BACKGROUND:Predictors of target lesion failure (TLF) after percutaneous coronary intervention with drug-coated balloon therapy in patients with in-stent restenosis, as opposed to de novo disease, are limited. This post hoc analysis of the AGENT IDE trial (Agent Paclitaxel-Coated PTCA Balloon Catheter for the Treatment of Subjects With In-Stent Restenosis) aimed to identify predictors of TLF in patients with in-stent restenosis treated with a paclitaxel-coated balloon. METHODS:Of the 600 patients with in-stent restenosis in the AGENT IDE trial, 406 were randomized to treatment with the paclitaxel-coated balloon. Among this cohort, demographic, clinical, and core laboratory angiographic data were assessed using a Cox proportional hazards model to identify independent predictors of TLF, defined as the composite occurrence of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death, at 2-year follow-up. RESULTS:Independent risk factors for 2-year TLF, which occurred in 106 (27.0%) of patients, included multiple stent layers (hazard ratio, 1.80 [95% CI, 1.23-2.65]), White race (hazard ratio, 1.71 [95% CI, 1.03-2.85]), and postlesion preparation in-lesion % diameter stenosis (per 10% increment; hazard ratio, 1.16 [95% CI, 1.03-1.31]). The presence of the target lesion in the left anterior descending artery was associated with a reduced risk of 2-year TLF (hazard ratio, 0.56 [95% CI, 0.36-0.87]). CONCLUSIONS:Our findings highlight the variable risk of in-stent restenosis governed by relatively few patient and lesion factors and underscore the significance of optimal lesion preparation before drug-coated balloon therapy as a potentially modifiable factor. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04647253.

Abstract Background Pulsed field ablation (PFA) has demonstrated comparable efficacy to radiofrequency ablation (RFA) in the treatment of atrial fibrillation (AF), with enhanced safety due to its cardiac selectivity. More recently, however, market recalls of some PFA catheters have raised concerns about the cerebrovascular safety of PFA. Purpose To compare the incidence of 30-day complications following PFA versus RFA for AF, focusing on strokes and transient ischemic attacks (TIAs). Methods We analyzed a prospective registry from a high-volume U.S. academic center including all consecutive AF ablations from 2022 to 2025. All procedural complications were recorded. Strokes/TIAs were adjudicated by three independent neurologists blinded to treatment assignment. Inverse probability of treatment weighting (IPTW) was applied to balance clinical differences between the PFA and RFA groups, and propensity scores were used to compare stroke/TIA rates at 30 days (primary endpoint). Secondary endpoints included other non-fatal complications at 30 days, and stroke/TIA rates at 7 days. Results Between January 2022 and July 2025, we identified 1,504 PFA and 2,062 RFA cases performed by 12 operators. Patients in both arms had mean age of 67 years, 31% were female, and with comparable comorbidity profiles (45% paroxysmal and 50% persistent AF; mean CHA2DS2-VASc 2.4 with 7% prior stroke/TIA; mean HAS-BLED 1.5). Compared to RFA procedures, patients received PFA earlier in their disease course, as evidenced by lower use of antiarrhythmic medications (75%PFA vs 81%RFA, p<.001) and cardioversions (40%PFA vs 32%RFA, p<.001). PFA procedures had shorter left atrial dwell time (1.8 vs 2.4 hours, p<.001); PVI-only was performed in 18.8%PFA and 46%RFA cases (p<.001) while PVI/posterior wall isolation in 57%PFA and 25.5%RFA (p<.001), with similar amounts of additional lesions in both groups (e.g. mitral lines in ~20% cases). Overall, 9 patients (0.20%) experienced stroke/TIA events at 30 days, which were all confirmed by MRI or fundoscopy: 7 (0.47%) after PFA and 2 (0.10%) after RFA (unadjusted risk difference 0.37%, 95%CI –0.00 to 0.74; p=0.05). After IPTW adjustment, groups were well balanced and PFA remained associated with significantly higher stroke/TIA rates at both 7-days (0.43%PFA vs 0.05%RFA; 95%CI 0.04-0.72%; p=0.03) and 30-days (0.51%PFA vs 0.10%RFA; 95%CI 0.02-0.79%; p=0.03). No atrioesophageal fistulas were observed. The adjusted rates of other complications like phrenic nerve injury (0%PFA vs 0.15%RFA, p=0.34), coronary vasospasm (0%PFA vs 0.05%RFA, p=0.60) and pericardial tamponade (0.07%PFA vs 0.24%RFA, p=0.34) were similar in both arms. Conclusion PFA procedures were associated with a significantly higher risk of stroke/TIA within 30 days compared to RFA in this high-volume single center experience. Further studies are needed to confirm these findings, define mechanisms, and optimize procedural protocols to mitigate the cerebrovascular risk.Central IllustrationTemporal Trend in Stroke/TIA Events

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: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.

Introduction: Hospitalization for COVID-19 in the Pre-Omicron era was associated with an increased risk of major adverse cardiovascular events (MACE), but data from the Omicron era are sparse. Hypothesis: We investigated the hypothesis that the risk of MACE among older adults hospitalized for COVID-19 during the Omicron era is lower than in the Pre-Omicron era, and is similar to that in a historical influenza cohort. Methods: Retrospective cohort study using 100% of Medicare fee-for-service claims, including beneficiaries aged ≥ 65 years hospitalized for COVID-19 in the Omicron era (11/26/21–09/30/2022), for COVID-19 in the Pre-Omicron era (03/01/20 –11/25/21), or for influenza in the pre-COVID-19 era (03/01/16 – 09/30/18). Outcomes were measured at 1 year of follow-up after the index hospital admission date. The primary endpoint was the cumulative incidence proportion (risk) of MACE (composite of all-cause death, myocardial infarction, ischemic stroke/ transient ischemic attack, pulmonary embolism, deep vein thrombosis, heart failure hospitalization, and cardiac arrest). Secondary outcomes included individual components of MACE and hospitalization for atrial fibrillation. We used inverse probability weighting to allow comparisons to a common standard (Omicron cohort), the Kaplan-Meier method to estimate the cumulative incidence of outcomes including death, and the Aalen-Johansen method for outcomes that did not include death. Results The analysis included 363,719 patients in the Omicron cohort (mean age 79 years; 51% women; 18% dual enrollees), 724,657 in the Pre-Omicron cohort, and 149,572 in the influenza cohort. The risk of MACE at 1 year was lower in the Omicron than in the pre-Omicron cohort (48.6% vs. 49.3%, risk difference after standardization [RD], -0.7%; 95% CI -0.9% to -0.5%) but higher than in the influenza cohort (48.6% vs. 30.3%; RD, 18.3%; 18.1% – 18.6%). Compared with the pre-Omicron cohort, the Omicron cohort had a significantly lower risk of death at 1 year (34.2% vs. 40.1%, RD, -5.9%; -6.1% to -5.7%) but a higher risk of hospitalizations for myocardial infarction, stroke, heart failure, and atrial fibrillation (figure). Conclusions Among older adults, the risk of MACE within 1 year after COVID-19 hospitalization in the Omicron era has declined since the Pre-Omicron era, driven by all-cause death, but it remains elevated. Notably, during the Omicron period the risk of MACE is still higher than that observed in a historical influenza cohort.

Background Use of pulmonary vein isolation (PVI) to treat atrial fibrillation continues to increase. Despite great interest in leveraging administrative data for real‐world analyses, contemporary procedural codes for identifying PVI have not been evaluated. Methods and Results In this observational retrospective cohort study, inpatient PVIs were identified among US Medicare fee‐for‐service beneficiaries using Current Procedural Terminology (CPT) code 93656 in Carrier Line Files. Each patient was matched with their claims from Medicare Provider Analysis and Review to compare CPT with International Classification of Diseases , Tenth Revision , Procedure Coding System ( ICD‐10‐PCS ) claims submitted by health care facilities to bill for PVIs. We performed the reverse for commonly matched ICD‐10‐PCS codes, to identify corresponding CPT‐billed procedures. Finally, we reviewed institutional cases for additional comparison of CPT and ICD‐10‐PCS assignation for PVI. We identified 25 617 inpatient PVIs from January 2017 to December 2021, of which 18 165 (71%) were linked to Medicare Provider Analysis and Review. Of these, 16 672 (92%) were billed as ICD‐10‐PCS 02583ZZ: “Destruction of Conduction Mechanism, Percutaneous Approach.” The reverse process yielded heterogeneous results: among 75 003 procedures billed as ICD‐10‐PCS 02583ZZ, only 15 691 (21%) matched with CPT 93656 (PVI), as several other unrelated procedures were billed under this ICD‐10‐PCS code. Institutional case review confirmed the greater specificity of CPT codes. Conclusions The ICD‐10‐PCS code associated with CPT‐billed PVI procedures actually referred to ablation of the atrioventricular junction. Yet this ICD‐10‐PCS code also matched with a wide range of other procedures distinct from PVI. We conclude that ICD‐10‐PCS codes alone are not sensitive nor specific for identifying PVI in claims and cannot be reliably used in isolation for health services research on this important procedure.

ImportanceCardiovascular disease is the leading cause of death in the US. However, it remains unclear how the burden of cardiovascular events in the US compares with that of other high-income countries with distinct health care systems like Denmark, both overall and by income.ObjectiveTo compare cardiovascular hospitalization rates (acute myocardial infarction [MI], heart failure [HF], ischemic stroke) and associated outcomes among adults 65 years or older, overall and by income, between the US and Denmark.Design, Setting, and ParticipantsThis population-based cross-sectional study used national data from the US and Denmark from January 1, 2021, to January 1, 2022. The study population included all Medicare beneficiaries 65 years or older in the US and all adults 65 years or older in Denmark.Main Outcomes and MeasuresThe primary outcome was age- and sex-standardized hospitalization rates for MI, HF, and ischemic stroke, as well as 30-day all-cause mortality rates.ResultsThe US study population included 58 614 110 adults 65 years or older (mean [SE] age, 74.6 [7.7] years; 32 179 146 female [54.9%]) of whom 1 171 058 (2.0%) were hospitalized for a cardiovascular event. The Danish study population included 1 176 542 adults 65 years or older (mean [SE] age, 75.3 [7.1] years; 634 217 female [53.9%]) of whom 16 305 (1.4%) were hospitalized with a cardiovascular event. The overall age- and sex-standardized cardiovascular hospitalization rate was significantly higher in the US compared with Denmark (risk ratio [RR], 1.50; 95% CI, 1.47-1.52), as were associated 30-day all-cause mortality rates (RR, 1.12; 95% CI, 1.06-1.17). Across conditions, the risk of hospitalization for MI (RR, 1.56; 95% CI, 1.51-1.61) and HF (RR, 2.37; 95% CI, 2.31-2.43) was significantly higher in the US compared with Denmark, whereas hospitalizations for ischemic stroke were lower (RR, 0.90; 95% CI, 0.88-0.93). Overall cardiovascular hospitalization rates in the US were more than 2-fold higher among low-income adults compared with higher-income adults (RR, 2.38; 95% CI, 2.25-2.47), whereas the magnitude of income-based disparities was smaller in Denmark (RR, 1.45; 95% CI, 1.39-1.50).Conclusions and RelevanceIn this international cross-sectional study, cardiovascular hospitalization rates were significantly higher in the US compared with Denmark. There were income-based differences in the burden of cardiovascular hospitalizations in both countries, although the magnitude of these disparities was much greater in the US.