Chemokines, a family of chemotactic cytokines, mediate leukocyte migration to and entrance into inflamed tissue, contributing to the intensity of local inflammation. We performed an analysis of chemokine and immune cell responses to cardiac arrest (CA). Forty-two patients resuscitated from cardiac arrest were analyzed, and twenty-two patients who underwent coronary artery bypass grafting (CABG) surgery were enrolled. Quantitative antibody array, chemokines, and endotoxin quantification were performed using the patients blood. Analysis of CCL23 production in neutrophils obtained from CA patients and injected into immunodeficient mice after CA and cardiopulmonary resuscitation (CPR) were done using flow cytometry. The levels of CCL2, CCL4, and CCL23 are increased in CA patients. Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a delayed elevation in CCL23 at forty-eight hours after CA. A high level of CCL23 was associated with an increased number of neutrophils, neuron-specific enolase (NSE), worse cerebral performance category (CPC) score, and higher mortality. To investigate the role of neutrophil activation locally in injured brain tissue, we used a mouse model of CA/CPR. CCL23 production was increased in human neutrophils that infiltrated mouse brains compared to those in the peripheral circulation. It is known that an early intense inflammatory response (within hours) is associated with poor outcomes after CA. Our data indicate that late activation of neutrophils in brain tissue may also promote ongoing injury via the production of CCL23 and impair recovery after cardiac arrest.

Objectives: Risk assessment models for cardiac surgery do not distinguish between degrees of liver dysfunction. We have previously shown that preoperative liver stiffness is associated with hospital length of stay following cardiac surgery. The authors hypothesized that a liver stiffness measurement (LSM) ≥ 9.5 kPa would rule out a short hospital length of stay (LOS < 6 days) following isolated coronary artery bypass grafting (CABG) surgery. Methods: A prospective observational study of one hundred sixty-four adult patients undergoing non-emergent isolated CABG surgery at a single university hospital center. Preoperative liver stiffness measured by ultrasound elastography was obtained for each participant. Multivariate logistic regression models were used to assess the adjusted relationship between LSM and a short hospital stay. Results: We performed multivariate logistic regression models using short hospital LOS (<6 days) as the dependent variable. Independent variables included LSM (< 9.5 kPa, ≥ 9.5 kPa), age, sex, STS predicted morbidity and mortality, and baseline hemoglobin. After adjusting for included variables, LSM ≥ 9.5 kPa was associated with lower odds of early discharge as compared to LSM < 9.5 kPa (OR: 0.22, 95% CI: 0.06–0.84, p = 0.03). The ROC curve and resulting AUC of 0.76 (95% CI: 0.68–0.83) suggest the final multivariate model provides good discriminatory performance when predicting early discharge. Conclusions: A preoperative LSM ≥ 9.5 kPa ruled out a short length of stay in nearly 80% of patients when compared to patients with a LSM < 9.5 kPa. Preoperative liver stiffness may be a useful metric to incorporate into preoperative risk stratification.

Gastrointestinal complications after cardiac surgery are relatively rare entities but carry a high mortality. We identified over 70 articles written since 2010 using the PubMed database. We included 40 in our review. The most common complications include paralytic ileus, gastrointestinal bleeding, and bowel ischemia. Patients who undergo cardiac procedures are at risk for poor perfusion of the gastrointestinal tract and, thus, at risk for resulting complications. Risk factors for these complications include peri-operative use of vasopressors, prolonged operative time, and the time of cardiopulmonary bypass. Presentation of gastrointestinal complications tends to differ as patients after open heart surgery can remain intubated, and exams can be limited. Early recognition and aggressive therapy are paramount. We aim to provide a review that will help the reader get familiar with the most common gastrointestinal complications that can negatively affect outcomes after cardiac surgery.

Background and Objective:The most common valvular heart disease in the US is moderate to severe mitral regurgitation (MR). Function MR or secondary MR comprises many of these cases. Moderate and severe secondary MR are independently associated with increased all-cause mortality and rehospitalization for heart failure. Both ischemic and nonischemic cardiomyopathy can cause secondary MR via similar pathophysiology that leads to inadequate valve leaflets coaptation. The management of secondary MR is complex. The optimal treatment strategy for secondary MR remains controversial, reflected in the vast array of treatment options and the complexity of therapeutic decision-making. Several surgical mitral valve repair techniques have been described in the literature. Many of these aims to facilitate adequate valve leaflet coaptation. In this review, the pathophysiology of MR is described with a focus on evaluating and managing secondary MR. Methods:A literature review was performed using PubMed and Google Scholar. Clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews were considered from January 1, 1995 through December 31, 2022. Articles published in languages other than English with limited text availability were excluded. Key Content and Findings:Optimal therapeutic approach in severe secondary MR is complex and several patient factor should be considered. We provide a framework for the surgical management of secondary MR based on echocardiographic parameters, the presence of ischemia, and myocardial viability. Conclusions:Further study is needed to guide the selection of patients most likely to benefit from mitral valve repair or replacement in the setting of secondary MR.

Introduction: Recent national guidelines recommending mitral valve replacement (MVR) for severe secondary mitral regurgitation have resulted in increased utilization of mitral bioprostheses. We examined long-term survival and risk of re-operation between patients having bovine vs porcine MVR. Methods: A retrospective analysis of MVR or MVR+CABG from 2001 - 2017 among seven hospitals reporting to a prospectively maintained clinical registry was conducted. The analytic cohort included 1,308 patients undergoing MVR (811 bovine and 497 porcine). Baseline comorbidities were balanced using 1:1 propensity score matching with 432 patients in each group. . The primary end point was all-cause mortality. Secondary end points included in-hospital morbidity, 30-day mortality, length of stay, and risk of reoperation. Results: In the analytic cohort, patients receiving porcine valves were more likely to have diabetes (19% bovine vs. 29% porcine; P<.001), COPD (21% bovine vs. 27% porcine; P=.01), dialysis or creatinine >2 mg/dL (4% bovine vs. 7% porcine; P=.03) and coronary artery disease (65% bovine vs. 76% porcine; P<.001). In the overall cohort there was no difference in long-term survival (porcine HR 1.17 [95% CI 1.00-1.37; P=0.050]) or reoperation (porcine HR 0.56 [95% CI 0.23-1.32; P=0.19). In the propensity-matched cohort, the bovine valve patients were less likely to return to the OR for bleeding (6% vs. 9.3%; absolute standardized difference 0.12), but were more likely to have a stroke (3.7% vs. 1.9%; absolute standardized difference 0.11). There was no difference in in-hospital and 30-day mortality. After 1:1 propensity score matching, there was no difference in long-term survival (porcine HR 0.97 [95% CI 0.81-1.17; P=0.76]) or risk of reoperation (porcine HR 0.54 [95% CI 0.20-1.47; P=0.23). Conclusions: In this multicenter analysis of patients undergoing bioprosthetic MVR there was no difference in long-term survival, and risk of reoperation.

In 2018, 34.2 million or 10.5% of the US population were affected by diabetes, and 88 million Americans aged 18 and older had prediabetes [1]. These individuals carry up to eight times the risk of cardiovascular events compared to nondiabetic individuals, making cardiovascular disease the largest cause of mortality in this population [2]. The prevalence of coronary artery disease (CAD) has been estimated to be as high as 55% in the diabetic population [3]. It has been shown that diabetes is a major independent risk factor for cardiovascular disease after adjustment for other risk factors such as age, hypertension, hypercholesterolemia, and tobacco abuse [4]. Patients with diabetes appear to develop accelerated and more severe CAD and also exhibit a diminished angiogenic response to myocardial ischemia as shown angiographically [5] and in autopsy studies [6]. This diminished angiogenic response is associated with coronary microvascular and endothelial dysfunction as well as the presence of an overall anti-angiogenic milieu leading to fewer collateral blood vessels [7, 8]. Hyperglycemia, hyperinsulinemia, and insulin resistance further add to the development of CAD, cardiomyopathy, and heart failure (Fig. 24.1). This culminates in a greater tendency toward more frequent and more severe adverse cardiovascular events. The relative risk of myocardial infarction is 50% greater in diabetic men and 150% greater in diabetic women [9]. Approximately, 20–30% of patients who have undergone coronary artery bypass grafting (CABG) have diabetes mellitus [10]. Thus, diabetic patients undergoing surgical coronary revascularization represent a large and complex patient population. There continue to be advancements in both percutaneous coronary interventions (PCI), primarily the use of drug-eluting stents, and surgical techniques, such as off-pump CABG and the use of multiple arterial grafts, that have continued to improve methods of coronary revascularization. While there is evidence to suggest that these new techniques have improved outcomes in diabetic patients [11], the optimal treatment for multivessel CAD continues to evolve for the diabetic patient population, which still suffers from worse long-term outcomes compared to the nondiabetic population.

Complete circumferential aortic dissection with bidirectional intimo-intimal intussusception is a rare occurrence in Stanford type A dissections. The antegrade dissection flap can obstruct the left ventricular outflow tract and coronary sinuses, whereas the retrograde flap can obstruct the aortic arch and branch vessels. Sequelae include aortic regurgitation, myocardial ischemia, and neurologic complications. This case series highlights the need for prompt diagnosis with electrocardiography-gated computed tomography and surgical intervention for this unique pathologic process.

Background. The Perceval S is a sutureless, bovine pericardial aortic prosthesis on a nitinol stent, which has limited data on outcomes, as well as cost, from the United States. Methods. We performed a retrospective review of Perceval S implantation at a single center between 2015 and 2018. After exclusion criteria, we compared 234 patients who underwent sutureless aortic valve (SLV) implantation with 370 patients who underwent standard sutured aortic valves (SAVR). Hospital cost data were reviewed, and risk adjustment, done by propensity score and inverse probability weighting, was used to compare outcomes. Results. Compared to those undergoing SAVR, the SLV group was older and had a higher proportion of multicomponent operations, higher preoperative white blood cell count, higher rate of previous percutaneous coronary interventions, more comorbid conditions (diabetes, renal insufficiency, and dialysis), and more three-vessel coronary disease. For isolated AVR, partial upper hemisternotomy was more frequent in SLV. The mean cardiopulmonary bypass and cross-clamp times for isolated SLV were significantly lower than SAVR. After adjustment, the cohort was balanced. Operative differences for SLV were lower cross-clamp and pump time, larger valve size, more minimally invasive approaches, and shorter operating room times. There were no differences in other postoperative complications (postoperative atrial fibrillation, stroke, renal failure, prolonged ventilation, and in-hospital mortality; p > 0.05 for all). Mean and median hospital costs were higher in the SLV group, largely due to the cost of the implant. Conclusion. Sutureless tissue aortic valves can be used safely with lower cardiopulmonary bypass and clamp times than sutured prostheses and facilitate use of minimally invasive approaches. This valve may be advantageous in older, higher risk patients requiring more complex operations.

Introduction: Chemokines mediate the entrance and migration of leukocytes to inflamed tissue areas, contributing to the intensity of local inflammation. We found a high level of circulating chemokines, CCL2, CCL4, and CCL23, in patients resuscitated after cardiac arrest (CA). Hypothesis: The level of circulating chemokines is associated with systemic immune cell response, neurologic injury, and outcome after cardiac arrest. Goal: To characterize temporal chemokine and immune cell responses to cardiac arrest. Methods: A total of 42 patients after CA and 22 control subjects who underwent coronary artery bypass grafting (CABG) were enrolled. ELISA was used to determine chemokines in plasma at 6 hr, 24 hr, 48 hr, and 72 hr after CA and in CABG patients pre-operatively. Flow cytometry was used to determine subpopulations of immune cells. We measured changes in chemokines over time and the association of chemokine levels with outcome, markers of inflammation, and brain injury. A mouse model of CA was employed to assess the activation of human neutrophils locally in brain tissue. Results: Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a late elevation in CCL23 at 48 hours after resuscitation. A higher level of CCL23 was associated with a worse cerebral performance category score (r s =0.3, p=0.042) and higher mortality (r s =0.3, p=0.039). Positive correlations were found between CCL23 and an increased number of neutrophils, cellular mediators of inflammation, and levels of neuron-specific enolase. To study the potential role of neutrophil activation locally in injured brain tissue, we injected human post-CA neutrophils into the bloodstream of successfully resuscitated mice and measured the CCL23 in human neutrophils in mouse blood and brain 24 hours after resuscitation. An increased level of CCL23 production was found in mouse brain neutrophils compared to those in the peripheral circulation. Conclusion: It is well known that an early intense inflammatory response is associated with poor outcomes after CA. Our new data indicate that late activation of neutrophils in brain tissue may represent an additional mechanism contributing to ongoing brain tissue injury via the production of CCL23 after cardiac arrest.

Mitral and aortic valve disease commonly coexist, requiring intervention at the same time. In a study examining the Society of Thoracic Surgeons (STS) database, 11% of patients undergoing valve operations were double valves, with aortic and mitral being the most common.1 Rheumatic disease has traditionally been the most common etiology, but over time, degenerative disease has become predominant. Degenerative disease can involve heavy calcification of the valve leaflets and annuli. In this setting, current transcatheter options for the mitral valve may not be effective.2 The risk of mortality in combined aortic and mitral valve surgery has remained high. In a review of the STS database, mortality was approximately 10% for all years examined. At the same time mortality for isolated aortic or mitral valve operations went down.1 It appears there is an opportunity to achieve better outcomes in this patient population. It has been well documented that patients do better with shorter bypass times and cross-clamp times. Elderly patients in need of multivalve operations are especially vulnerable to complications associated with extended time on bypass.3 The use of Perceval (Corcym, London, UK) has been shown in many studies to decrease the time on bypass.4,5 There has been increasing interest in the use of Perceval in multivalve operations. Several studies have examined this topic.4,6-9 The most recent and largest paper examined 114 patients undergoing combined aortic valve replacement (AVR) and mitral operations with either Perceval or a sutured aortic bioprosthesis. The average age in both groups was over 70 years, and the average EuroSCORE was about 6. The operative times were shorter in the Perceval group, but there were no differences in mortality or morbidity in this high-risk group of patients.8 As the experience and knowledge grows in this area, there will be opportunity for improvement in outcomes, and further studies will be needed. In combined AVR with Perceval and mitral operations, there are some considerations to help ensure success.

SUPERIOR VENA CAVA (SVC) syndrome, which occurs because of obstruction of the SVC, may manifest with plethora and swelling of the face and arm due to venous congestion and edema.

We investigated the cell surface expression of ErbB receptors on left ventricular (LV) epicardial endothelial cells and CD105+ cells obtained from cardiac biopsies of patients undergoing coronary artery bypass grafting surgery (CABG). Endothelial cells and CD105+ non-endothelial cells were freshly isolated from LV epicardial biopsies obtained from 15 subjects with diabetes mellitus (DM) and 8 controls. The expression of ErbB receptors was examined using flow cytometry. We found that diabetes mellitus (DM) and high levels of hemoglobin A1C are associated with reduced expression of ErbB2. To determine if the expression of ErbB2 receptors is regulated by glucose levels, we examined the effect of high Glucose in human microvascular endothelial cells (HMEC-1) and CD105+ non-endothelial cells, using a novel flow cytometric approach to simultaneously determine the total level, cell surface expression, and phosphorylation of ErbB2. Incubation of cells in the presence of 25 mM Dglucose resulted in decreased cell surface but not total levels of ErbB2. The level of ErbB2 at the cell surface is controlled by disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) that is expressed on LV epicardial cells. Inhibition of ADAM10 prevented the high glucose-dependent decrease in the cell surface expression of ErbB2. We suggest that high Glucose depresses ErbB receptor signaling in endothelial cells and cardiac progenitor cells via the promotion of ADAM10-dependent cleavage of ErbB2 at the cell surface, thus contributing to vascular dysfunction and adverse remodeling seen in diabetic patients.

OBJECTIVES:Patients with hypertrophic cardiomyopathy often have concomitant pulmonary hypertension, which has a negative prognostic effect in patients undergoing myectomy. Our objective was to investigate the effect of myectomy on pulmonary artery pressure obtained via Swan-Ganz catheter and characterize how changes in pulmonary artery systolic pressure may indicate outcomes in these patients. METHODS:We performed a single-center retrospective analysis of 271 patients with recordings of intraoperative pulmonary artery pressures during surgical myectomy. We analyzed primary composite outcomes as 30-day or in-hospital major cardiopulmonary adverse events. RESULTS:There was a 5.17% adverse event rate. Patients with adverse events were older, were more likely to be female, had chronic obstructive pulmonary disease, and had longer cardiopulmonary bypass times. Some 35.7% of those with adverse events had moderate to severe pulmonary hypertension (pulmonary artery systolic pressure ≥50 mm Hg) on postbypass stress test, compared with 4.3% of those without adverse events (P < .001). Further, 21.4% of patients with adverse events had pulmonary artery systolic pressure 50 mm Hg or greater at the end of surgery, compared with 1.9% of patients without adverse events (P < .001). The pulmonary artery systolic pressure decrease after surgery in those without adverse events was on average 5 mm Hg more than in those with adverse events. CONCLUSIONS:Postoperative pulmonary hypertension was associated with a higher rate of adverse cardiopulmonary events. This may influence the decision to use Swan-Ganz catheters in patients undergoing septal myectomy in monitoring pulmonary artery pressures to better risk stratify and manage these patients postoperatively.

Small increases in serum creatinine postoperatively reflect an acute kidney injury (AKI) that likely occurred during cardiopulmonary bypass (CPB). Maintaining adequate oxygen delivery (DO2) during CPB, known as GDP (goal-directed perfusion), improves outcomes. Whether GDP improves outcomes of patients at high risk for acute renal failure (ARF) is unknown. Forty-seven adult patients undergoing cardiac surgery with CPB utilizing GDP with Cleveland Clinic Acute Renal Failure Score of 3 or greater were compared with a matched cohort of patients operated upon using a flow-directed strategy. CPB flow in the GDP cohort was based on a DO2 goal of 260 mL/min/m2. Serum creatinine values were used to determine whether postoperative AKI occurred according to AKIN (Acute Kidney Injury Network) guidelines. We examined the distribution of all variables using proportions for categorical variables and means (standard deviations) for continuous variables and compared treatment groups using t tests for categorical variables and tests for differences in distributions for continuous and count variables. We used inverse probability of treatment weighting to adjust for treatment selection bias. In adjusted models, GDP was not associated with a decrease in AKI (odds ratio [OR]: .97; confidence interval [CI]: .62, 1.52), but was associated with higher odds of ARF (OR: 3.13; CI: 1.26, 7.79), mortality (OR: 3.35; CI: 1.14, 9.89), intensive care unit readmission (OR: 2.59; CI: 1.31, 5.15), need for intraoperative red blood cell transfusion (OR: 2.02; CI: 1.26, 3.25), and postoperative platelet transfusion (OR: 1.78; CI: 1.05, 3.01) when compared with the historic cohort. In patients who are at high risk for postoperative renal failure, GDP was not associated with a decrease in AKI when compared to the historical cohort managed traditionally by determining CPB flows based on body surface area. Surprisingly, the GDP cohort performed significantly worse than the retrospective control group in terms of ARF, mortality, intensive care unit readmission, and RBC and platelet transfusions.

Septal myectomy as initially popularized by Morrow is sucexperienced centers, the mortality rate is less than 1%, survival compared with medical therapy, and surgical myectomy appears to have superior results compared with septum was resected emphasize extension of the resection myectomy is now accepted as the standard of care for surgical treatment of obstructive HCM. Most centers do not have the patient volume for adequate surgical training in this specialized procedure.12 Indeed, Cardiac Surgery Database revealed that the majority of centers (75%) performed less than 1 myectomy for HCM annuand lack of familiarity with the various phenotypic subimplications.

Valve‐in‐valve (ViV) transcatheter aortic valve replacement (TAVR) offers an alternative to reoperative surgical aortic valve replacement. The short‐ and intermediate‐term outcomes after ViV TAVR in the real world are not entirely clear.

In this E-Challenge, the authors report on a patient with symptoms of exertional dyspnea and angina, scheduled to have surgical unroofing of an identified myocardial bridge (MB). An MB is very common in patients with hypertrophic cardiomyopathy (HCM). Intraoperative transesophageal echocardiography with provocative maneuvers revealed the patient had a systolic anterior motion of the mitral valve with septal contact and resulting outflow tract obstruction despite the notable absence of significant basal septal hypertrophy. HCM has many phenotypic variants that can make the identification of patients with latent left ventricular outflow tract obstruction difficult in the absence of a high index of suspicion. In this report, the authors discuss the association between MBs and HCM and the importance of recognizing phenotypic variants of HCM.

Background Myeloid cells play an important role in a wide variety of cardiovascular disorders, including both ischemic and non-ischemic cardiomyopathies. Neuregulin-1 (NRG-1)/ErbB signaling has recently emerged as an important factor contributing to the control of inflammatory activation of myeloid cells after an ischemic injury. However, the role of ErbB signaling in myeloid cells in non-ischemic cardiomyopathy is not fully understood. This study investigated the role of ErbB3 receptors in the regulation of early adaptive response using a mouse model of transverse aortic constriction (TAC) for non-ischemic cardiomyopathy. Methods and results TAC surgery was performed in groups of age- and sex-matched myeloid cell-specific ErbB3-deficient mice (ErbB3MyeKO) and control animals (ErbB3MyeWT). The number of cardiac CD45 immune cells, CD11b myeloid cells, Ly6G neutrophils, and Ly6C monocytes was determined using flow cytometric analysis. Five days after TAC, survival was dramatically reduced in male but not female ErbB3MyeKO mice or control animals. The examination of lung weight to body weight ratio suggested that acute pulmonary edema was present in ErbB3MyeKO male mice after TAC. To determine the cellular and molecular mechanisms involved in the increased mortality in ErbB3MyeKO male mice, cardiac cell populations were examined at day 3 post-TAC using flow cytometry. Myeloid cells accumulated in control but not in ErbB3MyeKO male mouse hearts. This was accompanied by increased proliferation of Sca-1 positive non-immune cells (endothelial cells and fibroblasts) in control but not ErbB3MyeKO male mice. No significant differences in intramyocardial accumulation of myeloid cells or proliferation of Sca-1 cells were found between the groups of ErbB3MyeKO and ErbB3MyeWT female mice. An antibody-based protein array analysis revealed that IGF-1 expression was significantly downregulated only in ErbB3MyeKO mice hearts compared to control animals after TAC. Conclusion Our data demonstrate the crucial role of myeloid cell-specific ErbB3 signaling in the cardiac accumulation of myeloid cells, which contributes to the activation of cardiac endothelial cells and fibroblasts and development of an early adaptive response to cardiac pressure overload in male mice.

Introduction: ErbB signaling contributes to the regulation of vascular function through endothelial cell differentiation, proliferation, survival, and regulation of barrier integrity. Patients with diabetes (DM) are at an increased risk for endothelial dysfunction and worse outcomes after CABG. We investigated the level of ErbB expression on CD31 endothelial cells and CD105+ cells in DM and non-DM patients undergoing CABG. Methods: With IRB approval, left ventricular (LV) epicardial biopsies and blood samples from 25 patients (non-DM=9, DM=16), were obtained during surgery. Flow cytometry was used to determine the cell surface expression of ErbB receptors on cardiac endothelial and CD105+ cells isolated from the LV. Subpopulations of white blood cells were determined in blood samples. Plasma levels of IL-6, IL-8, and TNFα were measured. Results: Lower levels of ErbB1 and ErbB2 receptors expression on endothelial cells isolated from LV biopsies were found in patients with DM compared to non-DM control, and the expression of ErbB receptors negatively correlated with HgbA1c level. There were fewer CD105+ cells in DM patients (122 vs 153 cell/mg tissue, P=.021). Trends toward a negative association were found between the expression of ErbB2 in CD105+ cells and the number of neutrophils, as well as, HgbA1c level. No differences were found between DM and non-DM patients in the number of white blood cell subsets or plasma levels of IL-6, IL-8 and TNFα. Conclusions: We demonstrated that DM and high glucose blood levels are associated with reduced expression of ErbB1 and ErbB2 on endothelial cells and decreased number of CD105+ cells in the LV. Cardiac CD105+ are endothelial progenitor cells that differentiate in response to ErbB ligands. A decreased pool of CD105 endothelial progenitors in combination with down-regulation of ErbB1 and ErbB2 receptors in endothelial cells represent a novel mechanism for vascular dysfunction and adverse remodeling seen in diabetic patients.