Characteristics of Clinical Trial Sites for Novel Transcatheter Mitral and Tricuspid Valvular Therapies.

Importance: Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials. Efforts have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, there may be differences in the patient populations of the sites that participate in clinical trials. Objective: To identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did vs did not participate in trials for novel transcatheter therapies. Design, Setting, and Participants: This cross-sectional analysis used Medicare Provider Claims from 2019 for patients admitted to hospitals in the US. All clinical trials for transcatheter mitral and tricuspid valve therapies and the hospitals participating in each of the trials were identified using ClinicalTrials.gov. Hospitals with active cardiac surgical programs that did not participate in the trials were also identified. Data analysis was performed between July 2021 and July 2022. Exposures: Multivariable linear regression models were used to identify differences in racial, ethnic, and socioeconomic characteristics among patients undergoing cardiac surgery or transcatheter aortic valve replacement at trial vs nontrial hospitals. Main Outcome and Measures: The main outcome of the study was participation in a clinical trial for novel transcatheter mitral or tricuspid valve therapies. Results: A total of 1050 hospitals with cardiac surgery programs were identified, of which 121 (11.5%) participated in trials for transcatheter mitral or tricuspid therapies. Patients treated in trial hospitals had a higher median zip code-based household income (difference of $5261; 95% CI, $2986-$7537), a lower Distressed Communities Index score (difference of 5.37; 95% CI, 2.59-8.15), and no significant difference in the proportion of patients dual eligible for Medicaid (difference of 0.86; 95% CI, -2.38 to 0.66). After adjusting for each of the socioeconomic indicators separately, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating vs not participating in clinical trials. Conclusions and Relevance: In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than nontrial hospitals, with a similar proportion of Black and Hispanic patients. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.

Identifying Racial, Ethnic, and Socioeconomic Inequities in the Use of Novel P2Y12 Inhibitors After Percutaneous Coronary Intervention.

BACKGROUND: Novel P2Y12 inhibitors prasugrel and ticagrelor were approved for patients with acute coronary syndrome (ACS) in 2009 and 2011, respectively. We assessed the association of racial, ethnic, and socioeconomic factors with initiation of and adherence to novel P2Y12 inhibitors in a commercially insured population. METHODS: We performed a retrospective cohort analysis of adults undergoing percutaneous coronary intervention with placement of a drug-eluting stent, stratified by ACS status, between January 2008 and December 2016 using Clinformatics Data Mart (OptumInsight). We estimated multivariable logistic regression models to identify factors associated with the initiation of clopidogrel vs novel P2Y12 inhibitors as well as subsequent 6-month medication adherence, assessed via pharmacy records. RESULTS: A total of 55,664 patients were included in the analysis. Hispanic ethnicity was independently associated with the initiation of clopidogrel compared with novel P2Y12 inhibitors among ACS patients (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.04-1.36; P<.01). ACS patients with an annual median household income of over $100,000 were less likely to be started on clopidogrel when compared with those who earned less than $40,000 (OR, 0.67; 95% CI, 0.61-0.75; P<.01). Black race, Hispanic ethnicity, and lower household income were each associated with significantly reduced odds of P2Y12 inhibitor adherence. CONCLUSION: Hispanic ethnicity and lower household income were associated with novel P2Y12 inhibitor initiation, and non-White race and ethnicity were associated with lower P2Y12 inhibitor adherence over 6-month follow-up. These findings highlight continued inequity of care, even in an insured population, and point to a need for new strategies to close these gaps.

Safety of Intravenous Cangrelor Administration for Antiplatelet Bridging in Hospitalized Patients: A Retrospective Study.

OBJECTIVE: We aimed to characterize outcomes associated with cangrelor administration used in an antiplatelet bridging strategy in real-world clinical scenarios within a large academic medical system. BACKGROUND: Cangrelor has been used for antiplatelet bridging in perioperative settings or for patients unable to take oral medications. Prior studies in these settings have reported bleeding rates from 0%-40%. METHODS: Patients were retrospectively identified via chart review and included if they were over 18 years old, had coronary or peripheral arterial stents, and had received at least 1 hour of cangrelor infusion during inpatient admission. The primary endpoint was Bleeding Academic Research Consortium (BARC) 3-5 bleeding during cangrelor infusion or within 48 hours of discontinuation; secondary endpoints were bleeding events defined by Thrombolysis in Myocardial Infarction (TIMI), Global Use of Strategies to Open Occluded Arteries (GUSTO), and International Society on Thrombosis and Hemostasis (ISTH) criteria, as well as BARC 2 bleeding. RESULTS: Thirty-one patients met the inclusion criteria. Cangrelor indications were bridging to procedure in 22 patients (71.0%) and inability to take oral P2Y12 inhibitors in 9 patients (29.0%). Twenty-three patients (74.2%) were men, 11 patients (35.5%) were in cardiogenic shock, and 4 patients (12.9%) were on extracorporeal membrane oxygenation (ECMO) at the time of administration. No patients received cangrelor for routine percutaneous coronary intervention. Of the 31 patients, 13 (41.9%) had BARC 3-5 bleeding and 7 (22.6%) expired during hospitalization. All 4 patients on ECMO suffered BARC 3-5 bleeding. CONCLUSIONS: We reviewed the use of cangrelor for antiplatelet bridging in real-world clinical scenarios and observed higher rates of clinically significant bleeding than seen in other similar studies. Our study suggests careful consideration when using cangrelor in a sick patient population.

Observational study assessing changes in timing of readmissions around postdischarge day 30 associated with the introduction of the Hospital Readmissions Reduction Program.

BACKGROUND: The Hospital Readmissions Reduction Program (HRRP) initially penalised hospitals for excess readmission within 30 days of discharge for acute myocardial infarction (AMI), congestive heart failure (CHF) or pneumonia (PNA) and was expanded in subsequent years to include readmissions for chronic obstructive pulmonary disease, elective total hip arthroplasty, total knee arthroplasty and coronary artery bypass graft surgery. We assessed whether HRRP was associated with delays in readmissions from immediately before the 30-day penalty threshold to just after it. METHODS: We included Medicare fee-for-service beneficiaries discharged between 1 January 2007 and 31 October 2015. Readmissions were assessed until December 31, 2015. The study period was divided into three phases: January 2007 to March 2009 (pre-HRRP), April 2009 to September 2012 (implementation) and October 2012 to December 2015 (penalty). We estimated additional readmissions between postdischarge days 31-35 compared with days 26-30 using a negative binomial difference-in-differences model, comparing target HRRP versus non-HRRP conditions at the same hospital in the same month in the pre-HRRP and penalty phases. RESULTS: HRRP was not associated with a significant difference in AMI readmissions between postdischarge days 31-35 versus postdischarge days 26-30 for each hospital in the penalty phase, as compared with non-HRRP conditions and the pre-HRRP phase (p=0.19). There were statistically significant increases in readmissions CHF (0.040%, 95% CI 0.024% to 0.056%, p<0.01), PNA (0.022%, 95% CI 0.002% to 0.042%, p=0.03) and stroke (0.035%, 95% CI 0.010% to 0.060%, p<0.01); however, these readmissions represent <0.01% of readmissions during this time period. CONCLUSION: We did not identify consistently significant associations between HRRP and delayed readmissions, and importantly, any findings suggesting delayed readmissions were extremely small and unlikely to be clinically relevant.

Federal Payments for Coronary Revascularization Procedures Among Dual Enrollees in Medicare Advantage and the Veterans Affairs Health Care System.

Importance: More than 1 million US veterans are dually enrolled in a Medicare Advantage (MA) plan and in the Veterans Affairs (VA) health care system. The federal government prepays private MA plans to cover veterans; if a dually enrolled veteran receives an MA-covered service at the VA, the government is making 2 payments for the same service. It is not clear what proportion of veterans dually enrolled in VA and MA are undergoing coronary revascularization at VA vs non-VA hospitals. Objective: To describe where veterans who are enrolled in both VA and MA undergo coronary revascularization and the associated costs. Design, Settings, and Participants: This is a cohort study consisting of US veterans dually enrolled in VA and MA from January 1, 2010, to December 31, 2013, who had at least 1 VA encounter and underwent coronary revascularization during the study period. Data were analyzed from April 2019 to September 2019. Main Outcomes and Measures: Number of coronary artery bypass graft (CABG) operations and percutaneous coronary interventions (PCIs) performed through the VA and through MA during years 2010 to 2013, and the associated VA costs of coronary revascularization. In addition, multivariable logistic regression was performed to assess patient factors associated with receiving care through the VA. Results: A total of 18 874 VA users with concurrent MA enrollment who underwent coronary revascularization during 2010 to 2013 were identified (mean [SD] age, 75.3 [8.8] years; 18 739 men [99.0%]). Enrollees were predominantly white (17 457 patients [92.0%]). Among patients, 4115 (22.0%) underwent either CABG or PCI through the VA only, 14 281 (75.0%) did so through MA only, and 478 (2.5%) underwent coronary revascularization procedures through both payers. From 2010 to 2013, these veterans underwent 4764 coronary revascularization procedures (721 CABGs and 3043 PCIs) that cost the VA $214.7 million ($115.8 million for CABGs and $99.0 million for PCIs). In multivariable analysis, nonwhite patients were more likely than white patients to undergo coronary revascularization through the VA (odds ratio, 1.73; 95% CI, 1.52-1.96; P < .001), and for each year of age, veterans were less likely to undergo coronary revascularization through the VA (odds ratio, 0.95; 95% CI, 0.94-0.95; P < .001). There was no statistically significant association between undergoing coronary vascularization through the VA and distance in miles to the nearest VA hospital (odds ratio, 1.00; 95% CI, 0.99-1.00; P = .30). Conclusions and Relevance: A substantial share of VA users concurrently enrolled in an MA plan underwent coronary revascularization procedures through the VA, incurring significant duplicative federal health care spending. Given the financial pressures facing both Medicare and the VA, government officials should consider policy solutions to mitigate redundant spending.

The influence of an aligned nanofibrous topography on human mesenchymal stem cell fibrochondrogenesis.

Fibrocartilaginous tissues serve critical load-bearing functions in numerous joints throughout the body. As these structures are often injured, there exists great demand for engineered tissue for repair or replacement. This study assessed the ability of human marrow-derived mesenchymal stem cells (MSCs) to elaborate a mechanically functional, fibrocartilaginous matrix in a nanofibrous microenvironment. Nanofibrous scaffolds, composed of ultra-fine biodegradable polymer fibers, replicate the structural and mechanical anisotropy of native fibrous tissues and serve as a 3D micro-pattern for directing cell orientation and ordered matrix formation. MSCs were isolated from four osteoarthritic (OA) patients, along with meniscal fibrochondrocytes (FC) which have proven to be a potent cell source for engineering fibrocartilage. Cell-seeded nanofibrous scaffolds were cultured in a chemically-defined medium formulation and mechanical, biochemical, and histological features were evaluated over 9 weeks. Surprisingly, and contrary to previous studies with juvenile bovine cells, matrix assembly by adult human MSCs was dramatically hindered compared to donor-matched FCs cultured similarly. Unlike FCs, MSCs did not proliferate, resulting in sparsely colonized constructs. Increases in matrix content, and therefore changes in tensile properties, were modest in MSC-seeded constructs compared to FC counterparts, even when normalized to the lower cell number in these constructs. To rule out the influence of OA sourcing on MSC functional potential, constructs from healthy young donors were generated; these constructs matured no differently than those formed with OA MSCs. Importantly, there was no difference in matrix production of MSCs and FCs when cultured in pellet form, highlighting the sensitivity of human MSCs to their 3D microenvironment.

The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers.

Aligned electrospun scaffolds are promising tools for engineering fibrous musculoskeletal tissues, as they reproduce the mechanical anisotropy of these tissues and can direct ordered neo-tissue formation. However, these scaffolds suffer from a slow cellular infiltration rate, likely due in part to their dense fiber packing. We hypothesized that cell ingress could be expedited in scaffolds by increasing porosity, while at the same time preserving overall scaffold anisotropy. To test this hypothesis, poly(epsilon-caprolactone) (a slow-degrading polyester) and poly(ethylene oxide) (a water-soluble polymer) were co-electrospun from two separate spinnerets to form dual-polymer composite fiber-aligned scaffolds. Adjusting fabrication parameters produced aligned scaffolds with a full range of sacrificial (PEO) fiber contents. Tensile properties of scaffolds were functions of the ratio of PCL to PEO in the composite scaffolds, and were altered in a predictable fashion with removal of the PEO component. When seeded with mesenchymal stem cells (MSCs), increases in the starting sacrificial fraction (and porosity) improved cell infiltration and distribution after three weeks in culture. In pure PCL scaffolds, cells lined the scaffold periphery, while scaffolds containing >50% sacrificial PEO content had cells present throughout the scaffold. These findings indicate that cell infiltration can be expedited in dense fibrous assemblies with the removal of sacrificial fibers. This strategy may enhance in vitro and in vivo formation and maturation of functional constructs for fibrous tissue engineering.