Arya, Namrata

ABSTRACT Background Valve‐in‐valve transcatheter aortic valve replacement (ViV‐TAVR) is increasingly used to treat structural valve degeneration. Permanent pacemaker implantation (PPI) following TAVR is associated with increased morbidity and mortality, yet predictors specific to ViV‐TAVR remain poorly defined. Objective To identify clinical and procedural predictors of PPI in patients undergoing ViV‐TAVR. Methods We conducted a retrospective observational study of consecutive ViV‐TAVR cases at the Mayo Clinic from 2012 to 2022. Clinical, ECG, procedural data and fluoroscopic measurements were analyzed, and propensity score matching was used to adjust for confounding. Predictors of PPI were identified using multivariable logistic regression. Results Among 261 patients, 24 (9.2%) underwent PPI. Balloon‐expandable valves were used in 66.7% and self‐expanding valves in 33.3%. Predictors of PPI included Preprocedural bifascicular block (OR 12.15, 95% CI: 2.52–68.89, p = 0.003), greater septal implantation depth (OR 1.29, 95% CI: 1.04–1.65, p = 0.019), and post‐procedural new left (OR 23.56, 95% CI: 4.91–48.52, p = 0.0004) and right bundle branch blocks (OR 24.4, 95% CI: 3.82–30.51, p = 0.001). Aortic regurgitation as the mechanism of prosthetic valve failure was associated with reduced PPI odds (OR 0.28, 95% CI: 0.10–0.76, p = 0.014). Pacing requirement—defined as > 90% ventricular pacing—increased from 25% at 3 months to 56.25% at 12 months. At a median follow‐up of 962.5 days (IQR 481.5–1555.3), adjusted mortality was significantly higher in the PPI group (aOR 9.4, 95% CI: 1.9–60.4, p = 0.028). Conclusion Bifascicular block, greater septal depth, and new bundle branch blocks predict PPI post‐ViV‐TAVR, while aortic regurgitation appears protective. Risk stratification and procedural planning are critical.

Background Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) is increasingly used to treat structural valve degeneration. Permanent pacemaker implantation (PPI) following TAVR is associated with increased morbidity and mortality, yet predictors specific to ViV-TAVR remain poorly defined. Objective To identify clinical and procedural predictors of PPI in patients undergoing ViV-TAVR. Methods We conducted a retrospective observational study of consecutive ViV-TAVR cases at the Mayo Clinic from 2012 to 2022. Clinical, ECG, procedural data and fluoroscopic measurements were analyzed, and propensity score matching was used to adjust for confounding. Predictors of PPI were identified using multivariable logistic regression. Results Among 261 patients, 24 (9.2%) required PPI. Balloon-expandable valves were used in 66.7% and self-expanding valves in 33.3%. Predictors of PPI included pre-procedural bifascicular block (OR 12.15, 95% CI: 2.52–68.89, p=0.003), greater septal implantation depth (OR 1.29, 95% CI: 1.04–1.65, p=0.019), and post-procedural new left (OR 23.56, 95% CI: 4.91–48.52, p=0.0004) and right bundle branch blocks (OR 24.4, 95% CI: 3.82–30.51, p=0.001). Aortic regurgitation as the mechanism of prosthetic valve failure was associated with reduced PPI odds (OR 0.28, 95% CI: 0.10–0.76, p=0.014). Pacing requirement—defined as >90% ventricular pacing—increased from 25% at 3 months to 56.25% at 12 months. At a median follow-up of 962.5 days (IQR 481.5–1555.3), adjusted mortality was significantly higher in the PPI group (aOR 9.4, 95% CI: 1.9–60.4, p=0.028). Conclusion Bifascicular block, greater septal depth, and new bundle branch blocks predict PPI post-ViV-TAVR, while aortic regurgitation appears protective. Risk stratification and procedural planning are critical.

9569 Background: Immune-checkpoint inhibitor (ICI) immunotherapy increases survival in patients with melanoma. Yet only half of the patients respond, and 10-40% of patients experience immune-related adverse events (irAEs). Previous studies have found a correlation between the development of an irAE and treatment response. Modifying the gut microbiome could positively affect response to ICIs and reduce toxicities. We sought to determine if the microbiome at the onset of treatment, during an irAE, and at 12 weeks, can predict the response or toxicity during ICI treatment for metastatic melanoma. Methods: Melanoma patients (pts) > 18 yo treated with ICI enrolled in a prospective observational cohort study at The Ohio State University Comprehensive Cancer Center Skin Cancer Clinic. Excluded were patients on corticosteroids at the start of ICI cycle 1, except for adrenal physiologic replacement. Stools were collected at baseline, within 2 days of an adverse event assessed by physician chart review using CTCAE (Common Terminology Criteria for Adverse Events) v5.0, and at 12 weeks. Response (ORR) to ICIs was assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) q12 weeks and progression-free survival recorded. Metagenomic whole-genome shotgun sequencing was performed on an Illumina NovaSeq 6000 and classified using HUMAnN3. The effect of microbe relative abundances on irAEs was modeled by logistic regression with the R package glmm. Results: Of the 88 patients enrolled, 48 had metastatic disease with 32 assessable for response. ORR at 12 weeks was 28% (1 CR, 8 PR, 17 SD, and 6 PD) and 24 patients showed PFS at 12 months. Grade > 2 irAEs were observed in 11/48 pts. Abundance of Bacteroides dorei (False Discovery Rate Corrected p-value = 9.5E-07) and Blautia species CAG:257 (padj = 0.001) were enriched in responders, Prevotella Stercorea (padj = 1.1E-07) and a phage with a predicted target of Salmonella (padj = 8.3E-09) in non-responders. Responders with an irAE had enrichment of Bacteroides plebeius (padj = 4.2E-13) and Bacteroides coprophilus (padj = 0.0002) whereas responders without irAE had enrichment of Eubacterium siraeum (padj = 7.2E-05). Conclusions: Longitudinal and event-driven biospecimen collection in patients treated with ICIs showed several bacteria and viruses but no fungi associated with response, with and without the development of an irAE. The abundance of the two high-taxonomic rank microbe groups is significantly associated with irAEs. The association with the Bacteroides Genus is consistent with previous studies and is associated with response to ICIs. A microbiome abundant in Bacteroides and lacking Prevotella is associated with response to ICI. An abundance of Bacteroides could be a biomarker for irAEs, and an abundance of Eubacterium, a biomarker for response without irAEs. Future analyses are necessary to assign causal roles for microbe biomarkers with specific irAEs. Clinical trial information: NCT05102773 .