Jeffrey G. Gaca

Intraoperative Systolic Blood Pressure Variability Predicts 30-day Mortality in Aortocoronary Bypass Surgery Patients

Background:Few data support an association between blood pressure variability and clinical outcomes during cardiac surgery. We tested the hypothesis that intraoperative systolic blood pressure variability outside a targeted blood pressure range predicts 30-day mortality in patients undergoing cardiac surgery. Methods:Electronically captured blood pressure data from 7,504 consecutive coronary bypass surgery procedures between September 1, 1996, and December 31, 2005, were divided into development and validation cohorts. Systolic blood pressure variability episodes outside a blood pressure range (e.g., higher than 135 or lower than 95 mmHg) were characterized by number of episodes, magnitude of episode, duration of episode, and magnitude × duration of excursion (i.e., area under the curve). Multiple logistic regression analysis was used to assess 30-day mortality association. The most predictive mortality risk characteristic and blood pressure range was tested in the validation cohort. Results:A total of 3.1 million intraoperative blood pressure evaluations were analyzed. Systolic blood pressure variability was derived in 5,038 patients and validated in 2,466 patients (8% without cardiopulmonary bypass and 6% with valve procedure). Among all tested indices of blood pressure variability, mean duration of systolic excursion (outside a range of 105–130 mmHg) was most predictive of 30-day mortality (odds ratio = 1.03 per minute, 95% CI 1.02–1.39, P < 0.0001). Conclusions:Intraoperative blood pressure variability is associated with 30-day postoperative mortality in patients undergoing aortocoronary bypass surgery.

Laparoscopic antireflux surgery in the lung transplant population

Background: Lung transplantation has emerged as a viable therapeutic option for patients with a variety of end-stage pulmonary diseases. As immediate posttransplant surgical outcomes have improved, the greatest limitation of lung transplantation remains chronic allograft dysfunction. Gastroesophageal reflux disease (GERD) with resultant aspiration has been implicated as a potential contributing factor in allograft dysfunction. GERD is prevalent in end-stage lung disease patients, and it is even more common in patients after transplantation. We report here on the safety of laparoscopic fundoplication surgery for the treatment of GERD in lung transplant patients. Methods: Eighteen of the 298 lung transplants performed at Duke University Medical Center underwent antireflux surgery for documented severe GERD. The safety and benefit of laparoscopic fundoplications in this population was evaluated. Results: The antireflux surgeries included 13 laparoscopic Nissen fundoplications, four laparoscopic Toupets, and one open Nissen (converted secondary to extensive adhesions). Two of the 18 patients reported recurrence of symptoms (11%), and two others reported minor GI complaints postoperatively (nausea, bloating). There were no deaths from the antireflux surgery. After fundoplication surgery, 12 of the 18 patients showed measured improvement in pulmonary function (67%). Conclusions: GERD occurs commonly in the posttransplant lung population. Laparoscopic fundoplication surgery, when indicated, can be done safely with minimal morbidity and mortality. In addition to the resolution of reflux symptoms, improvement in pulmonary function may be seen in this population after fundoplication. Lung transplant patients with severe GERD should be strongly considered for antireflux surgery.

Prolonged function of macrophage, von willebrand factor-deficient porcine pulmonary xenografts

Porcine von Willebrand factor (vWF) activates human and primate platelets. Having determined the importance of pulmonary intravascular macrophages (PIMs) in pulmonary xenotransplantation, we evaluated whether, in the absence of PIMs, vWF might play a role in pulmonary xenograft dysfunction.

Outcomes of Acute Type A Dissection Repair Before and After Implementation of a Multidisciplinary Thoracic Aortic Surgery Program

OBJECTIVES The purpose of this study was to compare the results of acute type A aortic dissection (ATAAD) repair before and after implementation of a multidisciplinary thoracic aortic surgery program (TASP) at our institution, with dedicated high-volume thoracic aortic surgeons, a multidisciplinary approach to thoracic aortic disease management, and a standardized protocol for ATAAD repair. BACKGROUND Outcomes of ATAAD repair may be improved when operations are performed at specialized high-volume thoracic aortic surgical centers. METHODS Between 1999 and 2011, 128 patients underwent ATAAD repair at our institution. Records of patients who underwent ATAAD repair 6 years before (n = 56) and 6 years after (n = 72) implementation of the TASP were retrospectively compared. Expected operative mortality rates were calculated using the International Registry of Acute Aortic Dissection pre-operative prediction model. RESULTS Baseline risk profiles and expected operative mortality rates were comparable between patients who underwent surgery before and after implementation of the TASP. Operative mortality before TASP implementation was 33.9% and was statistically equivalent to the expected operative mortality rate of 26.0% (observed-to-expected mortality ratio 1.30; p = 0.54). Operative mortality after TASP implementation fell to 2.8% and was statistically improved compared with the expected operative mortality rate of 18.2% (observed-to-expected mortality ratio 0.15; p = 0.005). Differences in survival persisted over long-term follow-up, with 5-year survival rates of 85% observed for TASP patients compared with 55% for pre-TASP patients (p = 0.002). CONCLUSIONS ATAAD repair can be performed with results approximating those of elective proximal aortic surgery when operations are performed by a high-volume multidisciplinary thoracic aortic surgery team. Efforts to standardize or centralize care of patients undergoing ATAAD are warranted.

Prevention of acute lung injury in swine: depletion of pulmonary intravascular macrophages using liposomal clodronate

BACKGROUND Swine contain large numbers of pulmonary intravascular macrophages (PIMs) that mediate the physiological response observed in acute lung injury (ALI). As the hyperacute dysfunction observed in pulmonary xenotransplantation is similar to endotoxin-induced ALI, PIMs may play a critical role in pulmonary xenograft dysfunction. We used liposomal clodronate to eliminate the PIM population in a model of acute swine lung injury. MATERIALS AND METHODS Experimental swine (n = 6) received liposomal clodronate (1.25 g/10 kg) and control swine (n = 5) received saline containing liposomes before infusion of lipopolysaccharide (450 ng/kg). RESULTS Control swine demonstrated higher peak pulmonary artery pressures (41.8 +/- 2.2 versus 16.8 +/- 1.2 mm Hg; P < 0.0001) and higher peak pulmonary vascular resistances (1405 +/- 209 versus 353 +/- 81 dynes. s. cm(-5); P = 0.0016) in response to lipopolysaccharide infusion. Clodronate treated swine also had significantly lower serum levels of tumor necrosis factor-alpha, interleukin-6, and thrombin. CONCLUSIONS Liposomal clodronate effectively attenuates acute swine lung injury induced by endotoxin. This method of depletion of the PIM population presents a promising new treatment of swine lungs before xenotransplantation.

Pathologic nodal status predicts disease-free survival after neoadjuvant chemoradiation for gastroesophageal junction carcinoma

BackgroundThe incidence of carcinoma of the gastroesophageal junction (GEJ) is rapidly increasing, and the prognosis remains poor. We examined outcomes in patients who received neoadjuvant chemoradiation for GEJ tumors to identify factors that predict disease-free (DFS) and overall (OS) survival.MethodsA retrospective analysis was performed of 101 consecutive patients who received chemoradiation and surgery for GEJ carcinoma between 1992 and 2001.ResultsThe median DFS and OS of all patients were 16 and 25 months, respectively. Twenty-eight patients with a complete histological response (T0N0) experienced greater DFS compared with all others (P = .02). Node-negative patients, regardless of T stage, experienced improved median DFS (24 months) compared with N1 patients (9 months; P = .01). Preoperative stage, age, tumor location, or Barrett’s esophagus did not independently predict OS by univariate analysis. Multivariate analysis demonstrated that only posttreatment nodal status (P = .03)—not the degree of primary tumor response—predicted DFS.ConclusionsThe nodal status of patients with GEJ tumors after neoadjuvant therapy is predictive of DFS after resection. The poor outcome in node-positive patients supports postneoadjuvant therapy nodal staging, because surgical aggressiveness should be tempered by the realization that cure is unlikely and median survival is short.

Disseminated intravascular coagulation in association with pig-to-primate pulmonary xenotransplantation

BACKGROUND Profound coagulopathy has been proposed as a barrier to xenotransplantation. Disseminated intravascular coagulation (DIC) has been observed with the rejection of renal and bone marrow xenografts but has not yet been described in pulmonary xenografts. METHODS This study examined the coagulation parameters in five baboons that received pulmonary xenografts and one baboon that was exposed to porcine lung during an extracorporeal perfusion. Platelet counts, prothrombin times (PT), and levels of fibrinogen, D-dimers, and thrombin-antithrombin III complex (TAT) were analyzed. In addition, serum levels of plasminogen activator inhibitor-1 (PAI-1), thrombomodulin (TM), tissue plasminogen activator (tPA), and tissue factor (TF) were determined. RESULTS Hyperacute pulmonary xenograft dysfunction, which occurred within 0-9 hr of graft reperfusion, was associated with clinically evident DIC. This coagulopathy was characterized by thrombocytopenia, decreased fibrinogen levels, elevations in PT, and increases in D-dimers and TAT. Furthermore, transient increases in PAI-1, increases in TM, and increases in tPA were observed in the serum of some but not all recipients. None of the baboons demonstrated measurable increases in soluble TF. CONCLUSIONS Although DIC in renal or bone marrow xenotransplantation develops over a period of days, DIC associated with hyperacute pulmonary xenograft dysfunction develops within hours of graft reperfusion. Thus, the DIC in pulmonary xenotransplantation may represent a unique and/or accelerated version of the coagulopathy observed with renal and bone marrow xenotransplantation.

Practice Patterns and Clinical Outcomes After Hybrid Coronary Revascularization in the United States An Analysis From the Society of Thoracic Surgeons Adult Cardiac Database

Background— Hybrid coronary revascularization (HCR) involves a combination of surgical and percutaneous techniques, which in selected patients may present an alternative to conventional coronary artery bypass grafting (CABG). Methods and Results— Patients were included who underwent HCR (staged/concurrent) or isolated CABG in the Society of Thoracic Surgeons Adult Cardiac Surgery Database (July 2011 to March 2013). HCR represented 0.48% (n=950; staged=809, concurrent=141) of the total CABG volume (n=198 622) during the study period, and was performed in one-third of participating centers (n=361). Patients who underwent HCR had higher cardiovascular risk profiles in comparison with patients undergoing CABG. In comparison with CABG, median sternotomy (98.5% for CABG, 61.1% for staged HCR, and 52.5% for concurrent HCR), direct vision harvesting (98.9%, 66.0%, and 68.1%) and cardiopulmonary bypass (83.4%, 45%, and 36.9%) were less frequently used for staged and concurrent HCR, whereas robotic assistance (0.7%, 33.0%, and 30.5%) was more common. After adjustment, no differences were observed for the composite of in-hospital mortality and major morbidity (odds ratio, 0.93; 95% confidence interval, 0.75–1.16; P=0.53 for staged HCR, and odds ratio, 0.94; 95% confidence interval, 0.56–1.56; P=0.80 for concurrent HCR in comparison with CABG). There was no statistically significant association between operative mortality and either treatment group (odds ratio, 0.74; 95% confidence interval, 0.42–1.30; P=0.29 for staged HCR, and odds ratio, 2.26; 95% confidence interval, 0.99–5.17; P=0.053 for concurrent HCR in comparison with CABG). Conclusion— HCR, either as a staged or concurrent procedure, is performed in one-third of US hospitals and is reserved for a highly selected patient population. Although HCR may appear to be an equally safe alternative for CABG surgery, further randomized study is warranted.Background— Hybrid coronary revascularization (HCR) involves a combination of surgical and percutaneous techniques, which in selected patients may present an alternative to conventional coronary artery bypass grafting (CABG). Methods and Results— Patients were included who underwent HCR (staged/concurrent) or isolated CABG in the Society of Thoracic Surgeons Adult Cardiac Surgery Database (July 2011 to March 2013). HCR represented 0.48% (n=950; staged=809, concurrent=141) of the total CABG volume (n=198 622) during the study period, and was performed in one-third of participating centers (n=361). Patients who underwent HCR had higher cardiovascular risk profiles in comparison with patients undergoing CABG. In comparison with CABG, median sternotomy (98.5% for CABG, 61.1% for staged HCR, and 52.5% for concurrent HCR), direct vision harvesting (98.9%, 66.0%, and 68.1%) and cardiopulmonary bypass (83.4%, 45%, and 36.9%) were less frequently used for staged and concurrent HCR, whereas robotic assistance (0.7%, 33.0%, and 30.5%) was more common. After adjustment, no differences were observed for the composite of in-hospital mortality and major morbidity (odds ratio, 0.93; 95% confidence interval, 0.75–1.16; P =0.53 for staged HCR, and odds ratio, 0.94; 95% confidence interval, 0.56–1.56; P =0.80 for concurrent HCR in comparison with CABG). There was no statistically significant association between operative mortality and either treatment group (odds ratio, 0.74; 95% confidence interval, 0.42–1.30; P =0.29 for staged HCR, and odds ratio, 2.26; 95% confidence interval, 0.99–5.17; P =0.053 for concurrent HCR in comparison with CABG). Conclusion— HCR, either as a staged or concurrent procedure, is performed in one-third of US hospitals and is reserved for a highly selected patient population. Although HCR may appear to be an equally safe alternative for CABG surgery, further randomized study is warranted. # CLINICAL PERSPECTIVE {#article-title-21}

Intraoperative use of low-dose recombinant activated factor VII during thoracic aortic operations.

BACKGROUND Numerous studies have supported the effectiveness of recombinant activated factor VII (rFVIIa) for the control of bleeding after cardiac procedures; however safety concerns persist. Here we report the novel use of intraoperative low-dose rFVIIa in thoracic aortic operations, a strategy intended to improve safety by minimizing rFVIIa exposure. METHODS Between July 2005 and December 2010, 425 consecutive patients at a single referral center underwent thoracic aortic operations with cardiopulmonary bypass (CPB); 77 of these patients received intraoperative low-dose rFVIIa (≤60 μg/kg) for severe coagulopathy after CPB. Propensity matching produced a cohort of 88 patients (44 received intraoperative low-dose rFVIIa and 44 controls) for comparison. RESULTS Matched patients receiving intraoperative low-dose rFVIIa got an initial median dose of 32 μg/kg (interquartile range [IQR], 16-43 μg/kg) rFVIIa given 51 minutes (42-67 minutes) after separation from CPB. Patients receiving intraoperative low-dose rFVIIa demonstrated improved postoperative coagulation measurements (partial thromboplastin time 28.6 versus 31.5 seconds; p=0.05; international normalized ratio, 0.8 versus 1.2; p<0.0001) and received 50% fewer postoperative blood product transfusions (2.5 versus 5.0 units; p=0.05) compared with control patients. No patient receiving intraoperative low-dose rFVIIa required postoperative rFVIIa administration or reexploration for bleeding. Rates of stroke, thromboembolism, myocardial infarction, and other adverse events were equivalent between groups. CONCLUSIONS Intraoperative low-dose rFVIIa led to improved postoperative hemostasis with no apparent increase in adverse events. Intraoperative rFVIIa administration in appropriately selected patients may correct coagulopathy early in the course of refractory blood loss and lead to improved safety through the use of smaller rFVIIa doses. Appropriately powered randomized studies are necessary to confirm the safety and efficacy of this approach.

Antegrade versus retrograde cerebral perfusion for hemiarch replacement with deep hypothermic circulatory arrest: Does it matter? A propensity-matched analysis

OBJECTIVE The choice of cerebral perfusion strategy for aortic arch surgery has been debated, and the superiority of antegrade (ACP) or retrograde (RCP) cerebral perfusion has not been shown. We examined the early and late outcomes for ACP versus RCP in proximal (hemi-) arch replacement using deep hypothermic circulatory arrest (DHCA). METHODS A retrospective analysis of a prospectively maintained database was performed for all patients undergoing elective and nonelective hemiarch replacement at a single referral institution from June 2005 to February 2013. Total arch cases were excluded to limit the analysis to shorter DHCA times and a more uniform patient population for whom clinical equipoise regarding ACP versus RCP exists. A total of 440 procedures were identified, with 360 (82%) using ACP and 80 (18%) using RCP. The endpoints included 30-day/in-hospital and late outcomes. A propensity score with 1:1 matching of 40 pre- and intraoperative variables was used to adjust for differences between the 2 groups. RESULTS All 80 RCP patients were propensity matched to a cohort of 80 similar ACP patients. The pre- and intraoperative characteristics were not significantly different between the 2 groups after matching. No differences were found in 30-day/in-hospital mortality or morbidity outcomes. The only significant difference between the 2 groups was a shorter mean operative time in the RCP cohort (P = .01). No significant differences were noted in late survival (P = .90). CONCLUSIONS In proximal arch operations using DHCA, equivalent early and late outcomes can be achieved with RCP and ACP, although the mean operative time is significantly less with RCP, likely owing to avoidance of axillary cannulation. Questions remain regarding comparative outcomes with straight DHCA and lesser degrees of hypothermia.