Norman E. Shumway

Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease.

: We report our initial experience with three patients who received heart-lung transplants. The primary immunosuppressive agent used was cyclosporin A, although conventional drugs were also administered. In the first patient, a 45-year-old woman with primary pulmonary hypertension, acute rejection of the transplant was diagnosed 10 and 25 days after surgery but was treated successfully; this patient still had normal exercise tolerance 10 months late. The second patient, a 30-year-old man, underwent transplantation for Eisenmengers syndrome due to atrial and ventricular septal defects. His graft was not rejected, and his condition was markedly improved eight months after surgery. The third patient, a 29-year-old woman with transposition of the great vessels and associated defects, died four days postoperatively of renal, hepatic, and pulmonary complications. We attribute our success to experience with heart-lung transplantation in primates, to the use of cyclosporin A, and to the anatomic and physiologic advantages of combined heart-lung replacement. We hope that such transplants may ultimately provide an improved outlook for selected terminally ill patients with pulmonary vascular disease and certain other intractable cardiopulmonary disorders.

Cardiac Transplantation in Man VII. Cardiac Allograft Pathology

To date, 12 of 18 patients receiving cardiac allografts at the Stanford Medical Center have died. Five of these died with some degree of graft failure resulting from rejection injury. The remaining seven demonstrated some morphologic evidence of rejection, but death was due to other causes including pulmonary hypertension in two, hemorrhage and sepsis in one, infection in two, cerebral embolism in one, and hepatic failure in one. Acute rejection injury was defined in 10 allografts, accelerated acute rejection in one, and chronic rejection in nine.The clinical signs of allograft rejection and their morphologic correlates were essentially as predicted from the study of orthotopic canine cardiac allografts. The clinical features and most of the anatomic lesions of acute rejection were usually reversible by current methods of immunosuppressive therapy. Chronic rejection, manifested primarily by obliterative intimal proliferation in coronary arteries, was present in most allografts obtained from patients surviving at least 1 month. Its severity was apparently not related to the quality of the host-donor leukocyte antigen match, and it was not routinely detectable clinically. This intimal thickening may limit long survival of patients undergoing cardiac transplantation.

Treatment of endocarditis with valve replacement: the question of tissue versus mechanical prosthesis

BACKGROUND It remains unknown whether there is any important clinical advantage to the use of either a bioprosthetic or mechanical valve for patients with native or prosthetic valve endocarditis. METHODS Between 1964 and 1995, 306 patients underwent valve replacement for left-sided native (209 patients) or prosthetic (97 patients) valve endocarditis. Mechanical valves were implanted in 65 patients, bioprostheses in 221 patients, and homografts in 20 patients. RESULTS Operative mortality was 18+/-2% and was independent of replacement valve type (p > 0.74). Long-term survival was superior for patients with native valve endocarditis (44+/-5% at 20 years) compared with those with prosthetic valve endocarditis (16+/-7% at 20 years) (p < 0.003). Survival was independent of valve type (p > 0.27). The long-term freedom from reoperation for patients who received a biologic valve who were younger than 60 years of age was low (51+/-5% at 10 years, 19+/-6% at 15 years). For patients older than 60 years, however, freedom from reoperation with a biological valve (84+/-7% at 15 years) was similar to that for all patients with mechanical valves (74+/-9% at 15 years) (p > 0.64). CONCLUSIONS Mechanical valves are most suitable for younger patients with native valve endocarditis; however, tissue valves are acceptable for patients greater than 60 years of age with native or prosthetic valve infections and for selected younger patients with prosthetic valve infections because of their limited life expectancy.

Hemodynamic Observations One and Two Years after Cardiac Transplantation in Man

Cardiac catheterization studies were performed in eight patients 1 year after cardiac transplantation and in two of these again at 2 years. Intracardiac pressures at rest were normal in all patients, both 1 and 2 years postoperatively. Average cardiac index at rest at 1 year was 2.3 liters/min/m2 and average heart rate was 90 beats/min. Responses to amyl nitrite, atropine, and tyramine failed to demonstrate efferent autonomic reinnervation of the donor hearts. Findings associated with a 10-min period of submaximal supine bicycle exercise 1 year after transplantation included: (1) a gradual rise in heart rate throughout most of the exercise period; (2) prompt elevation of left ventricular end-diastolic pressure by an average increment of 10 mm Hg, followed by a decrease during late exercise in some patients; (3) a progressive increase in LV systolic pressure throughout the first half of the exercise period; (4) a continuously positive change in LV rate of pressure change (dp/dt) throughout exercise; (5) an average 44% increase in stroke volume; and (6) an average 92% increase in cardiac output. The slope of the regression of cardiac output on oxygen uptake during exercise was within the range of normal. Cardiac output, however, was lower than normal both at rest and during exercise, and the arteriovenous oxygen diflerence was accordingly widened.In one patient studied 1 and 2 years after transplantation, hemodynamic findings were comparable on both occasions. In the other, however, the cardiac output response to exercise was distinctly diminished at 2 years as compared to 1 year, due almost entirely to failure of the stroke volume to increase. Coronary arteriography in this recipient revealed evidence of occlusive coronary disease compatible with graft atherosclerosis.These studies demonstrate the sustained capacity of the transplanted human heart to support normal physical activity late in the postoperative period. Although utilizing atypical adaptive mechanisms characteristic of the denervated heart, the transplanted heart responds in a directionally appropriate manner to the metabolic demands of exercise.

A Reconsideration of Cerebral Perfusion in Aortic Arch Replacement

Ten patients underwent aortic arch replacement for aneurysmal disease from 1970 to 1985 using a simplified cardiopulmonary bypass (CPB) technique with partial brachiocephalic perfusion, low CPB flow (30 to 50 ml/kg/min), moderate systemic cooling (26 degrees to 28 degrees C), and topical hypothermic myocardial protection. The arterial line from a single pump head has a Y shape to perfuse the femoral artery (20F cannula) and either the innominate or left carotid artery (14F). Of the 10 patients (mean age, 58 years) with arch aneurysm (6 atherosclerotic, 2 dissections, and 2 degenerative), 3 had previously undergone major cardiovascular operations. Concomitant procedures included aortic valve replacement in 4 and coronary artery bypass grafting in 3. Eight patients survived the procedure, and 1 died three weeks after operation of a ruptured abdominal aneurysm. Among the survivors, CPB time was 119 +/- 36 minutes (+/- standard deviation), myocardial ischemia time was 79 +/- 32 minutes, and intraoperative blood requirement was 5.9 +/- 3.4 units. There were no postoperative strokes. Neurological complications were only minor and included an asymptomatic miosis and ulnar nerve paresthesias in 1 patient and transient vocal cord palsy in another. Applicable in most patients undergoing elective resection of degenerative and atherosclerotic arch aneurysms and in selected patients with arch dissections, this simplified technique of brachiocephalic perfusion without circulatory arrest provides an attractive and safe alternative; the potential advantages are technical simplicity, reduced CPB and operating times, and satisfactory cerebral protection.

Twenty-year clinical experience with porcine bioprostheses

BACKGROUND For the past 25 years, porcine valves have been the most widely implanted bioprosthesis, thereby becoming the standard for comparison with newer bioprosthetic valves. METHODS We retrospectively analyzed 2,879 patients who underwent aortic (AVR; n = 1,594) or mitral (MVR; n = 1,285) valve replacement between 1971 and 1990. Follow-up was 97% complete and extended to 20 years (total, 17,976 patient-years). Patient age ranged from 16 to 94 years; mean age in patients who underwent AVR was 60 +/- 15 (+/- standard deviation) years; that for patients who underwent MVR was 58 +/- 13 years. RESULTS The operative mortality rates were 7% +/- 1% (70% confidence limits) for AVR and 10% +/- 1% for MVR. Actuarial estimates of freedom from structural valve deterioration at 10 and 15 years were 78% +/- 2% (SE) and 49% +/- 4%, respectively, for the AVR subgroup; and 69% +/- 2% and 32% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from reoperation at 10 and 15 years were 76% +/- 2% and 53% +/- 4%, respectively, for the AVR subgroup and 70% +/- 2% and 33% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from thromboembolism at 10 and 15 years were 92% +/- 1% and 87% +/- 2%, respectively, for the AVR subgroup and 86% +/- 1% and 77% +/- 3%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from anticoagulant-related hemorrhage at 10 and 15 years were both 96% +/- 1% for the AVR subgroup and 93% +/- 1% and 90% +/- 2%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from valve-related mortality at 10 and 15 years were 86% +/- 1% and 78% +/- 3%, respectively, for the AVR subgroup and 84% +/- 2% and 70% +/- 4%, respectively, for the MVR subgroup (p = not significant). Multivariate analysis (Cox model) showed younger age, later year of operation, and valve site (MVR > AVR) to be significant risk factors for structural valve deterioration. Younger age, later year of operation, valve site (MVR > AVR), and renal insufficiency were the significant, independent risk factors for reoperation. Multivariate analysis revealed that higher New York Heart Association functional class, longer cardiopulmonary bypass time, congestive heart failure, renal insufficiency, and longer cross-clamp time were significant risk factors for valve-related mortality. Valve manufacturer did not emerge as a factor in any analysis. CONCLUSIONS These long-term results with porcine bioprostheses were satisfactory, particularly in older patients and those undergoing AVR. As expected, younger age was a significant risk factor for structural valve deterioration and reoperation in both groups. Surprisingly, the durability of porcine bioprosthetic valves has not improved over time, which possibly can be attributed to more enhanced postoperative surveillance and earlier reintervention. These first-generation Hancock and Carpentier-Edwards porcine bioprostheses achieved similar long-term performance.

Infectious Complications After Cardiac Transplantation in Man

Abstract Infectious complications developed postoperatively in 12 of 20 patients undergoing cardiac transplantation. In five, infection was considered to have caused or contributed directly to deat...

Percutaneous Transvenous Endomyocardial Biopsy in Human Heart Recipients: Experience with a New Technique

Abstract Sixty-seven cardiac biopsy procedures have been performed in 17 cardiac transplant recipients at Stanford University Medical Center. Six other patients were biopsied as part of their assessment prior to transplantation. Biopsies were performed percutaneously through a sheath inserted into the right internal jugular vein. Two instruments were used, a Konno-Sakakibara bioptome and a new catheter biopsy forceps of our own design. Biopsies of the endomyocardium sufficient for examination by light and electron microscopy were obtained on all but one occasion. There were no deaths and no serious complications. Serial biopsies performed in the first two months after transplantation were used to diagnose and aid the management of acute rejection episodes. Biopsies on long-term survivors permitted the recognition of late acute rejection episodes and provided a new assessment of the myocardium following cardiac transplantation. Percutaneous transvenous endomyocardial biopsy is simple and safe to perform and is an important new aid in the management of patients following cardiac transplantation.

Valve Replacement in Patients with Native Valve Endocarditis: What Really Determines Operative Outcome?

The influence of 27 variables on operative mortality and late complications (defined as residual or recurrent endocarditis or late bland periprosthetic leak) was determined using discriminant analysis for 108 patients undergoing valve replacement for native valve endocarditis at Stanford University Medical Center from March, 1964, to January, 1983. Congestive heart failure was the indication for valve replacement in 86% of patients. Aortic valve replacement was required in 68% and mitral valve replacement, in 26%. Patients were arbitrarily defined as having active (58%) or healed (42%) endocarditis. Follow-up included 515 patient-years and extended to a maximum of 19 years. Operative mortality was 15 +/- 4%, and 17 patients had late complications (linearized rate, 3.3% per patient-year). Seven variables were significantly related to operative mortality in the univariate analysis, but only organism (Staphylococcus aureus versus all others, p = 0.0302) was a significant independent predictor of operative mortality. For late complications, only 2 of 7 significant univariate covariates proved to be significant independent determinants: organisms on valve culture or gram stain and the presence of annular abscess. Patients with S. aureus endocarditis not showing prompt response to antibiotic treatment must be considered for early operation. Similarly, timely operative intervention for patients with annular abscess will be essential in decreasing late valve infections and perivalvular leaks.

Thirty years of cardiac transplantation at stanford university

BACKGROUND The experience with 30 years of cardiac transplantation at Stanford University Medical Center was reviewed. A total of 954 transplants were performed in 885 patients. Patients were divided into 3 groups based on immunosuppression received: group I, no cyclosporine (INN: ciclosporin) (n = 201) (January 1968-November 1980); group II, cyclosporine (n = 248) (December 1980-June 1987); and group III, cyclosporine + OKT3 (n = 436) (July 1987-March 1998). RESULTS The 1-, 5-, and 10-year actuarial survivals were 68%, 41%, and 24% (group I); 80%, 57%, and 37% (group II); and 85%, 68%, and 46% (group III) (I vs II, P <.01; I vs III, P <.005; and II vs III, P <.005). The 1-, 5-, and 10-year actuarial death rates from rejection were 8%, 12%, and 14% (group I); 5%, 7%, and 7% (group II); and 2%, 5%, and 5% (group III) (I vs II, P = not significant; I vs III, P <.005; and II vs III, P <.005). The 1-, 5-, and 10-year actuarial death rates from infection were 25%, 43%, and 50% (group I); 8%, 17%, and 29% (group II); and 6%, 11%, and 16% (group III) (I vs II, P <.005; I vs III, P <.005; and II vs III, P <.05). The 1-, 5-, and 10-year actuarial death rates from graft coronary artery disease were 0%, 5%, and 13% (group I); 0%, 12%, and 19% (group II); and 1%, 6%, and 9% (group III) (I vs II, P <.01; I vs III, P <.005; and II vs III, P = not significant). There have been 69 retransplants in 67 patients with 1-, 5-, and 10-year actuarial survivals of 49%, 27%, and 15%, respectively. CONCLUSIONS The evolution of 3 decades of experience with cardiac transplantation has resulted in improved overall survival. The incidence of rejection and of death from infection and graft coronary artery disease have decreased over time, primarily as a result of improvements in immunosuppression and in the prevention and treatment of infection. Continued advances in perioperative management and the development of more specific, less toxic immunosuppressive agents could further refine this initial experience and improve the survival and quality of life of patients after cardiac transplantation.