Faculty Bibliography

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

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

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

The formation of blood capillaries from preexisting vessels (angiogenesis) and vascular remodeling secondary to atherosclerosis or vessel injury are characterized by endothelial cell migration and proliferation. Numerous growth factors control these cell functions. Basic fibroblast growth factor (FGF-2), a potent angiogenesis inducer, stimulates endothelial cell proliferation, migration, and proteinase production in vitro and in vivo. However, mice genetically deficient in FGF-2 have no apparent vascular defects. We have observed that endothelial cell migration in response to mechanical damage in vitro is accompanied by activation of the extracellular signal-regulated kinase (ERK) pathway, which can be blocked by neutralizing anti-FGF-2 antibodies. Endothelial cells from mice that are genetically deficient in FGF-2 neither migrate nor activate ERK in response to mechanical wounding. Addition of exogenous FGF-2 restores a normal cell response, which shows that impaired migration results from the genetic deficiency of this growth factor. Injury-induced ERK activation in endothelial cells occurs only at the edge of the wound. In addition, FGF-2-induced ERK activation mediates endothelial cell migration in response to wounding without a significant effect on proliferation. These data show that FGF-2 is a key regulator of endothelial cell migration during wound repair

The purpose of this study was to impact of a clinical pathway on the postoperative management of children undergoing surgical closure of atrial septal defects (ASDs). Three groups of children were studied: group 1 (14 patients), before introduction of an intensive care team, minimally invasive surgery, and the clinical pathway; group 2 (17 patients), after the introduction of the intensive care team and minimally invasive surgical techniques but before the pathway; and group 3 (30 patients), after implementation of the clinical pathway. Average hospital length of stay fell from 118.52 +/- 19.83 hours (4.9 +/- 0.83 days) in group 1 to 95.92 +/- 66.48 hours (3.99 +/-2.77 days) in group 2 and declined further to 54.29 +/- 20.17 hours (2.26 +/- 0.84 days) in group 3 (p <.05). There were statistically significant decreases in laboratory resource utilization (p <.05). The addition of a dedicated intensive care team and utilization of minimally invasive surgical techniques reduced mean length of stay (by 20%) and resource utilization (by 50%). However, only the implementation of the pathway provided the consistency necessary for maximal quality management, cost saving, and reduction in length of stay (additional 44% reduction in mean length of stay and 40% reduction in resource utilization). These results show the incremental advantage of implementing a defined clinical pathway for postoperative management of children with atrial septal defects

BACKGROUND: Vascular endothelial cell apoptosis is central in atherosclerosis and intimal hyperplasia. Transforming growth factor (TGF)-beta1 induces endothelial cell apoptosis through unidentified mechanism(s). Although TGF-beta1 signals through the Smad proteins, in some nonendothelial cell types it also activates the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK [p38(MAPK)]). p38(MAPK) relays apoptotic signals in several cell types. We hypothesized that TGF-beta1 activates endothelial cell MAPKs and induces apoptosis through p38(MAPK) activation. METHODS: Human umbilical vein or bovine capillary endothelial cells were incubated with TGF-beta1 for 0.5 to 12 hours. MAPK activation was characterized by Western blotting with antibodies to phosphorylated extracellular signal-regulated kinase 1/2, p38(MAPK), or c-Jun N-terminal kinases 1/2. To study apoptosis, extracts of cells incubated with TGF-beta1 for 6 hours with or without MAPK inhibitors were characterized by Western blotting analysis of poly (ADP-Ribose) polymerase degradation. RESULTS: TGF-beta1 induced p38(MAPK), extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase 1/2 activation and increased apoptosis. Inhibition of p38(MAPK) significantly reduced TGF-beta1-induced apoptosis. In contrast, inhibition of other signaling pathways was ineffective. CONCLUSIONS: TGF-beta1 induces endothelial cell apoptosis through p38(MAPK) activation. Because TGF-beta1 is upregulated in vascular remodeling, p38(MAPK) is a potential target to prevent endothelial cell apoptosis during this process