Pulmonary veno-occlusive disease following hematopoietic stem cell transplantation: a rare model of endothelial dysfunction.

Veno-occlusive disease is among the most serious complications following hematopoietic stem cell transplantation. While hepatic veno-occlusive disease occurs more commonly, the pulmonary variant remains quite rare and often goes unrecognized antemortem. Endothelial damage may represent the pathophysiologic foundation of these clinical syndromes. Recent advances in the treatment of hepatic veno-occlusive disease may have application to its pulmonary counterpart.

Prevention of recurrent sudden cardiac arrest: role of provocative electropharmacologic testing.

This study evaluates the usefulness of serial provocative electropharmacologic testing for predicting the efficacy of prophylactic antiarrhythmic treatment regimens in patients resuscitated from sudden cardiac arrest in the absence of acute myocardial infarction. Testing was carried out in 34 consecutive patients (28 men and 6 women) who required cardiopulmonary resuscitation and direct current countershock for treatment of primary ventricular fibrillation (28 patients), ventricular tachycardia (5 patients) or excessively rapid heart rate during atrial fibrillation with preexcitation (1 patient). In 8 (24%) of the 34 patients, drug testing either was not feasible because of absence of inducible arrhythmia or was incomplete because of patient withdrawal from study; and 3 of these 8 patients had recurrent sudden cardiac arrest within 10 to 19 months. In an additional five patients, treatment regimens failed to prevent initiation of sustained ventricular tachyarrhythmias in the catheterization laboratory, and two of these five patients had cardiac arrest recurrences within 2 weeks to 25 months of follow-up. In the remaining 21 (62%) of the 34 patients, including 3 patients with preexcitation syndrome, a drug regimen or surgical treatment, or both, was found that prevented inducible life-threatening tachyarrhythmias in the laboratory. Subsequently, only 1 (5%) of these 21 patients died suddenly within a 7 to 38 month (mean +/- standard deviation, 18 +/- 8.3) follow-up period. Thus, provocative electropharmacologic testing appears to be useful in predicting response to therapy in survivors of sudden cardiac arrest.

Bromocriptine treatment of digitalis-induced ventricular tachyarrhythmias: studies in a canine model.

Ventricular tachyarrhythmias associated with digitalis toxicity are believed to be due, in part, to cardiac glycoside-mediated increased central sympathetic neural activity. Because dopaminergic receptor agonists reduce sympathetic outflow, this study assessed effectiveness of the available dopaminergic agonist, bromocriptine, in slowing or terminating ouabain-induced ventricular tachycardia in anesthetized dogs. In all experiments, ouabain was administered intravenously (20 micrograms/kg body weight bolus injection, followed by 2.5 micrograms/kg per min infusion) until the onset of stable ventricular tachycardia. Of seven untreated dogs (Group 1), ouabain-induced ventricular tachyarrhythmias resulted in ventricular fibrillation in three, while in four dogs tachycardia persisted without significant change in rate until the study was terminated. Fourteen dogs (Group 2) received bromocriptine, either 30 micrograms/kg (Group 2A) or 50 micrograms/kg (Group 2B), after the onset of ventricular tachycardia. Tachycardia slowed in all 14 dogs and terminated with resumption of sinus rhythm in 8 of the 14. In all six dogs pretreated with the peripheral dopaminergic antagonist domperidone (Group 3), bromocriptine, 50 micrograms/kg, slowed ventricular tachycardia and in three of the six, tachycardia terminated. In contrast, of five dogs pretreated with haloperidol, a central and peripheral dopaminergic receptor antagonist (Group 4), bromocriptine, 50 micrograms/kg, failed to slow ventricular tachycardia in three, and two of the three developed ventricular fibrillation. In summary, the dopaminergic receptor agonist, bromocriptine, presumably acting at central dopaminergic receptor sites, consistently slowed and in most cases reversed ouabain-induced ventricular tachycardia in a canine model.

Upper airway obstruction during head flexion in Morquio's disease.

Previous reports of pulmonary function in patients with Morquio's disease have emphasized the restrictive nature of their ventilatory defect. We describe a patient in whom pulmonary disability was secondary to upper airway obstruction from collapse of the trachea during head flexion. The same phenomenon was demonstrated in one of two other patients with Morquio's disease, both of whom were asymptomatic. Positionally dependent airway obstruction may be an important cause of pulmonary disability in Morquio's disease.

Practices of cardiothoracic transplant centers regarding hepatitis C-seropositive candidates and donors.

The purpose of this survey was to determine current practices of cardiothoracic transplant centers regarding transplantation of hearts and lungs into hepatitis C (HCV)-seropositive candidates and the use of organs from HCV-seropositive donors. A telephone survey of 48 cardiothoracic transplant centers was conducted in October 1992. Questions included the center's policy for listing HCV-seropositive candidates; if, and under what conditions, organs from HCV-seropositive donors would be used; and which HCV assays were used. Forty-five programs responded; 75% will list an HCV-seropositive candidate, either directly or by lack of routine screening to exclude such patients; only 16% will not accept HCV-seropositive candidates; 9% had no policy. Overall, 69% will accept organs from HCV-seropositive donors, at least for selected recipients (22% for any recipient, 45% for HCV-seropositive and/or status I recipients; 2% do not screen donors). A total of 27% will never accept organs from an HCV-seropositive donor, and 4% had no policy. Thirty centers provided information on HCV methodology. All but one use a second generation ELISA or EIA as a first-line test. A positive result will be followed by a confirmatory assay/liver biopsy in 42%. The variation in practices reflects the ambiguity in the literature. Adequate evaluation of morbidity and mortality due to HCV infection in this population has not yet been possible, although currently available reports do not show a substantial increase. Prospective controlled trials in cardiothoracic transplant patients are necessary.

Transesophageal study of infant supraventricular tachycardia: electrophysiologic characteristics.

Programmed electrical stimulation of the heart to initiate and terminate tachycardia and analysis of the temporal relation between ventricular and atrial activation during tachycardia have been useful in the evaluation of supraventricular tachycardia (SVT). Such techniques have rarely been applied to evaluate infants with SVT. We used a silicone rubber-coated bipolar electrode catheter (15 or 22 mm interelectrode spacing), positioned in the esophagus, for electrical stimulation of the heart and recording of electrograms for the evaluation of 14 infants aged 1 to 84 days with SVT. Three infants had electrocardiographic features of Wolff-Parkinson-White syndrome, and no infant had other manifestations of congenital heart disease. Tachycardia cycle lengths ranged from 180 to 295 ms and ventriculoatrial intervals recorded from the esophagus were 80 to 220 ms. In 12 infants, transesophageal atrial stimulation was used to terminate and initiate SVT using stimuli of 9.9 ms and 10 to 20 mA. Initiation and termination of SVT by electrical stimulation suggest that SVT in infants is due to reentry, and the presence of ventriculoatrial intervals greater than 70 ms further suggests that accessory atrioventricular connections (usually concealed) constitute a portion of the reentry circuit.

Electrophysiologic effects of theophylline in young patients with recurrent symptomatic bradyarrhythmias.

In this study, both acute electrophysiologic actions of intravenously administered theophylline and clinical effects of chronic oral theophylline therapy were assessed in 10 young patients (aged 9 to 41 years) without clinically significant cardiac disease, in whom recurrent symptoms of syncope and dizziness were attributed to transient bradyarrhythmias (sinus pauses, marked sinus bradycardia or paroxysmal atrioventricular [AV] block). Intravenous theophylline infusion (serum concentration range 9.5 to 12.0 mg/liter) shortened means sinus cycle length (control 973 +/- 285 ms versus theophylline 880 +/- 226 ms, p less than 0.005) and decreased both the estimated sinoatrial conduction time (control 169 +/- 56.0 ms versus theophylline 143 +/- 55.3 ms, p less than 0.05) and the maximum corrected sinus node recovery time (control 442 +/- 251.0 ms versus theophylline 255 +/- 146.2 ms, p less than 0.05). In addition, theophylline infusion shortened the minimum atrial paced cycle length with sustained 1:1 AV conduction (control 414 +/- 86 ms versus theophylline 379 +/- 97 ms, p less than 0.05) and consistently reduced AV node functional refractory periods. Subsequent chronic oral theophylline therapy (serum levels 9 to 12 mg/liter) was tolerated in 8 patients (80%). During a follow-up of 5 to 24 months, suppression of symptoms was achieved in 6 of the 8 patients. Thus, theophylline exhibits positive chronotropic and dromotropic effects in man at serum concentrations in the usual therapeutic range (10 to 15 mg/liter). Furthermore, suppression of symptoms during follow-up suggests that theophylline treatment may be a useful therapeutic consideration in some patients with recurrent symptomatic bradyarrhythmias.

Cardiac arrest in young, ostensibly healthy patients: clinical, hemodynamic, and electrophysiologic findings.

This study examines the clinical, hemodynamic, and electrophysiologic findings in a unique group of 11 young (aged 15 months to 29 years) survivors of a cardiac arrest. All patients were previously in good health, and cardiac arrest was the initial manifestation of cardiac disease in all. Overt clinical and hemodynamic abnormalities were not as common as previously reported, and in some instances apparent cardiac abnormalities failed to provide a link to cardiac arrest. No patient had congenital heart disease or hypertrophic cardiomyopathy. However, during multicatheter electrophysiologic study, sustained tachyarrhythmia was reproducibly initiated in 8 of 11 patients (73%). Young, ostensibly healthy patients who survive cardiac arrest form a diverse group. Diligent programmed intracardiac electrical stimulation may demonstrate life-threatening tachycardias in these patients. Treatment to prevent recurrence of cardiac arrest is difficult in this group of patients. However, the ability to initiate tachycardia in the electrophysiologic laboratory may be useful in the management of these patients.

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate in primary ventricular fibrillation or life-threatening ventricular tachycardia.

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate, a chemical analog of bretylium tosylate, were studied using programmed cardiac electrical stimulation in 14 survivors of out-of-hospital cardiac arrest unassociated with acute myocardial infarction. Before bethanidine sulfate was administered sustained ventricular tachyarrhythmias (VT) were inducible in 11 patients and reproducible nonsustained VT was induced in 3 patients. Bethanidine sulfate shortened sinus cycle length and absolute and relative ventricular refractory periods measured during sinus rhythm, but did not alter ventricular effective refractory period measured during ventricular pacing. Bethanidine sulfate prevented inducible VT in 8 patients (57%), increased the number of extrastimuli needed to induce VT in 2 patients, and was ineffective in 4 patients. In contrast, in only 1 of 26 trials with other conventional and investigational antiarrhythmic drugs in these patients was VT prevented. Orthostatic hypotension was a prominent side effect of bethanidine sulfate therapy, but could be reversed in most patients by concomitant administration of protriptyline. Five patients in whom bethanidine sulfate was effective in the laboratory have been treated chronically (400 to 600 mg 4 times daily), and all are alive at 3 to 40 months. In the remaining 9 patients, 8 were treated empirically because no drug was effective in the laboratory and 1 was treated with quinidine, which appeared to be protective during testing. Four of these 9 patients, including the patient treated with quinidine, died suddenly during follow-up. Thus, although bethanidine sulfate therapy is difficult to initiate because of orthostatic hypotensive side effects, it may be useful in treating patients at high risk of recurrent cardiac arrest.

Onset of atrial fibrillation during antidromic tachycardia: association with sudden cardiac arrest and ventricular fibrillation in a patient with Wolff-Parkinson-White syndrome.

Electrophysiologic evaluation in an 18 year old youth with the Wolff-Parkinson-White syndrome who had a sudden cardiac arrest while playing racquetball revealed two types of paroxysmal reciprocating tachycardia: (1) A normal QRS tachycardia with a short ventriculoatrial (V-A) interval fulfilled the criteria for reentry within the atrioventricular (A-V) node; and (2) a wide QRS tachycardia with a QRS configuration of maximal preexcitation was demonstrated to be the result of an antidromic mechanism. During laboratory study, the wide QRS tachycardia spontaneously degenerated into atrial fibrillation. In the basal state, the shortest R-R interval between preexcited QRS complexes was 270 ms, but after infusion of isoproterenol (1.6 microgram/min intravenously), the shortest R-R interval became 180 ms. Consequently, this electrophysiologic study suggested that evolution of antidromic reciprocating tachycardia into atrial fibrillation with a rapid ventricular response during exercise-induced catecholamine release may have been the mechanism for ventricular fibrillation in this patient.

Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group.

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.

A combined atrial/ventricular lead for permanent dual-chamber cardiac pacing applications.

A new urethane insulated dual unipolar atrial/ventricular transvenous lead has been developed to facilitate implantation of permanent dual-chamber cardiac pacing systems in man. The atrial portion of the lead has tines and is designed to retain a permanent J configuration, while the coaxially situated ventricular lead is freely and independently adjustable and incorporates a ring tip electrode with four urethane tines. Our initial experience with the dual lead in one patient is reported herein and suggests that combined atrial/ventricular pacing leads are feasible and may obviate need for implantation of two separate pacing electrodes in patients being considered for permanent dual-chamber pacing.

Treatment of end-stage chronic obstructive pulmonary disease with double lung transplantation.

Six patients with end-stage emphysema (age 44 +/- 2 years) underwent double lung transplantation (Tx) from June 1988 through May 1990. All suffered from severe inanition and required oxygen therapy. The ischemic time was 193 +/- 28 minutes. Post-Tx immune suppression was OKT3 (14 days), cyclosporine (trough levels of 150 +/- 25 ng/ml), azathioprine to keep WBC at 3,000 to 5,000/cu mm (1 to 3.0 mg/kg/day) and following OKT3, a tapering prednisone regimen. Two rejection episodes that occurred in two patients on post-Tx day 5 and 10 were treated with bolus doses of methylprednisolone. The mean hospital stay was 32 +/- 7 days (range, 20 to 69 days). Four patients required treatment of cytomegalovirus (CMV) infection: gastritis (+donor, +recipient) in one and CMV pneumonia in two (+donor, -recipient). A fourth (+donor, -recipient) had right-sided Candida empyema six weeks post-Tx, developed CMV and staphylococcal sepsis, and died 64 days post-Tx. One patient required pyloroplasty eight weeks post-Tx and one patient underwent tracheal suture line repair at eight weeks. During a follow-up of 81 patients months (range, 8 to 24 months), one patient had developed Epstein-Barr viral (EBV) induced lymphoproliferative disease in the lung and one patient had developed EBV lymphoma. Three patients are at work, one is continuing rehabilitation, and one is at home. Double lung Tx offers a definitive benefit to patients with emphysema; however, a prolonged postoperative course can be expected. Viral infections remain serious but treatable problems.

The impact of steroid withdrawal on the development of lipid abnormalities and obesity in heart transplant recipients.

Hyperlipidemia and obesity are common problems after heart transplantation, which may increase the risk of chronic graft atherosclerosis. The intent of this study was to (1) determine the impact of a history of hyperlipidemia on the occurrence of lipid abnormalities after transplantation, (2) compare lipid profiles of those patients being treated with triple-drug immunosuppression versus those patients weaned from prednisone therapy, and (3) identify any factors that would predict which patients are at highest risk for the development of hyperlipidemia after transplantation. Of 89 patients who lived for more than 12 months, 35 patients had a history of hyperlipidemia before heart transplantation (cholesterol level of more than 240 mg/dl; low-density lipoprotein cholesterol level of more than 160 mg/dl). The most dramatic rise in cholesterol level was observed in patients with no history of hyperlipidemia who were treated with triple-drug immunosuppression, in whom a 64% increase occurred versus a 24% increase in patients receiving steroid-free immunosuppression (p < 0.001). In patients with a history of hyperlipidemia, cholesterol level increased by 20% with triple-drug immunosuppression versus 14% with steroid-free immunosuppression (p = 0.613); however, 83% of the patients in the triple-drug group and 92% in the steroid-free group had elevated cholesterol levels. Multiple regression analysis revealed that significant independent and additive (p < 0.00001) contributions with respect to percent change in cholesterol level were evident for (1) a negative history of hyperlipidemia (p = 0.005), (2) triple-drug immunosuppression (p = 0.0021), and (3) female sex (p = 0.0113). A negative history of hyperlipidemia was predictive of the percent change in low-density lipoprotein cholesterol level (p = 0.0049), and triple-drug immunosuppression administration predicted the percent change in high-density lipoprotein cholesterol (p = 0.0119). Patients with a positive history of hyperlipidemia had higher lipid values at 12 and 24 months after transplantation; however, patients with no previous history of hyperlipidemia experienced the greatest percent change in both cholesterol and low-density lipoprotein levels. Patients receiving prednisone therapy gained more weight (9.0 +/- 7.0 kg) as compared with those patients tapered from prednisone therapy (5.9 +/- 8.6 kg); however, neither the increase in actual weight (p = 0.120) nor the increase in percent ideal body weight (14% +/- 11% versus 9% +/- 13%, respectively) were significant (p = 0.133). This study identified that postoperative weight gain is best predicted by premorbid habitus, rather than the type of immunosuppression used.(ABSTRACT TRUNCATED AT 400 WORDS)

Implantation of the implantable cardioverter defibrillator in the heart transplant candidate.

Because the major cause of death in patients awaiting heart transplantation results from out-of-hospital sudden cardiac arrest, the use of the implantable cardioverter defibrillator has been proposed as a bridge to transplantation. To provide a safe and simple implantation procedure that also easily allows access to cardiopulmonary bypass at the time of transplantation, a modified subxiphoid approach is reported.

Cytomegalovirus after heart transplantation. Risk factors for infection and death: a multiinstitutional study. The Cardiac Transplant Research Database Group.

Cytomegalovirus infection is a major cause of morbidity and rehospitalization after heart transplantation. To assess its incidence and risk factors in the current era of heart transplantation, we analyzed cytomegalovirus infection data in 1553 patients from 26 institutions (Cardiac Transplant Research Database Group) undergoing primary heart transplantation between Jan. 1, 1990, and June 30, 1992. There were 230 treated cytomegalovirus infections in 200 patients, of which 16 were fatal (6%; 70% confidence limits 5% to 9%). Actuarial freedom from cytomegalovirus infection was 98% 1 month, 88% 3 months, and 83% 24 months after transplantation, with a peak incidence of initial infection at 2 months. Twenty-five (12%) of 200 patients with cytomegalovirus infection had recurrent cytomegalovirus infection during a mean follow-up of 13.9 months. The primary location of cytomegalovirus infection was blood in 100 infections (43%), lung in 69 (30%), gastrointestinal tract in 54 (23%), and other sites in seven patients (3%). Cytomegalovirus pneumonia exhibited the highest mortality rate (13%). Risk factors by multivariate analysis for earlier development of cytomegalovirus infection included pretransplantation cytomegalovirus serology (positive donor, negative recipient [p < 0.0001]; positive donor, positive recipient [p = 0.0002]; and negative donor, positive recipient [p = 0.02]) and cytolytic induction therapy (p = 0.05). A cytomegalovirus-positive recipient with a cytomegalovirus-positive donor had a 15% chance of having cytomegalovirus infection, whereas a cytomegalovirus-negative recipient with a cytomegalovirus-positive donor had a 24% chance. Ganciclovir treatment was administered in 227 (99%) of 230 infections. By multivariable analysis, the likelihood of a fatal cytomegalovirus infection was increased with a higher number of infections of any type during the first post transplantation month (p < 0.0001). There was no increased mortality rate in cytomegalovirus infections associated with cytomegalovirus-positive donor and cytomegalovirus-negative recipient (6% mortality rate) versus all other cytomegalovirus infections (6% mortality rate) (p = 0.9) or with OKT3 induction therapy (0% mortality rate) versus all others (noninduction and induction with other than OKT3) (1.4%) (p = 0.03). In conclusion, the biggest determinant of cytomegalovirus infection is donor and recipient pretransplantation cytomegalovirus serologic results with cytolytic induction therapy adding a small additional risk. The overall mortality rate from cytomegalovirus infections is low (7%) in the current era with rapid culture techniques and ganciclovir therapy. Cytomegalovirus infections are more likely to be fatal if there are more frequent preceding infections of any type, but mortality rates are not increased by OKT3 induction or with a cytomegalovirus-positive donor organ transplanted into a cytomegalovirus-negative recipient.

Cardiac tamponade masked by bilateral internal jugular vein thrombosis: its occurrence in an orthotopic heart transplant recipient.

We present a case of cardiac tamponade masked by bilateral internal jugular vein thrombosis occurring in a patient 1 month after orthotopic heart transplantation. Because patients who undergo heart transplantation undergo both heart surgery and multiple endomyocardial biopsies, they are at risk for both of these complications. Therefore when evaluating hypotensive patients who are at risk for both pericardial effusion and bilateral internal jugular vein thrombosis, cardiac tamponade should not be excluded, even in the absence of jugular vein distention.

Steroid-free maintenance immunotherapy: Minneapolis Heart Institute experience.

Recent advances in immunotherapy have resulted in improved survival after heart transplantation. The use of OKT3 as an induction agent has allowed the identification of a subset of patients who can be successfully withdrawn from prednisone and maintained on only cyclosporine and azathioprine. The latter regimen offers several theoretic advantages in terms of freedom from complications of long-term steroid therapy. To compare both the long-term efficacy and toxicity of steroid-free maintenance immunosuppression with triple-drug therapy, the medical records of 68 patients undergoing transplantation at the Minneapolis Heart Institute during a 3-year period (1988 through 1990) were reviewed. Thirty-six patients were treated with OKT3 induction immunotherapy, 29 were successfully tapered off prednisone by 114 +/- 44 days after transplantation, whereas 32 patients were maintained on triple-drug therapy. The incidence of treated rejection was equivalent in both groups; however, the time to first rejection was longer in patients treated with OKT3/steroid-free maintenance (205 +/- 214 vs 27 +/- 17 days) (p = 0.02). Bacterial infections during the early posttransplant period were more common in the OKT3/steroid-free maintenance group (p = 0.008); however, fungal and viral infections were equally distributed between both groups. The incidence of hypertension was slightly higher in patients maintained on prednisone (67% vs 51%; p = 0.242).(ABSTRACT TRUNCATED AT 250 WORDS)

Policies regarding the transplantation of hepatitis C-positive candidates and donor organs.

Whether hepatitis C virus (HCV)-positive candidates or donor organs should undergo transplantation remains controversial. Seventy-two thoracic transplantation centers responded to a survey soliciting specific information about policies regarding the listing of HCV-positive candidates and the use of HCV-positive donor organs. Most centers (64%) list HCV-positive candidates for heart transplantation. Twenty-six percent of centers refuse to use HCV-positive organs, whereas the remainder restrict the use of HCV-positive organs to status 1 recipients or HCV-positive candidates. More information is needed regarding the clinical outcomes of HCV-positive candidates and recipients of HCV-positive organs before clear-cut candidate selection and organ allocation policies can be established.

OKT3 induction and steroid-free maintenance immunosuppression for treatment of high-risk heart transplant recipients.

A group of high-risk heart transplant patients (n = 35) were treated from May 1987 through June 1990, with murine-derived monoclonal CD3 antibody (OKT3) induction therapy and steroid-free maintenance immunosuppression. This group was compared with a group of transplant patients (n = 47) who were not considered high risk and who were treated simultaneously with triple-drug immunosuppression (cyclosporine, azathioprine, and prednisone). The 1- and 3-year actuarial survival rates were similar: 97% and 91% for the OKT3 and 92% and 85% for the triple-drug immunosuppression groups, respectively. The overall incidence of rejection was equal for both groups (56%). No rejection occurred during the OKT3 course and rejection episodes occurred significantly later in patients treated with OKT3, with a mean first rejection episode of 111 +/- 104 days versus 27 +/- 21 days for the triple-drug immunosuppression group (p less than or equal to 0.05). Bacterial infections were seen more frequently (29% vs 6% of the patients treated) in the early period (less than 3 months) in the OKT3 group (p = 0.01) and were associated with the use of mechanical assistance in this group. The incidence of late infections or cytomegalovirus disease was similar for both groups. Patients treated with OKT3 and subsequent steroid-free maintenance immunosuppression had no significant posttransplantation increases of serum cholesterol levels, and hypertension was less common. Initial hospitalization was longer (p less than or equal to 0.05) in the OKT3 group (23 +/- 19 vs 13 +/- 5 days) but after the initial discharge the number of hospital days for the first year was similar for both groups (8 +/- 14 vs 9 +/- 13 days). Ventricular function at 1 year after transplantation was similar for both groups with average ejection fraction of 57% and 59% for the OKT3 and triple-drug immunosuppression groups, respectively. In conclusion, high-risk patients treated with OKT3 and steroid-free maintenance immunosuppression were managed on smaller doses of immunosuppressive drugs in the early postoperative period, and had excellent long-term survival rates. In this group of patients, rejection was delayed and the incidence of hypercholesterolemia, hypertension, and steroid-induced complications was decreased. Such a regimen offers a relatively drug-free period in the early posttransplant stages and freedom from the long-term complications of steroids.