Faculty Bibliography

BACKGROUND: Patients with severe atheromatous aortic disease (AAD) who undergo coronary artery bypass (CABG) have an increased risk of death and stroke. We hypothesized that in these high risk patients, off-pump coronary artery bypass (OPCAB) technique is associated with lower morbidity and mortality. METHODS AND RESULTS: Between June 1993 and January 2002, 5737 patients undergoing CABG had routine intra-operative TEE with 913 (15.9%) found to have severe AAD in the aortic arch or ascending aorta. Of these, 211 patients who underwent OPCAB were matched with 211 on-pump CABG patients by age, ejection fraction, history of stroke, cerebrovascular disease, diabetes, renal disease, nonelective operation, and previous cardiac surgery. Hospital mortality was 11.4% (24/211) for on-pump CABG and 3.8% (8/211) for OPCAB (P=0.003). Multivariate analysis revealed that increased mortality was associated with on-pump CABG (P=0.001), acute MI (P=0.03), number of grafts (P=0.01), age (P=0.01), history of stroke or cerebrovascular disease (P=0.04), CHF (P=0.02), and peripheral vascular disease (P=0.03). Multivariate analysis showed that OPCAB technique was associated with decreased stroke (P=0.05). Freedom from any complication was 78.7% for on-pump CABG and 91.9% for OPCAB (P<0.001). At 36 month follow-up multivariate analysis revealed that increased mortality was associated with age (P=0.001), previous MI (P=0.03), and renal disease (P=0.04), whereas increased survival was associated with increased number of grafts (P=0.001) and OPCAB (P=0.01). CONCLUSIONS: OPCAB surgery in patients with severe AAD is associated with lower risk of death, stroke and complications and improved mid-term survival. Routine intra-operative TEE allows identification of these patients and directs choice of appropriate surgical technique

OBJECTIVE: Long-term durability of saphenous vein grafts used for coronary artery bypass grafting is limited by neointimal formation. Arterial vascular injury is known to activate intracellular mitogen-activated protein kinases, including extracellular signal-regulated kinases and c-jun N-terminal kinases, that affect cell differentiation, proliferation, migration, and apoptosis. This study tests the hypothesis that these mitogen-activated protein kinases are activated in saphenous veins during preparation for coronary artery bypass grafting. METHODS: Saphenous veins were harvested from 10 patients undergoing coronary artery bypass grafting. A specimen from each vein was placed in ice-cold lysis buffer immediately after harvesting (t = 0). The remaining tissue was incubated at room temperature in normal saline, 0.1% dimethylsulfoxide (vehicle), or 50 mmol/L PD98059 (mitogen-activated protein kinase kinase-1/2 inhibitor) until the vein was grafted (mean 50 minutes). To study kinetics of intracellular signaling pathways, canine saphenous veins were harvested, and mitogen-activated protein kinases and PI-3 kinase pathways were studied after different incubation time intervals. Extracted proteins were analyzed by Western blotting or in vitro kinase assay. RESULTS: The human saphenous veins showed elevated levels of active extracellular signal-regulated kinase after harvesting (t = 0) and prior to implant (t = 1). Incubation with PD98059 resulted in decreased activation of extracellular signal-regulated kinase. Kinetics of canine saphenous veins showed extracellular signal-regulated kinase and c-jun N-terminal kinase activation, in a time-dependent manner, along with activation of the growth factor-regulated PI3 kinase pathway. CONCLUSIONS: This study characterizes activation of extracellular signal-regulated kinases and c-jun N-terminal kinases during vein graft preparation and demonstrates the ability to inhibit extracellular signal-regulated kinase activation by simple incubation with a specific inhibitor. Further studies are needed to evaluate the significance of these findings with respect to graft durability.

BACKGROUND: Patients with severe atheromatous aortic disease (AAD) undergoing coronary artery bypass grafting (CABG) have increased operative risks. The 'off-pump' CABG (OPCAB) technique was evaluated in patients given the diagnosis of severe AAD by routine transesophageal echocardiography. METHODS: A total of 5737 patients underwent CABG, with 913 having transesophageal echocardiography findings of severe AAD. Of the patients with severe AAD, 678 (74.3%) had conventional CABG and 235 (25.7%) had OPCAB. RESULTS: Hospital mortality was 8.7% for conventional CABG and 5.1% for OPCAB (P =.08). Multivariate analysis revealed that increased mortality was significantly associated with acute myocardial infarction, conventional CABG, age, renal disease, history of stroke, and ejection fraction < 30%. Neurologic complications occurred in 6.3% of patients undergoing CABG and in 2.1% undergoing OPCAB (P =.01). Freedom from any complication was significantly greater with OPCAB. CONCLUSION: Routine intraoperative transesophageal echocardiography identifies patients with severe AAD. In these patients, OPCAB technique is associated with a lower risk of death, stroke, and all complications

OBJECTIVE: The development of intimal hyperplasia involves smooth muscle cell (SMC) migration into the intima and proliferation. Matrix metalloproteinases and their tissue inhibitors play important roles in this process. In this study, we describe a novel in vitro model for studying SMC migration through the vessel wall. METHODS AND RESULTS: Human aortic SMCs (hASMCs) labeled with 125I-iododeoxyuridine or unlabeled were grown on the stromal aspect of the human amniotic membrane. Mechanical damage to endothelial cells grown on the basement membrane and addition of growth factors or platelets were characterized for their effect on SMC migration into the stroma both by histological methods and by measuring the radioactivity associated with the membrane after removal of noninvasive SMCs. To assess the reliability of the model, the cells were infected with a recombinant adenovirus encoding the tissue inhibitor of metalloproteinase-1 (TIMP-1). Addition of a platelet-derived growth factor gradient stimulated hASMC infiltration into the stroma. This effect was abolished with TIMP-1-transduced hASMC, confirming that TIMP-1 overexpression blocks SMC invasion of the stroma. CONCLUSIONS: This in vitro model of SMC migration in the vessel wall provides an inexpensive, quantitative, and reliable tool to study the molecular and cellular mechanisms of intimal hyperplasia

BACKGROUND: Patients with reduced ventricular function undergoing aortic valve replacement have increased operative risks, but the impact of valvular pathophysiology and other risk factors has not been clearly defined. METHODS: From June 1992 through June 2002, 1,402 consecutive patients underwent isolated aortic valve surgery with or without coronary artery bypass grafting; of these patients, 416 had an ejection fraction less than 40% and are the subject of this report. These patients (mean age, 68.6) had severe stenosis (62.5%), severe regurgitation (30.3%), or mixed disease (7.2%). Aortic valve replacement plus coronary artery bypass grafting was performed in 48.4% of patients, and 27% had previous cardiac surgery. Follow-up included echocardiography and survival analysis. RESULTS: Hospital mortality was 10.1% (42 of 416), with no difference between aortic stenosis (9.6%) and regurgitation (11.1%). Multivariate analysis revealed that age (p = 0.002) and renal disease (odds ratio = 4.2; 95% confidence interval, 1.9 to 9.3; p = 0.001) were independently associated predictors of mortality. Valvular pathophysiology had no impact on mortality. Peripheral vascular disease, multivessel coronary disease, and renal disease were associated risks for any postoperative complication. Peripheral vascular disease (odds ratio = 12.3, p = 0.02), history of cerebrovascular disease (odds ratio = 4.8, p = 0.038), and diabetes (odds ratio = 2.7, p = 0.04) were associated risks for stroke. The ejection fraction was more than 40% in 52% of the patients who had postoperative echocardiography (mean follow-up, 6 months). Actuarial survival revealed no difference between pathophysiologic groups. CONCLUSIONS: Aortic valve surgery in patients with impaired ventricular function carries an acceptable operative risk that can be stratified by age and comorbidities. The type of valvular pathophysiology does not significantly affect mortality

OBJECTIVE: Although minimally invasive aortic valve replacement (MIAVR) has recently become popular, additional outcome evaluation is required. This study analyzed a single institutional experience with MIAVR with respect to hospital morbidity and mortality. METHODS: Between 12/96 and 06/02, 482 consecutive patients at a single institution underwent MIAVR, including concomitant procedures in 123 pts: 55 multiple valves, 18 CABGs, 21 myomectomies, and 29 other procedures. These patients (mean age 65 yrs; range 15-94) had severe stenosis (58.9%), severe insufficiency (33.0%), or mixed disease (8.1%). Thirty-three percent had a previous MI, 13.3% had a previous cardiac operation, and 17.3% were >80 years old. Right anterior minithoracotomy was performed in 87.3%. Ascending aortic cannulation was used in 68% of the patients while direct external cross clamping was used in 97% of cases. RESULTS: Hospital mortality was 6.2% (30/482) overall and 5.3% (19/359) for isolated AVR. Mean aortic crossclamp and cardiopulmonary bypass times were 87 and 122 min, respectively. Postoperative complications included stroke in 2.3% (11/482) and 82.5% of patients were free from any complications. Neither aortic dissection nor mediastinitis was observed. Univariant analysis demonstrated that female gender, renal failure, CHF, and age >80 years were risk factors for mortality. Multivariable analysis revealed that age and CHF were independently associated with increased risk of mortality (p<0.05). CONCLUSIONS: These results demonstrate that MIAVR is a safe procedure, with low morbidity and acceptable perioperative mortality, and may be used routinely in a large series of patients