Chamberlain, Alanna M.

ObjectiveWe aimed to characterize presentation and care pathways of patients with systemic lupus erythematosus (SLE), and delays in access to SLE‐specialized care.MethodsWe included patients with incident SLE from the Lupus Midwest Network registry. Time from the first medical encounter for SLE clinical manifestation to access to SLE‐specialized care, physician diagnosis, and treatment was estimated. Delays were defined as ≥6 months to access specialized care. We compared SLE manifestations, disease activity, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage indexes (SDI) between patients with and without delays. Logistic regression models assessed associations with delays.ResultsThe study included 373 patients with SLE. The median time to access SLE‐specialized care was 1.1 (95% confidence interval [CI] 0.9–1.5) months, time to diagnosis was 30.6 (95% CI 18.9–48.1) months, and time to treatment initiation was 4.7 (95% CI 3.9–8.4) months. Approximately 25% of patients (93 out of 373) experienced delays accessing specialized care, which were associated with fewer SLE manifestations at first SLE‐related encounter (fewer than two SLE domains; 92% vs 72%, P < 0.001). Patients with mucocutaneous or musculoskeletal manifestations were less likely to experience delays, whereas hematologic (odds ratio [OR] 1.71, 95% CI 1.03–2.84) or antiphospholipid antibodies domains (OR 6.05, 95% CI 2.46–14.88) were associated with delays. Delays were associated with damage at first access to SLE‐specialized care (SDI ≥1; 30% vs 7%, P < 0.001).ConclusionPatients follow a heterogeneous pathway to receive care. One‐fourth of patients experienced delays accessing SLE‐specialized care, which was associated with disease‐related damage. Fewer manifestations, hematologic manifestations, or antiphospholipid antibodies were associated with delays.image

Abstract Objectives Heart failure (HF) impacts millions of patients worldwide, yet the variability in treatment responses remains a major challenge for healthcare professionals. The current treatment strategies, largely derived from population based evidence, often fail to consider the unique characteristics of individual patients, resulting in suboptimal outcomes. This study aims to develop computational models that are patient-specific in predicting treatment outcomes, by utilizing a large Electronic Health Records (EHR) database. The goal is to improve drug response predictions by identifying specific HF patient subgroups that are likely to benefit from existing HF medications. Materials and Methods A novel, graph-based model capable of predicting treatment responses, combining Graph Neural Network and Transformer was developed. This method differs from conventional approaches by transforming a patient's EHR data into a graph structure. By defining patient subgroups based on this representation via K-Means Clustering, we were able to enhance the performance of drug response predictions. Results Leveraging EHR data from 11 627 Mayo Clinic HF patients, our model significantly outperformed traditional models in predicting drug response using NT-proBNP as a HF biomarker across five medication categories (best RMSE of 0.0043). Four distinct patient subgroups were identified with differential characteristics and outcomes, demonstrating superior predictive capabilities over existing HF subtypes (best mean RMSE of 0.0032). Discussion These results highlight the power of graph-based modeling of EHR in improving HF treatment strategies. The stratification of patients sheds light on particular patient segments that could benefit more significantly from tailored response predictions. Conclusions Longitudinal EHR data have the potential to enhance personalized prognostic predictions through the application of graph-based AI techniques.

Abstract Introduction Postoperative atrial fibrillation (POAF) after noncardiac surgery constitutes 10-15% of all cases of incident atrial fibrillation (AF) in the community and has been associated with an increased risk of stroke. The risk of subsequent AF among patients with POAF is not well defined. Purpose To evaluate the role of systematic 30-day electrocardiographic (ECG) monitoring in the detection of AF recurrence after POAF. Methods In a prospective interventional study, patients who underwent major noncardiac surgeries and had new AF documented by ECG in the post-operative period between May 2022 and April 2023 were identified. For these patients, a 30-day ambulatory ECG monitor was recommended upon discharge, with final ordering deferred to the primary inpatient teams. Rates of recurrent AF of any duration detected by 30-day monitoring plus routine care versus routine care alone after the surgery were compared. Results Eighty-five patients with new-onset POAF were included (mean age 72 years, male 67%). Of these, 35 (41%) patients underwent up to 30 days [median 23 (IQR 6-27) days] of continuous ECG monitoring after hospital discharge. There were no significant differences in baseline characteristics between patients who did or did not undergo monitoring (Table 1). During median 281 (IQR 197-385) days of follow-up, recurrent AF was documented in 14/35 (40%) patients in the monitoring group as opposed to 7/50 (14%) patients in the usual care group (log-rank p=0.003, Figure 1). The median time from day of surgery until documented AF recurrence was 25 (IQR 6-53) days in the monitoring group and 66 (IQR 25-145) in the usual care group. Overall, 81% of recurrent AF events in both groups were detected in the first 3 months after surgery. The median burden of AF in the cardiac monitoring group was 7% (IQR 1-15), with the longest AF event lasting a median of 6 (IQR 2-18) hours. Anticoagulation for AF was prescribed in 24/64 (37%) patients with POAF without recurrence and in 16/21 (76%) patients with recurrent AF. Conclusion Recurrent AF following POAF is common and detected most frequently in the first 3 months after noncardiac surgery. Systematic ambulatory rhythm monitoring is associated with a higher rate of AF detection following hospital discharge and may identify a patient subgroup who might benefit from anticoagulation therapy.Table 1Figure 1

Background: The COVID-19 pandemic resulted in reduced in-person clinic visits and declines in blood pressure (BP) control among patients with hypertension. The purpose of this study was to report on pre- to post-pandemic trends in BP control and related BP metrics through 2022. Methods: We utilized data from 17 US health systems with electronic health record data standardized to the PCORnet ® Common Data Model. Multiple BP control metrics were calculated as a series of quarterly, 12-month rolling measurement periods from 2017 to 2022 (i.e., 1/1/2017-12/31/2017, 4/1/2017-3/31/2018, …, 1/1/2022-12/31/2022). BP control was defined as the percentage of patients with hypertension whose most recent BP measurement at an ambulatory visit was <140/<90 mmHg. Improvement in BP was defined as the percentage of patients with a reduction of 10 mmHg in systolic BP or achievement of systolic BP <140 mmHg during the last 3 months of the measurement period in patients with previously uncontrolled hypertension. Results: In 2022, 1,499,418 persons with hypertension were included (50% 65-85 years old; 47% men; 11% Hispanic, 3% non-Hispanic Asian, 20% non-Hispanic Black, 63% non-Hispanic White). BP control was relatively stable within health systems prior to the COVID-19 pandemic. Worsening of BP control was seen for most health systems in the second quarter of 2020 coinciding with onset of the COVID-19 pandemic (Figure, left panel). The weighted average BP control was 65.3% in 2019, dropped to 61.8% in 2020, and increased to 62.9% in 2021 and 62.6% in 2022. Similar patterns were observed for the improvement in BP metric (Figure, right panel): weighted average 31.4% in 2019, 25.7% in 2020, 29.1% in 2021 and 28.6% in 2022. Conclusion: BP control and improvement in BP decreased substantially during the COVID-19 pandemic. While both metrics improved after 2020, they were still below pre-pandemic levels through 2022. These findings underscore the importance of continued surveillance of BP control and other health impacts of the COVID-19 pandemic.

BACKGROUND: Senescence, a mechanism of cellular aging, which is characterized by irreversible proliferation arrest and a proinflammatory secretory phenotype, has been documented in women with preeclampsia. As cellular senescence can persist and progress, we postulated that it is associated with accelerated aging phenotype and accumulation of comorbidities in women with a history of preeclampsia. METHODS: We included a cohort of women with a history of preeclampsia (n=40) age- and parity-matched to a group of referent women with normotensive pregnancies (n=40). Women with prior major cardiovascular events, neurological, or autoimmune conditions were excluded. We collected urine and blood samples to study markers of aging, data on multimorbidity at the time of enrollment, and prospectively followed them for events over the course of 6 years, on average. RESULTS: Women with a history of preeclampsia exhibited unfavorable aging profiles compared with referent women, including decreased urinary α-Klotho ( P =0.018); increased leptin ( P =0.016) and leptin/adiponectin ratio ( P =0.027), and increased extracellular vesicles positive for tissue factor ( P =0.025). Women with a history of preeclampsia likewise had a higher rate of comorbidities at the time of enrollment ( P =0.003) and had a 4× higher risk of developing major cardiovascular events compared with referent women ( P =0.003). CONCLUSIONS: Our data suggest that a history of preeclampsia is associated with accelerated aging as indicated by senescence marker differences and the accumulation of multimorbidity later in life. Targeting cellular senescence may offer novel, mechanism-based approaches for the diagnosis and treatment of adverse health outcomes in women with a history of preeclampsia.

Introduction: Peripheral artery disease impacts 202 million patients worldwide and is commonly diagnosed via ankle-brachial index. PAD is associated with endothelial dysfunction, which is also common to venous thromboembolism formation. Despite the suspected overlap in pathogenesis, few studies exist investigating the association between these pathologies. We investigated whether PAD with low or elevated ABI is an independent risk factor for VTE. Methods: We reviewed medical records of patients ≥18 years old undergoing ABI measurement with or without PAD symptoms from 01/01/1996 to 08/31/2018 and classified patients by ABI: severely low (ABI 0.00-0.39), moderately low (0.40-0.69), mildly low (0.70-0.90), borderline (0.91-0.99), normal (1.00-1.40), and elevated (>1.40). The primary outcome was incident VTE event after ABI measurement, defined as deep vein thrombosis or pulmonary embolism. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals after adjusting for age, sex, active smoking, cancer or VTE history, thrombophilia, anticoagulation, and revascularization within 14 days of VTE. Results: In 39,384 unique patients (mean age 66.3±14.2 years, median follow-up 34 months), 5,141 VTE events were observed. Increased VTE risk was observed in PAD patients with severely low ABI (HR 1.26, 95%CI [1.02, 1.29]) compared to patients with normal ABI after multivariable regression. Patients with elevated ABI did not demonstrate an increased risk of VTE. Conclusions: Patients with severe PAD are at higher risk for VTE than patients with normal ABI, which may be due to a multifactorial pathophysiology of profound endothelial injury as well as immobility due to claudication. Further exploration of VTE incidence in patients with severe PAD stratified by functional status is warranted to determine the optimal strategy to minimize thromboembolic morbidity and mortality in this population.

Introduction: Isolated cases of liver injury associated with the use of non-vitamin K antagonist oral anticoagulants (NOACs) have been reported. However, the comparative incidence of liver injury in users of different oral anticoagulants is unknown. Methods: We studied 113,717 patients (mean age 70, 39% women) with non-valvular atrial fibrillation (AF) included in the MarketScan® Commercial and Medicare Supplemental databases with a first prescription for oral anticoagulation after November 4, 2011, followed through December 31, 2014. Of these, 56,879 initiated warfarin, 17,286 initiated dabigatran, 30,347 initiated rivaroxaban, and 9,205 initiated apixaban. Liver injury hospitalizations were identified using selected inpatient diagnostic codes. Multivariable Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of liver injury by anticoagulant type. Results: During a median follow-up of 12 months, 960 hospitalizations with liver injury were identified. Rates of liver injury hospitalization (per 1000 person-years) by oral anticoagulant were 9.0 (warfarin), 4.0 (dabigatran), 6.6 (rivaroxaban), and 5.6 (apixaban). After multivariable adjustment, rates of liver injury hospitalization were lower in initiators of NOACs compared to warfarin: HR (95%CI) of 0.57 (0.46, 0.71), 0.88 (0.75, 1.03) and 0.70 (0.50, 0.97) for initiators of dabigatran, rivaroxaban, and apixaban, respectively (Table). Compared to dabigatran initiators, rivaroxaban initiators had a 56% increased risk of liver injury hospitalization (HR 1.56, 95%CI 1.22, 1.99). In addition to type of anticoagulant, prior liver, gallbladder, and kidney disease, cancer, anemia, heart failure, and alcoholism significantly predicted liver injury hospitalization. Conclusions: Among patients with non-valvular AF, NOACs were associated with lower risk of liver injury hospitalization compared to warfarin, with dabigatran showing the lowest risk.

Introduction: Perceived discrimination is known to play a role in the development of cardiovascular (CV) risk factors such as hypertension, but the association with CV outcomes is less clear. A recent report from a multi-ethnic cohort study found a modestly increased risk of CV disease in participants reporting discrimination. We explored this association in an African American (AA) cohort. Hypothesis: Greater perceived discrimination is associated with a higher risk of CV disease Methods: We examined CV outcomes among 5085 AAs in the Jackson Heart Study enrolled in 2000-2004 and followed through December 31, 2012. We stratified participants by quartiles of perceived everyday discrimination and estimated the associations with CV outcomes (all-cause mortality, incident coronary heart disease [CHD], incident stroke, and heart failure [HF] hospitalization) using Cox models. Results: Greater perceived discrimination was more common in participants who were younger, male, had higher education and income, a lower perceived standing in the community, worse perceived healthcare access, and fewer comorbidities. Over a median follow-up of 9.8 years (8.0 years for HF), 573 deaths, 193 incident CHD, 156 incident strokes, and 348 HF hospitalizations occurred. Prior to adjustment, greater perceived discrimination was associated with a lower risk of death, incident CHD, stroke, and HF hospitalization (Table). After adjustment for potential confounders, we found no association of perceived discrimination with incident CHD, stroke or HF hospitalization; however, a decrease in all-cause mortality risk with higher perceived discrimination persisted. Conclusions: We found no independent association of perceived discrimination with risk of incident CV disease or HF hospitalization and a paradoxical negative association with mortality in this AA population. The unexpected finding of a lower risk of death with greater perceived discrimination requires further study.

Moritz F Sinner, 2012 Finalist and Presenting Author

Abstract Background Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health‐related quality of life in patients with HF is not well understood. Methods Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF‐related prescription drugs from four U.S. institutions were mailed a survey to measure patient‐centric factors including functional status (activities of daily living [ADLs]) and health‐related quality of life (PROMIS‐29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non‐cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS‐29 sub‐scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. Results A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66–4.45), depression (OR: 3.11, 95% CI: 2.39–4.06), and fatigue (OR: 4.19, 95% CI: 3.25–5.40); worse sleep (OR: 2.14, 95% CI: 1.69–2.72) and pain (OR: 6.73, 95% CI: 5.15–8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19–12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. Conclusion Patients with only functional limitation have similar poor health‐related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well‐being of patients with HF.