Faculty Bibliography

BACKGROUND:Cardiometabolic risk factors diabetes, obesity, and hypertension are highly prevalent and contribute to increased cardiovascular disease (CVD). Endothelial dysfunction precedes CVD development. The current study aimed to investigate the EC transcriptome among individuals with varying degree of cardiometabolic risk. METHODS:Adult participants without CVD and various degrees of cardiometabolic risk factor burden (hypertension, diabetes, obesity) were included. Participants underwent brachial vein EC harvesting followed by RNA sequencing. To evaluate the association between cardiometabolic comorbidity burden and outcome transcripts we performed linear regression with multivariable models, adjusting for age, sex, and race/ethnicity. RESULTS:A total of 18 individuals were included in the present analysis (mean age 47 ± 14, 44% female, and 61% White adults). Endothelial cell RNA sequencing revealed 588 differentially expressed transcripts (p-adj <0.05) with excellent discrimination in unsupervised hierarchical clustering analysis. Gene ontology enrichment analysis revealed upregulated pathways associated with T-cell activation (NES = 2.22, p<0.001), leukocyte differentiation (NES= 2.16, p<0.001), leukocyte migration (NES= 2.12, p<0.001), regulation of cell-cell adhesion (NES= 1.91, p=0.006). Downregulated pathways of interest included endothelial cell proliferation (NES= -1.68, p=0.03) and response to interleukin-1 (NES= -1.61, p=0.04). Upregulated genes included VCAM1, CEACAM1, ADAM 17, and CD99L2, all with a log-2-fold change >3 and p-adj <0.05. These genes demonstrated a graded increase in mean normalized counts with increasing number of risk factors. CONCLUSIONS:We demonstrate a proinflammatory and pro-adhesive EC transcriptome associated with increased cardiometabolic risk factor burden offering insight into a potential mechanism linking these risk factors with the development of CVD.

INTRODUCTION:Cryoballoon ablation is commonly used to treat atrial fibrillation (AF). Femoral vein hemostasis after cryoballoon ablation for AF is routinely achieved with manual pressure (MP) after reversal of heparin and reassessment of the activated clotting time, or with a figure-of-eight suture (F8). The purpose of this randomized trial was to compare these two techniques for femoral vein hemostasis after cryoballoon ablation for AF in a patient population predominantly on novel anticoagulants (NOAC). METHODS AND RESULTS:Seventy consecutive patients who underwent cryoballoon ablation were randomized to either the MP or F8 for femoral vein hemostasis. Clinical and procedural characteristics were similar between the groups with the majority of patients treated with a NOAC. The total time in the electrophysiology laboratory for the MP group and the F8 group (197 ± 37 minutes vs 167 ± 36 minutes, respectively; P = .02), and the time from sheath removal until the patient left the laboratory (28 ± 9 minutes vs 20 ± 5 minutes, respectively; P < .0001) were significantly less in the F8 group. Additional pressure for hemostasis in the recovery suite was required more often in the MP Group, as opposed to the F8 group (29% vs 3%; P = .003). No major bleeding occurred and the rate of minor hematomas was statistically similar. CONCLUSIONS:Hemostasis obtained with a F8 suture after cryoballoon ablation for AF is associated with significantly less patient time in the electrophysiology laboratory, and an improved safety profile, compared with manual hemostasis, even amongst patients treated with a NOAC.

Women more often present with angina and non-obstructive coronary artery disease (ANOCA) and have poorer clinical outcomes than men. These findings may be related to sex associated differences in inflammation and thrombogenicity. Consecutive patients (n = 134) with ANOCA (luminal diameter stenosis < 50%) undergoing elective cardiac catheterization were included in post hoc analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Patients with prior revascularization, coronary artery bypass grafting or myocardial infarction were excluded. Blood for thromboelastography, oxidized LDL β2-glycoprotein complex (AtherOx), oxidized-LDL, lipid profile, and urine for 11-dehydrothromboxane B₂ (dTxB₂) were obtained before catheterization. All women (n = 75) were post-menopausal and tended to be older than men (61.4 ± 10.6 vs. 58.6 ± 9.9 year, p = 0.12), and were significantly more thrombogenic with higher thrombin-induced platelet-fibrin strength (TIP-FCS, mm) (68.0 ± 4.5 vs. 64.5 ± 6.2 mm, p = 0.001), clotting index (0.35 ± 2.22 vs. - 0.72 ± 2.75, p = 0.02), K (measure of the speed to reach 20 mm of clot strength from an amplitude of 2 mm) (2.2 ± 1.6 vs. 1.7 ± 0.5 min, p = 0.01), and fibrinogen activity (degrees) (66.6 ± 7.1 vs. 62.9 ± 7.5, p = 0.009). Markers of inflammation were not significantly different between the two groups. Women had higher total cholesterol, total LDL, LDL subtypes 1 and 2, total HDL, HDL subtypes 2 and 3, and ApoA1 (p < 0.05 for all). On multivariate regression, TIP-FCS remained significantly higher in women (p < 0.0001). Women with ANOCA are more thrombogenic than men. This fundamental difference in thrombogenicity may affect gender-related outcomes and warrants further investigation.

BACKGROUND:The Affordable Care Act's Medicaid expansion has been heavily debated due to skepticism about Medicaid's ability to provide high-quality care. Particularly, little is known about whether Medicaid expansion improves access to surgical cancer care at high-quality hospitals. To address this question, we examined the effects of the 2001 New York Medicaid expansion, the largest in the pre-Affordable Care Act era, on this disparity measure. STUDY DESIGN:We identified 67,685 nonelderly adults from the New York State Inpatient Database who underwent select cancer resections. High-quality hospitals were defined as high-volume or low-mortality hospitals. Disparity was defined as model-adjusted difference in percentage of patients receiving operations at high-quality hospitals by insurance type (Medicaid/uninsured vs privately insured) or by race (African American vs white). Levels of disparity were calculated quarterly for each comparison pair and then analyzed using interrupted time series to evaluate the impact of Medicaid expansion. RESULTS:Disparity in access to high-volume hospitals by insurance type was reduced by 0.97 percentage points per quarter after Medicaid expansion (p < 0.0001). Medicaid/uninsured beneficiaries had similar access to low-mortality hospitals as the privately insured; no significant change was detected around expansion. Conversely, racial disparity increased by 0.87 percentage points per quarter (p < 0.0001) in access to high-volume hospitals and by 0.48 percentage points per quarter (p = 0.005) in access to low-mortality hospitals after Medicaid expansion. CONCLUSIONS:Pre-Affordable Care Act Medicaid expansion reduced the disparity in access to surgical cancer care at high-volume hospitals by payer. However, it was associated with increased racial disparity in access to high-quality hospitals. Addressing racial barriers in access to high-quality hospitals should be prioritized.

BACKGROUND:Centralization of complex surgical care has led patients to travel longer distances. Emerging evidence suggested a negative association between increased travel distance and mortality after pancreatectomy. However, the reason for this association remains largely unknown. We sought to unravel the relationships among travel distance, receiving pancreatectomy at high-volume hospitals, delayed surgery, and operative outcomes. STUDY DESIGN/METHODS:We identified 44,476 patients who underwent pancreatectomy for neoplasms between 2004 and 2013 at the reporting facility from the National Cancer Database. Multivariable analyses were performed to examine the independent relationships between increments in travel distance mortality (30-day and long-term survival) after adjusting for patient demographics, comorbidity, cancer stage, and time trend. We then examined how additional adjustment of procedure volume affected this relationship overall and among rural patients. RESULTS:Median travel distance to undergo pancreatectomy increased from 16.5 to 18.7 miles (p for trend < 0.001). Although longer travel distance was associated with delayed pancreatectomy, it was also related to higher odds of receiving pancreatectomy at a high-volume hospital and lower postoperative mortality. In multivariable analysis, difference in mortality among patients with varying travel distance was attenuated by adjustment for procedure volume. However, longest travel distance was still associated with a 77% lower 30-day mortality rate than shortest travel among rural patients, even when accounting for procedure volume. CONCLUSIONS:Our large national study found that the beneficial effect of longer travel distance on mortality after pancreatectomy is mainly attributable to increase in procedure volume. However, it can have additional benefits on rural patients that are not explained by volume. Distance can represent a surrogate for rural populations.

BACKGROUND:Although the Affordable Care Act (ACA) expanded Medicaid access, it is unknown whether this has led to greater access to complex surgical care. Evidence on the effect of Medicaid expansion on access to surgical cancer care, a proxy for complex care, is sparse. Using New York's 2001 statewide Medicaid expansion as a natural experiment, we investigated how expansion affected use of surgical cancer care among beneficiaries overall and among racial minorities. STUDY DESIGN/METHODS:From the New York State Inpatient Database (1997 to 2006), we identified 67,685 nonelderly adults (18 to 64 years of age) who underwent cancer surgery. Estimated effects of 2001 Medicaid expansion on access were measured on payer mix, overall use of surgical cancer care, and percent use by racial/ethnic minorities. Measures were calculated quarterly, adjusted for covariates when appropriate, and then analyzed using interrupted time series. RESULTS:The proportion of cancer operations paid by Medicaid increased from 8.9% to 15.1% in the 5 years after the expansion. The percentage of uninsured patients dropped by 21.3% immediately after the expansion (p = 0.01). Although the expansion was associated with a 24-case/year increase in the net Medicaid case volume (p < 0.0001), the overall all-payer net case volume remained unchanged. In addition, the adjusted percentage of ethnic minorities among Medicaid recipients of cancer surgery was unaffected by the expansion. CONCLUSIONS:Pre-ACA Medicaid expansion did not increase the overall use or change the racial composition of beneficiaries of surgical cancer care. However, it successfully shifted the financial burden away from patient/hospital to Medicaid. These results might suggest similar effects in the post-ACA Medicaid expansion.