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Objective: Right ventricular (RV) dysfunction in cardiac surgery can lead to RV failure, which is associated with increased morbidity and mortality. Abnormal RV function can be identified using RV pressure monitoring. The primary objective of the study is to determine the proportion of patients with abnormal RV early to end-diastole diastolic pressure gradient (RVDPG) and abnormal RV end-diastolic pressure (RVEDP) before initiation and after cardiopulmonary bypass (CPB) separation. The secondary objective is to evaluate if RVDPG before CPB initiation is associated with difficult and complex separation from CPB, RV dysfunction, and failure at the end of cardiac surgery., Design: Prospective study., Setting: Tertiary care cardiac institute., Participants: Cardiac surgical patients., Intervention: Cardiac surgery., Measurements and Main Results: Automated electronic quantification of RVDPG and RVEDP were obtained. Hemodynamic measurements were correlated with cardiac and extracardiac parameters from transesophageal echocardiography and postoperative complications. Abnormal RVDPG was present in 80% of the patients (n = 105) at baseline, with a mean RVEDP of 14.2 ± 3.9 mmHg. Patients experienced an RVDPG > 4 mmHg for a median duration of 50.2% of the intraoperative period before CPB initiation and 60.6% after CPB separation. A total of 46 (43.8%) patients had difficult/complex separation from CPB, 18 (38.3%) patients had RV dysfunction, and 8 (17%) had RV failure. Abnormal RVDPG before CPB was not associated with postoperative outcome., Conclusion: Elevated RVDPG and RVEDP are common in cardiac surgery. RVDPG and RVEDP before CPB initiation are not associated with RV dysfunction and failure but can be used to diagnose them., Competing Interests: Declaration of competing interest Dr. Denault received a research grant from Edwards Lifesciences. He is a consultant for CAE Healthcare and on the speakers bureau for Masimo. Daniel Scherb, Kevin Moses, and Cristhian Potes are engineers from Edwards Lifesciences, Irvine, CA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To demonstrate the value of a viscoelastic-based intraoperative transfusion algorithm to reduce non-RBC product administration in adult cardiac surgical patients., Design: A prospective observational study., Setting: At a quaternary academic teaching hospital., Participants: Cardiac surgical patients., Interventions: Viscoelastic-based intraoperative transfusion algorithm., Measurements and Main Results: The study authors compared intraoperative blood product transfusion rates in 184 cardiac surgical patients to 236 historic controls after implementing a viscoelastic-based algorithm. The authors found a non-significant reduction in transfusion of 23.8% for fresh frozen plasma (FFP) units (0.84 ± 1.4 v 0.64 ± 1.38; p = ns), 33.4% for platelet units (0.90 ± 1.39 v 0.60 ± 131; p = ns), and 15.8% for cryoprecipitate units (0.19 ± 0.54 v 0.16 ± 0.50; p = ns). They found a 43.9% reduction in red blood cell (RBC) units transfused (1.98 ± 2.24 v 0.55 ± 1.36; p = 0.008). There were no statistically significant differences in time to extubation (8.0 hours (4.0-21.0) v 8.0 (4.0-22.3), reoperation for bleeding (15 [12.3%] v 10 [10.6%]), intensive care unit length of stay (ICU LOS) (51.0 hours [28.0-100.5] v 53.5 [33.3-99.0]) or hospital LOS (9.0 days [6.0-15.0] v 10.0 [7.0-17.0]). Deviation from algorithm adherence was 32.7% (48/147). Packed RBC, FFP, platelets, cryoprecipitate, and cell saver were significantly reduced in the Algorithm Compliant Cohort compared with historic controls, whereas times to extubation, ICU LOS, and hospital LOS did not reach significance., Conclusions: After the implementation of a viscoelastic-based algorithm, patients received fewer packed RBC, FFP, platelets, cryoprecipitate, and cell saver. Algorithm-compliant patients received fewer transfusions; however, reductions in times to extubation, ICU LOS, and hospital LOS were not statistically significant compared with historic controls., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Society of Cardiovascular Anesthesiologists (SCA) is committed to improving the quality, safety, and value that cardiothoracic anesthesiologists bring to patient care. To fulfill this mission, the SCA supports the creation of peer-reviewed manuscripts that establish standards, produce guidelines, critically analyze the literature, interpret preexisting guidelines, and allow experts to engage in consensus opinion. The aim of this report, commissioned by the SCA President, is to summarize the distinctions among these publications and describe a novel SCA-supported framework that provides guidance to SCA members for the creation of these publications. The ultimate goal is that through a standardized and transparent process, the SCA will facilitate up-to-date education and implementation of best practices by cardiovascular and thoracic anesthesiologists to improve patient safety, quality of care, and outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Background: The right ventricle (RV) plays a central  role in the maintenance of effective cardiac pump function. Despite overwhelming evidence that perioperative RV dysfunction (RVD) and failure (RVF) are associated with poor clinical outcomes, there are very few published recommendations or guidelines for comprehensive, evidence-based RV assessment on the risk of developing either during the perioperative period., Main Text: To address this gap, the Perioperative Quality Initiative-IX (POQI-IX) investigators group, comprised of clinical experts in anesthesiology, cardiovascular surgery, internal medicine, critical care medicine, and advanced practice nursing, has developed a consensus statement based on current literature, published society recommendations, and the clinical expertise of the group. Herein, the group provides recommendations and evidence-based tools related to perioperative RV assessment, functional screening, staging, and the clinical implications of each. These assessment tools are based on comprehensive patient evaluation consisting of physical examination, biomarker data, imaging, and hemodynamic assessment., Conclusion: This review presents a comprehensive tool for assessing perioperative RV function. We hope that this simple, intuitive tool can be applied to all phases of perioperative care and thereby improve patient outcomes., (© 2023. The Author(s).)

Change management in health care is the process of implementing new policies, procedures, and practices in order to improve the quality of patient care. It involves understanding the need for change, identifying the stakeholders involved, and developing a plan to implement and manage the change. Change management in health care requires a comprehensive and collaborative approach to ensure that changes are properly implemented, communicated, and monitored. It is essential for health care providers to be aware of the current trends in health care and to stay up to date with the latest technology in order to provide the best care possible., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose of Review: Modifiable patient-related risk factors, such as physical, emotional, and cognitive frailty, poor nutritional status, sleep hygiene, anemia, alcohol abuse, and smoking reduce a patient's ability to effectively recover from the insult of surgery. Herein, we review the value of implementing a comprehensive prehabilitation program for patients undergoing thoracic surgery., Recent Findings: Although prehabilitation is not a novel concept, recent evidence suggest that 4-6 weeks of prehabilitation prior to surgery is likely to increase a patient's preoperative functional status allowing patients to return to independence earlier after surgery. The value of a prehabilitation program can be determined using cost effectiveness analysis, cost-benefit analysis (CBA), cost-utility analysis (CUA), and cost-consequence analysis (CCA)., Summary: It stands to reason that well designed prehabilitation programs can add value by improving quality metrics at a lower cost to our healthcare system. Definitive randomized trials are needed to confirm this notion., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflicts of Interest: See Disclosures at the end of the article.

Objectives: Does point-of-care viscoelastic testing in patients undergoing left ventricular assist device implantation or orthotopic heart transplantation reduce non-red blood cell transfusion or improve postoperative outcomes?, Design: A retrospective observational study., Setting: At a single-center tertiary university hospital., Participants: Patients undergoing left ventricular assist device placement or heart transplantation INTERVENTIONS: The authors implemented a TEG-based transfusion algorithm to reduce non-red cell transfusion rates compared with historical controls., Measurements and Main Results: From May 15, 2019, through March 20, 2020, 68 patients underwent left ventricular assist device placement or heart transplantation. Algorithm adherence was 49.2%. After adjusting for relevant variables, platelet (odds ratio [OR] 0.58 [0.39-0.84]; p = 0.004) and cryoprecipitate (OR 0.37 [0.19-0.72]; p = 0.004) transfusion rates and time to extubation (OR -14.1 [-25.8 to -2.3]; p = 0.020) were significantly reduced compared with historical controls. After adjusting for relevant clinical variables, there was a statistically significant reduction in plasma (median [interquartile range] 0.16 [0.07-0.36], p < 0.001), platelets (0.06 [0.02-0.21], p < 0.001), and cryoprecipitate (0.06 [0.01-0.47], p = 0.007) transfusion rates and time to extubation (-16.95 [-27.20 to -6.71], p = 0.002) compared with historical controls., Conclusions: The authors report a statistically significant reduction in transfusion of platelets and cryoprecipitate and time to extubation after adjusting for relevant clinical variables compared with historical controls and a significant reduction in the transfusion of plasma, platelets, and cryoprecipitate and time to extubation in those patients for whom the transfusion algorithm was followed. Their results suggest the importance of implementing transfusion algorithms for patients undergoing heart transplantation and left ventricular assist device placement and of accounting for adherence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The incidence of surgical bailout during transcatheter aortic valve replacement (TAVR) is ∼1%, with an associated 50% in-hospital mortality. We performed an exploratory qualitative study of TAVR team perceptions regarding routine surgical bailout planning with patients., Methods: We developed a semistructed interview guide to explore clinician perspectives on the TAVR consent process, managing intraoperative emergencies, and involving patients in surgical contingency planning. We interviewed surgeons, cardiologists, and anesthesiologists involved with TAVR in 4 hospitals. We performed qualitative thematic analysis via independent coding of salient quotations from the transcribed texts. Codes were categorized based on shared meaning and the final themes were derived by identifying key content, and examining its relational nature., Results: Thirteen interviews were conducted, identifying 4 major themes. Participants agreed that eliciting patient preference for bailout is crucial, particularly when surgical outcome is ambiguous. In those cases, participants offered criteria for determining which patients should be engaged in a more nuanced discussion. The ethos of specialty clinicians impacted anticipation and response to procedural emergencies. Finally, physician attitudes reflected strong emotional responses to patient death/morbidity, particularly in iatrogenic injury. Participants expressed anxiety with performing TAVR without surgical backup, while also demonstrating willingness to respect patients' wishes., Conclusions: The TAVR team supports engaging patients regarding potential surgical bailout and honoring their preferences in the event of complication. However, clinical judgment about the expected outcome of bailout would frame that discussion. Participants described the emotional weight of not pursuing bailout if indicated and the importance of good coping mechanisms., (© 2022 The Author(s).)

Objective: The purpose of this study was to determine the relationship between blood product transfusion, with or without recombinant human activated factor VIIa, and survival after lung transplantation., Design: Retrospective analysis of a single center with follow-up out to 6 years post-transplantation., Setting: Single-center academic lung transplantation program., Participants: The study comprised 265 adult patients who underwent single or bilateral sequential lung transplantation from March 2011 to June 2017., Interventions: Overall survival using Kaplan-Meier curves was compared among the following 3 cohorts: those not transfused with blood products, those transfused with blood products, and those given blood products and recombinant human activated factor VIIa. Cox proportional hazards regression was used to estimate hazard ratios (HRs), confidence intervals (CIs), and p values., Measurements and Main Results: Seventy-eight patients received no packed red blood cell transfusions, 149 received packed red blood cell transfusions, and 38 received both packed red blood cell transfusions and recombinant human activated factor VII. Packed red blood cell transfusion was associated with an increased risk of mortality that did not reach statistical significance (HR 2.168, CI 0.978-4.805; p = 0.057). Additional packed red blood cells beyond 15 U were associated with worsened survival (HR 1.363, CI 1.137-1.633; p = 0.001), but recombinant human activated factor VIIa did not increase the risk of mortality., Conclusion: Blood product transfusion during and after lung transplantation is associated with decreased survival, especially with large-volume transfusions. Survival is not worse with recombinant human activated factor VIIa administration, but additional studies are needed to determine whether recombinant human activated factor VIIa administration reduces the need for blood product transfusions., Competing Interests: Declaration of interest for all other authors None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Viral myocarditis has an incidence rate of 10 to 22 per 100,000 individuals. The presentation pattern of viral myocarditis can range from nonspecific symptoms of fatigue and shortness of breath to more aggressive symptoms that mimic acute coronary syndrome. After the initial acute phase presentation of viral myocarditis, the virus may be cleared, resulting in full clinical recovery; the viral infection may persist; or the viral infection may lead to a persistent autoimmune-mediated inflammatory process with continuing symptoms of heart failure. As a result of these 3 possibilities, the diagnosis, prognosis, and treatment of viral myocarditis can be extremely unpredictable and challenging for the clinician. Herein, the incidence, etiology, definition and classification, clinical manifestation, diagnosis, pathogenesis, prognosis, and treatment of viral myocarditis are reviewed, and how acute clinical care teams might differentiate between viral myocarditis and other acute cardiac conditions is discussed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The cardiac operating room is a complex environment requiring efficient and effective communication between multiple disciplines. The objectives of this study were to identify and rank critical time points during the perioperative care of cardiac surgical patients, and to assess variability in responses, as a correlate of a shared mental model, regarding the importance of these time points between and within disciplines., Methods: Using Delphi technique methodology, panelists from 3 institutions were tasked with developing a list of critical time points, which were subsequently assigned to pause point (PP) categories. Panelists then rated these PPs on a 100-point visual analog scale. Descriptive statistics were expressed as percentages, medians, and interquartile ranges (IQRs). We defined low response variability between panelists as an IQR ≤ 20, moderate response variability as an IQR > 20 and ≤ 40, and high response variability as an IQR > 40., Results: Panelists identified a total of 12 PPs. The PPs identified by the highest number of panelists were (1) before surgical incision, (2) before aortic cannulation, (3) before cardiopulmonary bypass (CPB) initiation, (4) before CPB separation, and (5) at time of transfer of care from operating room (OR) to intensive care unit (ICU) staff. There was low variability among panelists' ratings of the PP "before surgical incision," moderate response variability for the PPs "before separation from CPB," "before transfer from OR table to bed," and "at time of transfer of care from OR to ICU staff," and high response variability for the remaining 8 PPs. In addition, the perceived importance of each of these PPs varies between disciplines and between institutions., Conclusions: Cardiac surgical providers recognize distinct critical time points during cardiac surgery. However, there is a high degree of variability within and between disciplines as to the importance of these times, suggesting an absence of a shared mental model among disciplines caring for cardiac surgical patients during the perioperative period. A lack of a shared mental model could be one of the factors contributing to preventable errors in cardiac operating rooms.

Background: The exact mechanisms that underlie the pathological processes of myocardial ischemia in humans are unclear. Cardiopulmonary bypass with cardioplegic arrest allows the authors to examine the whole transcriptional profile of human left ventricular myocardium at baseline and after exposure to cold cardioplegia-induced ischemia as a human ischemia model., Methods: The authors obtained biopsies from 45 patients undergoing aortic valve replacement surgery at baseline and after an average of 79 min of cold cardioplegic arrest. Samples were RNA sequenced and analyzed with the Partek Genomics Suite (Partek Inc., St. Louis, MO) for differential expression. Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, CA) and Biobase ExPlain (Biobase GmbH, Wolfenbuettel, Germany) systems were used for functional and pathway analyses., Results: Of the 4,098 genes with a mean expression value greater than 5, 90% were down-regulated and 9.1% were up-regulated. Of those, 1,241 were significantly differentially expressed. Gene ontology analysis revealed significant down-regulation in immune inflammatory response and complement activation categories and highly consistent was the down-regulation of intelectin 1, proteoglycan, and secretory leukocyte peptidase inhibitor. Up-regulated genes of interest were FBJ murine osteosarcoma viral oncogene homolog and the hemoglobin genes hemoglobin α1 (HBA1) and hemoglobin β. In addition, analysis of transcription factor-binding sites revealed interesting targets in factors regulating reactive oxygen species production, apoptosis, immunity, cytokine production, and inflammatory response., Conclusions: The authors have shown that the human left ventricle exhibits significant changes in gene expression in response to cold cardioplegia-induced ischemia during cardiopulmonary bypass, which provides great insight into the pathophysiology of ventricular ischemia, and thus, may help guide efforts to reduce myocardial damage during surgery.

Background: Increased peak postoperative B-type natriuretic peptide (BNP) is associated with increased major adverse cardiovascular events and all-cause mortality after coronary artery bypass graft (CABG) surgery. Whether increased postoperative BNP predicts worse postdischarge physical function (PF) is unknown. We hypothesized that peak postoperative BNP associates with PF assessed up to 2 yr after CABG surgery, even after adjusting for clinical risk factors. including preoperative PF., Methods: This two-institution prospective cohort study included patients undergoing primary CABG surgery with cardiopulmonary bypass. Short Form-36 questionnaires were administered to subjects preoperatively and 6 months, 1 yr, and 2 yr postoperatively. Short Form-36 PF domain scores were calculated using the Short Form-36 norm-based scoring algorithm. Plasma BNP concentrations measured preoperatively and on postoperative days 1-5 were log(10) transformed before analysis. To determine whether peak postoperative BNP independently predicts PF scores 6 months through 2 yr after CABG surgery, multivariable longitudinal regression analysis of the postoperative PF scores was performed, adjusting for important clinical risk factors., Results: A total of 845 subjects (mean ± SD age, 65 ± 10 yr) were analyzed. Peak postoperative BNP was significantly associated with postoperative PF (effect estimate for log(10) peak BNP, -7.66 PF score points [95% CI, -9.68 to -5.64]; P = <0.0001). After multivariable adjustments, peak postoperative BNP remained independently associated with postoperative PF (effect estimate for log(10) peak BNP, -3.06 PF score points [95% CI, -5.15 to -0.97]; P = 0.004)., Conclusions: Increased peak postoperative BNP independently associates with worse longer-term PF after primary CABG surgery. Future studies are needed to determine whether medical management targeted toward reducing increased postoperative BNP can improve PF after CABG surgery.

Uncorrected congenital interatrial septal defect can be found in nearly a third of all adults and are associated with significant morbidity, including pulmonary hypertension, right-heart failure, atrial arrhythmias, and paradoxical embolic stroke. With advancing technology, percutaneous closure of atrial septal defects has become a viable alternative to open surgical repair. In this review, the authors provide 3 examples in which 3-dimensional interventional transesophageal echocardiogram effectively provided more precise visualization of the dynamic surface and geometry of the atrial septum and related structures than 2-dimensional TEE, permitting accurate sizing and repair of the defects.

Background: Postoperative ventricular dysfunction (VnD) occurs in 9-20% of coronary artery bypass graft (CABG) surgical patients and is associated with increased postoperative morbidity and mortality. Understanding genetic causes of postoperative VnD should enhance patient risk stratification and improve treatment and prevention strategies. We aimed to determine if genetic variants associate with occurrence of in-hospital VnD after CABG surgery., Methods: A genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with postoperative VnD in male subjects of European ancestry undergoing isolated primary CABG surgery with cardiopulmonary bypass. VnD was defined as the need for ≥2 inotropes or mechanical ventricular support after CABG surgery. Validated SNPs were assessed further in two replication CABG cohorts and meta-analysis was performed., Results: Over 100 SNPs were associated with VnD (P<10(-4)), with one SNP (rs17691914) encoded at 3p22.3 reaching genome-wide significance (P(additive model) = 2.14×10(-8)). Meta-analysis of validation and replication study data for 17 SNPs identified three SNPs associated with increased risk for developing postoperative VnD after adjusting for clinical risk factors. These SNPs are located at 3p22.3 (rs17691914, OR(additive model) = 2.01, P = 0.0002), 3p14.2 (rs17061085, OR(additive model) = 1.70, P = 0.0001) and 11q23.2 (rs12279572, OR(recessive model) = 2.19, P = 0.001)., Conclusions: No SNPs were consistently associated with strong risk (OR(additive model)>2.1) of developing in-hospital VnD after CABG surgery. However, three genetic loci identified by meta-analysis were more modestly associated with development of postoperative VnD. Studies of larger cohorts to assess these loci as well as to define other genetic mechanisms and related biology that link genetic variants to postoperative ventricular dysfunction are warranted.

Background: Preoperative B-type natriuretic peptide (BNP) is known to predict adverse outcomes after cardiac surgery. The value of postoperative BNP for predicting adverse outcomes is less well delineated. The authors hypothesized that peak postoperative plasma BNP (measured postoperative days 1-5) predicts hospital length of stay (HLOS) and mortality in patients undergoing primary coronary artery bypass grafting, even after adjusting for preoperative BNP and perioperative clinical risk factors., Methods: This study is a prospective longitudinal study of 1,183 patients undergoing primary coronary artery bypass grafting surgery. Mortality was defined as all-cause death within 5 yr after surgery. Cox proportional hazards analyses were conducted to separately evaluate the associations between peak postoperative BNP and HLOS and mortality. Multivariable adjustments were made for patient demographics, preoperative BNP concentration, and clinical risk factors. BNP measurements were log10 transformed before analysis., Results: One hundred fifteen deaths (9.7%) occurred in the cohort (mean follow-up = 4.3 yr, range = 2.38-5.0 yr). After multivariable adjustment for preoperative BNP and clinical covariates, peak postoperative BNP predicted HLOS (hazard ratio [HR] = 1.28, 95% CI = 1.002-1.64, P = 0.049) but not mortality (HR = 1.62, CI = 0.71-3.68, P = 0.25), whereas preoperative BNP independently predicted HLOS (HR = 1.09, CI = 1.01-1.18, P = 0.03) and approached being an independent predictor of mortality (HR = 1.36, CI = 0.96-1.94, P = 0.08). When preoperative and peak postoperative BNP were separately adjusted for within the clinical multivariable models, each independently predicted HLOS (preoperative BNP HR = 1.13, CI = 1.05-1.21, P = 0.0007; peak postoperative BNP HR = 1.44, CI = 1.15-1.81, P = 0.001) and mortality (preoperative BNP HR = 1.50, CI = 1.09-2.07, P = 0.01; peak postoperative BNP HR = 2.29, CI = 1.11-4.73, P = 0.02)., Conclusions: Preoperative BNP may be better than peak postoperative BNP for predicting HLOS and longer term mortality after primary coronary artery bypass grafting surgery.

Background: Ventricular dysfunction (VnD) after primary coronary artery bypass grafting is associated with increased hospital stay and mortality. Natriuretic peptides have compensatory vasodilatory, natriuretic, and paracrine influences on myocardial failure and ischemia. The authors hypothesized that natriuretic peptide system gene variants independently predict risk of VnD after primary coronary artery bypass grafting., Methods: A total of 1,164 patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass at two institutions were prospectively enrolled. After prospectively defined exclusions, 697 patients of European descent (76 with VnD) were analyzed. VnD was defined as need for at least 2 new inotropes and/or new mechanical ventricular support after coronary artery bypass grafting. A total of 139 haplotype-tagging single nucleotide polymorphisms (SNPs) within 7 genes (NPPA, NPPB, NPPC, NPR1, NPR2, NPR3, CORIN) were genotyped. SNPs univariately associated with VnD were entered into logistic regression models adjusting for clinical covariates predictive of VnD. To control for multiple comparisons, permutation analyses were conducted for all SNP associations., Results: After adjusting for clinical covariates and multiple comparisons within each gene, seven NPPA/NPPB SNPs (rs632793, rs6668352, rs549596, rs198388, rs198389, rs6676300, rs1009592) were associated with decreased risk of postoperative VnD (additive model; odds ratios 0.44-0.55; P = 0.010- 0.036) and four NPR3 SNPs (rs700923, rs16890196, rs765199, rs700926) were associated with increased risk of postoperative VnD (recessive model; odds ratios 3.89-4.28; P = 0.007-0.034)., Conclusions: Genetic variation within the NPPA/NPPB and NPR3 genes is associated with risk of VnD after primary coronary artery bypass grafting. Knowledge of such genotypic predictors may result in better understanding of the molecular mechanisms underlying postoperative VnD.

Coronary artery bypass graft surgery is associated with several frequent postoperative adverse events. Outcome prediction is valued by patients and practitioners, because it provides some measure of balancing risks and benefits and provides expensive or higher-risk therapies to individuals at highest risk. Surgeons and anesthesiologists traditionally have relied on demographic, preoperative, and intraoperative risk factors to predict outcomes after cardiac surgery. Yet, such predictions often have poor positive and negative predictive value for the individual patient. Perioperative genetics attempts to determine the impact of an individual's genetic variation on the risk of developing adverse postoperative outcomes. In this article, the authors discuss emerging evidence that a patient's genetic makeup predisposes him or her to adverse outcomes following cardiac surgery and provide examples from perioperative bleeding, myocardial injury/infarction, and atrial fibrillation.

Background: An estimated 275,000 patients undergo heart valve replacement each year. However, existing solutions for valve replacement are complicated by the morbidity associated with lifelong anticoagulation of mechanical valves and the limited durability of bioprostheses. Recent advances in tissue engineering and our understanding of stem cell biology may provide a lifelong solution to these problems., Methods and Results: Mesenchymal stem cells were isolated from ovine bone marrow and characterized by their morphology and antigen expression through immunocytochemistry, flow cytometry, and capacity to differentiate into multiple cell lineages. A biodegradable scaffold was developed and characterized by its tensile strength and stiffness as a function of time in cell-conditioned medium. Autologous semilunar heart valves were then created in vitro using mesenchymal stem cells and the biodegradable scaffold and were implanted into the pulmonary position of sheep on cardiopulmonary bypass. The valves were evaluated by echocardiography at implantation and after 4 months in vivo. Valves were explanted at 4 and 8 months and examined by histology and immunohistochemistry. Valves displayed a maximum instantaneous gradient of 17.2+/-1.33 mm Hg, a mean gradient of 9.7+/-1.3 mm Hg, an effective orifice area of 1.35+/-0.17 cm2, and trivial or mild regurgitation at implantation. Gradients changed little over 4 months of follow-up. Histology showed disposition of extracellular matrix and distribution of cell phenotypes in the engineered valves reminiscent of that in native pulmonary valves., Conclusions: Stem-cell tissue-engineered heart valves can be created from mesenchymal stem cells in combination with a biodegradable scaffold and function satisfactorily in vivo for periods of >4 months. Furthermore, such valves undergo extensive remodeling in vivo to resemble native heart valves.

Tissue engineering may offer patients new options when replacement or repair of an organ is needed. However, most tissues will require a microvascular network to supply oxygen and nutrients. One strategy for creating a microvascular network would be promotion of vasculogenesis in situ by seeding vascular progenitor cells within the biopolymeric construct. To pursue this strategy, we isolated CD34(+)/CD133(+) endothelial progenitor cells (EPC) from human umbilical cord blood and expanded the cells ex vivo as EPC-derived endothelial cells (EC). The EPC lost expression of the stem cell marker CD133 but continued to express the endothelial markers KDR/VEGF-R2, VE-cadherin, CD31, von Willebrand factor, and E-selectin. The cells were also shown to mediate calcium-dependent adhesion of HL-60 cells, a human promyelocytic leukemia cell line, providing evidence for a proinflammatory endothelial phenotype. The EPC-derived EC maintained this endothelial phenotype when expanded in roller bottles and subsequently seeded on polyglycolic acid-poly-l-lactic acid (PGA-PLLA) scaffolds, but microvessel formation was not observed. In contrast, EPC-derived EC seeded with human smooth muscle cells formed capillary-like structures throughout the scaffold (76.5 +/- 35 microvessels/mm(2)). These results indicate that 1) EPC-derived EC can be expanded in vitro and seeded on biodegradable scaffolds with preservation of endothelial phenotype and 2) EPC-derived EC seeded with human smooth muscle cells form microvessels on porous PGA-PLLA scaffolds. These properties indicate that EPC may be well suited for creating microvascular networks within tissue-engineered constructs.

Optimization of cell seeding and culturing is an important step for the successful tissue engineering of vascular conduits. We evaluated the effectiveness of using a hybridization oven for rotational seeding and culturing of ovine vascular myofibroblasts onto biodegradable polymer scaffolds suitable for replacement of small- and large-diameter blood vessels. Large tubes (12 mm internal diameter and 60 mm length, n = 4) and small tubes (5 mm internal diameter and 20 mm length, n = 4) were made from a combination of polyglycolic acid/poly-4-hydroxybutyrate and coated with collagen solution. Tubes were then placed in culture vessels containing a vascular myofibroblast suspension (10(6) cells/cm(2)) and rotated at 5 rpm in a hybridization oven at 37 degrees C. Light and scanning electron microscopy analyses were performed after 5, 7, and 10 days. Myofibroblasts had formed confluent layers over the outer and inner surfaces of both large and small tubular scaffolds by day 5. Cells had aligned in the direction of flow by day 7. Multiple spindle-shaped cells were observed infiltrating the polymer mesh. Cell density increased between day 5 and day 10. All conduits maintained their tubular shape throughout the experiment. We conclude that dynamic rotational seeding and culturing in a hybridization oven is an easy, effective, and reliable method to deliver and culture vascular myofibroblasts onto tubular polymer scaffolds.

Having a reliable method of delivering cells to polymer scaffolds in vitro is fundamental to the development of tissue engineered structures. This paper compares the efficacy of two rotating systems for this purpose. Ten conduits, measuring 40 mm by 10 mm, were fabricated from polyglycolic acid mesh and poly-4-hydrobutyrate. Five conduits were placed in a rotating wall vessel (RWV, Synthecon Inc., Houston, TX), developed by the National Aeronautics and Space Administration (NASA); five conduits were also placed in rotating individual sealed tubes (RISTs). Medium in the RWV was left unchanged for the duration of the experiment; medium in the RISTs required daily change. Samples of the discarded medium and samples from the RWV were analyzed for pH, pCO2, pO2, and lactate concentration. Constructs were assayed for DNA content as a surrogate for cell number. In the RWV, pH, pCO2, and pO2 remained stable, while the lactate concentration gradually increased. The measure of PO2 did not differ significantly between the RWV and the RISTs, but the pH was lower and the pCO2 and the lactate concentration measurements were higher in the RIST system at each time point (p = 0.001). After 6 days (p = 0.001), the total DNA per conduit was 226+/-7 microg for the conduits seeded in the RISTs and 396+/-18 microg for the conduits in the RWV, suggesting that the RWV is superior to the RIST system for delivering cells to polymer scaffolds.