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.

[Traumatic rupture of tricuspid valve: report of 3 cases]. / Rotura traumática de la válvula tricúspide: presentación de tres casos.

Tricuspide valve lesions due to non-penetrating trauma are rare and their diagnosis is difficult. Nevertheless, over 100 cases of post-traumatic valve regurgitation have been described in the last 35 years. We present 3 such cases diagnosed and operated at our center in the last 8 years.

Burden of myocardial damage in cardiac allograft rejection: scintigraphic evidence of myocardial injury and histologic evidence of myocyte necrosis and apoptosis.

BACKGROUND: Because myocardial damage determines morbidity and outcomes in heart transplant rejection, assessment of total burden of myocardial damage is highly desirable. In addition to myocyte necrosis, programmed cell death, or apoptosis, has recently been shown to contribute to cardiac allograft rejection. In the present study, we noninvasively determined myocardial damage by antimyosin scintigraphy and compared it with necrotic and apoptotic myocardial damage in endomyocardial biopsy (EMB) specimens. METHODS AND RESULTS: Forty scintigraphic and histologic studies were simultaneously performed. Of these, 19 patients had no EMB evidence of allograft rejection (group I, International Society of Heart and Lung Transplantation [ISHLT] grade 0/4), 12 had mild rejection (group II, ISHLT grades 1A and 1B), and 9 had evidence of moderate allograft rejection (group III, ISHLT grades 2, 3A, and 3B). None of the biopsies demonstrated severe allograft rejection (ISHLT grade 4/4). The severity of global myocyte damage in 40 patients was assessed by antimyosin scintigraphy. Endomyocardial biopsies were performed in these patients within 48 hours of imaging study; biopsy specimens were characterized for presence of myocyte necrosis and apoptosis. Evidence of myocyte necrosis was observed in 9 (23%) of 40 EMB specimens. Nineteen EMB specimens of group I had no inflammation and no myocyte necrosis, 12 of group II specimens showed interstitial mononuclear cell infiltration (only) but no myocyte necrosis, and all 9 of group III specimens had evidence of cellular infiltration and myocyte damage. Myocyte necrosis was assessed by hematoxylin-eosin and trichrome staining of EMB specimens. On the other hand, apoptosis of myocytes, as assessed by TUNEL staining of DNA fragments, was seen in 22 (55%) of the 40 biopsy specimens: 47%, 58%, and 67% in groups I, II and III, respectively. Abnormal antimyosin scan findings, indicating presence of myocardial damage, were observed in 9 of the 19 patients in group I and in all patients in groups II and III. Although positive antimyosin scan results in group III patients are concordant with the presence of histologic myocardial necrosis, myocardial uptake of antimyosin antibodies in groups I and II (no apparent myocyte damage at light microscopic examination) could reflect either sampling error of the biopsy or ongoing apoptotic myocyte damage. CONCLUSIONS: Apoptosis of myocytes is frequently observed during cardiac allograft rejection. The presence of apoptotic myocytes in the absence of histologic rejection activity in patients with antimyosin uptake suggests that apoptosis could be an additional mechanism of transplant-associated myocardial damage.

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.

[Myxoma of the left ventricle: a cause of syncope in an adolescent]. / Mixoma de ventrículo izquierdo como causa de síncope en adolescente.

Clinical diagnosis of cardiac tumours is often difficult. We present the case of a 17 year-old boy in whom a left ventricular tumour was discovered during on diagnostic work-up for a syncope. The tumour was removed and histology confirmed the diagnosis of myxoma.

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.

[Transmyocardial revascularization with laser]. / Revascularización transmiocárdica con láser.

Patients with severe angina pectoris, refractory to medical treatment, in which conventional revascularization (PTCA or bypass surgery) is not possible because they present advanced coronary artery disease with a poor distal bed, account for an important clinical problem due to an increasing incidence, combined with poor quality of life, an elevated risk of severe complications, repeated hospital admissions and high mortality rate. Laser transmyocardial revascularization provides a new therapeutic alternative for these patients. Although up to now there are only a few published series, with a small number of patients, the results obtained in the two ongoing multicentric studies in Europe and the United States (including more than 500 patients at present) are quite promising. It is a simple surgical procedure, but its associated mortality is not to be dismissed (in the beginning 12% and currently 5%), because patients are in an advanced evolutionary stage. In Spain this procedure has been available since April 1996 and the results have been encouraging. In our small series we have noted a significant symptomatic improvement and better quality of life.

[Intramural hematomas of the ascending aorta]. / Hematomas intramurales en aorta ascendente.

We present four patients with intramural hematomas in the ascending aorta. Diagnostic suspicion was aortic dissection in two of them. Prompt surgical procedures were performed in all of them. After reviewing other series, we conclude that ascending aorta hematomas should be treated as true aortic dissections.

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.

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.

[Modified Takeuchi in adults]. / Takeuchi modificado en adultos.

Anomalous origin of left coronary artery from pulmonary artery is a rare congenital anomaly (0.25-0.46%). Mortality is high in the first months (65%). Paradoxically, some patients reach adulthood because of a net made of collaterals from the right coronary artery. Thus, we classify the entity in two ways of clinical onset: childhood and adulthood. Ideally, the best surgical approach is the arrangement of a double coronary system. The most well-known technique is the one described by Takeuchi, that links the aorta and the left coronary artery by a tunnel through the pulmonary artery, made from a pulmonary artery frontal wall flap (closing the defect with a pericardial patch). We present a case of anomalous origin of the left coronary artery in an adult, treated in our institution using a modified Takeuchi technique.

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.

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.

[The diagnosis of rejection activity in the heart transplant by monoclonal antimyosin antibodies]. / Diagnóstico de la actividad de rechazo en el trasplante cardíaco mediante anticuerpos monoclonales antimiosina.

A novel noninvasive sensitive mean to detect cardiac rejection is described: myocardial uptake of 111In-labeled monoclonal antimyosin antibodies (MAA). All patients showing rejection at cardiac biopsy disclosed positive MAA studies. However, a large percentage of positive studies in the presence of negative biopsies were detected. This discrepancy can be ascribed to a false-negative biopsy result. During the first year posttrasplantation MAA studies are useful to predict severe rejection-related complications, but due to high sensitivity of MAA, treatment for rejection in this period must be based on biopsies, as criterium to treat for rejection on the basis of MAA scans would lead to excessive immunosuppression. After the first year of transplantation, individual patient management can ben implemented on the basis of risk stratification using MAA scans: Negative MAA scans entail an almost nil probability of detecting rejection during long-term follow-up (low-risk group), whereas positive MAA scans imply a probability of detecting near 1 episode of rejection and requirement for treatment per year. In summary, at our institution biopsies are avoided as from the first year after transplantation; after such period, MAA scans allow risk stratification and treatment for rejection based on the results of MAA scans in individual patients.

[A report of a rare case of primary angiosarcoma of left atrium and a review of the literature]. / Presentación de un caso raro de angiosarcoma primario de aurícula izquierda y revisión de la literatura.

A 66[correction of 60]-year-old female patient was admitted to hospital for clinical signs of pericardial tamponade. The pericardiocentesis revealed an hematic effusion and a left appendage mass was diagnosed by transesophageal echocardiography. At surgery, a left atrial tumour was resected which histological examination showed to be an undifferentiated angiosarcoma-endothelioma with difficult histological classification. The tumoral screening was negative and the patient was discharged from the hospital. Seven months later the patient was readmitted for two parasternal tumours which anatomopathologic study revealed to be subcutaneous metastases. The rare localization in the left atrium and subcutaneous metastatic spread were discussed.

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)

[The implantation of a sequential endocavitary pacemaker in a patient with transposition of the great vessels after the Mustard correction]. / Implantación de marcapasos endocavitario secuencial en un paciente con transposición de grandes vasos con corrección de Mustard.

A 31-year-old male patient, underwent Mustard operation in childhood for complete transposition of the great arteries. He required a sequential (DDD-mode) pacemaker due to a complete symptomatic auriculoventricular block, 25 years after the operation. Wires were inserted through the left cephalic vein and placed in the systemic atrium and ventricle, achieving correct sensing and stimulating thresholds. Atrial rhythm disturbances, specially sinus node dysfunction, are frequent after Mustard's operation and increase through the years following the surgical procedure. Atrioventricular conduction disturbances are rare. Treatment by endocavitary pacemaker implies a correct knowledge of the special anatomy in this congenital disease and its surgical correction.

[Conservative mitral surgery for a tear of the valvular leaflets post-percutaneous mitral commissurotomy]. / Cirugía mitral conservadora por desgarro de velos valvulares poscomisurotomía mitral percutánea.

A case of a 32-year-old woman who developed acute mitral insufficiency after percutaneous mitral dilatation is presented. In spite the fact of having torn both leaflets, successful plastic repair of her valve was performed.