Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction. Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in NaV1.5 and Cx43. By sequencing and transgenic approaches, we identify Notch signaling as a mechanistic contributor to NaV1.5 upregulation after RT. Clinically, RT was associated with increased NaV1.5 expression in 1 of 1 explanted heart. On electrocardiogram (ECG), post-RT QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients. Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in VT patients.

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.

Reactive arthritis (ReA) following bacterial infection from the urogenital and gastrointestinal tract is widely described but is not typical post-viral infections. This report presents the second case of ReA after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States. A 45-year-old black male with chronic low back pain was hospitalized for 45 days with coronavirus disease 2019 (COVID-19), complicated due to the development of multiorgan failure managed with intubation, extracorporeal membrane oxygenation, and hemodialysis. He was subsequently discharged to an acute rehabilitation facility where he complained of new-onset pain in his shoulders, left elbow, and left knee three weeks after a negative SARS-CoV-2 test. He was readmitted from his acute rehabilitation facility due to recurrent fever and the development of a swollen, warm left knee. Laboratory studies at readmission showed elevated inflammatory markers, negative extensive infectious disease workup, and aseptic inflammatory left knee synovial fluid without crystals. Testing returned negative for most common antibodies seen in immunemediated arthritides (e.g., rheumatoid arthritis, systemic lupus erythematosus), as well as for common respiratory and gastrointestinal tract pathogens responsible for viral arthritis. The multidisciplinary inpatient medical team deemed the clinical presentation and laboratory findings most consistent with ReA. The patient received a course of oral corticosteroids, followed by a second course due to the recurrence of symptoms weeks after initial treatment and recovery. The current body of medical literature on SARS-CoV-2 pathophysiology supports plausible mechanisms on how this infection may induce ReA. Such a scenario should be considered in the differential of COVID-19-recovered patients presenting with polyarthritis as prompt steroid treatment may help patient recovery.

Background 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 colocalize with ganglionated plexi (GP). Methods 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. Results 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 2–3 cm2. 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). Conclusions 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.

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 2 independent mapping methods. METHODS We studied patients with AF referred for ablation, in whom bi-atrial 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.

Introduction 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. Methods 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 ± 6 cm, 38% persistent AF). Both atria were mapped in both rhythms by 64-electrode baskets, traditional activation maps and entrainment. Results 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 ± 0.2 mV vs 0.49 ± 0.2 mV p = 0.03). Conclusions 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.

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