Computationally guided personalized targeted ablation of persistent atrial fibrillation

Boyle, Patrick; Zghaib, Tarek; Zahid, Sohail; Ali, Rheeda L.; Deng, Dongdong; Franceschi, William H.; Hakim, Joe B.; Murphy, Michael J.; Prakosa, Adityo; Zimmerman, Stefan L.; Ashikaga, Hiroshi; Marine, Joseph E.; Kolandaivelu, Aravindan; Nazarian, Saman; Spragg, David D.; Calkins, Hugh; Trayanova, Natalia A.

doi:10.1038/s41551-019-0437-9

Cited by 214 publications

(231 citation statements)

References 65 publications

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“…Note that, although we have used a simple and phenomenological aFK model for the LA simulations, our results are consistent with other studies [14,15,53] performed using more detailed atrial myocyte model such as Coutemanche-Ramirez-Nattel (CRN) model [54], which have also reported anchoring of RDs to fibrotic regions. Moreover, we tested our protocol on 3D slab with the CRN atrial cell model and demonstrated similar behaviour of the RDs (further details provided in the S4 Fig).…”

Section: Limitationssupporting

confidence: 90%

Identifying locations of re-entrant drivers from patient-specific distribution of fibrosis in the left atrium

et al. 2020

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Clinical evidence suggests a link between fibrosis in the left atrium (LA) and atrial fibrillation (AF), the most common sustained arrhythmia. Image-derived fibrosis is increasingly used for patient stratification and therapy guidance. However, locations of re-entrant drivers (RDs) sustaining AF are unknown and therapy success rates remain suboptimal. This study used image-derived LA models to explore the dynamics of RD stabilization in fibrotic regions and generate maps of RD locations. LA models with patient-specific geometry and fibrosis distribution were derived from late gadolinium enhanced magnetic resonance imaging of 6 AF patients. In each model, RDs were initiated at multiple locations, and their trajectories were tracked and overlaid on the LA fibrosis distributions to identify the most likely regions where the RDs stabilized. The simulations showed that the RD dynamics were strongly influenced by the amount and spatial distribution of fibrosis. In patients with fibrosis burden greater than 25%, RDs anchored to specific locations near large fibrotic patches. In patients with fibrosis burden below 25%, RDs either moved near small fibrotic patches or anchored to anatomical features. The patient-specific maps of RD locations showed that areas that harboured the RDs were much smaller than the entire fibrotic areas, indicating potential targets for ablation therapy. Ablating the predicted locations and connecting them to the existing pulmonary vein ablation lesions was the most effective in-silico ablation strategy.

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Section: Limitationssupporting

confidence: 90%

Identifying locations of re-entrant drivers from patient-specific distribution of fibrosis in the left atrium

et al. 2020

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“…Today, radio-frequency catheter ablation is considered to be one of the most effective treatment options, however, the successful outcome is reported to be from 56% to 89% by different clinical trials, moreover, post-operational complications are quite common [2]. On the other hand, several groups reported that personalized mathematical simulation of the action potential (AP) propagation in atria is capable to reproduce clinical measurements and consequently might be used to improve the outcome of the operation by choosing optimal ablation targets [3,4]. One important challenge that remains in the field is inter-subject AP variability present in cardiac electrophysiological recordings [5].…”

Section: Introductionmentioning

confidence: 99%

Personalization of mathematical models of human atrial action potential

Pikunov

Syunyaev

Steckmeister

et al. 2020

Preprint

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AbstractAtrial cardiomyocytes demonstrate a wide spectrum of patient-specific, tissue-specific, and pathology-specific action potential (AP) phenotypes due to differences in protein expression and posttranslational modifications. Accurate simulation of the AP excitation and propagation in healthy or diseased atria requires a mathematical model capable of reproducing all the differences by parameter rescaling. In the present study, we have benchmarked two widely used electrophysiological models of the human atrium: the Maleckar and the Grandi models. In particular, patch-clamp AP recordings from human atrial myocytes were fitted by the genetic algorithm (GA) to test the models' versatility. We have shown that the Maleckar model results in a more accurate fitting of heart rate dependence of action potential duration (APD) and resting potential (RP). On the other hand, both models demonstrate the poor fitting of the plateau phase and spike-and-dome morphologies. We propose that modifications to L-type calcium current-voltage relationships are required to improve atrial models' fidelity.

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“…To realize accurate radical treatment, ablation strategies and mapping systems of cardiac excitation are being considered [3][4][5][6][7]. Recently, a patient-tailored computer simulation model was proposed to determine the appropriate ablation site for each patient [8]. However, cardiac ablation is an irreversible procedure, and only non-paroxysmal patients can undergo cardiac ablation and can be treated.…”

Section: Introductionmentioning

confidence: 99%

Cardiac Spiral Wave Termination by Linear Regional Cooling Toward the Anatomical Boundary of the Heart

et al. 2020

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Purpose We hypothesized that linear regional cooling (LRC) toward the atrio-ventricular groove (AV-G) can move the spiral wave (SW) center to the AV-G effectively and terminate SW. The effectiveness of LRC in ex vivo 2D ventricle rabbit experiments was tested. Methods We developed an experimental system to operate LRC and optical mapping simultaneously. To realize simultaneous cooling and optical mapping, a transparent cooling device was developed. LRC for 60 s toward 2D subepicardial ventricular myocardium of Langendorff-perfused rabbit hearts (n = 4) was conducted during constant pacing and persistent ventricular tachyarrhythmias (VTs). Results Action potential duration at 90% repolarization (APD 90 ) at the cooling area was prolonged by LRC from 187 to 228 ms. 41% of persistent VTs were terminated by LRC (12/29 cases). Cases where the original SW center moved toward the AV-G were observed via optical mapping. However, there were some cases where VT was not terminated by LRC. When the action potential duration (APD) of VT sustained cases were analyzed, LRC prolonged APD, but the APD prolonged area did not move toward the AV-G in most VT sustained cases Conclusion Proper LRC toward the AV-G near the original SW center could move this center toward the AV-G and terminate SW excitation.

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Computationally guided personalized targeted ablation of persistent atrial fibrillation

Cited by 214 publications

References 65 publications

Identifying locations of re-entrant drivers from patient-specific distribution of fibrosis in the left atrium

Identifying locations of re-entrant drivers from patient-specific distribution of fibrosis in the left atrium

Personalization of mathematical models of human atrial action potential

Cardiac Spiral Wave Termination by Linear Regional Cooling Toward the Anatomical Boundary of the Heart

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