Eugene Dong

Determinants of operative risk in human heart transplantation

Abstract In the past two and a half years twenty-six patients have received heart transplants at Stanford. Over-all survival is 45 per cent at six months, 38 per cent at twelve and eighteen months, and 30 per cent at two years. Analysis of mortality after operation allows separation of these patients into three groups. Three patients died within seventy-two hours of operation, all secondary to markedly elevated pulmonary vascular resistance resulting in progressive right heart failure (group I). Nine patients died in the hospital within two months of operation of infection or rejection (group II). Thirteen patients were discharged in satisfactory condition one to four months after operation (group III). One patient died in the early postoperative period from a cerebrovascular accident apparently unrelated to transplantation. Patients in group I differed significantly from those in groups II and III in having a higher pulmonary artery mean pressure and a higher calculated pulmonary vascular resistance. Patients in group II differed from those in group III with respect to age and the duration of known heart disease. No differences were found between the three groups with respect to number of HL-A antigen mismatches, duration of severe heart disease, cardiac index, mean left atrial pressure, or preoperative bilirubin or blood urea nitrogen levels. Follow-up study of the thirteen patients who survived the immediate postoperative period shows 84 per cent survival at six months, 75 per cent at twelve and eighteen months, and 60 per cent at two years. For patients with end-stage myocardial insufficiency, heart transplantation in appropriately selected cases offers a substantial probability for return to normal activity.

Cardiac transplantation in man

Abstract The primary surgical aspects of cardiac transplantation in nine patients are presented. Most organ donors required vasopressor support prior to transplantation and in three reversible cardiac arrest occurred. Postoperative complications of wound healing have necessitated modification of cannulation technics for cardiopulmonary bypass to avoid peripheral incisions. Postoperative disturbances in cardiac rhythm may be minimized by appropriate tailoring of the right atrium of the donor. In all cases satisfactory myocardial preservation has been achieved with local hypothermia alone. In the immediate postoperative period management has included the use of right ventricular pacing, isoproterenol, and intravenous digitalization in most recipients. Postoperative complications have included immediate failure of the homograft in one patient, requiring retransplantation six hours postoperatively. Infectious complications have been most frequent and contributed directly to death in four patients. At the present time three patients survive at five and a half, four, and three months postoperatively.

New instrument for transvenous cardiac biopsy

Abstract A new forceps is described for obtaining serial endomyocardial biopsy specimens from the human heart. The instrument is introduced percutaneously into the right internal jugular vein and used to obtain tissue from the apex of the right ventricle. Eighty-five biopsy procedures have been performed in 19 patients after cardiac transplantation. The tchnique used was 100 percent successful in obtaining endomyocardial biopsy specimens, and there were no significant complications. A biopsy procedure may be performed within 5 minutes. Serial percutneous transvenous endomyocardial biopsies are now routinely performed with this instrument in new heart transplant recipients and in patients with primary cardiomyopathy.

Successful homotransplantation of the canine heart after anoxic preservation for seven hours

Abstract Experiments are described in which successful homotransplantation of the dog heart was carried out after seven hours of cardiac anoxia. During the period of extracorporeal preservation, the arrested heart was maintained at 2 to 4 °C. by immersion in cold saline solution. Two animals recovered after transplantation and lived for seven and eleven days, respectively, at which time death was caused by homograft rejection.

Observations on the behavior of recipient atria after cardiac transplantation in man

Abstract During cardiac transplantation the posterior and lateral portions of the recipients right and left atria and a posterior rim of interatrial septum are left intact. Persistent electrophysiologic activity of these residual recipient atrial remnants has been manifest as P waves dissociated from the donor heart rhythm and recorded in both standard and intracardiac electrocardiograms. Physiologically appropriate changes in recipient atrial rate have occurred in response to the respiratory cycle, donor heart systole, atropine, tyramine, amyl nitrite, carotid sinus pressure, the Valsalva maneuver and exercise. In several patients synchronization of the recipient atrial rate with the donor heart rate has been observed during exercise when these rates approached a similar level. Fibrillation and flutter of the recipient atria, independent of the donor heart rhythm, have been observed in 3 recipients. In 4 patients studied by cardiac catheterization 1 year postoperatively mechanical effects of recipient atrial contractions were detected in both right- and left-sided pressure measurements. Recipient left atrial contraction occurring simultaneously with donor atrial systole increased left ventricular end-diastolic pressure by 2 to 4 mm Hg and produced significantly greater peak left ventricular and arterial systolic pressures as well as augmented left ventricular ejection times. In several patients, especially during episodes of threatened graft rejection, diastolic heart sounds related to recipient atrial contraction were noted clinically and recorded on phonocardiograms. Such recipient atrial gallop sounds simulated both atrial and ventricular gallop sounds of donor heart origin, and occurred in addition to both to produce hybrid diastolic gallop rhythms. The physiologic mechanisms and implications of recipient atrial behavior are discussed.

Initial clinical experience with heart transplantation

Abstract Clinical experience with cardiac transplantation in 2 patients with terminal heart disease is described. The first patient suffered chronic and progressive heart failure due to postviral myocardial fibrosis and coronary artery disease. Following successful operation multiple complications occurred, and the patient died on the fifteenth postoperative day of gastrointestinal bleeding and gram negative sepsis. Histologic evidence of mild rejection was present at postmortem examination. The second patient presented with terminal ischemic heart disease complicated by severe pulmonary hypertension. Postoperatively severe and unremitting arterial hypoxemia caused death on the third postoperative day. Postmortem examination failed to show evidence of rejection but revealed advanced obliterative changes in the pulmonary vasculature. Despite the disappointing outcome of these 2 cases, cardiac transplantation in man deserves extensive clinical trial. The methods of clinical study and eventual objectives are outlined.

Acute Rejection of the Allografted Human Heart: Diagnosis and Treatment

Abstract Twenty-six patients have received heart transplants at Stanford University Medical Center. Of these, 11 were alive at six months (42%), 10 at twelve and eighteen months (37%), and 7 at twenty-four months (26%). Sixty episodes of acute allograft rejection were diagnosed in 21 patients. No correlation between histocompatibility match and rejection history was apparent. Emphasis was placed on early diagnosis of rejection episodes and intermittent use of high-dose immunosuppressive therapy. Useful indexes of early graft rejection included electrocardiographic changes (decreasing QRS voltage, appearance of arrhythmias, right shift of the electrical axis, ST-T wave changes), clinical findings (appearance of gallop rhythm, decreased precordial activity, hypotension), and ultrasound echocardiographic findings (increased thickness of left ventricular wall, increased right ventricular diameter). Fifty-seven rejection episodes were reversed with increased immunosuppressive therapy, and 3 progressed to graft failure and the patients death. In the cardiac transplant recipient, monitoring multiple indexes of allograft function allows the early diagnosis and successful treatment of most episodes of acute rejection.

Electrocardiograms of Dogs with Heart Homografts

Serial electrocardiograms from 50 dogswhich survived 4 days to 12 months with orthotopic cardiac homografts have been evaluated. Although sinus rhythm is the basic mechanism in all homografted hearts, arrhythmias are frequently encountered early in the post-transplant period and later during episodes of threatened rejection. The decrease in QRS voltage which consistently accompanies impending rejection makes the electrocardiogram indispensable in monitoring the cardiac homograft.

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 Stanford 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 immunosuppressive 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.

Suppression of Rejection Crises In the Cardiac Homograft

aboratory studies of cardiac transplantation have brought to light several unique problems in operative and postoperative manageA ment which require thorough evaluation before clinical trials are to be considered seriously. Attention in this report is focused on two areas: posttransplantation recovery of the heart, and recognition and treatment of cardiac rejection. Observations have been drawn from 20 control homotransplants living 4 to 21 days and 25 animals treated with immunosuppressants surviving from 6 to 230 days.