Transient receptor potential vanilloid 4 channel inhibition attenuates lung ischemia-reperfusion injury in a porcine lung transplant model.

OBJECTIVE: Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel important in many physiological and pathophysiological processes, including pulmonary disease. Using a murine model, we previously demonstrated that TRPV4 mediates lung ischemia-reperfusion injury, the major cause of primary graft dysfunction after transplant. The current study tests the hypothesis that treatment with a TRPV4 inhibitor will attenuate lung ischemia-reperfusion injury in a clinically relevant porcine lung transplant model. METHODS: A porcine left-lung transplant model was used. Animals were randomized to 2 treatment groups (n = 5/group): vehicle or GSK2193874 (selective TRPV4 inhibitor). Donor lungs underwent 30 minutes of warm ischemia and 24 hours of cold preservation before left lung allotransplantation and 4 hours of reperfusion. Vehicle or GSK2193874 (1 mg/kg) was administered to the recipient as a systemic infusion after recipient lung explant. Lung function, injury, and inflammatory biomarkers were compared. RESULTS: After transplant, left lung oxygenation was significantly improved in the TRPV4 inhibitor group after 3 and 4 hours of reperfusion. Lung histology scores and edema were significantly improved, and neutrophil infiltration was significantly reduced in the TRPV4 inhibitor group. TRPV4 inhibitor-treated recipients had significantly reduced expression of interleukin-8, high mobility group box 1, P-selectin, and tight junction proteins (occludin, claudin-5, and zonula occludens-1) in bronchoalveolar lavage fluid as well as reduced angiopoietin-2 in plasma, all indicative of preservation of endothelial barrier function. CONCLUSIONS: Treatment of lung transplant recipients with TRPV4 inhibitor significantly improves lung function and attenuates ischemia-reperfusion injury. Thus, selective TRPV4 inhibition may be a promising therapeutic strategy to prevent primary graft dysfunction after transplant.

Five-Year Sustained Impact of a Thoracic Enhanced Recovery After Surgery Program.

BACKGROUND: Our thoracic enhanced recovery program (ERP) decreased the use of postoperative morphine equivalents and hospital costs 1 year after implementation at our tertiary center. The sustainability and potential increasing benefit of this program were evaluated. METHODS: From 2015 to 2021, we prospectively analyzed the outcomes of patients who underwent elective pleural, pulmonary, or mediastinal operations at our institution. Patients were separated on the basis of the incision (video-assisted thoracoscopic surgery [VATS] or thoracotomy). The ERP protocol was initiated on May 1, 2016, and includes preoperative education, carbohydrate loading, opioid-sparing analgesia, conservative fluid management, protective ventilation, and early ambulation. Outcomes of patients before (2015, pre-VATS and pre-thoracotomy) and after (May 1, 2016, to December 31, 2021, ERP-VATS and ERP-thoracotomy) ERP implementation were compared. RESULTS: The cohort included 1079 patients (pre-ERP era, n = 224 [21%]; ERP era, n = 855 [79%]). There was a median reduction of 1.5 hospital days per patient for ERP-thoracotomy and 1 hospital day per patient for ERP-VATS. Median postoperative morphine equivalents decreased in both groups (125 vs 45 mg, in ERP-thoracotomy; 84 vs 23 mg, ERP-VATS; P < .001), as did total admission cost ($32,118 vs $23,775, ERP-thoracotomy; $17,367 vs $11,560, ERP-VATS; P < .001). Median total fluid balance during the hospital stay decreased significantly. Rates of postoperative atrial fibrillation and urinary retention decreased across both subgroups. CONCLUSIONS: ERP for thoracic surgery is sustainable and has been demonstrated to improve patient outcomes, to decrease opioid use, and to lower hospital costs. Therefore, it has the potential to become the standard of care.

Effect of Cardiopulmonary Bypass on SARS-CoV-2 Vaccination Antibody Levels.

Background Adults undergoing heart surgery are particularly vulnerable to respiratory complications, including COVID-19. Immunization can significantly reduce this risk; however, the effect of cardiopulmonary bypass (CPB) on immunization status is unknown. We sought to evaluate the effect of CPB on COVID-19 vaccination antibody concentration after cardiac surgery. Methods and Results This prospective observational clinical trial evaluated adult participants undergoing cardiac surgery requiring CPB at a single institution. All participants received a full primary COVID-19 vaccination series before CPB. SARS-CoV-2 spike protein-specific antibody concentrations were measured before CPB (pre-CPB measurement), 24 hours following CPB (postoperative day 1 measurement), and approximately 1 month following their procedure. Relationships between demographic or surgical variables and change in antibody concentration were assessed via linear regression. A total of 77 participants were enrolled in the study and underwent surgery. Among all participants, mean antibody concentration was significantly decreased on postoperative day 1, relative to pre-CPB levels (-2091 AU/mL, P<0.001). Antibody concentration increased between postoperative day 1and 1 month post CPB measurement (2465 AU/mL, P=0.015). Importantly, no significant difference was observed between pre-CPB and 1 month post CPB concentrations (P=0.983). Two participants (2.63%) developed symptomatic COVID-19 pneumonia postoperatively; 1 case of postoperative COVID-19 pneumonia resulted in mortality (1.3%). Conclusions COVID-19 vaccine antibody concentrations were significantly reduced in the short-term following CPB but returned to pre-CPB levels within 1 month. One case of postoperative COVID 19 pneumonia-specific mortality was observed. These findings suggest the need for heightened precautions in the perioperative period for cardiac surgery patients.

Center case volume is associated with Society of Thoracic Surgeons-defined failure to rescue in cardiac surgery.

OBJECTIVE: Our understanding of the impact of a center's case volume on failure to rescue (FTR) after cardiac surgery is incomplete. We hypothesized that increasing center case volume would be associated with lower FTR. METHODS: Patients undergoing a Society of Thoracic Surgeons index operation in a regional collaborative (2011-2021) were included. After we excluded patients with missing Society of Thoracic Surgeons Predicted Risk of Mortality scores, patients were stratified by mean annual center case volume. The lowest quartile of case volume was compared with all other patients. Logistic regression analyzed the association between center case volume and FTR, adjusting for patient demographics, race, insurance, comorbidities, procedure type, and year. RESULTS: A total of 43,641 patients were included across 17 centers during the study period. Of these, 5315 (12.2%) developed an FTR complication, and 735 (13.8% of those who developed an FTR complication) experienced FTR. Median annual case volume was 226, with 25th and 75th percentile cutoffs of 136 and 284 cases, respectively. Increasing center-level case volume was associated with significantly greater center-level major complication rates but lower mortality and FTR rates (all P values < .01). Observed-to-expected FTR was significantly associated with case volume (P = .040). Increasing case volume was independently associated with decreasing FTR rate in the final multivariable model (odds ratio, 0.87 per quartile; confidence interval, 0.799-0.946, P = .001). CONCLUSIONS: Increasing center case volume is significantly associated with improved FTR rates. Assessment of low-volume centers' FTR performance represents an opportunity for quality improvement.

Changes in Controllable Coronary Artery Bypass Grafting Practice for White and Black Americans.

BACKGROUND: Racial disparities in outcomes after cardiac surgery are well reported. We sought to determine whether variation by race exists in controllable practices during coronary artery bypass graft surgery (CABG). We hypothesized that racial disparities exist in CABG quality metrics, but have improved over time. METHODS: All patients undergoing isolated CABG (2000 to 2019) in a multiple state database were stratified into three eras by race. Analysis included propensity matched White Americans and Black Americans. Primary outcomes included left internal mammary artery use, multiple arterial grafting, revascularization completeness, and guideline-directed medication prescription. RESULTS: Of 72 248 patients undergoing CABG, Black American patients (n = 10 270, 15%) had higher rates of diabetes mellitus, hypertension, prior stroke, and myocardial infarction. After matching, 19 806 patients (n = 9903 per group) were well balanced. Left internal mammary artery use was significantly different early (era 1, Black Americans 84.7% vs White Americans 86.6%; P = .03), but equalized over time. Importantly, multiarterial grafting differed between Black Americans and White Americans over the entire study (9.1% vs 11.5%, P < .001) and within each era. Black Americans had more incomplete revascularization during the study period (14% vs 12.8%, P = .02) driven by a large disparity in era 1 (9.5% vs 7.2%, P < .001). Despite similar rates of preoperative use, Black Americans were more often discharged on a regimen of ß-blockers (91.8% vs 89.6%, P < .001). CONCLUSIONS: Coronary artery bypass graft surgery metrics of left internal mammary artery use and optimal medical therapy have improved over time and are similar despite patient race. Black Americans undergo less frequent multiarterial grafting and greater discharge ß-blocker prescription. Identifying changes in controllable CABG quality practices across races supports a continued focus on standardizing such efforts.

Operating Room Versus Intensive Care Unit Extubation Within 6 Hours After On-Pump Cardiac Surgery: Early Results and Hospital Costs.

Time-directed extubation (fast-track) protocols may decrease length of stay and cost but data on operating room (OR) extubation is limited. The objective of this study was to compare the outcomes of extubation in the OR versus fast-track extubation within 6 hours of leaving the operating room. Patients undergoing nonemergent STS index cases (2011-2021) who were extubated within 6 hours were identified from a regional STS quality collaborative. Patients were stratified by extubation in the OR versus fast track. Propensity score matching (1:n) was performed to balance baseline differences. Of the 24,962 patients, 498 were extubated in the OR. After matching, 487 OR extubation cases and 899 fast track cases were well balanced. The rate of reintubation was higher for patients extubated in the OR [21/487 (4.3%) vs 16/899 (1.8%), P = 0.008] as was the incidence of reoperation for bleeding [12/487 (2.5%) vs 8/899 (0.9%), P = 0.03]. There was no significant difference in the rate of any reoperation [16/487 (3.3%) vs 15/899 (1.6%), P = 0.06] or operative mortality [4/487 (0.8%) vs 6/899 (0.6%), P = 0.7]. OR extubation was associated with shorter hospital length of stay (5.6 vs 6.2 days, P < 0.001) and lower total cost of admission ($29,602 vs $31,565 P < 0.001). OR extubation is associated with a higher postoperative risk of reintubation and reoperation due to bleeding, but lower resource utilization.Future research exploring predictors of extubation readiness may be required prior to widespread adoption of this practice.

Perioperative acetaminophen is associated with reduced acute kidney injury after cardiac surgery.

BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is associated with increased postoperative morbidity and mortality. Evidence suggests an association between perioperative acetaminophen administration and decreased incidence of postoperative AKI in pediatric cardiac surgery patients; however, an effect in adults is unknown. METHODS: All patients (n = 6192) undergoing coronary and/or valve surgery with a recorded Society of Thoracic Surgeons (STS) risk score at our institution between 2010 and 2018 were stratified by acetaminophen exposure on the day of surgery using institutional pharmacy records. AKI was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) staging criteria. Logistic regression was used to analyze the association between perioperative acetaminophen and postoperative kidney injury or STS major morbidity. A sensitivity analysis using propensity score matching on the STS predicted risk of renal failure and cardiopulmonary bypass time was performed to account for time bias. RESULTS: Perioperative acetaminophen exposure was associated with lower odds of stage 1 to 3 acute kidney injury (odds ratio [OR], 0.68; 95% CI, 0.56-0.83; P < .001) and decreased prolonged postoperative ventilation (OR, 0.53; 95% CI, 0.37-0.76; P < .001). A sensitivity analysis provided well-balanced (standard mean difference <0.10) groups of 401 pairs, in which acetaminophen was associated with a decreased incidence of postoperative AKI (OR, 0.7; 95% CI, 0.52-0.94; P = .016). CONCLUSIONS: Exposure to acetaminophen on the day of surgery was associated with a decreased incidence of AKI in our patients undergoing cardiac surgery. These data serve as a measure of effect size to further explore the therapeutic potential of acetaminophen to reduce postoperative AKI after cardiac surgery and to elucidate the mechanisms involved.

Minimally Invasive Approaches Are Safe for Concomitant Mitral and Tricuspid Valve Surgery.

OBJECTIVE: The need for concomitant tricuspid surgery during mitral valve surgery is associated with higher operative risk. We hypothesized that concomitant tricuspid surgery through a minimally invasive thoracotomy (MICS) is associated with noninferior risk compared with a sternotomy. METHODS: All patients undergoing mitral valve surgery at a single institution (2010 to 2020) were evaluated. After excluding endocarditis, emergent operations, and concomitant aortic valve or coronary artery bypass grafting procedures, patients were stratified by MICS versus sternotomy. Multivariable logistic regression assessed the risk-adjusted association between concomitant tricuspid valve procedure and Society of Thoracic Surgeons major morbidity or mortality. An interaction term evaluated the impact of approach on concomitant tricuspid surgery. RESULTS: A total of 772 patients underwent mitral valve surgery, including 138 (17.9%) with concomitant tricuspid valve operation. Of the total cohort, 243 patients (31.5%) underwent the MICS approach. Concomitant tricuspid operation was performed in 104 sternotomy patients (19.7%) compared with 34 MICS patients (14.0%, P = 0.056). After risk adjustment, patients who underwent concomitant tricuspid valve surgery via sternotomy had nearly 2 times greater odds of morbidity and mortality relative to those undergoing isolated mitral surgery via sternotomy (adjOR = 1.86, P = 0.049), while patients who underwent concomitant tricuspid surgery via the MICS approach had no increased risk of the composite outcome (adjOR = 0.66, P = 0.543), relative to isolated mitral surgery via MICS approach. CONCLUSIONS: Concomitant tricuspid surgery at the time of mitral valve surgery carries additional risk in a broad patient population. A minimally invasive approach appears to be safe for selected patients requiring concomitant tricuspid valve surgery.

Gastric Aspiration and Ventilator-Induced Model of Acute Respiratory Distress Syndrome in Swine.

INTRODUCTION: Mainstays of current treatment for acute respiratory distress syndrome (ARDS) focus on supportive care and rely on intrinsic organ recovery. Animal models of ARDS are often limited by systemic injury. We hypothesize that superimposing gastric aspiration and ventilator-induced injury will induce a lung-specific injury model of severe ARDS. MATERIALS AND METHODS: Adult swine (n = 8) were subject to a 12 h injury development period followed by 24 h of post-injury monitoring. Lung injury was induced with gastric secretions (3 cc/kg body weight/lung, pH 1-2) instilled to bilateral mainstem bronchi under direct bronchoscopic vision. Ventilator settings within the injury period contradicted baseline settings using high tidal volumes and low positive end-expiratory pressure. Baseline settings were restored following the injury period. Arterial oxygenation and lung compliance were monitored. RESULTS: At 12 h, PaO2/FiO2 ratio and static and dynamic compliance were significantly reduced from baseline (P < 0.05). During the postinjury period, animals showed no signs of recovery in PaO2/FiO2 ratio and lung compliance. Lung edema (wet/dry weight ratio) of injured lungs was significantly elevated versus noninjured lungs (8.5 ± 1.7 versus 5.6 ± 0.3, P = 0.009). Expression of proinflammatory cytokines IL-6 and IL-8 were significantly elevated in injured lungs (P < 0.05). CONCLUSIONS: Twelve hours of high tidal volume and low positive end-expiratory pressure in conjunction with low-pH gastric content instillation produces significant acute lung injury in swine. This large animal model may be useful for testing severe ARDS treatment strategies.

Socioeconomic distress is associated with failure to rescue in cardiac surgery.

OBJECTIVE: The influence of socioeconomic determinants of health on failure to rescue (mortality after a postoperative complication) after cardiac surgery is unknown. We hypothesized that increasing Distressed Communities Index, a comprehensive socioeconomic ranking by ZIP code, would be associated with higher failure to rescue. METHODS: Patients undergoing Society of Thoracic Surgeons index operation in a regional collaborative (2011-2021) who developed a failure to rescue complication were included. After excluding patients with missing ZIP code or Society of Thoracic Surgeons predicted risk of mortality, patients were stratified by Distressed Communities Index scores (0-no distress, 100-severe distress) based on education level, poverty, unemployment, housing vacancies, median income, and business growth. The upper 2 quintiles of distress (Distressed Communities Index >60) were compared to all other patients. Hierarchical logistic regression analyzed the association between Distressed Communities Index and failure to rescue. RESULTS: A total of 4004 patients developed 1 or more of the defined complications across 17 centers. Of these, 582 (14.5%) experienced failure to rescue. High socioeconomic distress (Distressed Communities Index >60) was identified among 1272 patients (31.8%). Before adjustment, failure to rescue occurred more frequently among those from socioeconomically distressed communities (Distressed Communities Index >60; 16.9% vs 13.4%, P = .004). After adjustment, residing in a socioeconomically distressed community was associated with 24% increased odds of failure to rescue (odds ratio, 1.24; confidence interval, 1.003-1.54; P = .044). CONCLUSIONS: Increasing Distressed Communities Index, a measure of poor socioeconomic status, is associated with greater risk-adjusted likelihood of failure to rescue after cardiac surgery. These findings highlight that current quality metrics do not account for socioeconomic status, and as such underrepresent procedural risk for these vulnerable patients.

Secondary Burn Progression Mitigated by an Adenosine 2A Receptor Agonist.

Current burn therapy is largely supportive with limited therapies to curb secondary burn progression. Adenosine 2A receptor (A2AR) agonists have anti-inflammatory effects with decreased inflammatory cell infiltrate and release of proinflammatory mediators. Using a porcine comb burn model, we examined whether A2AR agonists could mitigate burn progression. Eight full-thickness comb burns (four prongs with three spaces per comb) per pig were generated with the following specifications: temperature 115°C, 3-kg force, and 30-second application time. In a randomized fashion, animals (four per group) were then treated with A2AR agonist (ATL-1223, 3 ng/kg/min, intravenous infusion over 6 hours) or vehicle control. Necrotic interspace development was the primary outcome and additional histologic assessments were conducted. Analysis of unburned interspaces (72 per group) revealed that ATL-1223 treatment decreased the rate of necrotic interspace development over the first 4 days following injury (p < .05). Treatment significantly decreased dermal neutrophil infiltration at 48 hours following burn (14.63 ± 4.30 vs 29.71 ± 10.76 neutrophils/high-power field, p = .029). Additionally, ATL-1223 treatment was associated with fewer interspaces with evidence of microvascular thrombi through postburn day 4 (18.8% vs 56.3%, p = .002). Two weeks following insult, the depth of injury at distinct burn sites (adjacent to interspaces) was significantly reduced by ATL-1223 treatment (2.91 ± 0.47 vs 3.28 ± 0.58 mm, p = .038). This work demonstrates the ability of an A2AR agonist to mitigate burn progression through dampening local inflammatory processes. Extended dosing strategies may yield additional benefit and improve cosmetic outcome in those with severe injury.

Prediction of Prolonged Intensive Care Unit Length of Stay Following Cardiac Surgery.

Intensive care unit (ICU) costs comprise a significant proportion of the total inpatient charges for cardiac surgery. No reliable method for predicting intensive care unit length of stay following cardiac surgery exists, making appropriate staffing and resource allocation challenging. We sought to develop a predictive model to anticipate prolonged ICU length of stay (LOS). All patients undergoing coronary artery bypass grafting (CABG) and/or valve surgery with a Society of Thoracic Surgeons (STS) predicted risk score were evaluated from an institutional STS database. Models were developed using 2014-2017 data; validation used 2018-2019 data. Prolonged ICU LOS was defined as requiring ICU care for at least three days postoperatively. Predictive models were created using lasso regression and relative utility compared. A total of 3283 patients were included with 1669 (50.8%) undergoing isolated CABG. Overall, 32% of patients had prolonged ICU LOS. Patients with comorbid conditions including severe COPD (53% vs 29%, P < 0.001), recent pneumonia (46% vs 31%, P < 0.001), dialysis-dependent renal failure (57% vs 31%, P < 0.001) or reoperative status (41% vs 31%, P < 0.001) were more likely to experience prolonged ICU stays. A prediction model utilizing preoperative and intraoperative variables correctly predicted prolonged ICU stay 76% of the time. A preoperative variable-only model exhibited 74% prediction accuracy. Excellent prediction of prolonged ICU stay can be achieved using STS data. Moreover, there is limited loss of predictive ability when restricting models to preoperative variables. This novel model can be applied to aid patient counseling, resource allocation, and staff utilization.

Commentary: Cardiothoracic surgery training made SIMPL.

BACKGROUND: Effective cardiothoracic surgical training requires an emphasis on education through timely feedback and constructive criticism. AIMS: Review of the implementation of the System for Improving and Measuring Procedural Learning application within a cardiothoracic surgical training program. MATERIALS & METHODS: Here, we review a report by Bergquist et al. to the Journal of Cardiac Surgery detailing their implementation of the System for Improving and Measuring Procedural Learning application. CONCLUSION: It is feasible for the SIMPL application to be implemented with acceptable use in a cardiothoracic training program.

Mixed type TAPVR-Measure twice, cut once.

Total anomalous pulmonary venous return (TAVR) can have varying drainage configurations. Here, we review a report by Nagulakonda et al. to the Journal of Cardiac Surgery detailing how additional computed tomography imaging revealed a mixed type presentation of TAPVR not identified on echocardiography.

Commentary: When will the robots come marching in?

Minimally invasive techniques for coronary artery bypass grafting (CABG), specifically robotic-assisted CABG has increased in popularity despite conflicting evidence. Here, we review a report by Yokoyama and colleagues to the Journal of Cardiac Surgery investigating outcomes of robotic versus nonrobotic CABG utilizing the National Inpatient Sample (NIS).

Surgical versus transcatheter mitral valve replacement in functional mitral valve regurgitation.

Surgical mitral valve intervention for severe functional, or secondary mitral regurgitation is a viable option for patients deemed to be operative candidates and can be performed via traditional sternotomy or by minimally invasive techniques with similar outcomes. Transcatheter mitral valve replacement is an emerging technology with a potential role in the treatment of functional mitral valve regurgitation. A plethora of devices are currently in development and in various stages of clinical investigation. Operative approach to transcatheter mitral valve replacement varies from a percutaneous transseptal approach to a hybrid percutaneous/surgical apical approach. The Tendyne, Intrepid and Evoque systems show promising results from their early feasibility studies in treatment of patients with mitral regurgitation that were too high risk for surgery. In this review, we describe considerations for surgical and transcatheter mitral valve replacement for functional mitral valve regurgitation.