Monday Afternoon, April 24, 1995

1:30 pm PLENARY SESSION

Auditorium, Hynes Convention Center

Moderators: Aldo R. Castaneda, M.D.

John A. Waldhausen, M.D.

6. LATE HEMODYNAMIC RESULTS FOLLOWING LEFT VENTRICULAR PATCH REPAIR ASSOCIATED WITH CORONARY GRAFTING IN PATIENTS WITH POST-INFARCTION AKINETIC OR DYSKINETIC LEFT VENTRICULAR ANEURYSM

Vincent Dor, M.D., Michel Sabatier, M.D.*, Francoise Montiglio, M.D.*, Anna Toso, M.D.*, Mauro Maioli, M.D.* and Marisa Di Donate, M.D.*

Monte-Carlo, Monaco and Florence, Italy

Aim of the study: To evaluate hemodynamic, clinical and electrophysio-logic data one year after intervention of left ventricular patch repair (LVR) and associated coronary revascularization in patients (pts) with postinfarction akinetic and dyskinetic LV aneurysm.

Patients: Among 580 pts who underwent this type of surgery since 1984, we report the results obtained in 141 pts (132 men and 9 women, mean age 58±8 yrs) who accepted to be controlled 1 year postoperatively with the same protocol. All these pts had right and left heart catheterization, ventricular and coronary angiography, programmed ventricular stimulation (PVS) unless contraindicated, before, one month and one year after surgery. Site of the aneurysm was anterior in 135 and posterior in 6. Mean delay from first infarction was 36 months (range 1-198). Fifty-three pts had one vessel (V), 55 two V and 33 three V disease. Eleven pts were in NYHA class I, 51 in class II, 54 in class III, and 25 in class IV. Clinical ventricular arrhythmias (VA) were present in 35 pts (25%) and ventricular tachycardia was inducible in 43/94 pts who underwent preop PVS (46%). Indications for surgery were a combination of cardiac insufficiency, angina and VA in the majority of pts. Twenty-one pts were operated in emergency.

Results: All pts had LVR by endoventricular patch plasty with synthetic or autologous patch. Associated procedures included subtotal endocardectomy and cryotherapy in pts with clinical or inducible VT; ventricular septal defect closure in two pts; mitral valve replacement in two and repair in six pts; aortic valve replacement in one pt and repair in another patient. One hundred thirty-five pts (96%) had associated myocardial revascularization (IV in 49 pts, 2 V in 57, 3 V in 27 and 4 V grafts in 2). Internal mammary artery was implanted in 120 pts, almost always on LAD, and was found to be patent after one year in 113 (94%). The mean number of by-pass was 1.89±.86. Mean cardiopulmonary by-pass time was 110±33 min. Twenty-two pts required intraaortic balloon pump preoperatively (10 elective and 11 in emergency). Perioperative complications were cardiac insufficiency requiring inotropic drugs in 20 pts; mechanical assistance in 8 pts; renal failure in 6 pts; bleeding requiring blood transfusion in 11 pts; conduction disturbances requiring temporary pacing in 30 pts.

After 1 year from surgery mean EF significantly increased (from 35±13 to 46±12%, p<.0001); end diastolic and end systolic volume index significantly decreased (from 116±43 to 96±29 and from 76±41 to 54±26 ml/m2, respectively p<.001). Table reports early and late results on the basis of basal value in EF

	EF<30%	30	EF>40%
Base	22±5	37±2	50±7
Early postop	42±10	49±11	57±8
Late postop	41±11	44±11	52±12

All data are significant at two way variance analysis.

Spontaneous VT were significantly reduced (only two pts had documented clinical VTs during 1 year period); VT was inducible in 8/117 pts who underwent late PVS (7%) p<.001. One out of the 8 pts was not inducible before surgery; 76 pts were in NYHA class I; 50 pts in NYHA II; 11 pts in NYHA III and 4 in NYHA IV. Angina was still present in 8 pts (6%) while 102 pts (72%) complained of angina before surgery.

Conclusions: Our results demonstrate that LV aneurysm patch repair associated with complete coronary revascularization and with subtotal endocardectomy and cryotherapy (when indicated), induces: 1) a long-term significant improvement in LV pump function especially in pts with a low basal EF; 2) a significant improvement in clinical status; and 3) a significant reduction of clinical and inducible ventricular arrhythmias.

*By invitation

7. REDUCTION OF PERIOPERATIVE NEUROLOGICAL MORBIDITY IN CORONARY BYPASS SURGERY: A RANDOMIZED TRIAL OF HIGH VERSUS LOW INTRAOPERATIVE BLOOD PRESSURE MANAGEMENT

Jeffrey P. Gold, M.D, Mary E. Charlson, M..D.*, Karl H. Krieger, M.D., Pamela Williams-Russo, M.D.*, Stephen J. Thomas, M.D.*, Ted P. Szatrowski, M.D., Denise Barbut, M.D.*, Janey Peterson, R.N.*, Paul Pirraglia, M.S.* and O. Wayne Isom, M.D.

New York, New York

Optimal management of the mean arterial blood pressure (MAP) on cardiopulmonary bypass (CPB) during coronary artery bypass grafting (CABG) remains controversial. Patients (248) undergoing elective multivessel coronary artery bypass grafting were randomized preoperatively to a low (50-60 mmHg) or high (80-100mmHg) MAP group. All patients were evaluated preoperatively with a cardiac, neurologic, cognitive, and functional test battery which was repeated one week and six months postoperatively. Intraoperative transesophageal echocardiography (TEE) studies complemented standard monitoring and management. CPB temperatures and flow were fixed, and MAP was adjusted with a standardized regimen of vasoactive drugs.

The study groups did not differ with respect to age, gender, race, cardiac history, extent of coronary artery disease, LV-EF, as well as all preoperative aspects of the neurological, psychometric, functional, and cognitive test batteries. The mean age was 66 years; 80% were male. Preoperatively the mean LV-EF was 48%, and 53% had a previous MI. There were no difference in the operative mortality (1.6%), crossclamp time (41"), pump time (8"), number of grafts (3.1), or in post-operative bleeding. Postoperative cardiopulmonary events were defined as shock, MI, pulmonary edema, and ARDS. Neurologic events were defined as persistent (>24 hr) deficits correllated with CT scan findings (paresis, plegia, aphasia, central sensory, hemianppsia & cortical blindness). Cognitive deterioration was defined as a clinically important decline on three of twelve neuropsychiatric tests, and a functional deterioration as a five point decline in the SF-36 score.

Patients with MAP maintained within the high pressure range had fewer neurological complications (1.6% vs 6.4%, p<0.001) than their low MAP counterparts (independent of preoperative risk factors and TEE assessed degree of aortic ASVD). In patients with advanced aortic ASVD on TEE (16%), the perioperative CVA rate was 30% in the low MAP group, compared to 10% in the high MAP group (p<0.001). There were no significant differences in the incidence of long term cognitive (11.4% vs. 12.3%) or functional (13.7% vs. 10.5%) changes. These findings indicated that patients with mean arterial pressure on CPB maintained at a higher range (presumably closer to their auto-regulatory range ) have a substantial reduction in perioperative neurological morbidity following elective CABG when compared to patients with conventional intraoperative pressure management.

*By invitation

8. REPAIR OF LONG SEGMENT TRACHEAL STENOSIS IN INFANCY

Robert D.B. Jaquiss, M.D.*, Rodney M. Lusk, M.D.*, Thomas L. Spray, M.D. and Charles B. Huddleston, M.D.*

St. Louis, Missouri

Congenital long segment stenosis of the trachea (LSTS) presents a considerable surgical challenge because of the difficulty in providing distal ventilation during the repair and because the optimal type of repair is not clearly defined. This report summarizes our experience with an anterior rib cartilage tracheoplasty using cardiopulmonary bypass (CPB) to avoid direct intubation of the distal airway. Six patients underwent repair of LSTS between September 1987 and the present. The median age was 14 weeks (range = 1 to 58 weeks) and the mean weight was 4.8 kg (range = 2.9 to 9.9 kg). All patients had involvement of at least 70% of the tracheal length, typically from the thoracic inlet to the carina with complete cartilaginous rings over much of the stenotic segment. Two patients also had involvement of one or both mainstem bronchi. Associated anomalies were present in two patients (tetralogy of Fallot in one and patent ductus arteriosus in one). In all patients a median sternotomy was employed and the anterior surface of the trachea was exposed from the thoracic inlet to the carina. After identification of the upper extent of the stenosis by rigid bronchoscopy, a vertical incision was made in the anterior trachea through the entire stenotic segment. A previously harvested segment of rib cartilage, with intact perichondrium, was then fashioned to correspond to the long tracheotomy and sewn in place as an augmentation patch with the perichondrium facing the lumen. In order to avoid distal airway intubation, all procedures were performed on CPB with a mean bypass duration of 110 minutes (range = 54 to 175 minutes). Mechanical ventilation was required postoperatively for a median of 11 days (range = 7 to 81 days), and the median postoperative hospital stay was 17 days (range = 12 to 180 days). There were no operative deaths and all patients are long term survivors. Complications include the need for ECMO support to treat unexplained ventricular dysfunction in one patient and graft dehiscence requiring re-exploration and placement of additional sutures in another. The patient who developed graft dehiscence has required several bronchoscopies for removal of granulation tissue. All other patients are asymptomatic without evidence of airway obstruction and have normal growth and development with a mean follow-up of 4.4 years (range = 1 month to 7.3 years). We conclude that rib cartilage tracheoplasty for LSTS provides excellent results in short and intermediate follow-up. In addition, the use of CPB allows an unobstructed view of the tiny infant airway, and thus permits a precise repair.

*By invitation

9. RECURRENCE OF OBLITERATIVE BRONCHIOLITIS AND DETERMINANTS OF OUTCOME IN 139 PULMONARY RETRANSPLANT RECIPIENTS.

Richard J. Novick M.D., Hans-Joachim Schafers, M.D.*, Larry W. Stitt, M.Sc.*, Walter Kleptko, M.D.*, Bernard Andr6assian, M.D.*, Jean-Pierre Duchatelle, M.D.*, Robert L. Hardesty, M.D., Adaani E. Frost, M.D.*, and G. Alexander Patterson, M.D.

London, Ontario, Canada, Hannover, Germany, Vienna, Austria, Paris, France, Pittsburgh, Pennsylvania, Houston, Texas and St. Louis, Missouri

An international series of pulmonary retransplantation (retx) was updated in order to identify the determinants of outcome and the prevalence and recurrence rate of obliterative bronchiolitis (OB) postoperatively. The study cohort included 139 patients who underwent retx in 34 institutions in North America and Europe from 1985 to 1994. Eighty patients were retransplanted for OB, 34 for acute graft failure, 13 for intractable airway problems, 8 for acute rejection and 4 for other indications. Survivors were followed for a mean of 706 ± 67 days, with 48 patients alive at 1 year, 30 at 2 years and 16 at 3 years after retx. Follow-up was 100% complete. Actuarial survival was 65 ± 4% at one month, 45 ± 4% at 1 year, 38 ± 5% at 2 years and 36 ± 5% at 3 years; nonetheless, of 90 day postoperative survivors, 65 ± 6% were alive 3 years after retx. Most deaths were caused by infection (48/85, 56%), followed by acute failure of the second graft (22%), recurrent OB (14%), an airway complication (4%) or other causes (4%). Life table and univariate Cox analysis of 18 variables revealed that more recent year of retransplantation (p = 0.009), ABO blood group identity (p = 0.01), absence of a donor-recipient cytomegalovirus mismatch (p = 0.04) and being ambulatory immediately prior to retx (p = 0.04) were associated with survival. There was a trend toward improved outcome (p = 0.5610) in centers with experience in at least 5 pulmonary retx procedures. On multivariate Cox analysis, being ambulatory prior to retx was the most significant predictor of survival (p = 0.008).

Complete pulmonary function test results were obtained yearly from every survivor of retx. Bronchiolitis Obliterans Syndrome (BOS) stages were assigned according to standard criteria, based on absolute FEV] values (J Heart Lung Transplant 1993; 12:713-6). The percentage of retx patients in each BOS stage is shown in the table:

Postop Interval	No. of Patients	Stage 0	Stage 1	Stage 2	Stage 3
1 year	48	79%	4%	6%	11%
2 years	30	63%	10%	7%	20%
3 years	16	69%	6%	0%	25%

Absolute FEV] values decreased by 6 ± 4% at 1 year and 18 ± 5% at 2 years from postoperative baseline values (p=0.07, year 2 versus year 1). There were no significant differences in BOS stages or the rate of FEVj decrease between patients reoperated for OB versus other conditions or between single or double lung retx patients. We conclude that survival after pulmonary retx is improving with increasing experience. Optimal results can be obtained in patients who are ambulatory prior to retx and receive an ABO-identical graft. OB does not appear to recur in a more accelerated manner after retx. As long as early mortality due to infection can be minimized, pulmonary retx appears to offer a reasonable option in highly selected patients.

2:50 pm INTERMISSION - VISIT EXHIBITS

*By invitation

3:30 pm PLENARY SESSION

Auditorium, Hynes Convention Center

Moderators: Aldo R. Castaneda, M.D.

John A. Waldhausen, M.D.

10. COMBINED LUNG AND LIVER TRANSPLANTATION IN CYSTIC FIBROSIS PATIENTS. A 4.5 YEAR EXPERIENCE

Jean-Paul A. Couetil, M.D.*, Didier Houssin, M.D.*, Patrick Chevalier, M.D.*, Bertrand Dousset, M.D.*, Didier F. Loulmet, M.D.*, Olivier Soubrane, M.D.*, Romain J. Guillemain, M.D.*, Catherine I. Amrein, M.D.*, Alain Guinvarch, M.D.* and Alain F. Carpentier, M.D., Ph.D.

Paris, France

Cystic fibrosis (CF) patients (pts) with end stage respiratory failure and associated liver cirrhosis have been considered as poor candidates for lung transplantation because of high morbidity and mortality due to hepatic insufficiency following the operation. Since June 1990 our policy has been to combine lung or heart-lung and liver transplantation in this group of pts. Among the 15 pts enrolled in the program, 5 died while awaiting transplantation and 10 underwent one of the following procedures: heart-lung-liver (n=5), En bloc double-lung-liver (n=1), sequential double-lung-liver (n=3), bilateral lobar lung from a split left lung and reduced liver (n=1). The latter was performed because of a large size discrepancy between donor and recipient. All pts were infected with persistent Pseudomonas, and 2 had in addition Aspergillus species. Pre-operative forced vital capacity and forced expiratory volume/sec were 35 ± 8% and 30 ± 5% of predicted values. All pts were on continuous oxygen and all suffered from severe cirrhosis with portal hypertension. Four had a history of esophageal variceal bleeding and two had had previous portosystemic shunts. Selection of donor organs was based on established criteria for lung and liver transplantation. The operation was performed as a two-stage procedure, the intra-thoracic stage being completed before commencing the abdominal stage. Results: 2 pts died in the post-operative period, one from primary liver failure (at 10 days), the second from pulmonary edema (at 21 days). Other complications included tracheal stenosis (n=1), biliary stenosis (n=3) and severe ascites (n=3). All were successfully treated. Four pts developed established diabetes post-operatively. Obliterative bronchiolitis (OB) developed in 2 pts at one year and 1 pt at two years. Of those, 2 pts were successfully treated with FK506. The other pt who was not treated with FK.506 continued to deteriorate and required heart-lung transplantation at 38 months but eventually died from bleeding. Estimated actuarial survival is 68.6 ± 12% at 3 years which is comparable to survival achieved for lung transplantation alone in CF pts in our unit. Conclusion: This series, the largest reported, demonstrates that in CF patients suffering from chronic respiratory failure with advanced cirrhosis, and thus having minimal life expectancy, lung transplantation combined with liver transplantation can be performed with satisfactory outcome.

*By invitation

11. PHASE I TRIAL OF FK506 IN CLINICAL HEART TRANSPLANTATION: IMMEDIATE TERM RESULTS

Si M. Pham, M.D.*, Robert L. Kormos, M.D., Brack G. Hattler, M.D.*, Athabassios C. Tsamandas, M.D.*, Anthony J. Demetris, M.D.*, Frederick J. Fricker, M.D.*, Thomas E. Starzl, M.D.* and Hartley P. Griffith, M.D. Pittsburgh, Pennsylvania

FK506, a macrolide antibiotic and a potent T-cell suppressor, recently received FDA approval for treatment of liver recipients. A phase I trial of FK506 in clinical heart transplantation was initiated at our center in 1989. The present study reports the intermediate term results of this trial.

Between 01/01/89 and 10/01/94, 136 primary heart recipients (age=0-65 years) received FK506/steroids/azathioprine regimen (FK), while 121 others were treated with cyclosporine-based immunosuppression (CBIS) consisting of triple drugs (cyclosporine A, azathioprine, steroids) and lympholytic induction with either rabbit antithymocyte globulin (RATG) or OKT3. The actuarial 1-, 2-, and 4-year survival for the FK and CBIS groups were 86%, 83% and 77%, and 93%, 89% and 73%, respectively (p=NS). Renal toxicity was the major side effect of both drugs. Mean serum creatinine values at 1 year were slightly higher for FK506 recipients (FK=2.2±1.2 vs CBIS=1.8±0.6; p=0.06). This probably reflected our learning curve for the use of FK506. By two years, the difference in creatinine disappeared (FK506=2.2±0.9 vs CBIS=2.1±0.9; p=0.5). There was a higher rate of intractable rejection (refractory to steroid bolus and RATG or OKT3) in the CBIS group (p<0.05). Fourteen CBIS patients had intractable rejection; all resolved with FK506 rescue. Two FK patients had intractable rejection requiring total lymphoid irradiation and methotrexate rescue. Endomyocardial specimens of 132 adult patients (FK=52, CBIS=50) were available for histopathological analysis. There was a trend toward a greater incidence of ISHLT Grade 2 or higher rejections (57% vs 40%, p=0.07) during the first 30 days in the FK506 arm. In contrast, there was a trend toward more Quilty lesion (27% vs 15%, p<0.27) and endocardia! fibrosis in the one-year biopsies of the CBIS recipients. The intermediate term outcome of cardiac recipients under FK506 compares favorably with those under the cyclosporine-based protocol plus lympholytic induction. FK506 is an effective rescue agent for intractable rejection under conventional immunosuppression.

*By invitation

12. COMPARATIVE STUDY OF CONVENTIONAL AND "TOTAL" (WITH CAVAL ANASTOMOSIS) ORTHOTOPIC HEART TRANSPLANTATION

Dominique R. Metras, M.D., Bernard Kreitmann, M.D.*, Alberto Riberi, M.D.*, Gilbert Habib, M.D.*, Pierre Ambrosi, M.D.* and Adrienne Pannetier, M.D.*

Marseille, France

Conventional orthotopic heart transplantation (OHT) has been reported to modify size and geometry of both atria and to cause mitral and tricuspid regurgitation affecting ventricular filling. Since 1992 we have systematically performed a modified technique of OHT with extensive resection of the recipient's heart, anastomosis of a small peri-venous cuff of left atrium and of both venae cavae. Our total experience includes 120 OHT, with 70 conventional technique (group I) and 50 modified technique (group II). Both groups were similar in age, pre-transplant characteristics, post-operative management including immunosuppression, and routine antithrombotic therapy (low molecular weight heparin followed by anti-agregant). The recipient aortic cross clamping time (i.e., time of heart excision and heart implantation) was longer in Group II (87 ± 19 mn vs 65 ± 15 mn; p<0.001). No haemorrhagic complication or surgical problems (such as caval thrombosis and/or stenosis) imputable to the technique were noted. Peri-operative and subsequent mortality were similar in both groups. Five patients in Group I presented a documented systemic embolism one month to five years after OHT, two of them with neurologic sequelae. No thromboembolic episode occurred in Group II.

Two comparable groups of 25 patients were studied at 6 months post-transplant (Group A after conventional OHT; Group B after modified OHT) with EKG, 24 hours EK.G Holter examination, and trans-thoracic and oesophagial echodoppler. A higher number of EKG anomalies, a significant increase in atrial size, a significantly higher proportion of mitral and tricuspid insufficiencies and a significantly higher coefficient of variation of the E/A ratio (parameter of left ventricular filling) were noted in Group A. Spontaneous echocontrast and atrial thrombi were present in the left atrium of several patients of Group A (50% and 20%, respectively) and never noted in Group B. We conclude that this modification of OHT lengthening surgery by about 20 mn achieves a closer to normal cardiac anatomy and geometry. Less anomalies of the cardiac function were found, the long term significance of which are yet unknown. A lower number of echocardiographic features of left atrial thrombosis and an absence of systemic embolism prompt us to think there is a definite advantage in this technically simple approach.

*By invitation

13. MEDIASTINAL LYMPH NODE STAGING OF NON-SMALL CELL LUNG CANCER: A PROSPECTIVE COMPARISON OF COMPUTED TOMOGRAPHY AND POSITRON EMISSION TOMOGRAPHY

Walter J. Scott, M.D.*, Lisa S. Gobar, M.D.*, John D. Terry, M.D.*, John J. Sunderland, Ph.D.*, Naresh A, Dewan, M.D.* and Jeffrey T. Sugimoto, M.D.*

Omaha, Nebraska

New York, New York

Auditorium, Hynes Convention Center

Sponsored by: Alex G. Little, Las Vegas, Nevada