Citations

BACKGROUND: Pulsed field ablation is now widely used for atrial fibrillation (AF) ablation, but atrial tachyarrhythmia recurrence remains common and postablation risk tools are limited. We assessed whether a validated sinus‑rhythm artificial intelligence— enabled ECG AF probability score, and its early postablation change, predicts recurrence after pulsed field ablation. METHODS: We studied consecutive patients undergoing index pulsed field ablation across 3 Mayo Clinic sites (February 2024–March 2025) with ≥1 sinus‑rhythm ECG within 180 days preprocedure. Baseline artificial intelligence—enabled ECG AF score (range 0–1) was the mean across baseline ECGs. Recovery indices (RI30/60/90), defined as mean postprocedure artificial intelligence—enabled ECG score within days 1–30/60/90 minus baseline, predicted post‑blanking recurrence using corresponding 30‑, 60‑, and 90‑day blanking windows. The primary outcome was time to first documented AF/atrial flutter/atrial tachycardia episode >30 seconds, ascertained via clinic ECGs, ambulatory monitoring, and device interrogations. Cox regression adjusted for prespecified clinical and echocardiographic covariates assessed associations; Harrell C‑statistic quantified discrimination. RESULTS: Among 1052 patients (67±10 years; 33% women), median baseline score was 0.35; 320 (30%) recurred over 188 days. Higher baseline score independently predicted recurrence (hazard ratio per 0.1 increase, 1.08 [95% CI, 1.03–1.14]). Scores rose on day 0 after ablation, then declined over subsequent weeks, with persistently higher, less‑improving trajectories among patients who recurred (time×recurrence interaction P <0.001). Day 0 score was not independently associated with recurrence after adjustment. Attenuated early recovery (higher recovery index) was independently associated with recurrence, most robustly for RI-90 (hazard ratio per 0.1 increase, 1.15 [95% CI, 1.07–1.24]), and improved discrimination beyond baseline and covariates (C‑statistic, 0.63–0.67; ΔC=0.04). Findings were consistent in a historical thermal ablation cohort. CONCLUSIONS: Baseline and early postablation dynamics of a sinus‑rhythm artificial intelligence—enabled ECG AF probability score are associated with pulsed field ablation recurrence and may aid multivariable risk stratification; prospective validation is warranted.

ABSTRACT Background Pulsed field ablation (PFA) is an emerging non‐thermal ablation modality with proven safety in atrial arrhythmia ablation. However, data on its performance for ventricular arrhythmias (VA) remain limited. Objective To evaluate the feasibility, safety, and efficacy of PFA for complex VA in a multicenter real‐world US registry. Methods This retrospective study included consecutive patients undergoing PFA for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) at three Mayo Clinic centers (April 2024 to July 2025). The primary feasibility outcome was the successful delivery of PFA lesions to the intended target substrate. Primary efficacy outcomes included acute procedural success; sustained VT recurrence requiring implantable cardioverter‐defibrillator (ICD) shocks or multiple antitachycardia pacing therapies; and ≥ 80% reduction in PVC burden. Safety outcomes included procedural complications, valvular function, thromboembolic events, renal function, and conduction disturbances. Results Twenty‐six patients were included (13 PVC, 13 VT). Acute success was achieved in all VT ablations (69.2% complete; 30.8% partial) and in 92.3% of PVC ablations. Complications occurred in 11.5% of patients (transient LBBB [ n = 1] and vascular complications [ n = 2]). No thromboembolic events, intracardiac thrombus, or acute kidney injury were observed. Lesions near the mitral valve apparatus did not worsen mitral regurgitation, including in patients with pre‐existing valve disease. After a median follow‐up of 365 days, one patient experienced VT recurrence requiring ICD shocks. Estimated recurrence‐free survival after VT ablation was 61.5% at 12 months; 58.3% of PVC patients achieved ≥ 80% burden reduction. Conclusion PFA for VA appears feasible and acutely effective, with a low rate of procedure‐related complications. While acute success was high, long‐term outcomes were acceptable for VT ablation and relatively modest for PVC ablation, highlighting the need for continued refinement of technology and energy‐delivery strategies. Larger prospective studies are warranted.

Abstract Background/Introduction Atrial fibrillation (AF) is a common finding in patients with wild-type TTR amyloidosis. AF ablation represents a cornerstone of rhythm control in this population; however, the role of pulsed field ablation (PFA) remains unclear. Purpose This study aimed to describe the safety and efficacy of PFA for the treatment of atrial fibrillation in patients with wild-type TTR amyloidosis. Methods We conducted a prospective data collection of consecutive patients who underwent PFA for AF and had a confirmed diagnosis of wild-type TTR amyloidosis. The study included three centres within a major US health system. All procedures were performed between May 2024 and May 2025. A standardised follow-up strategy was applied, including 48-hour Holter monitoring between 90 and 180 days after ablation. The primary safety endpoint was the occurrence of procedural complications. The primary efficacy outcomes were acute procedural success and AF-free survival at six months after a blanking period of 30 days. AF recurrence was defined as any electrocardiographically documented episode lasting more than 30 seconds. Results A total of 13 patients were included in the study. The mean age was 72.6 ± 4.8 years, and all patients were male. Three patients (23.1%) underwent an index "redo" ablation. Seven patients (53.8%) had paroxysmal atrial fibrillation (AF). The median CHA2DS2-VASc score was 3 [2, 4.5], with a mean ejection fraction of 50.4 ± 14.8% and a mean left atrial volume index of 47.6 ± 15.7 mL/m². Eleven patients underwent PFA with the pentaspline Farawave catheter, and two with the focal Sphere-9 catheter. Additional extra-pulmonary vein lesions were performed in 11 patients, including posterior wall ablation in ten patients, cavotricuspid isthmus ablation in five, and mitral isthmus ablation in four patients. The primary endpoint occurred in one patient (7.7%) who developed acute respiratory failure complicated by pulseless electrical activity (PEA) arrest. The patient was successfully resuscitated but required prolonged hospital admission. All patients achieved acute pulmonary vein isolation, and six-month atrial fibrillation-free survival was 54.4%. Conclusion In this multicentre experience, pulsed field ablation (PFA) in patients with cardiac amyloidosis was feasible and acutely safe; however, the mid-term efficacy was suboptimal, with a relatively low six-month arrhythmia-free survival despite complete acute pulmonary vein isolation. These findings suggest that the current PFA strategies may not provide durable rhythm control in this population, underscoring the need for tailored ablation approaches and further research to improve long-term outcomes in patients with cardiac amyloidosis and atrial fibrillation.Figure 1

e13683 Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are frequently complicated by immune-related adverse events (irAEs), which may result in treatment interruption, hospitalization and mortality. Reliable pre-treatment tools to identify patients at higher risk for irAEs, particularly checkpoint inhibitor pneumonitis (CIP) remain limited. Artificial intelligence (AI)-based prediction models have emerged but their clinical performance and readiness for implementation are unclear. Methods: We systematically searched PubMed, Embase, Scopus and Web of Science (inception-January 2025) for studies developing AI-based models to predict irAEs or CIP in patients receiving ICIs. Eligible studies included radiomics, deep learning, natural language processing and clinical machine-learning approaches. Two reviewers independently extracted data on cancer type, toxicity endpoint, modality, algorithm, validation strategy and model performance. Study design and reporting characteristics were assessed. Due to substantial methodological heterogeneity, results were synthesized descriptively. Results: Fifteen studies met inclusion criteria, including mixed solid tumor cohorts and lung-predominant populations. Predictive targets included any-grade irAEs and organ-specific toxicities, most commonly pneumonitis. Model approaches ranged from clinical and electronic health record–based models to CT- and PET/CT-based radiomics and multimodal imaging-clinical frameworks. Reported discriminatory performance varied widely, with AUC values ranging from 0.64 to > 0.90 across model types. The most consistent performance was observed in deep learning and multimodal radiomics-clinical models for pneumonitis, with AUCs frequently between 0.75 and 0.92, whereas several clinical-only models demonstrated more modest performance. Most studies were retrospective and single-center, used heterogeneous irAE definitions and lacked standardized imaging protocols. External validation and calibration assessment were uncommon. Conclusions: AI-based models for predicting irAEs in ICI-treated patients demonstrate promising performance, particularly for pneumonitis using radiomics and multimodal approaches. However, current evidence is limited by heterogeneity, scarce external validation and uncertain generalizability. Prospective, multi-institutional validation and standardized outcome definitions are needed before AI-driven irAE risk prediction can be integrated into routine oncology practice to guide surveillance and patient counseling.

Abstract Background: Hematologic toxicity, including early and prolonged neutropenia, anemia, and thrombocytopenia, is among the most common and clinically significant complications after CD19, CD20, CD22 and BCMA-directed CAR-T therapy. Several clinical scoresmost notably CAR-HEMATOTOX (CAR-HT) and the refined ALL-HThave been developed to predict post-infusion cytopenias, but their comparative performance across diseases has not been systematically evaluated. No prior review has summarized existing models or assessed the need for AI-based predictive approaches. Methods: We conducted a systematic review of studies that developed or validated predictive models or risk scores for hematologic toxicity after CAR-T therapy in hematologic malignancies. Eligible studies included clinical, cytokine-based, or composite predictors and reported discrimination metrics such as area under the curve (AUC). Extracted variables included CAR-T product, target antigen, disease type, predictors used, model type, validation strategy, and performance statistics. Results were synthesized qualitatively due to heterogeneity in model structure and outcome definitions. Results: Studies on the CAR-HT score in B-cell lymphomas and multiple myelomas reported AUC values of 0.89 and 0.82, respectively, for predicting severe or long-term neutropenia after CD19 and BCMA-directed CAR-T therapy. Studies on the ALL-HT score (a modified/refined version of CAR-HT replacing ferritin with bone-marrow burden to improve discrimination in B-ALL) reported AUC 0.84-0.90 for predicting prolonged neutropenia and worse overall survivability (OS) after CD19/CD22 CAR-T. A multicenter study including aggressive/indolent NHL, MM/PCL, and ALL patients treated with CD19, CD20, or BCMA CAR-T reported AUC 0.87 (eIPM-Pre) and 0.88 (eIPM-Post) for predicting ICA-HT. A CD19 CAR-T study in B-ALL and LBCL reported AUC 0.85 for an early hematotoxicity nomogram using TNF- and CRP. Conclusion: Existing prediction tools for hematologic toxicity after CAR-T therapy demonstrate strong but disease-specific performance. Yet inconsistent endpoints and heterogeneous predictors limit clinical generalizability. No current model incorporates contemporary AI or machine-learning methods, underscoring a significant unmet need. Advanced predictive frameworks may allow earlier identification of patients at risk for severe or prolonged cytopenias and guide more individualized supportive care, with the potential to reduce downstream complications. Citation Format: Mansha Gupta, Abhijith Vemulapalli, Swathi Cherukuri, Rithish Nimmagadda, Akhil Jain. Predictive models for hematologic toxicity after CAR-T therapy: A systematic review of current risk scores and unmet AI needs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5202.

Abstract Aims The clinical significance of early recurrences during the blanking period following pulmonary vein isolation (PVI) remains uncertain, particularly after pulsed field ablation (PFA). This study aimed to evaluate the prognostic impact of early recurrences at 30-, 60-, and 90-day thresholds on outcomes following PFA for atrial fibrillation (AF). Methods and results Consecutive patients who underwent PFA for AF across multiple centres within the Mayo Clinic health system were included. The primary endpoint was AF-free survival. Kaplan–Meier and multivariate Cox regression analyses were performed to compare outcomes between patients with and without early recurrences using 30-, 60-, and 90-day thresholds. A total of 1162 patients were included. The estimated AF-free survival at 1 year was 70%. Early recurrences within 30-, 60-, and 90-days post-ablation were significantly associated with late recurrences beyond 90 days (hazard ratio [HR] 5.9, 95% confidence interval [CI] 4.4–7.9, P &lt; 0.01; HR 6.6, 95% CI: 5.0–8.6, P &lt; 0.01; and HR 9.1, 95% CI: 7.0–11.7, P &lt; 0.01, respectively). These findings remained significant among patients undergoing continuous rhythm monitoring. Early recurrences within 30 days in this subgroup were significantly associated with a 1-year AF burden &gt;1% or the need for repeat AF ablation (odds ratio 25.0, 95% CI: 6.6–126.8, P &lt; 0.01). Conclusion Early recurrences following PFA are strongly predictive of long-term arrhythmia recurrence and are unlikely to represent transient inflammatory phenomena. Accordingly, the applicability of the conventional blanking interval after PFA should be reconsidered.

175 Background: BRAF V600E mutations occur in ~8–12% of metastatic colorectal cancer (mCRC) and are linked to poor prognosis, therapy resistance, and limited response to anti-EGFR monotherapy. While the BEACON trial established encorafenib plus cetuximab as standard, the added value of triplet regimens remains unclear. Clarifying the efficacy and toxicity of doublet vs triplet therapies is essential to optimize care in this high-risk group. Methods: Studies published across PubMed, Embase, and Google Scholar from inception till May 2025 with reported outcomes of the desired targeted therapies for BRAF V600E-mutated mCRC were screened and finally 12 studies included in this review. Data on efficacy parameters such as overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) as well as safety indicators such as adverse events (AEs), and discontinuation rates were extracted and analyzed. Results: In the ≥2nd-line setting, doublet and triplet regimens (doublet plus binimetinib) demonstrated improved outcomes compared with cetuximab plus irinotecan/FOLFIRI, with higher OS (7.2–9.2 vs 5.6 months), PFS (4.2–4.6 vs 1.5 months), DCR (65–75% vs 31%), and a comparable incidence of severe AEs (3–5% vs 4%). Panitumumab plus vemurafenib, also in the ≥2nd-line setting, reported an OS of 7.6 months, PFS of 3.2 months, and a DCR of 27%. In the 1st-line setting, the doublet regimen plus mFOLFOX6 with longer treatment duration (~50 weeks) showed improved outcomes compared with the doublet regimen plus higher-dose cetuximab, with higher OS (30.3 vs 19.5 months), PFS (12.8 vs 6.8 months), ORR (65.7% vs 45.6%), but also a higher incidence of severe AEs (46% vs 30%). Similarly, the cetuximab + vemurafenib + irinotecan regimen outperformed conventional chemotherapy (mFOLFOX6, FOLFOXIRI, or CAPOX) ± bevacizumab, with improved OS (25.3 vs 10–15 months), PFS (11.9 vs 7.5 months), ORR (63.2% vs 37–40%), DCR (94.7% vs 75%), and a lower rate of grade ≥3 AEs (34.2% vs 65%). Conclusions: The survival benefit observed with the doublet regimen was comparable to that of the triplet, but with lower rates of adverse events and treatment discontinuation, supporting current evidence that the doublet remains the preferred option for patients with BRAF V600E–mutated mCRC who have received one or more prior lines of therapy. Although adding conventional agents such as mFOLFOX6 to the doublet in the first-line setting improved OS, PFS, ORR, and DCR, this approach was associated with higher toxicity and discontinuation rates, raising questions about its overall benefit. Emerging data on vemurafenib in combination with cetuximab and conventional agents show promise, but further studies directly comparing encorafenib- versus vemurafenib-based regimens are warranted to optimize outcomes in this patient population.

BACKGROUND: Cavotricuspid isthmus (CTI) ablation is frequently performed either as a standalone procedure or in combination with pulmonary vein isolation. With the rapid adoption of pulsed field ablation for atrial fibrillation, it is essential to delineate the utility of this modality in treating CTI-dependent atrial flutter (AFL). This study aims to evaluate the procedural and clinical outcomes of CTI ablation using pulsed field energy. METHODS: We conducted a retrospective analysis of consecutive patients who underwent pulsed field ablation for CTI-dependent AFL between January 2024 and March 2025. The primary end points were acute procedural success, periprocedural complications, and CTI-dependent AFL recurrence during follow-up. RESULTS: A total of 132 patients underwent CTI nonthermal ablation. The median age was 69.5 years, and 27.3% were female. The Farawave catheter was used in 93.9% of cases, PulseSelect in 4.5%, and Sphere-9 in 1.5%. Acute block was achieved in 99.2% of patients, although 8 required adjunctive radiofrequency ablation to complete the line. Periprocedural complications included transient ST-segment elevation in 2 patients and transient conduction disturbances in 3. During a median follow-up of 114 days (n=131), 5 patients (3.8%) experienced recurrence of typical AFL. The 6-month typical AFL-free survival estimate was 93.6%. CONCLUSIONS: Pulsed field ablation appears to be a feasible and effective strategy for CTI-dependent AFL. However, anatomic variability may limit its universal applicability with current catheter designs. Although acute procedural success is high, the long-term durability of the CTI block and its comparative efficacy versus conventional thermal ablation remain areas requiring further investigation.

ABSTRACT Background While radiofrequency ablation (RFA) and cryoablation (CBA) are established treatments for atrial fibrillation (AF), pulsed field ablation (PFA) offers potential benefits. This study compares PFA's procedural outcomes with RFA and CBA. Methods A PRISMA‐guided systematic review searched PubMed, Cochrane, Embase, and Scopus through September 2024. Studies comparing PFA to RFA or CBA in paroxysmal and persistent AF were included. Results From 1413 titles, 28 studies (7944 patients, 4–13 months follow‐up) met inclusion criteria. PFA showed lower recurrence versus RFA (RR = 0.85, p < 0.05) and CBA (RR = 0.81, p < 0.01). Procedure times were shorter versus RFA (‐46.39 min, p < 0.01) and CBA (‐9.26 min, p < 0.01). PFA had fewer complications than CBA (RR = 0.45, p < 0.01) and thermal ablation (RR = 0.55, p < 0.01), with similar rates to RFA (RR = 0.81, p = 0.25). Fluoroscopy times were higher. Conclusion Promising results with PFA suggest it as a viable alternative to thermal ablation.