Publications

BACKGROUND: Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), which has persisted despite refinements in technique and increased operator experience. While cerebral embolic protection devices (EPDs) have been developed to mitigate this risk, data regarding their impact on stroke and other outcomes after TAVR are limited.

METHODS: We performed an observational study using data from the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients were included if they underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. The primary outcome was in-hospital stroke. To adjust for confounding, the association between EPD use and clinical outcomes was evaluated using instrumental variable analysis, a technique designed to support causal inference from observational data, with site-level preference for EPD use within the same quarter of the procedure as the instrument. We also performed a propensity score-based secondary analysis using overlap weights.

RESULTS: Our analytic sample included 123 186 patients from 599 sites. The use of EPD during TAVR increased over time, reaching 28% of sites and 13% of TAVR procedures by December 2019. There was wide variation in EPD use across hospitals, with 8% of sites performing >50% of TAVR procedures with an EPD and 72% performing no procedures with an EPD in the last quarter of 2019. In our primary analysis using the instrumental variable model, there was no association between EPD use and in-hospital stroke (adjusted relative risk, 0.90 [95% CI, 0.68-1.13]; absolute risk difference, -0.15% [95% CI, -0.49 to 0.20]). However, in our secondary analysis using the propensity score-based model, EPD use was associated with 18% lower odds of in-hospital stroke (adjusted odds ratio, 0.82 [95% CI, 0.69-0.97]; absolute risk difference, -0.28% [95% CI, -0.52 to -0.03]). Results were generally consistent across the secondary end points, as well as subgroup analyses.

CONCLUSIONS: In this nationally representative observational study, we did not find an association between EPD use for TAVR and in-hospital stroke in our primary instrumental variable analysis, and found only a modestly lower risk of in-hospital stroke in our secondary propensity-weighted analysis. These findings provide a strong basis for large-scale randomized, controlled trials to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR.

Pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality. Recent hospitalization or surgery is a leading risk factor for PE, yet there are minimal data examining its effect on treatment and outcomes. We conducted a retrospective review of institutional billing codes for hospitalized patients with acute PE from August 2012 to August 2018. Patients were stratified based on whether they had a recent major medical encounter (MME), defined as surgery or hospitalization within 90 days. Primary outcomes included in-hospital mortality and 30- and 90-day readmission rates. Secondary outcomes included length of stay (LOS), use of advanced therapies, major bleeding, discharge anticoagulation and recurrent venous thromboembolism (VTE) at 90 days. Outcomes were adjusted for confounders using multivariable regression modeling. 2063 patients were hospitalized for an acute PE; 633 (30.7%) had a recent MME. Patients with a recent MME had a higher average Charlson Comorbidity Index (4.6 vs. 4.0, p < 0.01). Both 30- and 90-day readmission rates were higher in patients with a recent MME (21.7% vs. 14.4%; adjusted OR 1.06 [1.00, 1.12], p = 0.037; 30.8% vs 18.7%; adjusted OR 1.11 [1.11, 1.62], p = 0.003, respectively). After adjustment, there were no between-group differences in in-hospital mortality, LOS, use of advanced therapies, major bleeding, or recurrent VTE at 90 days. In-hospital mortality was higher for patients with a recent medical hospitalization compared to those with a recent surgery (10.2% vs. 5.6%, adjusted OR 1.08 [1.01, 1.15] p = 0.032). Despite recent hospitalization and/or surgery and greater number of comorbidities, patients admitted with a PE and recent MME had similar in-hospital outcomes, but experienced higher readmission rates. In-hospital mortality was higher in those with a recent medical compared to surgical encounter. Clinicians should optimize post-discharge transitional care in this subset of patients.

BACKGROUND: Randomized controlled trials have reported excess mortality in patients treated with paclitaxel-coated devices versus uncoated devices, while observational studies have reported the opposite. This study aims to determine the underlying factors and cohort differences that may explain these opposite results, with specific focus on sex differences in treatment and outcomes.

METHODS: Multicenter health insurance claims data from a large insurance fund, BARMER, were studied. A homogeneous sample of patients with an index of endovascular revascularization for symptomatic peripheral arterial occlusive disease between 2013 and 2017 was included. Adjusted logistic regression and Cox regression models were used to determine the factors predicting allocation to paclitaxel-coated devices and sex-specific 5-year all-cause mortality, respectively.

RESULTS: In total, 13,204 patients (54% females, mean age 74 ± 11 years) were followed for a median of 3.5 years. Females were older (77 vs. 71 years), and had less frequent coronary artery disease (23% vs. 33%), dyslipidemia (44% vs. 50%), and diabetes (29% vs. 41%), as well as being less likely to have a history of smoking (10% vs. 15%) compared with males. Mortality differences were mostly attributable to the female subgroup who were revascularized above the knee (hazard ratio, HR 0.78, 95% CI: 0.64-0.95), while no statistically significant differences were observed in males.

CONCLUSIONS: This study found that females treated above the knee benefited from paclitaxel-coated devices, while no differences were found in males. Ongoing and future registries and trials should take sex disparities into account.

Background In the United States, hospitalizations for pulmonary embolism (PE) are increasing among older adults insured by Medicare. Although efforts to reduce health disparities have intensified, it remains unclear whether clinical outcomes differ between socioeconomically disadvantaged and nondisadvantaged Medicare beneficiaries hospitalized with PE. Methods and Results In this study, there were 53 386 Medicare fee-for-service beneficiaries age ≥65 years hospitalized for PE between October 2015 and January 2017. Of these, 5494 (10.3%) were socioeconomically disadvantaged and 47 892 (89.7%) were nondisadvantaged. Socioeconomically disadvantaged adults were of similar age as nondisadvantaged adults (77.1 versus 77.0), more likely to be female (68.5% versus 54.2%), and less likely to receive advanced therapies (11.0% versus 12.1%). After adjustment for demographics, 90-day all-cause mortality rates were similar between disadvantaged and nondisadvantaged adults. In contrast, 1-year mortality rates were higher among socioeconomically disadvantaged adults (hazard ratio [HR], 1.16; 95% CI, 1.10-1.22), although these differences were partially attenuated after additional adjustments for comorbidities and PE severity (HR, 1.09; 95% CI, 1.02-1.16). Risk-adjusted 30-day and 90-day all-cause readmission rates were substantially higher among socioeconomically disadvantaged patients (30-day HR, 1.14 [95% CI, 1.06-1.22]; 90-day HR, 1.18 [95% CI, 1.12-1.25]). In addition, 90-day readmissions attributed to PE, deep vein thrombosis, and/or bleeding were higher among socioeconomically disadvantaged patients (HR, 1.16; 95% CI, 1.02-1.32). Conclusions Socioeconomically disadvantaged older adults hospitalized with PE have higher 1-year mortality rates compared with their nondisadvantaged counterparts. Nearly 1 in 3 socioeconomically disadvantaged older adults was readmitted within 90 days of a hospitalization for PE. Targeted strategies are needed to improve transitional and ambulatory care for this vulnerable population.

Statistical analyses are a crucial component of the biomedical research process and are necessary to draw inferences from biomedical research data. The application of sound statistical methodology is a prerequisite for publication in the American Heart Association (AHA) journal portfolio. The objective of this document is to summarize key aspects of statistical reporting that might be most relevant to the authors, reviewers, and readership of AHA journals. The AHA Scientific Publication Committee convened a task force to inventory existing statistical standards for publication in biomedical journals and to identify approaches suitable for the AHA journal portfolio. The experts on the task force were selected by the AHA Scientific Publication Committee, who identified 12 key topics that serve as the section headers for this document. For each topic, the members of the writing group identified relevant references and evaluated them as a resource to make the standards summarized herein. Each section was independently reviewed by an expert reviewer who was not part of the task force. Expert reviewers were also permitted to comment on other sections if they chose. Differences of opinion were adjudicated by consensus. The standards presented in this report are intended to serve as a guide for high-quality reporting of statistical analyses methods and results.

Heart failure (HF) is common in patients presenting with acute myocardial infarction (MI), but incidence and predictors of new onset HF after hospitalization for MI are less well characterized. We evaluated patients hospitalized for acute MI without preceding or concurrent HF in the National Cardiovascular Data Registry (NCDR) CathPCI and Chest Pain-MI registries linked with claims data between April 2010 and March 2017. Cumulative incidence and independent predictors of HF after discharge were determined, and a simplified risk score was developed to predict incident HF following MI. In 337,274 patients with acute MI and no history of HF, 8.0% developed incident HF within 1 year after discharge and 18.8% developed HF within 5 years. Significant predictors of HF after MI included advanced chronic kidney disease (CKD) (HR 2.34, 95% confidence interval [CI] 2.23-2.46 for Stage IV vs Stage I, and HR 2.18, 95% CI 2.07-2.29 for Stage V vs. Stage I), recurrent MI following index MI (HR 2.24, 95% CI 2.19-2.28), African-American race (HR 1.44, 95% CI 1.40-1.48), and diabetes (HR 1.39, 95% CI 1.37-1.42). A risk score of 8 variables predicted HF with modest discrimination (optimism-corrected c-statistic 0.64) and good calibration. In conclusion, nearly 1 in 5 patients in a large nationally representative cohort without preceding or concurrent heart failure at time of MI developed incident HF within 5 years after discharge. Advanced CKD and recurrent MI were the strongest predictors of future HF. Increased recognition of specific risk factors for HF may help inform care strategies following MI.

IMPORTANCE: Paclitaxel-coated peripheral devices have been associated with increased mortality, yet this harm signal has not been replicated outside of meta-analyses of small trials.

OBJECTIVE: To provide a longitudinal assessment of the safety of femoropopliteal endovascular treatment with peripheral drug-coated devices (DCDs) among Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS: SAFE-PAD (Safety Assessment of Femoropopliteal Endovascular Treatment With Paclitaxel-Coated Devices) was a retrospective cohort study designed with the US Food and Drug Administration to evaluate the noninferiority of mortality between DCDs and non-drug-coated devices (NDCDs) for femoropopliteal revascularization performed in 2978 inpatient and outpatient facilities in the US from April 1, 2015, through December 31, 2018. Evaluation of the primary outcome was assessed through May 31, 2020. Participants were Medicare fee-for-service beneficiaries 66 years and older with 1 or more years of enrollment prior to femoropopliteal revascularization. Prespecified subgroups included low-risk cohorts, procedure location, disease severity, and device type. Inverse probability weighting was used to account for imbalances of observed characteristics. Sensitivity analyses were used to evaluate the potential influence of unmeasured confounding.

EXPOSURES: Treatment with DCDs vs NDCDs as determined by claims codes during the index procedure.

MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality. Secondary outcomes included repeated hospitalization, repeated lower extremity revascularization, and lower extremity amputation. Falsification end points were acute myocardial infarction, congestive heart failure, and pneumonia.

RESULTS: Of 168 553 patients, 70 584 (41.9%) were treated with a DCD. The mean (SD) age was 77.0 (7.6) years, 75 744 (44.9%) were female, 136 916 of 167 197 (81.9%) were White individuals, 85 880 of 168 553 (51.0%) had diabetes, 82 554 of 168 553 (49.0%) used tobacco, 78 665 of 168 553 (45.7%) had critical limb ischemia (CLI), and 13 296 of 168 553 (7.9%) had a prior amputation. Median follow-up was 2.72 years (interquartile range, 0.87-3.77; longest, 5.16 years). After weighting, the cumulative incidence of all-cause mortality was 53.8% with DCDs and 55.1% with NDCDs (hazard ratio [HR], 0.95; 95% CI, 0.94-0.97; noninferiority P < .001). Cox regression and instrumental variable analyses were consistent with the primary findings. No harm associated with DCDs was observed among subgroups, including those treated with stents (HR, 0.97; 95% CI, 0.95-1.00) or balloons (HR, 0.94; 95% CI, 0.92-0.96), with or without CLI (CLI: HR, 0.95; 95% CI, 0.93-0.97; non-CLI: HR, 0.97; 95% CI, 0.95-0.99), and those within the lowest quartile of total comorbidities (HR, 0.95; 95% CI, 0.92-0.99).

CONCLUSIONS AND RELEVANCE: In this initial report from the SAFE-PAD cohort study, DCDs were found to be noninferior to NCDCs in respect to mortality through a median follow-up of 2.72 years. This finding remained robust in sensitivity analyses and was consistent across prespecified subgroups.