Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation.

OBJECTIVES: The present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial perfusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy. BACKGROUND: Allograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy. METHODS: In 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every year after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and 12 months after transplantation and twice a year thereafter. Prospective follow-up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin. RESULTS: Twenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, two were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first year (40%) (p = 0.033). Eighty percent of patients who responded to follow-up. CONCLUSIONS: The present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease.

Quantitative assessment of valvular function after cardiac transplantation by pulsed Doppler echocardiography.

In 31 patients who had undergone cardiac orthotopic transplantation, valvular regurgitation was studied by echocardiographic and pulsed Doppler over 2 years. The first week after cardiac transplantation, transplant recipients had an increase in the severity of tricuspid, mitral (group II), and aortic regurgitation, as well as a greater number of simultaneously regurgitating valves when compared with those in a group of 60 normal subjects of similar age to heart donors: transplant recipients, trivalvular regurgitation 48% (95% confidence interval [CI] 30 to 66) vs control group, 5% (CI 1 to 13; p < 0.001). Moderate-severe tricuspid regurgitation (TR) was the most frequent occurrence (55%, CI 36 to 73) followed by pulmonary (PR) (42%, CI 25 to 61), moderate mitral (MR) (32%, CI 15 to 51), and mild aortic (AR) (23%, CI 10 to 43) regurgitation. These regurgitations were asymptomatic at rest except for TR. TR was associated with right-sided heart failure in 76% of patients in the early postoperative period and controlled with diuretic drugs. This regurgitation correlated with persistence of post-transplant pulmonary hypertension (r = 0.6) and was not related to pulmonary hypertension before cardiac transplant. There was also no relation found between donor ischemia time or episodes of cardiac rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler-derived gradients in normally functioning Monostrut Björk-Shiley prostheses.

In summary, reference values of Doppler gradients obtained in a large number of patients with normal-functioning mitral and aortic Monostrut Björk-Shiley prostheses are reported. It is shown that the value of the transprosthetic gradient increases with decreasing valve size in patients with aortic prostheses. No individual significant variations of the transprothetic Doppler gradient during a 3-year follow-up were observed.

Assessment of the appropriateness of the decision of heart transplantation in idiopathic-dilated cardiomyopathy.

One hundred thirty patients with idiopathic-dilated cardiomyopathy were referred for heart transplantation to our center and followed for 18 months. Heart transplantation was performed on 63 patients, 17 patients died before transplantation due to heart failure, and 50 patients never had transplantation. Clinical, electrocardiographic, echocardiographic, and hemodynamic data of the 50 nontransplanted survivors and the 17 patients who died were used to identify independent risk variables with discriminant analysis. Using a statistical model based on the results of discriminant analysis, each of the remaining 63 transplanted patients were predicted as being alive or dead in absence of transplantation. The discriminant analysis identified right atrial pressure, cardiac index, and the New York Heart Association functional class as the strongest predictors of 18-month outcome. The accuracy of the model in predicting survival without transplantation in the nontransplanted group of patients, based on the concordance between actual and predicted outcome, was 85% (kappa = 0.62). Subsequent application of this model to the transplanted group of patients suggested that the decision for transplantation was appropriate in 41 of the 63 patients, and could have been premature in the remaining 22 patients predicted as alive. These results suggest that two-thirds of patients receiving transplants would have died without intervention, but the decision to transplant could have been premature in the remaining patients.

Coronary angioplasty in iatrogenic coronary artery stenosis.

Iatrogenic coronary artery stenosis as a serious complication of aortic valve procedures is a difficult condition to solve. We present a case in which both ostia were involved. As the patient refused reoperation, percutaneous transluminal coronary angioplasty (PTCA) was used.

Clinical and hemodynamic results of cardiac valve replacement with the Monostrut Björk-Shiley prosthesis.

Between May 1983 and April 1986, 318 patients underwent cardiac valve replacement with the Monostrut Björk-Shiley prosthesis. There were 136 aortic valve replacements, 128 mitral valve replacements, and 54 multiple replacements. A total of 373 valves were implanted. Associated procedures were done in 79 (25%) of the patients. Hospital (30-day) mortality rate was 5.6% (18 patients): 2.9% (n = 4) after aortic, 7.8% (n = 10) after mitrals and 7.4% (n = 4) after multiple valve replacement. Follow-up was obtained in all 300 operative survivors, for a total of 500 patient-years (mean 18 months). Actuarial survival rate, excluding operative deaths, at 4 years was 94.7% +/- 1.5% (mean +/- standard error of the mean). There were 16 thromboembolic episodes (3.2/100 patient-years). Freedom from all valve-related complications was 87% +/- 2.4% at 3 1/2 years. Neither valve thrombosis nor structural failure has been observed. Eighty percent of the patients are in New York Heart Association functional class I. Forty-two patients (26 with aortic and 16 with mitral valve replacement) underwent cardiac catheterization a mean of 6 1/2 months after the operation. In the aortic position, peak gradients were an average of 6.9 +/- 1.2 mm Hg. Mean systolic gradients were 12.4 +/- 6.3 mm Hg and did not increase with exercise. In the mitral position, end-diastolic gradients were an average of 2.1 +/- 2 mm Hg and mean gradients, 5.9 +/- 2 mm Hg. Discharge coefficient (estimated orifice area/geometric area) was 0.63 +/- 0.2 for the aortic and 0.53 +/- 0.2 for the mitral prostheses. Disc opening was maximal in most patients. These results indicate that the Monostrut prosthesis has a low rate of thromboembolic events, no structural failures or thrombotic obstructions and excellent hemodynamic performance, especially in the small aortic sizes (discharge coefficient for 19 and 21 mm valves, 0.77).

Arterial line filtration during cardiopulmonary bypass. Neurologic, neuropsychologic, and hematologic studies.

One hundred patients who underwent elective cardiac operations were randomized into two groups. Group 1 had a 20 micron nylon screen filter in the arterial line. In Group 2 no filter was used in the arterial line. Neurologic and neuropsychologic examination of the patients was performed with seven psychometric tests of the Wechsler Memory Scale and the Wechsler Adult Intelligence Scale. These tests were conducted before and a mean of 10 days after the operation. Platelet counts and hemoglobin and total protein levels were measured at the onset and at the end of cardiopulmonary bypass. Two patients died during their hospital stay. Neurologic damage with focal signs was found in the postoperative examination in six patients (three in each group). Twenty-eight patients (28.5%) exhibited signs of mild cerebral dysfunction as assessed by the presence of archaic (primitive) reflexes. Fifteen were in Group 1 and 13 in Group 2 (no significant difference). Sixty patients (61%) had decrements greater than one standard deviation in at least one of the three tests that showed most decreased postoperative scores. There were 32 in Group 1 and 28 in Group 2 (no significant difference). When each test was analyzed individually, there were no significant differences between the two groups. Platelet counts decreased, during cardiopulmonary bypass, a mean of 33% in Group 1 and 34.5% in Group 2 (no significant difference). Both hemoglobin and total protein levels remained virtually unchanged. These results indicate that the addition of a small-pore filter in the arterial line does not prevent the neurologic and neuropsychologic disturbances frequently encountered after cardiopulmonary bypass. The filter itself does not appear to have a direct effect on the blood components. Routine use of an arterial line filter remains questionable.

Hemodynamic effects of prostaglandin E1 and isoproterenol early after cardiac operations for mitral stenosis.

Patients with mitral stenosis and some degree of right ventricular failure may benefit from inotropic or pulmonary vasodilator drugs in the early postoperative period. Thirty patients undergoing an operation for mitral stenosis were randomized into three groups. In group I (n = 10), isoproterenol (5 micrograms/kg/min) was started in the immediate postoperative period. In group P (n = 10), prostaglandin E1 (0.08 microgram/kg/min) was given, and in group C, the control group (n = 10), no drugs were used. After the operation and before drug therapy was begun, basal measurements of cardiac index, mean pulmonary arterial and mean arterial pressures, and pulmonary vascular resistance were taken. Measurements were repeated at 6, 12, and 24 hours. Mean measurements of cardiac index (basal up to 24 hours) were as follows: 1.39 +/- 0.3, 1.92 +/- 0.4, 2.4 +/- 0.5, and 2.34 +/- 0.3 L/min/m2 for group C; 1.54 +/- 0.5, 2.64 +/- 0.4, 2.68 +/- 0.7, and 2.2 +/- 0.6 L/min/m2 for group I, and 1.57 +/- 0.3, 2.2 +/- 0.6, 2.72 +/- 0.7, and 2.27 +/- 0.4 L/min/m2 for group P (p less than 0.05 between groups C and I at 6 and 12 hours). Mean pulmonary artery pressures were as follows: 19.5 +/- 3.2, 24.8 +/- 7, 27.7 +/- 7.3 and 28.8 +/- 5.7 mm Hg in group C; 21.4 +/- 8.7, 25.7 +/- 7.2, 26.4 +/- 7, and 29.4 +/- 8.6 mm Hg in group I, and 19.1 +/- 4, 19.2 +/- 3, 20.4 +/- 6, and 20.7 +/- 5 mm Hg in group P (p less than 0.05, group P versus groups C and I at 6, 12, and 24 hours). Mean pulmonary vascular resistances were as follows: 3.9 +/- 2.4, 3.9 +/- 1, 3.36 +/- 2, and 3.2 +/- 1.4 Wood units in group C; 4.84 +/- 4, 3.37 +/- 2.2, 3.69 +/- 3, and 4.69 +/- 4.1 Wood units in group I, and 3.29 +/- 1.3, 1.71 +/- 0.5, 1.61 +/- 0.5, and 1.96 +/- 0.8 Wood units in group P (p less than 0.05, group P versus groups C and I at 6, 12, and 24 hours). There was no difference in mean systemic arterial pressure among the three groups. Our results indicate that patients subjected to mitral valve operations have a low cardiac index. Isoproterenol increases cardiac index but has little effect on pulmonary resistance. At low doses, prostaglandin E1 effectively decreases pulmonary vascular resistance without altering systemic arterial pressure or heart rate.

The Monostrut Björk-Shiley valve. Seven years' experience.

The results of cardiac valve replacement with the Monostrut Björk-Shiley prosthesis (Shiley, Inc., Irvine, Calif.) during a 7-year period are presented. A total of 984 valves were implanted in 820 patients from May 1983 to April 1990. Aortic valve replacement was performed in 378 patients, mitral replacement in 294, and multiple replacement in 148. In addition, 180 patients (22%) underwent associated procedures. Mean age was 52.6 +/- 11 years. Operative (30 days) mortality was 5.9% (49 patients): 3.9% (15 patients) for aortic, 7.8% (23 patients) for mitral, and 7.4% (11 patients) for multiple valve replacement. All patients were given long-term anticoagulation therapy. Follow-up was 99% complete (eight patients were lost to follow-up), with a closing interval of 3 months, and totaled 2422 patient-years. Valve-related complications, expressed as percentage event-free (+/- standard error) at seven years were as follows: structural deterioration, 100%; nonstructural dysfunction, 98.3% +/- 0.6%; thromboembolism, 90.2% +/- 1.7%; anticoagulant-related hemorrhage, 88.7% +/- 2.8%; and prosthetic valve endocarditis, 98.1% +/- 0.8%. There were no cases of valve thrombosis. Actuarial survival (free from operative, valve-related, and sudden death) was 88.4% +/- 1.2% at 7 years. Freedom from reoperation was 96.8% +/- 0.1%. Probability of being free from all valve-related morbidity and mortality was 70% +/- 3%, and 708 (93%) of the survivors were in New York Heart Association class I or II. Serial Doppler echocardiograms were done prospectively in 243 patients (with 154 aortic and 120 mitral prostheses), both postoperatively and at regular intervals up to 3 years. Mean prosthetic gradients ranged from an average of 20.9 to 7 mm Hg in the aortic prostheses (21 to 29 mm) and from 6.1 to 4.8 mm Hg in the mitral prostheses (25 to 31 mm). The gradients in each patient did not change significantly during the follow-up period. Our 7 year's experience with the Monostrut valve shows a low rate of valve-related complications, a durable design, and good hemodynamic and functional results.

Coronary endothelial dysfunction as a predictor of intimal thickening in the long term after heart transplantation.

OBJECTIVES: The mechanisms of cardiac allograft vasculopathy and its predisposing factors are multifactorial and as yet not well established. To determine the influence of endothelial dysfunction on the development of intimal thickening, we prospectively analyzed the vasomotor response to acetylcholine and nitroglycerin, as well as other donor and recipient variables. Findings were correlated with the coronary intimal thickness, which was evaluated by means of intravascular ultrasonography. METHODS: Nineteen patients who had undergone heart transplantation 4.89 +/- 2.35 years previously and who had angiographically normal coronary arteries were included. Endothelial function was analyzed by quantitative coronary analysis of the vasomotor response of the left anterior descending artery to acetylcholine. An intimal thickness index, reflecting the percentage of intima obstructing the coronary lumen, was calculated. RESULTS: Nine (47%) patients showed endothelial dysfunction, and the remaining 10 (53%) patients had a normal response. Four (44%) of 9 patients with a weight gain of greater than 20% after the operation showed endothelial dysfunction compared with none of the 10 patients with normal responses (P <.04). The severity of the intimal thickness correlated with the years after transplant (r = 0.45, P <.05). Patients with endothelial dysfunction had more intimal thickening than those without (32% +/- 17% vs 17% +/- 12%, respectively; P <.05). Furthermore, the degree of intimal thickening correlated with the magnitude of the vasomotor response to acetylcholine (r = -0.60, P =.006). No relationship was found between intimal thickness and the vasodilatory response to nitroglycerin. As independent variables for intimal thickness, multivariate analysis detected the magnitude of the response to acetylcholine (P =.0005), years after transplant (P =.01), and ischemic time (P =.03). CONCLUSIONS: Cardiac allograft vasculopathy is a multifactorial disease the severity of which increases over time. Endothelial dysfunction is a predictive factor of intimal thickening severity. Predisposing factors that provoke endothelial injury, such as perioperative ischemic time and obesity, may contribute to the development of allograft vasculopathy.

Aprotinin versus desmopressin for patients undergoing operations with cardiopulmonary bypass. A double-blind placebo-controlled study.

BACKGROUND: Aprotinin reduces blood loss in operations done with cardiopulmonary bypass, whereas the use of desmopressin remains controversial. We compared aprotinin, desmopressin, and placebo in a double-blind, randomized trial to evaluate bleeding and transfusion requirements. METHODS AND RESULTS: One hundred forty-nine patients (48 received aprotinin, 50 desmopressin, 51 placebo) were included. Blood loss and transfusion requirements were recorded and levels of Factor VIII coagulant activity, von Willebrand's factor, thrombin-antithrombin complexes, and D-dimer were measured. Overall blood loss was 195 +/- 146 ml/m2 in the aprotinin group, 400 +/- 192 ml/m2 in the desmopressin group, and 489 +/- 361 ml/m2 in the placebo group (95% confidence intervals: difference between desmopressin and aprotinin 98 to 312 ml/m2, p < 0.001; difference between placebo and aprotinin 190 to 398 ml/m2, p < 0.001). Twenty-six percent of patients treated with aprotinin, 66% of those treated with desmopressin, and 56% of those treated with placebo were given transfusion (95% confidence intervals: difference between aprotinin versus placebo plus desmopressin 51% to 71%, p < 0.001). Fibrinolytic activation throughout cardiopulmonary bypass was markedly higher with placebo or desmopressin administration. D-dimer level correlated with overall blood loss in patients receiving desmopressin or placebo, but not in those receiving aprotinin. CONCLUSION: Aprotinin administration reduces blood loss and transfusion requirements in cardiopulmonary bypass. This benefit may be explained by a lower activation of fibrinolysis.

Improved surgical field for composite arterial grafts.

A simple method to obtain a motionless surgical field with excellent exposure and access to perform internal thoracic or radial artery composite grafts for myocardial revascularization is described.

Long-term results of mitral valve surgery in patients with severe pulmonary hypertension.

Mitral valve surgery was performed in 88 patients with severe pulmonary hypertension (average systolic pulmonary artery pressure, 94.7 +/- 22 mm Hg; range, 70-180 mm Hg) over a 10-year period. Sixty-four patients (73%) were in New York Heart Association Functional Class III or IV. There were 64 valve replacements and 24 open mitral commissurotomies. Operative mortality was 5.6% (5 patients) and was not related to the degree of pulmonary hypertension, surgical procedure performed, or type of valve lesion. A 100% follow-up was obtained, ranging from nine months to 10 years, with a mean of 44 months. Six late cardiac deaths (7.2%) occurred, 5 in patients with valve replacement and 1 in a patient who underwent a commissurotomy. Actuarial survival was 86 +/- 3% at five years and 83 +/- 4% at 10 years. Fourteen patients underwent right ventricular catheterization a mean of 24 months following operation. Systolic pulmonary artery pressure had decreased from a mean preoperative value of 101 +/- 22 to 40.5 +/- 7 mm Hg (p less than 0.001). Cardiac index increased by 55% of the preoperative values. Functional status improved markedly; 71 survivors (93%) were in New York Heart Association Class I or II. These results indicate that, in patients with mitral valve lesions and severe pulmonary hypertension, (1) surgical procedures can be performed with an acceptable operative mortality; (2) excellent long-term survival and functional results can be obtained; and (3) pulmonary hypertension decreases significantly after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

True aneurysm of the main pulmonary artery: surgical correction.

A 23-year-old man who underwent surgical correction of a true pulmonary artery aneurysm is presented. Pathological features and the different surgical alternatives for treatment of this lesion are discussed.

Creation of an atrial septal defect for acute postperfusion right ventricular failure.

Acute postperfusion right ventricular failure following mitral and aortic valve replacement in a patient with severe double-valve incompetence secondary to endocarditis is presented. The situation was reversed by creating an atrial septal defect that decompressed the right ventricle and increased left ventricular filling pressure.

Mitral valve repair after excision of a fibrolipoma.

A 2-year-old patient with severe mitral regurgitation associated with a mass originating from the anterior leaflet of the mitral valve is reported. Excision of the tumor and mitral valve repair was performed. Four years later the child remains asymptomatic with no recurrence of the tumor or regurgitation.

Combined aortocoronary bypass and intraoperative transluminal angioplasty in left main coronary artery disease.

Transaortic intraluminal angioplasty of the left main coronary artery by Grüntzig's technique has been used intraoperatively in 4 patients who underwent multiple aortocoronary bypasses. Angiographic and clinical results were excellent in 3 of them. It is suggested that this combined technique be used to obtain more complete revascularization at the time of coronary artery bypass. The technique is easy to perform without x-ray facilities in the operating room, and it seems reasonable to assume that it may improve the myocardial blood supply of those areas irrigated by small arteries originating between the stenosed main trunk and other subsequent lesions.

Ebstein's anomaly: surgical treatment with tricuspid replacement without right ventricular plication.

Two patients with Ebstein's anomaly and severe cardiac impairment underwent surgical repair with tricuspid valve replacement and closure of associated congenital septal defects. No attempt was made to plicate the atrialized right ventricle. Good cardiac function was obtained at the end of the procedure, with uniform contractions of the whole right ventricle. Both patients are leading normal and active lives 38 and 32 months after operation. We believe that successful repair is achieved chiefly by placing a competent tricuspid valve on its true anatomical position, leaving the underlying atrialized portion of the ventricular wall undisturbed. That portion will contract and work synchronously with the rest of the right ventricle.

One-stage surgical treatment of cardiac and pulmonary echinococcosis.

The case of a 26-year-old woman with cardiac and pulmonary echinococcosis is presented. Surgical treatment of the intrathoracic disease was done in a one-stage operation. Under cardiopulmonary bypass, a left ventricular hydatid cyst and a lower lobe pulmonary cyst were removed. The patient is completely asymptomatic and is leading a normal life two years after operation.

Hemodynamic evaluation of the integral monostrut Björk-Shiley prosthesis in the aortic position.

Between May, 1983, and November, 1984, the new integral monostrut Björk-Shiley prosthesis was used for aortic valve replacement in 62 patients. The prosthesis is machined from a solid piece of cobalt alloy and has no welded joints. The traditional U-shaped outlet strut has been replaced by a projecting metal finger that holds the disc in place. The disc opens to 70 degrees and is convexoconcave. Successful transseptal heart catheterization was performed in 23 patients an average of 6 months following operation to evaluate the hemodynamic performance of the prosthesis. The mean peak-to-peak gradient was 7.73 +/- 7.49 mm Hg (+/- standard deviation). In five valves it was 0, and in only three was it higher than 15 mm Hg. Significant peak gradients were directly related to the valve index (valve area/body surface area). Mean systolic gradient at rest was 12.7 +/- 6.27 mm Hg and did not increase after exercise. Effective orifice areas were adequate, and the discharge coefficient ranged from 0.77 for the 21-mm prosthesis to 0.48 for the 29-mm prosthesis. Minimal regurgitation, which was washed out on the next systole, was observed with all sizes of the prosthesis. Disc opening was maximal (70 degrees) in all but one of the observed instances. Longer clinical follow-up is required, but the new integral monostrut Björk-Shiley prosthesis, with its important design changes and excellent hemodynamic performance, appears to be a promising aortic valve substitute.