Electrophysiologic Determinants of Isoelectric Intervals on Surface Electrocardiograms During Atrial Tachycardia: Insights From High-Density Mapping.

BACKGROUND: Substrate abnormalities can alter atrial activation during atrial tachycardias (ATs) thereby influencing AT-wave morphology on the surface electrocardiogram. OBJECTIVES: This study sought to identify determinants of isoelectric intervals during ATs with complex atrial activation patterns. METHODS: High-density activation maps of 126 ATs were studied. To assess the impact of the activated atrial surface on the presence of isoelectric intervals, this study measured the minimum activated area throughout the AT cycle, defined as the smallest activated area within a 50-millisecond period, by using signal processing algorithms (LUMIPOINT). RESULTS: ATs with isoelectric intervals (P-wave ATs) included 23 macro-re-entrant ATs (40%), 26 localized-re-entrant ATs (46%), and 8 focal ATs (14%), whereas those without included 46 macro-re-entrant ATs (67%), 21 localized-re-entrant ATs (30%), and 2 focal ATs (3%). Multivariable regression identified smaller minimum activated area and larger very low voltage area as independent predictors of P-wave ATs (OR: 0.732; 95% CI: 0.644-0.831; P < 0.001; and OR: 1.042; 95% CI: 1.006-1.080; P = 0.023, respectively). The minimum activated area with the cutoff value of 10 cm2 provided the highest predictive accuracy for P-wave ATs with sensitivity, specificity, and positive and negative predictive values of 96%, 97%, 97%, and 95%, respectively. In re-entrant ATs, smaller minimum activated area was associated with lower minimum conduction velocity within the circuit and fewer areas of delayed conduction outside of the circuit (standardized ß: 0.524; 95% CI: 0.373-0.675; P < 0.001; and standardized ß: 0.353; 95% CI: 0.198-0.508; P < 0.001, respectively). CONCLUSIONS: Reduced atrial activation area and voltage were associated with isoelectric intervals during ATs.

Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8+ T-cells and CD56dimCD57+ NK cells. Bayesian network analyses revealed nine key regulators of this module, including TBX21, a central coordinator of exhausted CD8+ T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.

Characterization of Complex Atrial Tachycardia in Patients With Previous Atrial Interventions Using High-Resolution Mapping.

OBJECTIVES: This study systematically evaluated mechanisms of atrial tachycardia (AT) by using ultra-high-resolution mapping in a large cohort of patients. BACKGROUND: An incomplete understanding of the mechanism of AT is a major determinant of ablation failure. METHODS: Consecutive patients with ≥1 AT (excluding cavotricuspid isthmus-dependent flutter) were included. Mapping was performed with a 64-pole mapping catheter. The AT mechanism was defined based on activation mapping and confirmed by entrainment in selected cases. RESULTS: A total of 132 patients were included (60 ± 12 years; 31 [23%] female; 111 [84%] previous atrial fibrillation [AF] ablation; 5 [4%] previous left atriotomy). One hundred four (94%) of the 111 post-AF ablation AT patients had substrate-based ablation during the index AF ablation. A total of 214 ATs were mapped, with complete definition of the AT mechanism in 206 (96%). A total of 129 (60%) had anatomic macro-re-entry (circuit diameter 44.2 ± 9.6 mm), 57 (27%) had scar-related localized re-entry (circuit diameter 25.8 ± 12.2 mm), and 20 (9%) had focal AT. Fifty-eight (45%) patients had multiple ATs (27 [20%] dual-loop re-entry; 60 [43%] sequential AT) with complex and highly variable transitions between AT circuits. A total of 116 (90%) of 129 macro-re-entrant ATs, 56 (98%) of 57 localized AT, and 20 (100%) of 20 focal ATs terminated after radiofrequency ablation. After a mean follow-up of 13 ± 9 months, 57 (46%) patients experienced recurrence of AT. CONCLUSIONS: Among patients with AT in the context of previous atrial interventions, particularly post-AF ablation patients, multiple complex AT circuits are common. Despite complete delineation of arrhythmia circuits using ultra-high-resolution mapping and high acute ablation success rates, long-term freedom from AT is modest.

Do technical parameters affect the diagnostic accuracy of virtual bronchoscopy in patients with suspected airways stenosis?

PURPOSE: Virtual bronchoscopy has gained popularity over the past decade as an alternative investigation to conventional bronchoscopy in the diagnosis, grading and monitoring of airway disease. The effect of technical parameters on diagnostic outcome from virtual bronchoscopy has not been determined. This meta-analysis aims to estimate accuracy of virtual compared to conventional bronchoscopy in patients with suspected airway stenosis, and evaluate the influence of technical parameters. MATERIALS AND METHODS: A MEDLINE search was used to identify relevant published studies. The primary endpoint was the "correct diagnosis" of stenotic lesions on virtual compared to conventional bronchoscopy. Secondary endpoints included the effects of the technical parameters (pitch, collimation, reconstruction interval, rendering method, and scanner type), and date of publication on the diagnostic accuracy of virtual bronchoscopy. RESULTS: Thirteen studies containing 454 patients were identified. Meta-analysis showed good overall diagnostic performance with 85% calculated pooled sensitivity (95% CI 77-91%), 87% specificity (95% CI 81-92%) and area under the curve (AUC) of 0.947. Subgroups included collimation of 3mm or more (AUC 0.948), pitch of 1 (AUC 0.955), surface rendering technique (AUC 0.935), and reconstruction interval of more than 1.25 mm (AUC 0.914). There was no significant difference in accuracy accounting for publication date, scanner type or any of the above variables. Weighted regression analysis confirmed none of these variables could significantly account for study heterogeneity. CONCLUSION: Virtual bronchoscopy performs well in the investigation of patients with suspected airway stenosis. Overall sensitivity and specificity and diagnostic odds ratio for diagnosis of airway stenosis were high. The effects of pitch, collimation, reconstruction interval, rendering technique, scanner type, and publication date on diagnostic accuracy were not significant.