Publications

BACKGROUND: Staphylococcus aureus bacteremia in patients with cardiac implantable electronic devices (CIED) is often associated with infective endocarditis (CIED-IE). The CIED-IE diagnosis is syndromic. Diagnostic uncertainty is common. Frequently, these patients are classified possible CIED-IE, resulting in guideline non-compliant treatment and heterogeneous outcomes. Improved outcomes require accurate diagnoses. In these patients, we evaluated whether metagenomic sequencing of microbial cell-free DNA (mcfDNA) in serial plasma specimens could improve diagnostic precision.

METHODS: We studied 16 patients with staphylococcal bacteremia who were classified definite or possible CIED-IE and recommended for device removal, if there was a positive blood culture within 7 days and no concurrent deep infection. Plasma specimens obtained at consent, before extraction, and during 96 hours after extraction underwent metagenomic sequencing and quantification of staphylococcal mcfDNA.

RESULTS: In 10 of 11 definite CIED-IE patients, mcfDNA persisted during antibiotic therapy for prolonged durations (median 11 days, IQR 7.5 days [7.5,15]). In these cases, mcfDNA concentration in plasma obtained early after lead extraction increased significantly and thereafter decreased rapidly. In 5 cases of possible CIED-IE, mcfDNA was undetectable after 6 days (IQR 2 days [5.5,7.5]) of antibiotic therapy and remained undetectable after CIED extraction. These mcfDNA patterns differ significantly (p=0.001), suggesting two distinct patient populations: one with definite CIED-IE and one without lead infection.

CONCLUSIONS: If confirmed, these mcfDNA patterns can serve as biomarkers, together with clinical features, to improve precision in diagnosing or rejecting S. aureus CIED-IE. Strategically timed mcfDNA testing before and after CIED extraction may aid in planning therapy.

BACKGROUND: Endovascular technologies continue to evolve to meet the large and growing burden of peripheral arterial disease. The overall quality of published RCTs in endovascular treatments for peripheral arterial disease is low, resulting in uncertainty over treatment effectiveness. The aim of this study was to develop a framework to improve the design, conduct, and reporting of future clinical trials for infrainguinal endovascular treatments of peripheral arterial disease.

METHODS: The authors undertook the design, development, and pilot testing of a novel framework. The study comprised four distinct phases. Phase 1 represented the development of a preliminary framework using content analysis of endovascular interventions described in previously published RCTs. Phase 2 consisted of focus groups with key stakeholders to further develop, revise, and achieve initial consensus on the framework. Phase 3 corresponded to the creation of a modified Delphi questionnaire to achieve final consensus on the framework. Phase 4 included cognitive interviews with professionals designing or undertaking endovascular lower limb trials to pilot test the framework.

RESULTS: Content analysis of 228 endovascular interventions from 112 RCTs identified six key themes, relevant to endovascular peripheral arterial disease interventions, for the framework: expertise; setting; anaesthesia; imaging; intervention components (access; crossing lesion; treating lesion (lesion preparation; intervention; intervention optimization; bailout intervention; and treatment of non-target lesions); and closure of artery); and pharmacological interventions. Further refinements were made to the framework as a result of feedback from three focus groups and a Delphi questionnaire. The framework deconstructs an endovascular intervention into its component parts. The final framework can be accessed at www.endo-star.com. Pilot testing evaluated comprehension, clarity, and completeness of interpretation.

CONCLUSION: The Endo-STAR framework deconstructs endovascular interventions into their key component parts and has been designed and pilot tested to enhance the quality of RCTs of endovascular interventions in peripheral arterial disease. It may be used to assist in developing future trial protocols, the standardization of infrainguinal endovascular interventions, the monitoring of adherence to the trial protocol, and as a standardized reporting guideline.

BACKGROUND: Risk stratification in patients with nonischemic dilated cardiomyopathy (DCM) remains challenging. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance is recognized as a major risk factor for ventricular tachycardia/ventricular fibrillation (VT/VF), the prognostic value of LGE radiomics is unknown.

OBJECTIVES: The purpose of this study was to investigate if radiomic analysis of LGE images can improve arrhythmia risk stratification in patients with DCM beyond current clinical and imaging markers.

METHODS: In a 2-center retrospective study, patients with DCM were identified among those who received primary prevention implantable cardioverter-defibrillators (ICDs) according to the clinical guidelines and had a cardiovascular magnetic resonance before ICD implantation. The study included patients with DCM from the Cleveland Clinic Foundation for model development and patients with DCM from Beth Israel Deaconess Medical Center for external validation. Left ventricular myocardial radiomic features were extracted from LGE images. The primary outcome was appropriate ICD intervention defined as shock or antitachycardia pacing for VT/VF. Consensus clustering and pairwise correlation were used to identify the radiomic signature. To assess the prognostic value of LGE radiomics, we built 2 logistic regression models using the development data: 1) model 1, including clinical risk factors and scar presence and 2) model 2, which combines model 1 and LGE radiomics.

RESULTS: In total, 270 patients with DCM (61% male, age 58 ± 13 years) in development data and 113 patients with DCM (71% male, age 55 ± 14 years) in external validation were included. VT/VF occurred in 40 (15%) patients in development and 16 (15%) in external validation cohorts over a median follow-up period of 4.0 (IQR: 2.5-6.1) and 2.6 (IQR: 1.2-4.1) years, respectively. Consensus clustering and pairwise correlation revealed 3 distinct radiomic features. Model 2 showed a higher C-statistic than model 1 (0.71 [95% CI: 0.62-0.80] vs 0.61 [95% CI: 0.53-0.71]; P = 0.028 in development and 0.70 [95% CI: 0.59-0.85] vs 0.61 [95% CI: 0.46-0.77]; P = 0.025 in external validation). This also significantly improved risk stratification with a continuous net reclassification index of 0.60 [95% CI: 0.29-0.91; P < 0.001] in development and of 0.29 [95% CI: 0.26-0.56; P = 0.03] in external validation. Additionally, 1 radiomic feature, namely the gray level co-occurrence matrix autocorrelation, was an independent predictor of VT/VF in both development (HR: 1.45 [95% CI: 1.10-1.91]; P = 0.01) and in external validation (HR: 2.38 [95% CI: 1.28-4.42]; P = 0.01).

CONCLUSIONS: In this proof-of-concept study, radiomic analysis of LGE images provides additional prognostic value beyond LGE presence in predicting arrhythmia in patients with DCM.

Glucagon-like peptide 1 receptor agonists (GLP1-RA) are anti-diabetes agents recently approved for weight loss. Obesity is an established risk factor for venous thromboembolism (VTE). Moreover, preclinical studies have shown that GLP1-RA may attenuate thromboxaneinduced platelet activation. Therefore, we hypothesized that GLP1-RA use may reduce the risk of VTE. We performed a target trial emulation using a population-based database of electronic health records to evaluate whether GLP1-RA use is associated with a reduction in VTE in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidas e-4 inhibitors (DPP4i). Patients who were newly initiated on GLP1-RA were propensity scorematched to patients who were newly initiated on DPP4i. We evaluated the primary outcome, composite VTE, identified using ICD-10 codes, within 12 months of the initiation of GLP1-RA or DPP4i. The study cohort comprised 540,258 patients with 270,129 individuals receiving either GLP1-RA or DPP4i. Over 12 months of follow-up, patients who received GLP1-RA had a lower incidence of VTE compared with patients who received DPP4i (6.1 vs. 7.6 events per 1000 patient-years, hazard ratio [HR], 0.78 [95% CI: 0.73-0.83]). This was similar for PE (2.9 vs. 3.8 events per 1000 patient-years, HR, 0.74 [95% CI: 0.68-0.82]) and DVT (3.9 vs. 4.7 events per 1000 patient-years, HR, 0.81 [95% CI: 0.75-0.88]). In this propensity scorematched, target trial emulation study, patients with T2DM who received a GLP1-RA had a lower risk of VTE at one year compared with patients who received DPP4i.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2025 AHA Statistical Update is the product of a full year's worth of effort in 2024 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. This year's edition includes a continued focus on health equity across several key domains and enhanced global data that reflect improved methods and incorporation of ≈3000 new data sources since last year's Statistical Update.

RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.

CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

IMPORTANCE: The Southern Community Cohort Study (SCCS) Polypill Trial showed that a cardiovascular polypill (a single pill containing a statin and 3 half-standard dose antihypertensive medications) effectively controls cardiovascular disease (CVD) risk factors in a majority Black race and low-income population. The cost-effectiveness of polypill treatment in this population has not been previously studied.

OBJECTIVE: To determine the cost-effectiveness of the cardiovascular polypill.

DESIGN, SETTING, AND PARTICIPANTS: A discrete-event simulation version of the well-established CVD policy model simulated clinical and economic outcomes of the SCCS Polypill Trial from a health care sector perspective. A time horizon of 10 years was adopted. Polypill treatment was priced at $463 per year in the base-case analysis. Model input data were derived from the National Health and Nutrition Examination Survey, Medical Expenditure Panel Survey, pooled longitudinal cohort studies, the SCCS Polypill Trial, and published literature. Two cohorts were analyzed: an SCCS Polypill Trial-representative cohort of 100 000 individuals and all trial-eligible non-Hispanic Black US adults. Study parameters and model inputs were varied extensively in 1-way and probabilistic sensitivity analysis.

EXPOSURES: Polypill treatment or usual care.

MAIN OUTCOME AND MEASURES: Primary outcomes were direct health care costs (US dollar 2023) and quality-adjusted life-years (QALYs), both discounted 3% annually, and the incremental cost per QALY gained.

RESULTS: In the trial-representative cohort of 100 000 individuals (mean [SD] age, 56.9 [5.9] years; 61 807 female [61.8%]), polypill treatment was projected to yield a mean of 1190 (95% uncertainty interval, 287-2159) additional QALYs compared with usual care, at a cost of approximately $10 152 000. Hence, polypill treatment was estimated to cost $8560 per QALY gained compared with usual care and was high value (<$50 000 per QALY gained) in 99% of simulations. Polypill treatment was estimated to be high value when priced at $559 or less per year and cost saving when priced at $443 or less per year. In almost all sensitivity analyses, polypill treatment remained high value. In a secondary analysis of 3 602 427 trial-eligible non-Hispanic Black US adults (mean [SD] age, 55.4 [7.6] years; 2 006 597 female [55.7%]), polypill treatment was high value, with an estimated cost of $13 400 per QALY gained.

CONCLUSIONS AND RELEVANCE: Results of this economic evaluation suggest that polypill treatment could be a high value intervention for a low-income, majority Black population with limited access to health care services. It could additionally reduce health disparities.

PURPOSE: Cardiac rehabilitation (CR) is a valuable secondary preventive intervention for Veterans given their increased risk of cardiovascular disease. Adults cared for in the Veterans Affairs (VA) healthcare system are a unique population that receives healthcare from the largest integrated care network in the United States. Yet, this group faces distinct challenges in utilizing CR. In this review, we evaluated the existing data regarding CR utilization and outcomes among U.S. Veterans.

REVIEW METHODS: A literature search was conducted using PubMed and Scopus for cardiac rehabilitation and U.S. Veterans.

SUMMARY: Veterans have 3 potential options for attending CR: in-person at their local VA medical centers, home-based CR through their local VA medical centers, and in-person at community CR centers. However, participation remains low. A significant barrier to participation is transportation to in-person CR. Home-based CR shows promise in addressing this barrier and has demonstrated resilience in the face of pandemic restrictions. Cardiac rehabilitation outcomes among Veterans who participate include improved exercise capacity, fewer depressive symptoms, and decreased mortality. Despite its benefits for secondary prevention among Veterans, there remains a paucity of data about the current uptake of CR, the impact of mental health on uptake, possible sex-based or racial disparities, and long-term outcomes.