Publications

Most of the 800 000 people living with end-stage kidney disease in the United States rely on a functioning vascular access to provide life-sustaining hemodialysis, yet one-third of arteriovenous fistulas experience early failures. Determining the safety and effectiveness of systemic heparin during fistula creation could improve the quality and quantity of life for these vulnerable patients. In this article, a pragmatic randomized trial was emulated to assess the effect of systemic heparin administration (vs none) during radiocephalic arteriovenous fistula creation on early bleeding and thrombosis, using data from 2 international, multicenter, randomized trials performed between 2014 and 2019. Marginal risks were estimated using inverse probability weighted parametric survival analysis and CIs were generated with bootstrapping. A total of 914 patients were enrolled and 61% received systemic heparin; their median (IQR) age was 58 (49, 67) years and 45% were on hemodialysis at enrollment. No difference in the risk of bleeding events was observed, with a risk difference (95% CI) at 14 days of -0.1% (-1.6 to 1.4). The risk of access thrombosis was lower in the heparin group, with a risk of 3.7% (2.6-4.8) after heparin and 5.3% (3.4-7.4) without heparin at 14 days (risk ratio = 0.72; 95% CI, 0.50-0.98). Trial registration: ClinicalTrials.gov. Identifiers: NCT02110901 and NCT02414841.

A global treatment algorithm was developed for the endovascular revascularization of femoropopliteal lesions and chronic total occlusions, aiming toward a more standardized approach to endovascular treatment in patients with peripheral artery disease. The following steps are proposed. 1) Evaluation of lesion morphology based on preprocedural imaging by Duplex sonography and intravenous ultrasound for selection of lesion preparation tools. Lesion characteristics are mainly defined by calcification, lesion length, and the presence of total occlusion and in-stent restenosis. 2) Selection of vessel preparation strategies, which encompass plain old balloon angioplasty, atherectomy, thrombectomy, intravascular lithotripsy and specialty balloons, or a combination of the preceding, based on lesion and patient-specific characteristics. In addition, a Delphi consensus was applied for the appropriateness of lesion preparation strategies, depending on lesion anatomy, length, plaque morphology, and subintimal versus intraluminal guidewire crossing. 3) Definitive lesion treatment strategies using drug-coated balloons, bare-metal stents, drug-eluting stents, and/or covered stents or a combination. By establishing this treatment algorithm in routine practice, improvements in vessel- and patient-specific outcomes are anticipated, which will be further enhanced by continuous collaboration among experts from different countries and disciplines and by randomized controlled trials.

OBJECTIVE: Routine imaging surveillance following endovascular aortic aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) is critical for the timely diagnosis of late postoperative complications. Compliance with recommended EVAR surveillance is variable, and disparities in post-EVAR surveillance remain unclear. This study examines variability in EVAR surveillance and emergency health service use across several sociodemographic populations.

METHODS: All Medicare fee-for-service beneficiaries who underwent infrarenal EVAR for intact abdominal aortic aneurysm between January 2011 and December 2019 were included. Patients were stratified by several sociodemographic characteristics: age category (66-74, 75-84, >85 years), sex (male, female), race (White, Black, Asian, other), dual enrollment in Medicare and Medicaid (dual enrolled, Medicare only), and distressed communities index (distressed >80th percentile, nondistressed ≤80th percentile). The following postoperative health care use metrics were assessed: EVAR-related office visits, imaging studies, emergency department (ED) visits, and hospital readmissions. Annual incidence rates were calculated for each health care use metric at 2 and 5 years after EVAR and compared across groups using Poisson regression models, adjusting for sociodemographic and hospital characteristics and comorbidities.

RESULTS: In 111,381 Medicare beneficiaries who underwent EVAR, postoperative health care use varied substantially across sociodemographic groups. After adjustment, annual incidence rates of EVAR-related office visits at 2 years post EVAR were lower in patients who were >85 years vs 66-75 years (adjusted rate ratio [aRR], 0.95; 95% confidence interval [CI], 0.93-0.97), female vs male (aRR, 0.94; 95% CI, 0.93-0.95), dual enrolled vs Medicare only (aRR, 0.83; 95% CI, 0.81-0.85), and residing in distressed vs nondistressed communities (aRR, 0.95; 95% CI, 0.93-0.96). Rates of imaging studies were lower in patients who were >85 years (aRR, 0.98; 95% CI, 0.96-0.99), dual enrolled (0.97; 95% CI, 0.95-0.98), and residing in distressed communities (aRR, 0.97; 95% CI, 0.96-0.98). There was higher use of hospital services in patients who were >85 years (ED: aRR, 1.37; 95% CI, 1.33-1.41; readmission: aRR, 1.23; 95% CI,1.19, 1.28), female (ED: aRR, 1.19; 95% CI, 1.16-1.22; readmission: aRR, 1.15; 95% CI, 1.12-1.19), Black (ED: aRR, 1.10; 95% CI, 1.05-1.15; readmission: aRR, 1.15; 95% CI, 1.09-1.22), dual-enrolled (ED: 1.29; aRR, 95% CI, 1.26-1.33; readmission: aRR, 1.14; 95% CI, 1.09-1.18), and residing in distressed communities (ED: aRR, 1.03; 95% CI, 1.01-1.06; readmission: aRR, 1.02; 95% CI, 0.99-1.05). At 5 years post EVAR, similar trends across sociodemographic groups were observed, with the added finding of lower rates of EVAR-related office visits in Black vs White patients.

CONCLUSIONS: Significant variation in post-EVAR health care use exists among Medicare beneficiaries. Patients who were older age, of female sex, of Black race, or socioeconomically disadvantaged had lower rates of EVAR-specific follow-up and higher use of emergency health service. Barriers in access to care are apparent, underscoring the need for targeted interventions to enhance post-EVAR surveillance and improve outcomes in these populations.

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: 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: 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.