMedID 28108014

• Editorial commentary: What can lung transplantation teach us about the mechanisms of atrial arrhythmias? Trends in cardiovascular medicine Baykaner, T. n., Rogers, A. J., Zaman, J. A., Narayan, S. M. 2017

  View details for PubMedID 28893519

• Recurrent Post-Ablation Paroxysmal Atrial Fibrillation Shares Substrates With Persistent Atrial Fibrillation : An 11-Center Study. JACC. Clinical electrophysiology Zaman, J. A., Baykaner, T. n., Clopton, P. n., Swarup, V. n., Kowal, R. C., Daubert, J. P., Day, J. D., Hummel, J. n., Schricker, A. A., Krummen, D. E., Mansour, M. n., Tomassoni, G. F., Wheelan, K. R., Vishwanathan, M. n., Park, S. n., Wang, P. J., Narayan, S. M., Miller, J. M. 2017; 3 (4): 393–402

  Abstract

  The role of atrial fibrillation (AF) substrates is unclear in patients with paroxysmal AF (PAF) that recurs after pulmonary vein isolation (PVI). We hypothesized that patients with recurrent post-ablation (redo) PAF despite PVI have electrical substrates marked by rotors and focal sources, and structural substrates that resemble persistent AF more than patients with (de novo) PAF at first ablation.In 175 patients at 11 centers, we compared AF substrates in both atria using 64 pole-basket catheters and phase mapping, and indices of anatomical remodeling between patients with de novo or redo PAF and first ablation for persistent AF.Sources were seen in all patients. More patients with de novo PAF (78.0%) had sources near PVs than patients with redo PAF (47.4%, p=0.005) or persistent AF (46.9%, p=0.001). The total number of sources per patient (p=0.444), and number of non-PV sources (p=0.701) were similar between groups, indicating that redo PAF patients had residual non-PV sources after elimination of PV sources by prior PVI. Structurally, left atrial size did not separate de novo from redo PAF (49.5±9.5 vs. 49.0±7.1mm, p=0.956) but was larger in patients with persistent AF (55.2±8.4mm, p=0.001).Patients with paroxysmal AF despite prior PVI show electrical substrates that resemble persistent AF more closely than patients with paroxysmal AF at first ablation. Notably, these subgroups of paroxysmal AF are indistinguishable by structural indices. These data motivate studies of trigger versus substrate mechanisms for patients with recurrent paroxysmal AF after PVI.

  View details for PubMedID 28596994

• Spatial relationship of sites for atrial fibrillation drivers and atrial tachycardia in patients with both arrhythmias. International journal of cardiology Baykaner, T. n., Zaman, J. A., Rogers, A. J., Navara, R. n., AlHusseini, M. n., Borne, R. T., Park, S. n., Wang, P. J., Krummen, D. E., Sauer, W. H., Narayan, S. M. 2017; 248: 188–95

  Abstract

  Atrial fibrillation (AF) often converts to and from atrial tachycardia (AT), but it is undefined if these rhythms are mechanistically related in such patients. We tested the hypothesis that critical sites for AT may be related to regional AF sources in patients with both rhythms, by mapping their locations and response to ablation on transitions to and from AF.From 219 patients undergoing spatial mapping of AF prior to ablation at 3 centers, we enrolled 26 patients in whom AF converted to AT by ablation (n=19) or spontaneously (n=7; left atrial size 42±6cm, 38% persistent AF). Both atria were mapped in both rhythms by 64-electrode baskets, traditional activation maps and entrainment.Each patient had a single mapped AT (17 reentrant, 9 focal) and 3.7±1.7 AF sources. The mapped AT spatially overlapped one AF source in 88% (23/26) of patients, in left (15/23) or right (8/23) atria. AF transitioned to AT by 3 mechanisms: (a) ablation anchoring AF rotor to AT (n=13); (b) residual, unablated AF source producing AT (n=6); (c) spontaneous slowing of AF rotor leaving reentrant AT at this site without any ablation (n=7). Electrogram analysis revealed a lower peak-to-peak voltage at overlapping sites (0.36±0.2mV vs 0.49±0.2mV p=0.03).Mechanisms responsible for AT and AF may arise in overlapping atrial regions. This mechanistic inter-relationship may reflect structural and/or functional properties in either atrium. Future work should delineate how acceleration of an organized AT may produce AF, and whether such regions can be targeted a priori to prevent AT recurrence post AF ablation.

  View details for PubMedID 28733070

• Determining conduction patterns on a sparse electrode grid: Implications for the analysis of clinical arrhythmias PHYSICAL REVIEW E Vidmar, D., Narayan, S. M., Krummen, D. E., Rappel, W. 2016; 94 (5)

  View details for DOI 10.1103/PhysRevE.94.050401

  View details for Web of Science ID 000387541400001

• Determining conduction patterns on a sparse electrode grid: Implications for the analysis of clinical arrhythmias. Physical review. E Vidmar, D., Narayan, S. M., Krummen, D. E., Rappel, W. 2016; 94 (5-1): 050401-?

  Abstract

  We present a general method of utilizing bioelectric recordings from a spatially sparse electrode grid to compute a dynamic vector field describing the underlying propagation of electrical activity. This vector field, termed the wave-front flow field, permits quantitative analysis of the magnitude of rotational activity (vorticity) and focal activity (divergence) at each spatial point. We apply this method to signals recorded during arrhythmias in human atria and ventricles using a multipolar contact catheter and show that the flow fields correlate with corresponding activation maps. Further, regions of elevated vorticity and divergence correspond to sites identified as clinically significant rotors and focal sources where therapeutic intervention can be effective. These flow fields can provide quantitative insights into the dynamics of normal and abnormal conduction in humans and could potentially be used to enhance therapies for cardiac arrhythmias.

  View details for PubMedID 27967050

• Terminating atrial fibrillation by cooling the heart. Heart rhythm Narayan, S. M., Baykaner, T., Sahli Costabal, F., Kuhl, E. 2016; 13 (11): 2259-2260

  View details for DOI 10.1016/j.hrthm.2016.07.017

  View details for PubMedID 27435588

• Challenging the complementarity of different metrics of left atrial function: insight from a cardiomyopathy-based study. European heart journal cardiovascular Imaging Kobayashi, Y., Moneghetti, K. J., Boralkar, K., Amsallem, M., Tuzovic, M., Liang, D., Yang, P. C., Narayan, S., Kuznetsova, T., Wu, J. C., Schnittger, I., Haddad, F. 2016

  Abstract

  Left ventricular (LV) strain provides incremental values to LV ejection fraction (LVEF) in predicting outcome. We sought to investigate if similar relationship is observed between left atrial (LA) emptying fraction and LA strain.In this study, we selected 50 healthy subjects, 50 patients with dilated, 50 hypertrophic, and 50 infiltrative (light-chain (AL) amyloidosis) cardiomyopathy (CMP). Echocardiographic measures included LVEF and LA emptying fraction as well as LV and LA longitudinal strain (LVLS and LALS). After regression analysis, comparison of least square means of LA strain among aetiologies was performed. Intraclass correlation coefficient (ICC) and coefficient of variation (COV) were used in the assessment of variability and reproducibility of LV and LA metrics. The mean LVLS and all LA metrics were impaired in patients with all CMP compared with healthy subjects. In contrast to the moderate relationship between LVEF and LVLS (r = -0.51, P < 0.001), there was a strong linear relationship between LA emptying fraction and LA strain (r = 0.87, P < 0.001). In multiple regression analysis, total LA strain was associated with LVLS (β = -0.48, P < 0.001), lateral E/e' (β = -0.24, P < 0.001), age (β = -0.21, P < 0.001), and heart rate (β = -0.14, P = 0.02). The least square mean of LA strain adjusted for the parameters was not different among aetiologies (ANOVA P = 0.82). The ICC (>0.77) and COV (<13) were acceptable.In contrast to LV measures, there is a strong linear relationship between volumetric and longitudinal deformation indices of left atrium irrespective of CMP aetiology. Either LA emptying fraction or LA strain could be used as an important parameter in predictive models.

  View details for PubMedID 27638850

• Mechanisms linking electrical alternans and clinical ventricular arrhythmia in human heart failure. Heart rhythm Bayer, J. D., Lalani, G. G., Vigmond, E. J., Narayan, S. M., Trayanova, N. A. 2016; 13 (9): 1922-1931

  Abstract

  Mechanisms of ventricular tachycardia (VT) and ventricular fibrillation (VF) in patients with heart failure (HF) are undefined.The purpose of this study was to elucidate VT/VF mechanisms in HF by using a computational-clinical approach.In 53 patients with HF and 18 control patients, we established the relationship between low-amplitude action potential voltage alternans (APV-ALT) during ventricular pacing at near-resting heart rates and VT/VF on long-term follow-up. Mechanisms underlying the transition of APV-ALT to VT/VF, which cannot be ascertained in patients, were dissected with multiscale human ventricular models based on human electrophysiological and magnetic resonance imaging data (control and HF).For patients with APV-ALT k-score >1.7, complex action potential duration (APD) oscillations (≥2.3% of mean APD), rather than APD alternans, most accurately predicted VT/VF during long-term follow-up (+82%; -90% predictive values). In the failing human ventricular models, abnormal sarcoplasmic reticulum (SR) calcium handling caused APV-ALT (>1 mV) during pacing with a cycle length of 550 ms, which transitioned into large magnitude (>100 ms) discordant repolarization time alternans (RT-ALT) at faster rates. This initiated VT/VF (cycle length <400 ms) by steepening apicobasal repolarization (189 ms/mm) until unidirectional conduction block and reentry. Complex APD oscillations resulted from nonstationary discordant RT-ALT. Restoring SR calcium to control levels was antiarrhythmic by terminating electrical alternans.APV-ALT and complex APD oscillations at near-resting heart rates in patients with HF are linked to arrhythmogenic discordant RT-ALT. This may enable novel physiologically tailored, bioengineered indices to improve VT/VF risk stratification, where SR calcium handling and spatial apicobasal repolarization are potential therapeutic targets.

  View details for DOI 10.1016/j.hrthm.2016.05.017

  View details for PubMedID 27215536

  View details for PubMedCentralID PMC4996715

• Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties. PLoS computational biology Lombardo, D. M., Fenton, F. H., Narayan, S. M., Rappel, W. 2016; 12 (8)

  Abstract

  Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF). A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP) morphology, action potential duration (APD) restitution and conduction velocity (CV) restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy.

  View details for DOI 10.1371/journal.pcbi.1005060

  View details for PubMedID 27494252

  View details for PubMedCentralID PMC4975409

• Can Cardiac Conduction System Disease Be Prevented? JAMA internal medicine Narayan, S. M., Baykaner, T., Maron, D. J. 2016; 176 (8): 1093-1094

  View details for DOI 10.1001/jamainternmed.2016.2863

  View details for PubMedID 27367299

• Organized Sources Are Spatially Conserved in Recurrent Compared to Pre-Ablation Atrial Fibrillation: Further Evidence for Non-Random Electrical Substrates JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Lalani, G. G., Coysh, T., Baykaner, T., Zaman, J., Hopper, K., Schricker, A. A., Trikha, R., Clopton, P., Krummen, D. E., Narayan, S. M. 2016; 27 (6): 661-669

  Abstract

  CONSERVED ROTORS IN RECURRENT AF.Recurrent atrial fibrillation (AF) after ablation is associated with reconnection of initially isolated pulmonary vein (PV) trigger sites. Substrates are often targeted in addition to PVI, but it is unclear how substrates progress over time. We studied if substrates in recurrent AF are conserved or have developed de novo from pre-ablation AF.Of 137 patients undergoing Focal Impulse and Rotor Mapping (FIRM) at their index procedure for AF, 29 consecutive patients (60±8 years, 79% persistent) recurred and were also mapped at repeat procedure (21±20 months later) using carefully placed 64-pole baskets and RhythmView(TM) (Topera, Menlo Park, CA) to identify AF sources and disorganized zones. Compared to index AF, recurrent AF had a longer cycle length (177±21 vs. 167±19ms, p = 0.01). All patients (100%) had one or more conserved AF rotors between procedures with surrounding disorganization. The number of sources was similar for recurrent AF post-PVI versus index AF (3.2±1.4 vs. 3.1±1.0, p = 0.79), but was lower for recurrent AF after FIRM+PVI versus index AF (4.4±1.4 vs. 2.9±1.7, p = 0.03). Overall, 81% (61/75) of AF sources lay in conserved regions, while 19% (14/75) were detected de novo.Electrical propagation patterns for recurrent AF after unsuccessful ablation are similar in individual patients to their index AF. These data support temporospatial stability of AF substrates over 1-2 years. Trials should determine the relative benefit of adding substrate-mapping and ablation to PVI for recurrent AF. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/jce.12964

  View details for Web of Science ID 000378396900001

  View details for PubMedID 26918971

• Comparative efficacy of stellate ganglion block with bupivacaine vs pulsed radiofrequency in a patient with refractory ventricular arrhythmias. Journal of clinical anesthesia Hayase, J., Vampola, S., Ahadian, F., Narayan, S. M., Krummen, D. E. 2016; 31: 162-5

  Abstract

  There is increasing interest in interventional therapies targeting the cardiac sympathetic nervous system to suppress ventricular arrhythmias. In this case report, we describe an 80-year-old patient with ischemic cardiomyopathy and multiple implantable cardioverter-defibrillator shocks due to refractory ventricular tachycardia and ventricular fibrillation who was unable to continue biweekly stellate ganglion block procedures using bupivacaine 0.25% for suppression of his arrhythmias. He had previously failed antiarrhythmic drug therapy with amiodarone, catheter ablation, and attempted surgical autonomic denervation. He underwent pulsed radiofrequency treatment (3 lesions, 2 minutes each, temperature 42°C, 2-Hz frequency, 20-millisecond pulse width) of the left stellate ganglion resulting in persistent arrhythmia suppression for more than 12 months duration. This represents the first report of a pulsed radiofrequency stellate ganglion lesion providing long-term suppression of ventricular arrhythmias. Further study of this technique in patients with refractory ventricular tachycardia or ventricular fibrillation is warranted.

  View details for DOI 10.1016/j.jclinane.2016.01.026

  View details for PubMedID 27185701

• Mechanistically based mapping of human cardiac fibrillation JOURNAL OF PHYSIOLOGY-LONDON Narayan, S. M., Zaman, J. A. 2016; 594 (9): 2399-2415

  Abstract

  The mechanisms underpinning human cardiac fibrillation remain elusive. In his 1913 treatise on 'Dynamic Equilibrium in the Heart', Mines proposed that an activation wave front could propagate repeatedly in a circle, initiated by a stimulus in the vulnerable period. While the dynamics of activation and recovery are central to cardiac fibrillation, these physiological data are rarely used in clinical mapping. Fibrillation is a rapid irregular rhythm with spatiotemporal disorder resulting from 2 fundamental mechanisms - sources in preferred cardiac regions or spatially diffuse self-sustaining activity, i.e. with no preferred source. On close inspection, however, this debate may also reflect mapping technique. Fibrillation is initiated from triggers by regional dispersion in repolarization, slow conduction and wavebreak, then sustained by non-uniform interactions of these mechanisms. Notably, optical mapping of action potentials in atrial fibrillation (AF) show spiral wave sources (rotors) in nearly all studies including humans, while most traditional electrogram analyses of AF do not. Techniques may diverge in fibrillation because electrograms summate non-coherent waves within an undefined field whereas optical maps define waves with a visually defined field. Also fibrillation operates at the limits of activation and recovery, that are well represented by action potentials while fibrillatory electrograms poorly represent repolarization. We conclude by suggesting areas for study that may be used, until such time as optical mapping is clinically feasible, to improve mechanistic understanding and therapy of human cardiac fibrillation. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1113/JP270513

  View details for Web of Science ID 000375601400006

  View details for PubMedID 26607671

• Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure: A Randomized Clinical Trial. JAMA cardiology Hammond, H. K., Penny, W. F., Traverse, J. H., Henry, T. D., Watkins, M. W., Yancy, C. W., Sweis, R. N., Adler, E. D., Patel, A. N., Murray, D. R., Ross, R. S., Bhargava, V., Maisel, A., Barnard, D. D., Lai, N. C., Dalton, N. D., Lee, M. L., Narayan, S. M., Blanchard, D. G., Gao, M. H. 2016; 1 (2): 163-171

  Abstract

  Gene transfer has rarely been tested in randomized clinical trials.To evaluate the safety and efficacy of intracoronary delivery of adenovirus 5 encoding adenylyl cyclase 6 (Ad5.hAC6) in heart failure.A randomized, double-blind, placebo-controlled, phase 2 clinical trial was conducted in US medical centers (randomization occurred from July 19, 2010, to October 30, 2014). Participants 18 to 80 years with symptomatic heart failure (ischemic and nonischemic) and an ejection fraction (EF) of 40% or less were screened; 86 individuals were enrolled, and 56 were randomized. Data analysis was of the intention-to-treat population. Participants underwent exercise testing and measurement of left ventricular EF (echocardiography) and then cardiac catheterization, where left ventricular pressure development (+dP/dt) and decline (-dP/dt) were recorded. Participants were randomized (3:1 ratio) to receive 1 of 5 doses of intracoronary Ad5.hAC6 or placebo. Participants underwent a second catheterization 4 weeks later for measurement of dP/dt. Exercise testing and EF were assessed 4 and 12 weeks after randomization.Intracoronary administration of Ad5.hAC6 (3.2 × 109 to 1012 virus particles) or placebo.Primary end points included exercise duration and EF before and 4 and 12 weeks after randomization and peak rates of +dP/dt and -dP/dt before and 4 weeks after randomization. Fourteen placebo participants were compared (intention to treat) with 24 Ad5.hAC6 participants receiving the highest 2 doses (D4 + 5).Fifty-six individuals were randomized and monitored for up to 1 year. Forty-two participants (75%) received Ad5.hAC6 (mean [SE] age, 63 [1] years; EF, 30% [1%]), and 14 individuals (25%) received placebo (age, 62 [1] years; EF, 30% [2%]). Exercise duration showed no significant group differences (4 weeks, P = .27; 12 weeks, P = .47, respectively). The D4 + 5 participants had increased EF at 4 weeks (+6.0 [1.7] EF units; n = 21; P < .004), but not 12 weeks (+3.0 [2.4] EF units; n = 21; P = .16). Placebo participants showed no increase in EF at 4 weeks or 12 weeks. Exercise duration showed no between-group differences (4-week change from baseline: placebo, 27 [36] seconds; D4 + 5, 44 [25] seconds; P = .27; 12-week change from baseline: placebo, 44 [28] seconds; D4 + 5, 58 [29 seconds, P = .47). AC6 gene transfer increased basal left ventricular peak -dP/dt (4-week change from baseline: placebo, +93 [51] mm Hg/s; D4 + 5, -39 [33] mm Hg/s; placebo [n = 21]; P < .03); AC6 did not increase arrhythmias. The admission rate for patients with heart failure was 9.5% (4 of 42) in the AC6 group and 28.6% (4 of 14) in the placebo group (relative risk, 0.33 [95% CI, 0.08-1.36]; P = .10).AC6 gene transfer safely increased LV function beyond standard heart failure therapy, attainable with one-time administration. Larger trials are warranted.clinicaltrials.gov Identifier: NCT00787059.

  View details for DOI 10.1001/jamacardio.2016.0008

  View details for PubMedID 27437887

• The precise timing of tachycardia entrainment is determined by the postpacing interval, the tachycardia cycle length, and the pacing rate: Theoretical insights and practical applications HEART RHYTHM Kaiser, D. W., Hsia, H. H., Dubin, A. M., Liem, L. B., Viswanathan, M. N., Zei, P. C., Wang, P. J., Narayan, S. M., Turakhia, M. P. 2016; 13 (3): 695-703

  Abstract

  Previous observations have reported that the number of pacing stimuli required to entrain a tachycardia varies on the basis of arrhythmia type and location, but a quantitative formulation of the number needed to entrain (NNE) that unifies these observations has not been characterized.We sought to investigate the relationship between the number of pacing stimulations, the tachycardia cycle length (TCL), the overdrive pacing cycle length (PCL), and the postpacing interval (PPI) to accurately estimate the timing of tachycardia entrainment.First, we detailed a mathematical derivation unifying electrophysiological parameters with empirical confirmation in 2 patients undergoing catheter ablation of typical atrial flutter. Second, we validated our formula in 44 patients who underwent various catheter ablation procedures. For accuracy, we corrected for rate-related changes in conduction velocity.We derived the equations NNE = |(PPI - TCL)/(TCL - PCL)| + 1 and Tachycardia advancement = (NNE - 1) × (TCL - PCL) - (PPI - TCL), which state that the NNE and the amount of tachycardia advancement on the first resetting stimulation are determined using regularly measured intracardiac parameters. In the retrospective cohort, the observed PPI - TCL highly correlated with the predicted PPI - TCL (mean difference 5.8 ms; r = 0.97; P < .001), calculated as PPI - TCL = (NNE - 1) × (TCL - PCL) - tachycardia advancement.The number of pacing stimulations required to entrain a reentrant tachycardia is predictable at any PCL after correcting for cycle length-dependent changes in conduction velocity. This relationship unifies established empirically derived diagnostic and mapping criteria for supraventricular tachycardia and ventricular tachycardia. This relationship may help elucidate when antitachycardia pacing episodes are ineffective or proarrhythmic and could potentially serve as a theoretical basis to customize antitachycardia pacing settings for improved safety and effectiveness.

  View details for DOI 10.1016/j.hrthm.2015.11.032

  View details for Web of Science ID 000372367800012

  View details for PubMedCentralID PMC4770895

• The precise timing of tachycardia entrainment is determined by the postpacing interval, the tachycardia cycle length, and the pacing rate: Theoretical insights and practical applications. Heart rhythm Kaiser, D. W., Hsia, H. H., Dubin, A. M., Liem, L. B., Viswanathan, M. N., Zei, P. C., Wang, P. J., Narayan, S. M., Turakhia, M. P. 2016; 13 (3): 695-703

  Abstract

  Previous observations have reported that the number of pacing stimuli required to entrain a tachycardia varies on the basis of arrhythmia type and location, but a quantitative formulation of the number needed to entrain (NNE) that unifies these observations has not been characterized.We sought to investigate the relationship between the number of pacing stimulations, the tachycardia cycle length (TCL), the overdrive pacing cycle length (PCL), and the postpacing interval (PPI) to accurately estimate the timing of tachycardia entrainment.First, we detailed a mathematical derivation unifying electrophysiological parameters with empirical confirmation in 2 patients undergoing catheter ablation of typical atrial flutter. Second, we validated our formula in 44 patients who underwent various catheter ablation procedures. For accuracy, we corrected for rate-related changes in conduction velocity.We derived the equations NNE = |(PPI - TCL)/(TCL - PCL)| + 1 and Tachycardia advancement = (NNE - 1) × (TCL - PCL) - (PPI - TCL), which state that the NNE and the amount of tachycardia advancement on the first resetting stimulation are determined using regularly measured intracardiac parameters. In the retrospective cohort, the observed PPI - TCL highly correlated with the predicted PPI - TCL (mean difference 5.8 ms; r = 0.97; P < .001), calculated as PPI - TCL = (NNE - 1) × (TCL - PCL) - tachycardia advancement.The number of pacing stimulations required to entrain a reentrant tachycardia is predictable at any PCL after correcting for cycle length-dependent changes in conduction velocity. This relationship unifies established empirically derived diagnostic and mapping criteria for supraventricular tachycardia and ventricular tachycardia. This relationship may help elucidate when antitachycardia pacing episodes are ineffective or proarrhythmic and could potentially serve as a theoretical basis to customize antitachycardia pacing settings for improved safety and effectiveness.

  View details for DOI 10.1016/j.hrthm.2015.11.032

  View details for PubMedID 26611239

• New Mechanism-based Approaches to Ablating Persistent AF: Will Drug Therapy Soon Be Obsolete? JOURNAL OF CARDIOVASCULAR PHARMACOLOGY Zaman, J. A., Baykaner, T., Narayan, S. M. 2016; 67 (1): 1-8

  View details for DOI 10.1097/FJC.0000000000000270

  View details for Web of Science ID 000368504500001

• New Mechanism-based Approaches to Ablating Persistent AF: Will Drug Therapy Soon Be Obsolete? Journal of cardiovascular pharmacology Zaman, J. A., Baykaner, T., Narayan, S. M. 2016; 67 (1): 1-8

  Abstract

  Persistent atrial fibrillation (AF) represents a major public health and medical challenge. The progressive nature of the disease, high morbidity and increasing health-economic costs ensure it remains at the forefront of novel research into mechanisms and potential therapies. These are largely divided into pharmacological (drugs) and electrical (ablation), with patients often going from former to latter. AF ablation has improved sufficiently to be offered as first line for paroxysmal AF, but there is uncertainty on whether drug therapy will improve from its current role or be relegated to niche status. In this review we shall outline the progress in mechanistic understanding of AF that may allow results from ablation to diverge dramatically from drug therapy, to identify populations in whom drug therapy may become less relevant. We end by looking ahead to future developments which we hope will spur on therapeutic efficacy in both fields.

  View details for DOI 10.1097/FJC.0000000000000270

  View details for PubMedID 25923323

• Atrial Fibrillation: Can Electrograms Be Interpreted Without Repolarization Information? Heart rhythm : the official journal of the Heart Rhythm Society Narayan, S. M., Zaman, J., Baykaner, T., Franz, M. R. 2015

  View details for DOI 10.1016/j.hrthm.2015.12.025

  View details for PubMedID 26711801

• Phase synchrony reveals organization in human atrial fibrillation AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Vidmar, D., Narayan, S. M., Rappel, W. 2015; 309 (12): H2118-H2126

  View details for DOI 10.1152/ajpheart.00407.2015

  View details for Web of Science ID 000367288700013

• Phase synchrony reveals organization in human atrial fibrillation. American journal of physiology. Heart and circulatory physiology Vidmar, D., Narayan, S. M., Rappel, W. J. 2015; 309 (12): H2118-26

  Abstract

  It remains unclear if human atrial fibrillation (AF) is spatially nonhierarchical or exhibits a hierarchy of organization sustained by sources. We utilize activation times obtained at discrete locations during AF to compute the phase synchrony between tissue regions, to examine underlying spatial dynamics throughout both atria. We construct a binary synchronization network and show that this network can accurately define regions of coherence in coarse-grained in silico data. Specifically, domains controlled by spiral waves exhibit regions of high phase synchrony. We then apply this analysis to clinical data from patients experiencing cardiac arrhythmias using multielectrode catheters to simultaneously record from a majority of both atria. We show that pharmaceutical intervention with ibutilide organizes activation by increasing the size of the synchronized domain in AF and quantify the increase in temporal organization when arrhythmia changes from fibrillation to tachycardia. Finally, in recordings from 24 patients in AF we show that the level of synchrony is spatially broad with some patients showing large spatially contiguous regions of synchronization, while in others synchrony is localized to small pockets. Using computer simulations, we show that this distribution is inconsistent with distributions obtained from simulations that mimic multiwavelet reentry but is consistent with mechanisms in which one or more spatially conserved spiral waves is surrounded by tissue in which activation is disorganized.

  View details for DOI 10.1152/ajpheart.00407.2015

  View details for PubMedID 26475585

  View details for PubMedCentralID PMC4698428

• Mechanisms for the Termination of Atrial Fibrillation by Localized Ablation Computational and Clinical Studies CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Rappel, W., Zaman, J. A., Narayan, S. M. 2015; 8 (6): 1325-1333

  View details for DOI 10.1161/CIRCEP.115.002956

  View details for Web of Science ID 000366604600007

  View details for PubMedID 26359479

• Ablation of Atrial Fibrillation: How Can Less Be More? Circulation. Arrhythmia and electrophysiology Zaman, J. A., Narayan, S. M. 2015; 8 (6): 1303-5

  View details for DOI 10.1161/CIRCEP.115.003495

  View details for PubMedID 26671931

• Mechanisms for the Termination of Atrial Fibrillation by Localized Ablation: Computational and Clinical Studies. Circulation. Arrhythmia and electrophysiology Rappel, W., Zaman, J. A., Narayan, S. M. 2015; 8 (6): 1325-1333

  Abstract

  -Human atrial fibrillation (AF) can terminate after ablating localized regions, that supports the existence of localized rotors (spiral waves) or focal drivers. However, it is unclear why ablation near a spiral wave tip would terminate AF and not anchor reentry. We addressed this question by analyzing competing mechanisms for AF termination in numerical simulations, referenced to clinical observations.-Spiral wave reentry was simulated in monodomain 2D myocyte sheets using clinically realistic rate-dependent values for repolarization and conduction. Heterogeneous models were created by introduction of parameterized variations in tissue excitability. Ablation lesions were applied as non-conducting circular regions. Computational models confirmed localized ablation may anchor spiral wave reentry, producing organized tachycardias. Several mechanisms also explained termination of AF to sinus rhythm. First, lesions may create an excitable gap vulnerable to invasion by fibrillatory waves. Second, ablation of rotors in regions of low-excitability (from remodeling) produced reentry in more excitable tissue allowing collision of wave-front and back. Conversely, ablation of rotors in high-excitability regions migrated spiral waves to less excitable tissue, where they detached to collide with non-conducting boundaries. Third, ablation may connect rotors to non-conducting anatomic orifices. Fourth, reentry through slow conducting channels may terminate if ablation closes these channels.-Limited ablation can terminate AF by several mechanisms. These data shed light on how clinical AF may be sustained in patients' atria, emphasizing heterogeneities in tissue excitability, slow-conducting channels and obstacles that are increasingly detectable in patients and should be the focus of future translational studies.

  View details for DOI 10.1161/CIRCEP.115.002956

  View details for PubMedID 26359479

• Modifying Ventricular Fibrillation by Targeted Rotor Substrate Ablation: Proof-of-Concept from Experimental Studies to Clinical VF JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Krummen, D. E., Hayase, J., Vampola, S. P., Ho, G., Schricker, A. A., Lalani, G. G., Baykaner, T., Coe, T. M., Clopton, P., Rappel, W., Omens, J. H., Narayan, S. M. 2015; 26 (10): 1117-1126

  View details for DOI 10.1111/jce.12753

  View details for PubMedID 26179310

• When is Structure, Function? Revisiting an Old Concept in Atrial Fibrillationx. Journal of cardiovascular electrophysiology Zaman, J. A., Narayan, S. M. 2015

  Abstract

  The mechanistic role of cardiac structure is central to the conceptualization and therapy of arrhythmias, yet it is poorly understood in all but the simplest cases. A century after Mines first conceptualized reentry based on structural pathways, (1,2) it is common to dichotomize reentry into 'anatomical' and 'functional'. However, in many ways this is an uneasy distinction. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/jce.12836

  View details for PubMedID 26359793

• Ablation of atrial fibrillation TRENDS IN CARDIOVASCULAR MEDICINE Wright, M., Narayan, S. M. 2015; 25 (5): 409-419

  View details for DOI 10.1016/j.tcm.2014.11.009

  View details for Web of Science ID 000356997800007

• Ablation of atrial fibrillation. Trends in cardiovascular medicine Wright, M., Narayan, S. M. 2015; 25 (5): 409-19

  Abstract

  Ablation is increasingly used to treat AF, since recent trials of pharmacological therapy for AF have been disappointing. Ablation has been shown to improve maintenance of sinus rhythm compared to pharmacological therapy in many multicenter trials, although success rates remain suboptimal. This review will discuss several trends in the field of catheter ablation, including studies to advance our understanding of AF mechanisms in different patient populations, innovations in detecting and classifying AF, use of this information to improve strategies for ablation, technical innovations that have improved the ease and safety of ablation, and novel approaches to surgical therapy and imaging. These trends are likely to further improve results from AF ablation in coming years as it becomes an increasingly important therapeutic option for many patients.

  View details for DOI 10.1016/j.tcm.2014.11.009

  View details for PubMedID 25572010

  View details for PubMedCentralID PMC4764083

• Is Human Long-Standing Persistent Atrial Fibrillation More Stable Than Assumed? JACC. Clinical electrophysiology Verma, A., Narayan, S. M. 2015; 1 (1-2): 25-28

  View details for DOI 10.1016/j.jacep.2015.02.016

  View details for PubMedID 29759335

• Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping. Methodist DeBakey cardiovascular journal Zaman, J. A., Narayan, S. M. 2015; 11 (2): 76-81

  Abstract

  Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes.

  View details for DOI 10.14797/mdcj-11-2-76

  View details for PubMedID 26306123

  View details for PubMedCentralID PMC4547681

• The role of rotors in atrial fibrillation. Journal of thoracic disease Krummen, D. E., Swarup, V., Narayan, S. M. 2015; 7 (2): 142-151

  Abstract

  Despite significant advances in our understanding of atrial fibrillation (AF) mechanisms in the last 15 years, ablation outcomes remain suboptimal. A potential reason is that many ablation techniques focus on anatomic, rather than patient-specific functional targets for ablation. Panoramic contact mapping, incorporating phase analysis, repolarization and conduction dynamics, and oscillations in AF rate, overcomes many prior difficulties with mapping AF. This approach provides evidence that the mechanisms sustaining human AF are deterministic, largely due to stable electrical rotors and focal sources in either atrium. Ablation of such sources (Focal Impulse and Rotor Modulation: FIRM ablation) has been shown to improve ablation outcome compared with conventional ablation alone; independent laboratories directly targeting stable rotors have shown similar results. Clinical trials examining the role of stand-alone FIRM ablation are in progress. Looking forward, translating insights from patient-specific mapping to evidence-based guidelines and clinical practice is the next challenge in improving patient outcomes in AF management.

  View details for DOI 10.3978/j.issn.2072-1439.2014.11.15

  View details for PubMedID 25713729

  View details for PubMedCentralID PMC4321066

• Rotor mapping and ablation to treat atrial fibrillation CURRENT OPINION IN CARDIOLOGY Zaman, J. A., Peters, N. S., Narayan, S. M. 2015; 30 (1): 24-32

  Abstract

  Rotors have long been postulated to drive atrial fibrillation, but evidence has been limited to animal models. This changed recently with the demonstration using focal impulse and rotor modulation (FIRM) mapping that rotors act as human atrial fibrillation sources. This mechanistic approach to diagnosing the causes of atrial fibrillation in individual patients has been supported by substantially improved outcomes from FIRM-guided ablation, resulting in increased attention to rotors as therapeutic targets.In this review, we outline the pathophysiology of rotors in animal and in-silico studies of fibrillation, and how this motivated FIRM mapping in humans. We highlight the characteristics of rotors in human atrial fibrillation, now validated by several techniques, with discussion on similar and discrepant findings between techniques. The interventional approaches to eliminate atrial fibrillation rotors are explained and the ablation results in latest studies using FIRM are discussed.We propose that mapping localized sources for human atrial fibrillation, specifically rotors, is moving the field towards a unifying hypothesis that explains several otherwise contradictory observations in atrial fibrillation management. We conclude by suggesting areas of potential research that may reveal more about these critical sites and how these may lead to better and novel treatments for atrial fibrillation.

  View details for DOI 10.1097/HCO.0000000000000123

  View details for Web of Science ID 000346157200004

  View details for PubMedID 25389649

• Progress toward the prevention and treatment of atrial fibrillation: A summary of the Heart Rhythm Society Research Forum on the Treatment and Prevention of Atrial Fibrillation, Washington, DC, December 9-10, 2013. Heart rhythm Van Wagoner, D. R., Piccini, J. P., Albert, C. M., Anderson, M. E., Benjamin, E. J., Brundel, B., Califf, R. M., Calkins, H., Chen, P., Chiamvimonvat, N., Darbar, D., Eckhardt, L. L., Ellinor, P. T., Exner, D. V., Fogel, R. I., Gillis, A. M., Healey, J., Hohnloser, S. H., Kamel, H., Lathrop, D. A., Lip, G. Y., Mehra, R., Narayan, S. M., Olgin, J., Packer, D., Peters, N. S., Roden, D. M., Ross, H. M., Sheldon, R., Wehrens, X. H. 2015; 12 (1): e5-e29

  View details for DOI 10.1016/j.hrthm.2014.11.011

  View details for PubMedID 25460864

• Stability of Rotors and Focal Sources for Human Atrial Fibrillation: Focal Impulse and Rotor Mapping (FIRM) of AF Sources and Fibrillatory Conduction JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Swarup, V., Baykaner, T., Rostamian, A., Daubert, J. P., Hummel, J., Krummen, D. E., Trikha, R., Miller, J. M., Tomassoni, G. F., Narayan, S. M. 2014; 25 (12): 1284-1292

  Abstract

  Several groups report electrical rotors or focal sources that sustain atrial fibrillation (AF) after it has been triggered. However, it is difficult to separate stable from unstable activity in prior studies that examined only seconds of AF. We applied phase-based focal impulse and rotor mapping (FIRM) to study the dynamics of rotors/sources in human AF over prolonged periods of time.We prospectively mapped AF in 260 patients (169 persistent, 61 ± 12 years) at 6 centers in the FIRM registry, using baskets with 64 contact electrodes per atrium. AF was phase mapped (RhythmView, Topera, Menlo Park, CA, USA). AF propagation movies were interpreted by each operator to assess the source stability/dynamics over tens of minutes before ablation.Sources were identified in 258 of 260 of patients (99%), for 2.8 ± 1.4 sources/patient (1.8 ± 1.1 in left, 1.1 ± 0.8 in right atria). While AF sources precessed in stable regions, emanating activity including spiral waves varied from collision/fusion (fibrillatory conduction). Each source lay in stable atrial regions for 4,196 ± 6,360 cycles, with no differences between paroxysmal versus persistent AF (4,290 ± 5,847 vs. 4,150 ± 6,604; P = 0.78), or right versus left atrial sources (P = 0.26).Rotors and focal sources for human AF mapped by FIRM over prolonged time periods precess ("wobble") but remain within stable regions for thousands of cycles. Conversely, emanating activity such as spiral waves disorganize and collide with the fibrillatory milieu, explaining difficulties in using activation mapping or signal processing analyses at fixed electrodes to detect AF rotors. These results provide a rationale for targeted ablation at AF sources rather than fibrillatory spiral waves.

  View details for DOI 10.1111/jce.12559

  View details for Web of Science ID 000346020800004

  View details for PubMedID 25263408

• Structural contributions to fibrillatory rotors in a patient-derived computational model of the atria. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Gonzales, M. J., Vincent, K. P., Rappel, W. J., Narayan, S. M., McCulloch, A. D. 2014; 16 Suppl 4: iv3-iv10

  Abstract

  The aim of this study was to investigate structural contributions to the maintenance of rotors in human atrial fibrillation (AF) and possible mechanisms of termination.A three-dimensional human biatrial finite element model based on patient-derived computed tomography and arrhythmia observed at electrophysiology study was used to study AF. With normal physiological electrical conductivity and effective refractory periods (ERPs), wave break failed to sustain reentrant activity or electrical rotors. With depressed excitability, decreased conduction anisotropy, and shorter ERP characteristic of AF, reentrant rotors were readily maintained. Rotors were transiently or permanently trapped by fibre discontinuities on the lateral wall of the right atrium near the tricuspid valve orifice and adjacent to the crista terminalis, both known sites of right atrial arrhythmias. Modelling inexcitable regions near the rotor tip to simulate fibrosis anchored the rotors, converting the arrhythmia to macro-reentry. Accordingly, increasing the spatial core of inexcitable tissue decreased the frequency of rotation, widened the excitable gap, and enabled an external wave to impinge on the rotor core and displace the source.These model findings highlight the importance of structural features in rotor dynamics and suggest that regions of fibrosis may anchor fibrillatory rotors. Increasing extent of fibrosis and scar may eventually convert fibrillation to excitable gap reentry. Such macro-reentry can then be eliminated by extending the obstacle or by external stimuli that penetrate the excitable gap.

  View details for DOI 10.1093/europace/euu251

  View details for PubMedID 25362167

• Rotors and Focal Sources for Human Atrial Fibrillation - Mechanistic Paradigm With Direct Clinical Relevance CIRCULATION JOURNAL Lalani, G. G., Trikha, R., Krummen, D. E., Narayan, S. M. 2014; 78 (10): 2357-2366

  View details for DOI 10.1253/circj.CJ-14-0478

  View details for Web of Science ID 000343249600003

• Human Atrial Fibrillation Initiates via Organized Rather Than Disorganized Mechanisms. Circulation. Arrhythmia and electrophysiology Schricker, A. A., Lalani, G. G., Krummen, D. E., Rappel, W. J., Narayan, S. M. 2014; 7 (5): 816-24

  Abstract

  It is unknown how atrial fibrillation (AF) is actually initiated by triggers. Based on consistencies in atrial structure and function in individual patients between episodes of AF, we hypothesized that human AF initiates when triggers interact with deterministic properties of the atria and may engage organized mechanisms.In 31 patients with AF, we mapped AF initiation after spontaneous triggers or programmed stimulation. We used 64-pole basket catheters to measure regional dynamic conduction slowing and to create biatrial activation maps during transitions to AF. Sixty-two AF initiations were recorded (spontaneous, n=28; induced, n=34). Notably, AF did not initiate by disorganized mechanisms, but by either a dominant reentrant spiral wave (76%) or a repetitive focal driver. Both mechanisms were located 21±17 mm from their triggers. AF-initiating spirals formed at the site showing the greatest rate-dependent slowing in each patient. Accordingly, in 10 of 12 patients with multiple observed AF episodes, AF initiated using spatially conserved mechanisms despite diverse triggers.Human AF initiates from triggers by organized rather than disorganized mechanisms, either via spiral wave re-entry at sites of dynamic conduction slowing or via repetitive focal drivers. The finding that diverse triggers initiate AF at predictable, spatially conserved functional sites in each individual provides a novel deterministic paradigm for AF with therapeutic implications.

  View details for DOI 10.1161/CIRCEP.113.001289

  View details for PubMedID 25217042

  View details for PubMedCentralID PMC4206587

• Human Atrial Fibrillation Initiates via Organized Rather Than Disorganized Mechanisms CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Schricker, A. A., Lalani, G. G., Krummen, D. E., Rappel, W., Narayan, S. M. 2014; 7 (5): 816-U94

  View details for DOI 10.1161/CIRCEP.113.001289

  View details for Web of Science ID 000344156200010

• Rotors and focal sources for human atrial fibrillation: mechanistic paradigm with direct clinical relevance. Circulation journal : official journal of the Japanese Circulation Society Lalani, G. G., Trikha, R., Krummen, D. E., Narayan, S. M. 2014; 78 (10): 2357-66

  Abstract

  Outcomes for patients with atrial fibrillation (AF) have changed little despite many advances in technology. In large part, this reflects fundamental uncertainty about the mechanisms for AF in humans, which must reconcile diverse observations. Despite the complexity of AF, many electrophysiologists have witnessed modulation of 'chaotic' AF after the first few ablation lesions, or before lines are complete or trigger sites are isolated, and numerous analyses demonstrate temporospatial stability in AF. These common observations challenge the concept that AF is driven by spatially disorganized, widespread mechanisms. Using mathematical techniques applied to other complex systems, evidence is rapidly accumulating that human AF is largely sustained by localized rotors and focal sources. Elimination of sources by Focal Impulse and Rotor Modulation (FIRM)-guided ablation has been shown by independent laboratories to substantially improve success compared with pulmonary vein isolation alone. These data advance our mechanistic understanding of AF. Randomized trials are underway to verify the relative efficacy of ablation at AF sources (substrate) vs. conventional trigger ablation. The renewed focus on AF substrates is a paradigm shift, but also a re-alignment of concepts for AF towards those for other cardiac arrhythmias that are generally defined by sustaining mechanisms (substrates).

  View details for PubMedID 25213002

• Mapping and ablating stable sources for atrial fibrillation: summary of the literature on Focal Impulse and Rotor Modulation (FIRM) JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY Baykaner, T., Lalani, G. G., Schricker, A., Krummen, D. E., Narayan, S. M. 2014; 40 (3): 237-244

  Abstract

  Atrial fibrillation (AF) is the most common sustained arrhythmia and the most common indication for catheter ablation. However, despite substantial technical advances in mapping and energy delivery, ablation outcomes remain suboptimal. A major limitation to AF ablation is that the areas targeted for ablation are rarely of proven mechanistic importance, in sharp contrast to other arrhythmias in which ablation targets demonstrated mechanisms in each patient. Focal impulse and rotor modulation (FIRM) is a new approach to demonstrate the mechanisms that sustain AF ("substrates") in each patient that can be used to guide ablation then confirm elimination of each mechanism. FIRM mapping reveals that AF is sustained by 2-3 rotors and focal sources, with a greater number in patients with persistent than paroxysmal AF, lying within spatially reproducible 2.2 ± 1.4-cm(2) areas in diverse locations. This temporospatial reproducibility, now confirmed by several groups using various methods, changes the concepts regarding AF-sustaining mechanisms, enabling localized rather than widespread ablation. Mechanistically, the role of rotors and focal sources in sustaining AF has been demonstrated by the acute and chronic success of source (FIRM) ablation alone. Clinically, adding FIRM to conventional ablation substantially improves arrhythmia freedom compared with conventional ablation alone, and ongoing randomized trials are comparing FIRM-ablation with and without conventional ablation to conventional ablation alone. In conclusion, ablation of patient-specific AF-sustaining mechanisms (substrates), as exemplified by FIRM, may be central to substantially improving AF ablation outcomes.

  View details for DOI 10.1007/s10840-014-9889-8

  View details for Web of Science ID 000341693100006

  View details for PubMedID 24647673

• Initial Independent Outcomes from Focal Impulse and Rotor Modulation Ablation for Atrial Fibrillation: Multicenter FIRM Registry JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Miller, J. M., Kowal, R. C., Swarup, V., Daubert, J. P., Daoud, E. G., Day, J. D., Ellenbogen, K. A., Hummel, J. D., Baykaner, T., Krummen, D. E., Narayan, S. M., Reddy, V. Y., Shivkumar, K., Steinberg, J. S., Wheelan, K. R. 2014; 25 (9): 921-929

  Abstract

  The success of pulmonary vein isolation (PVI) for atrial fibrillation (AF) may be improved if stable AF sources identified by Focal Impulse and Rotor Mapping (FIRM) are also eliminated. The long-term results of this approach are unclear outside the centers where FIRM was developed; thus, we assessed outcomes of FIRM-guided AF ablation in the first cases at 10 experienced centers.We prospectively enrolled n = 78 consecutive patients (61 ± 10 years) undergoing FIRM guided ablation for persistent (n = 48), longstanding persistent (n = 7), or paroxysmal (n = 23) AF. AF recordings from both atria with a 64-pole basket catheter were analyzed using a novel mapping system (Rhythm View(TM) ; Topera Inc., CA, USA). Identified rotors/focal sources were ablated, followed by PVI.Each institution recruited a median of 6 patients, each of whom showed 2.3 ± 0.9 AF rotors/focal sources in diverse locations. 25.3% of all sources were right atrial (RA), and 50.0% of patients had ≥1 RA source. Ablation of all sources required a total of 16.6 ± 11.7 minutes, followed by PVI. On >1 year follow-up with a 3-month blanking period, 1 patient lost to follow-up (median time to 1st recurrence: 245 days, IQR 145-354), single-procedure freedom from AF was 87.5% (patients without prior ablation; 35/40) and 80.5% (all patients; 62/77) and similar for persistent and paroxysmal AF (P = 0.89).Elimination of patient-specific AF rotors/focal sources produced freedom-from-AF of ≈80% at 1 year at centers new to FIRM. FIRM-guided ablation has a rapid learning curve, yielding similar results to original FIRM reports in each center's first cases.

  View details for DOI 10.1111/jce.12474

  View details for Web of Science ID 000341821200003

  View details for PubMedID 24948520

• Rhythm control in heart failure patients with atrial fibrillation: contemporary challenges including the role of ablation. Journal of the American College of Cardiology Trulock, K. M., Narayan, S. M., Piccini, J. P. 2014; 64 (7): 710-21

  Abstract

  Because nonpharmacological interventions likely alter the risks and benefits associated with rhythm control, this paper reviews the role of current rhythm control strategies in atrial fibrillation. This report also focuses on the specific limitations of pharmacological interventions and the utility of percutaneous ablation in this growing population of patients with concomitant atrial fibrillation and heart failure.

  View details for DOI 10.1016/j.jacc.2014.06.1169

  View details for PubMedID 25125304

• CrossTalk proposal: Rotors have been demonstrated to drive human atrial fibrillation JOURNAL OF PHYSIOLOGY-LONDON Narayan, S. M., Jalife, J. 2014; 592 (15): 3163-3166

  View details for DOI 10.1113/jphysiol.2014.271031

  View details for Web of Science ID 000340404100001

  View details for PubMedID 25085968

• Defining Arrhythmic Risk and Defibrillator Therapy in ARVC Shocking Rhythm? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY McGarry, T. J., Narayan, S. M. 2014; 64 (2): 126-128

  View details for DOI 10.1016/j.jacc.2014.05.010

  View details for Web of Science ID 000340238400002

  View details for PubMedID 25011715

• Rotor Stability Separates Sustained Ventricular Fibrillation From Self-Terminating Episodes in Humans JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Krummen, D. E., Hayase, J., Morris, D. J., Ho, J., Smetak, M. R., Clopton, P., Rappel, W., Narayan, S. M. 2014; 63 (24): 2712-2721

  Abstract

  This study mapped human ventricular fibrillation (VF) to define mechanistic differences between episodes requiring defibrillation versus those that spontaneously terminate.VF is a leading cause of mortality; yet, episodes may also self-terminate. We hypothesized that the initial maintenance of human VF is dependent upon the formation and stability of VF rotors.We enrolled 26 consecutive patients (age 64 ± 10 years, n = 13 with left ventricular dysfunction) during ablation procedures for ventricular arrhythmias, using 64-electrode basket catheters in both ventricles to map VF prior to prompt defibrillation per the institutional review board-approved protocol. A total of 52 inductions were attempted, and 36 VF episodes were observed. Phase analysis was applied to identify biventricular rotors in the first 10 s or until VF terminated, whichever came first (11.4 ± 2.9 s to defibrillator charging).Rotors were present in 16 of 19 patients with VF and in all patients with sustained VF. Sustained, but not self-limiting VF, was characterized by greater rotor stability: 1) rotors were present in 68 ± 17% of cycles in sustained VF versus 11 ± 18% of cycles in self-limiting VF (p < 0.001); and 2) maximum continuous rotations were greater in sustained (17 ± 11, range 7 to 48) versus self-limiting VF (1.1 ± 1.4, range 0 to 4, p < 0.001). Additionally, biventricular rotor locations in sustained VF were conserved across multiple inductions (7 of 7 patients, p = 0.025).In patients with and without structural heart disease, the formation of stable rotors identifies individuals whose VF requires defibrillation from those in whom VF spontaneously self-terminates. Future work should define the mechanisms that stabilize rotors and evaluate whether rotor modulation may reduce subsequent VF risk.

  View details for DOI 10.1016/j.jacc.2014.03.037

  View details for Web of Science ID 000337358800010

  View details for PubMedID 24794115

• Ablation of Rotor and Focal Sources Reduces Late Recurrence of Atrial Fibrillation Compared With Trigger Ablation Alone Extended Follow-Up of the CONFIRM Trial (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Narayan, S. M., Baykaner, T., Clopton, P., Schricker, A., Lalani, G. G., Krummen, D. E., Shivkumar, K., Miller, J. M. 2014; 63 (17): 1761-1768

  Abstract

  The aim of this study was to determine if ablation that targets patient-specific atrial fibrillation (AF)-sustaining substrates (rotors or focal sources) is more durable than trigger ablation alone at preventing late AF recurrence.Late recurrence substantially limits the efficacy of pulmonary vein isolation for AF and is associated with pulmonary vein reconnection and the emergence of new triggers.Three-year follow-up was performed of the CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial, in which 92 consecutive patients with AF (70.7% persistent) underwent novel computational mapping. Ablation comprised source (focal impulse and rotor modulation [FIRM]) and then conventional ablation in 27 patients (FIRM guided) and conventional ablation alone in 65 patients (FIRM blinded). Patients were followed with implanted electrocardiographic monitors when possible (85.2% of FIRM-guided patients, 23.1% of FIRM-blinded patients).FIRM mapping revealed a median of 2 (interquartile range: 1 to 2) rotors or focal sources in 97.7% of patients during AF. During a median follow-up period of 890 days (interquartile range: 224 to 1,563 days), compared to FIRM-blinded therapy, patients receiving FIRM-guided ablation maintained higher freedom from AF after 1.2 ± 0.4 procedures (median 1; interquartile range: 1 to 1) (77.8% vs. 38.5%, p = 0.001) and a single procedure (p < 0.001) and higher freedom from all atrial arrhythmias (p = 0.003). Freedom from AF was higher when ablation directly or coincidentally passed through sources than when it missed sources (p < 0.001).FIRM-guided ablation is more durable than conventional trigger-based ablation in preventing 3-year AF recurrence. Future studies should investigate how ablation of patient-specific AF-sustaining rotors and focal sources alters the natural history of arrhythmia recurrence. (The Dynamics of Human Atrial Fibrillation; NCT01008722).

  View details for DOI 10.1016/j.jacc.2014.02.543

  View details for Web of Science ID 000335312200011

  View details for PubMedID 24632280

• Lone Atrial Fibrillation Does it Exist? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Wyse, D. G., van Gelder, I. C., Ellinor, P. T., Go, A. S., Kalman, J. M., Narayan, S. M., Nattel, S., Schotten, U., Rienstra, M. 2014; 63 (17): 1715-1723

  Abstract

  The historical origin of the term "lone atrial fibrillation" (AF) predates by 60 years our current understanding of the pathophysiology of AF, the multitude of known etiologies for AF, and our ability to image and diagnose heart disease. The term was meant to indicate AF in patients for whom subsequent investigations could not demonstrate heart disease, but for many practitioners has become synonymous with "idiopathic AF." As the list of heart diseases has expanded and diagnostic techniques have improved, the prevalence of lone AF has fallen. The legacy of the intervening years is that definitions of lone AF in the literature are inconsistent so that studies of lone AF are not comparable. Guidelines provide a vague definition of lone AF but do not provide direction about how much or what kind of imaging and other testing are necessary to exclude heart disease. There has been an explosion in the understanding of the pathophysiology of AF in the last 20 years in particular. Nevertheless, there are no apparently unique mechanisms for AF in patients categorized as having lone AF. In addition, the term "lone AF" is not invariably useful in making treatment decisions, and other tools for doing so have been more thoroughly and carefully validated. It is, therefore, recommended that use of the term "lone AF" be avoided.

  View details for DOI 10.1016/j.jacc.2014.01.023

  View details for Web of Science ID 000335312200004

  View details for PubMedID 24530673

• Intermittent Atrial Tachycardia Promotes Repolarization Alternans and Conduction Slowing During Rapid Rates, and Increases Susceptibility to Atrial Fibrillation in a Free-Behaving Sheep Model JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Monigatti-Tenkorang, J., Jousset, F., Pascale, P., Vesin, J., Ruchat, P., Fromer, M., Narayan, S. M., Pruvot, E. 2014; 25 (4): 418-427

  Abstract

  Paroxysmal atrial fibrillation (AF) may be triggered by intermittent atrial tachycardia, and ultimately lead to persistent AF. However, the mechanisms by which intermittent atrial tachycardia promotes sustained AF are not well understood.Eight sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms, and for the delivery of electrophysiological stimulation protocols and intermittent right atrial tachycardia. Right atrial kinetics of activation recovery interval (ARI) as a surrogate for action potential duration, of conduction time and velocity, and of repolarization alternans were analyzed at incremental pacing rates during the remodeling process induced by weeks of intermittent atrial tachycardia until the development of sustained AF. Intermittent atrial tachycardia decreased ARI and blunted its rate adaptation, facilitated atrial capture, and slowed conduction at high rates, and increased susceptibility to pacing-induced AF. In spite of blunted ARI rate adaptation, right atrial repolarization alternans was maintained during remodeling, and further increased in magnitude just before rapid pacing-induced AF.This study suggests that weeks of intermittent right atrial tachycardia result in a gradual electrical remodeling favorable for wavebreaks and reentry that may facilitate fibrillation.

  View details for DOI 10.1111/jce.12353

  View details for Web of Science ID 000334165500013

  View details for PubMedID 24383960

• Highlights of the Year in JACC 2013 JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY DeMaria, A. N., Adler, E. D., Bax, J. J., Ben-Yehuda, O., Feld, G. K., Greenberg, B. H., Hall, J. L., Hlatky, M. A., Lew, W. Y., Lima, J. A., Mahmud, E., Maisel, A. S., Narayan, S. M., Nissen, S. E., Sahn, D. J., Tsimikas, S. 2014; 63 (6): 570-602

  View details for DOI 10.1016/j.jacc.2014.01.002

  View details for Web of Science ID 000331081700015

• Highlights of the year in JACC 2013. Journal of the American College of Cardiology DeMaria, A. N., Adler, E. D., Bax, J. J., Ben-Yehuda, O., Feld, G. K., Greenberg, B. H., Hall, J. L., Hlatky, M. A., Lew, W. Y., Lima, J. A., Mahmud, E., Maisel, A. S., Narayan, S. M., Nissen, S. E., Sahn, D. J., Tsimikas, S. 2014; 63 (6): 570-602

  View details for DOI 10.1016/j.jacc.2014.01.002

  View details for PubMedID 24524815

• A case of a human ventricular fibrillation rotor localized to ablation sites for scar-mediated monomorphic ventricular tachycardia HEART RHYTHM Hayase, J., Tung, R., Narayan, S. M., Krummen, D. E. 2013; 10 (12): 1913-1916

  View details for DOI 10.1016/j.hrthm.2013.07.049

  View details for Web of Science ID 000327767600035

  View details for PubMedID 23911894

• What Tissue Does Circumferential PV Isolation Actually Modulate? Journal of cardiovascular electrophysiology McGarry, T. J., Narayan, S. M. 2013

  View details for DOI 10.1111/jce.12310

  View details for PubMedID 24152088

  View details for PubMedCentralID PMC3997629

• Frequency Analysis of Atrial Action Potential Alternans A Sensitive Clinical Index of Individual Propensity to Atrial Fibrillation CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Lalani, G. G., Schricker, A. A., Clopton, P., Krummen, D. E., Narayan, S. M. 2013; 6 (5): 859-867

  Abstract

  Few clinical indices identify the propensity of patients to atrial fibrillation (AF) when not in AF. Repolarization alternans has been shown to indicate AF vulnerability, but is limited in its sensitivity to detect changes in action potential (AP) duration (APD), which may be subtle. We hypothesized that spectral analysis would be a more sensitive and robust marker of AP alternans and thus a better clinical index of individual propensity to AF than APD alternans.In 31 patients (12 persistent AF, 15 paroxysmal AF, 4 controls with no AF), we recorded left (n=27) and right (n=6) atrial monophasic APs during incremental pacing from cycle length 500 ms (120 beats per minute) to AF onset. Alternans was measured by APD and spectral analysis. At baseline pacing (median cycle length [1st, 3rd quartiles], 500 ms [500, 500]), APD alternans was detected in only 7 of 27 AF patients (no controls), whereas spectral AP alternans was detected in 18 of 27 AF patients (no controls; P=0.003); AP alternans was more prevalent in persistent than paroxysmal AF, and absent in controls (P=0.018 APD; P=0.042 spectral). Spectral AP alternans magnitude at baseline was highest in persistent AF, with modest rate-dependent amplification, followed by paroxysmal AF, with marked rate dependence, and undetectable in controls until just before induced AF.Spectral AP alternans near baseline rates can identify patients with, versus those without, clinical histories and pathophysiological substrates for AF. Future studies should examine whether the presence of spectral AP alternans during sinus rhythm may obviate the need to actually demonstrate AF, such as on ambulatory ECG monitoring.

  View details for DOI 10.1161/CIRCEP.113.000204

  View details for Web of Science ID 000329923700014

  View details for PubMedID 23995250

• Targeted Ablation at Stable Atrial Fibrillation Sources Improves Success Over Conventional Ablation in High-Risk Patients: A Substudy of the CONFIRM Trial CANADIAN JOURNAL OF CARDIOLOGY Baykaner, T., Clopton, P., Lalani, G. G., Schricker, A. A., Krummen, D. E., Narayan, S. M. 2013; 29 (10): 1218-1226

  Abstract

  Pulmonary vein (PV) isolation has disappointing results in patients with obesity, heart failure, obstructive sleep apnea (OSA) and enlarged left atria (LA), for unclear reasons. We hypothesized that these comorbidities may cause higher numbers or non-PV locations of atrial fibrillation (AF) sources, where targeted source ablation (focal impulse and rotor modulation [FIRM]) should improve the single-procedure success of ablation.The Conventional Ablation of AF With or Without Focal Impulse and Rotor Modulation (CONFIRM) trial prospectively enrolled 92 patients at 107 AF ablation procedures, in whom computational mapping identified AF rotors or focal sources. Patients underwent FIRM plus conventional ablation (FIRM-guided), or conventional ablation only, and were evaluated for recurrent AF quarterly with rigourous, often implanted, monitoring. We report the n = 73 patients undergoing first ablation in whom demographic information was available (n = 52 conventional, n = 21 FIRM-guided).Stable sources for AF were found in 97.1% of patients. The numbers of concurrent sources per patient (2.1 ± 1.1) rose with LA diameter (P = 0.021), lower left ventricular ejection fraction (P = 0.039), and the presence of OSA (P = 0.002) or hypomagnesemia (P = 0.017). Right atrial sources were associated with obesity (body mass index ≥ 30; P = 0.015). In patients with obesity, hypertension, OSA, and LA diameter > 40 mm, single-procedure freedom from AF was > 80% when FIRM-guided was used vs. < 50% when conventional ablation was used (all; P < 0.05).Patients with "difficult to treat" AF exhibit more concurrent AF sources in more widespread biatrial distributions than other patients. These mechanisms explain the disappointing results of PV isolation, and how FIRM can identify patient-specific AF sources to enable successful ablation in this population.

  View details for DOI 10.1016/j.cjca.2013.07.672

  View details for Web of Science ID 000324858700011

  View details for PubMedID 23993247

• Direct or Coincidental Elimination of Stable Rotors or Focal Sources May Explain Successful Atrial Fibrillation Ablation On-Treatment Analysis of the CONFIRM Trial (Conventional Ablation for AF With or Without Focal Impulse and Rotor Modulation) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Narayan, S. M., Krummen, D. E., Clopton, P., Shivkumar, K., Miller, J. M. 2013; 62 (2): 138-147

  Abstract

  This study sought to determine whether ablation of recently described stable atrial fibrillation (AF) sources, either directly by Focal Impulse and Rotor Modulation (FIRM) or coincidentally when anatomic ablation passes through AF sources, may explain long-term freedom from AF.It is unclear why conventional anatomic AF ablation can be effective in some patients yet ineffective in others with similar profiles.The CONFIRM (Conventional Ablation for AF With or Without Focal Impulse and Rotor Modulation) trial prospectively revealed stable AF rotors or focal sources in 98 of 101 subjects with AF at 107 consecutive ablation cases. In 1:2 fashion, subjects received targeted source ablation (FIRM) followed by conventional ablation, or conventional ablation alone. We determined whether ablation lesions on electroanatomic maps passed through AF sources on FIRM maps.Subjects who completed follow-up (n = 94; 71.2% with persistent AF) showed 2.3 ± 1.1 concurrent AF rotors or focal sources that lay near pulmonary veins (22.8%), left atrial roof (16.0%), and elsewhere in the left (28.2%) and right (33.0%) atria. AF sources were ablated directly in 100% of FIRM cases and coincidentally (e.g., left atrial roof) in 45% of conventional cases (p < 0.05). During a median (interquartile range) of 273 days (138 to 636 days) after one procedure, AF was absent in 80.3% of patients if sources were ablated but in only 18.2% of patients if sources were missed (p < 0.001). Freedom from AF was highest if all sources were ablated, intermediate if some sources were ablated, and lowest if no sources were ablated (p < 0.001).Elimination of stable AF rotors and focal sources may explain freedom from AF after diverse approaches to ablation. Patient-specific AF source distributions are consistent with the reported success of specific anatomic lesion sets and of widespread ablation. These results support targeting AF sources to reduce unnecessary ablation, and motivate studies on FIRM-only ablation.

  View details for DOI 10.1016/j.jacc.2013.03.021

  View details for Web of Science ID 000321338600010

  View details for PubMedID 23563126

• Panoramic Electrophysiological Mapping but not Electrogram Morphology Identifies Stable Sources for Human Atrial Fibrillation Stable Atrial Fibrillation Rotors and Focal Sources Relate Poorly to Fractionated Electrograms CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Narayan, S. M., Shivkumar, K., Krummen, D. E., Miller, J. M., Rappel, W. 2013; 6 (1): 58-67

  Abstract

  The foundation for successful arrhythmia ablation is the mapping of electric propagation to identify underlying mechanisms. In atrial fibrillation (AF), however, mapping is difficult so that ablation has often targeted electrogram features, with mixed results. We hypothesized that wide field-of-view (panoramic) mapping of both atria would identify causal mechanisms for AF and allow interpretation of local electrogram features, including complex fractionated atrial electrograms (CFAE).Contact mapping was performed using biatrial multipolar catheters in 36 AF subjects (29 persistent). Stable AF rotors (spiral waves) or focal sources were seen in 35 of 36 cases and targeted for ablation (focal impulse and rotor modulation) before pulmonary vein isolation. In 31 of 36 subjects (86.1%), AF acutely terminated (n=20; 16 to sinus rhythm) or organized (n=11; 19±8% slowing) with 2.5 minutes focal impulse and rotor modulation (interquartile range, 1.0-3.1) at one source, defined as the primary source. Subjects exhibited 2.1±1.0 concurrent AF sources of which the primary, by phase mapping, precessed in limited areas (persistent 2.5±1.7 versus paroxysmal 1.7±0.5 cm(2); P=0.30). Notably, source regions showed mixed electrogram amplitudes and CFAE grades that did not differ from surrounding atrium (P=NS). AF sources were not consistently surrounded by CFAE (P=0.67).Stable rotors and focal sources for human AF were revealed by contact panoramic mapping (focal impulse and rotor modulation mapping), but not by electrogram footprints. AF sources precessed within areas of ≈2 cm(2), with diverse voltage characteristics poorly correlated with CFAE. Most CFAE sites lie remote from AF sources and are not suitable targets for catheter ablation of AF.

  View details for DOI 10.1161/CIRCEP.111.977264

  View details for Web of Science ID 000320670700013

  View details for PubMedID 23392583

• HRS Policy Statement: Clinical Cardiac Electrophysiology Fellowship Curriculum: Update 2011 HEART RHYTHM Link, M. S., Exner, D. V., Anderson, M., Ackerman, M., Al-Ahmad, A., Knight, B. P., Markowitz, S. M., Kaufman, E. S., Haines, D., Asirvatham, S. J., Callans, D. J., Mounsey, J. P., Bogun, F., Narayan, S. M., Krahn, A. D., Mittal, S., Singh, J., Fisher, J. D., Chugh, S. S. 2011; 8 (8): 1340-1356

  View details for DOI 10.1016/j.hrthm.2011.06.008

  View details for Web of Science ID 000293013600033

  View details for PubMedID 21699868

  View details for PubMedCentralID PMC4073645

• Highlights of the Year in JACC 2010 JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY DeMaria, A. N., Bax, J. J., Ben-Yehuda, O., Feld, G. K., Greenberg, B. H., Hall, J., Hlatky, M., Lew, W. Y., Lima, J. A., Maisel, A. S., Narayan, S. M., Nissen, S., Sahn, D. J., Tsimikas, S. 2011; 57 (4): 480-514

  View details for DOI 10.1016/j.jacc.2010.12.007

  View details for Web of Science ID 000286376500015

  View details for PubMedID 21251590

• Highlights of the Year in JACC 2009 JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY DeMaria, A. N., Bax, J. J., Ben-Yehuda, O., Feld, G. K., Greenberg, B. H., Hall, J., Hlatky, M., Lew, W. Y., Lima, J. A., Maisel, A. S., Narayan, S. M., Nissen, S., Sahn, D. J., Tsimikas, S. 2010; 55 (4): 380-407

  View details for DOI 10.1016/j.jacc.2009.12.007

  View details for Web of Science ID 000273802200023

  View details for PubMedID 20117446