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1.  Outcome following Surgery and Percutaneous Intervention for Cardiogenic Shock and Left Main Disease 
The Annals of thoracic surgery  2008;86(1):29-34.
The ideal revascularization strategy (bypass surgery vs. percutaneous coronary intervention [PCI]) for patients with cardiogenic shock in the setting of left main coronary artery (LMCA) disease is unknown.
The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock Trial and Registry included 164 patients with LMCA disease who underwent revascularization. Although the standard of care at the time and the trial protocol recommended bypass surgery for patients with LMCA disease, the revascularization strategy (79 bypass surgery and 85 PCI) was individualized for each patient by site investigators.
The median time from myocardial infarction to revascularization was 24.3 hours (interquartile range, 8.7 to 82.5 hours) in the surgical group and 7.4 hours (interquartile range, 3.7 to 19.5 hours) in the PCI group (p <0.05). Overall 30-day survival with surgery in this setting was 569% (95% confidence interval (0.43, 0.69) and was significantly superior to the 21% (95% confidence interval (0.09, 0.35) in the PCI group (p <0.01). When the LMCA was the infarct-related artery, the 30-day survival rate was 40% in the surgical group (n=6) and 16% in the PCI group (n=15) (p=0.03). Bypass surgery [hazard ratio 0.41, 95% confidence interval (0.22, 0.77), p=0.006) and age [per 10 years, hazard ratio 1.04, 95% confidence interval (1.01-1.08); p=0.02] were independently associated with 30-day survival.
Bypass surgery appeared to provide a survival advantage over PCI at 30-day follow up in patients with LMCA disease. The impact of current PCI strategies on this subgroup is undetermined.
PMCID: PMC4056020  PMID: 18573394
Coronary artery bypass grafts; Myocardial infarction
2.  Cyclosporine Preserves Mitochondrial Morphology After Myocardial Ischemia/Reperfusion Independent of Calcineurin Inhibition 
The Annals of thoracic surgery  2008;86(4):1286-1292.
Opening of the mitochondrial permeability transition pore (MPTP) has been shown to contribute to myocardial ischemia/reperfusion injury. We sought to demonstrate that the myocardial protective effect of inhibiting MPTP opening with cyclosporine A (CsA) results in stabilization of mitochondrial morphology and is independent of CsA-induced calcineurin inhibition.
Thirty-seven rabbits were divided into three groups: control (n = 15), CsA (MPTP and calcineurin inhibitor, n = 12), or FK506 (calcineurin inhibitor, n = 10). Each group received a 1-hour infusion of either a saline vehicle, 25 mg/kg CsA or 1 mg/kg FK506. All animals underwent 30 minutes of regional ischemia and 3 hours of reperfusion. Myocardial infarct size was determined using Evans blue dye and triphenyltetrazolium chloride. In situ oligo ligation was used to assess apoptotic cell death. Transmission electron microscopy was used to quantitatively evaluate morphologic differences in the mitochondria between groups.
Infarct size in the CsA group (39% ± 3%) was significantly reduced compared with the control group (60% ± 2%, p < 0.001) and FK506 group (55% ± 3%, p = 0.001). Apoptotic cell death was also attenuated in the CsA group (1.2% ± 0.5%) compared with the control group (4.3% ± 0.8%, p = 0.01) and FK506 group (4.1% ± 0.9%, p = 0.05). Transmission electron microscopy revealed a preservation of normal mitochondrial morphology and a reduction in the percentage of disrupted mitochondria in the CsA group (20% ± 7%) compared with the control group (53% ± 12%) and FK506 group (47% ± 9%).
Cyclosporine A–induced MPTP inhibition preserves mitochondrial morphology after myocardial ischemia/reperfusion and limits myocyte necrosis and apoptosis. These effects are independent of calcineurin inhibition.
PMCID: PMC4041111  PMID: 18805178
3.  Does the Timing of Esophagectomy after Neoadjuvant Chemoradiation Affect Outcome? 
The Annals of thoracic surgery  2011;93(1):207-213.
After neoadjuvant chemoradiation (CXRT) for esophageal cancer, surgery has traditionally been recommended to be performed within 8 weeks. However, surgery is often delayed for various reasons. Data from other cancers suggests that delaying surgery may increase the pathologic complete response rate. However, there are theoretical concerns that waiting longer after radiation may lead to a more difficult operation and more complications. The optimal timing of esophagectomy after CXRT is unknown.
From a prospective database, we analyzed 266 patients with resected esophageal cancer who were treated with neoadjuvant CXRT from 2002–2008. Salvage resections were excluded from this analysis. We compared patients who had surgery within 8 weeks of CXRT and those who had surgery after 8 weeks. We used multivariable analysis to determine whether increased interval between chemoradiation and surgery was independently associated with perioperative complication, pathologic response, or overall survival.
150 patients were resected within 8 weeks and 116 were resected greater than 8 weeks after completing CXRT. Mean length of operation, intraoperative blood loss, anastomotic leak rate, and perioperative complication rate were similar for the two groups. Pathologic complete response rate and overall survival were also similar for the two groups (p=NS). In multivariable analysis, timing of surgery was not an independent predictor of perioperative complication, pathologic complete response, or overall survival.
The timing of esophagectomy after neoadjuvant CXRT is not associated with perioperative complication, pathologic response, or overall survival. It may be reasonable to delay esophagectomy beyond 8 weeks for patients who have not yet recovered from chemoradiation.
PMCID: PMC4041623  PMID: 21962263
Adjuvant/neoadjuvant therapy; Esophageal Cancer; Radiation Therapy; Esophageal Surgery
4.  Biventricular Finite Element Modeling of the Acorn CorCap Cardiac Support Device on a Failing Heart 
The Annals of thoracic surgery  2013;95(6):2022-2027.
The Acorn CorCap Cardiac Support Device (CSD; Acorn Cardiovascular Inc, St. Paul, MN) is a woven polyester jacket that is placed around the heart and designed to reverse the progressive remodeling associated with dilated cardiomyopathy. However, the effects of the Acorn CSD on myofiber stress and ventricular function remain unknown. We tested the hypothesis that the Acorn CSD reduces end-diastolic (ED) myofiber stress.
A previously described weakly coupled biventricular finite element (FE) model and circulatory model based on magnetic resonance images of a dog with dilated cardiomyopathy was used. Virtual applications of the CSD alone (Acorn), CSD with rotated fabric fiber orientation (rotated), CSD with 5% prestretch (tight), and CSD wrapped only around the left ventricle (LV; LV-only) were performed, and the effect on myofiber stress at ED and pump function was calculated.
The Acorn CSD has a large effect on ED myofiber stress in the LV free wall, with reductions of 55%, 79%, 92%, and 40% in the Acorn, rotated, tight, and LV-only cases, respectively. However, there is a tradeoff in which the Acorn CSD reduces stroke volume at LV end-diastolic pressure of 8 mm Hg by 23%, 25%, 30%, and 7%, respectively, in the Acorn, rotated, tight, and LV-only cases.
The Acorn CSD significantly reduces ED myofiber stress. However, CSD wrapped only around the LV was the only case with minimal negative effect on pump function. Findings suggest that LV-only CSD and Acorn fabric orientation should be optimized to allow maximal myofiber stress reduction with minimal reduction in pump function.
PMCID: PMC3702266  PMID: 23643546
5.  Completion Pneumonectomy: Outcomes for Benign and Malignant Indications 
The Annals of thoracic surgery  2013;95(6):1885-1891.
Past series have identified completion pneumonectomy (CP) as a high-risk operation. We evaluated factors affecting outcomes of CP with a selective approach to offering this operation.
We analyzed a prospective institutional database and abstracted information on patients undergoing pneumonectomy. Patients undergoing CP were compared to those undergoing primary pneumonectomy (PP).
Between 1/2000 and 2/2011, 211 patients underwent pneumonectomy, of which 35 (17%) were CPs. Ten of 35 (29%) CPs were for benign disease and 25/35 (71%) for cancer. Major perioperative morbidity was seen in 21/35 (60%) with 4 (11%) perioperative deaths. In univariate analysis, postoperative bronchopleural fistula (p=0.05) and benign diagnosis (p=0.07) tended to be associated with perioperative mortality.
All 10 patients undergoing CP for benign disease developed a major complication compared to 11/25 (44%) with malignancy, p=0.002. A bronchopleural fistula (4/35, 11%) was more likely to occur in patients undergoing CP shortly after the primary operation (interval between lobectomy and CP; 0.28 vs. 4.5 years; p=0.018) with a trend towards a benign indication for operation (p=0.07). Median survival after CP for benign and malignant indications was 24.3 months and 36.5 months respectively.
Comparing CP patients to those undergoing PP (n=176), CP patients were more likely to undergo surgery for benign disease (10/35, 29% vs. 14/176, 8%, p=0.001). Perioperative mortality for PP was 10/176 (5.7%), and was statistically similar to CP (11%).
Despite a selective approach, CP remains a morbid operation particularly for benign indications. Rigorous preoperative optimization, ruling out contraindications to surgery and attention to technical detail are recommended.
PMCID: PMC3718051  PMID: 23647859
Lung cancer surgery; Pneumonectomy
6.  Favorable Outcomes for Multi- and Extensively Drug Resistant Tuberculosis Patients Undergoing Surgery 
The Annals of thoracic surgery  2013;95(6):1892-1898.
New approaches are needed in the treatment of multi- and extensively drug resistant pulmonary tuberculosis (M/XDR-PTB). We evaluated the role of adjunctive surgical therapy in the treatment of M/XDR-PTB in the setting of DOTS-Plus implementation.
We conducted an observational cohort study consisting of M/XDR-PTB patients who underwent thoracic surgery at the National Tuberculosis Center in Tbilisi, Georgia between October 2008 and February 2011. Indications for surgery included presence of M/XDR-PTB, localized pulmonary disease, fit to undergo surgery, and either medical treatment failure or such extensive drug-resistance that failure was likely. Second-line anti-tuberculosis medical therapy was administered per WHO recommendations.
80 patients (55 MDR, 25 XDR) with PTB underwent adjunctive thoracic surgery. Median age was 30 years and average duration of preoperative M/XDR-PTB medical therapy was 350 days. The following surgical procedures were performed: pneumonectomy (10%), lobectomy (51%), segmentectomy (33%), and thoracoplasty (6%). Mean postoperative follow up time was 372 days. Of 77 patients with evaluable outcomes, 64 (83%) had favorable outcomes including 90% of MDR and 68% of XDR-TB patients. There was no postoperative mortality; postoperative complications occurred in 7 patients (9%). Risk factors for poor treatment outcomes in univariate analysis included cavitary disease, XDR, increasing effective drugs received, positive preoperative sputum culture, and major postoperative surgical complication.
Patients with M/XDR-PTB undergoing adjunctive thoracic surgery had high rates of favorable outcomes, no surgical related mortality, and low rates of complications. Adjunctive surgery appears to play an important role in the treatment of select patients with M/XDR-PTB.
PMCID: PMC3728898  PMID: 23642435
tuberculosis; infection; thoracotomy
7.  The Cardioprotective Mechanism of Diazoxide Involves the Inhibition of Succinate Dehydrogenase 
The Annals of thoracic surgery  2013;95(6):2042-2050.
The adenosine triphosphate-sensitive potassium (KATP) channel opener, diazoxide, preserves myocyte volume homeostasis and contractility during stress via an unknown mechanism. Pharmacologic overlap has been suggested between succinate dehydrogenase (SDH) activity and KATP channel modulators. Diazoxide may be cardioprotective due to the inhibition of SDH which may form a portion of the mitochondrial KATP channel. To determine the role of inhibition of SDH in diazoxide's cardioprotection, this study utilized glutathione to prevent the inhibition of SDH.
SDH activity was measured in isolated mitochondria exposed to succinate (control), malonate (inhibitor of succinate dehydrogenase), diazoxide, and varying concentrations of glutathione alone or in combination with diazoxide. Enzyme activity was measured by spectrophotometric analysis.
To evaluate myocyte volume and contractility, cardiac myocytes were superfused with Tyrode's physiologic solution (20 minutes), followed by test solution (20 minutes) including: Tyrode's, hyperkalemic cardioplegia (stress), cardioplegia + diazoxide, cardioplegia + diazoxide + glutathione, or glutathione alone; followed by Tyrode's (20 minutes). Myocyte volume and contractility were recorded using image grabbing software.
Both malonate and diazoxide inhibited succinate dehydrogenase. Glutathione prevented the inhibition of succinate dehydrogenase by diazoxide in a dose dependent manner.
The addition of diazoxide prevented the detrimental myocyte swelling due to cardioplegia alone and this benefit was lost with the addition of glutathione. However, glutathione elicited an independent cardioprotective effect on myocyte contractility.
The ability of diazoxide to provide beneficial myocyte homeostasis during stress involves the inhibition of succinate dehydrogenase, which may also involve the opening of a purported mitochondrial KATP channel.
PMCID: PMC3745224  PMID: 23642436
Myocardial Protection; Cardioplegia
8.  Outcomes Before and After Implementation of a Pediatric Rapid-Response Extracorporeal Membrane Oxygenation Program 
The Annals of thoracic surgery  2013;95(6):2140-2147.
Rapid-response extracorporeal membrane oxygenation (RR-ECMO) has been implemented at select centers to expedite cannulation for patients placed on ECMO during cardiopulmonary resuscitation (ECPR). In 2008, we established such a program and used it for all pediatric veno-arterial ECMO initiations. This study was designed to compare outcomes before and after program implementation.
Between 2003 and 2011, 144 pediatric patients were placed on veno-arterial ECMO. Records of patients placed on ECMO before (17 ECPR and 62 non-ECPR) or after (14 ECPR and 51 non-ECPR) RR-ECMO program implementation were retrospectively compared.
The peak performance of the ECMO team was assessed by measuring ECMO initiation times for the ECPR patient subgroup (n=31). There was a shift towards more ECPR initiations achieved in under 40 minutes (24% pre-RR-ECMO vs. 43% RR-ECMO, P=0.25) and fewer requiring more than 60 minutes (47% pre-RR-ECMO vs. 21% RR-ECMO, P=0.14) after program implementation, although these changes did not reach statistical significance. After multivariable risk-adjustment, RR-ECMO was associated with a 52% reduction in neurologic complications for all patients (adjusted odds ratio, 0.48; confidence interval, 0.23–0.98; P=0.04), but the risk of in-hospital death remained unchanged (adjusted odds ratio, 0.99; confidence interval, 0.50–1.99; P=0.99).
Implementation of a pediatric RR-ECMO program for veno-arterial ECMO initiation was associated with reduced neurologic complications but not improved survival during the first three years of program implementation. These data suggest that development of a coordinated system for rapid ECMO deployment may benefit both ECPR and non-ECPR patients, but further efforts are required to improve survival.
PMCID: PMC3747953  PMID: 23506632
Extracorporeal membrane oxygenation (ECMO); outcomes; pediatric
9.  Blood Transfusion and Infection After Cardiac Surgery 
The Annals of thoracic surgery  2013;95(6):2194-2201.
Cardiac surgery is the largest consumer of blood products in medicine; although believed life saving, transfusion carries substantial adverse risks. This study characterizes the relationship between transfusion and risk of major infection after cardiac surgery.
5,158 adults were prospectively enrolled to assess infections after cardiac surgery. The most common procedures were isolated coronary artery bypass grafting (31%) and isolated valve surgery (30%); 19% were reoperations. Infections were adjudicated by independent infectious disease experts. Multivariable Cox modeling was used to assess the independent effect of blood and platelet transfusions on major infections within 60±5 days of surgery.
Red blood cells (RBCs) and platelets were transfused in 48% and 31% of patients, respectively. Each RBC unit transfused was associated with a 29% increase in crude risk of major infection (P<0.001). Among RBC recipients, the most common infections were pneumonia (3.6%) and bloodstream infections (2%). Risk factors for infection included postoperative RBC units transfused, longer duration of surgery, and transplant or ventricular assist device implantation, in addition to chronic obstructive pulmonary disease, heart failure, and elevated preoperative creatinine. Platelet transfusion decreased the risk of infection (P=.02).
Greater attention to management practices that limit RBC use, including cell salvage, small priming volumes, vacuum-assisted venous return with rapid autologous priming, and ultrafiltration, and pre- and intraoperative measures to elevate hematocrit could potentially reduce occurrence of major postoperative infections.
PMCID: PMC3992887  PMID: 23647857
Bleeding; reoperation; surgery; complications; cardiopulmonary bypass; CPB; CPB; cell saver; wound infection
10.  Peak Wall Stress Predicts Expansion Rate in Descending Thoracic Aortic Aneurysms 
The Annals of thoracic surgery  2012;95(2):593-598.
Aortic diseases, including aortic aneurysms, are the 12th leading cause of death in the United States. The incidence of descending thoracic aortic aneurysms is estimated at 10.4 per 100,000 patient-years. Growing evidence suggests that stress measurements derived from structural analysis of aortic geometries predict clinical outcomes better than diameter alone.
Twenty-five patients undergoing clinical and radiologic surveillance for thoracic aortic aneurysms were retrospectively identified. Custom MATLAB algorithms were employed to extract aortic wall and intraluminal thrombus geometry from computed tomography angiography scans. The resulting reconstructions were loaded with 120 mm Hg of pressure using finite element analysis. Relationships among peak wall stress, aneurysm growth, and clinical outcome were examined.
The average patient age was 71.6 ± 10.0 years, and average follow-up time was 17.5 ± 9 months (range, 6 to 43). The mean initial aneurysm diameter was 47.8 ± 8.0 mm, and the final diameter was 52.1 ± 10.0 mm. Mean aneurysm growth rate was 2.9 ± 2.4 mm per year. A stronger correlation (r = 0.894) was found between peak wall stress and aneurysm growth rate than between maximal aortic diameter and growth rate (r = 0.531). Aneurysms undergoing surgical intervention had higher peak wall stresses than aneurysms undergoing continued surveillance (300 ± 75 kPa versus 229 ± 47 kPa, p = 0.01).
Computational peak wall stress in thoracic aortic aneurysms was found to be strongly correlated with aneurysm expansion rate. Aneurysms requiring surgical intervention had significantly higher peak wall stresses. Peak wall stress may better predict clinical outcome than maximal aneurysmal diameter, and therefore may guide clinical decision-making.
PMCID: PMC4037886  PMID: 23245445
11.  Arch Debranching versus Elephant Trunk Procedures for Hybrid Repair of Thoracic Aortic Pathologies 
The Annals of thoracic surgery  2011;91(2):465-471.
We compared outcomes of arch debranching (AD) and elephant trunk (ET) techniques when used with thoracic endovascular aortic repair.
A review was performed of consecutive patients with proximal thoracic aortic pathologies repaired with a hybrid approach.
Between 2005 and 2009, 58 patients underwent first stage ET (n = 21) or AD (n = 37). Cardiopulmonary bypass was utilized in 100% of ET and 68% of AD procedures (p<0.01). Circulatory arrest was used in 86% of ET and 27% of AD cases (p<0.01). The second stage was completed in 76% of ET and 76% of AD patients. Rates of spinal cord ischemia (ET 0/21, AD 0/37, p=1.0), stroke (ET 2/21, AD 4/37, p=1.0), and 30-day mortality (ET 4/21, AD 6/37, p=1.0) were similar. Each group had one major aortic complication between the two stages. Type Ia endoleak at 1 and 12 months occurred in 13% ET and 4% AD (p=0.54), and 0% and 4% (p=1.0), respectively. Kaplan-Meier estimates of survival at 1 and 12 months were 90.5% ± 6.4 and 73.1% ± 10 in the ET, and 86.5% ± 5.6 and 71.6% ± 8.5 in the AD group, respectively (p=0.68). The risk of a secondary procedure at 1 and 12 months were 76.2 ± 9.3 and 58.7% ± 12 in the ET, and 71.0% ± 7.8 and 52.8% ± 10 in the AD group, respectively (p=0.86).
Arch debranching achieves equivalent results to standard elephant trunk repair but with a decreased need for cardiopulmonary bypass and circulatory arrest.
PMCID: PMC4010941  PMID: 21256293
Aortic arch aneurysm; endovascular procedures
12.  Adenosine A3 Receptor Activation Attenuates Lung Ischemia-Reperfusion Injury 
The Annals of thoracic surgery  2013;95(5):1762-1767.
Severe ischemia-reperfusion (IR) injury leads to primary graft dysfunction following lung transplantation. Adenosine receptors modulate inflammation after IR, and the adenosine A3 receptor (A3R) is expressed in lung tissue and inflammatory cells. This study tests the hypothesis that A3R agonism attenuates lung IR injury via a neutrophil-dependent mechanism.
Wild-type and A3R knockout (A3R−/−) mice underwent 1 hr left lung ischemia followed by 2 hrs reperfusion (IR). Cl-IB-MECA, a selective A3R agonist, was administered (100 µg/kg i.v.) 5 min prior to ischemia. Study groups included sham, IR, and IR+Cl-IB-MECA (n=6/group). Lung injury was assessed by measuring lung function, wet/dry weight, histopathology, and proinflammatory cytokines and myeloperoxidase levels in bronchoalveolar lavage fluid. Parallel in vitro experiments were performed to evaluate neutrophil chemotaxis, and neutrophil activation was measured following exposure to acute hypoxia-reoxygenation.
Treatment of wild-type mice with Cl-IB-MECA significantly improved lung function and decreased edema, cytokine expression, and neutrophil infiltration after IR. Cl-IB-MECA had no effects in A3R−/− mice. Cl-IB-MECA significantly decreased activation of wild-type, but not A3R−/−, neutrophils after acute hypoxia-reoxygenation and inhibited chemotaxis of wild-type neutrophils.
Exogenous activation of A3R by Cl-IB-MECA attenuates lung dysfunction, inflammation, and neutrophil infiltration after IR in wild-type but not A3R−/− mice. Results with isolated neutrophils suggest that the protective effects of Cl-IB-MECA are due, in part, to the prevention of neutrophil activation and chemotaxis. The use of A3R agonists may be a novel therapeutic strategy to prevent lung IR injury and primary graft dysfunction after transplantation.
PMCID: PMC3725313  PMID: 23541429
lung transplantation; inflammation
13.  Short And Long-Term Outcomes After Esophagectomy For Cancer In Elderly Patients 
The Annals of thoracic surgery  2013;95(5):1741-1748.
As worldwide life expectancy rises, the number of candidates for surgical treatment of esophageal cancer over 70 years will increase. This study aims to examine outcomes after esophagectomy in elderly patients.
Retrospective review of 474 patients undergoing esophagectomy for cancer during 2002–2011. 334 (70.5%) patients were <70 years old (group A), 124 (26.2%) 70–79 years (group B) and 16 (3.4%) ≥80 years (group C). We analyzed the effect of age on outcome variables including overall and disease specific survival.
Major morbidity was observed to occur in 115 (35.6%) patients of group A, 58 (47.9%) of group B and 10 (62.5%) of group C (p=0.010). Mortality, both 30- and 90-day was observed in 2(0.6%) and 7(2.2%) of group A, 4(3.2%) and 7 (6.1%) of group B, and 1(6.3%) and 2(14.3%) of group C, respectively (p=0.032 and p=0.013). Anastomotic leak was observed in 16(4.8%) patients of group A, 6(4.8%) of group B and 0(0%) of group C (p=0.685). Anastomotic stricture (defined by the need for ≥2 dilations) was observed in 76(22.8%) of group A, 13(10.5%) of group B and 1(6.3%) of group C (p=0.005). Five-year overall and disease specific survival was 64.8% and 72.4% for group A, 41.7% and 53.4% for group B, 49.2% and 49.2% for group C patients (p=0.0006), respectively.
Esophagectomy should be carefully considered in patients 70–79 years old and can be justified with low mortality. Outcomes in octogenarians are worse suggesting esophagectomy be considered on a case by case basis. Stricture rate is inversely associated to age.
PMCID: PMC3732120  PMID: 23500043
Esophagus; Esophageal cancer; Esophageal surgery; Outcomes; Statistics-regression analysis
14.  Variation in Outcomes for Risk-Stratified Pediatric Cardiac Surgical Operations: An Analysis of the STS Congenital Heart Surgery Database 
The Annals of thoracic surgery  2012;94(2):564-572.
We evaluated outcomes for groups of risk-stratified operations in The Society of Thoracic Surgeons Congenital Heart Surgery Database to provide contemporary benchmarks and examine variation between centers.
Patients undergoing surgery from 2005 to 2009 were included. Centers with more than 10% missing data were excluded. Discharge mortality and postoperative length of stay (PLOS) among patients discharged alive were calculated for groups of risk-stratified operations using the five Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery mortality categories (STAT Mortality Categories). Power for analyzing between-center differences in outcome was determined for each STAT Mortality Category. Variation was evaluated using funnel plots and Bayesian hierarchical modeling.
In this analysis of risk-stratified operations, 58,506 index operations at 73 centers were included. Overall discharge mortality (interquartile range among programs with more than 10 cases) was as follows: STAT Category 1 = 0.55% (0% to 1.0%), STAT Category 2 = 1.7% (1.0% to 2.2%), STAT Category 3 = 2.6% (1.1% to 4.4%), STAT Category 4 = 8.0% (6.3% to 11.1%), and STAT Category 5 = 18.4% (13.9% to 27.9%). Funnel plots with 95% prediction limits revealed the number of centers characterized as outliers by STAT Mortality Categories was as follows: Category 1 = 3 (4.1%), Category 2 = 1 (1.4%), Category 3 = 7 (9.7%), Category 4 = 13 (17.8%), and Category 5 = 13 (18.6%). Between-center variation in PLOS was analyzed for all STAT Categories and was greatest for STAT Category 5 operations.
This analysis documents contemporary benchmarks for risk-stratified pediatric cardiac surgical operations grouped by STAT Mortality Categories and the range of outcomes among centers. Variation was greatest for the more complex operations. These data may aid in the design and planning of quality assessment and quality improvement initiatives.
PMCID: PMC4006082  PMID: 22704799
15.  Practice Patterns for Thoracic Aneurysms in the Stent Graft Era: Health Care System Implications 
The Annals of thoracic surgery  2010;90(6):1833-1839.
The FDA approved the first thoracic aneurysm endograft in 2005. However because the United States lacks a thoracic aneurysm endovascular repair registry, implications of FDA endograft approval on surgical management of thoracic aneurysms in clinical practice are unknown.
Retrospective review of thoracic aneurysm repair rates for 2000–07 and analysis of patient characteristics and complications for 2006 and 2007 cohorts uses the National Inpatient Sample. ICD-9 codes were used to identify unruptured descending thoracic aneurysm cases undergoing either thoracic endovascular aortic repair (39.73) or Open Repair (38.45).
Thoracic aneurysm Open Repair averaged 3.3 per million from 2000–2002 and increased to 5.6 per million in 2003 with introduction of 16 slice CT scanners. In 2005 endovascular repair was 1.2 repairs per million, which increased dramatically to 6.1 repairs per million in 2006. In 2007, endovascular repair decreased to 4.8 repairs per million while Open Repair rate was 3.1 repairs per million. The 2006 and 2007 Open Repair cohorts had more favorable baseline characteristics compared to the endovascular cohort. Open Repair mortality was significantly greater than endovascular mortality in 2006 (estimated relative risk=8.48, 95% CI 3.03–23.75), but not in 2007 (estimated relative risk=0.71, 95% CI 0.12–4.24). Length of stay was greater for Open Repair in 2006 and 2007.
Thoracic endovascular aortic repair has been rapidly adopted in the United States resulting in increased treatment of thoracic aortic aneurysms. Despite older age and comorbidities, endovascular repair had better outcomes and shorter hospital stays.
PMCID: PMC3976178  PMID: 21095320
Aneurysm (descending); Endovascular Stents
17.  Septuagenarians Bridged to Heart Transplantation with a Ventricular Assist Device Have Similar Outcomes as Younger Patients 
The Annals of thoracic surgery  2013;95(4):1251-1261.
Although orthotopic heart transplantation (OHT) is increasingly being offered to older patients, few studies have evaluated outcomes in patients over the age of 70 years. We undertook this study to characterize the outcomes of septuagenarians bridged to heart transplantation (BTT) in the modern era.
We conducted a retrospective cohort study of all adult OHT in the United Network for Organ Sharing database from 2005–2011. Primary stratification was by age≥70 years. Subgroup analysis evaluated BTT patients. The primary outcome was survival as determined by the Kaplan-Meier method.
From 01/2005–12/2011, 12,274 adults underwent OHT, including 3,243 (26.4%) who were BTT. In the entire cohort, 11,996 (97.7%) recipients were ages 18–70, and 277 (2.3%) were ≥70 years of age. Overall, OHT patients ≥70 had decreased 90-day (93.6 vs 88.8%, p<0.01), 1-year (89.0 vs 81.6%, p<0.01), and 2-year (85.4 vs 79.9%, p<0.01) survival compared to recipients of other ages. However, in the BTT subgroup, recipients ≥70 (n=43) had similar 90-day (91.2 vs 84.7%, p=0.2), 1-year (86.1 vs 81.7%, p=0.4), and 2-year (82.8 vs 81.7%, p=0.6) survival compared to recipients of other ages (n=3,200). After adjusting for multiple recipient and donor factors, age ≥70 was still not associated with an increased hazard of mortality at 90-days, 1-year, or 2-years. These results were verified by analysis of a propensity-matched cohort.
Although patients over the age of 70 years undergoing OHT have decreased survival, amongst patients bridged to heart transplantation, septuagenarians have similar outcomes as younger recipients. In carefully selected, LVAD-dependent patients, recipient age ≥70 should not be viewed as a contraindication to OHT.
PMCID: PMC3732406  PMID: 23462263
Transplantation; Heart; Geriatric; Circulatory assist devices
18.  Long-Term Mortality of Coronary Artery Bypass Graft Surgery and Stenting with Drug-Eluting Stents 
The Annals of thoracic surgery  2013;95(4):1297-1305.
Few studies have examined differences in long-term mortality between coronary artery bypass graft surgery and stenting with drug-eluting stents (DES) for multivessel disease without left main coronary artery stenosis. This study compares the risks of long-term mortality between these 2 procedures during a follow-up of up to 5 years.
Patients who underwent isolated bypass surgery (n=13,212) and stenting with DES (n=20,161) between October 2003 and December 2005 in New York State were followed for their vital status through 2008. To control for treatment selection bias, bypass and stenting patients were matched on age, number of diseased coronary vessels, presence of proximal or nonproximal left anterior descending (LAD) artery disease, and propensity of undergoing bypass surgery. Five-year survival rates for the 2 procedures were compared and hazard ratios for death of bypass surgery compared to stenting were obtained.
The respective 5-year survival rates in the 8,121 pairs of matched bypass and stenting patients were 80.4%and 73.6% (P<0.001), and the risk of death following bypass surgery was 29% lower than for stenting (hazard ratio=0.71, 95% confidence interval: 0.67-0.77, P<0.001). Significantly lower risks of death for bypass surgery were observed in patients with LAD artery disease but not in patients without LAD artery disease. Significantly lower risks of death for bypass surgery were also found in all patient subgroups defined by the presence of selected baseline risk factors.
Bypass surgery is associated with lower risk of death than stenting with DES for multivessel disease without left main stenosis.
PMCID: PMC3756666  PMID: 23391171
CABG; stents; outcomes
19.  HCV Infected Resident: End of Residency, End of Career? 
The Annals of thoracic surgery  2013;95(3):779-786.
PMCID: PMC3724342  PMID: 23438517
Ethics; Health policy; HCV infection; Professional affairs; Education
20.  In-Vitro Mitral Valve Simulator Mimics Systolic Valvular Function of Chronic Ischemic Mitral Regurgitation Ovine Model 
The Annals of thoracic surgery  2013;95(3):825-830.
This study was undertaken to evaluate an in vitro mitral valve simulator's ability to mimic the systolic leaflet coaptation, regurgitation, and leaflet mechanics of a healthy and chronic ischemic mitral regurgitation (IMR) ovine model.
Mitral valve size and geometry of both healthy and chronic IMR ovine animals was used to recreate systolic mitral valve function in vitro. A2-P2 coaptation length, coaptation depth, tenting area, anterior leaflet strain, and mitral regurgitation were compared between the animal groups and valves simulated in the bench-top model.
For the control conditions, no differences were observed between the healthy animals and simulator in coaptation length (p=.681), coaptation depth (p=.559), tenting area (p=.199), and anterior leaflet strain in the radial (p=.230) and circumferential (p=.364) directions. For the chronic IMR conditions, no differences were observed between the models in coaptation length (p=.596), coaptation depth (p=.621), tenting area (p=.879), and anterior leaflet strain in the radial (p=.151) and circumferential (p=.586) directions. Mitral regurgitation was similar between IMR models with an asymmetric jet originating from the tethered A3-P3 leaflets.
This study is the first to demonstrate the effectiveness of an in vitro simulator to emulate the systolic valvular function and mechanics of a healthy and chronic IMR ovine model. The in vitro IMR model provides the capability to recreate intermediary and exacerbated levels of annular and subvalvular distortion at which IMR repairs can be simulated. This system provides a realistic and controllable test platform for the development and evaluation of current and future IMR repairs.
PMCID: PMC3739970  PMID: 23374445
in-vitro studies; mitral valve; ischemic heart disease
21.  Robotic Posterior Mitral Leaflet Repair: Neochordal versus Resectional Techniques 
The Annals of thoracic surgery  2012;95(3):787-794.
Resectional techniques are the established method of posterior mitral valve leaflet repair for degenerative disease; however, use of neochordae in a robotically assisted approach is gaining acceptance because of its versatility for difficult multi-segment disease. The purposes of this study were to compare the versatility, safety, and effectiveness of neochordal vs. resectional techniques for robotic posterior mitral leaflet repair.
From 12/2007 to 7/2010, 334 patients underwent robotic posterior mitral leaflet repair for degenerative disease by a resectional (n=248) or neochordal (n=86) technique. Outcomes were compared unadjusted and after propensity score matching.
Neochordae were more likely to be used than resection in patients with two (28% vs. 13%, P=.002) or three (3.7% vs. 0.87%, P=.08) diseased posterior leaflet segments. Three resection patients (0.98%) but no neochordal patient required reoperation for hemodynamically significant systolic anterior motion (SAM). Residual mitral regurgitation (MR) at hospital discharge was similar for matched neochordal vs. resection patients (P=.14) (MR 0+, 82% vs. 89%; MR 1+, 14% vs. 8.2%; MR 2+, 2.3% vs. 2.6%; one neochordal patient had 4+ MR and was reoperated). Among matched patients, postoperative mortality and morbidity were similarly low.
Compared with a resectional technique, robotic posterior mitral leaflet repair with neochordae is associated with shorter operative times and no occurrence of SAM. The versatility, effectiveness, and safety of this repair make it a good choice for patients with advanced multi-segment disease.
PMCID: PMC3782067  PMID: 23103008
mitral regurgitation; mitral systolic anterior motion; minimally invasive; surgery; outcomes
22.  Neurodevelopmental Outcomes Following Regional Cerebral Perfusion with Neuromonitoring for Neonatal Aortic Arch Reconstruction 
The Annals of thoracic surgery  2012;95(2):648-655.
In this study we report magnetic resonance imaging (MRI) brain injury, and 12 month neurodevelopmental outcomes, when regional cerebral perfusion (RCP) is utilized for neonatal aortic arch reconstruction.
Fifty seven neonates receiving RCP during aortic arch reconstruction were enrolled in a prospective outcome study. RCP flows were determined by near-infrared spectroscopy and transcranial Doppler monitoring. Brain MRI were performed preoperatively and 7 days postoperatively. Bayley Scales of Infant Development III was performed at 12 months.
Mean RCP time was 71 ± 28 minutes (range 5–121), mean flow 56.6 ± 10.6 ml/kg/min. New postoperative MRI brain injury was seen in 40% of patients. For 35 RCP patients at age 12 months, mean Bayley III composite standard scores were: Cognitive = 100.1 ± 14.6,(range 75–125); Language = 87.2 ± 15.0, (range 62–132); Motor = 87.9 ± 16.8, (range 58–121).Increasing duration of RCP was not associated with adverse neurodevelopmental outcomes.
Neonatal aortic arch repair with RCP utilizing a neuromonitoring strategy results in 12-month cognitive outcomes that are at reference population norms; language and motor outcomes are lower than the reference population norms by 0.8–0.9 standard deviation. This largest RCP group with neurodevelopmental outcomes published to date demonstrates that this technique is effective and safe in supporting the brain during neonatal aortic arch reconstruction.
PMCID: PMC3586430  PMID: 22766302
Anesthesia; brain; cardiopulmonary bypass (CPB); CHD; hypoplastic left heart syndrome; neurocognitive deficits
23.  ADAMTS-1 and ADAMTS-4 levels are Elevated in Thoracic Aortic Aneurysms and Dissections 
The Annals of thoracic surgery  2012;95(2):570-577.
ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) is a recently identified family of extracellular metalloproteinases that has been shown to participate in tissue destruction. We hypothesized that ADAMTS-1 and ADAMTS-4 expression is increased in aortic tissues from patients with thoracic aortic aneurysms and dissections.
We examined ADAMTS-1 and ADAMTS-4 expression in human descending thoracic aortic aneurysms (n=14), chronic descending thoracic aortic dissections (n=16), and descending thoracic aortas from age-matched control organ donors (n=12). In these tissues, we also evaluated the degradation of versican, a proteoglycan substrate of ADAMTS-1 and ADAMTS-4. In cultured macrophages, we examined whether ADAMTS-4 functions in macrophage infiltration by using a transwell assay.
ADAMTS-1 and ADAMTS-4 protein and mRNA expression was significantly higher in thoracic aortic aneurysm and dissection tissues than in control aortic tissues. Double immunofluorescence staining showed the expression of ADAMTS-1 and ADAMTS-4 in smooth muscle cells and macrophages. Consistent with the upregulation of ADAMTS-1 and ADAMTS-4 in thoracic aortic aneurysm and dissection tissues, versican was degraded significantly more in these tissues than in control aortic tissues. In cultured macrophages, transforming growth factor-β increased ADAMTS-4 protein levels and induced macrophage invasion; knocking down ADAMTS-4 reduced cell invasion.
Increased expression of ADAMTS proteins may promote thoracic aortic aneurysm progression by degrading versican and facilitating macrophage invasion.
PMCID: PMC3593585  PMID: 23245439
Aneurysm (thoracic aortic); inflammatory cells (macrophages); inflammatory mediators (metalloproteinases); pathology (aorta); vascular science (pathology)
24.  The Role of Head CT Imaging in the Evaluation of Postoperative Neurologic Deficits in Cardiac Surgery Patients 
The Annals of thoracic surgery  2012;95(2):548-554.
Computed tomography(CT) scans of the head without contrast are routinely obtained to evaluate neurologic deficits after cardiac surgery(CS), but their utility is unknown. We evaluated our experience with this imaging modality to determine its value.
We retrospectively identified CS patients with postoperative neurologic deficits occurring during the first week after surgery between January 2000 and December 2012. Stroke was defined by neurologist’s determination, while a non-focal deficit(NFD) was defined by the presence of seizure, delirium, or cognitive impairment. We defined early non-contrast head CT as occurring within 7 days of surgery. Outcomes included positive findings on CT, in-hospital mortality and length of stay(LOS). Multivariate logistic regression identified predictors of positive findings on head CT.
Within the population of 11,070 postoperative patients, 451 had early non-contrast head CT scans (4%). 202(44.7%) were associated with stroke and 249(55.2%) with NFD. Among stroke patients, 40/202(20%) showed acute infarction, 17/202(8%) showed sub-acute infarction, and 5/202(2%) showed hemorrhage. Among NFD patients, 1/248(0.4%) showed acute infarction, 4/248(1.6%) sub-acute infarction, and 1/248(0.4%) hemorrhage. There was no difference in in-hospital mortality(S:42/201(21%) versus NFD:41/248(16%), p=0.2) or LOS (S:24d versus NFD:22d, p=0.5). On multivariable logistic regression, only focal deficits and aortic procedures predicted a positive finding on CT scan.
To our knowledge, this is the only modern study to review the utility of early postoperative non-contrast head CT in CS patients. With focal neurologic deficits, this imaging modality was positive for approximately one third of patients, but rarely positive for NFD. Its use in this setting has limited utility.
PMCID: PMC3602972  PMID: 23218967
Cerebral Complications; Intensive Care
25.  The Effect of Surgical and Transcatheter Aortic Valve Replacement on Mitral Annular Anatomy 
The Annals of thoracic surgery  2012;95(2):614-619.
The effect of aortic valve replacement on three-dimensional (3D) mitral annular geometry has not been well-described. Emerging transcatheter approaches for aortic valve replacement employ fundamentally different mechanical techniques for achieving fixation and seal of the prosthetic valve than standard surgical aortic valve replacement. This study compares the immediate impact of transcatheter aortic valve replacement (TAVR) and standard surgical aortic valve replacement (AVR) on mitral annular anatomy.
Real-time 3D echocardiography was performed in patients undergoing TAVR using the Edwards Sapien® valve (n=10) or AVR (n=10) for severe aortic stenosis. Mitral annular geometric indexes were measured using Tomtec EchoView to assess regional and global annular geometry.
Mixed between-within ANOVA showed no differences between TAVR and AVR groups in any of the mitral annular geometric indices pre-operatively. However, post-operative analysis did demonstrate an effect of AVR on geometry. Patients undergoing open AVR had significant decrease in annular height, septolateral diameter, mitral valve transverse diameter and mitral annular area after valve replacement (P≤.006). Similar changes were not noted in the TAVR group.
TAVR preserves mitral annular geometry better than AVR. Thus, TAVR may be a more physiological approach to aortic replacement.
PMCID: PMC3607374  PMID: 23245440
Aortic Valve Replacement; Echocardiography; Mitral Valve; Modeling

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