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Back to Annual Meeting Program
WEDNESDAY MORNING, APRIL 26, 1995
7:00 am FORUM SESSION II Grand Ballroom, Sheraton Boston Hotel
Moderators: Robert A. Guyton, M.D. Shukri F. Khuri, M.D.
F9. THE EXPRESSION OF TNFα AND CHEMOKINES (ENA-78 AND GROα) DURING ISCHEMIA/ REPERFUSION INJURY ASSOCIATED WITH LUNG TRANSPLANTATION K..E. Magliato, M.D.*, D.L. Swiderski, Ph.D.*, S.L. Kunkel, Ph.D.*, C.A. Wilke, B.S.*, M.D. Burdick, B.S.*, G.M. Deeb, M.D. and R.M. Stricter, M.D.* Akron, Ohio and Ann Arbor, Michigan
The reimplantation response or ischemia/reperfusion injury is potentially an important cause of morbidity during lung transplantation. While a number of cellular events are involved in this response, the neutrophil appears to play a pivotal role in mediating lung injury during reimplantation. The mechanisms that lead to neutrophil sequestration and activation are complex and have not been fully elucidated. We postulated that the generation of the early response cytokine, tumor necrosis factor alpha (TNFα), and the chemokines, epithelial cell neutrophil activating protein (ENA-78), and growth related oncogene alpha (GROα ), would be significantly elevated during the reimplantation response and be associated with maximal neutrophil sequestration and subsequent lung injury. To test this hypothesis, we evaluated pulmonary microvascular permeability as index of injury, neutrophil influx , and expression of TNFα, ENA-78, and GROα during the reimplantation response using a rat orthotopic single-lung syngeneic transplant model. Cytokine expression in plasma, lung tissue homogenates, and bronchoalveolar lavage (BAL) at 4, 12, 24, 36, and 48 hours post-reimplantation was measured by specific ELISAs (n=30). Cytokine levels from the transplant recipient animals were similar to sham operated control animals until 24 hrs post-reimplantation. At 24 hrs post-reimplantation, TNFa, ENA-78, and GROα were all significantly elevated (2-fold) from the lung tissue homogenates of the transplant recipients, as compared to sham operated controls. The concentrations of all cytokines returned to levels similar to the sham operated animals by 48 hours. Pulmonary neutrophil sequestration, as evaluated by BAL cell counts, paralleled the changes in lung tissue cytokine levels. At 24 hours, neutrophil absolute and relative levels were higher in transplant recipients (6.5± 4.4 x 105, 69.7±5.8% of the total) than in sham operated controls (2.4±1.1 x 105, 12.3±5.7% of the total) (p=.002). The findings of BAL neutrophil levels were corroborated by elevated levels of myeloperoxidase activity from transplanted lung tissue homogenates (100.8±22.8) as compared with sham controls (35.1±8.1) (p=.02). Using Evan's blue dye as marker of pulmonary microvascular permeability, transplant recipients at 24 hours post-reimplantation demonstrated a 2.5-fold greater index of lung permeability, as compared to sham operated control animals (p=.01). In addition, transplanted animals pretreated with neutralizing TNF antisera showed a 50% decrease in lung injury by Evan's blue dye lung permeability assessment. These findings suggest that the temporal expression of TNFcc, ENA-78, GROa correlates with maximal neutrophil sequestration and lung injury associated with the reimplantation response and neutralizing TNF antisera has a protective role in ischemia/reperfusion injury.
*By invitation F10. THERAPEUTIC ANGIOGENESIS: ACIDIC FIBROBLAST GROWTH FACTOR ACCELERATES COLLATERAL VESSEL FORMATION AND REVASCULARIZATION OF ISCHEMIC TISSUES Todd K. Rosengart, M.D.*, Martin A. Duenas, B.S.*, Qing-Xue Zhang, Ph.D.*, Karl H. Krieger, M.D. and O. Wayne Isom, M.D. New York, New York
Angiogenesis, the growth of new blood vessels, is thought to be an important biological mechanism allowing for the revascularization of ischemic tissues. Acidic fibroblast growth factor (aFGF) is a potent stimulant of angio-genesis that may prove useful in accelerating collateral vessel development following vascular occlusion. We therefore assessed the ability of aFGF to enhance angiogenesis and improve perfusion in the setting of acute ischemia. Ligation of the left common femoral artery was performed in the rat followed by the daily transcutaneous injections into the ischemic hind limb region of saline (1ml) or recombinant human aFGF (1 mcgm in 1 ml saline) for 10 days following ligation (n=4). Following the treatment period, 2 x 106 color micro-spheres were injected via the infrarenal abdominal aorta and the relative perfusion of the ligated limb versus the unligated, contralateral control limb was determined from the microsphere counts per gram of tissue harvested from each limb. Relative perfusion of the ligated limb in the aFGF-treated animals was 62 ± 16% (mean ± SEM) of that to the unligated, contralateral control limb compared with 10 ± 3% relative perfusion in the saline-treated animals (p=0.004). These results were confirmed by histologic analysis of hind limb tissue specimens, which demonstrated 27 ± 2 vs 4 ± 1 vessels per high power field in the aFGF and saline-treated animals, respectively (p=0.001). Proliferating cell nuclear antigen (PCNA) analysis was utilized to assess mitogenic activity and demonstrated that the percentage of PCNA-labelled cells per total cell nuclei was 68 ± 4% vs 5 ± 1% in the two respective groups (p<0.001). The six-fold increase in perfusion noted in these studies, confirmed by analysis of vascularization and cell replication, suggest that exogenous aFGF administration may represent a useful means of enhancing collateral vessel growth and relieving acute ischemia. The administration of aFGF may potentially allow the revascularization of myocardial or other tissues not salvageable by bypass procedures or other conventional means.
*By invitation F11. MYOBLAST TRANSPLANTATION IN THE PORCINE MODEL. A POTENTIAL TECHNIQUE FOR MYOCARDIAL REPAIR Clifford H. Van Meter, Jr., M.D.*, Frank Smart, M.D.*, William Claycomb, Ph.D.*, Joseph DelCarpio, Ph.D.* and John L. Ochsner, M.D. New Orleans, Louisiana
The increasing shortage of organ donors continues to fuel the search for other methods to manage heart failure. The use of transgenic cells transplanted in syngeneic rodents has shown modest success, but allogeneic and xenogeneic transplants have not been uniformly successful. To assess the feasibility of xenogeneic and allogeneic myoblast transplantation, six adult swine underwent transplantation of murine atrial tumor cells (xenogeneic) and neonatal porcine (allogeneic) into the left ventricular wall. A subsequent seventh animal underwent transplantation of human neonatal myoblasts (16 weeks of age). Following general anesthesia, isolated cells were injected along the anterior and posterior wall of the porcine left ventricle (6 to 8 sites per animal). All the animals were immunosuppressed with cyclosporine and prednisone and were followed for one month post-injection at which time they were sacrificed. In all injected sites, the transplanted cells proliferated within the host myocardium with no significant rejection. CPK MB isoenzymes did not increase after the procedure indicating that there was no damage to the host myocardium from the injection of cells. Moreover, transplant cells formed close associations with host myocytes that resembled intercalated discs on electron mycroscopy, and were composed of PAN cadherin on immuno-fluorescent staining. These cells also contained myofibrils and other cell architecture that resembled normal AT-1 or neonatal myocytes. Additionally, these cells produced angiogenic factors resulting in a proliferation of the surrounding microvasculature. In conclusion, these findings indicate successful xenogeneic and allogeneic myocyte cell transplantation in a large animal model. These experiments set the stage for future studies to test the ability of these cells to form a syncytium, to contract, and potentially repair failed myocardium.
*By invitation F12. EFFICIENT CARDIAC GENE TRANSFER BY INTRA-CORONARY INFUSION OF ADENOVIRUS VECTOR MEDIATED REPORTER GENE IN TRANSPLANTED MOUSE HEART Jeongryul Lee, M.D.*, Alistair I. Fyfe, M.D.*, Hillel Laks, M.D., Davis C. Drinkwater, M.D., Yuji Shiraishi, M.D.* and Paul Chang, B.S.* Los Angeles, California
Gene transfer into the coronary arteries may offer an opportunity to modulate alloreactivity after cardiac transplantation. In the present study, we perfused the coronary arteries of donor mouse hearts with 107 pfu (200 |aL) of a recombinant adenovirus containing P-galactosidase encoding gene (AdCMV P gal) just prior to harvesting to demonstrate the feasibility, efficacy, and safety of adenovirus mediated in vivo transfer. The donor hearts were transplanted into the abdomen of the recipient mice of the same strain (BIO. BR). Both the grafts and recipient hearts were harvested at 3, 7, 15 and 30 days (n=6 in each group) after transplantation and P-galactosidase activity was assessed by immunohistochemistry. All grafts were functioning adequately at the time of harvest and P-galactosidase expression was seen throughout the myocardium, epicardium, and the surrounding coronary arteries. There were no significant differences in expression at least up to 30 days after transplantation. Staining was not seen in recipient hearts or sham control isografts (n=6) which were sacrificed 7 days after infusion of saline into the coronary arteries. This study revealed that intracoronary adenovirus mediated gene transfer is an efficient and feasible method for transfecting genes, with widespread expression, and there does not appear to be significant early cardiac graft dysfunction associated with the use of adenovirus. This approach may allow modification of graft immunogenicity in the future by allowing the production of therapeutic proteins that inhibit or delay the development of cardiac allograft vasculopathy.
*By invitation F13. INTRATHYMIC STEM CELL TRANSPLANTS PROLONGSKIN GRAFT SURVIVAL IN UNRELATED PRIMATES Margaret D. Allen, M.D., Hiroji Akimoto, M.D.*, John T. Weyhrich, D.V.M.*, Karen A. Nelson, Ph.D.*, Robert Thomas, B.S.* and Robert G. Andrews, M.D. Seattle, Washington
The intrathymic implantation of stem cells in transplant recipients may resolve several problems limiting the attainment of tolerance to transplanted organs. 1) Peripheral blood microchimerism has been associated with reduced rejection in clinical liver and renal transplantation but peripheral infusion of donor marrow to induce chimerism carries a risk of graft-versus-host disease (GVHD). Recent bone marrow transplants in primates suggest that stem cell fractions may result in less GVHD. 2) Intrathymic implantation of lymphocytes, splenocytes, class II peptides, and even islets in rodents pre-treated with myeloablation or anti-lymphocyte globulin can extend subsequent donor organ or skin graft survival, but hematopoietic microchimerism has not been reported. Stem cells might provide a self-perpetuating source of donor antigens. 3) If suppressor mechanisms are operative, less, rather than more, immunosuppression may be beneficial. This study examines whether the intrathymic implantation of donor CD34+ enriched marrow (97% CD34+) might produce hematopoietic chimerism and induce tolerance to donor-derived grafts in unrelated primates with or without immunosuppression. Four juvenile female baboons underwent intrathymic transplantation of CD34+ enriched marrow (1 x 106 cells) from unrelated male baboon donors through a left thoracotomy approach. Peripheral blood was sampled at biweekly intervals for the presence and persistence of donor cells using PCR for Y chromosome determinants. Two recipient animals were treated with standard triple drug immunosuppression consisting of cyclosporine, azathioprine, and steroids, in doses equivalent to the clinical cardiac transplant protocol. No myeloablative therapy or anti-lymphocyte serum induction was used. Two other recipients received no immunosuppression. All 4 recipients, both with and without immunosuppression, developed peripheral blood microchimerism within 2 weeks which is still persistent at 9-16 months. No clinical evidence of GVHD was observed. To test whether the implantation of intrathymic stem cells resulted in tolerance, two further juvenile female baboons were implanted with male donor CD34+ marrow without recipient immunosuppression. Chimerism was detected in both animals. Three months following the intrathymic implants, 9 skin grafts were placed on each recipient: 3 from autologous skin, 3 from the stem cell donor, and 3 from a third party baboon. Autologous grafts were incorporated without rejection. Third party grafts sloughed at 24 days post-transplant and, in both recipients, the grafts from the stem cell donor persisted DNA. Repetition of the skin grafts again demonstrated prolongation of the stem cell-donor over the third party-donor grafts. These results demonstrate that: l)the intrathymic implantation of donor CD34+ enriched marrow can induce peripheral microchimerism in non-human primates with or without immunosuppression; 2) 1 x 106 CD34+ cells is sufficient to induce peripheral chimerism; 3) donor-specific skin graft, prolongation was achieved; and 4) graft versus host disease was not observed. These findings have current applications in the field of thoracic transplantation tolerance as well as future potential in the treatment of genetic deficiency diseases of the newborn.
Nina S. Braunwald Career Development Award Recipient
*By invitation F14. INHIBITION OF INDUCIBLE NITRIC OXIDE AMELIORATES RAT LUNG ALLOGRAFT REJECTIONTakeshi Shiraishi, M.D.*, Neil K. Worrall, M.D.*, Steven R. DeMeester, M.D.*, Jon H. Ritter, M.D.*, Thomas P. Misko, Ph.D.*, T. Bruce Ferguson, M.D., Joel D. Cooper, M.D. and G. Alexander Patterson, M.D. St. Louis, Missouri
Inhibition of the production of nitric oxide (NO) by inhibition of inducible nitric oxide synthase (iNOS) has recently been demonstrated to attenuate the pathogenesis of acute cardiac allograft rejection. This study examined the effect of inhibition of NO production on rejection in a rat lung transplant model. Syngeneic (F344 to F344) (n=7) and allogeneic (Brown Norway to F344 recipient) (n=8) left lung transplants were performed. In this latter strain combination complete rejection occurs by postoperative day 8. Using the same allogeneic combination, a third group of animals (n=9) underwent allotransplantation and received aminoguanidine (a specific iNOS inhibitor) 200 mg/kg IP q6h from transplantation until sacrifice on postoperative day 7 (POD-7). NO production was demonstrated by measuring serum nitrite/nitrate levels (stable end products of NO metabolism). Allograft serum nitrite/nitrate levels [16.5 ± 1.7mM, n=4 (p<.01 by ANOVA)] were elevated above normal control (8.0 ± 1.0 mM, n=3) and isograft levels (9.0 ± 1.4 mM, n=4) on postoperative day 4 (POD-4), indicating that NO is produced during lung allograft rejection. Aminoguanidine treatment prevented the increased serum nitrite/nitrate levels in the allografts on POD-4 (9.8 ± 1.0 mM; p<0.01 vs untreated allografts). The effect of iNOS inhibition on acute rejection was determined by using three scoring systems. Severity of rejection was evaluated using a radiographic score (Aeration Score; 0=opaque to 6=normal appearing lung). The histologic rejection grade was determined at sacrifice on POD-7 using the International Working Formulation (I.W.F. score: 0=normal to 4=diffuse infiltration of mononuclear cells) and Prop's scoring system (0=latent phase to 3=destruction). Aminoguanidine treatment significantly attenuated acute rejection as determined radiographically [AS= 4.1 ± 1.4 vs 1.8 ± 0.9 for untreated allografts on POD-6 (p<.05) and 3.9 ± 1.5 vs 0.6 ± 0.5 on POD-7 (p<.01)]. Aminoguanidine treatment also significantly ameliorated the histologic degree of rejection as determined at sacrifice on POD-7 [2.6 ± 0.2 vs 3.8 ± 0.5 for untreated allografts by IWF score (p<.005) and 1.3 ± 0.4 vs 2.6 ± 0.7 by Prop's score (p<.005)]. These results demonstrate that NO is produced during acute lung allograft rejection and that selective inhibition of the inducible isoform of nitric oxide synthase significantly attenuated acute rejection. NO production may serve as a marker of early rejection and selective inhibition of iNOS may be a novel therapeutic modality in the management of acute lung allograft rejection.
*By invitation F15. THE EFFECT OF N-co-NITRO-L-ARGININE ON PULMONARY VASCULAR TONE IN THE MATURING NEWBORN PIG Patrick W. Domkowski, Ph.D.*, John T. Cockerham, M.D.*, Peter A. Kot, M.D.*, Jeffrey L. Myers, M.D.*, Yi-Ning Wang, M.D.*, Robert B. Wallace, M.D. and Richard A. Hopkins, M.D. Washington, DC
Current therapeutic modalities for treatment of newborn pulmonary hypertensive crisis include the administration of nitric oxide (endothelium derived relaxing factor, EDRF). However, few data are available on the role of endogenously produced EDRF in the modulation of newborn pulmonary arterial tone. We investigated the acute effects of a 10-minute intravenous infusion of N-oo-nitro-L-arginine (L-NA), a potent competitive inhibitor of EDRF synthase on the pulmonary vascular response, in 48-hour and 2-week-old anesthetized open-chest Yorkshire pigs. Fourier analysis of high fidelity main pulmonary artery pressure (PAP) and flow (PAF) waveforms was employed to distinguish between proximal and distal pulmonary arterial responses to L-NA. Input mean impedance (Zm, reflective of distal vasocon-striction) and characteristic impedance (Z0, reflecting proximal arterial disten-sibility) were calculated. Pulmonary vascular resistance (PVR) was also calculated. Data were collected at baseline and during intravenous infusion of L-NA.
Baseline hemodynamic parameters were significantly diminished in 2-week-old pigs, reflecting the expected decrease in both proximal and distal pulmonary arterial vasoconstriction with maturation. L-NA produced no significant pulmonary hemodynamic changes in 48-hour-old pigs. However, in 2-week-old pigs, L-NA caused a significant pulmonary arteriolar vasoconstriction. L-NA infusion did not cause any significant alterations in zq in either group. These data indicate that endogenously produced EDRF modulates distal pulmonary arterial tone in 2-week-old pigs, but not in 48-hour-old pigs. Pulmonary hypertensive crisis of the newborn may reflect an inability of the pulmonary endothelium to synthesize and release nitric oxide in quantities sufficient enough to modulate pulmonary vascular tone.
*By invitation F16. ELUCIDATION OF A TRIPARTITE MECHANISM UNDERLYING THE IMPROVEMENT IN CARDIAC TOLERANCE TO ISCHEMIA BY COENZYME Q10 PRETREATMENT Juan A. Crestanello, M.D.*, Joseph Kamelgard, M.D.*, David M. Lingle, M.D.*, Svend A. Mortensen, M.D.* and Glenn J.R. Whitman, M.D. Philadelphia, Pennsylvania and Copenhagen, Denmark
CoQ10, involved with mitochondrial ATP production, is also a powerful antioxidant. We hypothesize that CoQ10 pretreatment protects myocardium from ischemia reperfusion injury by both its ability to increase aerobic energy production and by its ability to protect creatine kinase (CK) from oxidative inactivation during reperfusion. Isolated hearts (n=6/group) from rats pretreated with either CoQ10 20 mg/kg i.m. and 10 mg/kg i.p. (CoQ) or vehicle only (CTRL) 24 and 2 hours prior to the experiment were subjected to 15 minutes of equilibration (EQ), 25 minutes of ischemia, and 40 minutes of reperfusion (RP). Developed pressure (DP), ±dP/dt, myocardial oxygen consumption (MVO2), and myocardial aerobic efficiency (DP/MVC^) were measured. In parallel groups of hearts, 31P NMR spectroscopy was used to determine P-ATP and PCr concentrations. Hearts were assayed for myocardial CK activity at end RP. Values are expressed as mean ± SEM with t-test used for statistical evaluation.
(MDP: Methylenediphosphonic acid standard) *p<0.05 vs Control **p<0 005 vs Control
CoQ10 pretreatment improves myocardial function after ischemia reperfusion. This results from a tripartite effect: 1) higher ATP and PCr concentrations initially and during reperfusion, 2) improved myocardial aerobic efficiency during reperfusion, and 3) protection of CK from oxidative inactivation during reperfusion with an improved bioenergetic profile.
*By invitation F17. INDUCED IMMUNOLOGIC UNRESPONSIVENESS INHIBITS CARDIAC GRAFT ARTERIOSCLEROSIS Yong T. Shin, M.D.*, Mohamed H. Sayegh, M.D.*, Lauri R. Wyner, B.A.*, Morris J. Karnovsky, M.B., B.Ch.* and David H. Adams, M.D.* Boston, Massachusetts Sponsored by: Lawrence H. Cohn, M.D., Boston, Massachusetts
Chronic rejection, manifested by the development of graft arteriosclerosis, remains the leading cause of late death in cardiac transplant recipients. Immunologic mechanisms have been implicated in both experimental and clinical studies, yet the pathogenesis and therapy of chronic allograft rejection remains poorly defined. Recent studies have shown that intrathymic (i.t.) injection of donor cells or processed allo-MHC antigens with or without transient immunosuppression induces specific systemic T cell tolerance and prevents acute allograft rejection in several experimental trasnplantation models. In this study we examined the effects of i.t injection of donor cells with or without systemic anti-lymphocyte serum (ALS) on the development of chronic rejection in the Lewis-to-F344 rat cardiac allograft model. Recipients were divided into 4 groups: control group A was pre-treated with saline i.t., group B received donor (Lewis) splenocytes i.t. (2x106), group C was pre-treated with a one-time dose of ALS (1 ml) via intraperitoneal injection (i.p.), and group D received both the splenocytes i.t. and a one-time dose of ALS i.p. two weeks prior to transplantation. Allografts were followed by daily palpation and graded from 0-4 (grade 0=non-palpable, grade 4=normal heartbeat). Graft survival on post-op day 90 for all three treated groups was 100% vs. 33% for the control (n=6/group), and mean heartbeat grade for the three treated groups (B=2.0±0.41, C=2.83±0.17, D=2.67±0.21) was significantly higher (p<0.01) vs. the control group (A=0.4±0.24). Histologic and immunocytochemical analysis of 90-day old grafts revealed the following results (*(p<0.02, **p<0.003vs Control):
Conclusions: (1) Treatment with donor splenocytes i.t. alone partially suppresses the immune response, prolonging graft survival and preserving function without inhibiting graft inflammation or arteriosclerosis. (2) The induction of systemic unresponsiveness with ALS i.p. or splenocytes i.t. plus ALS i.p. markedly reduces inflammation and inhibits graft arteriosclerosis, suggesting the development of therapies resulting in better control of the immune response remains the key to ameliorating this disease process.
Alton Ochsner Research Scholar .
*By invitation F18. MOLECULAR GENETIC DIFFERENTIATION BETWEEN PRIMARY LUNG CANCER AND LUNG METASTASES OF OTHER TUMORS Daniela Kandioler, M.D.*, Gerhard Dekan, M.D.*, Adelheid End, M.D.*, Michael Mttller, M.D.*, Michael Gnant, M.D.*, Eva Pasching*, Christine Mannhalter, Ph.D.*, Franz Eckersberger, M.D.*, and Ernst Wolner, M.D. Vienna, Austria
When single pulmonary tumors are observed in patients with history of other cancer, differentiation between metastasis and second primary lung cancer is crucial for appropriate therapy. Particularly in low differentiated tumors this determination by means of histology alone may be difficult or impossible even with the help of immunochemistry. Implicating that p53 mutations are conserved in metastases, we hypothesized that a genetic fingerprinting using the p53 gene could be a valuable tool in differentiating between metastases and second primary carcinomas since the p53 gene is frequently affected by various mutations in many different types of human carcinomas. Out of 267 resected lung tumors we analysed 9 cases of solid lung tumors whose origin could not exactly be defined histologically. As a control we used tumor material of a patient with adenocarcinoma of the lung and histologically defined brain and lymphnode metastases.
We extracted DNA from the shock frozen tissue of the unclassified lung tumors, from the paraffin embedded tissue of the "past primary cancers" and from peripheral blood of the patients. Exons 2 to 11 of the p53 gene were amplified separately by polymerase chain reaction (PCR) and directly sequenced. In all cases the presence of germline mutations could be excluded by analysis of the peripheral blood. The p53 mutation detected in the control tumor proved to be conserved in the lymph node as well as in the brain metastasis. In two cases the lung tumor was identified as (second) primary lung cancer since the genetically compared tumors exhibited different mutations. In five cases the lung tumors proved to be metastases exhibiting the identical p53 mutation as their "primary." In one case the lung tumor could be identified as metastases from renal cancer whereas a thyroid cancer metastasis could be excluded. One case remained inconclusive since no p53 mutation could be found in any tissue. Thus, due to genetic analysis using the p53 gene, correct surgical treatment could be approved in six cases regarded as metastatic disease of the lung, whereas further pulmonary surgery was mandatory in two cases identified as second primary lung cancer. We conclude that analysis of p53 mutations is a valuable tool in the exact diagnosis of metastases and recurrent tumors which are difficult to classify by standard methods. Since the information about tumor origin is essential in assessing an individual patient's treatment strategy, these results are clinically relevant.
*By invitation 9:30 am SIMULTANEOUS SCIENTIFIC SESSION D ADULT CARDIAC SURGERY Grand Ballroom, Sheraton Boston Hotel
Moderators: D. Glenn Pennington, M.D. Robert L. Hardesty, M.D.
41. REFERRAL SOURCE AS A RISK FACTOR FOR CORONARY BYPASS SURGERY: HMO VS. PRIVATE PRACTICE Albert Starr, M.D., Aftab Ahmad, M.D.* Anthony Furnary, M.D.*, Guo Wei He, M.D.*, Jeffrey Swanson, M.D.* and Gary Grunkemeier, Ph.D.* Portland, Oregon
We began performing coronary bypass surgery (CBS) for a large HMO in 1974, as the sole provider of their cardiac surgery. The HMO system entails pre-intervention, multi-disciplinary screening conferences and is absent of self-referral and personal financial incentives. Since 1985, the operative mortality for HMO patients has consistently been lower than for private patients. There were 8, 483 surgeries during this study period: 3, 168 (37%) HMO, with an overall operative mortality of 2.7%, and 5, 315 (63%) non-HMO, with an operative mortality of 4.6% (P=.00002). All patients were operated on in the same hospital by the same surgical group. We investigated this difference with univariate and multivariable analyses. 19 risk factors were found to univariately affect the risk of operative mortality (p<.05). For 11 of these risk factors there was a significant maldistribution between HMO and non-HMO patients; HMO patients had worse average values for 3 factors and better values for 8 (the latter included age, previous CBS, abnormal wall motion, chronic angina, and emergency surgery). We used logistic regression to explore the influence of this imbalance in risk factors. The model found 7 factors to significantly affect operative mortality, after which the variable indicating HMO membership was no longer significant (p=.006). Because of missing data, only 1, 279 (40%) HMO patients and 2, 407 (45%) non-HMO patients, with operative mortalities of 2.6% and 4.1%, respectively, could be used. A reasonable conclusion is that the difference in operative mortality between a coherent and chaotic system of cardiologic management results in a distribution of risk factors that enhance the operative results in the coherent group. The question of whether this selection process would be beneficial to a large population at risk has not been addressed.
*By invitation 42. REDUCING THE RISK OF INFECTIVE ENDOCARDITIS AFTER AORTIC VALVE REPLACEMENT Arvind K. Agnihotri, M.D.*, David C. McGiffin, M.D.*, Andrew J. Galbraith, M.D.* and Mark F. O'Brien, M.D. Birmingham, Alabama and Brisbane, Australia
Replacement valve endocarditis (RVE) occurred on 3.9% of 2, 686 aortic valve replacement devices inserted between December 31, 1969 and January 1, 1992, based on a cross-sectional follow-up in 1992 which was 98.8% complete. As shown by others, the risk (hazard function) for RVE was highest early after valve replacement, peaking 3 months after operation, then decreasing to reach a constant hazard by about 6 months after operation. By multivariable analysis, patients with active preoperative endocarditis (p<.0001) or those receiving a synthetic aortic root replacement (p=.0006) were at an increased early risk for RVE, but this increased risk was neutralized when an allograft valve was used (p<.0001; figure A [figures A and B are nomograms of the multivariable equation]). Late risk (later than 6 months after operation) was increased in younger patients (p<.0001), those with renal failure (p=.01), and in patients with active or remote preoperation endocarditis (p=.04). Late risk was particularly high in patients with preoperative Staphylococcus aureus endocarditis (p=.05), which tended to recur as another staphylococcal endocarditis. Use of some mechanical valves resulted in a reduction in late risk (p=.05; figure B, while use of some xenograft valves increased late risk (p=.02).
In patients without risk factors, valve replacement with any modern device results in a similar infectious risk (figure C). In the presence of early phase risk factors use of an allograft valve reduces the risk of RVE. In patients with only late phase risk factors the use of some mechanical valves may be preferable.
*By invitation 43. SURGICAL TREATMENT OF PROSTHETIC VALVE ENDOCARDITIS Bruce W. Lytle, M.D., Brian P. Priest, M.D.*, Paul C. Taylor, M.D.*, Floyd D. Loop, M.D., Robert W. Stewart, M.D.*, Patrick M. McCarthy, M.D.*, Derek Muehrcke, M.D.* and Delos M. Cosgrove, M.D. Cleveland, Ohio
From 1975 through 1992, we reoperated on 146 patients for the treatment of prosthetic valve endocarditis (PVE). Inclusion in the study stopped in 1992 to allow follow-up of all patients. PVE was considered early (<1 year after operation) in 46 cases, active in 103 cases, and the extent of the infection was prosthesis only, 66, annulus, 46, and cardiac invasion, 34. Surgical techniques evolved in the direction of increasingly radical debridement and reconstruction with biological materials. All patients were treated with prolonged postoperative antibiotic therapy. There were 19 (13%) in-hospital deaths. Univariate analyses demonstrated trends toward increasing risk for patients with active PVE and extension of infection beyond the prosthesis; however, the only variables with a significant (P<0.05) association with increased in-hospital mortality confirmed with multivariate testing were impaired LV function, heart block, major organ system failure and identification of organisms in the pathology specimen. During the study period, mortality decreased from 20% (1975-1984) to 10% (1984-1992). For hospital survivors the mean length of stay was 25 days. Follow-up (mean interval 62 months) documented late survival of 82% at 5 and 60% at 10 postoperative years. Increasing age was the only factor associated (P=0.006) with late mortality. Nineteen patients needed at least one further operation; reoperation-free survival was 75% at 5 and 50% at 10 postoperative years. Fever in the immediate preoperative period was the only factor associated with decreased late reoperation-free survival (P=0.049). PVE remains a serious complication of valve replacement but the in-hospital mortality of reoperations for PVE has declined. With extensive debridement of infected tissue and postoperative antibiotic therapy the extent and activity of PVE does not appear to have a major impact on late outcome and the majority of patients with PVE survive for 10 years after surgery.
*By invitation 44. THE ADDITIONAL HOSPITAL COSTS GENERATED IN THE MANAGEMENT OF COMPLICATIONS OF PACEMAKER AND DEFIBRILLATOR IMPLANTATIONS T. Bruce Ferguson, Jr., M.D., Candice Lilley Ferguson, M.S.P.H.* and Patricia Crimmins-Reda, R.N., M.S.N.* St. Louis, Missouri
The rapid approach of capitated reimbursement mandates that providers examine their practice patterns associated with all surgical procedures. As part of this effort, documentation of 1) the complications associated with these procedures; and 2) the additional hospital costs associated with the management of these complications, is critical for comprehensive fiscal accountability. This study analyzed the fully-loaded hospital costs generated in the management of the most common surgical complications - infection, lead-related problems and hematoma formation requiring evacuation - associated with pacemaker and non-thoracotomy implantable defibrillator therapies. Between July 1989 and September 1994 a total of 1, 031 pacemaker (PM) and 331 implantable defibrillator (ICD) procedures were performed by a cardiac surgeon in a tertiary-level teaching hospital setting. Over the past two years, 105 of these ICD procedures involved non-thoracotomy (NT-ICD) systems. Because of the commonly presumed similarities between PM and NT-ICD procedures, these two groups will be examined in this analysis. There were no deaths associated with the 1, 136 procedures. The overall in-house PM infection rate was 0.58% (6/1, 031). An additional nine PM patients were transferred from outside institutions for definitive therapy of infected systems. The in-house PM lead reposition/replacement rate was 4.1% (37/902 procedures involving lead placement), performed from 1-78 days post-initial implant. Four PM patients developed pocket hematomas requiring evacuation; all were on systemic anticoagulation for medical problems. The overall in-house infection rate for NT-ICD was 0.95% (1/105). Two patients, both on systemic anticoagulation, developed pocket hematomas requiring reexplora-tion; both required lead configuration modifications due to elevated defibrilla-tion thresholds (DFTs) at the second procedure. Two patients had ICD system malfunctions, and four other patients (3.8%) had lead fractures (N=2) or dis-lodgements that necessitated surgical reexploration. The additional fully-loaded hospital costs were documented as additional length of stay (LOS) in-hospital, ICU requirement, OR procedure costs, device costs and additional pharmacy, administrative and miscellaneous costs directly associated with the complication (data are expressed as mean ± SD):
Thus management of these common complications of PM and NT-ICD therapies is expensive. For all Medicare patients with complications in this study, costs exceeded reimbursement, suggesting that similar shortfalls would occur under a capitation scheme. The study demonstrates that accurate identification of the costs associated with complications of interventional procedures is feasible. This information is critical to a complete understanding of the financial impact of surgical procedures in a capitated reimbursement environment.
10:50 am INTERMISSION
*By invitation 11:10 am SIMULTANEOUS SCIENTIFIC SESSION D ADULT CARDIAC SURGERYGrand Ballroom, Sheraton Boston Hotel
Moderators: D. Glenn Pennington, M.D. Robert L. Hardesty, M.D.
45. A PROSPECTIVE RANDOMIZED TRIAL OF EARLY EXTUBATION AFTER CORONARY ARTERY BYPASS Charles M. Peniston, M.D., C.M.*, Davy Cheng, M.D.*, Jacek Karski, M.D.*, Zhao Sun, M.A.*, Susan Armstrong, M.Sc.* and Tirone E. David, M.D. Toronto, Ontario, Canada
Early extubation within the first few hours after cardiac surgery has been proposed as a safe method of cost containment by reducing ICU-and hospital stay. Early extubation has been possible in most cardiac patients by modifying the anaesthetic. All patients who had this modified anaesthetic were retrospectively reviewed to determine the predictors of failure of early extubation. Stepwise logistic regression analysis revealed that age > 65 years, female gender, moderate or severe left ventricular function and urgent operations were associated with a lower probability of early extubation. We then undertook a prospective study to determine if early extubation is safe and reduces the length of ICU and hospital stay after coronary artery bypass (CAB). Methods: After institutional approval, 89 patients undergoing elective CAB were randomized to either conventional anaesthesia (CONVENTIONAL) (induction with fentanyl 50 meg/kg; maintenance with isoflurane and midazo-lam 0.1 mg/kg/hr) and assisted ventilation until next morning after surgery, or modified anaesthesia (EARLY EXTUBATION) (induction with fentanyl 15 meg/kg, isoflurane and propafol 2-4 mg/kg/hr) and early extubation (1 to 6 hours post-op). Continuous ST analysis was performed with pre-op baseline to 48 hrs postop. CK and CK-MB were measured at 6, 12, 24, 36, and 48 hrs after X-clamp release. Arterial and venous blood gases were measured at 240 mins after extubation. Respiratory patterns and shunt fraction (Qs/Qt) were monitored for 24 hours after extubation. Unless indicated data are expressed as mean ± S.D. and were compared by Student's t-test.
Data from 784 patients undergoing CAB or valve procedures were also examined. ICU length of stay was reduced from 2.5±4.7 days to 1.43±0.9 days (p<0.0001) and hospital stay was reduced from 10.6±7.5 days to 8.3±4.2 days (p<0.0001). Conclusion: These results indicate that early extubation after elective CAB is safe and reduces the length of ICU and hospital stay.
*By invitation 46. ANTI-ISCHEMIC AND ANTI-ARRHYTHMIC PROTECTION BY PERIOPERATIVE INFUSION OF NIFEDIPINE AND ETOPROLOL IN PATIENTS UNDERGOING ELECTIVE AORTOCORONARY BYPASS SURGERY Bruno K. Podesser, M.D.*, Severin S. Schwarzacher, M.D.*, Werner Zwolfer, M.D.*, Friedrich Peschl, M.D.*, Thomas Binder, M.D.*, Ernst Wolner, M.D. and Rainald Seitelberger, M.D.* Vienna, Austria
A randomised study was performed on 70 patients undergoing elective coronary bypass procedure to examine whether the combined perioperative 24-hour infusion of nifedipine (10 ug/kg/h) and metopropol (12 ug/kg/h) reduces the incidence of perioperative myocardial ischemia and arrhythmias (group NM, n=34). The control group (group N, n=36) received nifedipine only. Repeated assessments of serum enzyme levels (CK, CK-MB) and 12-lead-ECG together with a 3-channel Holier monitoring over 48h were used to classify perioperative myocardial ischemia (transient ischemic event, myocardial infarction) and supraventricular and ventricular arrhythmias. The two groups did not differ with respect to their demographic data, extracorporeal circulation, aortic cross-clamping time, or number of distal anastomosis. No perioperative myocardial infarction in either group was detected. However, a significantly lower incidence of transient ischemic events was observed in the NM group as compared to the N group (3% versus 11%; p<0.05). In addition, there was a tendency towards lower CK-MB-levels and peak-values of CK- and CK-MB-enzymes in the NM group. With regard to perioperative dysrhythmias, there was a significantly lower incidence of sinus tachycardia (9%) and atrial flutter/fibrillation (6%) in the NM group as compared to the N group (33% and 27%, p<0.05). In addition, postoperative heart rate was lower in the NM group starting from the 6th hour after opening the aortic cross-clamp. In conclusion, the combined perioperative infusion of nifedipine and metoprolol is superior in preventing perioperative myocardial ischemia and decreasing the incidence of supraventricular arrhythmias as compared to a single-drug regimen with nifedipine.
*By invitation 47. TRANSPLANT CANDIDATES' CLINICAL STATUS RATHER THAN RIGHT VENTRICULAR FUNCTION DEFINES NEED FOR UNIVENTRICULAR VS. BIVENTRICULAR SUPPORT Robert L. Kormos, M.D, Si M. Pham, M.D.*, Thomas A. Gasior, M.D.*, Srinivas Murali, M.D.*, Brack G. Rattier, M.D., Ph.D.* and Hartley P. Griffith, M.D. Pittsburgh, Pennsylvania
We have studied our experience since 1988 in 31 patients who required a mechanical circulatory bridge to transplantation who also had biventricular failure (mean RV ejection fraction [RVEF] = 12%) to better define the need for biventricular or total artificial heart support vs univentricular support (LVAS). Clinical factors including preoperative inotropic need, fever without detectable infection, radiographic diffuse pulmonary edema, postoperative blood transfusion and RV thickness were compared with hemodynamic parameters including cardiac index, RVEF, CVP, mean PAP, and total pulmonary resistance for their ability to predict need for mechanical or high dose inotropic support for the RV. Patients were grouped as to the need for RV support following LVAS implantation: None (I)=14, inotropic drugs (II)=7, and RV mechanical support (III)=10. There were no differences in preimplant hemodynamic variables. Groups II and III had a significantly lower mixed venous oxygen saturation (39.2% vs 52.4% in Group I; p<0.001), a greater level of inotropic need (p<0.02), greater impairment of mental status, and a lower ratio of RVEF to inotropic need (0.37 vs 0.56 for Group I; p<0.02) before LVAS implantation. A significant discriminator between Groups II and III was the presence of a fever without infection within 10 days of LVAS implant (14% in Group II vs 80% in Group III). Group III had more patients with preimplant pulmonary edema on chest radiograph and a greater requirement for postoperative blood transfusion (6 units cells in Group II vs 38 in Group III). RV thickness at LVAS explant was 0.87 cm in Group III vs. 44 cm in Group II (p<0.05). Transplantation rates after bridging were 100% in Group I, 71 % in Group II and 50% in Group III. Clinical factors which reflect preimplant degree of illness and perioperative factors which result in impairment of pulmonary blood flow or reduced perfusion of the right ventricle after LVAS implantation are now felt to be more predictive of the need for additional RV support than preimplant measures of RV function or hemodynamics.
12:10pm ADJOURN
*By invitation 9:30 am SIMULTANEOUS SCIENTIFIC SESSION E GENERAL THORACIC SURGERY Republic Ballroom, Sheraton Boston Hotel
Moderators: Victor F. Trastek, M.D. Martin F. McKneally, M.D.
48. RESULTS AND PROGNOSTIC FACTORS IN RESECTIONS OF PRIMARY TRACHEAL TUMORSJ.F. Regnard, M.D.*, P. Fourquier, M.D.* and Ph.Levasseur, M.D.* Paris, France Sponsored by: Peter C. Pairolero, M.D., Rochester Minnesota
From 1970 to 1993, 208 patients with primary tracheal tumors were evaluated in a multicentric retrospective study including 26 centers. Ninety-four patients had a squamous cell carcinoma of the trachea, 4 had adeno-carcinoma, 65 had adenoid cystic carcinoma and 45 patients, miscellaneous tumors. The following resections were performed: tracheal resection with primary anastomosis, 146; partial tracheal resection, 19; carinal resection, 24; and tracheo-laryngeal resection, 19. In average, the length of the resected specimen was 38.5 mm (10-60). Postoperative complications occurred in 41% and postoperative mortality was 10.5%. Postoperative morbidity and mortality were statistically correlated (PO.05) to the length of the resection, to the need of a laryngeal release, to the type of resection and to the histologic type. Follow-up was complete for all but 10 patients with a mean follow-up of 5 years. Fifty-nine percent of the patients with tracheal cancers and 43% of the patients with adenoid cystic carcinomas had postoperative radiotherapy. In complete resection, the 5 and 10-year actuarial survival were respectively 55% and 30% in tracheal cancers, 82% and 25% in adenoid cystic carcinomas. Long-term survival was altered by the occurrence of second primary cancer (ORL, lung) in the group of patients with tracheal cancers and by late metastases in adenoid cystic carcinomas. Postoperative radiotherapy did not improve survival in the group of patients with tracheal cancer when the resection was complete, even if nodes were involved. However, in case of incomplete resection, postoperative radiotherapy did not improve survival in the group of patients with tracheal cancer when the resection was complete, even if nodes were involved. However, in case of incomplete resection, postoperative radiotherapy improved survival (P<0.02). For adenoid cystic carcinomas, the actuarial survival seemed better in complete resection than in incomplete resection but the difference was not statistically significant (PO.20). Postoperative radiotherapy did not improve survival in adenoid cystic carcinoma, even in incomplete resection. Surgery is the treatment of choice of primary tracheal tumors.
*By invitation 49. THE IMPORTANCE OF SURGICAL STAGING IN THE TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA Valerie W. Rusch, M.D. and Ennapadam Venkatraman, Ph.D.* New York, New York
Progress in the therapy of malignant pleural mesothelioma (MPM) is hindered by the lack of an adequate staging system and controversy about prognostic factors. This personal surgical series was analyzed to determine the value of a new TNM staging system proposed by the International Mesothelioma Interest Group (IMIG), and to examine factors that could affect the design of future clinical trials. Methods: Thoracotomy was done in previously untreated patients (pts) if CT scans showed technically resectable tumor confined to one hemitnorax. Pleurectomy/decortication (P/D) was used in pts with minimal visceral pleural tumor, extrapleural pneumonectomy (EPP) in pts with more locally advanced disease. Complete resection was defined as no gross residual tumor. Adjuvant therapy was given as required by serial clinical trials. Pts were followed by chest and abdomen CT scans every 3 months after death. Prognostic factors were examined by log rank and Cox regression analyses. Results: From 10/83 to 7/94 there were 131 consecutive thoracotomies, 101 resections, 72 complete. EPP:P/D=50:51. Men:women=108:23. Median age=63 years (range=32-80). Operative mortality 5/131 pts (3.8%), 3/50 EPP (6%). Most frequent morbidity: atrial arrhythmias, 14/131 pts (11%), 11/50 EPP (22%). 95/131 tumors were epithelial. 51/89 pts (57%) having node dissections had (+) nodes, 45 (50%) N2.
By univariate analysis, type of resection (EPP vs P/D), T and N status, stage, histology and adjuvant therapy but not gender or age, significantly affected survival. Type of resection, stage and histology were significant in a multivariate analysis. 99 known sites of relapse occurred in 60 pts. In EPP pts these were local in 5/30 (16%) and distant in 32/48 (66%) instances. Conclusions: (1) N2 nodal disease is more frequent than previously reported; (2) The prognostic importance of histology is confirmed; (3) Both T and N status significantly influence outcome, and the IMIG staging system successfully identifies poor prognosis pts; (4) despite more locally advanced disease in most EPP pts, it provided better local control than P/D but failed to improve survival because of distant metastatic disease. Contrary to past practice, future clinical trials should stratify for histology, must control for TNM stage and must consider the impact of type of surgical resection on the pattern of relapse.
*By invitation 50. ASSESSMENT OF PREOPERATIVE ACCELERATED RADIOTHERAPY AND CHEMOTHERAPY IN STAGE IIIA NON-SMALL CELL LUNG CANCER (NSCLC) Douglas J. Mathisen, M.D., Noah Choi, M.D.*, Robert Carey, M.D.*, John C. Wain, M.D.*, Alan Hilgenberg, M.D., William Daly, M.D.*, Ashby Moncure, M.D.*, Cameron Wright, M.D.*, Thomas Lynch, M.D.* and Hermes Grillo, M.D. Boston, Massachusetts
Mediastinoscopy proven N2 disease in non-small cell lung cancer carries a poor prognosis (less than 10%) with surgery and radiation therapy. Neoadjuvant therapy offers the promise of improved results. The optimum regimen has yet to be found. We have utilized preoperative accelerated radiotherapy (RT) (42Gy in 2 sessions - 21Gy in 1.5Gy bid, 5 days per week in 2 5-day-intervals) cisplatin 100mg/m2 days 1 and 29, Velban 3mg/m2 days 1 and 3 and 29 and 31, and 5-FU 30mg/kg/day by continuous infusion days 1 to 3 and 29 to 31. Surgery was performed on day 56. Postoperative therapy consisted of 1 cycle of chemotherapy and 15 to 18Gy of accelerated RT. The patient age ranged from 38 to 77 years, and male to female ratio was 2.3:1. The tumor stages included T1N2MO 5, T2N2MO 28, T3N2MO 3, and T4N2MO 2 pts. Histologic types consisted of squamous cell carcinoma 14, adenocarcinoma 13, and large cell carcinoma 8. Major clinical response (> 50% reduction in tumor volume) was obtained in 92% (35/38) of pts. Curative resection was performed in 92% (35/38) of pts with their resection margins being negative in 82% (31/38) and microscopically positive in 11% (4/38). Tumor down staging was achieved in 70% of pts. Two patients were unable to undergo surgery because of distant metastasis. Moderate dysphagia and leukopenia were noted in 50% of patients. The mortality of this regimen was 8% (3/38): pulmonary embolism during induction CT+RT, 1 and postoperative death, 2. The median survival time was 24M and their survival rates by Kaplan-Meier method were 50%, 43% and 43% at 2, 3, and 5 years, respectively. Control of local-regional tumor was obtained in 89% (34/38) of patients. This regimen offers superior resectability rates and improved survival at 2, 3, and 5 years.
*By invitation 51. MANAGEMENT OF UNILATERAL VOCAL CORD PARALYSIS IN INTRATHORACIC MALIGNANCY Muhammed K. Ali, M.D.*, Dennis H. Kraus, M.D.*, Robert J. Ginsberg, M.D., Christopher J. Hughes, M.D.*, Valerie W. Rusch, M.D, Michael E. Hurt, M.D. and Patricia M. McCormack, M.D. New York, New York
Patients with unilateral vocal cord paralysis (UVCP) from intrathoracic malignancies can suffer from significant dysfunction of speech, swallowing, ventilation, and the ability to cough effectively unless the non-paralysed cord can accommodate. In patients with already compromised pulmonary function, aspiration can be a life threatening event. Acute post-operative UVCP can also be life threatening, the paralyzed vocal cord interfering with effective cough, endogenous PEEP, and the ability of the patients to protect the airway from acute aspiration events. In symptomatic patients medialization of the affected vocal cord allows effective glottal closure and immediately improves dysfunction. Materials and Methods: Fifty-seven patients with intrathoracic malignancies required surgical correction of UVCP between 1991 and 1994. Primary pathology included lung cancer (46), esophageal cancer (8), and miscellaneous tumors (3). Paralysis was due to invasion of the vagus/recurrent laryngeal nerve in 32 and as result of the surgical procedure in 25. There were 46 left-sided paralyses and 11 right-sided. Presenting symptoms included hoarseness (56), dyspnea (18), aspiration (24), weight loss (16), and pneumonia (12). Surgical procedure consisted of silastic medialization (44), temporary Gelfoam injection (5), and Teflon injection (8) to medialize the affected cord. In 9 patients, the surgery was performed in the acute post-operative setting, the others being done electively (48). Results: Of the presenting symptoms, the following table summarizes the results:
Overall success of the intervention was 52 of 57 patients (91%). All 9 patients treated in the acute setting were immediately improved. Minor complications including transient airway compromise (3), tracheostomy (1), tooth fracture (1), hematoma (1), foreign body sensation (2), and transient laryngeal edema (6), occurred in 23% of patients. Currently, 33 patients are alive, only one of whom had an unsuccessful long-term result. Conclusions: Surgical management of UVCP in patients with intra-thoracic malignancies prevents life threatening pulmonary complications in the acute post-operative setting. In chronic situations it provides patients with improved speech, swallowing, and pulmonary function, resulting in improved quality of life, including patients not cured of disease.
10:50 am INTERMISSION
*By invitation 11:10 am SIMULTANEOUS SCIENTIFIC SESSION E GENERAL THORACIC SURGERY Republic Ballroom, Sheraton Boston Hotel
Moderators: Victor F. Trastek, M.D. Martin F. McKneally, M.D.
52. IMPROVED AIRWAY HEALING AFTER LUNG TRANSPLANTATION - AN ANALYSIS OF 348 BRONCHIAL ANASTOMOSES Hiroshi Date, M.D.*, Elbert P. Trulock, M.D.*, Joseph Arcidi, M.D.*, Sudhir Sundaresan, M.D., Joel D. Cooper, M.D. and G. Alexander Patterson, M.D. St. Louis, Missouri
Although less commonly encountered than in the early days of lung transplantation, airway complications following lung transplantation remain a significant cause of morbidity. We evaluated various clinical factors to identify predictors of airway complication following lung transplantation. Two hundred and twenty-nine consecutive single (SLT, n=110) and bilateral (BLT, n=119) lung transplants were performed in our center between September 1988 and August 1994. These 348 bronchial anastomoses were retrospectively analyzed. Airway complication requiring clinical intervention occurred in 33 anastomoses (9.5%), 29 patients (12.8%). Conservative therapy such as dilation, stent and/or laser resulted in excellent improvement in 22 patients. There were five deaths (2.2%) attributable to airway complications. Recipient factors (age, sex, diagnosis, preoperative steroid use), donor factors (age, sex, Pa02, sputum gram stain, ischemic time), operation factors (side of transplant, use of cardiopulmonary bypass, type of anastomosis [end-to-end vs. telescope], type of wrapping [omentum vs. peribronchial tissue vs. pericardial fat], suture material) and postoperative factors (Pa02, mean PAP, method of steroid administration, biopsy proved rejection, CMV status, CMV pneumonitis) were not predictors of airway complication. Mattress suture technique (21/153=13.7%) was associated with more frequent complications than was simple interrrupted (8/122=6.6%) or figure of eight suture (4/73=5.5%), (p=0.02). Complication occurred more often in SLT (16/110=14.4%) than in BLT (17/238=7.1%, p=0.02) Patients who subsequently developed airway complications required longer mechnical ventilation than those without airway complications (12.9 ± 18.4 days vs. 5.5 ± 20.5 days, p<0.01). The chronologic incidence of airway complications was evaluated by separating the 229 transplants into three groups: Phase I, the first 77 transplants; Phase II, the next 76 transplants; and Phase III, the last 76 transplants. The airway complication rate per anastomosis was significantly lower in Phase III (5/126=4.0%) than in Phase I (12/110=10.9%) and Phase II (16/112=14.3%) (pO.Ol). All parameters noted above were similar for the three phases. However, immunosuppression and rejection monitoring was different in Phase III. Early low dose corticosteroid administration, induction cytolytic therapy with antithymocyte globulin, and rejection therapy based on histologic (transbronchial lung biopsy) rather than clinical diagnosis were routinely employed in Phase III. Mattress suture technique, SLT and prolonged mechanical ventilation are predictors of airway complication. The majority of airway complications are successfully treated and are rarely fatal. The recent reduction in incidence of airway complications is likely due to better maintenance immunsuppression and rejection surveillance.
*By invitation 53. UNILATERAL THORACOSCOPIC SURGICAL APPROACH FOR DIFFUSE BULLOUS EMPHYSEMA Robert J. Keenan, M.D.*, Rodney J. Landreneau, M.D., Frank C. Sciurba, M.D.*, Peter F. Person, M.D.*, Lynda S. Fetterman, M.D.*, Claudia M. Bowers, B.S.N.* and Hartley P. Griffith, M.D. Pittsburgh, Pennsylvania
We are currently evaluating the use of a lateral thoracoscopic approach to improve lung function in patients with diffuse bullous emphysema. Patients entered into the study include those with end-stage emphysema recalcitrant to medical therapy and with disabling dyspnea based on a Baseline Dyspnea Index. Preoperative testing included pulmonary function testing with exercise oxygen consumption studies, chest x-ray, CT scan, quantitative ventilation-perfusion scan, transthoracic echocardiography and six-minute walk. Forty-two consecutive patients (29 males, 13 females) with a mean age of 63.4 years (range 36-78 years) underwent surgery for type III or IV bullous emphysema with 81% requiring preoperative supplemental oxygen. Operative side was determined by pre-operative imaging (right 56%, left 44%). Operative procedure was laser ablation in 10 pts, stapler resection in 11 pts and combined laser/stapler in 21 pts. Chest tube duration averaged 10 days (range 3-50 days) with median length of hospital stay being 13 days (range 6-99 days). Four pts (9.5%) required conversion to open thoracotomy to control air leaks and 5 pts (12%) were treated for pneumonia; 1 pt suffered a significant postoperative stroke. Three pts (7%) died from cardiopulmonary failure. Among the 39 survivors, 31 were discharged within 30 days and 28 returned for evaluation at 3 weeks. Seven pts experienced prolonged hospitalization due to cardiopulmonary problems and have not undergone postoperative testing. Significant (p<0.005) improvements were seen in FVC (2.7L post vs. 2.31L pre) and FEVj (1.05L post vs. 0.79L pre) with 18/28 pts (64%) showing a >20% improvement and only 1 pt experiencing a decline of >10%. At the time of this analysis, 9 pts had undergone their procedures greater than 3 months previously. Significant (p<0.05) increases were seen in postoperative FEV] (average improvement of 74.8%) and DLCO (average increase of 84%); pOj and pCO2 did not change. The significance of hypercarbia and/or reduced DLCO (Burrows predicted equation corrected for Hgb) as predictors of poor outcome was examined. Six/ten pts (60%) with poor outcome (death or hospitalization>30 days) demonstrated hypercarbia (pCO2 ^ 50 torr) or reduced DLCO (< 25%) compared to only 5/28 (17.9%) of the remaining pts (p=0.0193). The combination of hypercarbia and reduced DLCO was significantly more frequent (p=0.0026) in pts with a poor outcome and was 86% specific (5/6 pts) in identifying serious postoperative risk. We conclude that the lateral thoracoscopic surgical approach to diffuse bullous emphysema offers significant improvement in pulmonary function for many pts but that pts with a combination of hypercarbia and reduced DLCO should not be offered this procedure because of significant perioperative risk.
*By invitation 54. SURGICAL TREATMENT OF DIFFUSE EMPHYSEMA. A RANDOMIZED, PROSPECTIVE TRIAL OF LASER BULLECTOMY VERSUS LUNG REDUCTION SURGERY WITH STAPLES AND BOVINE PERICARDIUM Robert J. McKenna, Jr., M.D.*, Matthew Brenner, M.D.*, Michael J. Mullin, M.D.*, Narindar Singh, M.D.* and Michael Berns, Ph.D.* Los Angeles, Orange, Tustin and Irvine, California Sponsored by: Quentin R. Stiles, M.D., Los Angeles, California
Both the efficacy and the optimal method for surgical treatment of diffuse emphysema are controversial. This is an interim analysis of a randomized, prospective study of laser bullectomy versus lung reduction surgery with staples and the bovine pericardial patch. All patients had diffuse emphysema with no bulla greater than 2 cm in size, and underwent the surgical treatment of one lung by thoracoscopy. 21 patients underwent laser bullectomy with a 10-watt contact tip YAG laser (average 24, 200 Joules, range 16.5K-29.1K) and 23 patients underwent lung reduction surgery (average 8 firings of the endoscopic 60 mm stapler). The average length of stay was 11.4 days for laser and 12.4 days for staples. There was no mortality for the laser and 1 mortality (2%) for the staple group due to contralateral tension pneumothrorax postoperatively. Complications included prolonged air leak at least 10 days in 7 laser cases (33%) and 8 staple cases (35%). The average hospital charge was $44, 482 for laser and $57, 858 for staples. Multivariate analysis showed prolonged length of stay was related to adhesions found at surgery and the use of the staples. Major clinical improvement (defined as significantly increased activity, decreased pulmonary medicines, termination of prednisone, and the termination or significant reduction of oxygen therapy) was seen in 11 laser cases (52%) and 13 staple cases (57%). Some clinical improvement (increased activity with decreased oxygen) was seen in 6 laser cases (29%) and 4 staple cases (17%), and no improvement in 4 laser cases (19%) and 5 staple cases (22%). Poor outcome was related to poor diffusion capacity (<10%) and the presence of emphysema worse in the lower lobe than in the upper lobe.
12:10 pm ADJOURN
*By invitation 9:30 am SIMULTANEOUS SCIENTIFIC SESSION F CONGENITAL HEART DISEASE Independence Ballroom, Sheraton Boston Hotel
Moderators: Edward L. Bove, M.D. John L. Myers, M.D.
55. SURGICAL APPROACHES FOR DOUBLE OUTLET RIGHT VENTRICLE OR TRANSPOSITION OF THE GREAT ARTERIES ASSOCIATED TO STRADDLING ATRIOVENTRICULAR VALVES. Alain Serraf, M.D.*, Tomohiro Nakamura, M.D.*, Francois Lacour-Gayet, M.D.*, Dominique Piot, M.D.*, Jacqueline Bruniaux, M.D.*, Anita Touclot, M.D.*, Miguel SousaUva, M.D.*, Lucile Houyel, M.D.* and Claude Planche, M.D. Le Plessis Robinson, France
The surgical management of pts with DORV or TGA and straddling AV valves remains controversial. Biventricular repair (BVR) has theoretical advantages because it establishes normal anatomy and physiology; however, in some instances it seems to carry a too high operative risk and a univentricular heart repair (UVH) is preferred. Since 1984, 34 patients with DORV (15) or TGA (19) with isolated straddling tricuspid valve (10), isolated straddling mitral valve (8), both mitral and tricuspid valves straddling (2) or abnormal insertion of tricuspid (10) or mitral (2) chordae in the left ventricular outlet precluding an adequate tunnel construction were operated on. Straddling were categorized according to the location of the papillary muscle (PM) insertion in the opposite ventricular chamber: type A, on the edge of the VSD (10); type B, on the opposite side of the ventricular septum away from the edge of the VSD (7); type C, on the free wall of the opposite ventricular chamber (3). Abnormal chordal inertion were classified according to the location of their attachments around the edges of the VSD. There were 3 types of chordal distribution: on the aortic conus, on the pulmonary conus crossing the VSD, or around the VSD closing it like a curtain. All but 1 patient had 2 adequately sized ventricles. Sixteen pts underwent palliation. Median age at definitive surgery was 6.5 months (range: 1-130). Thirty pts underwent a BVR, whereas 4 had UVH repair. BVR was carried out by means of arterial switch operation in 18 and tunnel construction from the left ventricle to the aorta in 12. In isolated straddlings type A and B, closure of the VSD was performed by adjusting the septal patch on the ventricular side above the straddled PM. In type C, the patch was oversewn over the PM by applying it on the septum. In double straddling, the ventricular septum was incised between the 2 PM and an ellipsoid patch was used to reconstruct the septal defect rejecting each subvalvar apparatus in its own ventricular chamber. When insertion of abnormal chordae in the left outflow tract was on the aortic conus or on the pulmonary conus, they were tailored in order to make a flap leaving an unobstructed left ventricular outflow tract. In 2 pts, the subvalvar apparatus was resected and reattached to the patch. Curtain-like chordae were a contraindication to BVR in DORV but not in TGA. There were 4 early and 1 late deaths, all occurring in the BVR group. Death was due to myocardial ischemia (1), to RV hypoplasia (1), to pulmanary hypertension (1) and to residual subaortic stenosis (1). Two pts demonstrated moderate to severe postoperative AV valve incompetence, once due to a cleft in the mitral valve. Three pts were reoperated on for SAS (1), PS (1) and MR (1). Mean follow-up of 27.4 ± 19.3 months was achieved in all survivors. All but one (UVH repair) were in NYHA class 1, without AV valves incompetence. Five years actuarial survival was 85.3 ± 3%. It is concluded that straddling or abnormal distribution of chordae tendinae of the AV valves do not preclude BVR in DORV or TGA provided that ventricular sizes are adequate. Curtain like abnormal tricuspid chordae remain a contra indication to BVR in DORV.
1993-94 Graham Fellow
*By invitation 56. AORTICOVENTRICULOPLASTY USING PULMONARY AUTOGRAFT: THE "ROSS-KONNO" PROCEDURE V. Mohan Reddy, M.D.*, J.A.M. vanSon, M.D.*, Hiranya A. Rajasinghe, M.D.* and Frank L. Hanley, M.D.* San Francisco, California Sponsored by: Benson B. Roe, San Francisco, California
Background: For patients with hypoplastic aortic annulus and severe diffuse subaortic stenosis various aorticoventriculoplasty procedures (e.g., Konno) have been associated with less than optimal results. Younger patients often require reoperation for valve replacement. Pulmonary autograft is being increasingly used for aortic valve replacement. Long term follow up shows that the pulmonary autograft functions well as the systemic arterial (neo-aortic) valve. Methods and results: We have extended the application of pulmonary autograft to patients with complex left ventricular outflow tract (LVOT) obstruction. Since July 1992 through October 1994, 7 patients (age: 3 weeks to 19 years) have undergone plumonary autograft replacement in association with aorticoventriculplasty (Ross-Konno procedure). The diagnoses were aortic stenosis (AS) and insufficiency with subaortic stenosis (n=4), Shone's complex (n=2), and interrupted aortic arch with subAS (n=1). On average each patient underwent 2.2 previous operations including a previous Konno procedure in one patient. The aortic valve was replaced with a pulmonary autograft conduit. The subannular left ventricular outflow tract was enlarged with a dacron patch in 4 patients and with right ventricular infundibular muscular patch in 3 patients. At the time of harvesting the pulmonary autograft, a portion of the right ventricular infundibular wall was included. This infundibular muscular patch was used for enlarging the LVOT. With this procedure the use of prosthetic valve as well as prosthetic patch is avoided. Intraoperative transesophageal echocardiographic assessment revealed no AI. One patient had a residual LVOT gradient of 15 mmHg. Significant complications were cardiac tamponade from bleeding (1 pt) and complete heart block requiring a permanent pacemaker (1 pt). Follow up ranged from 2 months to 12 months. There have been no early or late deaths. Aortic valve function and LVOT was evaluted by echocardiography. Three patients had trivial AI and none of the patients had LVOT obstruction. Conclusions: Initial experience suggests that aorticoventriculoplasty using pulmonary autograft is an excellent alternative for patients with complex LVOT obstruction. Since pulmonary autograft has been shown to grow, future reoperations may not be required in young patients.
*By invitation 57. RESULTS OF AN AUTOLOGOUS TISSUE RECONSTRUCTION FOR REPLACEMENT OF OBSTRUCTED EXTRACARDIAC CONDUITS Robert J. Cerfolio, M.D.*, Gordon K. Danielson, M.D., Francisco J. Puga, M.D, Hartzell V. Schaff, M.D. and Carole A. Warnes, M.D.* Rochester, Minnesota
Between May 1983 and August 1, 1994, 42 patients having replacement of an obstructed pulmonary ventricle-to-pulmonary artery conduit underwent an autologous tissue reconstruction in which a prosthetic roof was placed over the fibrous tissue bed of the explanted conduit. The roof was constructed with xenograft pericardium (most recently) (n=35), homograft dura mater (n=5), or dacron (n=2). The explanted conduits were: Hancock (n=28), Tascon (n=6), dacron tube (n=3), homograft (n=3), and others (n=2). There were 26 males and 16 females, and the ages ranged from 5 to 34 years (median=16). Diagnoses included transposition of the great arteries (n=15), pulmonary atresia (n=11), truncus arteriosus (n=8), tetralogy of Fallot (n=4), double outlet right ventricle (n=3), and corrected transposition (n=1). The original conduit sizes ranged from 8 to 25 mm (median=22). Preoperative peak systolic gradients by cardiac catheterization or echocardiography ranged from 40 to 140 mmHg (median=79). Valves were placed in 13 reconstructions (2 were mechanical); no valve was inserted in the others. It was possible to place large valves in the autologous tissue reconstructions, ranging from 23 to 29 mm (median=25). Thirty-two concomitant procedures were performed in 25 patients which included pulmonary angioplasty (n=11), closure of residual VSD (n=9), tricuspid annuloplasty (n=5), closure of residual ASD (n=2), aortic valve replacement (n=2), and others (n=3). Cardiopulmonary bypass time ranged from 34 to 223 minutes (median=84) and the aortic cross-clamp time ranged from 0 (in 28 patients) to 109 minutes (median=0). Five patients required partial sternal resection to prevent conduit compression. There was no early mortality. The total hospital stay ranged from 6 to 23 days (median=9). Post repair peak systolic gradients from pulmonary ventricle to pulmonary artery ranged from 0 to 36 mmHg (median=13). Follow-up was complete in all patients and ranged from 5 months to 10.6 years (median-6.1 years). There was no late mortality. Three patients with non-valved conduits required reoperation for aortic (truncal) valve insufficiency, tricuspid valve insufficiency, and defibrillator implantation, respectively. None of the autologous tissue conduits developed an obstructive peel or valve obstruction. At 8 years, the acturial freedom from reoperation for conduit obstruction was 100%, and freedom from reoperation for any cause was 97%. This technique simplified conduit replacement, allows for a generous-sized outflow tract, has a low risk, and yields late results which appear superior to those of cryopreserved homografts or other types of extracardiac conduits.
*By invitation 58. UNIVENTRICULAR REPAIR - EARLY AND MIDTERM RESULTS Rajeesh Sharma, M.Ch.*, Krishna S. Iyer, M.Ch.*, Balram Airan, M.Ch.*, Kamales Saha, M.S.*, Bhabha Das, M.Ch.*, Anil Bhan, M.Ch.*, I. M. Rao, M.Ch.* and P. Venugopal, M.Ch.* New Delhi, India Sponsored by: Richard A. Jones, M.D., Boston, Massachusetts
Two hundred and two (62 tricuspid atresia and 140 non-tricuspid atresia) patients underwent univentricular repair at our unit, from January 1990 to September 1994. 182 of these patients had nonfenestrated while 20 had fenes-trated interatrial baffles. Early mortality was 15.9% (29/182) in the nonfenestrated and 5% (1/20) in the fenestrated group. Follow-up period ranged from 2 months to 58 months. There were 7 late deaths and 5 patients were lost to follow-up. Out of 160 patients, who have been evaluated in the out-patient department in the last 3 months, 142 (88.75%) were off all medications and were in functional class-I. Risk factors analyzed for early mortality and significant effusion were: age, preoperative diagnosis, type of Fontan modification, duration of cardiopulmonary bypass (CPB) and aortic cross clamp, pulmonary artery size, associated pulmonary arterioplasty, takedown of systemic to pulmonary artery shunt and pulmonary artery debanding along with Fontan operation. CPB time exceeding 120 minutes was associated with higher early mortality (12/47 vs 18/155 p value = 0.0187). CPB time exceeding 120 minutes (p value = 0.0456) and aortic cross clamp time exceeding 60 minutes (p value = 0.0278) were associated with significant effusion postoperatively. Other factors were not associated with any significantly increased risk for early mortality or postoperative effusions. Fenestration of interatrial baffle appeared to decrease early mortality although the numbers are too small to be statistically significant. There was no difference in the incidence of effusions in the fenestrated and non-fenestrated group.
10:50 am INTERMISSION
*By invitation 11:10 am SIMULTANEOUS SCIENTIFIC SESSION F CONGENITAL HEART DISEASE Independence Ballroom, Sheraton Boston Hotel
Moderators: Edward L. Bove, M.D. John L. Myers, M.D.
59. SUBAORTIC STENOSIS IN THE SPECTRUM OF ATRIOVENTRICULAR SEPTAL DEFECTS: SOLUTIONS MAY BE COMPLEX AND PALLIATIVE Glen S. Van Arsdell, M.D.*, William G. Williams, M.D, George A. Trusler, M.D, John G. Coles, M.D, Ivan M. Rebeyka, M.D.* and Robert M. Freedom, M.D.* Toronto, Ontario, Canada
From November 1982 through September 1994 seventeen children with atrioventricular spetal defects (AVSD's) underwent 24 operations for subaortic stenosis. Age at initial subaortic resection was 17 months to 13 years (6.2±3.7). Specific diagnosis included 9 transitional AVSD's, 5 septum primum defects, 1 complete AVSD, 1 inlet VSD with malattached chordae, and 1 complete AVSD with tetralogy of Fallot. Eight patients had Down's syndrome. All but 2 operations were performed in this institution. Indications for a subaortic procedure were subaortic stenosis at initial operation (2), severe subaortic stenosis (12), or progressively worsening subaortic stenosis (3). Two patients had resection at initial repair treated by fibromyectomy (1) and fibrous membrane resection with minor papillary muscle excision (1). Fifteen patients had sub-aortic resection following AVSD repair. Average time to resection was 4.7y ± 3.4. Pathology included isolated fibromuscular stenosis (8), combined fibromuscular stenosis and mitral valve abnormalities (5), fibromuscular stenosis and papillary muscle obstruction (1), and tunnel stenosis (1). Fourteen of these patients had fibromyectomy and 1 an apicoaortic conduit. Additionally, there was papillary muscle thinning, mitral valve replacement, pericardial patch augmentation of the aortic mitral continuity, and resection of accessory chordae and tissue of the left AV valve. Six patients (35%) required 8 reoperations for previously resected sub-aortic stenosis: 2 fibromyectomies, 2 radical fibromyectomies with VSD creation and infundibular patch, 1 fibromyectomy with papillary muscle thinning, 1 conduit replacement, and 9 years following the initial conduit, successful conversion to antegrade flow by radical subaortic resection, removal of accessory chordae and tissue of the left AV valve and conduit excision. Follow-up ranges from 10 days to 9 years (median 3.2y). There were no major cardiac morbidities and no mortalities. Gradients are not significant in 10 patients (0-10 mmHg), mild in 5 patients (11-20 mmHg), and moderate in 2 patients (21-50 mmHg). The treatment of subaortic stenosis associated with AVC defects can be complex and only palliative. Aggressive resections at the initial presentation should be considered.
*By invitation 60. SURGICAL MANAGEMENT OF THE LEFT ATRIOVENTRICULAR VALVE IN COMPLETE ATRIOVENTRICULAR SEPTAL DEFECTS: A TWENTY-YEAR EXPERIENCE Ko Bando, M.D.*, Mark W. Turrentine, M.D.*, Kyung Sun, M.D.*, Thomas G. Sharp, M.D.*, Andrew P. Miller, B.S.*, Robert S. Binford, M.D.*, Kenneth A. Kesler, M.D.*, Gregory J. Ensing, M.D.*, Timothy M. Cordes, M.D.*, Donald A. Girod, M.D.*, Roger A. Hurwitz, M.D.*, Randall L. Caldwell, M.D.*, Joyce Hubbard, M.D.*, Harold King, M.D. and John W. Brown, M.D. Indianapolis, Indiana
Background and Purpose: Creation of a competent left atrioventricular (AV) valve is a cornerstone in surgical repair of complete AV septal defects. The purpose of this study was to identify risk factors for mortality and failure of left AV valve repair and to determine the impact of "cleft" closure on postoperative AV valve function. Method: Two hundred patients operated between January 1974 and October 1994 were included in this study. Using univariate and multiple regression analysis, risk of early and late mortality and need for reoperation for postoperative left AV valve regurgitation was estimated. Results: Overall early mortality was 8% (16/200 patients). Operative mortality decreased significantly over the period of the study from 19% (4/21) before 1980 to 3% (2/64) after 1990 (p=0.03). By multiple logistic regression, risk factors for early death included double orifice left AV valve (p<0.001) and post-operative pulmonary hypertensive crisis (/><0.001). At a mean follow-up of 94 months, late survival was 99% (182/184 operative survivors); all are NYHA class I or II. Preoperative AV valve regurgitation was assessed in 198 patients by angiography or echocardiography and was absent or mild in 103 (52%), moderate in 81 (41%), and severe in 16 (8%). Left AV valve "cleft" was closed in 93% (186/200), but left alone when valve leaflet tissue was inadequate and closure of "cleft" might cause significant stenosis. More complex valvuloplasty was required in 4 patients. Reoperation for severe postoperative left AV valve regurgitation was necessary in 8 patients (4%); 6 patients initially did not have closure of "cleft" and 2 patients had "cleft" closure. Six patients had reoperation with annuloplasty and 2 patients required left AV valve replacement. Five patients survived reoperation and are currently NYHA class I or II. On most recent evaluation assessed by angiography or echocardiography (a mean of 59 months after repair), left AV valve regurgitation was absent or mild in 129 of the 138 survivors (93%) examined; none had moderate or severe left AV valve stenosis. Preoperative severe AV valve regurgitation (p<0.001) and double orifice AV valve (p<0.001) predicted reoperation for residual left AV valve regurgitation. Conclusion: These results indicate that complete AV septal defect can be repaired with low mortality and good mid- to long-term results. Routine approximation of the cleft is safe and has a low incidence of reoperation for left AV valve insufficiency.
1991-92 Graham Fellow
*By invitation 61. RESULTS OF NORWOOD OPERATION FOR LESIONS OTHER THAN HYPOPLASTIC LEFT HEART SYNDROME Marshall L. Jacobs, M.D.*, Jack Rychik, M.D.*, John D. Murphy, M.D.*, Susan C. Nicolson, M.D.*, James M. Steven, M.D.* and William I. Norwood, M.D. Philadelphia, Pennsylvania
Norwood's operation provides satisfactory palliation for neonates with hypoplastic left heart syndrome. The dominant physiologic features of hypo-plastic left heart syndrome, ductal dependency of the systemic circulation and parallel pulmonary and systemic circulations, are shared by a multitude of other less common congenital heart malformations. Theoretically, these should be equally amenable to palliation by Norwood's operation. From January 1990 through June 1994, 60 neonates with malformations other than hypoplastic left heart syndrome have undergone initial surgical palliation by Norwood's procedure. Diagnoses include single left ventricle with L-transposition of the great arteries (12), critical aortic stenosis (8), complex double outlet right ventricle (8), interrupted aortic arch with ventricular septal defect and subaortic stenosis (7), ventricular septal defect, subaortic stenosis, and coarctation of the aortia (7), aortic atresia with large ventricular septal defect (6), tricuspid atresia with transposition of the great arteries (6), heterotaxy syndrome with subaortic obstruction (3), and other (3). There were 10 hospital deaths and 50 survivors (83% survival). After the introduction of inspired carbon dioxide into the postoperative management protocol (1991), 42 of 47 patients survived (89% survival). Mortality is independent of diagnosis, and essentially the same as for hypoplastic left heart syndrome. With minor technical modifications, Norwood's operation provides satisfactory initial palliation for the wide variety of malformations characterized by ductal dependency of the systemic circulation, in anticipation of either a Fontan procedure or a biventricular repair.
12:10 pm ADJOURN
*By invitation |
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