Spatial analysis and characteristics of persistent late potentials after ablation of scar-related VT substrate- implications for late potential elimination as a procedural endpoint with high-resolution mapping.

BACKGROUND: Late potential elimination has been proposed as a surrogate endpoint for scar-related VT ablation procedures. The characteristics, distribution, and predictors of persistent LPs (pLP) after ablation have not been studied. OBJECTIVE: We sought to characterize the spatial distribution and features of pLP after catheter ablation of VT substrate with high-resolution mapping. METHODS: Cases of scar-related VT ablation with adequate pre- and post-ablation electroanatomical maps (EAM) acquired exclusively using a high-density grid (HDG) catheter were reviewed from 2021-2023. RESULTS: A total of 62 EAM (pre- and post-ablation) from 31 cases using HDG were reviewed. Persistent late potentials (pLP) were observed in 19 cases after ablation (61%). New LP, spatially distinct from pre-ablation LP, at the periphery of the ablation area comprised the majority of pLP (16/19, 84%). Isolated pLP were more prevalent than fractionated pLP with a median amplitude of 0.26mV (0.09-0.59mV). The presence of pLP was associated with a significantly lower LVEF and septal ablation but not low voltage, late potential, or ablation area as compared to absence of pLP (22.8±7.8% vs 31.5±8.0% [p =0.008] for LVEF, and 83% vs 44% [p = 0.033] for septal ablation). CONCLUSIONS: Formation of spatially distinct new LP after targeted VT ablation is common especially in patients with lower LVEF and septal substrate independent of ablation burden. This finding highlights the limitations of complete LP elimination as an endpoint to VT ablation procedures.

Sympathetic toggled paroxysmal atrial fibrillation and recurrent premature atrial contractions in ambulatory patients.

BACKGROUND: Autonomic nerve activity is important in the mechanisms of paroxysmal atrial fibrillation (PAF). OBJECTIVE: The purpose of this study was to test the hypothesis that a single burst of skin sympathetic nerve activity (SKNA) can toggle on and off PAF or premature atrial contraction (PAC) clusters. METHODS: Simultaneous recording of SKNA and electrocardiogram (neuECG) recording was performed over 7 days in patients with PAF. RESULTS: In study 1, 8 patients (7 men and 1 woman; age 62 ± 8 years) had 124 episodes of PAF. An SKNA burst toggled both on and off PAF in 8 episodes (6.5%) (type 1), toggled on but not off in 12 episodes (9.7%) (type 2), and toggled on a PAC cluster followed by PAF in 4 episodes (3.2%) (type 3). The duration of these PAF episodes was <10 minutes. The remaining 100 episodes (80.6%) were associated with active SKNA bursts throughout PAF (type 4) and lasted longer than type 1 (P = .0185) and type 2 (P = .0027) PAF. There were 47 PAC clusters. Among them, 24 (51.1%) were toggled on and off, and 23 (48.9%) were toggled on but not off by an SKNA burst. In study 2, 17 patients (9 men and 8 women; age 58 ± 12 years) had <10 minutes of PAF (4, 8, 0, and 31 of types 1, 2, 3, and 4, respectively). There were significant circadian variations of all types of PAF. CONCLUSION: A single SKNA burst can toggle short-duration PAF and PAC cluster episodes on and off. The absence of continued SKNA after the onset might have affected the maintenance of these arrhythmias.

Sarcoma in patients with Lynch syndrome and response to immunotherapy.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant genetic predisposition to multiple malignancies and is characterized by deficient DNA mismatch repair. Increased incidence of sarcomas is not formally ascribed to LS; however, increasing evidence suggests a preponderance of these malignancies in affected families. Sarcomas typically possess a low tumor mutational burden and incite a poor immune infiltrate, thereby rendering them poorly responsive to immunotherapy. METHODS: We searched the University of California, Los Angeles (UCLA) sarcoma program database for patients with a diagnosis of sarcoma and LS from 2016 to 2023. Three such patients were identified and all three were treated with PD1 blockade. RESULTS: We present three cases of LS-associated sarcomas (two soft tissue sarcoma and one osteosarcoma) with increased tumor mutational burdens. These patients were each treated with an anti-PD1 antibody and experienced a response far superior to that reported for non-LS-associated sarcomas. CONCLUSIONS: Increased mutational burden and immune infiltrate are observed for sarcomas associated with LS. Although unselected patients with sarcoma have demonstrated poor response rates to immunotherapy, our findings suggest that patients with Lynch-associated sarcomas are more likely to respond to treatment with anti-PD1. These patients should be given consideration for immunotherapy.

Respiratory control minimizes diaphragmatic contraction and dry cough during pulsed-field ablation of atrial fibrillation.

AIMS: Pulsed-field ablation (PFA) is a promising new ablation modality to treat atrial fibrillation. However, PFA can cause varying degrees of diaphragmatic contraction and dry cough, especially under conscious sedation. This prospective study presents a method to minimize the impact of PFA on diaphragmatic contraction and dry cough during the procedure. METHODS AND RESULTS: Twenty-eight patients underwent PFA for pulmonary vein (PV) and superior vena cava isolation under conscious sedation. Each patient received two groups of ablations in each vein: the control group allowed PFA application during any phase of respiratory cycle, while the test group used respiratory control, delivering PFA energy only at the end of expiration. A rating score system was developed to assess diaphragmatic contraction and dry cough. A total of 1401 control ablations and 4317 test ablations were performed. The test group had significantly lower scores for diaphragmatic contraction (P < 0.01) and dry cough (P < 0.001) in all PVs compared to the control group. The average relative reductions in scores for all PVs were 33-47% for diaphragmatic contraction and 67-83% for dry cough. The percentage of ablations with scores ≧2 for diaphragmatic contraction decreased significantly from 18.5-28.0% in the control group to 0.4-2.6% in the test group (P < 0.001). For dry cough, the percentage decreased from 11.9-43.7% in the control group to 0.7-2.1% in the test group. CONCLUSION: Pulsed-field ablation application at the end of expiration can reduce the severity of diaphragmatic contraction and eliminate moderate and severe dry cough during PV isolation performed under conscious sedation.