Is cardioplegia system pressure the optimal measure of coronary perfusion during antegrade cardioplegia delivery? A critical review of pressure measurements for optimal antegrade delivery.

Antegrade cardioplegia is routinely given during cardiac surgery. The delivery of antegrade cardioplegia from the cardiopulmonary bypass machine has many variables. Many perfusionists rely exclusively on cardioplegia system pressure to ensure safe antegrade delivery. Our group reviewed antegrade cardioplegia delivery in 50 patients undergoing coronary artery bypass graft. The data collected included the cardioplegia system pressure and the patient's direct aortic root pressure. The analysis of the data found weak correlation between the two pressures with a large mean difference and a wide standard deviation. The results suggest the direct measurement of aortic root pressure as guidance to antegrade cardioplegia instead of relying solely on cardioplegia system pressure.

Mandatory public reporting of cardiac surgery outcomes: The 2003 to 2014 Massachusetts experience.

OBJECTIVES: Beginning in 2002, all 14 Massachusetts nonfederal cardiac surgery programs submitted Society of Thoracic Surgeons (STS) National Database data to the Massachusetts Data Analysis Center for mandatory state-based analysis and reporting, and to STS for nationally benchmarked analyses. We sought to determine whether longitudinal prevalences and trends in risk factors and observed and expected mortality differed between Massachusetts and the nation. METHODS: We analyzed 2003 to 2014 expected (STS predicted risk of operative [in-hospital + 30-day] mortality), observed, and risk-standardized isolated coronary artery bypass graft mortality using Massachusetts STS data (N = 39,400 cases) and national STS data (N = 1,815,234 cases). Analyses included percentage shares of total Massachusetts coronary artery bypass graft volume and expected mortality rates of 2 hospitals before and after outlier designation. RESULTS: Massachusetts patients had significantly higher odds of diabetes, peripheral vascular disease, low ejection fraction, and age ≥75 years relative to national data and lower odds of shock (odds ratio, 0.66; 99% confidence interval, 0.53-0.83), emergency (odds ratio, 0.57, 99% confidence interval, 0.52-0.61), reoperation, chronic lung disease, dialysis, obesity, and female sex. STS predicted risk of operative [in-hospital + 30-day] mortality for Massachusetts patients was higher than national rates during 2003 to 2007 (P < .001) and no different during 2008 to 2014 (P = .135). Adjusting for STS predicted risk of operative [in-hospital + 30-day] mortality, Massachusetts patients had significantly lower odds (odds ratio, 0.79; 99% confidence interval, 0.66-0.96) of 30-day mortality relative to national data. Outlier programs experienced inconsistent, transient influences on expected mortality and their percentage shares of Massachusetts coronary artery bypass graft cases. CONCLUSIONS: During 12 years of mandatory public reporting, Massachusetts risk-standardized coronary artery bypass graft mortality was consistently and significantly lower than national rates, expected rates were comparable or higher, and evidence for risk aversion was conflicting and inconclusive.

Thromboresistant surfaces with low-dose anticoagulation alleviate clopidogrel-related complications in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Numerous studies have shown that, when using conventional perfusion methodology, patients undergoing coronary artery bypass grafting within 7 days of receiving clopidogrel are at increased risk of bleeding, re-exploration, and blood transfusion. The purpose of this study was to evaluate the effect of clopidogrel administration before coronary artery bypass grafting on patients using thromboresistant surfaces with low-dose heparin during surgical intervention. METHODS: Patients who underwent isolated coronary artery bypass grafting between 2005 and 2009 were incorporated in this retrospective study. Of these, 52 (22.2%) received clopidogrel within 5 days before the operation, and 182 (77.8%) did not. Regression models determined the effect of clopidogrel on the rate of chest re-exploration because of bleeding, 24-hour chest tube output, perioperative blood product transfusion, length of stay, morbidity, and perioperative mortality. Hemorrhage-related preoperative risk factors, as well as those found to be significant in univariate models, were included in the multivariate model. RESULTS: Chest tube drainage was significantly increased during the first 24 hours after the operation in the clopidogrel group (679.7 ± 305.8 vs 516.6 ± 209.8 mL, P = .0007). The need for intraoperative blood product transfusion was similar; nevertheless, more patients receiving clopidogrel required fresh frozen plasma postoperatively (7.7% vs 1.1%, P = .0232). However, risk-adjusted logistic regression showed that exposure to clopidogrel was not a predictor of intraoperative or postoperative blood product transfusion. Lengths of stay in the intensive care unit and hospital were shorter in patients receiving clopidogrel. CONCLUSIONS: Hemostatic complications related to clopidogrel exposure within 5 days before an isolated coronary artery bypass grafting operation can be alleviated by the application of a biocompatible perfusion strategy using low-dose heparin in conjunction with a closed thromboresistant circuit.

Intraoperative myocardial acidosis as a risk for hospital readmission after cardiac surgery.

BACKGROUND: This study elucidates the relationship between intraoperative myocardial acidosis/ischemia and the risk of unplanned hospital readmissions within 30 days and 6 months after cardiac surgery. METHODS: Myocardial tissue pH (corrected to 37 degrees C: pH(37C)) was monitored in 221 patients during cardiac surgery. Regional myocardial acidosis was defined in terms of specific pH thresholds. RESULTS: Fourteen percent and 27% of the patients were readmitted within 30 days and 6 months postoperatively, respectively. The mean number of readmissions was 1.67 +/- 1.24; pH(37C) <6.85 at the end of cardiopulmonary bypass (CPB) was identified as the threshold most significantly associated with readmission. This threshold was associated with a 6-fold increased risk of readmission within 30 days and a 5-fold increased risk within 6 months. CONCLUSIONS: Persistent regional myocardial acidosis after weaning from CPB independently determines unplanned readmission rates up to 6 months postoperatively. This study underscores the importance of avoiding myocardial tissue acidosis during cardiac surgery.

Patients with diabetes mellitus undergoing cardiac surgery are at greater risk for developing intraoperative myocardial acidosis.

OBJECTIVE: In patients undergoing cardiac surgery, intraoperative myocardial acidosis, which quantifies regional myocardial ischemia, has been shown to increase the risk of adverse postoperative outcomes. In this study, we sought to determine the course of intraoperative myocardial acidosis and its impact on postoperative survival in patients with diabetes mellitus undergoing cardiac surgery. METHODS: Intraoperative myocardial tissue pH(37C) was continuously measured in the anterior and posterior left ventricular walls in 264 patients undergoing cardiac surgery; 74 (28.0%) of the patients had diabetes (insulin-dependent diabetes: 54%; non-insulin dependent diabetes: 46%). The shortest time required to reach intraoperative myocardial tissue pH < 6.34 during aortic occlusion and > 6.73 during reperfusion were compared in 3 patient groups: insulin-dependent, non-insulin dependent, and nondiabetic. These pH thresholds have been demonstrated to be associated with adverse postoperative long-term survival. RESULTS: The median times to reach intraoperative myocardial tissue pH(37C) < 6.34 during aortic occlusion were 14, 23, and 36 minutes in the insulin-dependent, non-insulin dependent, and non-diabetic groups, respectively (P = .003). The time taken to reach intraoperative myocardial tissue pH(37C) > 6.73 during reperfusion was similar between the 3 groups. After adjusting for relevant pre- and intraoperative parameters, the risk of developing intraoperative myocardial tissue pH < 6.34 during aortic occlusion was 73% higher in patients with insulin-dependent diabetes mellitus (P = .022) but the same in with patients with non-insulin dependent diabetes mellitus (P = .98) when compared with patients without diabetes. Patients with insulin-dependent diabetes mellitus also had nearly threefold decrease in long-term survival compared with that of patients without diabetes (P = .0007). CONCLUSIONS: Patients with insulin-dependent diabetes mellitus undergoing cardiac surgery are at a greater risk of developing intraoperative myocardial acidosis/ischemia and of decreased survival postoperatively compared with patients without diabetes.

Adverse 30-day outcomes after cardiac surgery: predictive role of intraoperative myocardial acidosis.

BACKGROUND: Regional myocardial acidosis in patients undergoing cardiac surgery has been shown to be reflective of regional myocardial ischemia. This study elucidates the relationship between intraoperative regional myocardial acidosis and 30-day postoperative outcomes after cardiac surgery. METHODS: Intramyocardial tissue pH in the anterior and posterior left ventricular walls was measured in 397 adult patients undergoing valve replacement or coronary revascularization surgery between 1987 and 2001. Dedicated nurses and research assistants prospectively collected preoperative, intraoperative, and outcomes data. Regional myocardial acidosis was defined in terms of pH thresholds identified by recursive partitioning. Adverse 30-day outcome, defined as death or any one of six complications, was the dependent variable in a multivariate logistic regression analysis. A morbidity score was developed on the basis of the sensitivity of each of the six complications in predicting death, and was the dependent variable in a multivariate linear regression analysis. RESULTS: During the period of aortic clamping, a mean intramyocardial tissue pH less than 6.85 was identified to be significant by recursive partitioning, and was encountered in either the anterior or posterior left ventricular wall in 85.4% of patients. After adjusting for preoperative and intraoperative variables, this pH threshold was found to be significantly associated with increased adverse outcomes within 30 days after surgery (p = 0.045). It was also significantly associated with increase in the morbidity score (p = 0.05). CONCLUSIONS: Regional myocardial acidosis of a magnitude frequently encountered during aortic clamping is an independent determinant of adverse 30-day outcomes after cardiac surgery. Its reversal by pH-guided myocardial management has the potential of improving postoperative patient outcomes.

Atherosclerosis is associated with delirium after coronary artery bypass graft surgery.

OBJECTIVES: To investigate whether atherosclerosis of the ascending aorta, internal carotid arteries, and coronary arteries is predictive of postoperative delirium in subjects undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective cohort study. SETTING: Boston Veterans Affairs Healthcare System. PARTICIPANTS: Thirty-six male veterans undergoing primary CABG surgery. MEASUREMENTS: Subjects underwent Duplex ultrasound to assess stenosis in the internal carotid arteries. Information on the ascending aortic plaque, as assessed by transesophageal echocardiogram, and the number of coronary vessels bypassed was collected. To create an atherosclerosis score, the number of atherosclerotic areas was added. A validated delirium battery was administered to the subjects preoperatively and on postoperative Days 2 and 5. RESULTS: Fifteen subjects (41.7%) developed delirium postoperatively. In bivariate analysis, carotid stenosis of 50% or more (relative risk (RR)=3.5, 95% confidence interval (CI)=1.5-8.1) and moderate-severe ascending aortic plaque (RR=2.9, 95% CI=1.0-8.5) were significantly associated with the development of delirium. There was a trend toward a significant association for three or more vessels bypassed (RR=9.6, 95% CI=0.6-145.3). After controlling for age, baseline cognition, and medical comorbidity, the atherosclerosis score was significantly associated with postoperative delirium (adjusted RR=2.7, 95% CI=1.1-6.8). CONCLUSION: In this preliminary report, atherosclerosis in the carotid arteries, aorta, and coronary circulation is associated with the development of delirium after CABG surgery. Further investigation into atherosclerosis as a risk factor for delirium is warranted.

Intraoperative regional myocardial acidosis and reduction in long-term survival after cardiac surgery.

BACKGROUND: Regional myocardial acidosis, as measured with tissue pH electrodes during cardiac surgery, has been shown to be reflective of regional myocardial ischemia. This study examined the relationship between intraoperative regional myocardial acidosis and long-term survival of patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: A total of 496 adult patients who underwent valve replacement, coronary artery revascularization, or both with intraoperative myocardial pH monitoring in the anterior and posterior left ventricular walls were followed up for 3 to 17 years (average 10.2 +/- 4.9 years) for all cause mortality. Regional myocardial acidosis in each patient was defined by the lower of the anterior and posterior wall pH values. RESULTS: A bivariate automatic interaction detection analysis identified three significant regional myocardial acidosis thresholds that affected long-term mortality: pH 37C less than 6.63 before aortic crossclamping, integrated mean pH 37C less than 6.34 during the period of aortic crossclamping, and pH 37C less than 6.73 at discontinuation of cardiopulmonary bypass. Cox proportional hazard regression analysis identified each of these thresholds to be independently determinant of survival, with pH 37C during aortic crossclamping having the highest risk ratio (risk ratio 2.15, 95% confidence interval 1.37-3.37). Raising pH 37C from lower than threshold before aortic crossclamping to higher than threshold during clamping increased the median survival by 40.2%. CONCLUSION: In adult patients undergoing cardiac surgery with cardiopulmonary bypass, regional myocardial ischemic acidosis before aortic crossclamping, during aortic crossclamping, and at discontinuation of cardiopulmonary bypass are independently associated with reduced long-term postoperative survival. Reversing or avoiding myocardial acidosis during cardiac surgery improves long-term patient survival.

Intraoperative regional myocardial acidosis predicts the need for inotropic support in cardiac surgery.

OBJECTIVE: To determine the impact of regional myocardial acidosis encountered during cardiac surgery on the need for inotropic and intra-aortic balloon (IAB) support. METHODS: Intramyocardial tissue pH(37C) was measured in 247 patients undergoing cardiopulmonary bypass (CPB). Inotropic support (INO) was defined as requiring one or more of norepinephrine/epinephrine/amrinone/dobutamine/>2.5 mug/kg/min dopamine, for at least 45 minutes intraoperatively, and intraoperative or postoperative IAB use. PH (corrected to 37 degrees C, pH(37C)) during surgery was compared in patients who needed INO versus those who did not. Multivariate logistic regression models identified the determinants of INO. RESULTS: Fifty patients (20.2%) required INO intraoperatively. pH(37C) was significantly lower throughout reperfusion in patients needing INO. Preoperative ejection fraction and pH(37C) during reperfusion were identified as independent predictors of INO. CONCLUSIONS: This is the first study to show that intraoperative regional myocardial acidosis, a preventable condition, independently determines the need for intraoperative INO. Increased INO is associated with greater postoperative mortality and morbidity.

Determinants of regional myocardial acidosis during cardiac surgery.

BACKGROUND: Intraoperative regional myocardial acidosis (RMA) during cardiac surgery has been shown to be reflective of regional myocardial ischemia and an independent predictor of adverse postoperative outcomes. This study identifies the determinants of intraoperative RMA. METHODS: Intramyocardial tissue pH(37C) in the anterior and posterior LV walls was measured in 641 adult patients during cardiac surgery. RMA at two intraoperative periods was quantified as integrated mean pH(37C) < 6.35 during aortic clamping (AC) and pH(37C) < 6.73 at the end of cardiopulmonary bypass (CPB). These pH thresholds were chosen because of their demonstrated relationship to long-term patient survival. Multivariate logistic regression models were constructed. An acidosis prediction score was constructed based on the factors determining RMA at the end of CPB. RESULTS: Independent determinants of RMA during AC were preoperative New York Heart Association class III/IV (P = .007), current smoker (P = .0088), pH(37C) < 6.63 prior to AC (P < .0001), and intraoperative myocardial management technique (P = .0001). Independent determinants of RMA at end of CPB were ASA class IV/V (P = .0042), pH(37C) < 6.63 prior to AC (P = .035), pH(37C) < 6.35 during AC (P = .001), and total duration of CPB > or = 212 minutes (P = .001). CONCLUSIONS: RMA during cardiac surgery is determined by patient risk factors, the magnitude of preceding regional myocardial acidosis, and the duration of CPB.

Acidosis-induced apoptosis in human and porcine heart.

BACKGROUND: Acidosis-mediated injury to cardiac myocytes during surgery may lead to progressive heart failure. The nature of this injury, although not well defined, may be caused by induction of apoptosis in cardiac myocytes. We applied fluorescence imaging and biochemical techniques to assess apoptosis in cardiac myocytes excised from human patients and porcine subjects maintained on cardiopulmonary bypass to demonstrate the relationship between acidosis and apoptosis. METHODS: Multiphoton microscopy was used to image fluorescence signals generated in myocytes deep within atrial and ventricular biopsies for identification of apoptotic changes. The biopsies, obtained during cardiac surgery, were subjected to ex vivo or in vivo acidosis. Proapoptotic markers such as exposure of phosphatidyl serine, cytochrome c, apoptotic protease-activating factor-1, and caspase-3 were identified using fluorescence-based imaging and biochemical assays. RESULTS: Within 30 minutes of storage in low pH (<7) buffers, apoptosis was detected in human atrial samples, the severity of which correlated well with low pH. Apoptosis was also detected in atrial and ventricular biopsy samples obtained from three porcine subjects maintained on cardiopulmonary bypass and undergoing 110 minutes of aortic cross-clamp and 10 minutes of reperfusion, in which the cardiac pH was 6.36, 7.14, and 7.48. The apoptosis level detected in postacidotic reperfused cardiac tissue was pH dependent and approximately threefold greater than the precross-clamp levels. CONCLUSIONS: Using fluorescence multiphoton microscopy and biochemical techniques we have assessed a direct correlation between low pH and induction of apoptosis in cardiac samples obtained both from human patients undergoing cardiac surgery and porcine subjects maintained on cardiopulmonary bypass simulating cardiac surgery.

Multi-photon microscopic evaluation of saphenous vein endothelium and its preservation with a new solution, GALA.

BACKGROUND: Injury to endothelium can compromise the patency of bypass grafts harvested during coronary artery bypass graft (CABG) surgery. Maintaining structural and functional viability of endothelium in grafts may lead to improved long-term patency. The information gained from the application of multi-photon microscopy in transmission and epifluorescence mode was used to assess the structural and functional integrity of human saphenous vein segments stored in multiple preservation solutions, and to design a superior storage solution. METHODS: Multi-photon microscopy was used to image deep within saphenous vein tissue harvested from patients undergoing CABG for analysis of endothelial structure and function. Endothelial cell structural viability, calcium mobilization, and nitric oxide generation were determined using specific fluorescence markers. RESULTS: Within 60 minutes of harvest and storage in standard preservation solutions, calcium mobilization and nitric oxide generation were markedly diminished with more than 90% of endothelial cells no longer viable in the vein. In contrast, veins could be stored for 24 hours without substantial loss in cell viability in a newly formulated heparinized physiologic buffered salt solution containing glutathione, ascorbic acid, and L-arginine (GALA). CONCLUSIONS: Standard solutions in clinical use today led to a profound decline in saphenous vein endothelial cell viability, whereas the newly designed physiologic salt solution (GALA) maintained endothelial function and structural viability for up to 24 hours. The improvements seen from using GALA as a vessel storage medium may lead to greater long-term vein graft patency following CABG surgery.

Percutaneous coronary intervention versus coronary bypass graft surgery for diabetic patients with unstable angina and risk factors for adverse outcomes with bypass: outcome of diabetic patients in the AWESOME randomized trial and registry.

OBJECTIVES: This study compared survival after percutaneous coronary intervention (PCI) with survival after coronary artery bypass graft surgery (CABG) among diabetics in the Veterans Affairs AWESOME (Angina With Extremely Serious Operative Mortality Evaluation) study randomized trial and registry of high-risk patients. BACKGROUND: Previous studies indicate that CABG may be superior to PCI for diabetics, but no comparisons have been made for diabetics at high risk for surgery. METHODS: Over five years (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior CABG, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, or an intra-aortic balloon being required to stabilize) were identified. A total of 781 were acceptable for CABG and PCI, and 454 consented to be randomized. The 1,650 patients not acceptable for both CABG and PCI constitute the physician-directed registry, and the 327 who were acceptable but refused to be randomized constitute the patient-choice registry. Diabetes prevalence was 32% (144) among randomized patients, 27% (89) in the patient-choice registry, and 32% (525) in the physician-directed registry. The CABG and PCI survival rates were compared using Kaplan-Meier curves and log-rank tests. RESULTS: The respective CABG and PCI 36-month survival rates for diabetic patients were 72% and 81% for randomized patients, 85% and 89% for patient-choice registry patients, and 73% and 71% for the physician-directed registry patients. None of the differences was statistically significant. CONCLUSIONS: We conclude that PCI is a relatively safe alternative to CABG for diabetic patients with medically refractory unstable angina who are at high risk for CABG.

Percutaneous coronary intervention versus coronary bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: The VA AWESOME multicenter registry: comparison with the randomized clinical trial.

OBJECTIVES: This study was designed to compare the three-year survival after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) in physician-directed and patient-choice registries with the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial results. BACKGROUND: The AWESOME multicenter randomized trial and registry compared the long-term survival after PCI and CABG for the treatment of patients with medically refractory myocardial ischemia and at least one additional risk factor for adverse outcome with CABG. The randomized trial demonstrated comparable three-year survival. METHODS: Over a five-year period (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior heart surgery, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, intra-aortic balloon required to stabilize) were identified. By physician consensus, 1,650 patients formed a physician-directed registry assigned to CABG (692), PCI (651) or further medical therapy (307), and 781 were angiographically eligible for random allocation; 454 of these patients constitute the randomized trial, and the remaining 327 constitute a patient choice registry. Survival for CABG and PCI was compared using Kaplan-Meier curves and log-rank tests. RESULTS: The CABG and PCI 36-month survival rates for randomized patients were 79% and 80%, respectively. The CABG and PCI 36-month survival rates were both 76% for the physician-directed subgroup; comparable survival rates for the patient-choice subgroup were 80% and 89%, respectively. None of the global log-rank tests for survival demonstrated significant differences. CONCLUSIONS: Both registries support the randomized trial conclusion: PCI is an alternative to CABG for some medically refractory high-risk patients.