Scott, Christopher G.

Introduction: Bioprosthetic valve thrombosis is a recognized cause of bioprosthetic valve dysfunction. It was found to be associated with accelerated bioprosthetic degeneration and higher rates of valve re-replacement. Hypothesis: Warfarin for 3 months after transcatheter aortic valve replacement (TAVR) protects against accelerated valve degeneration and is therefore associated with better outcomes compared to dual antiplatelet (DAPT) and single antiplatelet therapies (SAPT). Methods: Adult patients who underwent TAVR (2012-2019) were identified retrospectively (n=1,501). Patients with atrial fibrillation were excluded (n=657). Patients were classified into warfarin, DAPT, and SAPT groups based on antithrombotic regimen. Structural valve degeneration (SVD) was considered when patients developed new ≥ moderate trans-prosthetic regurgitation, increase in mean gradients ≥10 mmHg from baseline, or when gradients exceeded 20 mmHg. Discharge date was considered time zero. Results: Overall, 844 patients [mean age 80 (±9), 43% females, mean Society of Thoracic Surgeons risk score 6.7 (±5.0)] were included. Warfarin was used in 633 (75%) patients, DAPT in 164 (19%), and SAPT in 47 (6%). Median follow-up time was 2.5 (IQR 1.2-3.9) years. There was no difference in outcomes of ischemic stroke, death, valve re-intervention, SVD, their composite endpoint, or hemorrhagic stroke and hemorrhagic stroke/RBC transfusion events (Figures 1 & 2), even after adjustment for confounders. Conclusion: Warfarin after TAVR was not associated with better clinical or hemodynamic outcomes or with worse adverse events compared to DAPT and SAPT.

Background: Atrial fibrillation (AF) in severe aortic stenosis (AS) is associated with worse outcomes compared to sinus rhythm (SR). The prevalence of AF and its impact on outcomes in very severe AS (vsAS) is unknown. Objectives: To determine the prevalence and prognostic significance of AF in vsAS. Methods: A total of 563 patients with vsAS (transaortic valve peak velocity ≥5 m/sec) were identified retrospectively out of 3139 with aortic valve area ≤1.0 cm 2 or ≤0.6 cm 2 /m 2 and left ventricular ejection fraction (LVEF) ≥50%. Patients were divided by rhythm (AF vs SR) at the time of index transthoracic echocardiogram. Outcomes in AF versus SR were compared in propensity-matched analyses (2 SR:1 AF). Results: AF was present in 50/563 patients (9%) and SR in 513/563 (91%). In propensity-matched analyses (100 SR:50 AF), the mean age was 83.2±7.3 years, 54% were female. There was no difference in comorbidity index (p=0.84). There was no difference in AF compared to SR in aortic valve area (0.7±0.1 vs 0.7±0.1 cm 2 , p=0.94), peak velocity (5.3±0.3 vs 5.3±0.3 m/sec, p=0.32), LVEF (63±7 vs 65±7%, p=0.14) or E/e’ (23±13 vs 21±12, p=0.48), but patients with AF had larger left atrial volume index (60±16 vs 48±15 mL/m 2 , p<0.001), higher right ventricular systolic pressure (52±15 vs 41±16 mmHg, p<0.001), and higher prevalence of moderate or more tricuspid regurgitation (33% vs 5%, p<0.001) and right ventricular systolic dysfunction (23% vs 6%, p=0.003). Age-, sex-, comorbidity index-adjusted all-cause mortality was higher in AF vs SR (HR 2.33 [1.40, 3.87], p=0.001) ( Figure: Observed overall survival ). Aortic valve replacement (AVR) was associated with improved survival (HR 0.44 [0.25, 0.76], p=0.004) with no evidence of interaction of AVR and rhythm (p=0.15). Conclusion: AF was not uncommon among patients with vsAS and identified a subset of patients with vsAS at much higher risk of mortality. Whether AVR should be considered earlier in vsAS when associated with AF needs to be investigated.

Introduction: The prevalence of metabolic syndrome (MS), and diabetes mellitus (DM) is increasing, and the use of biomarkers to identify subjects at risk of developing MS or DM may be useful for disease prevention. Natriuretic peptides (NPs) are well known for their role as biomarkers in heart failure (HF), but are increasingly being recognized for their favorable metabolic actions and potential role as risk modifiers for the development of DM and MS. To date, however, this risk relationship has not been well defined in the general population. Hypothesis: Adults in the general population with lower NP levels are at higher risk for developing DM or MS. Methods: A retrospective review of the Olmsted County Heart Function Study cohort, a population-based random sample of 2042 Olmsted County, MN residents aged ≥ 45 years. A subgroup of community-dwelling subjects without MS or DM at Visit 1 was identified and subjects returned for followup after 4 years (Visit 2). We compared the characteristics of subjects that developed MS or DM after 4 years to those that did not. Results: Of the 911 subjects who did not have MS or DM at visit 1, 93 (10.2%) developed either MS or DM at visit 2. Subjects who developed MS or DM at visit 2 were more likely to have higher baseline BMI (p <0.001), lower HDL (p<0.001), higher triglycerides (p < 0.001), higher insulin (p< 0.001), higher aldosterone (p < 0.001) levels, lower NT-proANP (p<0.001) and lower NT-proBNP levels (p < 0.01) compared to those that did not develop MS or DM. Those that developed MS or DM were also at higher risk for development of HF when controlling for age and sex (HR 2.73 CI 1.25-5.96). On univariate analysis, higher baseline levels of NT-proANP and NT pro-BNP had a significant negative association with developing new MS or DM (ORs per 1 SD increase: 0.64, CI 0.51-0.79 p < 0.0001 and 0.76, CI 0.62-0.95 p=0.016, respectively). Conclusions: Among adults aged ≥ 45 years in the community, low levels of NT- ANP and NT-proBNP are associated with increased risk of development of DM and MS. Further studies are warranted to determine if potentiating the natriuretic peptide system would delay the development of DM or MS.

Introduction: patients exposed to chest, breast or mediastinal RT, may present with accelerated atherosclerosis and CAD due to diffuse micro and macrovascular fibrosis. However, CAD risk has not been well established in a community-based study. Aims: Describe CAD risk in patients treated with chemotherapy with and without RT and evaluate the cumulative incidence of CAD (coronary revascularization, MI and abnormal stress test and coronary angiogram). Methods: From 1985-2010, we identified 744 patients with a new diagnosis of breast cancer or lymphoma, using the Rochester Epidemiology Project (REP) who received chemotherapy with or without RT. CAD risk was assessed by a proportional hazards model for time to event. RT was treated as a time dependent co-variable, with index date being chemotherapy start date, significance was considered as a p<.05. Characteristics were evaluated by a multivariable Cox model to consider RT and time censoring. Results: 744 patients treated with chemotherapy were identified, of these 488 (65.6%) had breast cancer, 256 (34.4%) lymphoma, and 367 (49%) also received RT. The mean total RT dose was 5.5 ± 1.2 (Gy) for those that had CAD and 5.4 (Gy) ± 1.1 for non-CAD patients, p=0.4. The cumulative incidence of CAD events (accounting for death as a competing risk) at 5 and 10 years of follow-up was 1.9% (CI 1.14-3.2) and 3.06% (CI 2.01-4.7), respectively p<.05 figure1. Baseline differences between those receiving RT or not, were not significant for DM and HTN; however, males and ages 70-79 were less likely to receive RT, table1. In a multivariable model, there was no difference in the CAD outcomes between those with and without RT, HR= 1.21 [0.48-3.06] p=.69, after adjusting for age, gender, DM, and HTN and those <49 y/o had a lower risk of CAD. Table2 Conclusion: In this REP retrospective cohort study, the risk of developing a CAD event was similar between chemotherapy plus RT and chemotherapy only regimens, even after considering gender, age, HTN and DM.

Abstract Hypertrophic Cardiomyopathy (HCM) is an inheritable heart disease with the highest rate of sudden cardiac death (SCD) in young adults. Implantable Cardioverter Defibrillator (ICD) therapy is recommended for HCM patients at high risk for SCD. Reviewing the recent clinical literature revealed the potential to improve the selection of candidates for ICD implantation. The current study uses information extracted from echocardiography reports to evaluate HCM patients with ICD and aims to provide a comparative insight into patients who benefited the most from the device therapy, including shock and anti-tachycardia pacing (ATP). The proposed interpretable machine learning approach has used the XGboost algorithm. The model’s performance was considered satisfactory, as evidenced by an accuracy score of 81% and an area under the receiver operating characteristic curve (AUC) value of 69% and SHapley Additive exPlanations (SHAP) identified common properties of HCM patients in each category and provided high-level reasoning and foundation for a clinical decision support tool.

PURPOSE Artificial intelligence (AI) algorithms improve breast cancer detection on mammography, but their contribution to long-term risk prediction for advanced and interval cancers is unknown. METHODS We identified 2,412 women with invasive breast cancer and 4,995 controls matched on age, race, and date of mammogram, from two US mammography cohorts, who had two-dimensional full-field digital mammograms performed 2-5.5 years before cancer diagnosis. We assessed Breast Imaging Reporting and Data System density, an AI malignancy score (1-10), and volumetric density measures. We used conditional logistic regression to estimate odds ratios (ORs), 95% CIs, adjusted for age and BMI, and C-statistics (AUC) to describe the association of AI score with invasive cancer and its contribution to models with breast density measures. Likelihood ratio tests (LRTs) and bootstrapping methods were used to compare model performance. RESULTS On mammograms between 2-5.5 years prior to cancer, a one unit increase in AI score was associated with 20% greater odds of invasive breast cancer (OR, 1.20; 95% CI, 1.17 to 1.22; AUC, 0.63; 95% CI, 0.62 to 0.64) and was similarly predictive of interval (OR, 1.20; 95% CI, 1.13 to 1.27; AUC, 0.63) and advanced cancers (OR, 1.23; 95% CI, 1.16 to 1.31; AUC, 0.64) and in dense (OR, 1.18; 95% CI, 1.15 to 1.22; AUC, 0.66) breasts. AI score improved prediction of all cancer types in models with density measures ( P LRT values < .001); discrimination improved for advanced cancer (ie, AUC for dense volume increased from 0.624 to 0.679, Δ AUC 0.065, P = .01) but did not reach statistical significance for interval cancer. CONCLUSION AI imaging algorithms coupled with breast density independently contribute to long-term risk prediction of invasive breast cancers, in particular, advanced cancer.

Abstract Aims Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle in patients with TR and to investigate their association with outcomes. The pulmonary artery pulsatility index (PAPi) has emerged as a haemodynamic risk predictor in left heart disease and pulmonary hypertension (PH). Whether PAPi discriminates risk in unselected patients with greater than or equal to moderate TR is unknown. Methods and results In 5079 patients with greater than or equal to moderate TR (regardless of aetiology) and PA systolic and diastolic pressures measured on their first echocardiogram, we compared all-cause mortality at 5 years based on the presence or absence of PH and PAPi levels. A total of 2741 (54%) patients had PH. The median PAPi was 3.0 (IQR 1.9, 4.4). Both the presence of PH and decreasing levels of PAPi were associated with larger right ventricles, worse right ventricular systolic function, higher NT-pro BNP levels, greater degrees of right heart failure, and worse survival. In a subset of patients who had an echo and right heart catheterization within 24 h, the correlation of non-invasive to invasive PA pressures and PAPi levels was very good (r = 0.76). Conclusion In patients with greater than or equal to moderate TR with and without PH, lower PAPi is associated with right ventricular dysfunction, right heart failure, and worse survival. Incorporating PA pressure and PAPi may help stratify disease severity in patients with greater than or equal to moderate TR regardless of aetiology.

Background: To identify factors that increase the specificity of the treadmill exercise test (TMET), and develop a novel scoring system which accounts for functional capacity to aid in determining the need for further testing. Methods: We retrospectively evaluated the electronic health records of 600 patients who had positive TMET results and follow-up stress echocardiography from 1-January-2004, through 31-December-2016. Correlations between clinical and aerobic variables and multivessel disease (MVD) were determined. Duke Treadmill Score (DTS) was calculated and compared with a novel scoring system titled the Intermediate-High-Workload Treadmill Score (IHWTS) that used variables associated with MVD. Results: In total, 124 of 600 patients (21%) had coronary catheterization, and 51 of these patients (41%) had MVD. Mean (SD) DTS was –2.10 (6.3) among patients with MVD vs –0.16 (5) among patients without MVD (p = 0.06). Mean (SD) functional aerobic capacity (FAC) was 76% (20%) among patients with MVD vs 90% (21%) among patients without MVD (p < 0.001). Mean (SD) metabolic equivalent (MET) was 7 (2) among patients with MVD vs 8 (2) among patients without MVD (p = 0.002). Only 6 (12%) of patients with MVD achieved 9 MET or greater on TMET. DTS less than 4 did not distinguish between patients with and without MVD (p = 0.67). Age, hypertension and FAC were independently associated with MVD (all p < 0.05). Conclusions: Our novel scoring system IHWTS utilized age, hypertension, and FAC appeared comparable to DTS to risk-stratify patients regardless of baseline symptoms. Clinical parameters such as hypertension along with exercise functional capacity should be considered when evaluating a positive TMET result in patients that achieve an intermediate-high workload >5 Metabolic Equivalents (METs).

Abstract Background The protective efficacy of prior coronavirus disease 2019 (COVID-19) with or without vaccination remains unknown. This study sought to understand if 2 or more messenger RNA (mRNA) vaccine doses provide additional protection in patients with prior infection, or if infection alone provides comparable protection. Methods We conducted a retrospective cohort study of the risk of COVID-19 from 16 December 2020 through 15 March 2022, among vaccinated and unvaccinated patients of all ages with and without prior infection. A Simon-Makuch hazard plot illustrated the incidence of COVID-19 between groups. Multivariable Cox proportional hazards regression was used to examine the association of demographics, prior infection, and vaccination status with new infection. Results Among 101 941 individuals with at least 1 COVID-19 polymerase chain reaction test prior to 15 March 2022, 72 361 (71.0%) received mRNA vaccination and 5957 (5.8%) were previously infected. The cumulative incidence of COVID-19 was substantially higher throughout the study period for those previously uninfected and unvaccinated, and lowest for those previously infected and vaccinated. After accounting for age, sex, and the interaction between vaccination and prior infection, a reduction in reinfection risk was noted during the Omicron and pre-Omicron phases of 26% (95% confidence interval [CI], 8%–41%; P = .0065) to 36% (95% CI, 10%–54%; P = .0108), respectively, among previously infected and vaccinated individuals, compared to previously infected subjects without vaccination. Conclusions Vaccination was associated with lower risk of COVID-19, including in those with prior infection. Vaccination should be encouraged for all including those with prior infection, especially as new variants emerge and variant-specific booster vaccines become available.

Abstract Breast parenchymal patterns on radiologic images are associated with breast cancer risk. Radiomic features have been proposed as quantitative measures of parenchymal patterns. We defined intrinsic imaging phenotypes of breast parenchymal patterns based on radiomic features extracted from full field digital mammography (FFDM) in breast screening populations and assessed whether these phenotypes are associated with breast cancer risk and masking. We selected 30,000 women with 4-view FFDM exams from Hologic machines from three institutions (Hospital of the University of Pennsylvania, Mayo Clinic, and San Francisco Mammography Registry), randomly split into a training (20,000 women) and test set (10,000 women). In total, 390 radiomic features were automatically extracted from each image using a validated software pipeline, standardized, and adjusted for site differences using ComBat. We used two methods, hierarchical clustering and Principal Components (PCs) analysis, to classify significant variation among the features in the training set and replicate among the test set. Next, we applied the replicated clusters and PCs to an independent nested case-control set [1082 invasive breast cancer (BC) cases (of which 151 were Black and 893 White women, 38 other race) matched to 2837 controls (411 Black and 2345 White women, 81 other race) on age, race, timing of images, and site]. We examined associations of the clusters and PCs with invasive breast cancer risk, as well as masking [defined as a false-negative (FN) screen (124 cases and 319 matched controls) and additionally the subset with symptomatic interval cancer (IC) within 12 months of negative screen (88 cases and 223 matched controls)] using conditional logistic regression. We evaluated their association with breast cancer alone, and with adjustment for age, body mass index (BMI) and breast density assessed by Breast Imaging Reporting and Data System (BI-RADS) using likelihood ratio tests. We estimated discrimination using area under the curve (AUC) and compared AUCs for models that included the radiomic clusters and PCs with the model that included only age, BMI and density. We also stratified analyses by race (Black/White). From hierarchical clustering, we defined six statistically significant phenotype clusters (each of at least 1000 women) in the training set which were replicated in the test set. For PC Analysis, we identified six PCs in the training set, explaining 85% of the variation in texture features and reproduced these in the test set. The six radiomic phenotype clusters (P&lt; 0.001) and six PCs (P&lt; 0.001) were both associated with invasive BC, including after adjusting for age, BMI, and density (cluster P=0.004; PCs P&lt; 0.001). Improvements in discrimination of invasive BC with inclusion of PCs or clusters were more pronounced among Black women (Table). Further, the PCs (P&lt; 0.001) and clusters (P&lt; 0.001) were significantly associated with FN overall and for symptomatic IC (PCs P&lt; 0.001; clusters P=0.001), but only PCs remained significant after adjusting for age, BMI and density (PCs P=0.004 for FN; PCs P=0.007 for symptomatic IC). Discrimination of masking also improved with inclusion of both clusters and PCs (Table). We identified reproducible radiomic phenotypes that are associated with invasive BC risk, above and beyond breast density with the strongest associations for invasive BC among Black women and symptomatic interval cancers. Citation Format: Stacey Winham, Anne Marie McCarthy, Aimilia Gastounioti, Christopher Scott, Aaron Norman, Walter C. Mankowski, Lauren Pantalone, Matthew Jensen, Eric A. Cohen, Hannah Horng, Kathleen Brandt, Emily F. Conant, Karla Kerlikowske, Despina Kontos, Celine Vachon. Radiomic phenotypes of breast texture and association with breast cancer risk and masking [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-06.