Heart and other organs. Increasing patient survival following heart transplantation.
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Acute Disease↗
Biomedical subjects
R B Griepp
Publications and source records attributed to R B Griepp.
Alterations in myocardial blood flow during acute rejection of orthotopic canine cardiac allografts.
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Acute Disease↗
Long-term experience with porcine aortic valve xenografts.
Between 1971 and 1975, glutaraldehyde-preserved porcine aortic valve xenografts were employed for isolated replacement of the mitral valve (MVR) in 243 patients, replacement of the aortic valve (AVR) in 167 patients, and double valve replacement (AVR and MVR) in 51 patients. Postoperatively, long-term anticoagulation was not routinely given. Operative mortality rates for AVR, MVR, and double valve groups were 7.8, 6.0, and 11.8 per cent, respectively; the majority of early postoperative deaths were associated with concomitant coronary artery disease. No death was attributable to xenograft dysfunction. Follow-up of all patients was obtained. The total duration of follow-up for the MVR group was 347 patient-years, for the AVR GROUP 148 148 patient-years, and for double valve replacement 37 patient-years; maximum follow-up for these three groups was 4.4, 4.0, and 2.4 years, respectively. Actuarial analysis of postoperative survival rates at a common interval of 3 years showed 78 per cent for MVR patients, 91 per cent for AVR patients, and 80 per cent (projected) for patients with double valve replacement (85, 96, and 91 per cent for operative survivors, respectively. At this same interval 92 per cent of MVR patients, 99 per cent of AVR patients, and 93 per cent (projected) of patients with double valve replacement were free of thromboembolic episodes. Altogether, 12 of the total 512 valves implanted exhibited some evidence of dysfunction during the entire period of follow-up evaluation, but in only 2 instances (both mitral) was intrinsic pathological involvement of the xenograft tissue documented. Actuarial analysis of xenograft dysfunction at a common interval of 3 years after operation showed 95 per cent of MVR patients, 98 per cent of AVR patients, and 97 per cent (projected) of patients with double valve replacement to be free of this complication. These data support the use of glutaraldehyde-preserved porcine xenografts as superior bioprostheses that pose a low risk of thromboembolism without anticoagulation. The over-all durability of such valves, within the restriction of a maximum current follow-up interval of 4.4 years, appears comparable to that of currently available mechanical prostheses and justifies continued clinical use.
Animals↗
Mitral valve replacement: long-term evaluation of prosthesis-related mortality and morbidity.
Over a 12-year period isolated mitral valve replacement (MVR) was performed in 897 patients including 49 Starr-Edwards no. 6000, 519 SE no. 6120, 115 aortic allograft, and 214 porcine xenograft valves. Mortality and morbidity specifically related to the prosthesis was determined for each valve type. Fifty-two of 505 (10%) discharged patients with SE valves, four of 108 (3.7%) with homografts, no patients with heterografts, died of valve-related causes (P less than 0.05). Actuarial analysis shows continued time-related risk with any valve for both thromboemboli and valve failure. Thromboemboli were much more frequent with SE than with either tissue valve (P less than 0.05). Primary valvular incompetence was more common as a cause of valve failure with tissue valves (P less than 0.05), whereas multiple embolic episodes were more often a cause of valve failure with SE (P less than 0.05). Five of 49 (10%) patients with SE no. 6000, 30 of 519 (5.8%) with SE no. 6120, 19 of 115 (16.5%) with allografts, and two of 214 (0.9%) with xenografts needed reoperation for valve failure. For SE, homograft, and heterograft valves, actuarially determined composite, prosthesis-related mortality show 14% (80/568), 7% (8/115), 0% patients dead 6 years after MVR, respectively (P less than 0.05), while 3 years after MVR, 65% (369/568), 37% (42/115), and 85% (181/214) patients were free of prosthesis-related death or complications, respectively (P less than 0.05). Specific prosthesis-related complications differ between valve types significantly affecting survival and morbidity post-MVR.
Adult↗
Long-term follow-up after isolated aortic valve replacement.
Follow-up information was obtained for 1,127 patients having had isolated aortic valve replacement between May, 1963 and April, 1976. The mean follow-up period was 4.4 years. Valves employed included Starr-Edwards Models 1000 (83 patients), 1200 (203 patients), 1260 (435 patients), and 2320 (52 patients), as well as homograft valves (103 patients) and porcine xenograft valves (251 patients). The over-all mortality rate was 7.6 percent, and the linear attrition rate thereafter was 2.7 percent per year. Long-term survival was found to be significantly related to the following preoperative variables: age, congestive heart failure, functional class, radiographic cardiac enlargement, history of acute or remote myocardial infarction, valvular lesion, left atrial mean pressure, pulmonary artery mean pressure, coronary artery disease, left ventricular angiogram, and cardiac index. From this analysis, we conclude that aortic valve replacement in asymptomatic severe aortic regurgitation, (AR) is indicated. Actuarial analysis of prosthetic valve-related death and complications suggest that the porcine xenograft valve is an excellent choice for aortic valve replacement.
Adolescent↗
Rehabilitation after cardiac transplantation.
The physical, occupational, and social status of 56 patients who survived six or more months after cardiac transplantation at Stanford University Medical Center was reviewed. Fifty-one (91%) were classified as successfully rehabilitated. Four (7%) retained substantial physical disability, and one (2%) experienced psychiatric disability. These results demonstrate the therapeutic usefulness of cardiac transplantation in carefully selected recipients.
Adaptation, Physiological↗
Immunodepressive serum treatment of acute heart transplant rejection.
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Adolescent↗
Surgical treatment of degenerative mitral regurgitation.
Between October 1965 and April 1975, mitral valve replacement was preformed in 66 patients with myxomatous degeneration of the mitral valve ("floppy valve syndrome"). Operative mortality was 6 percent (four patients). Current evaluation was obtained for all patients; the average postoperative follow-up interval for surviving patients was 3.5 years (range 1 month to 9.9 years); the total duration of postoperative follow-up for all patients was 180 patient-years. Overall survival rates, calculated by the actuarial method, were 81, 68 and 50 percent, respectively, 1, 2 and 5 years after mitral valve replacement. Preoperative variables with a significantly adverse effect on patient survival included patient age greater than 50 years, New York Heart Association functional class IV, left ventricular end-diastolic pressure greater than 12 mm Hg and mean pulmonary arterial wedge pressure greater than 16 mm Hg. Support is advanced for the concept that mitral valve dysfunction associated with myxomatous degeneration constitutes a broad spectrum of clinicopathologic involvement. Acute clinical and hemodynamic deterioration may often occur in the setting of chronic mitral valve dysfunction. Postoperative mortality is directly related to preoperative functional disability and hemodynamic evidence of impaired left ventricular function. Consideration should be given to earlier operative intervention in patients with myoxmatous mitral degeneration and mitral insufficiency before severe and probably irreversible impairment of ventricular function occurs.
Adolescent↗
Human heart transplantation: current status.
The overall survival rate for 97 heart transplant recipients operated on from 1968 to 1975 has been 49% at one year and 23% at five years. Progressive improvement in one-year survival has been achieved, from 22% in 1968 to 62% in 1974. The major factors responsible for increasing survival are better understanding and management of acute and chronic rejection. Current results suggest that heart transplantation deserves wider application in the treatment of selected patients with end-stage myocardial insufficiency.
Acute Disease↗
Use of rabbit antithymocyte globulin in cardiac transplantation. Relationship of serum clearance rates to clinical outcome.
Serum rabbit globulin (RG) clearance rates were determined in 30 consecutive cardiac transplant recipients by radioimmune assay of serum RG levels after completion of an initial postoperative course of rabbit anti-human antithymocyte globulin (RATG). Twenty patients, who exhibited rapid RG elimination rates (average half-life, 1.6 days), had a rejection onset time of 16.2 days rejection frequency of 3.9 episodes/100 patient days, and a 1-year survival rate of 59%, respectively, as compared with 28.3 days, 1.9 episodes/100 patient days, and 80%, respectively, for the 10 patients with more prolonged initial RG elimination rates (average half-life, 11.4 days); Nineteen patients received one or more repeat courses of RATG. In 16 of these a progressive increase in RG half-life during subsequent RATG administration could be demonstrated. A close correlation was observed between total RATG doses given in the initial course and peak serum levels of RG obtained (r = 0.82) and between onset of rejection and initial t1/2 RG (r = 0.69). This latter correlation was improved by the elimination of one of the 30 patients (r = 0.81) or by considering only those patients treated from a single RATG batch (r = 0.85; n = 15). No significant relationship was detected between any of the parameters assayed and (1) total RATG dose, or (2) rosette inhibition titers of RATG administered. Survival and rejection parameters of the first 30 patients receiving RATG were compared with the previous 20 receiving equine antithymocyte globulin; these 50 comprising the entire population in which rejection was confirmed by cardiac biopsy. Rejection onset was 20 versus 12 days, rejection frequency was 3.1 versus 5.0 episodes/100 patient days, and graft survival at 1 year was 66 versus 41% for the RATG-equine antithymocyte globulin-treated patients, respectively. From these data it was concluded that (1) RATG administration favorably affects transplantation outcome; (2) RATG half-life, as reflected by RG clearance rates, was the most important variable governing RATG effectiveness, (3) variation in rosette inhibition titers within RATG batches made in the same fashion from large rabbit pools were of minimal clinical importance; and (4) monitoring of serum RG levels provided a necessary and rational basis for effective modulation of immunosuppressive therapy.
Animals↗
Lymphocyte tissue culture studies on human heart transplant recipients. III. Prediction of outcome of transplantation based on immunologic studies.
Using in vitro lymphocyte tissue culture screening tests human heart transplant recipients during the academic year 1973/1974 were evaluated and an attempt made to predict their post-operative rejection course. The tests involved screening for serum depressive factors and screening for the recipient's lymphocyte reactivity. A scoring system was devised whereby the laboratory results could be converted to a predicted rejection score. Of the nine patients studied, eight are still doing well. Three recipient's who had a high postoperative rejection score as determined by an independent clinical team, were correctly identified pre-operatively and one of them had to be retransplanted. These screening tests may be helpful in the future in the selection of recipients.
Cells, Cultured↗
Does cardiac transplantation prolong life and improve its quality? An updated report.
The current status of the human cardiac transplant experience at Stanford University Medical Center is presented in order to reassess its role in the treatment of end-stage cardiac disease. Of 109 patients undergoing transplantation at Stanford between January 1968 and August 1976, 44 were still alive as of August 1, 1976. The overall 1- and 2-year survival rates for the series are 52% and 43%, respectively. Sixty-nine patients have survived more than 3 months, and their overall 1- and 2-year survival rates are 80% and 66%, respectively. Of the 3-month survivors, 62 (90%) returned to functional Class I New York Heart Association cardiac status and most of these returned to their pre-illness activities. Of 40 patients selected for transplantation for whom a donor did not become available, 38 were dead in less than 6 months. Complications related to immunosuppression with steroids are currently the major barrier to longer survival and improved rehabilitation postransplantation. On the basis of these data we conclude that cardiac transplantation not only prolongs survival, but can return carefully selected recipients to an active life.
Adolescent↗
Transplantation of the heart.
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Acute Disease↗
An intrathoracic solenoid drive system for chronic left ventricular bypass.
The performance of an implantable Left Ventricular Assist System (LVAS), utilizing an advanced solenoid energy converter, has been extensively studied in vivo. For optimum system efficiency, reliability and responsiveness, the energy converter and blood pump are integrated into a single compact unit, which is implanted intrathoracically in an 80 Kg calf. The MK19 LVAS is battery operated and controlled by a miniature analog computer and is completely self-regulating. The maximum hemodynamic power provided by this circulatory assist system is 4 watts with cardiac outputs up to 10 L/min and a total system efficiency of 30%. LVAS function has been studied in a series of 19 calf experiments progressing through acute, model and chronic evaluations. Development of the implantation protocols and hemodynamic characterization were achieved in a series of 8 acute experiments. Long-term studies were conducted for periods up to 43 days in a series, including 2 control experiments using non-functional models and 9 functional LVAS chronic experiments. Aortic, left ventricular and left atrial pressures, pulmonary artery flow and pump outflow were monitored with chronically implanted transducers. A dedicated minicomputer provided real-time hemodynamic analysis and continuous surveillance of physiologic and LVAS parameters. In acute studies and in the immediate post-operative period of chronic experiments, synchronous LVAS operation reduced peak LV pressures to 30 mm Hg with cardiac outputs of 5 to 7 L/min. In chronic studies, with recovery of normal LV function, long-term synchronous operation was maintained, without capture of the total cardiac output and with significantly reduced ventricular unloading.
Animals↗
Surgical management of transposition of the great arteries.
Sixty-two patients with transposition of the great arteries, ranging in age from one week to thirty-five years, underwent total corrective surgery during a seven year period at Stanford University Hospital. Reported herein are the first pateint to undergo complete correction at out hospital and every subsequent patient until October 1974. Eleven patients died, an overall hospital mortality of 18 per cent. Two of thirty-two patients with transposition of the great arteries and intact ventricular septum died, one of pulmonary hypertension at seven days of age. Nine of thirty patients with transposition of the great arteries and ventricular septal defect with or without pulmonary stenosis died. Cause of death usually was high pulmonary vascular resistance. The Donovan-Rastelli procedure was performed in ten patients, with three deaths, but all patients survived when the inserted right ventricular outflow contained a xenograft aortic valve. Transposition of the great arteries in the first weeks of life must be considered on the individual merits of each case, but the combined medical and surgical approach must be both expedient and thorough if the patient is to survive.
Adolescent↗
Radioimmune assay of heterologous serum gamma-globulin in patients receiving rabbit antihuman thymocyte globulin.
A radioimmune assay (RIA) method for detecting heterologous serum rabbit gamma-globulin (RG) and antibody to this protein is described. The methodology is used for monitoring serum levels of rabbit globulin in patients receiving rabbit ATG (RATG). In 7 cardiac recipients receiving RATG, maximum serum levels of RG were achieved 1-3 days after administration of final dose. RG half-life subsequent to peak serum levels was rapid (X = 36 hr) in 4 patients and prolonged (X = 18 days) in 3 patients. Patient antibody to rabbit gamma-globulin was detectable only in those patients with short RG half-life. Antirabbit antibody titers in these patients were extremely low and barely detectable by RIA.
Animals↗
The status of cardiac transplantation, 1975.
Since December 1967, 263 human cardiac transplant operations have been performed throughout the world. Eighty-two of these were performed at Stanford University Medical Center, In 1974, 27 such operations were performed, 15 at Stanford Survival rates for the entire Standford series are 48% at one year and 25% at three years; survival rates at one and three years for patients surviving the first three critical months after transplantation are 77% and 42%, respectively. Recipients under the age of 55 years, with New York Heart Association Class IV cardiac disability, are selected for transplant procedures according to criteria dictated by experience over the past seven years. A routine immunsuppressive regimen for organ transplantation, incorporating prednisone, azathioprine, and antithymocyte globulin is employed early postoperatively, and prednisone and azathioprine are used for indefinite maintenance therapy. Acute cardiac graft rejection in nearly all recipients is diagnosed by clinical signs, electrocardiographic changes, and percutaneous transvenous endomyocardial biopsy. Ninety-five percent of acute rejection episodes are reversible with appropriate immunosuppressive treatment, but infectious complications are common and have accounted for 56% of all postoperative deaths. The Stanford experience in cardiac transplantation has demonstrated the potential therapeutic value of this procedure. Maximum survival now extends beyond five years. Satisfactory graft function has been documented in long-term surviving patients, the majority of whom have enjoyed a high degree of social and physical rehabilitation.
Acute Disease↗
Survival and function after left ventricular aneurysmectomy.
Operative and late postoperative results in 55 patients undergoing resection of a discrete, saccular type left ventricular aneurysm are described. All patients had occlusive lesions of either the left anterior descending or left main coronary artery, and 72 per cent had significant multivessel disease. Preoperative factors that correlated significantly with decreased long-term survival were age greater than 60 years, severe congestive heart failure, and subnormal cardiac output at rest. The primary determinant of long-term postoperative survival appears to be the functional state of residual myocardium after aneurysmectomy. The survival rate for patients with multivessel disease was not less than that of patients with isolated lesions of the left anterior descending coronary artery. The impact of simultaneous aorto-coronary bypass grafting on postoperative results in patients with multivessel coronary disease is discussed. An advantage to concomitant revascularization with aneurysmectomy cannot be statistically corroborated in this series. However, improvement in results since the routine application of bypass grafting in appropriate cases, the uniform operative survival of bypassed patients with triple vessel disease, and the relatively high frequency of myocardial infarction as a cause of late postoperative death suggest that bypass grafting in patients with multivessel disease should be combined with aneurysmectomy to maximally improve long-term prognosis.
Adult↗