Correlation of spatial patterns of endocardial pace mapping to underlying scar topography in patients with scar-related ventricular tachycardia

Introduction

Endocardial pace mapping (PM) can identify conducting channels for ventricular tachycardia (VT) circuits in patients with structural heart disease (SHD). Recent findings show the temporal and spatial pattern of PM may aid identification of the surface harboring VT isthmii. The specific correlation of PM patterns to scar topography has not been examined.

Objective

To correlate the pattern of endocardial PMs to underlying scar topography in SHD patients with VT.

Methods

Data from patients undergoing VT ablation from August 2018 to February 2022 were reviewed.

Results

Sixty-three patients with SHD-related VT (mean age 65 ± 14 years) with 83 endocardial PM correlation maps were analysed. Two main correlation patterns were identified, an “abrupt-change correlation pattern (AC-pattern)” and “centrifugal-attenuation correlation pattern (CA-pattern).” AC-pattern had lower scar ratio (unipolar/bipolar % scar area; 1.1 vs. 1.5, p < .001), had longer maximal stimulus-QRS intervals (97.5 vs. 68 ms, p = .002), and higher likelihood of endocardial dominant scar (11/21 [52%] vs. 3/38 [8%], p < .001) than CA-pattern seen on intracardiac echocardiography (ICE). In contrast, CA-pattern was more likely to have epicardial dominant scar or mid-intramural scar on ICE (epicardial dominant scar; CA-pattern: 12/38 [32%] vs. AC-pattern: 1/21 [5%], p = .02, mid-intramural scar; CA-pattern: 15/38 [39%] vs. AC-pattern: 1/21 [5%], p = .005).

Conclusions

The spatial pattern of endocardial PM in SHD-related VT directly correlates with scar topography. AC-pattern is associated with endocardial dominant scar on ICE with lower scar ratio and longer stimulus-QRS intervals, whereas CA-pattern is strongly associated with epicardial dominant or mid-intramural scar with higher scar ratio and shorter stimulus-QRS intervals.     

Identification of a novel ALDH1A3-selective inhibitor by a chemical probe with unrelated bioactivity: An approach to affinity-based drug target discovery

The identification of biologically active target compounds and their binding proteins is important in mechanism-of-action studies for drug development. Additionally, the newly discovered binding proteins provide unforeseen ideas for novel drug discovery and for subsequent structural transformation to improve target specificity. Based on the lead and final candidate compounds related to the type 5 phosphodiesterase (PDE5) inhibitor E4021, we designed chemical probes and identified their target proteins by the affinity chromatography approach. Aldehyde dehydrogenase family 1 member A3 (ALDH1A3), currently reported as a cancer stem cell target, was clearly isolated as a binding protein of the lead ‘immature’ inhibitor probe against PDE5. In the early derivatization to the closely related structure, Compound 5 (ER-001135935) was found to significantly inhibit ALDH1A3 activity. The discovery process of a novel ALDH1A3-selective inhibitor with affinity-based binder identification is described, and the impact of this identification method on novel drug discovery is discussed.     

Timeliness of Early Identification and Referral of Infants with Social and Environmental Risks

The Early Intervention Parenting Partnerships (EIPP) program is a home visiting program that provides home visits, group services, assessments and screenings, and referrals delivered by a multidisciplinary team to expectant parents and families with infants who experience socioeconomic barriers, emotional and behavioral health challenges, or other stressors. The present study examines whether EIPP successfully meets its aims of screening families for social and environmental factors that may increase the risk of children’s developmental delays and connect them to the larger statewide early intervention (EI) system relative to families with similar background characteristics who do not receive EIPP. Coarsened exact matching was used to match EIPP participants who enrolled between 2013 and 2017 to a comparison group of families identified from birth certificates. Primary study outcomes including EI referrals, evaluations, and service receipt for children from 3 months to 3 years were measured using EI program data. Secondary outcomes included EI referral source, EI eligibility criteria (e.g., presence of biological, social, or environmental factors that may increase later risk for developmental delay), and information on service use. Impacts were assessed by fitting weighted regression models adjusted for preterm birth and maternal depression and substance use. EIPP participants were more likely than the comparison group to be referred to, evaluated for, and receive EI services. EIPP facilitated the identification of EI-eligible children who are at risk for developmental delays due to social or environmental factors, such as violence and substance use in the home, child protective services involvement, high levels of parenting stress, and parent chronic illness or disability. EIPP serves as an entry point into the EI system, helping families attain the comprehensive supports they may need to optimize their well-being and enhance children’s development.