Accelerated coronary atherosclerosis in cardiac transplantation.

The implications of this new aggressive form of coronary disease for the transplant population are obvious. It appears that for the majority of transplant patients we have simply bought some time. We have given them a temporary respite from congestive failure and cardiomyopathy while they surmount the daily challenges imposed by immunosuppression. Clearly, this issue now looms as a major stumbling block toward improving long-term survival. It is no longer enough to simply perform the procedure and submit the patient to the rigors of transplantation, only to obtain 50 percent 5-year survival. We must pay particular attention to the patient postoperatively and make those modifications necessary to improve the individual's risk profile. Moreover, we must continue to concentrate our research efforts on interventions in accelerated coronary disease.

Management and long-term followup of outpatient care in the cardiac transplant recipient.

Successful long-term management of the cardiac transplant patient requires the concerted effort of the patient, the cardiac transplant team, and the primary care physician. The long-term management of these patients will continue to evolve as new immunosuppressive agents are used and new methods of surveillance for rejection are found. The long-term management is indeed one of the most exciting parts of the care of the transplant patient, especially when all those involved can watch the patient enter into a normal lifestyle.

Hyperlipidemia after clinical heart transplantation.

Accelerated coronary atherosclerosis is a major cause of morbidity and death in the cardiac transplant recipient. Hypercholesterolemia has been implicated as a contributing risk factor. Because of this we reviewed lipoprotein profiles from transplant recipients from 1968 to 1986 in an attempt to identify the risk factors for the development of lipid disorders after transplantation. Patients were divided into three groups based on their immunosuppressive protocols. Group 1 consisted of 10 patients receiving azathioprine and prednisone. Group 2 consisted of 24 patients receiving cyclosporine and prednisone with or without azathioprine. Group 3 consisted of 18 patients receiving cyclosporine and azathioprine without prednisone. Total cholesterol levels at 1 year were highest in group 2 (266 mg/dl versus 236 mg/dl for group 1 [p = 0.16] and 223 mg/dl for group 3 [p = 0.005]). High-density lipoprotein cholesterol levels were lowest in group 3 (38 mg/dl versus 51 mg/dl for group 1 [p = 0.025] and 54 mg/dl for group 2 [p = 0.0001]). Subgroup analysis with multivariate and univariate analysis found that prednisone and preoperative coronary artery disease are the major contributors to the posttransplant lipid abnormalities.

Orthotopic cardiac transplantation: evaluation with CT.

As cardiac transplantation has become widely available, computed tomography (CT) of the chest has played a useful role in the examination of patients after heart transplantation. To determine anatomic features related to the procedure, the authors evaluated 59 scans in 46 patients who had undergone orthotopic cardiac transplantation. Aortic anastomosis (seen in 98% of scans) and altered spacing between the great vessels (83%) proved to be the most common and most reliable findings. Other features including atrial anastomosis, high main pulmonary artery segment, remnant superior vena cava, and cardiac reorientation were also seen. Accurate interpretation of adenopathy, mediastinal abscess, and pericardial effusion will be enhanced in these patients through a better understanding of the cardiovascular-pericardial complex, which is afforded by CT.

Nonpenetrating vascular injury to the subclavian artery.

Blunt subclavian artery injury has been uncommonly reported in the literature. Recent encounter with three such injuries prompted us to review our experience over the past 10 years uncovering only one additional case. These four cases and a review of pertinent literature form the basis for this article. Key clinical issues include a high index of suspicion in patients sustaining major blunt deceleration and rotational or direct injuries to the neck, thorax, and/or upper extremities. Prompt diagnosis remains obscured by the presence of severe associated injuries, the treatment of which requires prioritization. Arteriography is invaluable to elucidate injury because prompt vascular control is dictated by various approaches depending on the location. Expeditious surgical repair is indicated to prevent complications of hemorrhage, pseudoaneurysm, thromboembolism, and/or arteriovenous fistula. Long-term results appear to be good with major morbidity related to associated neurologic, soft tissue, and bony injuries.

Homograft replacement of single aortic valve cusps: 22 years follow-up.

Single aortic valve cusp replacement with fresh aortic homografts were performed in four patients from November 1966 to April 1970. All had preoperative aortic insufficiency due to destruction of a single cusp, with the remaining two cusps structurally and functionally intact. Replacement was performed using the noncoronary cusp from fresh aortic valve homografts. Patient one had homograft cusp replacement of the left coronary cusp at age 13 due to bacterial endocarditis. She recently underwent mitral valve replacement; study and inspection of the aortic valve showed it to be structurally and functionally intact 22 years following homograft cusp replacement. Patient two sustained a gunshot wound perforating his right coronary cusp. He underwent single cusp replacement in January 1967. Currently, he is asymptomatic and has been without evidence of significant aortic valve dysfunction for the past 21 years. Patient three had destruction of the noncoronary cusp due to endocarditis and had homograft cusp replacement in October 1967. Four and a half years later he developed recurrent endocarditis, presented with severe congestive heart failure due to aortic insufficiency, and died. Patient four had bacterial endocarditis affecting the right coronary cusp and had replacement in April 1970. In February 1980, he underwent aortic valve replacement for aortic stenosis. Inspection revealed calcification of the other two cusps with the homograft cusp structurally normal. In summary, follow-up of homograft replacement of single aortic valve cusps from 4 1/2 to 22 years, shows it to be a durable and feasible alternative to prosthetic valve replacement.

Expression of transferrin receptors on lymphocytes: its correlation with T-helper/T-suppressor cytotoxic ratio and rejection in heart transplant recipients.

Forty-one heart transplant recipients were monitored serially for the expression of transferrin receptors and T-helper/T-suppressor cytotoxic ratios on circulating lymphocytes during the hospitalization periods after heart transplantations (60.5 +/- 18.9 days). These values were retrospectively correlated with the patients' clinical status with respect to rejection and infection. During clinically stable periods the average values of percentage of transferrin receptor-positive lymphocytes and T-helper/T-suppressor cytotoxic ratios were 5.9 +/- 4.3 and 1.5 +/- 1.0, respectively. The percentage of transferrin receptor-positive lymphocytes increased to a level of 12.0 +/- 5.4 (p less than 0.001) during the early prerejection phase and remained at this level throughout the rejection period. T-helper/T-suppressor cytotoxic ratios increased to 1.96 +/- 0.92 during the early prerejection phase (p less than 0.05), peaked at 2.30 +/- 1.21 during the late prerejection phase (p less than 0.01), but began to decline by the rejection period. After rejection treatment percentage of transferrin receptor-positive lymphocytes decreased to 8.4 +/- 5.3 (p less than 0.05), and T-helper/T-suppressor cytotoxic ratios decreased to normal levels. In contrast, in patients with infectious complications, a remarkably elevated percentage of transferrin receptor-positive lymphocytes (20.7 +/- 11.7) and relatively low T-helper/T-suppressor cytotoxic ratios (1.3 +/- 0.5) were noted. The data show an association between the clinical status, such as rejection and infection, and these immunologic measurements as transferrin receptor-positive lymphocytes and T-helper/T-suppressor cytotoxic ratios in heart transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical significance of pericardial effusion after heart transplantation.

Fifty-two consecutive patients who underwent orthotopic heart transplantation at our institution were evaluated by two-dimensional (2D) echocardiography at frequent intervals for 12 weeks after transplantation and at three monthly intervals for 1 year. Thirty-eight of 52 patients had adequate 2D echocardiograms and comprised the retrospective study group. Pericardial effusion was documented in 15 of 38 patients (40%). Pericardial effusion was moderate in two (5%) and small in seven patients (18%). Large pericardial effusion was demonstrated in six of 38 patients (16%). Three of 38 patients (8%) developed cardiac tamponade manifested by hypotension in the presence of a large pericardial effusion. The diagnosis of cardiac tamponade was aided by 2D echocardiography leading to prompt pericardiocentesis. The presence of pericardial effusion in patients after their transplantation did not demonstrate independent correlation with chest tube output after operation, cyclosporine therapy, acute rejection, level of blood urea nitrogen (BUN), infection or preoperative diagnosis of idiopathic dilated cardiomyopathy. The presence of cyclosporine therapy, acute rejection, and a preoperative diagnosis of idiopathic dilated cardiomyopathy, however, yielded an 86% probability of having pericardial effusion. Follow-up 2D echocardiograms obtained 301 +/- 106 days after transplantation were available in 25 patients. Fifteen patients (60%) had no pericardial effusion present on either the initial or follow-up 2D echocardiogram. The majority of cases of the pericardial effusion present on initial or follow-up echocardiograms were resolving on the follow-up study.(ABSTRACT TRUNCATED AT 250 WORDS)

Are steroids essential for successful maintenance of immunosuppression in heart transplantation?

To determine the necessity for maintenance dosages of prednisone in the management of heart transplant patients, a retrospective study was made of 86 patients undergoing orthotopic heart transplantation and two patients having heart-lung transplantation from June 1985 through October 1986. Group 1 (n = 52) had maintenance immunosuppressive therapy that included cyclosporine, azathioprine, and prednisone. Group 2 (n = 36) received only cyclosporine and azathioprine with no maintenance dosage of steroids. Data were analyzed for frequency of rejections, infections, noninfectious complications, and mortality. The rate of rejection was 1.44 episodes per patient in group 1 and 1.58 episodes per patient in group 2. Twenty of 52 patients (38%) in group 1 had no rejection compared with 12 of 36 patients (33%) in group 2 (p = not significant [NS]). One or more infections occurred in 30 patients (58%) in group 1, whereas only 12 patients (33%) in group 2 had infections (p less than 0.05). Noninfectious complication rates were noted to be similar in both groups (27% versus 25%, p = not significant). There were five deaths in group 1: three from infections, one from rejection, and one from trauma. There were three deaths in group 2: two from infection and one from rejection. Although 14 patients in group 2 eventually were placed on low-dosage steroid maintenance, the remaining 22 patients (61%) never received maintenance dosages of steroids. We conclude that some patients can be successfully managed without maintenance dosages of steroids after heart transplantation. Such patients do not appear to have an increased risk of rejection and may have a reduced rate of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of prophylactic rabbit antithymocyte globulin in cardiac allograft recipients treated with cyclosporine.

The prophylactic use of rabbit antithymocyte globulin (RATG) was evaluated in 13 cardiac allograft recipients who received a low-dose of RATG (175 +/- 32 mg) after transplantation (group 1). The patients were retrospectively compared with 13 parallel cases receiving the same treatment except for the initial RATG (group 2). There were no differences in the patient composition and the level of the basic immunosuppression therapy with cyclosporine. The patients treated with RATG (group 1) showed substantially greater suppression of T helper and total T cells up to 10 and 20 days after surgery, respectively. The incidence of rejection episodes during the initial admission seemed lower in patients receiving RATG, with a borderline significance (1.4 versus 2.4, p = 0.06). This accounts for the reduced requirement of methylprednisolone in treating rejection in patients in group 1 (1.3 gm versus 4.0 gm, p less than 0.02). Moreover, the patients without initial doses of RATG (group 2) more frequently experienced recurrent rejection (five of 12 versus nine of 10, p less than 0.05), which necessitated rescue RATG; the initial difference in the RATG usage disappeared by the time of discharge. Serious infection occurring after antirejection therapy was common in the group 2 patients without initial doses of RATG, although the overall incidence of infection was not statistically different. Prophylactic use of RATG at the dosage used appeared to reduce the incidence of rejection and the requirement for intravenous steroids and other immunosuppressants. It seems warranted to test this approach in a prospective randomized manner.

Pretransplant transfusions in cardiac allograft recipients.

The role of pretransplant transfusion in cardiac allograft recipients was determined retrospectively in 68 patients. Three groups were studied: group 1 (n = 29) received no pretransplant transfusion, group 2 (n = 15) received transfusion over one year prior to transplantation, and Group 3 (n = 24) received 5 or 10 50-100 ml units of random donor red blood cells or buffy coat 2-4 weeks prior to transplantation. Data were analyzed for survival, number of rejection episodes, and number of infections. Immunosuppression included azathioprine, prednisone, and antithymocyte globulin. Survival in transfused patients (groups 2 and 3) was 68% and 51% at 1 and 5 years, respectively, while in the nontransfused population (group 1) it was 35% and 16%. The incidence of rejection episodes per year of survival was similar in the three groups (group 1: 1.3, group 2: 1.1, group 3: 1.3; P greater than 0.05). The number of infections per year of survival were greater in the transfused patients but this did not achieve statistical significance (group 1: 1.0, group 2: 1.2, group 3: 1.7; P greater than 0.05). Thus, we conclude that cardiac transplant recipients who have received blood transfusions prior to transplantation may have enhanced survival over patients who have not received preoperative transfusions.

Urinary thromboxane excretion in cardiac allograft rejection in immunosuppressed rats.

Increased urinary excretion of immunoreactive thromboxane B2 (iTxB2) was found to have a high predictive value, with high sensitivity as an indicator of cardiac allograft rejection in both the immunosuppressed and nonimmunosuppressed rat. In the animals receiving an allograft, urinary iTxB2 excretion significantly increased prior to the onset of rejection, remained elevated, and returned to basal values following completion of the episode. Urinary iTxB2 remained at baseline values in the control animals. The association between rejection and iTxB2 excretion was preserved regardless of the presence or nature of immunosuppression. Urinary iTxB2 excretion increased significantly prior to the reduction of graft beat or histological evidence of rejection. Evaluation of urinary iTxB2 monitoring as a noninvasive indicator for surveillance of clinical cardiac allograft rejection appears to be warranted.

Contrast injection bradycardia during coronary angiography: effects in the denervated human heart.

To assess the contribution of cardiac innervation toward understanding the mechanisms of bradycardia during contrast coronary angiography, heart rate (HR) responses in eight patients after heart transplantation were compared with 10 normal patients (control), 10 patients with coronary artery disease (CAD) and normal ventricular function, and 10 patients with congestive cardiomyopathy and normal coronary arteries. The longest P-P interval was measured beat to beat before (HR 1) and after (HR 2) coronary angiography. The coronary vessel perfusing the sinus node did not influence HR 2 responses within each group. HR 1 was significantly different from HR 2 (p less than 0.05) in the control and CAD groups but was not different in the transplant and cardiomyopathy groups. Compared with the control group, the percent decrease in HR was significantly less in transplant patients than in patients with cardiomyopathy. Thus contrast injection bradycardia is absent in denervated patients after heart transplant, and this response is markedly blunted in cardiomyopathy patients who are known to have diminished vasodepressor reflexes. These findings suggest that the bradycardia response is probably a neurally mediated phenomenon.