Faculty Bibliography

In this study, we sought to determine the use of transesophageal echocardiography (TEE) as the primary imaging technique to assist in the placement of endovascular catheters during minimally invasive, port-access cardiac surgery. The recent development of endovascular catheters that are placed via the femoral artery and vein has enabled patients to be placed on cardiopulmonary bypass without the need for direct visualization of the heart or great vessels via sternotomy. This has allowed cardiac surgery to be performed through smaller thoracotomy incisions. Placement of these catheters has previously been performed with fluoroscopic guidance, which has major imaging limitations. Thirty-six patients underwent port-access cardiac surgery at our institution during the study period. All patients underwent intraoperative TEE. We used TEE to visualize the coronary sinus os, right atrium and superior vena cava, and thoracic aorta to assist with placement of the coronary sinus catheter, venous cannula, and endoaortic clamp. Twenty patients underwent mitral valve surgery, 14 patients coronary artery bypass grafting, 1 patient aortic valve replacement, and 1 patient repair of an atrial septal defect by the port-access approach. TEE was able to adequately visualize the cardiac structures and assist in the placement of the endovascular catheters in all patients. Fluoroscopy was only helpful as an aid to TEE for placement of the coronary sinus catheter. TEE is an excellent imaging modality for the proper placement of these new endovascular catheters, obviating the need for fluoroscopy, except to be on standby and for placement of the coronary sinus catheter

BACKGROUND: This study reviews the results of an initial experience with minimally invasive coronary bypass surgery using the Port-Access approach in terms of early outcome and safety. METHODS: Between October 1996 and July 1997 49 Port-Access minimally invasive coronary artery bypass grafting procedures were performed at our institution. The patients' mean age was 59.8 years (range 34 to 82 years). Sixteen patients received single vessel and 37 patients received multivessel bypass grafts. RESULTS: There were no operative deaths and no perioperative myocardial infarctions, neurological deficits, or conversions to sternotomy. Early complications included reoperation due to bleeding in 4 patients, reoperation for a pulmonary embolus in 1 patient, and angioplasty for occlusion of a right coronary artery graft in 2 patients. Postoperative angiograms were obtained in 86% (42/49) of the patients and showed 100% patency for left internal mammary artery to left anterior descending artery grafts and 96% patency for all grafts. CONCLUSIONS: These results demonstrate that Port-Access coronary artery bypass grafting using endovascular techniques for cardiopulmonary bypass and cardioplegic arrest can be performed safely with minimal morbidity and mortality. This technique allows multivessel revascularization on a protected, arrested heart with excellent anastomotic precision and reproducible early graft patency. Expanded use of Port-Access techniques is indicated in patients with multivessel coronary artery disease and the technique should be considered for patients with left anterior descending artery restenosis and patients with complex left anterior descending artery lesions where angioplasty results are suboptimal

BACKGROUND: The purpose of this study was to review the short-term results of an initial experience with minimally invasive cardiac valve surgery using the Port-Access approach in terms of feasibility, safety, and reproducibility. METHODS: Between October 1995 and October 1997, 151 minimally invasive cardiac valve procedures were performed at our institution using the Port-Access approach. The patients' mean age was 58.1 years (range 21 to 91 years) and 50% were male. Aortic valve replacement was performed in 35 (23.2%) patients, mitral valve repair in 56 (37.1%) patients, mitral valve replacement in 36 (23.8%) patients, and complex valve procedures in 24 (15.9%) patients. RESULTS: The operative mortality rate for isolated mitral valve surgery was 1.1% (1/92) and for all mitral valve surgery 3.5% (4/113). The operative mortality rate for isolated aortic valve patients was 5.7% (2/35). For the total group the operating mortality was 4% (6/151). Early complications for mitral valve patients included reoperation for bleeding or tamponade in 5 (4.4%) patients, myocardial infarction in 2 (1.2%) patients, and transient ischemic attack and wound infection in 1 (0.1%) patient each. One patient required reoperation for mitral valve failure that resulted in aortic dissection unrelated to the Endoaortic Clamp catheter and ultimately led to death. Two (5.6%) aortic valve patients required reoperation for bleeding and two (5.6%) required reoperation for tamponade. CONCLUSIONS: Minimally invasive Port-Access techniques can be applied to most patients with valvular heart disease with minimal morbidity and mortality and good postoperative valve function and may be the preferred approach for isolated mitral and aortic valve surgery

FGF-2 and VEGF are potent angiogenesis inducers in vivo and in vitro. Here we show that FGF-2 induces VEGF expression in vascular endothelial cells through autocrine and paracrine mechanisms. Addition of recombinant FGF-2 to cultured endothelial cells or upregulation of endogenous FGF-2 results in increased VEGF expression. Neutralizing monoclonal antibody to VEGF inhibits FGF-2-induced endothelial cell proliferation. Endogenous 18-kD FGF-2 production upregulates VEGF expression through extracellular interaction with cell membrane receptors; high-Mr FGF-2 (22-24-kD) acts via intracellular mechanism(s). During angiogenesis induced by FGF-2 in the mouse cornea, the endothelial cells of forming capillaries express VEGF mRNA and protein. Systemic administration of neutralizing VEGF antibody dramatically reduces FGF-2-induced angiogenesis. Because occasional fibroblasts or other cell types present in the corneal stroma show no significant expression of VEGF mRNA, these findings demonstrate that endothelial cell-derived VEGF is an important autocrine mediator of FGF-2-induced angiogenesis. Thus, angiogenesis in vivo can be modulated by a novel mechanism that involves the autocrine action of vascular endothelial cell-derived FGF-2 and VEGF

OBJECTIVE: New techniques for minimally invasive coronary artery bypass grafting have recently emerged. The purpose of this study was to determine the safety and efficacy of Port-Access (Heartport, Inc., Redwood City, Calif.) coronary revascularization and to evaluate with angiography the early graft patency rate with this new approach. METHODS: From October 1996 to May 1997, 31 patients underwent Port-Access coronary artery bypass grafting with an anterior minithoracotomy and endovascular-occlusion cardiopulmonary bypass. There were 26 men and 5 women with a mean age of 62 years (range 42 to 82 years). Fifteen patients underwent single bypass; 12 patients underwent double bypass, and 4 patients underwent triple bypass. Bypass conduits included the left internal thoracic artery (n = 30), right internal thoracic artery (n = 2), radial artery (n = 10), and saphenous vein (n = 6). Three sequential grafts were used. Angiographic studies of the bypass grafts were performed in 27 of 31 patients (87%). RESULTS: There were no deaths, neurologic deficits, myocardial infarctions, or aortic dissections. Conversion to sternotomy was not required in any case. There were two reoperations for bleeding, one reoperation for tamponade, and one reoperation for pulmonary embolus. Postoperative angiography revealed anastomotic patency of the left internal thoracic artery to left anterior descending artery in 26 of 26 grafts (100%) with overall anastomotic patency in 43 of 44 grafts (97.7%). CONCLUSION: These results demonstrate that Port-Access coronary artery bypass can be performed accurately and safely with acceptable morbidity. This approach allows for multivessel revascularization on an arrested, protected heart with excellent anastomotic precision and reproducible early graft patency

BACKGROUND: Standard reconstruction for posterior mitral leaflet (PML) disease is quadrangular resection and annular plication; when the PML is excessively high, a sliding plasty is used. We have developed an alternative technique, a posterior leaflet folding plasty. It is performed by folding down the cut vertical edges of the PML. The central height of the PML is reduced, leaflet coaptation is moved posteriorly, and annular plication is unnecessary. METHODS: From March 1995 to August 1996, 26 (17.9%) of 145 patients undergoing mitral reconstruction had a posterior leaflet folding plasty. Concomitant procedures included anterior leaflet resection or resuspension and myotomy and myectomy. In 3 patients, the PML resection extended to a commissure. RESULTS: There was one death and no reoperations. The mean New York Heart Association class was improved from 2.4 preoperatively to 1.4. There was no major postoperative mitral insufficiency in the 26 patients. Systolic anterior motion was transiently seen in 1 patient in whom left ventricular outflow tract obstruction was present preoperatively. CONCLUSIONS: The data demonstrate the safety and short-term efficacy of posterior leaflet folding plasty. This technique may help avoid systolic anterior motion after reconstruction of the PML

OBJECTIVE: Polymorphonuclear leukocyte (PMN) infiltration and microvascular injury are hallmarks of the tissue remodeling associated with multiple organ failure. These processes require the concerted action of various proteolytic enzymes, including serine and matrix metalloproteinases (MMPs). Matrix metalloproteinase-2 (MMP-2) plays an important role in the turnover of various ECM components, including type IV collagen, fibronectin, and gelatins. Like all MMPs, MMP-2 is secreted as an inactive zymogen (proMMP-2) and activated extracellularly by limited proteolytic cleavage. The physiologic mechanism(s) of proMMP-2 activation remains unclear. This study was designed to characterize the effect of PMNs on the activation of proMMP-2 produced by endothelial cells. METHODS: PMNs and human umbilical vein endothelial cells (HUVECs) were grown either separately or together for 2-16 h. To evaluate the role of cell-cell contact, cocultures were also established in which the two cell types were separated by a semipermeable polycarbonate membrane. Alternatively, PMN-conditioned medium was added to HUVEC cultures with or without various proteinase inhibitors (aprotinin, 1,10-phenanthroline, Batimastat, E-64, eglin c peptide, or pepstatin A). After incubation, the culture supernatants were analyzed by gelatin zymography to characterize the gelatinases. RESULTS: HUVECs produce MMP-2 in its inactive (72 kDa) form. PMNs produce high levels of MMP-9 (gelatinase B, 92 kDa) but no MMP-2. Coculture of PMNs with or addition of PMN-conditioned medium to HUVECs results in the production of active (62 kDa) MMP-2. ProMMP-2 activation by PMN-conditioned medium is not blocked by inhibitors of plasmin, cysteine-, acid-, or metalloproteinases. CONCLUSION: PMNs release a soluble factor that activates endothelial cell MMP-2 through a novel mechanism independent of cell-cell contact and not attributable to the activities of plasmin, cysteine-, acid-, or metalloproteinases. These findings may provide insight into the tissue remodeling that accompanies PMN-mediated microvascular injury

Polymorphonuclear leukocyte (PMN) superoxide (.O2-) production has been implicated in the pathogenesis of cardiopulmonary bypass (CPB)-related end organ injury. PMN 'priming' has been described as an event which enhances the release of .O2- following a second, activating insult. We hypothesized that PMN priming occurs during CBP and is temporally related to the plasma level of complement (C3a), interleukin (IL)-6, and IL-8. PMNs were isolated from 10 CPB patients pre-bypass (preCPB), 5 min after protamine administration (PROT), and at 6 and 24 h post-CPB. PMN .O2- production was measured by a cytochrome c reduction assay in the presence or absence of either phorbol 12-myristate-13-acetate (PMA, 0.4 microgram/ml) or N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 microM) and also after priming with 2000 nM platelet-activating factor (PAF) followed by activation with either PMA or FMLP. Plasma levels of C3a, IL-6, and IL-8 were determined by enzyme-linked immunosorbent assay. PMA-activated PMN .O2- production was significantly elevated at 6 h post-CPB compared to pre-CPB levels (11.04 +/- 0.9 vs 7.62 +/- 0.57, P = 0.009), indicating that CPB is associated with in vivo PMN priming. When PMNs were primed in vitro with PAF and then activated with PMA or FMLP, .O2- release at 6 h post-CPB was also significantly greater than pre-CPB levels (16.04 +/- 0.74 vs 12.2 +/- 0.92, P = 0.038; and 17.33 +/- 1.38 vs 13.33 +/- 1.35, P < 0.05), indicating that CPB acts synergistically with PAF to prime PMNs. Levels of C3a rose significantly over pre-CPB levels at PROT (P = 0.001), and IL-6 and IL-8 rose over pre-CPB levels at 6 h post-CPB (P = 0.01 and P = 0.006, respectively). These findings demonstrate that CPB not only directly primes PMNs, but also potentiates priming of PMNs by PAF. This 'primed' PMN state, which coincided with the increased plasma levels of inflammatory mediators, may suggest a mechanism of predisposition to organ dysfunction following CPB

Experiences with 1,000 patients undergoing mitral valve reconstruction at New York University over the past 18 years are summarized. A continuing follow-up (98% complete) demonstrated that 88% of patients are free from recurrent insufficiency 10 years after the operation. Reconstruction is feasible in nearly 90% of patients with mitral valve prolapse, with an operative mortality near 2%. Accordingly, operation is now recommended at an early stage with the first sign of left ventricular systolic dysfunction, while the patient is still in sinus rhythm. Most operations have been done with the Carpentier techniques of segmental resection with annuloplasty and insertion of a Carpentier ring. Recently, two other repair techniques and a minimally invasive operative approach have been evaluated. A triangular resection of a prolapsing anterior leaflet has been done in more than 100 patients with excellent results. Also, a posterior 'folding plasty' has been employed in more than 40 patients with a large redundant posterior leaflet, minimizing the need for annular plication. A minimally invasive approach to the mitral valve has now been employed in 130 patients over the past year, using a right mini-thoracotomy and the Port-Access (Heartport, Inc, Menlo Park, CA) approach. This technique employs catheters introduced through femoral vessels to institute cardiopulmonary bypass and cardioplegic arrest. The operative approach and techniques for mitral valve reconstructive operations continue to evolve, with excellent results and improved patient benefits