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Background Sepsis is associated with an elevated risk of late cardiovascular events among hospital survivors. Methods and Results We included OptumLabs Data Warehouse patients from 2009 to 2019 who survived a medical/nonsurgical hospitalization lasting at least 2 nights. The association between sepsis during hospitalization, based on explicit and implicit discharge International Classification of Diseases, Ninth Revision ( ICD‐9 )/ Tenth Revision ( ICD‐10 ) diagnosis codes, with subsequent death and rehospitalization was analyzed using Kaplan–Meier survival analysis and multivariable Cox proportional‐hazards models. The study population included 2 258 464 survivors of nonsurgical hospitalization (5 396 051 total patient‐years of follow‐up). A total of 808 673 (35.8%) patients had a sepsis hospitalization, including implicit sepsis only in 448 644, explicit sepsis only in 124 841, and both in 235 188. Patients with sepsis during hospitalization had an elevated risk of all‐cause mortality (adjusted hazard ratio [HR], 1.27 [95% CI, 1.25–1.28]; P <0.001), all‐cause rehospitalization (adjusted HR, 1.38 [95% CI, 1.37–1.39]; P <0.001), and cardiovascular hospitalization (adjusted HR, 1.43 [95% CI, 1.41–1.44]; P <0.001), especially heart failure hospitalization (adjusted HR, 1.51 [95% CI, 1.49–1.53]). Patients with implicit sepsis had higher risk than those with explicit sepsis. A sensitivity analysis using the first hospitalization yielded concordant results for cardiovascular hospitalization (adjusted HR, 1.78 [95% CI, 1.76–1.78]; P <0.001), as did a propensity‐weighted analysis (adjusted HR, 1.52 [95% CI, 1.50–1.54]; P <0.001). Conclusions Survivors of sepsis hospitalization are at elevated risk of early and late post‐discharge death as well as cardiovascular and non‐cardiovascular rehospitalization. This hazard spans the spectrum of cardiovascular events and may suggest that sepsis is an important cardiovascular risk factor.

ImportanceOptimal diabetes care requires regular monitoring and care to maintain glycemic control. How high-deductible health plans (HDHPs), which reduce overall spending but may impede care by increasing out-of-pocket expenses, are associated with risks of severe hypoglycemia and hyperglycemia is unknown.ObjectiveTo examine the association between an employer-forced switch to HDHP and severe hypoglycemia and hyperglycemia.Design, Setting, and ParticipantsThis retrospective cohort study used deidentified administrative claims data for privately insured adults with diabetes from a single insurance carrier with multiple plans across the US between January 1, 2010, and December 31, 2018. Analyses were conducted between May 15, 2020, and November 3, 2022.ExposuresPatients with 1 baseline year of enrollment in a non-HDHP whose employers subsequently forced a switch to an HDHP were compared with patients who did not switch.Main Outcomes and MeasuresMixed-effects logistic regression models were used to examine the association between switching to an HDHP and the odds of severe hypoglycemia and hyperglycemia (ascertained using diagnosis codes in emergency department [ED] visits and hospitalizations), adjusting for patient age, sex, race and ethnicity, region, income, comorbidities, glucose-lowering medications, baseline ED and hospital visits for hypoglycemia and hyperglycemia, and baseline deductible amount, and applying inverse propensity score weighting to account for potential treatment selection bias.ResultsThe study population was composed of 42 326 patients who switched to an HDHP (mean [SD] age: 52 [10] years, 19 752 [46.7%] women, 7375 [17.4%] Black, 5740 [13.6%] Hispanic, 26 572 [62.8%] non-Hispanic White) and 202 729 patients who did not switch (mean [SD] age, 53 [10] years, 89 828 [44.3%] women, 29 551 [14.6%] Black, 26 689 [13.2%] Hispanic, 130 843 [64.5%] non-Hispanic White). When comparing all study years, switching to an HDHP was not associated with increased odds of experiencing at least 1 hypoglycemia-related ED visit or hospitalization (OR, 1.01 [95% CI, 0.95-1.06]; P = .85), but each year of HDHP enrollment did increase these odds by 2% (OR, 1.02 [95% CI, 1.00-1.04]; P = .04). In contrast, switching to an HDHP did significantly increase the odds of experiencing at least 1 hyperglycemia-related ED visit or hospitalization (OR, 1.25 [95% CI, 1.11-1.42]; P &amp;lt; .001), with each year of HDHP enrollment increasing the odds by 5% (OR, 1.05 [95% CI, 1.01-1.09]; P = .02).Conclusions and RelevanceIn this cohort study, employer-forced switching to an HDHP was associated with increased odds of potentially preventable acute diabetes complications, potentially because of delayed or deferred care. These findings suggest that employers should be more judicious in their health plan offerings, and health plans and policy makers should consider allowing preventive and high-value services to be exempt from deductible requirements.

Background This study aimed to compare percutaneous left atrial appendage occlusion (LAAO) with non‐vitamin K antagonist oral anticoagulants among patients with atrial fibrillation. Methods and Results Using a US administrative database, 562 850 patients with atrial fibrillation were identified, among whom 8397 were treated with LAAO and 554 453 were treated with non‐vitamin K antagonist oral anticoagulants between March 13, 2015 and December 31, 2018. Propensity score overlap weighting was used to balance baseline characteristics. The primary outcome was a composite end point of ischemic stroke or systemic embolism, major bleeding, and all‐cause mortality. The mean age was 76.4±7.6 years; 280 097 (49.8%) were female. Mean follow‐up was 1.5±1.0 years. LAAO was associated with no significant difference in the risk of the primary composite end point (hazard ratio [HR], 0.93 [0.84–1.03]), or the secondary outcomes including ischemic stroke/systemic embolism (HR, 1.07 [0.81–1.41]), and intracranial bleeding (HR, 1.08 [0.72–1.61]). LAAO was associated with a higher risk of major bleeding (HR, 1.22 [1.05–1.42], P =0.01) and a lower risk of mortality (HR, 0.73 [0.64–0.84], P <0.001). The lower risk of mortality associated with LAAO was most pronounced in patients with a prior history of intracranial bleeding. Conclusions In comparison to non‐vitamin K antagonist oral anticoagulants, LAAO was associated with no significant difference in the risk of the composite outcome and a lower risk of mortality, which suggests LAAO might be a reasonable option in select patients with atrial fibrillation. The observation of higher bleeding risk associated with LAAO highlights the need to optimize postprocedural antithrombotic regimens as well as systematic efforts to assess and address bleeding predispositions.

Background EAST‐AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) demonstrated clinical benefit of early rhythm‐control therapy (ERC) in patients with new‐onset atrial fibrillation (AF) and concomitant cardiovascular conditions compared with current guideline‐based practice. This study aimed to evaluate the generalizability of EAST‐AFNET 4 in routine practice. Methods and Results Using a US administrative database, we identified 109 739 patients with newly diagnosed AF during the enrollment period of EAST‐AFNET 4. Patients were classified as either receiving ERC, using AF ablation or antiarrhythmic drug therapy, within the first year after AF diagnosis (n=27 106) or not receiving ERC (control group, n=82 633). After propensity score overlap weighting, Cox proportional hazards regression was used to compare groups for the primary composite outcome of all‐cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction. Most patients (79 948 of 109 739; 72.9%) met the inclusion criteria for EAST‐AFNET 4. ERC was associated with a reduced risk for the primary composite outcome (hazard ratio [HR], 0.85; 95% CI, 0.75–0.97 [ P =0.02]) with largely consistent results between eligible (HR, 0.89; 95% CI, 0.76–1.04 [ P =0.14]) or ineligible (HR, 0.77; 95% CI, 0.60–0.98 [ P =0.04]) patients for EAST‐AFNET 4 trial inclusion. ERC was associated with lower risk of stroke in the overall cohort and in trial‐eligible patients. Conclusions This analysis replicates the clinical benefit of ERC seen in EAST‐AFNET 4. The results support adoption of ERC as part of the management of recently diagnosed AF in the United States.

Abstract Aims Artificial intelligence (AI) enabled electrocardiography (ECG) can detect latent atrial fibrillation (AF) in patients with sinus rhythm (SR). However, the change of AI-ECG probability before and after the first AF episode is not well characterized. We sought to characterize the temporal trend of AI-ECG AF probability around the first episode of AF. Methods and results We retrospectively studied adults who had at least one ECG in SR prior to an ECG that documented AF. An AI network calculated the AF probability from ECGs during SR (positive defined &gt;8.7%, based on optimal sensitivity and specificity). The AI-ECG probability was reported prior to and after the first episode of AF and stratified by age and CHA2DS2-VASc score. Mixed effect models were used to assess the rate of change between time points. A total of 59 212 patients with 544 330 ECGs prior to AF and 413 486 ECGs after AF were included. The mean time between the first positive AI-ECG and first AF was 5.4 ± 5.7 years. The mean AI-ECG probability was 19.8% 2–5 years prior to AF, 23.6% 1–2 years prior to AF, 34.0% 0–3 months prior to AF, 40.9% 0–3 months after AF, 35.2% 1–2 years after AF, and 42.2% 2–5 years after AF (P &lt; 0.001). The rate of increase prior to AF was higher for age &gt;50 years CHA2DS2-VASc score ≥4. Conclusion The AI-ECG probability progressively increases with time prior to the first AF episode, transiently decreases 1–2 years following AF and continues to increase thereafter.

Introduction: OAC are recommended for AF patients with CHA 2 DS 2 -VASc ≥2 in men or ≥3 in women (high-risk group), may be considered in patients with CHA 2 DS 2 -VASc 1 in men or 2 in women (medium-risk group), and are reasonable to omit in patients with CHA 2 DS 2 -VASc 0 in men or 1 in women (low-risk group). Furthermore, NOACs are recommended over warfarin in most AF patients. This study aimed to investigate AF stroke prevention treatment patterns in patients managed in routine practice, in particular, the under-use of OAC in the high-risk group and over-use in the low-risk group. Methods: Adult patients with AF were identified using de-identified claims for commercial and Medicare Advantage enrollees in the OptumLabs Data Warehouse. Prescription fills were assessed within 90 days of a patient’s AF encounter between 1/1/2016-12/31/2020. Patients with other indications for OAC, such as VTE, recent joint replacement, prior mechanical or bioprosthetic valve replacement, rheumatic mitral stenosis, and patients who underwent LAAO were excluded. Results: Among the 339,197 AF patients, 4.4%, 8.0%, and 87.6% were in the low-, medium-, and high-risk groups, respectively. The mean age was 51.2 ±10.5 yr, 59.9 ±9.4 yr, and 75.1 ±8.8 yr. In the low-risk group, 29.6% were treated with OAC, whereas in the high-risk group, 40.3% were not treated with any antithrombotic therapy and 7.5% used thienopyridine only. Although 71% of patients on OAC were on a NOAC, the proportion of patients on NOAC decreased from 91% in the low-risk group to 69% in the high-risk group. Conclusions: There are potentially both under-use of guideline-recommended stroke prevention therapies in the high-risk patients and over-use in the low-risk group. Because patients at a high risk of stroke are also at a high risk of major and intracranial bleeding who might benefit from NOACs, the decreased use of NOAC in high-risk patients might highlight the need for future quality improvement efforts.

Abstract Background The Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4) demonstrated clinical benefit of early rhythm-control therapy in patients with recently diagnosed atrial fibrillation (AF) and concomitant cardiovascular conditions (CHA2DS2-VASc-Score ≥2) compared to the current practice of limited rhythm-control therapy to improve AF-related symptoms. Purpose To evaluate the generalizability of the EAST-AFNET 4 trial in routine practice, we assessed the proportion of patients who would have met trial eligibility and examined the association between early rhythm-control and clinical outcomes. Methods Using a large US administrative database, we identified 109,739 patients with newly diagnosed AF from July 28th, 2011 to December 30th, 2016, the enrollment period of the EAST-AFNET 4 trial. Eligibility for trial inclusion was assessed based on inclusion criteria. Eligible patients were classified as either receiving early rhythm-control, i.e AF ablation and/or any antiarrhythmic drug therapy, within the first year after AF diagnosis (N=27,106) or patients not receiving early rhythm-control (N=82,633). The date 12 months after the first AF diagnosis was defined as the index date and the start of the follow up period. Propensity score overlap weighting was used to balance patients on 90 baseline characteristics. Cox proportional hazards regression was used to compare early rhythm-control with no early rhythm-control for the primary outcome of a composite end point of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction. Results Eligible for the trial were 72.9% (82,633/109,739) of all patients with newly diagnosed AF. Early rhythm-control therapy was associated with a reduction in the composite end point in the overall cohort of patients (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.75–0.97; P=0.015) with largely consistent treatment effects between patients eligible or ineligible for the trial. The reduction of stroke risk associated with early rhythm-control therapy was found in the overall cohort (HR 0.66; 95% CI 0.47–0.93; P=0.017) and in the trial-eligible cohort (HR 0.67; 95% CI 0.45–0.98; P=0.041). Conclusion In a large health care data set, the majority of patients with newly diagnosed AF were eligible for the trial. Early rhythm-control therapy was associated with a 15% reduction in the composite end point of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction, with the greatest benefit in the reduction of stroke risk. The treatment effect was consistent between patients eligible or ineligible for the trial. Patients in routine practice had higher rates of adverse outcomes than the trial, but the relative risk reduction with early rhythm-control therapy was similar. These data demonstrate the potential of early rhythm-control therapy to reduce outcomes in patients with AF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Heart Foundation (Mit Fördermitteln der Deutschen Herzstiftung e.V.)

OBJECTIVE To examine whether glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) are preferentially initiated among patients with cardiovascular disease, heart failure (HF), or nephropathy, where these drug classes have established benefit, compared with dipeptidyl peptidase 4 inhibitors (DPP-4i), for which corresponding benefits have not been demonstrated. RESEARCH DESIGN AND METHODS We retrospectively analyzed claims of adults with type 2 diabetes included in OptumLabs Data Warehouse, a deidentified database of commercially insured and Medicare Advantage beneficiaries, who first started GLP-1RA, SGLT2i, or DPP-4i therapy between 2016 and 2019. Using multinomial logistic regression, we examined the relative risk ratios (RRR) of starting GLP-1RA and SGLT2i compared with DPP-4i for those with a history of myocardial infarction (MI), cerebrovascular disease, HF, and nephropathy after adjusting for demographic and other clinical factors. RESULTS We identified 75,395 patients who started GLP-1RA, 58,234 who started SGLT2i, and 91,884 who started DPP-4i. Patients with prior MI, cerebrovascular disease, or nephropathy were less likely to start GLP-1RA rather than DPP-4i compared with patients without these conditions (RRR 0.83 [95% CI 0.78–0.88] for MI, RRR 0.77 [0.74–0.81] for cerebrovascular disease, and RRR 0.87 [0.84–0.91] for nephropathy). Patients with HF or nephropathy were less likely to start SGLT2i (RRR 0.83 [0.80–0.87] for HF and RRR 0.57 [0.55–0.60] for nephropathy). Both medication classes were less likely to be started by non-White and older patients. CONCLUSIONS Patients with cardiovascular disease, HF, and nephropathy, for whom evidence suggests a greater likelihood of benefiting from GLP-1RA and/or SGLT2i therapy, were less likely to start these drugs. Addressing this treatment/benefit paradox, which was most pronounced in non-White and older patients, may help reduce the morbidity associated with these conditions.