Faculty Bibliography

IMPORTANCE/UNASSIGNED:Transcatheter tricuspid valve replacement (TTVR) demonstrated superior outcomes over medical therapy in patients with severe tricuspid regurgitation (TR) in the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device II (TRISCEND II) randomized clinical trial, and received regulatory approval in the US in 2024. Contemporary real-world data on its effectiveness and safety remain limited. OBJECTIVE/UNASSIGNED:To evaluate 30-day clinical, echocardiographic, and health status outcomes of TTVR in real-world use. DESIGN, SETTING, AND POPULATION/UNASSIGNED:Retrospective cohort study of all consecutive patients who underwent TTVR in the US from February 2024 through March 2025 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients had symptomatic, severe TR despite optimal medical therapy and TTVR was deemed appropriate by a heart team. Statistical analysis was conducted from September 2025 to February 2026. EXPOSURE/UNASSIGNED:Device-enabled TTVR. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Thirty-day event rates (all-cause death, stroke, bleeding, new cardiac implantable electronic device [CIED] implantation, heart failure hospitalizations), TR reduction, and changes in health status (New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) are reported. Subgroup analyses examined the impact of baseline CIED status on outcomes. RESULTS/UNASSIGNED:Among 1034 attempted procedures at 82 centers (mean [SD] age, 77.1 [10.6] years; 69.1% female; 73.2% NYHA functional class III/IV), a valve was successfully implanted in 1017 patients (98.4%). Mild or less TR was achieved in 98.4% of patients post procedure and in 97.7% at 30 days. At 30 days, all-cause mortality was 3.1%; stroke, 0.2%; bleeding, 7.9%; new CIED, 15.9% in CIED-naive patients; and heart failure hospitalization, 3.1%. There were significant improvements in NYHA functional class (class I/II, 82.7%; P < .001) and mean KCCQ-OS score (22.4 points; P < .001) from baseline to 30 days. There were no significant differences in 30-day mortality (P = .47), heart failure hospitalization (P > .99), and functional outcomes (P = .55) when patients were stratified by baseline CIED status. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Early US real-world experience with TTVR confirms safety and effectiveness in patients with severe TR. Thirty-day outcomes are consistent with the TRISCEND II pivotal trial, demonstrating acceptable safety, near-complete TR elimination, and significant health status improvements in an older, comorbid population. Rates of new CIED implantation and bleeding were lower than randomized clinical trial experience.

IMPORTANCE/UNASSIGNED:Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. OBJECTIVE/UNASSIGNED:To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. EXPOSURES/UNASSIGNED:Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy-related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. RESULTS/UNASSIGNED:Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate (P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). CONCLUSIONS AND RELEVANCE/UNASSIGNED:These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01915615.

Stereotactic body radiotherapy (SBRT) is established as standard therapy for organ-confined prostate cancer (PC) based on 5-yr phase 2-3 outcomes, but 10-yr data are lacking. Here, we report 10-yr results of a trial conducted at 21 centers. Patients were treated from January 2008 to April 2010. SBRT was delivered on a noncoplanar robotic platform with real-time motion management, to a total dose of 40 Gy in five fractions. Adjuvant hormone therapy was not allowed. Late toxicities (>90 d) were assessed with Common Terminology Criteria for Adverse Events version 3 (CTCAE v3). Biochemical failure is defined as nadir+2. Relapses are defined as biochemical or clinical failure or salvage/systemic PC therapy. Out of 310 evaluable patients, median age 68 yr; 172 were low-risk (LR), and 138 patients were intermediate-risk (IR). Median follow-up was 9 yr. Ten-yr cumulative grade 3 gastrointestinal (GI) or genitourinary (GU) toxicities were 1.4% and 1.5% in the LR and IR cohorts, respectively. There were no grade 4-5 events observed. Ten year grade 2+ GI and GU toxicity rates were 2.1% and 14% respectively. Overall survival in 10 yr was 84%. Overall, relapse-free survival (RFS) was 90%; 94% in the LR cohort, 86% in the IR cohort, and 92% versus 77% in the favorable vs unfavorable intermediate subgroups. In this multi-institutional trial, the 10-yr follow-up demonstrates that prostate SBRT yields minimal toxicity and favorable RFS.

INTRODUCTION/BACKGROUND:Early lymph node (LN) metastasis often precedes systemic metastasis and corresponds with significantly inferior survival for patients diagnosed with early-stage breast cancer (EBC). To understand the biological pathways involved in early LN metastasis, differential gene expression (DGE) analysis compared large tumors without evidence of LN metastasis (pT2-3pN0) to small tumors with LN metastasis (pT1pN+). METHODS:This study included 2,349 patients with EBC who underwent MammaPrint and BluePrint testing as part of the FLEX (NCT03053193). DGE was performed between pT2-3pN0/pT1pN + and across their MP/BP subtypes. Immune deconvolution was assessed using gene-signature-based methods, complemented by conventional tumor-infiltrating lymphocyte (TIL) analyses on a representative subset of patients. RESULTS:Greater DGE was observed within the MammaPrint High Risk and BluePrint Luminal B subgroups compared to pathological stages. MammaPrint High Risk tumors saw 73 differentially expressed genes (DEGs), while 34 were found for Luminal B tumors. Gene set enrichment analysis (GSEA) of MammaPrint High Risk/Luminal B tumors showed upregulated proliferation pathways and downregulated epithelial-to-mesenchymal transition (EMT) and immune profiles in pT2-3pN0 vs. pT1pN+, respectively. Immune deconvolution analyses showed a higher abundance of T gamma delta cells and CD4 + Th1 cells and a lower abundance of T regulatory cells, M2 macrophages, and cancer-associated fibroblasts within pT2-3pN0 tumors. Conventional histological assessment revealed no significant differences in TILs. CONCLUSION/CONCLUSIONS:This study lays the groundwork for exploring mechanisms of LN metastasis in EBC and their relation to MammaPrint High Risk and Luminal B subtypes. These data support previous studies' association of LN metastasis with EMT and immune dysregulation.

INTRODUCTION/BACKGROUND:Endoscopic retrograde cholangiopancreatography (ERCP) is essential for pancreaticobiliary disease management; however, there are risks associated with the procedure, particularly post-ERCP pancreatitis (PEP). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in metabolic disease, possess anti-inflammatory and cytoprotective properties that may influence periprocedural outcomes. Their impact on ERCP adverse events remains unclear; therefore, we aimed to investigate whether GLP-1 influences short-term postprocedural outcomes using a large real-world database. METHODS:We conducted a retrospective cohort study using the TriNetX US Collaborative Network, identifying adults (18 y or older) who underwent ERCP between January 2015 and December 2024. Patients were categorized based on documented preprocedure GLP-1 receptor agonist exposure. Propensity score matching (1:1) was performed using demographic, clinical, procedural, and pharmacologic covariates to minimize confounding, yielding 2 well-balanced cohorts. Thirty-day post-ERCP outcomes-including acute pancreatitis, cholangitis, sepsis, gastrointestinal bleeding, biliary stricture, choledocholithiasis, and repeat ERCP-were assessed using ICD-10 and CPT codes. Risk ratios (RRs) and hazard ratios (HRs) with 95% CIs were calculated. RESULTS:Of 250,502 patients with ERCP screened, 21,818 propensity-matched individuals were included in the final analysis. Compared with matched nonusers, patients receiving GLP-1 receptor agonists had significantly lower 30-day rates of all major ERCP-related adverse events. GLP-1 RA exposure was associated with reduced risks of acute pancreatitis (RR: 0.47, 95% CI: 0.43-0.51), cholangitis (RR: 0.56, 95% CI: 0.50-0.62), sepsis (RR: 0.51, 95% CI: 0.46-0.57), gastrointestinal bleeding (RR: 0.49, 95% CI: 0.40-0.61), biliary stricture (RR: 0.52, 95% CI: 0.48-0.55), repeat ERCP (RR: 0.53, 95% CI: 0.48-0.58), and choledocholithiasis (RR: 0.66, 95% CI: 0.62-0.71). Results were consistent across time-to-event analyses over the 30-day follow-up period. CONCLUSIONS:In this large real-world analysis, preprocedure GLP-1 RA therapy was associated with markedly reduced 30-day ERCP-related adverse events, most notably PEP. These findings highlight a potential protective role of GLP-1 signaling in the periprocedural inflammatory response and support prospective studies evaluating GLP-1 RAs as adjunctive prophylactic agents in ERCP. Further prospective studies are needed.

BACKGROUND AND AIMS/OBJECTIVE:The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy versus medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity. METHODS:The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR and randomised 2:1 to TTVR (n=267) or control (n=133). In a post-hoc analysis, patients were stratified into severe TR (n=172) and massive/torrential TR (n=220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan-Meier estimates for all-cause mortality and heart failure (HF) hospitalisation assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board. RESULTS:One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe (1.64 [95% CI: 1.11, 2.43]) and massive/torrential (2.20 [1.55, 3.14]). At 18 months, TTVR patients had similar mortality to controls (rate difference: severe 0.2% [-11.6, 11.9], massive/torrential -5.8% [-17.6, 6.0], whereas HF hospitalisation rates favoured TTVR in the massive/torrential cohort (vs. control, severe 9.8% [-3.0, 22.7], massive/torrential -15.2% [-28.9, -1.5]). CONCLUSIONS:Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease.

The Patient-Oriented Eczema Measure (POEM) is a validated patient-reported outcome measure for atopic dermatitis (AD), though its use in routine pediatric dermatology practice remains underexplored. In this cross-sectional study of 297 pediatric patients with AD at a tertiary pediatric dermatology clinic, POEM scores were collected and compared with physician-rated investigator global assessment (IGA) and IGA × body surface area, as well as treatment selection. Older patients (> 12 years) had significantly higher mean POEM scores (17.5 vs. 10.4; p < 0.001) with no significant differences observed by race, ethnicity, or socioeconomic status; total POEM scores correlated strongly with IGA (r = 0.68) and moderately with IGA×BSA (r = 0.54), and higher severity scores were associated with more potent topical corticosteroids and systemic treatments (p < 0.001). POEM detected clinically relevant changes, aligned with physician-rated measures, and correlated with treatment intensity, underscoring its utility in both clinical practice and future predictive modeling applications.

BACKGROUND:Infection with the severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), the virus which causes the corona virus disease-2019 (COVID-19) has substantial evidence that patients with pre-existing coronary artery disease (CAD) have an increased risk of serious illness, adverse coronary events, and mortality following infection. The COVID-CT registry will assess whether COVID-19 alters progression of coronary atherosclerotic plaque in patients with previously defined anatomic CAD on coronary computed tomographic angiography (CCTA). Mediators and covariates such as disease severity, inflammation, and neighborhood deprivation will also be assessed. DESIGN/METHODS:The COVID-CT registry is a multicenter, longitudinal observational registry enrolling patients including patients with pre-pandemic atherosclerosis observed by CCTA from New York City and Long Island to determine the impact of COVID-19 infection. The primary aim is to test the hypothesis that patients with previously defined anatomic CAD by CCTA who are subsequently infected with SARS-CoV-2 have accelerated progression of total and noncalcified atherosclerotic plaque volumes when compared to uninfected patients. We hypothesize that systemic inflammation is a key promoter in the formation and progression of atherosclerotic plaque. Additionally, we will test whether measurement of the perivascular fat attenuation index detects high risk, coronary artery inflammation following COVID infection. SUMMARY/CONCLUSIONS:The impact of this first in-kind registry will be foundational for revising standard diagnostic pathways and risk assessment used to guide preventive care for millions of patients with CAD at increased risk from viral infection.

This AM Last Page provides a visual depiction of how to best implement successful hybrid learning practices in academic -medicine using the Community of Inquiry conceptual framework.

OBJECTIVES/OBJECTIVE:Most pediatric residency programs introduce PICU rotations in postgraduate year (PGY) 2, although it is unclear whether this timing best supports trainees' skill development. Introduction during PGY1 may pose challenges due to clinical intensity, but could also have benefits in uniquely preparing residents for PGY2 responsibilities and autonomy. To address this question, this study explored the experiences and self-perceived impacts of a PGY1 PICU rotation among senior pediatric residents. DESIGN/METHODS:A multi-institutional qualitative study was conducted using semi-structured interviews of senior (PGY2 and PGY3) residents who completed a PGY1 PICU rotation. Stratified purposive sampling was used at both institutional and resident levels. Data were coded using constant comparison and analyzed thematically. SETTING/METHODS:Seven institutions requiring a 4-week PGY1 PICU rotation. PARTICIPANTS/METHODS:Senior pediatric residents at participating institutions. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Twenty-one interviews across seven institutions identified three key themes: 1) PGY1s can succeed in the PICU setting when supervisors actively cultivate a learning environment of inclusion, support, and appropriate autonomy; 2) PGY1 PICU rotations can foster self-perceived competence in skills that translate to the PGY2 year; and 3) Participants generally believed the benefits of early PICU exposure outweighed the challenges. CONCLUSIONS:PGY1 PICU rotations can fall within the Zone of Proximal Development when the experience includes strong supervisory support. Findings highlighted the importance of psychologic safety for optimal learning, suggesting that strengthening psychologic safety may enhance the educational experience and outcomes. Further research exploring the impact of PGY1s on team dynamics and patient care, and comparing the effects of PGY1 vs. PGY2 introduction, could guide evidence-based recommendations on the optimal sequencing of PICU rotations for pediatric residents.