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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.

Coronary arterial narrowing in Takayasu's aortitis

A patient with Takayasus aortitis and angina pectoris due to severe narrowing of the right and left coronary arterial ostia is described. Takayasus arteritis produces a panaortitis, with thickening of the adventitia predominating, and an inflammatory cell infiltrate involving the adventitia, outer media and vasa vasorum. Narrowing of the coronary arteries in this disease is due to extension into these arteries of the processes of proliferation of the intima and contraction of the fibrotic media and adventitia that occur in the aorta. The distal coronary arteries usually do not manifest arteritis and are normal in caliber. Angina pectoris may be the first symptom of the disease if the coronary arteries are the initial site of severe arterial narrowing. The coronary arterial bypass graft operation is effective therapy for treating coronary arterial narrowing due to Takayasus arteritis.

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.

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.

Patient-Related Risk Factors as Predictors of Results Following Isolated Mitral Valve Replacement

Results following isolated mitral valve replacement in 897 consecutive patients over a twelve-year period were analyzed with regard to the influence of various preoperative patient-related risk factors. Actuarial data analysis allowed definition of major preoperative, etiological, clinical, and hemodynamic correlates to both perioperative and long-term postoperative patient survival. Patient age below 60 years, preoperative New York Heart Association Functional Class of III or less, cardiac index greater than 2.0, and left ventricular end-diastolic pressure of less than 12 mm Hg were all highly significant correlates of improved perioperative as well as long-term patient survival. Patients whose predominant functional lesion was mitral insufficiency had only a 53% five-year survival (187 of 352 patients) following mitral valve replacement as opposed to 70% (521 of 745 patients) for those who had mixed or stenotic mitral lesions. Primary ischemic mitral dysfunction was associated with only 31% five-year survival (17 of 54 patients) after mitral valve replacement in contrast to 69% (480 of 695 patients) for patients with rheumatic mitral lesions. The presence of occlusive coronary artery disease coexisting with, but not the primary cause of, mitral dysfunction was associated with decreased perioperative and late postoperative survival. Results support both earlier operative intervention and wider use of associated procedures, ie, coronary bypass grafting, with mitral valve replacement. Recognition of major preoperative patient-related risk factors should enhance survival following this procedure.

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.

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.

Clinical Experience with a Porcine Aortic Valve Xenograft for Mitral Valve Replacement

Abstract Between March, 1971, and July, 1973, 103 patients underwent mitral valve replacement with a glutaraldehyde-preserved porcine aortic valve mounted on a flexible polypropylene, Dacron-covered stent. Overall operative survival was 95.1%. Actuarial analysis of late postoperative results indicates 92% survival through 2 years, with functional improvement in nearly all patients. The rate of systemic thromboembolism has been approximately 1.7% per patient-year without anticoagulants. No valve failure has occurred. We conclude that this xenograft prosthesis provides a technically and functionally satisfactory valve substitute, the durability of which appears to significantly exceed that of previously available tissue valves for mitral replacement.

Acute retrograde dissection of the ascending thoracic aorta

Abstract The clinical, aortographic and pathologic features of six patients with acute retrograde dissection of the ascending thoracic aorta are presented and appropriate guidelines for surgical treatment are proposed. Although acute dissection of the aorta was the clinical diagnosis in these patients, clinical features were not helpful in identifying the pattern or extent of dissection. Aortography demonstrated that the site or sites of intimal tear occurred adjacent to the origin of the innominate artery (three patients) or left subclavian artery (two patients); an intimal tear was not seen in one patient. Five of the six patients also had acute or chronic (or both) antegrade dissection of the descending thoracic aorta. Retrograde dissection of the ascending aorta occurred in the outer portion of the media. The primary histologic changes were fragmentation of elastic fibers and fibrosis of the media. Three patients died, including two of the five patients who were treated surgically; the other three patients survived. Immediate replacement of the ascending aorta with a Dacron graft is recommended to prevent lethal complications due to extension of retrograde dissection, even though dissection may involve both the ascending and descending aorta and the site of intimai disruption may not be resected. The aortic arch or descending thoracic aorta, or both, can be replaced later, utilizing total body hypothermia and temporary circulatory arrest, if further dis-section or enlargement of the aorta occurs after emergency operation on the ascending aorta.

Tissue valve replacement of prosthetic heart valves for thromboembolism

Twenty-five patients who had repeated thromboemboli from a prosthetic mitral valve were treated with reoperation using a tissue valve prosthesis. Reoperation was performed an average of 4.0 years after the original valve replacement in 14 men and 11 women, with an average age of 50 (range 35 to 65) years. A stented allograft was used in the first 7 patients and a porcine xenograft in the last 18 patients. There were one hospital death and two late deaths. With the first prosthetic valve there were 66 documented embolic episodes in 101.5 patient years (0.65 embolus/year). Only four embolic episodes in 67.4 patient years (0.059 embolus/year) occurred after tissue valve replacement (P less than 0.001). These results indicate that in patients with recurrent or severe embolization after prosthetic heart valve replacement, rereplacement with a tissue prosthesis can be safely performed and significantly reduces the likelihood that additional embolic episodes will occur.