Increase in plasma plasminogen activators inhibitor type 1 concentration after fibrinolytic treatment in patients with acute myocardial infarction is associated with 4G/5G polymorphism of PAI-1 gene.

BACKGROUND: Preliminary data suggest that plasma concentration of plasminogen activators inhibitor type 1 (PAI-1) is genetically determined and may be related to differential regulation of plasma PAI-1 concentration at baseline and after stimulation. AIM: This study aimed to evaluate whether increase in the plasma PAI-1 antigen concentration or activity after fibrinolytic therapy in patients with acute myocardial infarction is associated with the -675 4G/5G genetic polymorphism in the promoter region of PAI-1 gene. RESULTS & CONCLUSIONS: Our study revealed that a rebound effect is observed in PAI-1 activity (ActPAI-1) and PAI-1 antigen (AgPAI-1) concentration after standard streptokinase treatment with maximal values of 3 h (t3) after the completion of streptokinase infusion. Both ActPAI-1 and AgPAI-1 were significantly higher at t3 compared to the levels before fibrinolytic treatment: 37.3 (20.0-67.7) vs. 10.0 (3.6-26.0) IU L(-1); P = 0.00001 and 29.9 (15.6-42.3) vs. 20.9 (13.0-30.2) ng mL(-1); P = 0.001, respectively. The stratification of the patients by genotype revealed that carriers of the 4G allele had higher concentrations of PAI-1 antigen 3 h after streptokinase infusion: 30.9 vs. 13.8 ng mL(-1); P = 0.019. No significant association between PAI-1 activity and genotype was found. In conclusion, the rebound effect in serum PAI-1 concentration observed after streptokinase treatment may be related to the 4G/5G polymorphism in the PAI-1 gene promoter.

Regression of left ventricular dilatation and hypertrophy after aortic valve replacement.

The aim of the study was to assess the influence of aortic valve replacement on left ventricular size and muscle hypertrophy according to the type of preexisting valve disease (aortic stenosis, insufficiency or combined disease). The study group consisted of 143 consecutive patients (pts) after aortic valve replacement (109 men, 34 women, mean age 48.1 +/- 10.9 years). Reason for the operation was aortic stenosis in 35 pts, aortic insufficiency in 64 pts and combined disease in 44 pts. Echocardiography was performed before surgery, 1 month and 1 year after operation, and yearly during 5-year follow-up. Transvalvular aortic pressure gradients decreased significantly after valve replacement in all subsets without further changes during follow-up (Pmax (mmHg): from 54.2 +/- 20.7 to 17.9 +/- 9.6 in combined disease pts, from 72.3 +/- 19.9 to 21.6 +/- 14.6 in aortic stenosis and from 34.5 +/- 24.2 to 15.6 +/- 11.3 in aortic insufficiency pts, respectively, P < 0.0005). One year after surgery the diastolic dimension of the left ventricle decreased significantly in all subjects, whereas the systolic dimension only in aortic insufficiency and combined disease pts (from 44 +/- 11.8 to 31.6 +/- 5.4 mm, P < 0.001 and from 41.9 +/- 11.5 to 33 +/- 6.7 mm, P < 0.05, respectively). Further decrease of both diastolic and systolic dimensions was observed only in the aortic insufficiency group. Ejection fraction of left ventricle increased only in combined disease pts (from 51.6 +/- 10% to 56.8 +/- 8.2%, P < 0.05). Wall thickness of the left ventricle decreased 1 year after valve replacement only in the aortic stenosis group and in further follow-up in the aortic stenosis and combined disease group. Normalization of left ventricular size is observed in more than 90% of patients during 5-year follow-up as opposed to left ventricular muscle hypertrophy, regressed only in less than a half of the study population. In patients with aortic valve disease the greatest hemodynamic improvement is observed 1 year after valve replacement. This is expressed by marked reduction of the left ventricular dimensions and wall thickness, without significant improvement of the ejection fraction. Further regression of left ventricle dimensions occurs in patients operated on due to predominant valve insufficiency, whereas regression of left ventricular hypertrophy is observed in patients with preexisting valvular stenosis.

Early and long-term outcome of aortic valve replacement with homograft versus mechanical prosthesis--8-year follow-up study.

BACKGROUND: Aortic valve disease is an important and frequent clinical problem with a mortality rate as high as 50-80% in a 5-year natural history of patients with severe aortic valve disease. Biological or mechanical prosthesis implantation is the only way to improve prognosis. HYPOTHESIS: The aim of our study was to assess the clinical outcome of aortic valve replacement according to the underlying valve pathology and the type of replacement device, that is, aortic homografts versus mechanical prostheses. METHODS: The study group consisted of 143 patients with a mean follow-up period of 4.1 +/- 2.7 years. All patients had annual clinical and Doppler echocardiographic evaluation. RESULTS: Total 8-year mortality was 4.9% (7/143) including early mortality of 1.4%. Eight-year survival probability was not significantly higher in the homograft than in the mechanical prosthesis recipients. No differences were found among subgroups with aortic stenosis, insufficiency, and combined disease. Overall early and late complication rate (13.3 and 24.8%, respectively) was similar in homograft and mechanical valve recipients. The most common late complications were ventricular arrhythmia (10%) (Lown class I-III), predominantly in the homograft recipients (17.7 vs. 3.7%), and heart failure (9.2%), more frequent in mechanical valve recipients (14.8 vs. 1.6%). Thromboembolic events occurred in 6.3%, infective endocarditis in 4.2% (more common in mechanical valve recipients), serious bleeding in 3.7% (only in mechanical valve recipients). There was no significant difference in early and late complication rate among subgroups (aortic stenosis, insufficiency, and combined disease). Of the patients studied, 91.6% improved in functional status after surgery, with significantly better outcome in homograft recipients. The type of preexisting valve disease did not influence clinical improvement. CONCLUSION: Early and late mortality as well as estimated probability of survival and hemodynamic improvement at 8-year follow-up after aortic valve replacement are independent of the type of implanted valve. Complication rate does not depend upon the type of preexisting valve pathology, but severe late complications are more common after mechanical valve implantation than after homograft implantation.

[HLA histocompatibility antigens in patients with aortic valve defects]. / Antygeny zgodnosci tkankowej HLA u chorych z wadami zastawki aortalnej.

HLA antigens A, B, C were determined in 61 patients with aortic valve disease and in 263 healthy controls. The patients were divided into two subgroups--with rheumatic fever in anamnesis (N = 24) and without (N = 37). In the whole group of patients with aortic valve disease there was a lower frequency of incidence of HLA A3 in comparison to the control group. In the subgroup with rheumatic fever in anamnesis there was a deficit of HLA A3 and a much more frequent incidence of HLA B17, in the subgroup without rheumatic fever a more frequent incidence of HLA A2, A9, A28, B15 was noted in comparison to the control group. This study shows that in 60% of patients with aortic valve disease the etiology is linked not to rheumatic fever but probably to a connective tissue disorder. A deficit of HLA A3 and presence of B17 can be a risk factor for rheumatic fever.

[Immunologic aspects of allogenic valve implantation]. / Immunologiczne aspekty wszczepienia zastawki allogennej.

Immunological response against myocardial antigens was assessed in 12 patients (pts) (9 males, 3 females, aged 24-62 years) with aortic homografts (AH) and 36 pts (29 males, 7 females, aged 26-61 years) with aortic valve prostheses (AVP). In all pts a titre of anti-myocardial antibodies, a concentration of free-circulating immune complexes and leucocytes migration inhibition test with myocardial antigen were assessed before operation and 1, 12, 24 months after operation. In 20 pts with AH immunological humoral response against HLA antigens was evaluated. After the operation pathological indexes of immunological response against myocardial antigens were observed both in pts with AH as in pts with AVP. The mean titre of anti-myocardial antibodies before operation was in both groups between 1:4 and 1:8, and 1 month after operation between 1:32 and 1:64. In 12 and 24 months after operation the mean titre in AH and AVP group was respectively 1:8 and 1:4. Before operation pathological concentration of immune complexes (> 0.084 mg/ml) was observed in 17% AH and 11% AVP pts. Pathological elevation of immune complexes 1, 12 and 24 months after operation was observed respectively in AH and AVP group in 58%, 42%, 33% and 67%, 50%, 42%. Leucocyte migration inhibition index was pathological (< 0.8) before operation in 58% in both groups, and 1, 12, 24 months after operation was pathological in AH and AVP group respectively in 67%, 17%, 17% and 61%, 33%, 31%. In most pts of both groups immunological response against myocardial antigens was transient and was terminated up to 12-24 months after operation.(ABSTRACT TRUNCATED AT 250 WORDS)