Sex Differences in In-Hospital Mortality After Open Cardiac Valve Surgery.

BACKGROUND: Cardiac valvular disease affects millions of people worldwide and is a major cause of morbidity and mortality. Female patients have been shown to experience inferior clinical outcomes after nonvalvular cardiac surgery, but recent data are limited regarding open valve surgical cohorts. The primary objective of our study was to assess whether female sex is associated with increased in-hospital mortality after open cardiac valve operations. METHODS: Utilizing the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID), we conducted a retrospective cohort study of patients who underwent open cardiac valve surgery from 2007 to 2018 in Washington, Maryland, Kentucky, and Florida; from 2007 to 2011 in California; and from 2007 to 2016 in New York. The primary objective of this study was to estimate the confounder-adjusted association between sex and in-hospital mortality (as recorded and coded by SID HCUP) after open cardiac valve surgery. We used multilevel multivariable models to account for potential confounders, including intrahospital practice patterns. RESULTS: A total of 272,954 patients (108,443 women; 39.73% of sample population with mean age of 67.6 ± 14.3 years) were included in our analysis. The overall mortality rates were 3.8% for male patients and 5.1% for female patients. The confounder-adjusted odds ratio (OR) for in-hospital mortality for female patients compared to male patients was 1.41 (95% confidence interval [CI], 1.35-1.47; P < .001). When stratifying by surgical type, female patients were also at increased odds of in-hospital mortality ( P < .001) in populations undergoing aortic valve replacement (adjusted OR [aOR], 1.38; 95% CI, 1.25-1.52); multiple valve surgery (aOR, 1.38; 95% CI, 1.22-1.57); mitral valve replacement (aOR, 1.22; 95% CI, 1.12 - 1.34); and valve surgery with coronary artery bypass grafting (aOR, 1.64; 95% CI, 1.54 - 1.74; all P < .001). Female patients did not have increased odds of in-hospital mortality in populations undergoing mitral valve repair (aOR, 1.26; 95% CI, 0.98 - 1.64; P = .075); aortic valve repair (aOR, 0.87; 95% CI, 0.67 - 1.14; P = .32); or any other single valve repair (aOR, 1.10; 95% CI, 0.82 - 1.46; P = .53). CONCLUSIONS: We found an association between female patients and increased confounder-adjusted odds of in-hospital mortality after open cardiac valve surgery. More research is needed to better understand and categorize these important outcome differences. Future research should include observational analysis containing granular and complete patient- and surgery-specific data.

COVID-19 increases the risk for the onset of atrial fibrillation in hospitalized patients.

COVID-19 is associated with significant extrapulmonary symptoms. Myocardial involvement has been described for infections with SARS-CoV-2 which may lead to an increase in morbidity and mortality. The objective of our study was to investigate the association of COVID-19 and atrial fibrillation (AF) or atrial flutter (AFl) in hospitalized patients. This retrospective study used electronic medical records to detect patients with COVID-19 and their comorbidities within the Mass General Brigham hospital system. All patients ≥ 18 years who were hospitalized and received a PCR test for SARS-CoV-2 were screened for inclusion as well as patients from a pre-pandemic cohort. We matched on common risk factors for AF and then used multivariable logistic regression to estimate the odds for AF or AFl. Of 78,725 patients eligible for analysis, 11,004 COVID-19 negative patients were matched to 3,090 COVID-19 positive patients and 5005 pre-pandemic patients were matched to 2283 COVID-19 positive patients. After adjusting for demographics and comorbidities, COVID-19 positive patients had 1.19 times the odds (95% CI 1.00, 1.41) of developing AF compared to COVID-19 negative patients and 1.57 times the odds (95% CI 1.23, 2.00) of developing AF compared to pre-pandemic patients. Our study demonstrated an increased risk for AF, directing the attention for improved screening and treatment regimens for the sequelae of COVID-19. While COVID-19 continues to affect many people around the world, AF may be a significant cause for morbidity and mortality. Adequate detection and treatment of AF is essential to reduce the burden of disease.

Association Between Early Extubation and Postoperative Reintubation After Elective Cardiac Surgery: A Bi-institutional Study.

OBJECTIVE: It is unknown if remaining intubated after cardiac surgery is associated with a decreased risk of postoperative reintubation. The primary objective of this study was to investigate whether there was an association between the timing of extubation and the risk of reintubation after cardiac surgery. DESIGN: A retrospective, observational study. SETTING: Two university-affiliated tertiary care centers. PARTICIPANTS: A total of 9,517 patients undergoing either isolated coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 6,609 isolated CABGs and 2,908 isolated AVRs were performed during the study period. Reintubation occurred in 112 patients (1.64%) after CABG and 44 patients (1.5%) after AVR. After multivariate logistic regression analysis, early extubation (within the first 6 postoperative hours) was not associated with a risk of reintubation after CABG (odds ratio [OR] 0.53, 95% CI 0.26-1.06) and AVR (OR 0.52, 95% CI 0.22-1.22). Risk factors for reintubation included increased age in both the CABG (OR per 10-year increase, 1.63; 95% CI 1.28-2.08) and AVR (OR per 10-year increase, 1.50; 95% CI 1.12-2.01) cohorts. Total bypass time, race, and New York Heart Association (NYHA) functional class were not associated with reintubation risk. CONCLUSION: Reintubation after CABGs and AVRs is a rare event, and advanced age is an independent risk factor. Risk is not increased with early extubation. This temporal association and low overall rate of reintubation suggest the strategies for extubation should be modified in this patient population.

Mediastinal Masses, Anesthetic Interventions, and Airway Compression in Adults: A Prospective Observational Study.

BACKGROUND: Central airway occlusion is a feared complication of general anesthesia in patients with mediastinal masses. Maintenance of spontaneous ventilation and avoiding neuromuscular blockade are recommended to reduce this risk. Physiologic arguments supporting these recommendations are controversial and direct evidence is lacking. The authors hypothesized that, in adult patients with moderate to severe mediastinal mass-mediated tracheobronchial compression, anesthetic interventions including positive pressure ventilation and neuromuscular blockade could be instituted without compromising central airway patency. METHODS: Seventeen adult patients with large mediastinal masses requiring general anesthesia underwent awake intubation followed by continuous video bronchoscopy recordings of the compromised portion of the airway during staged induction. Assessments of changes in anterior-posterior airway diameter relative to baseline (awake, spontaneous ventilation) were performed using the following patency scores: unchanged = 0; 25 to 50% larger = +1; more than 50% larger = +2; 25 to 50% smaller = -1; more than 50% smaller = -2. Assessments were made by seven experienced bronchoscopists in side-by-side blinded and scrambled comparisons between (1) baseline awake, spontaneous breathing; (2) anesthetized with spontaneous ventilation; (3) anesthetized with positive pressure ventilation; and (4) anesthetized with positive pressure ventilation and neuromuscular blockade. Tidal volumes, respiratory rate, and inspiratory/expiratory ratio were similar between phases. RESULTS: No significant change from baseline was observed in the mean airway patency scores after the induction of general anesthesia (0 [95% CI, 0 to 0]; P = 0.953). The mean airway patency score increased with the addition of positive pressure ventilation (0 [95% CI, 0 to 1]; P = 0.024) and neuromuscular blockade (1 [95% CI, 0 to 1]; P < 0.001). No patient suffered airway collapse or difficult ventilation during any anesthetic phase. CONCLUSIONS: These observations suggest a need to reassess prevailing assumptions regarding positive pressure ventilation and/or paralysis and mediastinal mass-mediated airway collapse, but do not prove that conventional (nonstaged) inductions are safe for such patients.

A Novel 3-Dimensional Approach for the Echocardiographic Evaluation of Mitral Valve Area After Repair for Degenerative Disease.

BACKGROUND: Currently available 2-dimensional (2D) echocardiographic methods for accurately assessing the mitral valve orifice area (MVA) after mitral valve repair (MVr) are limited due to its complex 3-dimensional (3D) geometry. We compared repaired MVAs obtained with commonly used 2D and 3D echocardiographic methods to a 3D orifice area (3DOA), which is a novel echocardiographic measurement and independent of geometric assumptions. METHODS: Intraoperative 2D and 3D transesophageal echocardiography (TEE) images from 20 adult cardiac surgery patients who underwent MVr for mitral regurgitation obtained immediately after repair were retrospectively reviewed. MVAs obtained by pressure half-time (PHT), 2D planimetry (2DP), and 3D planimetry (3DP) were compared to those derived by 3DOA. RESULTS: MVAs (mean value ± standard deviation [SD]) after MVr were obtained by PHT (3 ± 0.6 cm), 2DP (3.58 ± 0.75 cm), 3D planimetry (3DP; 2.78 ± 0.74 cm), and 3DOA (2.32 ± 0.76 cm). MVAs obtained by the 3DOA method were significantly smaller compared to those obtained by PHT (mean difference, 0.68 cm; P = .0003), 2DP (mean difference, 1.26 cm; P < .0001), and 3DP (mean difference, 0.46 cm; P = .003). In addition, MVA defined as an area ≤1.5 cm was identified by 3DOA in 2 patients and by 3DP in 1 patient. CONCLUSIONS: Post-MVr MVAs obtained using the novel 3DOA method were significantly smaller than those obtained by conventional echocardiographic methods and may be consistent with a higher incidence of MVA reduction when compared to 2D techniques. Further studies are still needed to establish the clinical significance of 3D echocardiographic techniques used to measure MVA after MVr.

Characteristics of Reported Adverse Events During Moderate Procedural Sedation: An Update.

BACKGROUND: Many interventional procedures are performed under moderate procedural sedation (MPS). It is important to understand the nature of and factors contributing to adverse events (AEs). Little data exist examining reportable AEs during MPS across specialties. A study was conducted to investigate adverse events during MPS and to compare associated patient and provider characteristics. METHODS: In a retrospective review, 83 MPS cases in which safety incidents were reported (out of approximately 20,000 annual cases during a 12-year period at a tertiary medical center) were analyzed. The type of AE and severity of harm were examined using bivariate and multivariate analyses to uncover associations between events with provider, procedure, and patient characteristics. RESULTS: The most common AEs were oversedation/apnea (60.2%), hypoxemia (42.2%), and aspiration (24.1%). The most common unplanned interventions were the use of reversal agents (55.4%) and prolonged bag-mask ventilation (25.3%). Cardiology, gastroenterology, and radiology were the specialties most frequently associated with AEs. Reversal agents, oversedation, and hypoxemia occurred most frequently in the gastroenterology and cardiology suites. Women were more likely to experience AEs than men, incurring higher rates of hypotension, prolonged bag-mask ventilation, and reversal agents. Increased body mass index was associated with lower rates of hypoxemia, while advanced age correlated with high rates of oversedation, harm done, and use of reversal agents. Malignancy and cardiovascular comorbidities were associated with increased AEs. Patients with respiratory comorbidities were less likely to be subject to AEs. CONCLUSION: Certain patient characteristics and types of procedures may be associated with increased risk of AEs during MPS.

Risk Factors and Outcomes Associated With Sepsis After Coronary Artery Bypass and Open Heart Valve Surgeries.

PURPOSE: Sepsis causes significant morbidity and mortality after cardiac surgery and carries a significant burden on health care costs. There is a general association of increased risk of post-cardiac surgery sepsis in patients with postoperative complications. We sought to investigate significant patient and procedural risk factors and outcomes associated with sepsis after cardiac surgery. MATERIALS AND METHODS: In this retrospective study, we analyzed 531 coronary artery bypass grafting and open heart valve surgery cases that developed postoperative sepsis in the National Surgical Quality Improvement Program database between 2007 and 2014. Patient-based and surgery-based parameters were analyzed for risk factors and outcomes reported in the 30 days postoperatively. The association between sepsis and patient outcomes was assessed in a propensity-matched cohort using univariable logistic regression. RESULTS: Modifiable and nonmodifiable patient characteristics, including age >80, poor preoperative functional status, chronic diseases such as diabetes mellitus, congestive heart failure, chronic kidney disease with serum creatinine ⩾1.5, as well as serum albumin <3.5 and emergent nature of the case were associated with post-cardiac surgery sepsis. Surgical outcomes associated with sepsis included mortality (15.4% vs 4.5%), unplanned intubation (29.8% vs 8.2%), transfusion (53.4% vs 48.4%), acute kidney injury (7.1% vs 1.4%), postoperative dialysis (18.8% vs 3.5%), and return to the operating room (29.8% vs 8.2%). CONCLUSIONS: We identified multiple patient and surgical characteristics as well as postoperative outcomes associated with postoperative sepsis development in the high-risk population of patients undergoing cardiac surgery. Early identification of patients who are at high risk for postoperative sepsis can facilitate early treatment interventions.

Echocardiographic Assessment of Mitral Stenosis Orifice Area: A Comparison of a Novel Three-Dimensional Method Versus Conventional Techniques.

BACKGROUND: A comprehensive evaluation of mitral stenosis (MS) severity commonly utilizes two-dimensional (2D) echocardiography techniques. However, the complex three-dimensional (3D) structure of the mitral valve (MV) poses challenges to accurate measurements of its orifice area by 2D imaging modalities. We aimed to assess MS severity by comparing measurements of the MV orifice area using conventional echocardiography methods to 3D orifice area (3DOA), a novel echocardiographic technique which minimizes geometric assumptions. METHODS: Routine 2D and 3D intraoperative transesophageal echocardiographic images from 26 adult cardiac surgery patients with at least moderate rheumatic MS were retrospectively reviewed. Measurements of the MV orifice area obtained by pressure half-time (PHT), proximal isovelocity surface area (PISA), continuity equation, and 3D planimetry were compared to those acquired using 3DOA. RESULTS: MV areas derived by PHT, PISA, continuity equation, 3D planimetry, and 3DOA (mean value ± standard deviation) were 1.12 ± 0.27, 1.03 ± 0.27, 1.16 ± 0.35, 0.97 ± 0.25, and 0.76 ± 0.21 cm, respectively. Areas obtained from the 3DOA method were significantly smaller than areas derived from PHT (mean difference 0.35 cm, P < .0001), PISA (mean difference: 0.28 cm, P = .0002), continuity equation (mean difference: 0.43 cm, P = .0015), and 3D planimetry (mean difference: 0.19 cm, P < .0001). MV 3DOAs also identified a significantly greater percentage of patients with severe MS (88%) compared to PHT (31%, P = .006), PISA (42%, P = .01), and continuity equation (39%, P = .017) but not in comparison to 3D planimetry (62%, P = .165). CONCLUSIONS: Novel measures of the stenotic MV 3DOA in patients with rheumatic heart disease are significantly smaller than calculated values obtained by conventional methods and may be consistent with a higher incidence of severe MS compared to 2D techniques. Further investigation is warranted to determine the clinical relevance of 3D echocardiographic techniques used to measure MV area.

Analysis of Adverse Events Associated With Adult Moderate Procedural Sedation Outside the Operating Room.

INTRODUCTION: Moderate sedation outside the operating room is performed for a variety of medical and surgical procedures. It involves the administration of different drug combinations by nonanesthesia professionals. Few data exist on risk stratification and patient outcomes in the adult population. Current literature suggests that sedation can be associated with significant adverse outcomes. OBJECTIVES: The aims of this study were to evaluate the nature of adverse events associated with moderate sedation and to examine their relation to patient characteristics and outcomes. METHODS: In this retrospective review, 52 cases with moderate sedation safety incidents were identified out of approximately 143,000 cases during an 8-year period at a tertiary care medical center. We describe types of adverse events and the severity of associated harm. We used bivariate and multivariate analyses to examine the links between event types and both patient and procedure characteristics. RESULTS: The most common adverse event and unplanned intervention were oversedation leading to apnea (57.7% of cases) and the use of reversal agents (55.8%), respectively. Oversedation, hypoxemia, reversal agent use, and prolonged bag-mask ventilation were most common in cardiology (84.6%, 53.9%, 84.6%, and 38.5% of cases, respectively) and gastroenterology (87.5%, 75%, 87.5%, and 50%) suites. Miscommunication was reported most frequently in the emergency department (83.3%) and on the inpatient floor (69.2%). Higher body mass index was associated with increased rates of hypoxemia and intubation but lower rates of hypotension. Advanced age boosted the rates of oversedation, hypoxemia, and reversal agent use. Women were more likely than men to experience oversedation, hypotension, prolonged bag-mask ventilation, and reversal agent use. Patient harm was associated with age, body mass index, comorbidities, female sex, and procedures in the gastroenterology suite. CONCLUSIONS: Providers should take into account patient characteristics and procedure types when assessing the risks of harmful sedation-related complications.

Toll-like receptor 7 stimulates production of specialized pro-resolving lipid mediators and promotes resolution of airway inflammation.

Although specialized pro-resolving mediators (SPMs) biosynthesized from polyunsaturated fatty acids are critical for the resolution of acute inflammation, the molecules and pathways that induce their production remain elusive. Here, we show that TLR7, a receptor recognizing viral ssRNA and damaged self-RNA, mobilizes the docosahexaenoic acid (DHA)-derived biosynthetic pathways that lead to the generation of D-series SPMs. In mouse macrophages and human monocytes, TLR7 activation triggered production of DHA-derived monohydroxy metabolome markers and generation of protectin D1 (PD1) and resolvin D1 (RvD1). In mouse allergic airway inflammation, TLR7 activation enhanced production of DHA-derived SPMs including PD1 and accelerated the catabasis of Th2-mediated inflammation. D-series SPMs were critical for TLR7-mediated resolution of airway inflammation as this effect was lost in Alox15(-/-) mice, while resolution was enhanced after local administration of PD1 or RvD1. Together, our findings reveal a new previously unsuspected role of TLR7 in the generation of D-series SPMs and the resolution of allergic airway inflammation. They also identify TLR stimulation as a new approach to drive SPMs and resolution of inflammatory diseases.

Affective interactions in medical visits: ethnic differences among American Indian older adults.

OBJECTIVE: Investigate influence of ethnicity on older American Indian patients' interpretations of providers' affective behaviors. METHOD: Using data from 115 older American Indian patients, random effects ordered logit models related patient ratings of providers' respect, empathy, and rapport first to separate measures of American Indian and White American ethnicity, then to "ethnic discordance," or difference between providers' and patients' cultural characteristics. RESULTS: In models accounting for patients' ethnicity only, high scores for American Indian ethnicity were linked to reduced evaluations for providers' respect; high scores on White ethnicity were associated with elevated ratings for empathy and rapport. In models accounting for provider-patient ethnic discordance, high discordance on either ethnicity scale was associated with reduced ratings for the same behaviors. DISCUSSION: Findings support "orthogonal ethnic identity" theory and extend "cultural health capital" theory, suggesting a pathway by which ethnicity becomes relevant to experience of health care among older adults.

Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain.

Self-resolving inflammatory exudates and lipid mediator metabolomics recently uncovered a new family of potent anti-inflammatory and proresolving mediators biosynthesized by macrophages (MΦs), denoted maresins. Here we determined that maresin 1 (MaR1) produced by human MΦs from endogenous docosahexaenoic acid (DHA) matched synthetic 7R,14S-dihydroxydocosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid. The MaR1 alcohol groups and Z/E geometry of conjugated double bonds were matched using isomers prepared by total organic synthesis. MaR1's potent defining actions were confirmed with synthetic MaR1, i.e., limiting polymorphonuclear neutrophil (PMN) infiltration in murine peritonitis (ng/mouse range) as well as enhancing human macrophage uptake of apoptotic PMNs. At 1 nM, MaR1 was slightly more potent than resolvin D1 in stimulating human MΦ efferocytosis, an action not shared by leukotriene B(4). MaR1 also accelerated surgical regeneration in planaria, increasing the rate of head reappearance. On injury of planaria, MaR1 was biosynthesized from deuterium-labeled (d(5))-DHA that was blocked with lipoxygenase (LOX) inhibitor. MaR1 dose-dependently inhibited TRPV1 currents in neurons, blocked capsaicin (100 nM)-induced inward currents (IC(50) 0.49±0.02 nM), and reduced both inflammation- and chemotherapy-induced neuropathic pain in mice. These results demonstrate the potent actions of MaR1 in regulating inflammation resolution, tissue regeneration, and pain resolution. These findings suggest that chemical signals are shared in resolution cellular trafficking, a key process in tissue regeneration. Moreover, immunoresolvents of the innate immune response, such as MaR1, offer new opportunities for assessing MΦs and their local DHA metabolome in the return to tissue homeostasis.

Novel proresolving aspirin-triggered DHA pathway.

Endogenous mechanisms in the resolution of acute inflammation are of interest because excessive inflammation underlies many pathologic abnormalities. We report an aspirin-triggered DHA metabolome that biosynthesizes a potent product in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1)]. The complete stereochemistry of AT-(NPD1/PD1) proved to be 10R,17R-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. The chirality of hydroxyl groups and geometry of the conjugated triene system essential for bioactivity were established by matching biological materials with stereochemically pure isomers prepared by organic synthesis. AT-(NPD1/PD1) reduced neutrophil (PMN) recruitment in murine peritonitis in a dose-dependent fashion whereby neither a Δ(15)-trans-isomer nor DHA was effective. With human cells, AT-(NPD1/PD1) decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. These results indicate that AT-(NPD1/PD1) is a potent anti-inflammatory proresolving molecule.