History of Psychoactive Medication a Risk Factor for Neurocognitive Decline After Cardiac Surgery.

INTRODUCTION: Neurocognitive decline (NCD) is a common complication after cardiac surgery with implications for outcomes and quality of life. Identifying risk factors can help surgeons implement preventative measures, optimize modifiable risk factors, and counsel patients about risk and prognosis. METHODS: Prospective cohort study at a single academic center. 104 patients planned to undergo cardiac surgery were enrolled. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to measure neurocognitive function preoperatively, on postoperative day four, and postoperative day 30. NCD is defined as a change in RBANS scaled score of < -8 from baseline to postoperative day 4. Patient charts were reviewed for medication history: beta-blockers, angiotensin-converting enzyme and angiotensin receptor blockers, calcium channel blockers, statins, oral hypoglycemic agents, and psychoactive medications. Charts were also reviewed to calculate postoperative opioid usage. RESULTS: NCD was detected in 42.9% of patients. Incidence of NCD was significantly higher in patients taking a psychoactive medication (56.8%) than patients not (31.9%), P < 0.03. There was no relationship between historical use of beta-blocker, calcium-channel blocker, statin, or oral hypoglycemic medications and incidence of NCD. Simple linear regression showed no relationship between change in RBANS total scaled score and opioid usage. There was no difference in incidence of NCD at 1 mo. CONCLUSIONS: Patients with a history of taking psychoactive medications prior to cardiac surgery have an increased risk of acute postoperative NCD.

Pneumonia initiates a tauopathy.

Pneumonia causes short- and long-term cognitive dysfunction in a high proportion of patients, although the mechanism(s) responsible for this effect are unknown. Here, we tested the hypothesis that pneumonia-elicited cytotoxic amyloid and tau variants: (1) are present in the circulation during infection; (2) lead to impairment of long-term potentiation; and, (3) inhibit long-term potentiation dependent upon tau. Cytotoxic amyloid and tau species were recovered from the blood and the hippocampus following pneumonia, and they were present in the extracorporeal membrane oxygenation oxygenators of patients with pneumonia, especially in those who died. Introduction of immunopurified blood-borne amyloid and tau into either the airways or the blood of uninfected animals acutely and chronically impaired hippocampal information processing. In contrast, the infection did not impair long-term potentiation in tau knockout mice and the amyloid- and tau-dependent disruption in hippocampal signaling was less severe in tau knockout mice. Moreover, the infection did not elicit cytotoxic amyloid and tau variants in tau knockout mice. Therefore, pneumonia initiates a tauopathy that contributes to cognitive dysfunction.

Glycemic control is not associated with neurocognitive decline after cardiac surgery.

BACKGROUND: Whether perioperative glycemic control is associated with neurocognitive decline (NCD) after cardiac surgery was examined. METHODS: Thirty patients undergoing cardiac surgery utilizing cardiopulmonary bypass (CPB) were screened for NCD preoperatively and on postoperative day 4 (POD4). Indices of glucose control were examined. Serum cytokine levels were measured and human transcriptome analysis was performed on blood samples. Neurocognitive data are presented as a change from baseline to POD4 in a score standardized with respect to age and gender. RESULTS: A decline in neurocognitive function was identified in 73% (22/30) of patients on POD4. There was no difference in neurocognitive function between patients with elevated HbA1c levels preoperatively (p = .973) or elevated fasting blood glucose levels the morning of surgery (>126 mg/dl, p = .910), or a higher maximum blood glucose levels during CPB (>180 mg/dl, p = .252), or higher average glucose levels during CPB (>160 mg/dl, p = .639). Patients with postoperative leukocytosis (WBC ≥ 10.5) had more NCD when compared to their baseline function (p = .03). Patients with elevated IL-8 levels at 6 h postoperatively had a significant decline in NCD at POD4 (p = .04). Human transcriptome analysis demonstrated unique and differential patterns of gene expression in patients depending on the presence of DM and NCD. CONCLUSIONS: Perioperative glycemic control does not have an effect on NCD soon after cardiac surgery. The profile of gene expression was altered in patients with NCD with or without diabetes.

Lactobacillus plantarum probiotic induces Nrf2-mediated antioxidant signaling and eNOS expression resulting in improvement of myocardial diastolic function.

Yorkshire swine were fed standard diet (n = 7) or standard diet containing applesauce rich in caffeic acid with Lactobacillus plantarum (n = 7) for 3 wk. An ameroid constrictor was next placed around the left coronary circumflex artery, and the dietary regimens were continued. At 14 wk, cardiac function, myocardial perfusion, vascular density, and molecular signaling in ischemic myocardium were evaluated. The L. plantarum-applesauce augmented NF-E2-related factor 2 (Nrf2) in the ischemic myocardium and induced Nrf2-regulated antioxidant enzymes heme oxygenase-1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Improved left ventricular diastolic function and decreased myocardial collagen expression were seen in animals receiving the L. plantarum-applesauce supplements. The expression of endothelial nitric oxide synthase (eNOS) was increased in ischemic myocardial tissue of the treatment group, whereas levels of asymmetric dimethyl arginine (ADMA), hypoxia inducible factor 1α (HIF-1α), and phosphorylated MAPK (pMAPK) were decreased. Collateral-dependent myocardial perfusion was unaffected, whereas arteriolar and capillary densities were reduced as determined by α-smooth muscle cell actin and CD31 immunofluorescence in ischemic myocardial tissue. Dietary supplementation with L. plantarum-applesauce is a safe and effective method of enhancing Nrf2-mediated antioxidant signaling cascade in ischemic myocardium. Although this experimental diet was associated with a reduction in hypoxic stimuli, decreased vascular density, and without any change in collateral-dependent perfusion, the net effect of an increase in antioxidant activity and eNOS expression resulted in improvement in diastolic function.NEW & NOTEWORTHY Colonization of the gut microbiome with certain strains of L. Plantarum has been shown to convert caffeic acid readily available in applesauce to 4-vinyl-catechol, a potent activator of the Nrf2 antioxidant defense pathway. In this exciting study, we show that simple dietary supplementation with L. Plantarum-applesauce-mediated Nrf2 activation supports vascular function, ameliorates myocardial ischemic diastolic dysfunction, and upregulates expression of eNOS.

Predictors of patient radiation exposure during transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) exposes patients to radiation. OBJECTIVES: We sought to identify factors associated with higher radiation exposure and to quantify their relative influence, which may inform reduction of this hazard. METHODS: All TAVR procedures at Rhode Island Hospital between March 20, 2012 and February 12, 2017 were included. Procedures were performed by two co-primary operators using a Siemens Artis Zeego system. Radiation metrics were generated by the imaging system. The primary metric was dose-area product (DAP, Gy*cm2 ), and secondary metrics were reference point air kerma (mGy) and fluoroscopy time (minutes). Data collected for the STS/ACC TVT Registry were utilized to develop a multivariable linear regression model predicting DAP. RESULTS: In 294 TAVRs, median DAP was 169 Gy*cm2 [interquartile range (IQR) 106-238]. The r2 values for the full 27-variable DAP model and reduced eight-variable model were 0.457 and 0.420, respectively. Valve area, aortic insufficiency, and procedure year (suggesting absence of a learning curve) were non-significant predictors in the full model, while increasing weight, cutdown transfemoral access, higher pre-procedure creatinine and hemoglobin, and vascular complications predicted higher DAP in both models. Results were unchanged when DAP was log-transformed. Secondary models for air kerma and fluoroscopy time revealed similar predictors. CONCLUSION: Factors associated with increased procedural complexity and duration as well as radiation attenuation and scatter predict increased patient radiation exposure during TAVR. Modification of procedural technique, especially using percutaneous femoral vascular access, may facilitate reduction in exposure.

Impact of Packed Red Blood Cell and Platelet Transfusions in Patients Undergoing Dissection Repair.

BACKGROUND: Transfusion of blood products commonly occur in patients undergoing repair of acute type A aortic dissection (AADA). MATERIALS AND METHODS: The medical records of 102 AADA patients were retrospectively reviewed and stratified into cohorts by packed red blood cell (PRBC) and platelet units received: PRBC ≤2 units (n = 68) versus PRBC >2 units (n = 34); platelets ≤1 unit (n = 74) versus platelets >1 unit (n = 28). Continuous and categorical variables were assessed by analysis of variance testing and chi-square or Fisher's testing as appropriate. Multivariate logistic regression was applied to derive P values for post-transfusion complications. Kaplan-Meier survival analyses were used to compare the hospital length of stay (LOS) and survival rate at 1 mo and 1 y. RESULTS: Patients receiving >2 units of PRBC had a median LOS of 14 d versus 9 d for those receiving ≤2 units (P < 0.002). Transfusion of >2 units of PRBC was a risk factor for postoperative infection (odds ratio [OR] = 5.4, 95% confidence interval [CI]: 1.5-19.0, P = 0.009). Survival at 1 mo was 91% versus 94% (P = 0.783) and 1 y survival was 82% versus 93% (P = 0.269) between the two groups. Patients receiving >1 unit of platelets had a median LOS of 15 d versus 10 d for those receiving ≤1 unit (P = 0.005). Transfusion of >1 unit of platelets was a risk factor for postoperative atrial fibrillation and acute kidney injury (OR = 2.9, 95% CI: 1.1-7.6, P = 0.031; OR = 3.3, 95% CI: 1.2-9.4, P = 0.025, respectively). Survival at 1 mo was 93% versus 93% (P = 0.872) and 1 y survival was 81% versus 92% (P = 0.582) between the two groups. CONCLUSIONS: Transfusion of PRBC and platelets above a threshold increases the incidence of postoperative complications and hospital LOS among patients undergoing repair of AADA.

New continuous-flow total artificial heart and vascular permeability.

BACKGROUND: We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability. METHODS: Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry. RESULTS: There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance. CONCLUSIONS: There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability.

Patients with uncontrolled hypertension subjected to cardiopulmonary bypass have altered coronary vasomotor responses to serotonin.

BACKGROUND: We previously found that cardioplegic arrest and cardiopulmonary bypass are associated with altered coronary arteriolar response to serotonin in patients undergoing cardiac surgery. In this study, we investigated the effects of hypertension on coronary microvascular vasomotor tone in response to serotonin and alterations in serotonin receptor protein expression in the setting of cardioplegic arrest and cardiopulmonary bypass. METHODS: Coronary arterioles were dissected from harvested pre- and post-cardioplegic arrest and cardiopulmonary bypass right atrial tissue samples of patients undergoing cardiac surgery with normotension, well-controlled hypertension, and uncontrolled hypertension. Vasomotor tone was assessed by video-myography, and protein expression was measured with immunoblotting. RESULTS: Pre-cardioplegic arrest and cardiopulmonary bypass, serotonin induced moderate relaxation responses of coronary arterioles in normotension and well-controlled hypertension patients, whereas serotonin caused moderate contractile responses in uncontrolled hypertension patients. Post-cardioplegic arrest and cardiopulmonary bypass, serotonin caused contractile responses of coronary arterioles in all 3 groups. The post-cardioplegic arrest and cardiopulmonary bypass contractile response to serotonin was significantly higher in the uncontrolled hypertension group compared with the normotension or well-controlled hypertension groups (P < .05). Pre-cardioplegic arrest and cardiopulmonary bypass, expression of the serotonin 1A receptor was significantly lower in the uncontrolled hypertension group compared with the well-controlled hypertension and normotension groups (P = .01 and P < .001). Serotonin 1B receptor expression was higher in the uncontrolled hypertension group compared with the normotension or well-controlled hypertension groups post-cardioplegic arrest and cardiopulmonary bypass (P = .03 and P = .046). CONCLUSION: Uncontrolled hypertension is associated with an increased coronary contractile response of coronary microvessels to serotonin and altered serotonin receptor protein expression after cardioplegic arrest and cardiopulmonary bypass. These findings may contribute to a worse postoperative coronary spasm and worsened recovery of coronary perfusion in patients with uncontrolled hypertension after cardioplegic arrest and cardiopulmonary bypass and cardiac surgery.

Palliative care in the cardiovascular intensive care unit: A systematic review of current literature.

BACKGROUND: There has been an evolution in the disease severity and complexity of patients presenting to the cardiac intensive care unit (CICU). There are limited data evaluating the role of palliative care in contemporary CICU practice. METHODS: PubMed Central, CINAHL, EMBASE, Medline, Cochrane Library, Scopus, and Web of Science databases were evaluated for studies on palliative care in adults (≥18 years) admitted with acute cardiovascular conditions - acute myocardial infarction, cardiogenic shock, cardiac arrest, advanced heart failure, post-cardiac surgery, spontaneous coronary artery dissection, Takotsubo cardiomyopathy, and pulmonary embolism - admitted to the CICU, coronary care unit or cardiovascular intensive care unit from 1/1/2000 to 8/8/2022. The primary outcome of interest was the utilization of palliative care services. Secondary outcomes of included studies were also addressed. Meta-analysis was not performed due to heterogeneity. RESULTS: Of 5711 citations, 30 studies were included. All studies were published in the last seven years and 90 % originated in the United States. Twenty-seven studies (90 %) were retrospective analyses, with a majority from the National Inpatient Sample database. Heart failure was the most frequent diagnosis (47 %), and in-hospital mortality was reported in 67 % of studies. There was heterogeneity in the timing, frequency, and background of the care team that determined palliative care consultation. In two randomized trials, there appeared to be improvement in quality of life without an impact on mortality. CONCLUSIONS: Despite the growing recognition of the role of palliative care, there are limited data on palliative care consultation in the CICU.

Bridging the literacy gap for surgical consents: an AI-human expert collaborative approach.

Despite the importance of informed consent in healthcare, the readability and specificity of consent forms often impede patients' comprehension. This study investigates the use of GPT-4 to simplify surgical consent forms and introduces an AI-human expert collaborative approach to validate content appropriateness. Consent forms from multiple institutions were assessed for readability and simplified using GPT-4, with pre- and post-simplification readability metrics compared using nonparametric tests. Independent reviews by medical authors and a malpractice defense attorney were conducted. Finally, GPT-4's potential for generating de novo procedure-specific consent forms was assessed, with forms evaluated using a validated 8-item rubric and expert subspecialty surgeon review. Analysis of 15 academic medical centers' consent forms revealed significant reductions in average reading time, word rarity, and passive sentence frequency (all P < 0.05) following GPT-4-faciliated simplification. Readability improved from an average college freshman to an 8th-grade level (P = 0.004), matching the average American's reading level. Medical and legal sufficiency consistency was confirmed. GPT-4 generated procedure-specific consent forms for five varied surgical procedures at an average 6th-grade reading level. These forms received perfect scores on a standardized consent form rubric and withstood scrutiny upon expert subspeciality surgeon review. This study demonstrates the first AI-human expert collaboration to enhance surgical consent forms, significantly improving readability without sacrificing clinical detail. Our framework could be extended to other patient communication materials, emphasizing clear communication and mitigating disparities related to health literacy barriers.

Effect of Patient Sex on Neurocognitive Decline after Cardiac Surgery.

BACKGROUND: Neurocognitive decline (NCD) is a common complication of cardiac surgery. Understanding risk factors helps surgeons counsel patients pre- and perioperatively about risk, prevention, and treatment. STUDY DESIGN: Patients undergoing cardiac surgery using cardiopulmonary bypass underwent pre- and postoperative neurocognitive testing. Neurocognitive data are presented as a change from baseline to either postoperative day 4 or to 1 month. The score is standardized with respect to age. RESULTS: Eighty-four patients underwent surgery and completed postoperative neurocognitive testing. There was no significant difference in baseline neurocognitive function. NCD was more common in female patients (71%) than male patients (26.4%) on postoperative day 4. By 1 month, the incidence of NCD is similar between female (15.0%) and male patients (14.3%). Of note, female patients differed from male patients in preoperative hematocrit, preoperative creatinine, and type of surgery. CONCLUSIONS: In the acute postoperative period, female patients are both more likely to experience NCD and experience a more severe change from baseline cognitive function. This difference between male and female patients resolves by the 1 month follow-up point. Female patients had a lower preoperative hematocrit and were more likely to receive intraoperative and perioperative blood transfusion. Lower preoperative hematocrit appears to mediate the difference in NCD between male and female patients.

Poorly controlled hypertension is associated with increased coronary myogenic tone in patients undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: Cardioplegia and cardiopulmonary bypass dysregulate coronary vasomotor tone, which can be further affected by common comorbidities in patients undergoing cardiac surgery. This study investigates differences in coronary myogenic tone and vasomotor responses to phenylephrine before and after cardioplegia and cardiopulmonary bypass based on hypertension history. METHODS: Coronary arterioles before and after cardioplegia and cardiopulmonary bypass were dissected from atrial tissue samples in patients with no hypertension, well-controlled hypertension, or uncontrolled hypertension, as determined by documented history of hypertension, antihypertensive agent use, and clinical blood pressure measurements averaged over 1 year. Myogenic tone in response to stepwise increases in intraluminal pressure was studied between pressure steps. Microvascular reactivity in response to phenylephrine was assessed via vessel myography. Protein expression was measured with immunoblotting. RESULTS: Coronary myogenic tone was significantly increased in the uncontrolled hypertension group compared with the no hypertension and well-controlled hypertension groups before cardioplegia and cardiopulmonary bypass at higher intraluminal pressures, and after cardioplegia and cardiopulmonary bypass across all intraluminal pressures (P < .05). Contractile responses to phenylephrine were significantly enhanced in patients in the uncontrolled hypertension group compared with the well-controlled hypertension group before cardioplegia and cardiopulmonary bypass, and in the uncontrolled hypertension group compared with the no hypertension and well-controlled hyertension groups after cardioplegia and cardiopulmonary bypass (P < .05). There were no differences in myogenic tone or phenylephrine-induced reactivity between the no hypertension and well-controlled hypertension groups (P > .05). There was increased expression of phosphorylated protein kinase C alpha in the uncontrolled hypertension group after cardiopulmonary bypass compared with before cardiopulmonary bypass and increased phosphorylated extracellular signal-regulated kinase 1/2 in the uncontrolled hypertension compared with the no hypertension group after cardiopulmonary bypass (P < .05). CONCLUSIONS: Uncontrolled hypertension is associated with increased coronary myogenic tone and vasoconstrictive response to phenylephrine that persists after cardioplegia and cardiopulmonary bypass.

Left Ventricular Septal Avulsion in the Setting of Blunt Cardiac Injury.

A 23-year-old man sustained blunt cardiac injury after a motor vehicle collision resulting in left ventricular septal avulsion, ruptured chordae tendineae, and moderate to severe tricuspid regurgitation that necessitated operative intervention. The patient underwent successful resection of a prolapsed avulsed septal wall segment and concomitant tricuspid valve repair.

Interpretable machine learning-based predictive modeling of patient outcomes following cardiac surgery.

BACKGROUND: The clinical applicability of machine learning predictions of patient outcomes following cardiac surgery remains unclear. We applied machine learning to predict patient outcomes associated with high morbidity and mortality after cardiac surgery and identified the importance of variables to the derived model's performance. METHODS: We applied machine learning to the Society of Thoracic Surgeons Adult Cardiac Surgery Database to predict postoperative hemorrhage requiring reoperation, venous thromboembolism (VTE), and stroke. We used permutation feature importance to identify variables important to model performance and a misclassification analysis to study the limitations of the model. RESULTS: The study dataset included 662,772 subjects who underwent cardiac surgery between 2015 and 2017 and 240 variables. Hemorrhage requiring reoperation, VTE, and stroke occurred in 2.9%, 1.2%, and 2.0% of subjects, respectively. The model performed remarkably well at predicting all 3 complications (area under the receiver operating characteristic curve, 0.92-0.97). Preoperative and intraoperative variables were not important to model performance; instead, performance for the prediction of all 3 outcomes was driven primarily by several postoperative variables, including known risk factors for the complications, such as mechanical ventilation and new onset of postoperative arrhythmias. Many of the postoperative variables important to model performance also increased the risk of subject misclassification, indicating internal validity. CONCLUSIONS: A machine learning model accurately and reliably predicts patient outcomes following cardiac surgery. Postoperative, as opposed to preoperative or intraoperative variables, are important to model performance. Interventions targeting this period, including minimizing the duration of mechanical ventilation and early treatment of new-onset postoperative arrhythmias, may help lower the risk of these complications.

Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

Extracellular vesicles improve diastolic function and substructure in normal and high-fat diet models of chronic myocardial ischemia.

OBJECTIVE: The burden of mortality and morbidity of cardiovascular disease is in part due to substantial fibrosis accelerated by coexisting risk factors. This study aims to evaluate the effect of extracellular vesicle therapy on diastolic function and myocardial fibrosis in the setting of chronic myocardial ischemia with and without a high-fat diet. METHODS: Forty male Yorkshire swine were administered a normal or high-fat diet. At 11 weeks of age, they underwent placement of an ameroid constrictor on their left circumflex coronary artery. Both dietary groups then received either intramyocardial injection of vehicle saline as controls or extracellular vesicles as treatment into the ischemic territory (normal diet control, n = 8; high-fat diet controls, n = 11) or extracellular vesicles (normal diet extracellular vesicles, n = 9; high-fat diet extracellular vesicles, n = 12). Five weeks later, hemodynamic parameters, histology, and selected protein expression were evaluated. RESULTS: Extracellular vesicles reduced end-diastolic pressure volume relationship (P = .002), perivascular collagen density (P = .031), calcium mineralization (P = .026), and cardiomyocyte diameter (P < .0001), and upregulated osteopontin (P = .0046) and mechanistic target of rapamycin (P = .021). An interaction between extracellular vesicles and diet was observed in the vimentin area (P = .044) and fraction of myofibroblast markers to total vimentin (P = .049). Significant changes across diet were found with reductions in muscle fiber area (P = .026), tumor necrosis factor α (P = .0002), NADPH oxidase 2 and 4 (P = .0036, P = .008), superoxide dismutase 1 (P = .034), and phosphorylated glycogen synthase kinase 3ß (P = .020). CONCLUSIONS: Extracellular vesicle therapy improved the myocardium's ability to relax and is likely due to structural improvements at the extracellular matrix and cellular levels.

Increased Access to Cardiac Surgery Did Not Improve Outcomes: Early Look Into Medicaid Expansion.

BACKGROUND: Cardiac surgery utilization has increased after passage of the Affordable Care Act. This multistate study examined whether changes in access after Medicaid expansion (ME) have led to improved outcomes, overall and particularly among ethnoracial minorities. METHODS: State Inpatient Databases were used to identify nonelderly adults (ages 18-64 years) who underwent coronary artery bypass grafting, aortic valve replacement, mitral valve replacement, or mitral valve repair in 3 expansion (Kentucky, New Jersey, Maryland) vs 2 nonexpansion states (North Carolina, Florida) from 2012 to 2015. Linear and logistic interrupted time series were used with 2-way interactions and adjusted for patient-level, hospital-level, and county-level factors to compare trends and instantaneous changes at the point of ME implementation (quarter 1 of 2014) for mortality, length of stay, and elective status. Interrupted time series models estimated expansion effect, overall and by race-ethnicity. RESULTS: Analysis included 22 038 cardiac surgery patients from expansion states and 33 190 from nonexpansion states. In expansion states, no significant trend changes were observed for mortality (odds ratio, 1.01; P = .83) or length of stay (ß = -0.05, P = .20), or for elective surgery (odds ratio, 1.00; P = .91). There were similar changes seen in nonexpansion states. Among ethnoracial minorities, ME did not impact outcomes or elective status. CONCLUSIONS: Despite an increase in cardiac surgery utilization after ME, outcomes remained unchanged in the early period after implementation, overall and among ethnoracial minorities. Future research is needed to confirm long-term trends and examine reasons behind this lack of improved outcomes.