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Background: Metabolic substrate utilization in HFpEF (heart failure with preserved ejection fraction), the leading cause of heart failure worldwide, is pivotal to syndrome pathogenesis and yet remains ill defined. Under resting conditions, oxidation of free fatty acids (FFA) is the predominant energy source of the heart, supporting its unremitting contractile activity. In the context of disease-related stress, however, a shift toward greater reliance on glucose occurs. In the setting of obesity or diabetes, major contributors to HFpEF pathophysiology, the shift in metabolic substrate use toward glucose is impaired, sometimes attributed to the lower oxygen requirement of glucose oxidation versus fat metabolism. This notion, however, has never been tested conclusively. Furthermore, whereas oxygen demand increases in the setting of increased afterload, myocardial oxygen availability remains adequate for fatty acid oxidation (FAO). Therefore, a "preference" for glucose has been proposed., Methods and Results: Pyruvate dehydrogenase complex (PDC) is the rate-limiting enzyme linking glycolysis to the TCA cycle. As PDK4 (PDC kinase 4) is up-regulated in HFpEF, we over-expressed PDK4 in cardiomyocytes, ensuring that PDC is phosphorylated and thereby inhibited. This leads to diminished use of pyruvate as energy substrate, mimicking the decline in glucose oxidation in HFpEF. Importantly, distinct from HFpEF-associated obesity, this model positioned us to abrogate the load-induced shift to glucose utilization in the absence of systemic high fat conditions. As expected, PDK4 transgenic mice manifested normal cardiac performance at baseline. However, they manifested a rapid and severe decline in contractile performance when challenged with modest increases in afterload triggered either by L-NAME or surgical transverse aortic constriction (TAC). This decline in function was not accompanied by an exacerbation of the myocardial hypertrophic growth response. Surprisingly, metabolic flux analysis revealed that, after TAC, fractional FAO decreased, even when glucose/pyruvate utilization was clamped at very low levels. Additionally, proteins involved in the transport and oxidation of FFA were paradoxically downregulated after TAC regardless of genotype., Conclusions: These data demonstrate that cardiomyocytes in a setting in which glucose utilization is robustly diminished and prevented from increasing do not compensate for the deficit in glucose utilization by up-regulating FFA use.

Objective: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting., Methods: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures., Results: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups., Conclusions: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy., Competing Interests: Conflict of Interest Statement Dr Hartwig receives research funding and/or consults for Transmedics, Biomedinnovations, Paragonix, and CSL Behring Ltd. Dr Bermudez serves on the medical advisory boards for Abiomed and Abbott. Dr Kon serves as a consultant for Medtronic and Breethe Inc. Dr Cantu receives research support from LignaMed Inc, Tbio Inc, and Xvivo Inc, and serves as a principal investigator for trials involving CareDx Inc and Pulmocide Ltd and additionally is a consultant for United Therapeutics Inc, CSL Behring Ltd, and the US Food and Drug Administration. Dr Whitson serves on the Clinical Events Committee of TransMedics OCS. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Coronary artery disease requiring surgical revascularization is prevalent in United States Veterans. We aimed to investigate preoperative predictors of 30-day mortality following coronary artery bypass grafting (CABG) in the Veteran population. The Veterans Affairs Surgical Quality Improvement (VASQIP) national database was queried for isolated CABG cases between 2008 and 2018. The primary outcome was 30-day mortality. A multivariable logistic regression was performed to assess for independent predictors of the primary outcome. A P-value of <0.05 was considered statistically significant. A total of 32,711 patients were included. The 30-day mortality rate was 1.37%. Multivariable analysis identified the following predictors of 30-day mortality: African-American race (OR 1.46, 95% CI 1.09-1.96); homelessness (OR 6.49, 95% CI 3.39-12.45); female sex (OR 2.15, 95% CI 1.08-4.30); preoperative myocardial infarction within 7 days (OR 1.49, 95% CI 1.06-2.10) or more than 7 days before CABG (OR 1.34, 95% CI 1.04-1.72); partially/fully dependent functional status (OR 1.44, 95% CI 1.07-1.93); chronic obstructive pulmonary disease (OR 1.54, 95% CI 1.24-1.92); mild (OR 1.48, 95% CI 1.04-2.11) and severe aortic stenosis (OR 2.06, 95% CI 1.37-3.09); moderate (OR 1.88, 95% CI 1.31-2.72), or severe (OR 2.99, 95% CI 1.71-5.22) mitral regurgitation; cardiomegaly (OR 1.73, 95% CI 1.35-2.22); NYHA Class III/IV heart failure (OR 2.05, 95% CI 1.10-3.83); and urgent/emergent operation (OR 1.42, 95% CI 1.08-1.87). The 30-day mortality rate in US Veterans undergoing isolated CABG between 2008 and 2018 was 1.37%. In addition to established clinical factors, African-American race and homelessness were independent demographic predictors of 30-day mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is the most prevalent arrhythmia and is often found during times of other cardiac pathologies that require surgical management including coronary revascularization and valve surgery. Surgical ablation of AF, most frequently performed through the Cox-Maze IV procedure, is highly effective in restoring sinus rhythm. Despite robust society guideline recommendations for concomitant surgical ablation (CSA) for AF, the practice has yet to be widely adopted. In this review, we discuss the current indications for CSA, its efficacy in maintaining freedom from atrial tachyarrhythmias, stroke, and adverse long-term outcomes, the safety profile of SA when performed alongside cardiac surgical cases, and challenges with its implementation across the most common concomitant cardiac operations. In conclusion, we present a reminder to multidisciplinary heart teams to consider CSA when indicated for their patients., Competing Interests: Declaration of competing interest RC is supported by the UTSW Training Resident Doctors as Innovators in Science (TARDIS) Fellowship, which is funded by the Burroughs-Wellcome Fund. The remaining authors have no competing interests to declare., (Published by Elsevier Inc.)

Objectives: Spontaneous sternoclavicular joint infection (SSCJI) is a rare and poorly understood disease process. This study aims to identify factors guiding effective management strategies for SSCJI by using data mining., Methods: An Institutional Review Board-approved retrospective review of patients from 2 large hospitals (2010-2022) was conducted. SSCJI is defined as a joint infection without direct trauma or radiation, direct instrumentation or contiguous spread. An interdisciplinary team consisting of thoracic surgeons, radiologists, infectious disease specialists, orthopaedic surgeons, hospital information experts and systems engineers selected relevant variables. Small set data mining algorithms, utilizing systems engineering, were employed to assess the impact of variables on patient outcomes., Results: A total of 73 variables were chosen and 54 analysed against 11 different outcomes. Forty-seven patients [mean age 51 (22-82); 77% male] met criteria. Among them, 34 underwent early joint surgical resection (<14 days), 5 patients received delayed surgical intervention (>14 days) and 8 had antibiotic-only management. The antibiotic-only group had comparable outcomes. Indicators of poor outcomes were soft tissue fluid >4.5 cm, previous SSCJI, moderate/significant bony fragments, HgbA1c >13.9% and moderate/significant bony sclerosis., Conclusions: This study suggests that targeted antibiotic-only therapy should be considered initially for SSCJI cases while concurrently managing comorbidities. Patients displaying indicators of poor outcomes or no symptomatic improvement after antibiotic-only therapy should be considered for surgical joint resection., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Socioeconomic disparities impact outcomes after cardiac surgery. At our institution, cardiac surgery cases from the safety-net, county funded hospital (CH), which primarily provides care for underserved patients, are performed at the affiliated university hospital. We aimed to investigate the association of socioeconomic factors and CH referral status with outcomes after coronary artery bypass grafting (CABG)., Methods: The institutional Adult Cardiac Surgery database was queried for perioperative and demographic data from patients who underwent isolated CABG between January 2014 and June 2020. The primary outcome was major adverse cardiovascular event (MACE), a composite of postoperative myocardial infarction, stroke, or death. Secondary outcomes included individual complications. Chi-square, Wilcoxon rank-sum, and logistic regression analyses were used to compare differences between CH and non-CH cohorts., Results: We included 836 patients with 472 (56.5%) from CH. Compared to the non-CH cohort, CH patients were younger, more likely to be Hispanic, non-English speaking, and be completely uninsured or require state-specific financial assistance. CH patients were more likely to have a history of tobacco and drug use, liver disease, diabetes, prior myocardial infarction, and greater degrees of left main coronary and left anterior descending artery stenosis. CH cases were less likely to be elective. The incidence of MACE was significantly higher in the CH cohort (16.3% versus 8.2%, P = 0.001). There were no significant differences in 30-d mortality, home discharge, prolonged mechanical ventilation, bleeding, sepsis, pneumonia, new dialysis requirement, cardiac arrest, or multiorgan system failure between cohorts. CH patients were more likely to develop renal failure and less likely to develop atrial fibrillation. On multivariable analysis, CH status (odds ratio 2.39, 95% confidence interval 1.25-4.55, P = 0.008) was independently associated with MACE., Conclusions: CH patients undergoing CABG presented with greater comorbidity burden, more frequently required nonelective surgery, and are at significantly higher risk of postoperative MACE., (Published by Elsevier Inc.)

Selective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs. However, current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even while preserving individual neuronal activity. Thus, we set out to mechanically render cerebral hemodynamics fully regulable to replicate or modify native pig brain perfusion. To this end, blood flow to the head was surgically separated from the systemic circulation and full extracorporeal pulsatile circulatory control (EPCC) was delivered via a modified aorta or brachiocephalic artery. This control relied on a computerized algorithm that maintained, for several hours, blood pressure, flow and pulsatility at near-native values individually measured before EPCC. Continuous electrocorticography and brain depth electrode recordings were used to evaluate brain activity relative to the standard offered by awake human electrocorticography. Under EPCC, this activity remained unaltered or minimally perturbed compared to the native circulation state, as did cerebral oxygenation, pressure, temperature and microscopic structure. Thus, our approach enables the study of neural activity and its circulatory manipulation in independence of most of the rest of the organism., (© 2023. Springer Nature Limited.)

Objective: Our objective was to evaluate for any changes in quality or cost when robotic lung resection is used with significant trainee participation. Methods: All anatomic lung resections between January 2006 and June 2016 were identified from a prospectively maintained database. Clinical data were recorded by double entry. Cost and cancer-related data were gathered from the business analytics department and tumor registry. Robotic outcomes were compared to an ongoing thoracotomy and video-assisted thoracic surgery (VATS) experience. Propensity scores using age, sex, and comorbidities were assigned for statistical analysis. Survival was evaluated using the Kaplan-Meier method. Results: Of 523 consecutive cases, 483 were included (211 robotic, 210 thoracotomy, 62 VATS). There were 74 robotic cases (35%) performed by trainees as the console surgeon. Length of stay was shortest for robotics (3 days) compared to thoracotomy (7 days, P  < 0.001) and VATS (5 days, P  = 0.010). Complications occurred in 33% of robotic cases, 42% of VATS cases ( P  = 0.854), and 52% of thoracotomy cases ( P  < 0.001). Stage I non-small cell lung cancer 3-year overall survival for robotics, thoracotomy, and VATS was 79.5%, 74.3%, and 74.0%, respectively ( P  > 0.25). There was no significant difference in negative margin rates. Total cost related to the hospitalization for surgery was $5,721 less for robotics compared to thoracotomy ( P  = 0.003) but comparable to VATS. Trainees served as console surgeon in 0% of cases in the first 2 years of robotics but increased to 79% in the last year of the study. Conclusions: Robotic lung resection can be safely performed and taught in an academic medical center without sacrificing quality or cost.

Objective: Up to 28% of patients may need mitral valve (MV) surgery after transcatheter edge-to-edge repair (TEER). This study evaluates the outcomes of minimally invasive MV surgery after TEER. Methods: International multicenter registry of minimally invasive MV surgery after TEER between 2013 and 2020. Subgroups were stratified by the number of devices implanted (≤1 vs >1), as well as time interval from TEER to surgery (≤1 year vs >1 year). Results: A total of 56 patients across 13 centers were included with a mean age of 73 ± 11 years, and 50% were female. The median Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) score for MV replacement was 8% (Q1-Q3 = 5% to 11%) and the ratio of observed to expected mortality was 0.9. The etiology of mitral regurgitation (MR) prior to TEER was primary MR in 75% of patients and secondary MR in 25%. There were 30 patients (54%) who had >1 device implanted. The median time between TEER and surgery was 252 days (33 to 636 days). Hemodynamics, including MR severity, MV area, and mean gradient, significantly improved after minimally invasive surgery and sustained to 1-year follow-up. In-hospital and 30-day mortality was 7.1%, and 1-year actuarial survival was 85.6% ± 6%. Conclusions: Minimally invasive MV surgery after TEER may be achieved as predicted by the STS PROM. Most patients underwent MV replacement instead of repair. As TEER is applied more widely, patients should be informed about the potential need for surgical intervention over time after TEER. These discussions will allow better informed consent and post-procedure planning.

Lung transplantation is an established treatment for patients with end-stage lung disease. However, a shortage of donors, low lung utilization among potential donors, and waitlist mortality continue to be challenges. In the last decade, ex vivo lung perfusion (EVLP) has expanded the donor pool by allowing prolonged evaluation of marginal donor lungs and allowing reparative therapies for lungs, which are otherwise considered not transplantable. In this review, we describe in detail our experience with EVLP including our workflow, setup, operative technique, and protocols. Our multidisciplinary EVLP program functions with the collaboration of surgeons, pulmonologists, and EVLP nurses who run the pump. EVLP program has been a valuable addition to our program. Since Food and Drug Administration (FDA) approval in 2019, we experienced incremental increased lung transplant volume of 12% annually., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

Lung transplantation is considered the gold standard for patients with chronic end-stage pulmonary disease. However, due to the complexity of management and relatively lower median survival as compared to other solid organs, many programs across the world have been slow to adopt the same. In our institution, we started lung transplantation in September 1990. And since then, we performed close to 900 lung transplantations. Here, we describe in detail the operative steps adopted in our institution for a successful lung transplantation. There have been very few variations over the years. We believe that having a standardized technique is one of the important features for success of a lung transplant program., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

Background: The optimal substrate for hypothermic machine perfusion preservation of donor hearts is unknown. Fatty acids, acetate, and ketones are preferred substrates of the heart during normothermic perfusion, but cannot replete the tricarboxylic acid (TCA) cycle directly. Propionate, an anaplerotic substrate, can replenish TCA cycle intermediates and may affect cardiac metabolism. The purpose of this study was to determine myocardial substrate preferences during hypothermic machine perfusion and to assess if an anaplerotic substrate was required to maintain the TCA cycle intermediate pool in perfused hearts., Methods: Groups of rat hearts were perfused with carbon-13 ( 13 C)-labeled substrates (acetate, β-hydroxybutyrate, octanoate, with and without propionate) at low and high concentrations. TCA cycle intermediate concentrations, substrate selection, and TCA cycle flux were determined by gas chromatography/mass spectroscopy and 13 C magnetic resonance spectroscopy., Results: Acetate and octanoate were preferentially oxidized, whereas β-hydroxybutyrate was a minor substrate. TCA cycle intermediate concentrations except fumarate were higher in substrate-containing perfusion groups compared with either the no-substrate perfusion group or the no-ischemia control group., Conclusions: The presence of an exogenous, oxidizable substrate is required to support metabolism in the cold perfused heart. An anaplerotic substrate is not essential to maintain the TCA cycle intermediate pool and support oxidative metabolism under these conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of severe aortic stenosis (AS) over the last decade. The results of the Placement of Aortic Transcatheter Valves (PARTNER) 3 and Evolut Low Risk trials demonstrated the safety and efficacy of TAVR in low-surgical-risk patients and led to the approval of TAVR for use across the risk spectrum. Heart teams around the world will now be faced with evaluating a deluge of younger, healthier patients with severe AS. Prior to the PARTNER 3 and Evolut Low Risk studies, this heterogenous patient population would have undergone surgical aortic valve replacement (SAVR). It is unlikely that TAVR will completely supplant SAVR for the treatment of severe AS in patients with a low surgical risk, as SAVR has excellent short- and long-term outcomes and years of durability data. In this review, we outline the critical role that SAVR will continue to play in the treatment of severe AS in the post-PARTNER 3/Evolut Low Risk era.

Background: Acute kidney injury after cardiac surgery significantly associates with morbidity and mortality. Despite not requiring cardiopulmonary bypass, transcatheter aortic valve replacement patients have an incidence of post-procedural acute kidney injury similar to patients who undergo open surgical aortic valve replacement. Packed red blood cell transfusion has been associated with morbidity and mortality after cardiac surgery. We hypothesized that packed red blood cell transfusion independently associates with acute kidney injury after transcatheter aortic valve replacement, after accounting for other risk factors., Methods: This is a single-center retrospective cohort study of 116 patients undergoing transcatheter aortic valve replacement. Post-transcatheter aortic valve replacement acute kidney injury was defined by Kidney Disease: Improving Global Outcomes serum creatinine-based criteria. Univariate comparisons between patients with and without post-transcatheter aortic valve replacement acute kidney injury were made for clinical characteristics. Multivariable logistic regression was used to assess independent association of packed red blood cell transfusion with post-transcatheter aortic valve replacement acute kidney injury (adjusting for pre-procedural renal function and other important clinical parameters)., Results: Acute kidney injury occurred in 20 (17.2%) subjects. Total number of packed red blood cells transfused independently associated with post-procedure acute kidney injury (OR = 1.67 per unit, 95% CI 1.13-2.47, P = 0.01) after adjusting for pre-procedure estimated glomerular filtration rate (OR = 0.97 per ml/min/1.73m 2 , 95% CI 0.94-1.00, P = 0.05), nadir hemoglobin (OR = 0.88 per g/dL increase, CI 0.61-1.27, P = 0.50), and post-procedure maximum number of concurrent inotropes and vasopressors (OR = 2.09 per inotrope or vasopressor, 95% CI 1.19-3.67, P = 0.01)., Conclusion: Packed red blood cell transfusion, along with post-procedure use of inotropes and vasopressors, independently associate with acute kidney injury after transcatheter aortic valve replacement. Further studies are needed to elucidate the pathobiology underlying these associations.

Background: Cardiac surgery-associated acute kidney injury (AKI) is associated with increased morbidity and mortality. We examined the utility of combining biomarkers of kidney function loss (serum cystatin C) and kidney tubular damage (urine neutrophil gelatinase-associated lipocalin [NGAL] and Kidney Injury Molecule-1 [KIM-1]) for the prediction of post-cardiac surgery AKI., Methods: Single-center prospective cohort study of 106 adults undergoing coronary artery bypass grafting and/or valve surgery with cardiopulmonary bypass (CPB). Primary outcome was postoperative in-hospital AKI defined by serum creatinine (SCr)-Kidney Disease: Improving Global Outcomes criteria. Biomarkers were measured preoperatively, 6 hours after CPB and on postoperative days (PODs) 1 to 4., Results: A total of 23 subjects (21.7%) developed AKI. After adjusting for preoperative left ventricular ejection fraction, body mass index >30 kg/m 2 , and estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m 2 , the combination of peak serum cystatin C and peak urine KIM-1/creatinine (Cr) (6 hours post-CPB to POD 1) above optimal cutoff significantly associated with postoperative AKI (odds ratio [OR]: 5.32; 95% confidence interval [CI]: 1.31-21.67; P  = 0.020). This biomarker combination significantly improved the performance of the clinical model for the prediction of postoperative AKI (area under the curve [AUC]: 0.77, 95% CI: 0.65-0.90 for the clinical model alone versus 0.83, 95% CI: 0.73-0.93 for the clinical model with the addition of biomarker data, P  = 0.049)., Conclusions: Combining biomarkers of postoperative kidney function loss and postoperative kidney tubular damage significantly improved prediction of in-hospital AKI following cardiac surgery. Future large, multicenter studies are warranted to assess whether panels of biomarkers reflecting distinct pathobiology can be used to guide interventions and improve short- and long-term outcomes in patients undergoing cardiac surgery.

Background: The influence of diabetic therapies on myocardial substrate selection during cardiac surgery is unknown but may be important to ensure optimal surgical outcomes. We hypothesized that metformin and insulin alter myocardial substrate selection during cardiac surgery and may affect reperfusion cardiac function., Methods: Rat hearts (n = 8 per group) were evaluated under 3 metabolic conditions: normokalemia, cardioplegia, or bypass. Groups were perfused with Krebs-Henseleit buffer in the presence of no additives, metformin, insulin, or both insulin and metformin. Perfusion buffer containing physiologic concentrations of energetic substrates with different carbon-13 ( 13 C) labeling patterns were used to determine substrate oxidation preferences using 13 C magnetic resonance spectroscopy and glutamate isotopomer analysis. Rate pressure product and oxygen consumption were measured., Results: Myocardial function was not different between groups. For normokalemia, ketone oxidation was reduced in the presence of insulin and the combination of metformin and insulin reduced fatty acid oxidation. Metformin reduced fatty acid and ketone oxidation during cardioplegia. Fatty acid oxidation was increased in the bypass group compared with all other conditions., Conclusion: Metformin and insulin affect substrate utilization and reduce fatty acid oxidation before reperfusion. These alterations in substrate oxidation did not affect myocardial function in otherwise normal hearts., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Risk-adjusted operative mortality is the most important quality metric in cardiac surgery for determining The Society of Thoracic Surgeons (STS) Composite Score for star ratings. Accurate 30-day status is required to determine STS operative mortality. The goal of this study was to determine the effect of unknown or missing 30-day status on risk-adjusted operative mortality in a regional STS Adult Cardiac Surgery Database cooperative and demonstrate the ability to correct these deficiencies by matching with an administrative database., Methods: STS Adult Cardiac Surgery Database data were submitted by 27 hospitals from five hospital systems to the Texas Quality Initiative (TQI), a regional quality collaborative. TQI data were matched with a regional hospital claims database to resolve unknown 30-day status. The risk-adjusted operative mortality observed-to-expected (O/E) ratio was determined before and after matching to determine the effect of unknown status on the operative mortality O/E., Results: TQI found an excessive (22%) unknown 30-day status for STS isolated coronary artery bypass grafting cases. Matching the TQI data to the administrative claims database reduced the unknowns to 7%. The STS process of imputing unknown 30-day status as alive underestimates the true operative mortality O/E (1.27 before vs 1.30 after match), while excluding unknowns overestimates the operative mortality O/E (1.57 before vs 1.37 after match) for isolated coronary artery bypass grafting., Conclusions: The current STS algorithm of imputing unknown 30-day status as alive and a strategy of excluding cases with unknown 30-day status both result in erroneous calculation of operative mortality and operative mortality O/E. However, external validation by matching with an administrative database can improve the accuracy of clinical databases such as the STS Adult Cardiac Surgery Database., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Importance: Identifying high-performing surgical valve centers with the best surgical outcomes is challenging. Hospital surgical volume is a frequently used surrogate for outcomes. However, its ability to distinguish low-performing and high-performing hospitals remains unknown., Objective: To examine the association of hospital procedure volume with hospital performance for aortic and mitral valve (MV) surgical procedures., Design, Setting, and Participants: Within an all-payer nationally representative data set of inpatient hospitalizations, this study identified 682 unique hospitals performing surgical aortic valve replacement (SAVR) and MV replacement and repair with or without coronary artery bypass grafting (CABG) between 2007 and 2011. Procedural outcomes were further assessed for a 10-year period (2005-2014) to assess representativeness of study period., Main Outcomes and Measures: In-hospital risk-standardized mortality rate (RSMR) calculated using hierarchical models and an empirical bayesian approach with volume-based shrinkage that allowed for reliability adjustment., Results: At 682 US hospitals, 70 295 SAVR, 19 913 MV replacement, and 17 037 MV repair procedures were performed between 2007 and 2011, with a median annual volume of 43 (interquartile range [IQR], 23-76) SAVR, 13 (IQR, 6-22) MV replacement, and 9 (IQR, 4-19) MV repair procedures. Of 225 SAVR hospitals in the highest-volume tertile, 34.7% and 36.0% were in the highest-RSMR tertile for SAVR + CABG and isolated SAVR procedures, respectively, while 21.5% and 17.5% of the 228 SAVR hospitals in the lowest-volume tertile were in the lowest respective RSMR tertile. Similarly, 36.8% and 43.5% of hospitals in the highest tertile of volume for MV replacement and repair, respectively, were in the corresponding highest-RSMR tertile, and 17.4% and 11.2% of the low-volume hospitals were in the lowest-RSMR tertile for MV replacement and repair, respectively. There was limited correlation between outcomes for SAVR and MV procedures at an institution. If solely volume-based tertiles were used to categorize hospitals for quality, 44.7% of all valve hospitals would be misclassified (as either low performing or high performing) when assessing performance based on tertiles of RSMR., Conclusions and Relevance: Hospital procedure volume alone frequently misclassifies hospital performance with regard to risk-standardized outcomes after aortic and MV surgical procedures. Valve surgery quality improvement endeavors should focus on a more comprehensive assessment that includes risk-adjusted outcomes rather than hospital volume alone.

Purpose: Acute kidney injury (AKI) is a potentially serious complication of cardiac surgery. Anemia and red blood cell (RBC) transfusion have individually been identified as potentially modifiable risk factors, but their interrelationship with AKI has not been clearly defined. The purpose of this study was to explore the interrelationship of preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery with AKI in cardiac surgery., Methods: This historical cohort study included 16 hospitals, each contributing data on approximately 100 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass. Acute kidney injury was defined as a > 50% increase in creatinine levels during the first postoperative week. Multivariable regression was used to identify the interrelationship between preoperative anemia (hemoglobin < 130 g·L(-1) in males and < 120 g·L(-1) in females), intraoperative anemia (hemoglobin < 80 g·L(-1) during cardiopulmonary bypass), RBC transfusion on the day of surgery, and their interaction terms, after adjusting for site and baseline AKI risk., Results: Of the 1,444 patients included in the study, 541 (37%) had preoperative anemia, 501 (35%) developed intraoperative anemia, 619 (43%) received RBC transfusions, and 238 (16%) developed AKI. After risk-adjustment, an individual with the combination of these three risk factors had a 2.6-fold (95% confidence interval 2.0 to 3.3) increase in the relative risk of AKI over an individual with none of these risk factors., Conclusions: Preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery are interrelated risk factors for AKI after cardiac surgery. Targeting these risk factors may reduce the burden of AKI.

Objective: High-quality prospective trials of hemostatic "rescue" therapy to control massive bleeding in cardiac surgery are lacking. Wide variability in the care of patients with severe bleeding following cardiopulmonary bypass has precluded accurate comparison of treatment groups in previous studies. This study identified the use of a management protocol for early identification and uniform treatment of patients with massive bleeding for application in future trials of hemostatic rescue agents., Design: A prospective, nonblinded, interventional feasibility study., Setting: A university teaching hospital., Participants: Forty-three adult patients undergoing complex cardiac surgery., Interventions: Study participants undergoing high-risk cardiac surgery received standardized treatment in accordance with a bleeding management protocol., Measurements and Main Results: Twenty-seven patients (63%) had severe bleeding following heparin reversal and received conventional hemostatic resuscitation per protocol. Six patients had massive refractory bleeding. Compliance with protocol tasks was≥90% in 4 of 5 categories (anticoagulation, hemostasis scoring, recording blood loss, protocol transfusion) with the exception being submission of laboratory samples (76%). Measured bleeding rates (mL/h) following heparin reversal were clearly differentiated in those with hemostasis scores≥3 compared to those with scores≤2 (1,420±957 v 147±96; p<0.001)., Conclusions: Adherence to a management protocol for massive bleeding is feasible and allows for homogenous treatment of patients before study arm randomization in future "rescue" therapy trials. The authors' protocol allowed for prompt and accurate identification of patients with severe bleeding refractory to conventional therapy. This review resolved several key barriers in the design of severe bleeding management trials., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Donation after circulatory determination of death (DCDD) involves variable definitions of death among hospitals, and DCDD hearts are not generally considered for transplantation. The definition can affect ischemic times, and machine perfusion preservation appears promising for recovery of DCDD hearts. The purpose of the current study was to investigate the agonal phase of DCDD donors and evaluate retrograde perfusion preservation of DCDD donor hearts in a large animal model of cardiac transplantation., Methods: Ten canines were anesthetized and then disconnected from mechanical ventilation. Time to loss of pulse (systolic blood pressure <50 mm Hg), loss of pressure, and asystole or fibrillation were recorded. Five minutes after asystole, hearts were exposed and arrested with 1 L of University of Wisconsin Machine Perfusion Solution. Eight hearts were cold preserved for 4 hours by retrograde machine perfusion or static storage (n = 4/group), then reimplanted and reperfused for 6 hours. The preload recruitable stroke work was used to measure myocardial function., Results: The agonal phase was similar between groups. Loss of pulse and pressure were consistent between animals (7.9 ± 0.5 minutes [range, 5 to 11 minutes], 10.2 ± 0.4 minutes [range, 9 to 13 minutes], respectively). Electrical silence was variable at 26.9 ± 3.8 minutes (range, 11 to 43 minutes). All perfused hearts separated and remained off cardiopulmonary bypass. Three of four static hearts initially separated from cardiopulmonary bypass, but two returned by the end of the reperfusion period. The preload recruitable stroke work was significantly higher in perfused hearts., Conclusions: Protocols for DCDD have implications on ischemic times of donor hearts. Machine perfusion preservation can recover DCDD hearts more consistently than static storage., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Machine perfusion of donor hearts is a promising strategy to increase the donor pool. Antegrade perfusion is effective but can lead to aortic valve incompetence and nonnutrient flow. Experience with retrograde coronary sinus perfusion of donor hearts has been limited. We tested the hypothesis that retrograde perfusion could support myocardial metabolism over an extended donor ischemic interval., Methods: Human hearts from donors that were rejected or not offered for transplantation were preserved for 12 hours in University of Wisconsin Machine Perfusion Solution by: (1) static hypothermic storage; (2) hypothermic antegrade machine perfusion; or (3) hypothermic retrograde machine perfusion. Myocardial oxygen consumption (MVO2), and lactate accumulation were measured. Ventricular tissue was collected for proton and phosphorus 31 magnetic resonance spectroscopy (MRS) to evaluate the metabolic state of the myocardium. Myocardial water content was determined at the end of the experiment., Results: Stable perfusion parameters were maintained throughout the perfusion period with both perfusion techniques. Lactate/alanine ratios were lower in perfused hearts compared with static hearts (P<.001). Lactate accumulation (antegrade 2.0±0.7 mM, retrograde 1.7±0.1 mM) and MVO2 (antegrade 0.25±0.2 mL, retrograde 0.26±0.3 mL O2/min/100 g) were similar in machine-perfused groups. High-energy phosphates were better preserved in both perfused groups (P<.05). Left ventricular myocardial water content was increased in retrograde perfused hearts (80.2±0.8%) compared with both antegrade perfused hearts (76.6±0.8%, P=.02) and static storage hearts (76.7±1%, P=.02)., Conclusions: Machine perfusion by either the antegrade or the retrograde technique can support myocardial metabolism over long intervals. Machine perfusion seems promising for long-term preservation of human donor hearts., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Most studies investigating machine perfusion preservation for heart transplantation perfuse through the aortic root (antegrade), but the coronary sinus (retrograde) is a potential option. We hypothesized that retrograde machine perfusion provides better functional protection than static storage, while avoiding the potential irregular perfusion seen when aortic insufficiency occurs with antegrade perfusion., Materials and Methods: Eighteen canine donor hearts were arrested, procured, and stored in modified Celsior solution for 4 hours by using either static storage at 0°C to 4°C (n = 6) or machine perfusion preservation at 5°C via the aortic root (antegrade, n = 6) or coronary sinus (retrograde, n = 6). Lactate and myocardial oxygen consumption were measured in perfused hearts. Hearts were reimplanted and reperfused for 6 hours with hourly function calculated by using the preload recruitable stroke work (PRSW) relation. Myocardial water content was determined at the end of the experiment., Results: Storage lactate levels and myocardial oxygen consumption were comparable in both perfused groups. The PRSW was increased immediately after bypass in the antegrade group (120.6 ± 19.1 mm Hg) compared with the retrograde (75.0 ± 11.3 mm Hg) and static (78.1 ± 10.5 mm Hg) storage groups (P < .05). At the end of reperfusion, PRSW was higher in the retrograde group (69.8 ± 7.4 mm Hg) compared with the antegrade (40.1 ± 6.8 mm Hg) and static (39.9 ± 10.9 mm Hg) storage groups (P < .05). Myocardial water content was similar among groups., Conclusions: Both antegrade and retrograde perfusion demonstrated excellent functional preservation, at least equivalent to static storage. Initial function was superior in the antegrade group, but the retrograde hearts displayed better function late after reperfusion. Neither perfused group developed significant edema. Machine perfusion preservation is a promising technique for improving results of cardiac transplantation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Although numerous reports describe the results of off-pump coronary artery bypass grafting (CABG) at specialized centers and in select patient populations, it remains unclear how off-pump CABG affects real-world patient outcomes. We conducted a large, multicenter observational cohort study of perioperative death and morbidity in on-pump (ON) versus off-pump (OFF) CABG. We reviewed Veterans Affairs Surgical Quality Improvement Program data for all patients (N=65,097) who underwent isolated CABG from October 1997 through April 2011 (intention-to-treat data were available from 2005 onward). The primary outcome was perioperative (30-day or in-hospital) death; the secondary outcomes were perioperative stroke, dialysis dependence, reoperation for bleeding, mechanical circulatory support, myocardial infarction, ventilator support ≥ 48 hr, and mediastinitis. Propensity scores calculated from age, 17 preoperative risk factors, and year of surgery were used to match 8,911 OFF with 26,733 ON patients. In the complete cohort, compared with the ON patients (n=53,468), the OFF patients (n=11,629) had less perioperative death (2.02% vs 2.53%, P=0.0012) and lower incidences of all morbidities except perioperative myocardial infarction. In the matched cohort, perioperative death did not differ significantly between OFF and ON patients (1.94% vs 2.28%, P=0.06), but the OFF group had lower incidences of all morbidities except for perioperative myocardial infarction and mediastinitis. A subgroup intention-to-treat analysis yielded similar but smaller outcome differences between the ON and OFF groups. Off-pump CABG might be associated with decreased operative morbidity but did not affect operative death, compared with on-pump CABG. Future studies should examine the effect of off-pump CABG on long-term outcomes.

Background: Reperfusion accounts for a substantial fraction of the myocardial injury occurring with ischemic heart disease. Yet, no standard therapies are available targeting reperfusion injury. Here, we tested the hypothesis that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor approved for cancer treatment by the US Food and Drug Administration, will blunt reperfusion injury., Methods and Results: Twenty-one rabbits were randomly assigned to 3 groups: (1) vehicle control, (2) SAHA pretreatment (1 day before and at surgery), and (3) SAHA treatment at the time of reperfusion only. Each arm was subjected to ischemia/reperfusion surgery (30 minutes coronary ligation, 24 hours reperfusion). In addition, cultured neonatal and adult rat ventricular cardiomyocytes were subjected to simulated ischemia/reperfusion to probe mechanism. SAHA reduced infarct size and partially rescued systolic function when administered either before surgery (pretreatment) or solely at the time of reperfusion. SAHA plasma concentrations were similar to those achieved in patients with cancer. In the infarct border zone, SAHA increased autophagic flux, assayed in both rabbit myocardium and in mice harboring an RFP-GFP-LC3 transgene. In cultured myocytes subjected to simulated ischemia/reperfusion, SAHA pretreatment reduced cell death by 40%. This reduction in cell death correlated with increased autophagic activity in SAHA-treated cells. RNAi-mediated knockdown of ATG7 and ATG5, essential autophagy proteins, abolished SAHA's cardioprotective effects., Conclusions: The US Food and Drug Administration-approved anticancer histone deacetylase inhibitor, SAHA, reduces myocardial infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during ischemia/reperfusion occur, at least in part, through the induction of autophagic flux.

Importance: Numerous studies have compared the results of on-pump and off-pump coronary artery bypass grafting (CABG), but little is known about how either the relative use of these procedures or their associated perioperative mortality have changed with time., Objective: To examine trends in off- and on-pump CABG use and outcomes over time., Design: Retrospective analysis of data from the Veterans Affairs Surgical Quality Improvement Program (VASQIP)., Setting: Data were collected from 42 Veterans Affairs cardiac surgery centers., Participants: All Veterans Affairs patients (n = 65,097) who underwent isolated primary CABG from October 1997 to April 2011., Interventions: Patients underwent either on-pump (ON) or off-pump (OFF) CABG., Main Outcomes and Measures: The percentages of ON vs OFF cases as a function of time. We also evaluated trends over time in rates of conversion from OFF to ON CABG, perioperative mortality (30-day or in-hospital), and VASQIP predicted risk of mortality., Results: The relative use of OFF CABG peaked at 24% in 2003, followed by a slow and mostly consistent decline to stabilize at about 19%. The conversion rate decreased with time and has stayed less than 3.5% since 2007 (P < .001). Perioperative mortality rates decreased over time for both ON and OFF CABG (P < .001) and have stayed less than 2% for the entire cohort since 2006. The mortality associated with converted cases was high regardless of the surgery year and exceeded the VASQIP predicted risk of mortality., Conclusions and Relevance: There has been a decline in the relative use of OFF CABG in the Veterans Affairs system since 2003. This trend may affect the training of future generations in OFF surgery and influence conversion rates and outcomes.

Objective: Simultaneous inhibition of the cardiac equilibrative-p-nitrobenzylthioinosine (NBMPR)-sensitive (es) type of the equilibrative nucleoside transport 1 (ENT1) nucleoside transporter, with NBMPR, and adenosine deaminase, with erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA), prevents release of myocardial purines and attenuates myocardial stunning and fibrillation in canine models of warm ischemia and reperfusion. It is not known whether prolonged administration of hypothermic cardioplegia influences purine release and EHNA/NBMPR-mediated cardioprotection in acutely ischemic hearts., Methods: Anesthetized dogs (n = 46), which underwent normothermic aortic crossclamping for 20 minutes on-pump, were divided to determine (1) purine release with induction of intermittent antegrade or continuous retrograde hypothermic cardioplegia and reperfusion, (2) the effects of postischemic treatment with 100 μM EHNA and 25 μM NBMPR on purine release and global functional recovery, and (3) whether a hot shot and reperfusion with EHNA/NBMPR inhibits purine release and attenuates ventricular dysfunction of ischemic hearts. Myocardial biopsies and coronary sinus effluents were obtained and analyzed using high-performance liquid chromatography., Results: Warm ischemia depleted myocardial adenosine triphosphate and elevated purines (ie, inosine > adenosine) as markers of ischemia. Induction of intermittent antegrade or continuous retrograde hypothermic (4°C) cardioplegia releases purines until the heart becomes cold (<20°C). During reperfusion, the levels of hypoxanthine and xanthine (free radical substrates) were >90% of purines in coronary sinus effluent. Reperfusion with EHNA/NBMPR abolished ventricular dysfunction in acutely ischemic hearts with and without a hot shot and hypothermic cardioplegic arrest., Conclusions: Induction of hypothermic cardioplegia releases purines from ischemic hearts until they become cold, whereas reperfusion induces massive purine release and myocardial stunning. Inhibition of cardiac es-ENT1 nucleoside transporter abolishes postischemic reperfusion injury in warm and cold cardiac surgery., (Published by Mosby, Inc.)

Background: There are ample data regarding the short-term outcomes of on-pump and off-pump coronary artery bypass grafting (CABG), but little is known about the long-term survival associated with these approaches., Methods: Using the Veterans Affairs (VA) Continuous Improvement in Cardiac Surgery Program, we identified all VA patients (n = 65,097) who underwent primary isolated CABG from October 1997 to April 2011. The primary outcome measure was all-cause mortality. Age, 17 preoperative risk factors, and year of operation were used to calculate propensity scores for each patient. A greedy-match algorithm using the propensity scores matched 8,911 off-pump with 26,733 on-pump patients. Survival functions were estimated by the Kaplan-Meier method and compared by using the log-rank test., Results: In the complete cohort, off-pump was used in 11,629 of 65,097 (17.9%) operations. For the matched cohort, the median follow-up was 6.7 years (interquartile range, 3.72 to 9.35 years). Risk-adjusted mortality did not differ significantly between the off-pump and on-pump groups at 1 year (4.67% vs 4.78%; risk ratio [RR], 0.98; 95% confidence interval [CI], 0.88 to 1.09) or 3 years (9.21% vs 8.89%; RR, 1.04; 95% CI, 0.96 to 1.12). However, risk-adjusted mortality was higher in the off-pump group at 5 years (14.47% vs 13.45%; RR, 1.08; 95% CI 1.02 to 1.15) and 10 years (25.18% vs 23.57%; RR, 1.07; 95% CI, 1.03 to 1.12). Overall, the hazard ratio for off-pump vs on-pump was 1.06 (95% CI, 1.00 to 1.13; p = 0.04)., Conclusions: Off-pump CABG may be associated with decreased long-term survival. Further studies are needed to identify the reasons behind this finding., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Presence of epicardial coronary artery chronic total occlusion (CTO) predicts higher referral rates for coronary bypass graft surgery (CABG). However, the impact of coronary artery CTO on CABG outcomes has never been systematically studied., Method: We examined one-year outcomes in 605 consecutive Veterans, discharged post-CABG between June 2005 and December 2008., Results: A coronary CTO was present in 256 patients (42%), predominantly (48.3%) in the right coronary artery distribution. Baseline clinical characteristics and medical therapy were similar in patients with and without a coronary CTO. A single CTO was present in 73.8%, and 26.2% patients had multiple CTO. All left anterior descending coronary artery CTO were successfully bypassed, as were >92% in left circumflex and right coronary arteries and 85% CTO in multiple coronary artery distributions. During the mean follow-up of 348.9 ± 4.5 days, incidence of all-cause death and myocardial infarction were similar in both groups (7.1% in CTO group and 7.4% in non-CTO group; p = 0.97). CTO >20 mm in length constituted 74.9% and >40 mm 37.8%. One-year survival post-CABG was significantly lower in patients with CTO lengths >40 mm compared to ≤20 mm (p = 0.04). CTO >40 mm was an independent predictor of post-CABG mortality controlling for age, number of CTO, comorbid diseases, clopidogrel use, severity of coronary artery disease, renal failure, and left ventricular ejection fraction., Conclusion: CABG achieves high success in grafting epicardial coronary vessels with CTO; however, presence of long coronary CTO (>40 mm) is an independent predictor of post-CABG survival., (© 2012 Wiley Periodicals, Inc.)