Faculty Bibliography

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) 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

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: To analyze the effectiveness of new techniques of mitral valve reconstruction (MVR) that have evolved over the last decade, such as aggressive anterior leaflet repair and minimally invasive surgery using an endoaortic balloon occluder. SUMMARY BACKGROUND DATA: MVR via conventional sternotomy has been an established treatment for mitral insufficiency for over 20 years, primarily for the treatment of patients with posterior leaflet prolapse. METHODS: Between June 1980 and June 2001, 1,195 consecutive patients had MVR with ring annuloplasty. Conventional sternotomy was used in 843 patients, minimally invasive surgery in 352 (since June 1996). Anterior leaflet repair was performed in 374 patients, with increasing use over the last 10 years. Follow-up was 100% complete (mean 4.6 years, range 0.5-20.5). RESULTS: Hospital mortality was 4.7% overall and 1.4% for isolated MVR (1.1% for minimally invasive surgery vs. 1.6% for conventional sternotomy; =.4). Multivariate analysis showed the factors predictive of increased operative risk to be age, NYHA functional class, concomitant procedures, and previous cardiac surgery. The 5-year results for freedom from cardiac death, reoperation, and valve-related complications among the 782 patients with degenerative etiology are, respectively, as follows ( >.05 for all end points): for anterior leaflet repair, 93%, 94%, 90%; for no anterior leaflet repair, 91%, 92%, 91%; for minimally invasive surgery, 97%, 89%, 93%; and for conventional sternotomy, 93%, 94%, 90%. CONCLUSIONS: These findings indicate that late results of MVR after minimally invasive surgery and after anterior leaflet repair are equivalent to those achievable with conventional sternotomy and posterior leaflet repair. These options significantly expand the range of patients suitable for mitral valve repair surgery and give further evidence to support wider use of minimally invasive techniques

BACKGROUND: This study analyzes a single institutional experience with minimally invasive mitral valve operations of 6 years, reviewing short-term morbidity and mortality and long-term echocardiographic follow-up data. METHODS: Seven hundred fourteen consecutive patients had minimally invasive mitral valve procedures between November 1995 and November 2001; concomitant procedures included 91 multiple valves and 18 coronary artery bypass grafts. Of these 714 patients, 561 patients had isolated mitral valve operations (375 repairs, 186 replacements). Mean age was 58.3 years (range, 14 to 96 years; 30.1% > 70 years), and 15.4% of patients had previous cardiac operations. Arterial cannulation was femoral in 79.0% and central in 21%, with the port access balloon endo-occlusion used in 82.3%. Cardioplegia was transjugular retrograde (54.1%) or antegrade (29.4%). Right anterior minithoracotomy was used in 96.6% and left posterior minithoracotomy in 2.2%. RESULTS: Hospital mortality for primary isolated mitral valve repair was 1.1% and 5.8% for isolated mitral valve replacement. Overall hospital mortality was 4.2% (30 of 714). Mean cross-clamp time was 92 minutes and mean cardiopulmonary bypass time was 127 minutes. Postoperatively, median ventilation time was 11 hours, intensive care unit time was 19 hours, and total hospital stay was 6 days. Complications for all patients included permanent neurologic deficit (2.9%), aortic dissection (0.3%); there was no mediastinal infection (0.0%). Follow-up echocardiography demonstrated 89.1% of the repair patients had only trace or no residual mitral insufficiency. CONCLUSIONS: This study demonstrates that the minimally invasive port access approach to mitral valve operations is reproducible with low perioperative morbidity and mortality and with late outcomes that are equivalent to conventional operations