Proteomic and phosphoproteomic characterization of cardiovascular tissues after long term exposure to simulated space radiation.

Introduction: It may take decades to develop cardiovascular dysfunction following exposure to high doses of ionizing radiation from medical therapy or from nuclear accidents. Since astronauts may be exposed continually to a complex space radiation environment unlike that experienced on Earth, it is unresolved whether there is a risk to cardiovascular health during long-term space exploration missions. Previously, we have described that mice exposed to a single dose of simplified Galactic Cosmic Ray (GCR5-ion) develop cardiovascular dysfunction by 12 months post-radiation. Methods: To investigate the biological basis of this dysfunction, here we performed a quantitative mass spectrometry-based proteomics analysis of heart tissue (proteome and phosphoproteome) and plasma (proteome only) from these mice at 8 months post-radiation. Results: Differentially expressed proteins (DEPs) for irradiated versus sham irradiated samples (fold-change ≥1.2 and an adjusted p-value of ≤0.05) were identified for each proteomics data set. For the heart proteome, there were 87 significant DEPs (11 upregulated and 76 downregulated); for the heart phosphoproteome, there were 60 significant differentially phosphorylated peptides (17 upregulated and 43 downregulated); and for the plasma proteome, there was only one upregulated protein. A Gene Set Enrichment Analysis (GSEA) technique that assesses canonical pathways from BIOCARTA, KEGG, PID, REACTOME, and WikiPathways revealed significant perturbation in pathways in each data set. For the heart proteome, 166 pathways were significantly altered (36 upregulated and 130 downregulated); for the plasma proteome, there were 73 pathways significantly altered (25 upregulated and 48 downregulated); and for the phosphoproteome, there were 223 pathways significantly affected at 0.1 adjusted p-value cutoff. Pathways related to inflammation were the most highly perturbed in the heart and plasma. In line with sustained inflammation, neutrophil extracellular traps (NETs) were demonstrated to be increased in GCR5-ion irradiated hearts at 12-month post irradiation. NETs play a fundamental role in combating bacterial pathogens, modulating inflammatory responses, inflicting damage on healthy tissues, and escalating vascular thrombosis. Discussion: These findings suggest that a single exposure to GCR5-ion results in long-lasting changes in the proteome and that these proteomic changes can potentiate acute and chronic health issues for astronauts, such as what we have previously described with late cardiac dysfunction in these mice.

Outcomes After Left Atrial Appendage Clip Placement During Cardiac Surgery: A Nationwide Analysis.

This study evaluated the nationwide associations between concomitant left atrial appendage clip (LAAC) placement during cardiac surgery and postoperative outcomes. We identified 1,260,999 patients who underwent coronary artery bypass grafting, valve, and aortic surgeries in the 2016 to 2020 Nationwide Readmissions Database and stratified by concomitant LAAC versus no LAAC placement. Patients who underwent surgical ablation were excluded. Mortality and complications were compared during index admissions and for patients readmitted within 30 and 90 days of the index discharge date for unmatched and propensity score-matched groups. Overall, 6.7% (84,293) of patients underwent cardiac surgery and concomitant LAAC placement without surgical ablation. After propensity score matching, the index admission mortality and overall complications were not different in patients with LAAC versus patients without LAAC. LAAC placement was associated with increased any-cause 30-day readmissions (15% vs 13%, p <0.01). In patients with LAAC, within 30 days, there were no differences in mortality (3.9% vs 3.8%, p = 0.60) or overall complications (64% vs 63%, p = 0.20), whereas stroke was lower (5.3% vs 6.5%, p <0.01) and heart failure was higher (35% vs 30%, p <0.01). For patients readmitted within 90 days, similar findings were observed for any-cause readmissions, mortality, overall complications, stroke, and heart failure. In conclusion, concomitant LAAC placement during cardiac surgery was associated with lower early postdischarge incidence of stroke and a favorable overall risk-benefit profile. Given these short-term findings in a real-world population of all patients who underwent cardiac surgery, longer-term studies with more granular data are needed to evaluate the potential benefit of this practice.

Ambulatory Electrocardiography Monitoring for Early Discharge After Minimally Invasive Valve Surgery.

INTRODUCTION: We sought to compare outcomes after early discharge in patients with and without predischarge diagnosis of arrhythmia following minimally invasive valve surgery (MIVS). MATERIALS AND METHODS: We retrospectively reviewed ambulatory electrocardiography (AECG) datasheets and medical records of patients discharged with 14-d AECG monitoring from our facility between October 2019 and March 2022 ≤ 3 d after MIVS. Baseline and clinical characteristics, arrhythmias during AECG monitoring, and 30-d adverse outcomes were reported for the population and stratified by presence or absence of predischarge arrhythmia. RESULTS: Of 41 patients discharged ≤3 d postoperatively of MIVS, 17 (41.5%) experienced predischarge arrhythmias and 24 (58.5%) did not. The population was predominantly male and White with a median age of 62 y [57, 70]. Baseline and clinical characteristics did not differ between subgroups. Most patients (92.7% [n = 38]) experienced one or more tachyarrhythmias during the AECG monitoring period. There were similar proportions of patients experiencing atrial fibrillation in both groups, but patients with predischarge arrhythmias had higher burden of atrial fibrillation on AECG monitoring (27.60% [6.57%, 100%] versus 1.65% [0.76%, 4.32%]; P = 0.004). The predischarge arrhythmia subgroup had higher proportions of patients experiencing nonsustained ventricular tachycardia but lower proportions experiencing supraventricular tachycardia. There were no mortalities within 30 d of surgery. Six (14.6%) patients were readmitted within 30 d with equal proportions of readmissions between subgroups (P = 0.662). CONCLUSIONS: Early discharge timelines and noninvasive monitoring techniques can allow patients to return to their normal activities quicker in the comfort of their own home with no increased risk of morbidity or mortality.

Opioid Use Disorder Increases Readmissions After Cardiac Surgery: A Call to Action.

BACKGROUND: Owing to the opioid epidemic, more cardiac surgery patients present with opioid use disorder (OUD). A better understanding of national readmissions among these patients is necessary to improve outcomes and optimize resource utilization. We sought to examine the effect of OUD on readmission after cardiac surgery. METHODS: Of 555 394 cardiac surgery patients from 2016 to 2017 in the Nationwide Readmissions Database, 6082 (1.1%) presented with OUD. These patients were assessed at 30, 90, and 180 days after discharge. The OUD patients and non-OUD patients were propensity score matched for patient- and procedure-level characteristics. Kaplan-Meier curves were compared using the log rank test. RESULTS: First-time readmissions were significantly higher among patients with OUD (30 days 19.7% vs 15.7%, P = .04; 90 days 31.8% vs 24.2%, P < .0001; and 180 days 42.3% vs 30.6%, P < .0001). There was a trend toward higher reoperation by 180 days, with 90% of those being isolated valve surgery. By 180 days, significantly more OUD patients had three or more readmissions (7.8% vs 4.5%) compared with non-OUD patients. Yet, only 2.4% of OUD patients received any counseling or treatment for substance abuse during the index admission. The most common readmitting diagnosis was infection (55% vs 41%, P < .0001) including endocarditis, prosthetic infections, and skin or subcutaneous infections. Respiratory failure, opioid overdose, and acute pain were also more common among patients with OUD. CONCLUSIONS: Cardiac surgery patients with OUD have multiple readmissions but are rarely provided adequate addiction management during their index admission. Greater emphasis on multidisciplinary management is necessary to limit costs and morbidity associated with readmission or reoperation.

Failure to Rescue After Cardiac Surgery at Minority-Serving Hospitals: Room for Improvement.

BACKGROUND: Despite living closer to high-performing centers, minority patients reportedly receive care at lower-quality hospitals. Investigating opportunities for improvement at minority-serving hospitals may help attenuate disparities in care among cardiothoracic surgery patients. We sought to investigate the relationship between hospital quality and failure to rescue (FTR). METHODS: Over 451,000 cardiac surgery patients from 2000 to 2011 at minority-serving hospitals (MSHs) were identified from the Nationwide Inpatient Sample. After stratifying patients by hospital mortality quartile, outcomes at poorly performing MSHs were compared with those at high-performing MSHs. Propensity score matching was used for comparisons. RESULTS: Though patients at poorly performing centers were more likely Black, there were no significant differences in admission status (urgent vs elective), income, insurance, or risk before matching. There were no differences in comorbidities between low-performing and high-performing MSHs including chronic lung disease, coagulopathy, hypertension, and renal failure. While complications remained similar across mortality quartiles (29%, 32%, 31%, and 36%, respectively; P < .0001), FTR increased in a stepwise manner (5.4%, 8.7%, 11.2%, and 15.5%, respectively; P < .0001). The same was true after propensity score matching-FTR nearly tripled in the highest-mortality centers (14.4% vs 5.3%; P < .0001), while complications only increased 1.2-fold from 31.1% to 36.7% (P = .0058). This finding persisted even when stratified by procedure type and by complication. CONCLUSIONS: Improving timely management of complications after cardiac surgery may serve as a promising opportunity for increasing quality of care at MSHs. When considering centralization of care in cardiac surgery, equal emphasis should be placed on collaboration between tertiary care centers and low-quality MSHs to mitigate disparities in care.

Improved outcomes in CABG patients with atrial fibrillation associated with surgical left atrial appendage exclusion.

BACKGROUND: We sought to determine the impact of left atrial appendage clip exclusion (LAACE) on coronary artery bypass grafting (CABG) outcomes among patients with pre-existing atrial fibrillation (AF). METHODS: From October 1, 2015 to October 1, 2017, 4210 Medicare beneficiaries with pre-existing AF underwent isolated CABG (i.e., without ablation) with (n = 931) or without (n = 3279) LAACE. Inverse probability of treatment weighting was used to evaluate the effect of concomitant LAACE on short- and long-term outcomes after CABG. Long term risks of thromboembolism and mortality were assessed using competing-risk regression and Cox proportional hazard models. RESULTS: Operative mortality, length of stay, and 30-day readmission did not differ between groups. Thromboembolism risk was 26% lower for the CABG + LAACE group compared with isolated CABG over a 2-year time-to-event analysis (sub hazard ratio [sHR] 0.74, 95% confidence interval [CI] 0.54-1.00, p = .049). There were no differences in ischemic stroke rates. All-cause mortality risk was 45% lower for CABG + LAACE during the late follow-up period (91-730 days; HR 0.55, 95% CI 0.32-0.95, p = .031). The late period annual absolute all-cause mortality rate was 3.7% for CABG + LAACE and 6.9% for isolated CABG. There were lower readmission rates (31% vs. 43%, p < .001) and total inpatient days (4.0 days vs. 7.2 days, p < .01.) for the CABG + LAACE during follow-up. Total hospital in and out-patient treatment costs were similar between groups through one year. CONCLUSIONS: Concomitant LAA exclusion via an epicardial closure device is associated with reduced CABG mortality, thromboembolic events, and readmissions in patients with pre-existing atrial fibrillation.

The Role of Frailty in Failure to Rescue After Cardiovascular Surgery.

BACKGROUND: Failure to rescue (FTR) is gaining popularity as a quality metric. The relationship between patient frailty and FTR after cardiovascular surgery has not been fully explored. This study aimed to utilize a national database to examine the impact of patient frailty on FTR. METHODS: Of 5,199,534 patients undergoing cardiovascular surgery between 2000 and 2014, 75,851 (1.5%) were identified from the Nationwide Inpatient Sample database as frail based on the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. Propensity-score matching was used to adjust for patient- and hospital-level characteristics and comorbidities when comparing frail and nonfrail patients. RESULTS: Frail patients were on average older (68 ± 12 years vs 65 ± 12 years; P < .001) and had more comorbidities including heart failure, and chronic lung, liver, or renal disease. Among 68,472 matched pairs, frail patients had significantly higher rates of FTR (13.4% vs 11.9%; P < .001). This contributed to a $39,796 increase in cost per hospitalization (P < .001). Renal failure, respiratory failure, pneumonia, and sepsis were most commonly associated with FTR in frail patients. When hospitals were stratified by risk-adjusted mortality, low-mortality (1st quintile) centers had significantly lower FTR rates and costs among frail patients when compared to high-mortality (5th quintile) centers. CONCLUSIONS: Frailty contributes significantly to FTR after cardiovascular surgery. Frail patients can expect better outcomes with lower costs at cardiac surgical centers of excellence that can adequately manage postoperative outcomes. Preoperative assessment of frailty may better guide risk estimation and identification of patients who would benefit from appropriate prehabilitative interventions to optimize outcomes.

Implications of Methicillin-Resistant Staphylococcus aureus Carriage on Cardiac Surgical Outcomes.

BACKGROUND: Staphylococcus aureus remains the most common cause of sternal surgical site infections (SSIs). Opinions on the postoperative implications of preoperative methicillin-resistant S aureus (MRSA) colonization currently differ. This study aimed to investigate whether MRSA carriage affects postoperative outcomes and safety of operation. METHODS: A total of 1,774,811 cardiac surgical patients from 2009 to 2014 were identified from the National Inpatient Sample database. Among these patients, 5798 (0.33%) were MRSA carriers. Propensity-score matching was used to determine the effect of MRSA colonization on outcomes. RESULTS: MRSA carriers did not differ in age or sex from noncarriers, but they more often presented for urgent surgery (P < .001). Among matched pairs, there was no difference in mortality (P = .76), stroke, SSIs, pneumonia, renal failure, cardiac complications, respiratory failure, or prolonged mechanical ventilation. MRSA infection (P < .001), MRSA septicemia (P = 0.03), and blood transfusion (P = .003) occurred more often among MRSA carriers. There was no increase in cost (P = .12), but the hospital length of stay was longer (P = .005). Predictors of MRSA infection among carriers included age older than 85 years, rural hospital location, and diabetes. Carriers with endocarditis and drug abuse were at highest risk for MRSA infection. CONCLUSIONS: MRSA carriers undergoing cardiac surgery are not at higher risk for mortality or SSIs and can expect outcomes similar to those of noncarriers. Higher rates of postoperative MRSA infection and septicemia among carriers, although still very low, support the need for selective preoperative screening and prophylaxis when possible.

Trends and Outcomes of Cardiovascular Surgery in Patients With Opioid Use Disorders.

Importance: Persistent opioid use is currently a major health care crisis. There is a lack of knowledge regarding its prevalence and effect among patients undergoing cardiac surgery. Objective: To characterize the national population of cardiac surgery patients with opioid use disorder (OUD) and compare outcomes with the cardiac surgery population without OUD. Design, Setting, and Participants: In this retrospective population-based cohort study, more than 5.7 million adult patients who underwent cardiac surgery (ie, coronary artery bypass graft, valve surgery, or aortic surgery) in the United States were included. Pregnant patients were excluded. Propensity matching was performed to compare outcomes between cardiac surgery patients with OUD (n = 11 359) and without OUD (n = 5 707 193). The Nationwide Inpatient Sample database was queried from January 1998 to December 2013. Data were analyzed in January 2018. Exposures: Persistent opioid use and/or dependence. Main Outcomes and Measures: In-hospital mortality, complications, length of stay, costs, and discharge disposition. Results: Among the 5 718 552 included patients, 3 887 097 (68.0%) were male; the mean (SD) age of patients with OUD was 47.67 (13.03) years and of patients without OUD was 65.53 (26.14) years. The prevalence of OUD among cardiac surgery patients was 0.2% (n = 11 359), with an 8-fold increase over 15 years (0.06% [262 of 437 641] in 1998 vs 0.54% [1425 of 263 930] in 2013; difference, 0.48%; 95% CI of difference, 0.45-0.51; P < .001). Compared with patients without OUD, patients with OUD were younger (mean [SD] age, 48 [0.30] years vs 66 [0.05] years; P < .001) and more often male (70.8% vs 68.0%; P < .001), black (13.7% vs 4.8%), or Hispanic (9.1% vs 4.8%). Patients with OUD more commonly fell in the first quartile of median income (30.7% vs 17.1%; P < .001) and were more likely to be uninsured or Medicaid beneficiaries (48.6% vs 7.7%; P < .001). Valve and aortic operations were more commonly performed among patients with OUD (49.8% vs 16.4%; P < .001). Among propensity-matched pairs, the mortality was similar between patients with vs without OUD (3.1% vs 4.0%; P = .12), but cardiac surgery patients with OUD had an overall higher incidence of major complications (67.6% vs 59.2%; P < .001). Specifically, the risks of blood transfusion (30.4% vs 25.9%; P = .002), pulmonary embolism (7.3% vs 3.8%; P < .001), mechanical ventilation (18.4% vs 15.7%; P = .02), and prolonged postoperative pain (2.0% vs 1.2%; P = .048) were significantly higher. Patients with OUD also had a significantly longer length of stay (median [SE], 11 [0.30] vs 10 [0.22] days; P < .001) and cost significantly more per patient (median [SE], $49 790 [1059] vs $45 216 [732]; P < .001). Conclusions and Relevance: The population of patients with persistent opioid use or opioid dependency undergoing cardiac surgery has increased over the past decade. Cardiac surgery in patients with OUD is safe but is associated with higher complications and cost. Patients should not be denied surgery because of OUD status but should be carefully monitored postoperatively for complications.