Publications

BACKGROUND: Stroke is a recognized complication following transcatheter aortic valve replacement (TAVR). Although women have historically had a higher rate of bleeding and vascular complications after TAVR, contemporary data on sex differences in post-TAVR stroke and stroke severity are lacking. Disabling strokes significantly affect quality of life and outcomes, underscoring the need to explore sex-specific variations in post-TAVR stroke risk.

METHODS: In this retrospective cohort study, we included all patients who underwent TAVR in the National Inpatient Sample from 2016 to 2021. Stroke and stroke severity were ascertained using validated claims-based algorithms. Disabling strokes were defined as those resulting in death or discharge to a nonhome location. We used multivariable logistic regression to evaluate the association between sex and stroke while adjusting for covariates, including cerebral embolic protection use, and accounting for survey weights.

RESULTS: Among our weighted sample of 379 410 patients (43.9% female), women demonstrated higher overall in-hospital stroke incidence compared with men (2.31% versus 1.69%; adjusted odds ratio [aOR], 1.208 [95% CI, 1.082-1.350]). This difference was driven primarily by disabling strokes, which were more common in women (1.61% versus 1.01%; aOR, 1.327 [95% CI, 1.158-1.520]). Conversely, the incidence of nondisabling stroke was not statistically different between sexes (0.70% versus 0.67%;( aOR, 1.013 [95% CI, 0.844-1.215]).

CONCLUSIONS: Among patients undergoing TAVR in contemporary practice, women had a higher rate of any stroke and disabling strokes compared with men. These findings emphasize the need for tailored strategies to mitigate stroke risk and improve outcomes for female TAVR patients.

BACKGROUND: Claims data are increasingly used for postmarketing surveillance of therapies such as transcatheter left atrial appendage occlusion (LAAO), but their accuracy remains uncertain.

OBJECTIVES: This study aimed to compare stroke and bleeding events in the National Cardiovascular Data Registry LAAO Registry with claims data.

METHODS: LAAO Registry data for patients aged ≥65 years were linked to 2016 to 2021 Medicare claims. Primary diagnosis International Classification of Diseases-Tenth Revision codes from inpatient hospitalizations were compared to adjudicated registry-reported stroke and major bleeding events after discharge, including estimation of sensitivity and positive predictive value of claims for identifying registry-reported events. Kappa statistics and incidence rates were also assessed.

RESULTS: Among 71,043 LAAO Registry patients, sensitivity and positive predictive value of claims were 60.8% and 50.5% for ischemic stroke (kappa 0.55), 42.7% and 50.5% for hemorrhagic stroke (kappa 0.46), 55.9% and 40.3% for gastrointestinal bleeding (GIB) (kappa 0.43), 62.2% and 38.0% for intracranial hemorrhage (kappa 0.47), and 20.4% and 10.0% for other major bleeding (kappa 0.12). Sensitivity and negative predictive values were >92% for all events. Two-year incidence rates were higher in claims vs registry data for ischemic stroke (2.5% vs 2.2%), GIB (6.8% vs 5.2%), intracranial hemorrhage (1.6% vs 1.1%), and other bleeding (3.1% vs 1.5%; P < 0.01 for all events), and lower for hemorrhagic stroke (0.4% vs 0.5%; P = 0.03).

CONCLUSIONS: In the LAAO Registry, International Classification of Diseases-Tenth Revision codes have moderate agreement with stroke, GIB, and intracranial hemorrhage, and overestimate most event rates compared to adjudicated registry-reported events. Nonclaims-based methods are needed to ensure accurate assessment of clinical events in postmarketing surveillance.

OBJECTIVE: Chronic limb-threatening ischemia (CLTI), the most severe manifestation of peripheral artery disease, is associated with high risk of major amputation and mortality. Although timely revascularization is a cornerstone of CLTI management, disparities in access to care and outcomes persist across U.S. geographic regions. This study aims to evaluate variations in endovascular revascularization for CLTI, health care utilization patterns, and outcomes stratified by U.S. regions to inform how we address these disparities.

METHODS: From 2016 through 2023, all endovascular revascularizations for CLTI among Medicare fee-for-service beneficiaries were included and evaluated by Northeast, South, Midwest, and West regions of the United States. Follow-up continued through December 31, 2023, with a median duration of 625 days (maximum 2921 days). The primary outcome was a composite of death or major amputation. Secondary outcomes included major amputation, all-cause mortality, repeat revascularization, change in ambulatory status, and health care utilization before and after revascularization. Multivariable Cox proportional hazards regression models were used to adjust for demographic, clinical, and procedural characteristics.

RESULTS: Among 381,173 beneficiaries, the South performed more than half of all revascularizations throughout the study period (52.18%), followed by the West (17.3%), Northeast (16.2%), and the Midwest (13.9%). After adjustment, the Midwest showed the highest risk for the primary outcome (hazard ratio [HR]: 1.20; 95% confidence interval [CI]: 1.18, 1.22; P < .0001), followed by the South (HR: 1.11; 95% CI: 1.10, 1.13; P < .0001) and West (HR: 1.04; 95% CI: 1.02, 1.06; P < .0001), all compared with the Northeast. Health care utilization analyses revealed fewer outpatient visits with a vascular provider before and after revascularization in all regions compared with the Northeast with the lowest rates in the Midwest (before revascularization: adjusted rate ratio: 0.73; 95% CI: 0.72, 0.74; P < .0001; after revascularization: adjusted rate ratio: 0.73; 95% CI: 0.72, 0.74; P < .0001).

CONCLUSIONS: Disparities in access to care and outcomes persist across U.S. regions for Medicare beneficiaries with CLTI and influence health care utilization and outcomes. The Midwest region, in particular, that cares for a high proportion of rural patients experiences the greatest risks of amputation and death related to CLTI, which may in part be due to less frequent health care contact after revascularization. Targeted improvements in health care access, especially in rural and economically disadvantaged regions, are needed to enhance outcomes in patients with CLTI.

BACKGROUND: Patients with coronary in-stent restenosis (ISR) within multiple layers of stent pose a specific clinical challenge because of higher rates of recurrent restenosis as well as a desire to avoid an additional layer of stent. Drug-coated balloons (DCBs) provide an alternative antiproliferative therapeutic option for multilayer ISR.

OBJECTIVES: We evaluated the efficacy and safety of a low-dose paclitaxel-coated vs uncoated balloon among patients with multilayer or single-layer ISR in the AGENT IDE (A Clinical Trial to Assess the Agent Paclitaxel Coated PTCA Balloon Catheter for the Treatment of Subjects With In-Stent Restenosis) trial.

METHODS: AGENT IDE is a prospective, multicenter trial that randomized patients with ISR (reference vessel diameter >2.0 mm to ≤4.0 mm and lesion length <26 mm) in a 2:1 allocation to paclitaxel-coated or an uncoated balloon following successful lesion preparation. Randomization was stratified by multi- vs single-layer ISR as well as by center. The primary study endpoint was 1-year target lesion failure (TLF): composite occurrence of ischemia-driven target lesion revascularization (TLR), target vessel-related myocardial infarction (MI), or cardiac death.

RESULTS: Of the 600 patients randomized in the trial, multilayer ISR was present in 258 (44%) patients. Patients with multilayer ISR had higher rates of TLF at 1 year compared with those with single-layer ISR (29.0% vs 15.7%, P < 0.0001). The overall study results were consistent irrespective of multilayer vs single-layer ISR (Pinteraction = 0.66). Among patients with multilayer ISR, TLF was lower with paclitaxel-coated balloon compared with an uncoated balloon (23.8% vs 40.0%; HR: 0.55; 95% CI: 0.34-0.87; P = 0.01), driven by reductions in both TLR and target vessel-related MI. Similar findings were observed among patients with single layer ISR (1-year TLF: 13.5% with paclitaxel-coated vs 20.2% with uncoated balloon; HR: 0.64; 95% CI: 0.37-1.11; P = 0.11), although absolute event rates were lower.

CONCLUSIONS: Patients with ISR of multiple stent layers had higher rates of adverse stent-related events compared with patients with single-layer ISR. Treatment with a paclitaxel-coated balloon led to greater absolute risk reduction in 1-year TLF among patients with multilayer ISR compared with an uncoated balloon. (A Clinical Trial to Assess the Agent Paclitaxel Coated PTCA Balloon Catheter for the Treatment of Subjects With In-Stent Restenosis [ISR] [AGENT IDE]; NCT04647253).

Wire-based indices of coronary physiology are the gold standard for guiding revascularisation decisions in patients with coronary artery disease and angiographically intermediate coronary stenoses. FFRangio is a novel angiography-based technology for assessing the functional significance of epicardial coronary stenoses without pressure wires or hyperaemic stimulus. The primary objective of the Advancing Cath Lab Results with FFRangio Coronary Physiology Assessment trial (ALL-RISE; ClinicalTrials.gov: NCT05893498) is to compare clinical outcomes in patients with chronic coronary syndromes or non-ST-segment elevation acute coronary syndromes undergoing coronary angiography with ≥1 coronary lesion suitable for physiological assessment. Patients will be randomised to FFRangio-guided or to pressure wire-guided treatment. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE) at 1 year (a composite of all-cause death, myocardial infarction, or unplanned clinically driven revascularisation), assessed for non-inferiority of FFRangio-based versus pressure wire-based guidance. If non-inferiority is met, reflex superiority guidance will be tested. Secondary endpoints include periprocedural and early complications up to 30 days, individual components of MACE at 1 year, patient-reported health status, procedural resource utilisation and healthcare-related costs, and operator-assessed usability of the FFRangio and pressure wire systems. With a sample size of 1,924 patients, the study has 82.7% power to assess non-inferiority with a non-inferiority margin of 3.5%. The ALL-RISE trial will provide prospective clinical outcomes data on the relative safety, efficacy, and cost-effectiveness of a workflow using FFRangio as compared with pressure wire-based approaches for coronary lesion assessment among patients being considered for percutaneous coronary intervention.

BACKGROUND: In recent years, there has been increasing utilization of catheter-based interventions (CBI) for the treatment of acute pulmonary embolism (PE). We aimed to investigate the trends and practice patterns associated with the utilization of CBI among older patients hospitalized with a PE in US hospitals.

METHODS: All Medicare fee-for-service beneficiaries hospitalized with a PE from June 1, 2018, to September 30, 2023, were identified. For outcomes analysis, a subset of patients hospitalized between June 1, 2018, and December 31, 2021, was identified to allow for follow-up to occur.

RESULTS: In total, 313,522 patients were hospitalized with a concomitant PE; of which, 9.12% (n = 28,597) underwent a CBI (4.76% [n = 14,914] catheter-directed thrombolysis and 4.76% [n = 14,918] mechanical thrombectomy). Utilization of CBI increased over time from 5.92% in 2018 to 14.1% in 2023, attributed to increases in mechanical thrombectomy. CBI was used more frequently at teaching hospitals (adjusted OR, 1.10; 95% CI, 1.04-1.15) and in male patients (adjusted OR, 1.15; 95% CI, 1.10-1.21), while less frequently at smaller institutions (adjusted OR, 0.14; 95% CI, 0.09-0.22) and in patients with Black race (adjusted OR, 0.90; 95% CI, 0.85-0.95) or dual enrollment (adjusted OR, 0.80; 95% CI, 0.76-0.86). Older age, Black race, geographic region, and distressed communities were associated with higher rates of death or periprocedural complications.

CONCLUSIONS: In this contemporary nationwide analysis of hospitalized patients with PE, we found that rates of CBI increased over time, although uptake of CBI remains heterogeneous. Our findings suggest that there are differences in access to advanced therapies and outcomes among particular populations following CBI for PE management.

BACKGROUND AND AIMS: Femoropopliteal artery disease is associated with high rates of post-revascularization restenosis. Drug-coated devices (DCD), including drug-coated balloons (DCBs) and drug-eluting stents (DES), have demonstrated efficacy in reducing restenosis rates compared to non-drug-coated devices (NDCDs). However, concerns about potential long-term mortality risks have led to regulatory scrutiny. This study represents the final report from the Safety Assessment of Femoropopliteal Endovascular Treatment with Paclitaxel-Coated Devices (SAFE-PAD) study, a pre-specified analysis designed with the US Food and Drug Administration to evaluate the long-term mortality associated with femoropopliteal DCD use.

METHODS: SAFE-PAD was a retrospective cohort study of 168 553 Medicare fee-for-service beneficiaries (≥66 years) who underwent femoropopliteal artery revascularization between 2015 and 2018. Device exposure (DCDs vs. NDCDs) was identified using Medicare claims data. The primary outcome was all-cause mortality, assessed between treatment groups using inverse probability treatment weighting. Secondary outcomes included all-cause hospitalizations, repeat revascularization, major amputation, and cardiovascular medication use. Sensitivity analyses included instrumental variable methods, falsification endpoints, and simulation of hypothetical unmeasured confounders. Subgroup analyses examined outcomes in inpatient vs outpatient settings, in younger/low-risk populations, and in high-risk chronic limb-threatening ischaemia patients.

RESULTS: At a median follow-up of 4.3 years (maximum: 9.0 years), DCD use was not associated with increased mortality (adjusted hazard ratio: 0.98; 95% confidence interval: 0.97, 0.99), meeting the pre-specified 5% non-inferiority relative margin. Sensitivity analyses supported the validity of the primary result. Secondary outcomes showed similar hospitalization and amputation rates between groups but an increase in repeat revascularization with DCDs. Subgroup analyses confirmed safety findings across high/low-risk subgroups and across clinical settings.

CONCLUSIONS: In this final report from the SAFE-PAD study, there was no evidence of long-term mortality risk associated with DCDs used for femoropopliteal revascularization. The SAFE-PAD study helped inform the reversal of regulatory warnings against routine DCD use.

BACKGROUND: Racial differences in the use and outcomes of intravascular imaging (IVI) and invasive physiology (IP) during percutaneous coronary intervention (PCI) are underreported in the United States.

METHODS: Medicare Fee-For-Service claims data were used to examine the use and outcomes of IVI- and IP-guided PCI by Black versus White race (2016-2023). Multivariable logistic regression was used to assess the association between race and IVI/IP use. The primary outcome was major adverse cardiovascular events, which included myocardial infarction, repeat revascularization, and death. Outcomes were compared by race according to the device used (IVI versus none; IP versus none; and among all IVI/IP recipients). Cox regression was used to estimate the association between race and 2-year outcomes, adjusting for all baseline characteristics.

RESULTS: The study included 1 481 343 PCI patients (5.9% Black patients, 63.6% male, mean age 75.3±7.0 years). IVI was used in 17.6% of PCIs in White patients and 15.0% in Black patients; IP use was 7.1% and 5.7%, respectively. After adjustment, Black adults were less likely to receive IVI (odds ratio, 0.94 [95% CI, 0.93-0.96]) or IP (odds ratio, 0.83 [95% CI, 0.81-0.85]). IVI- and IP-guided PCI had lower major adverse cardiovascular event risk at 2-years in both racial groups compared with angiography alone: IVI (White patients: hazard ratio [HR], 0.93 [95% CI, 0.92-0.94]; Black patients: HR, 0.85 [95% CI, 0.84-0.87]) and IP (White patients: HR, 0.95 [95% CI, 0.92-0.98]); Black patients: HR, 0.87 [95% CI, 0.83-0.91]). However, despite global benefits with IVI/IP, Black adults had a higher adjusted risk of major adverse cardiovascular events compared with White adults (HR, 1.02 [95% CI, 1.01-1.03]).

CONCLUSIONS: IVI- and IP-guided PCI were associated with improved outcomes in both Black and White beneficiaries, yet these technologies were less frequently used in Black adults, and overall PCI outcomes remained worse for this group.

OBJECTIVE: Centralized aortic hubs frequently exist in competitive markets, which have at times demonstrated inferior surgical outcomes. Here we evaluate the impact of local market competition specifically on complex aortic surgical outcomes.

METHODS: A retrospective review included all Vascular Quality Initiative (VQI) patients between 2013 and 2022 undergoing index complex endovascular aortic repair, thoracic endovascular aortic repair, or open aortic repair. Market competition was defined by the Herfindahl-Hirschman index (HHI), using surgeon-level market share within blinded VQI regions or metropolitan statistical areas (MSAs). A higher HHI indicates lower competition. Multivariable logistic 30-day mortality models and Cox survival models were used to examine the association between HHI and outcomes. A sensitivity analysis further adjusted for complexity among all complex and routine aortic surgical patients in the Vascular Implant Surveillance and Interventional Outcomes Network from 2017 to 2019, using generalized estimating equations with MSA-level clustering.

RESULTS: The VQI contained 10,868 complex aortic surgical patients, with 4372 additional patients in MSA-based Vascular Implant Surveillance and Interventional Outcomes Network sensitivity analysis. The median patient age was 75 years. Of these patients, 68.4% were male, with a greater number of patients in high competition regions (51.3%) and MSAs (34.6%) vs medium and low competition locales. Comorbidities and aneurysm diameter were broadly similar across HHI intervals. Lower 30-day mortality was observed in high competition regions (high, 23.7%; medium, 25.9%; low, 25.9%; P = .03). In multivariable logistic models, medium regional competition was associated with greater 30-day mortality odds vs high competition (odds ratio [OR], 1.39; 95% CI, 1.21-1.60; P < .001), with a trend toward increased mortality for low competition (OR, 1.20; 95% CI, 0.98-1.45; P = .07). MSA-based sensitivity analyses demonstrated a similar trend for medium competition MSAs (OR, 1.25; 95% CI, 0.98-1.58; P = .07), without significant relationship for low-competition MSAs. Regional interval was not associated with any long-term mortality difference.

CONCLUSIONS: More competitive regions demonstrate lower 30-day mortality after complex aortic surgery but equivalent long-term survival. Further efforts should focus on drivers of this difference to widen access to high-quality complex aortic care.