Edward P. Chen

Off-Pump Coronary Artery Bypass Disproportionately Benefits High-Risk Patients

BACKGROUND It is not known which patient subgroups may benefit most from off-pump coronary artery bypass grafting (OPCAB) rather than coronary artery bypass grafting on cardiopulmonary bypass (CPB). METHODS The Society of Thoracic Surgeons database was queried for all isolated, primary coronary artery bypass graft cases between January 1, 1997, and December 31, 2007, at a US academic center. The Society of Thoracic Surgeons Predicted Risk of Mortality (PROM) was calculated by a formula based on 30 preoperative risk factors. It was used in three ways to compare 30-day operative mortality between patients treated with OPCAB versus CPB. First, patients were divided into quartiles based on their PROM, and mortality rates were compared between OPCAB and CPB patients within each PROM quartile. Second, a logistic regression model tested for an interaction between surgery type and PROM; a significant interaction would indicate that the relative mortality risk of OPCAB versus CPB varied with different PROM levels. Finally, locally smoothed kernel regression curves were used to visually estimate a threshold PROM point at which mortality rates diverge for the surgery types. RESULTS There were 14,766 consecutive patients, 7,083 OPCAB (48.0%) and 7,683 CPB (52.0%). There was no difference in operative mortality between OPCAB and CPB for patients in the lower two risk quartiles. In the higher risk quartiles there was a mortality benefit for OPCAB (odds ratio, 0.62 and 0.45 for OPCAB in the third and fourth risk quartiles). Logistic regression analysis confirmed a significant interaction between surgery type and PROM (p = 0.005) meaning that OPCAB is especially beneficial to patients with higher PROM. This benefit is most significant for patients with PROM values above 2.5% to 3%, where mortality curves sharply diverge. CONCLUSIONS Off-pump coronary artery bypass grafting is associated with lower operative mortality than coronary artery bypass grafting on CPB for higher risk patients. This mortality benefit increases with increasing PROM.

Off-pump coronary bypass provides reduced mortality and morbidity and equivalent 10-year survival.

BACKGROUND This study compared in-hospital major adverse cardiac events (MACE) and long-term survival after off-pump (OPCAB) vs on-pump (CPB) coronary artery bypass grafting (CABG). METHODS Reviewed were 12,812 consecutive isolated CABG patients from 1997 to 2006. A propensity score (PS), including 40 preoperative risk factors, balanced characteristics between OPCAB and CPB groups. Multiple logistic regression models tested whether gender or surgery type, or their interaction, were associated with in-hospital mortality and MACE. A proportional hazards regression model and Kaplan-Meier curves related long-term survival with gender, surgery type, and their interaction, adjusted for PS and age. RESULTS OPCAB was associated with a significant reduction in operative mortality (adjusted odds ratio [AOR], 0.68; p = 0.045), stroke (AOR, 0.48; p < 0.001), and MACE (AOR, 0.66; p = 0.018). Female gender was associated with higher rates of death (AOR, 1.93), stroke (AOR, 1.82), myocardial infarction (AOR, 2.19), and MACE (AOR, 1.97; each p < 0.001). Women disproportionately benefited from OPCAB in operative mortality (p = 0.04). Odds of death for women on CPB were higher than for women treated with OPCAB (AOR, 2.07, p = 0.005). Odds of death for men on CPB were not significantly higher than for men treated with OPCAB (AOR, 1.16, p = 0.51). Male gender was associated with longer-term survival (p = .011), but surgery type (OPCAB vs CPB) was not (p = 0.23). CONCLUSIONS OPCAB provides significant early mortality and morbidity advantages, especially for women. During the 10-year follow-up, OPCAB and CPB result in similar survival, regardless of gender.

Long-Term Outcomes After Isolated Aortic Valve Replacement in Octogenarians: A Modern Perspective

BACKGROUND With the recent advent of percutaneous valve therapy, an increased need for the evaluation of outcomes after open aortic valve replacement (AVR) in elderly patients is warranted. This study compares the short- and long-term survival outcomes of octogenarians after AVR with younger age groups in the modern surgical era. METHODS A retrospective review was performed on patients who underwent isolated, primary AVR from 1996 to 2006 at the Emory Healthcare Hospitals. Five-hundred fifteen patients were divided into three age groups: 60 to 69 (n = 206), 70 to 79 (n = 221), and 80 to 89 years of age (n = 88). Outcomes were compared among the age groups using logistic regression and analysis of variance techniques. Long-term survival between age groups was compared using the Cox proportional hazards model. Kaplan-Meier plots were used to determine survival rates. RESULTS The groups were similar with respect to in-hospital mortality (p = 0.66) and hospital length of stay (p = 0.08). Preoperative predictors of in-hospital mortality included stroke (odds ratio [OR] 5.36), chronic lung disease (OR 4.51), and renal failure (OR 1.39). As expected, age significantly impacted long-term survival (hazard ratio [HR] 1.06). Other predictors of long-term survival included stroke (HR 2.15), current smoker (HR 2.03), diabetes (HR 1.53), and renal failure (HR 1.4). The Kaplan-Meier estimate of median survival for octogenarians was 7.4 years. CONCLUSIONS In the modern era, octogenarians have acceptable short- and long-term results after open AVR. Comparisons of less invasive techniques for AVR should rely on outcomes based in the modern era and decisions regarding surgical intervention in patients requiring AVR should not be based on age alone.

A comparative evaluation of rotation thromboelastometry and standard coagulation tests in hemodilution-induced coagulation changes after cardiac surgery

BACKGROUND: Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple perturbations in cellular and humoral elements of coagulation. A timely and comprehensive method to evaluate hemostasis would be helpful in the management of bleeding patients after CPB. The assessment of whole blood coagulation using rotation thromboelastometry (ROTEM) was compared to coagulation tests routinely performed during cardiac surgery.

Selective antegrade cerebral perfusion via right axillary artery cannulation reduces morbidity and mortality after proximal aortic surgery

INTRODUCTION Selective antegrade cerebral perfusion is a well-described neuroprotective technique used in proximal aortic surgery. This study investigated whether selective antegrade cerebral perfusion is associated with improved outcomes in both emergency and elective settings compared with deep hypothermic circulatory arrest alone. METHODS Retrospective review was performed for all cases of proximal aortic surgery between January 2004 and May 2007. Of these 271 patients, 105 had emergency and 166 had elective operation. Selection bias was controlled using propensity scoring methods. Multivariable logistic regression analysis was used to model adverse outcomes as a function of selective antegrade cerebral perfusion, emergency status, and their interaction, adjusted for the propensity score. Adjusted odds ratios were formulated with 95% confidence intervals. RESULTS Operative mortality occurred in 12.1% (33/271) of patients: 8.8% (18/205) in patients with selective antegrade cerebral perfusion versus 22.7% (15/66) in those with deep hypothermic circulatory arrest alone (P = .003). Temporary neurologic dysfunction occurred in 5.9% (15/255) of patients: 4.5% (9/198) in selective antegrade cerebral perfusion versus 10.5% (6/57) in deep hypothermic circulatory arrest alone (P = .09). Stroke occurred in 4.3% (11/255) of patients with no difference between groups. In the elective setting, selective antegrade cerebral perfusion was associated with a significant decrease in operative mortality compared with deep hypothermic circulatory arrest alone. Overall, selective antegrade cerebral perfusion was associated with shorter intensive care unit and ventilator times and fewer renal and pulmonary complications. Significant multivariable predictors of operative mortality were emergency status, previous coronary surgery, and cardiopulmonary bypass time. CONCLUSIONS Use of selective antegrade cerebral perfusion confers a survival advantage during proximal aortic surgery that is most apparent in the elective setting. Improved resource utilization and fewer pulmonary and renal complications were observed in patients with selective antegrade cerebral perfusion.

Moderate Hypothermia and Unilateral Selective Antegrade Cerebral Perfusion: A Contemporary Cerebral Protection Strategy for Aortic Arch Surgery

BACKGROUND Cerebral protection techniques during aortic arch surgery include deep hypothermic circulatory arrest, retrograde cerebral perfusion, and (or) antegrade cerebral perfusion. It is unclear whether unilateral selective antegrade cerebral perfusion (uSACP) in the setting of moderate hypothermic circulatory arrest (MHCA) constitutes an effective cerebral protective strategy during aortic arch reconstruction. METHODS A retrospective review was performed for all aortic arch cases involving uSACP between January 2004 and December 2009. Of these 412 patients, 97 (24%) were treated emergently. Adverse outcomes included operative mortality, permanent neurologic dysfunction, temporary neurologic dysfunction, and renal failure requiring dialysis. Potential selection bias was controlled by the inclusion of 11 covariates. Multivariable logistic regression analysis was used to model adverse outcome as a function of MHCA and the covariates. Adjusted odds ratios were formulated along with 95% confidence intervals. RESULTS Three hundred forty-four patients underwent hemiarch reconstruction and 68 patients underwent total arch replacement. The mean core body temperature at the initiation of uSACP was 25.7 degrees C + or - 2.8 degrees C with a uSACP time of 30 + or - 15 minutes. Overall operative mortality occurred in 29 (7.0%) patients. The incidence of permanent neurologic dysfunction and temporary neurologic dysfunction were 3.6% and 5.1%, respectively. Nineteen (4.6%) patients suffered postoperative renal failure requiring dialysis. In the adjusted analysis, MHCA was not found to be an independent predictor of mortality, permanent neurologic dysfunction, temporary neurologic dysfunction, or renal failure requiring dialysis. CONCLUSIONS The MHCA with adjunctive uSACP is not an independent risk factor for adverse outcomes after aortic arch surgery. These data suggest that MHCA combined with uSACP represents an effective cerebral protective strategy in patients undergoing arch reconstruction in both the elective and emergent settings.

Contemporary results for proximal aortic replacement in North America.

OBJECTIVES The purpose of this study was to characterize operative outcomes for ascending aorta and arch replacement on a national scale and to develop risk models for mortality and major morbidity. BACKGROUND Contemporary outcomes for ascending aorta and arch replacement in North America are unknown. METHODS We queried the Society of Thoracic Surgeons Database for patients undergoing ascending aorta (with or without root) with or without arch replacement from 2004 to 2009. The database captured 45,894 cases, including 12,702 root, 22,048 supracoronary ascending alone, 6,786 ascending plus arch, and 4,358 root plus arch. Baseline characteristics and clinical outcomes were analyzed. A parsimonious multivariable logistic regression model was constructed to predict risks of mortality and major morbidity. RESULTS Operative mortality was 3.4% for elective cases and 15.4% for nonelective cases. A risk model for operative mortality (c-index 0.81) revealed a risk-adjusted odds ratio for death after emergent versus elective operation of 5.9 (95% confidence interval: 5.3 to 6.6). Among elective patients, end-stage renal disease and reoperative status were the strongest predictors of mortality (adjusted odds ratios: 4.0 [95% confidence interval: 2.6 to 6.4] and 2.3 (95% confidence interval: 1.9 to 2.7], respectively; p < 0.0001). CONCLUSIONS Current outcomes for ascending aorta and arch replacement in North America are excellent for elective repair; however, results deteriorate for nonelective status, suggesting that increased screening and/or lowering thresholds for elective intervention could potentially improve outcomes. The predictive models presented may serve clinicians in counseling patients.

Total respiratory support from swine lungs in primate recipients

UNLABELLED The use of nonhuman lung donors, such as swine, has the potential to provide an unlimited supply of organs. However, hyperacute rejection has prevented pulmonary xenotransplantation. OBJECTIVE Our aim was to test the hypothesis that immunodepletion by pretransplantation swine lung perfusion will prevent hyperacute swine-to-primate pulmonary xenograft rejection and allow for a functional swine pulmonary xenograft. METHODS Seven baboons underwent left pneumonectomy followed by orthotopic transplantation of the swine left lung. Four baboons received immunodepletion by perfusion with swine lungs before transplantation, and three received no treatment before transplantation. RESULTS After transplantation, pulmonary xenografts from immunodepleted baboons had a low pulmonary vascular resistance and a high pulmonary blood flow compared with control animals, which had a high pulmonary vascular resistance and a low pulmonary blood flow. After 60 minutes of reperfusion, three of four immunodepleted animals also tolerated complete occlusion of the right pulmonary artery, with the baboon relying completely on the swine pulmonary xenograft for respiratory function for 11 hours. Pathologic analysis of peripheral lung biopsy specimens taken from control lungs displayed alveolar disruption and hemorrhage within small vessels, whereas swine lungs transplanted into immunodepleted baboons displayed little histologic evidence of injury. Furthermore, pulmonary xenografts transplanted into immunodepleted baboons demonstrated excellent respiratory function and adequate hemodynamics during occlusion of the right pulmonary artery. CONCLUSION Hyperacute pulmonary xenograft rejection can be prevented by pretransplantation swine lung perfusion. Swine pulmonary xenografts can provide complete respiratory support in primates when rejection is prevented.

Milrinone Improves Pulmonary Hemodynamics and Right Ventricular Function in Chronic Pulmonary Hypertension

BACKGROUND Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole-induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.

The impact of hematocrit on fibrin clot formation assessed by rotational thromboelastometry.

BACKGROUND: Rotational thromboelastometry (ROTEM®)–based FIBTEM is used perioperatively to assess the extent of fibrin polymerization in whole blood. In FIBTEM, cytochalasin D eliminates the contribution of platelets to whole blood clotting, but changing levels in fibrin(ogen) and erythrocytes may differently affect clot formation. Because dynamic changes of hematocrit are not reflected in plasma fibrinogen measurements, we hypothesized that the lack of erythrocytes in isolated plasma measurements would affect the relationship between the Clauss method and whole blood–based FIBTEM during cardiac surgery. Therefore, in the current study we investigated the influence of perioperative hematocrit changes on FIBTEM and fibrinogen measurements. METHODS: Blood samples were collected from 6 consenting healthy volunteers. FIBTEM tests were run before and after serial in vitro dilutions of whole blood with saline or autologous plasma (5:1, 2:1, and 1:1 v/v). We then evaluated the relationship between FIBTEM–maximal clot firmness (MCF) and the Clauss fibrinogen method in relation to hematocrit values before and after cardiac surgery. Pearson correlation coefficients were determined between laboratory test results and ROTEM variables. RESULTS: Upon in vitro hematocrit reduction, FIBTEM-MCF was progressively decreased depending on the extent of saline dilution, but it was increased by 31% after 1:1 volume replacement with autologous plasma (P < 0.05). In samples from cardiac patients (150 measurements in 50 patients), the overall correlation coefficient between FIBTEM-MCF and plasma fibrinogen was 0.80 (P < 0.001). In hemodiluted blood samples (during surgery or at intensive care unit), FIBTEM-MCF 10 mm corresponded to plasma fibrinogen levels of 200 mg/dL. In the subgroup analysis (n = 50 each), according to hematocrit levels (<25%, ≥25% to 30%, ≥30%), plasma fibrinogen levels of 200 mg/dL corresponded to 11 mm, 10 mm, and 8 mm of FIBTEM-MCF, respectively. The correlation between FIBTEM-MCF and plasma fibrinogen was higher at lower hematocrit (<25%) than at higher hematocrit (>30%) (r = 0.88 and 0.67, respectively). CONCLUSIONS: Perioperative changes in hematocrit affect the correlation between plasma fibrinogen levels and FIBTEM-MCF values. The higher correlation between FIBTEM-MCF and plasma fibrinogen with lower hematocrit (<25%) indicates that FIBTEM is a practical method to determine the need for fibrinogen replacement in bleeding patients who typically develop perioperative anemia.