[Coronary artery disease after renal transplantation: epidemiology, risk factors, and surgical approaches to treatment].

Coronary artery disease (CAD) is the main cause of death in renal transplant recipients. The aim of the present study was to determine the frequency and risk factors of post-transplantation CAD and its influence on the long-term results of surgery, as well as to evaluate the efficiency of myocardial revascularization in patients with severe CAD. Analysis of the observation of 479 renal recipients (332 men and 147 women) aged 38.69 +/- 11.2 was performed. The mean follow-up period was 64.56 +/- 37.44 months. Sixty-eight patients had diabetes mellitus. CAD was diagnosed in 14.8% (71 out of 479) renal recipients; in 12.7% of patients it developed de novo and was revealed 32.4 +/- 18.6 months after the surgery. Ten-year survival of renal recipients with CAD was only 39%, while in the group of non-CAD patients it was 75% (p < 0.0001). Age more than 45, male gender, diabetes mellitus, hypercholesterolemia, infections, pre-existing left ventricular myocardial hypertrophy, and renal transplant dysfunction were defined as significant risk factors of CAD de novo. Multi-factor Cox model found only age more than 45 (p < 0.009), male gender (p < 0.00001), and hyperlipidemia (p < 0.0058) to be independent risk factors of CAD. Myocardial revascularization was performed in 29 patients with coronary lesions: 27 patients underwent percutaneous transluminal coronary angioplasty with stenting and 2 patients underwent coronary artery bypass grafting (5 and 52 months after renal transplantation). However, angioplasty had to be repeated in 6 out of 27 (22%) patients within 3 to 6 months. The average follow-up duration was 23 months (2 to 74 months) after revascularization. Prolonged effect (more than 12 months) was achieved in 17 out of 29 (58.6%) patients. None of the patients developed myocardial infarction after revascularization. Two patients died 28 and 35 months after angioplasty due to extracardial complications (hepatic cirrhosis and an oncological disease); one patient died 78 months after repeated revascularization from progressive cardiac insufficiency while receiving dialysis due to a relapse of renal transplant insufficiency. Thus, CAD develops in 14.8% of renal transplant recipients; in 12.7 of patients it develops de novo. There are conventional and nonconventional post-transplantation CAD risk factors, which include renal transplant dysfunction and post-transplantation infections. Association with myocardial hypertrophy, observed in a significant number of patients, is a feature of post-transplantation CAD. Coronary revascularization, angioplasty with stenting in particular, may be considered to be an effective method of CAD treatment in renal transplant recipients.

[Results of clinical trials of a novel glycoprotein IIb-IIIa antagonist framon in high-risk coronary angioplasty].

New glycoprotein (GP) IIb-IIIa antagonist preparation framon (Monafram), is the F(ab')(2) fragment of a monoclonal antibody FRaMon directed against GP IIb-IIIa. This preparation blocks GP IIb-IIIa binding with fibrinogen and inhibits platelet aggregation both in vitro and upon intravenous administration. Safety and ability of framon to prevent thrombotic complications in high risk coronary angioplasty (CA) was evaluated in the present study. FRAMON was injected intravenously into 153 patients just before the start of procedure as a single bolus at the dose of 0.25 mg/kg. Control group was formed of 126 patients who underwent angioplasty without GP IIb-IIIa blockers. After framon administration there were no allergic reactions or major bleedings, deep thrombocytopenia (< 50000/microl) developed in 1 patient (< 1%), and antibodies against framon were detected in less than 5% of patients. Number of unfavorable outcomes (cardiovascular death, myocardial infarction, angina recurrence) within 1 month after CA was 3 times higher in control group than in the group of patients treated with framon (11.4% and 3.3%, respectively, p = 0.018). The effect of framon was most strongly pronounced within the first day after procedure -- administration of the drug reduced number of acute thromboses from 6.5% to 0.7% (p = 0.013). Significant differences between numbers of end points was still preserved at 6 months after procedure (25.7 and 14.2% in control and framon groups, respectively, p = 0.023). The data obtained proved safety and clinical efficacy of framon administration in coronary angioplasty with high risk of thrombotic complications.

[Sotahexal pharmacodynamics in patients with ischemic heart disease]. / Farmakodinamika sotageksala u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Therapeutic and prophylactic antiarrhythmic efficacy of sotalol hydrochloride (Sotahexal, "Hexal", Germany) and its effects in intracardiac hemodynamics and ECG parameters were evaluated in 95 patients with ischemic heart disease (IHD). The highest response to the drug was observed in ventricular extrasystoles, arterial flutter and fibrillation. Acute episodes of arrhythmia are managed by bolus administration of Sotahexal [correction of Hexal]. In this case greater risk of side effects exists. It is desirable to decide on the drug dose, mode of administration on the individual basis with due consideration of the risks and dangers which could be avoided in case of adequate instrumental control.

[Humoral immunopathologic changes in the myocardium after clinical allotransplantation of the heart]. / Gumoral'nye immunopatologicheskie izmeneniia v miokarde pri allotransplantatsii serdtsa v klinike.

Endomyocardial diagnostic biopsies, recipient heart removed at operation, endomyocardial biopsies of allotransplants and postmortem material were studied using immunofluorescence to specify immunopathological process and to detect humoral rejection. Altogether 306 samples from 55 patients were studied. In the early postoperative period (one year) 8 out of 18 patients with heart transplants repeatedly showed immunopathologic picture of acute humoral (vascular) rejection which was characterized by a widespread immunoglobulin G and complement fixation in the capillary walls accompanied by enhanced capillary permeability and fibrin deposition in intestitial tissue. Such patients often had graft dysfunction. 1 to 5 years after transplantation in 24 out of 37 patients discrete focal immunoglobulin and complement fixation was observed as one of chronic rejection component.

[Indicators of bicycle ergometry after heart transplantation]. / Pokazateli veloérgometrii u bol'nykh posle transplantatsii serdtsa.

Exercise tolerance in postcardiac transplantation patients versus healthy controls was studied at different intervals after the surgery using bicycle ergometry. Being low after the transplantation, exercise tolerance in the patients increased throughout the rehabilitation period but still did not reach the values characteristic for healthy subjects. Initial heart rate in the above patients was higher, while chronotropic and inotropic reserves of the transplanted heart appeared lower than in the controls. The data obtained help objectively assess the condition of the patients with transplanted heart.

[The contribution of the myocardial segmental nonhomogeneity of the left ventricular walls to its contractile and pumping functions]. / Vklad segmentarnoi neodnorodnosti miokarda stenok levogo zheludochka v ego sokratitel'nuiu i nasosnuiu funktsii.

A normalised variation coefficient of the partial systolic fraction served as the measure of nonhomogeneity of the segmentary kinetics of the left ventricle's wall (parameter J). A significant correlation was found between the parameter J and the fraction of the ventricle output (the correlation being negative one) both in normal subjects and in patients with cardiac pathology. The parameter J was also found to be a sensitive index of the heart pumping and contractile functions. The local cardiotopodynamics as expressed via the segmentary nonhomogeneity seems to be able to contribute much into the regulation or modulation of the heart pumping function.

[The hemodynamics of the lesser circulation before and after heart transplantation in patients with dilated cardiomyopathy]. / Gemodunamika malogo kruga krovoobrashcheniia do i posle transplantatsii serdtsa u bol'nykh s dilatatsionnoi kardiomiopatiei.

Studies of the lesser circulation hemodynamics in 150 patients with dilatation cardiomyopathy and in 15 after heart transplantation revealed secondary postcapillary pulmonary hypertension of more than 60 mm Hg in cases with dilatation cardiomyopathy with systolic pressure in the pulmonary artery (SPPA) in 30% of patients, transpulmonary gradient (TPG) of more than 15 mm Hg and pulmonary vascular resistance (PVR) or more than 4 Wood's U in 15.3% of patients. Two stages of pulmonary hypertension in dilatation cardiomyopathy should be singled out: I with SPPA of 60 mm Hg, TPG of 15 mm Hg, and PVR of less than 4 Wood's U, and II with SPPA of more than 60 mm Hg, TPG of more than 15 mm Hg, and PVR of more than 4 Wood's U. Orthotopic transplantation of the heart is indicated for patients with Stage I pulmonary hypertension. For patients with Stage II condition prolonged inotropic and vasodilator therapy is necessary, and if it fails, heterotopic transplantation of the heart or transplantation of the heart and lungs should be resorted to. The basic characteristics of the lesser circulation reflecting the reversibility of pulmonary circulation disorders are SPPA, TPG, and PVR. Failure of prolonged inotropic vasodilator therapy may be indicative of irreversible injury to pulmonary vessels. Lesser circulation hemodynamics usually normalizes a month after heart transplantation. If TPG is less than 15 mm Hg and PVR less than 2 Wood's U, the incidence of reversible posttransplantation right-ventricular insufficiency depends on SPPA pretransplantation level. Mortality because of right-ventricular insufficiency was 8.33%. One-year survival after heart transplantation is related to preoperative TPG and PVR values.(ABSTRACT TRUNCATED AT 250 WORDS)

[Echocardiographic diagnosis of acute rejection of transplanted heart]. / Ekhokardiograficheskaia diagnostika ostrogo ottorzheniia peresazhennogo serdtsa.

Comparing echocardiographic parameters with endomyocardial biopsy findings in 6 patients with acute crises of mild, moderate, and severe graft rejections and in 2 patients with persistent acute rejection crisis has shown that there are decreases in end-diastolic size and left ventricular end-diastolic ejection fraction volume, an increase in left ventricular myocardial mass, and thickening of the left ventricular posterior wall and ventricular septum, as evidenced by ultrasonic study. Such changes are detected in moderate and severe acute crises of graft rejection. Normalization of ultrasonic parameters of the grafted heart occurs 2-3 weeks after abolition of rejection crisis. A positive dynamics of echocardiographic parameters in persistent acute rejection crises suggests a good prognosis. Echocardiographic monitoring data obtained in the outpatient setting may serve an indication for unplanned endomyocardial biopsy.

Evidence for antibody and immune-complex deposition in heart transplantation: a report of three cases.

Immunofluorescence microscopy of endomyocardial biopsy specimens from heart allograft recipients identified immunopathologic changes in three of 17 patients. These changes included immunoglobulin G and complement C3 deposition in tissue structures such as capillary endothelium and basal membranes, cardiomyocyte sarcolemma, and interstitial tissue. Moreover, the immunopathologic changes could be correlated with acute cellular rejection episodes evidenced by endomyocardial biopsy criteria.

[Immunopathologic study of the myocardium in dilated cardiomyopathy]. / Immunopatologicheskoe issledovanie miokarda pri diliatatsionnoi kardiomiopatii.

Myocardial tissues of patients with dilated cardiomyopathy were studied by immunofluorescence. While immunoglobulin A fixation was observed in myocardial capillary wall and cardiomyocyte sarcolemma in the majority of patients (11 of 12), immunoglobulin G and C3 complement component were a rare finding. In the vessel wall of heart allografts immunoglobulin A fixation occurred 3-6 days after transplantation. As a result of the intensive immunosuppressive therapy which was used after the operation immunoglobulin A disappeared from heart allografts within 4-5 weeks. Immunoglobulin A fixation in the heart of patients with dilated cardiomyopathy is attributed to the anti-tissue or antivirus antibodies and probably is involved in the development of this disease.

[Surgical tactics in patients with ischemic heart disease, extensive cicatricial myocardial lesions and circulatory insufficiency]. / Khirurgicheskaia taktika u bol'nykh ishemicheskoi bolezn'iu serdtsa s obshirnymi rubtsovymi porazheniiami miokarda i nedostatochnost'iu krovoobrashcheniia.

The article discusses the results of surgical treatment of patients suffering from ischemic heart disease with extensive cicatricial affections of the myocardium and circulatory insufficiency. Thirteen patients of group I were treated by various reconstructive operations (resection of an aneurysm, formation of an aortocoronary shunt, septoplasty), 10 patients of group 2 underwent orthotopic heart transplantation. Perioperative and long-term (up to 3 years) mortality rates were, respectively, 7.6 and 8% in group I and, respectively, 30% and zero in group 2. The unfavorable prognosis of survival and medicamentous therapy in such patients, the lack of donors, and the acceptable results of reconstructive operations are evidence that they should be undertaken whenever possible. The main criteria of the selection of patients for a reconstructive operation are the values of regional contractility of the left ventricle, the severity of the dystrophic processes in the preserved segments, and the condition of the coronary arteries.

[Diagnosis of transplanted heart acute rejection on the basis of endomyocardial biopsy morphologic examination]. / Diagnostika ostroi reaktsii ottorzheniia transplantirovannogo serdtsa po dannym morfologicheskogo issledovaniia éndomiokardial'nykh bioptatov.

Results of morphological diagnosis of acute rejection on the material of 265 endomyocardial biopsies from 26 patients after an orthotopic donor heart transplantation are presented. The structural characteristics of different stages of acute rejection are given which is revealed in 85.7% observations. Ultrastructural myocardial changes in the early postoperative period not connected with the acute rejection crisis but resulting from a reperfusion cardiomyocytes damage are described. Results of electron microscopic examination of myocardium in rejection crisis are also given.

[Chronic rejection of a transplanted heart]. / Khronicheskoe ottorzhenie peresazhennogo serdtsa.

Three cases of chronic rejection occurring 7.5, 10, and 24 months after transplantation of the heart are analysed. The clinical features of chronic rejection in the late-term periods after transplantation of the heart are discussed. The problems of clinical diagnosis of chronic rejection, the role of endomyocardial biopsy and disorders of lipid metabolism are dealt with. Tactics of saving the patient are recommended. The authors substantiate the necessity for heart retransplantation and, in the absence of a donor's heart, for two-stage transplantation of the heart through an artificial heart or a biventricular approach by means of artificial heart ventricles.

[The first clinical experience with heart transplantation]. / Pervyi klinicheskii opyt transplantatsii serdtsa.

The article analyses the first clinical experience in orthotopic allotransplantation of the heart at the Scientific Research Institute of Transplantology and Artificial Organs, USSR Ministry of Health, in the period from October, 1986 to July, 1989 (26 transplantations of the heart and one two-stage transplantation of the heart with the use of "Poisk-10M" artificial heart for 3.5 days in the first stage). Eleven patients are alive. Follow-up periods: maximum over 2.5 years, minimum 3 months. Sixteen patients died in different periods (up to 12 months). Three-component therapy (cyclosporine A, methylprednisolone, azathioprine) was applied for immunosuppression. The authors analyse the problems of the selection of potential recipients (indications and contraindications) and donor, the optimum surgical techniques, complications of immunosuppressive therapy, and infectious complications. The first clinical experience in two-stage transplantation of the heart is analysed. The first experience in transplantation of the heart in patients allows the conclusion that the use of this method for the management of the terminal stage of congestive cardiac insufficiency is a reality.

[Hemodynamic evaluation of the effectiveness of preservation of subvalvular structures in mitral valve prosthesis]. / Gemodinamicheskaia otsenka éffektivnosti sokhraneniia podklapannykh struktur pri protezirovanii mitral'nogo klapana.

The article deals with the clinical evaluation of the results of mitral valve prosthetics with preservation of the subvalvular structures in 40 patients and comparative evaluation of the hemodynamic indices after prosthetics with preservation of the subvalvular structures of the posterior cusp and after routine mitral valve prosthetics. The authors show good clinical results in patients after valvar-preserving prosthetics of the mitral valve and essential improvement of left-ventricular contractile activity after such an operation. Comparative analysis showed that the total ejection fraction increased by 10.8 +/- 4.5% in the main group and reduced by 11.4 +/- 2.6% (p less than 0.01) in the control group. Left-ventricular end diastolic pressure did not change in the main group but increased significantly (p less than 0.05) in the control group. A conclusion is drawn that preservation of the subvalvular structures in mitral valve prosthetics is expedient even in patients with an initially grave condition because the method makes it possible to normalize intracardiac hemodynamics more rapidly in the postoperative period and essentially improve the contractility of the left ventricle.