Evaluation of intravascular hemolysis with erythrocyte creatine in patients with cardiac valve prostheses

STUDY OBJECTIVES: To detect intravascular hemolysis in patients with cardiac valve prostheses. Erythrocyte creatine, a marker of erythrocyte age that increases with shortening erythrocyte survival, was evaluated with other hemolytic markers and hemodynamic parameters. DESIGN: Prospective study. Patients and measurements: Erythrocyte creatine was enzymatically assayed in 33 patients with prosthetic valves, including 15 patients with aortic valve replacement, 13 patients with mitral valve replacement, and 5 patients with double-valve (aortic and mitral) replacement, and 33 control subjects. Blood flow velocity and valvular regurgitation were determined by Doppler echocardiography. Other hemolytic markers (lactate dehydrogenase [LDH], reticulocyte count, and haptoglobin) and cardiac muscle markers (myoglobin and myosin light chain 1) were also measured. RESULTS: Erythrocyte creatine and LDH levels were significantly higher (p < 0.0001) and the haptoglobin level was lower (p < 0.0001) in patients with a prosthetic valve as compared with control subjects. However, there were no significant differences in these markers between those with (n = 17) and without (n = 16) regurgitation. Patients with high erythrocyte creatine levels (> 1.8 micro mol/g hemoglobin) exhibited significantly higher total peak flow velocity (sum of peak flow velocities at mitral and aortic valves) than those with normal erythrocyte creatine levels (p = 0.006). Erythrocyte creatine had a significant correlation with total peak flow velocity (r = 0.64, p < 0.0001), but LDH and haptoglobin had no significant correlation with total peak flow velocity. Patients with high LDH levels (> 460 IU/L) showed significantly higher myoglobin (p = 0.008) and myosin light chain 1 (p = 0.02) than those with normal LDH levels, whereas erythrocyte creatine was not related to cardiac muscle markers. CONCLUSIONS: Erythrocyte creatine is a quantitative and reliable marker for intravascular hemolysis in patients with prosthetic valves. Mild hemolysis is ascribable to valvular flow velocity rather than regurgitation.     

Design studies of cardiac valve prostheses

This paper indicates the vital importance of considering prosthesis articulation in the design of cardiac valves. The prosthesis articulation interrelates with the fixed and the movable prosthetic components. Two basic physiological hemodynamic principles are reviewed: [List: see text] A bileaflet, free-tilting, swivelling prosthesis with a central articular mechanism is undergoing investigation. The four articulations have their own perennial preserving mechanisms to prevent potential failure mode by collecting blood elements in the valve tilting design.     

Risks and benefits of postoperative cardiac catheterization in patients with ball valve prostheses

Two studies were performed to evaluate the risks and benefits of post-operative cardiac catheterization in patients with a ball valve prosthesis. In Study 1, 106 consecutive catheterization procedures in 100 patients were retrospectively evaluated. There were no deaths, myocardial infarctions or infective endocarditis. Five patients who were in extremis were studied without complication. Major complications (occurring in 8.5 percent) included excessive bleeding (four patients), cerebral emboli (two patients), ventricular fibrillation (one patient) and other (two patients). The major complication rate for patients with transthoracic left ventricular puncture with ventriculography was 24 percent (4 of 17) and for patients with therapeutic anticoagulation 18 percent (6 of 34). Significant abnormalities were detected in 55 percent of all catheterizations. The incidence rate of significant abnormalities was 75 percent (47 of 63) when clinical-hemodynamic deterioration was an indication for catheterization and 19 percent (8 of 43) when it was not. The incidence rate of reoperation for all patients was 34 percent, 51 percent (32 of 63) in those with clinical-hemodynamic deterioration and 9 percent (4 of 43) in others. In Study 2, 45 patients with a reduced level of anticoagulation were evaluated prospectively to assess whether such reduction would eliminate most complications. One patient was in extremis at the time of study. There were no complications in these 45 patients.

We conclude the following: (1) Therapeutic anticoagulation is associated with increased risk from cardiac catheterization. In patients with a less than therapeutic level of anticoagulation, cardiac catheterization can be performed at low risk. (2) Patients with a ball valve prosthesis who manifest clinical-hemodynamic deterioration should undergo postoperative cardiac catheterization because of the high incidence rate of correctable abnormalities in these patients.     

Long-term outcome of valve prostheses. Apropos of 299 operated patients]

The authors report a series of 299 operated cases betwen 1966 and August 1975. The operative mortality was 16%, usually a result of low output states and arrhytmias. Long-term survival was 74% at 3 years and 64% at 6 years, being better in those with only one valve replacement. The late results were very good taken as a whole. The few poor results were associated especially with a degenerating myocardium. The mitral group were favoured with a better 5 year survival rate and by clinically, and above all haemodynamically severe tricuspid incompetence. Thromboembolic complications, which are a major hazard, were favoured by irregular and inadequate anticoagulant therapy. In patients under 20 it would seem possible to stop after 6 months' effective treatment. Children have had generally better results than adults, probably because of the better state of their myocardium.     

Long-term results after aortic valve replacement with four different prostheses

The long-term results after implantation of isolated aortic ball and disc prostheses were studied. The Starr-Edwards ball valve type 1200 was first used in 80 patients, thereafter type 2300 was used in 173, later the Björk-Shiley and the Lillehei-Kaster disc valves were implanted in 99 and 97 patients according to randomization. The surviving patients with the oldest ball valve were examined after 4.7 and 6.7 years on an average, the others after approximately 2.5 and 4.5 years.The early mortality rate was 15%, and did not differ between the four groups. Even the late mortality rate was quite similar in the patient groups, the five-year survival rate being 65% in patients with ball valves and 68% in those with disc valves, as estimated with the actuarial method.The average reduction of heart size was moderate and quite similar in the four groups, most pronounced in patients with isolated aortic valve involvement. The reduction was greater in patients who received larger rather than smaller valves of all types.Aortic valve replacement resulted in a considerable clinical improvement in patients with all valve types; it corresponded largely to one functional group according to the NYHA classification. The heart size reduction and functional improvement was most moderate in patients with smaller ball valves, which could be anticipated from higher peak systolic gradients than across the other valves used. No significant differences appeared between patients with the larger valves of the four types.The initial improvement, as recorded either by reduction of heart size or increase in functional capacity, had reached its maximum at the first follow-up examination in most patients.The preoperative myocardial function appeared to be the limiting factor which determined what late results could be obtained regardless of the type of valve implanted. The results therefore indicate that more can be achieved by earlier valve replacement than by improving the prostheses.     

Re-operations on patients with ball valve prostheses]

Out of 989 cases with a ball-valve prosthesis, 66 have been reoperated (6.7%). 2.9% of the cases reviewed annually have thus been reoperated. The main indications for reoperation were displacement (75.5%), malfunction (10.5%) which was related to a failure of the material of the prosthesis or to the deposition of fibrinous plaques, and associated lesions (14%) which were valvular, coronary or myocardial. There were multiple complications in 36 patients. The operative mortality was 31.8% (21.7% over the last two years). On statistical analysis, the significant risk factors were a previous history of bacterial endocarditis, grouping in Class IV of the NYHA classification, enlargement of the QRS complex (0.12 s), urgency of reoperation, and prolonged extracorporeal circulation (2 hours). The rapid fall in survival time was due in part to late deaths (16 patients). By way of contrast, the clinical result was satisfactory in 71% of the survivors. Analysis of the causes of failures has lead to a search for ways of preventing the necessity for reoperation.     

Blood rheology after cardiac valve replacement with mechanical prostheses or bioprostheses

Arterial thromboembolism is a serious complication in patients after heart valve replacement. Abnormalities in blood rheology may contribute to this complication. Therefore, the aim of this study was to compare various determinants of blood rheology in patients with substitute heart valves with those in healthy controls; furthermore, differences between patients with mechanical valves and those with bioprostheses should be investigated. The hemorrheologic determinants--fibrinogen, plasma viscosity, red cell aggregation, hematocrit and platelet aggregation--were studied in 92 patients with mechanical bileaflet valves, in 28 patients with bioprostheses and in 29 control subjects; the time since valve replacement was greater than or equal to 9 months. Fibrinogen, plasma viscosity, red cell and spontaneous platelet aggregation were found to be increased in all patients after heart valve replacement compared with normal subjects (fibrinogen: 348 +/- 87 vs 267 +/- 66 mg/dl, p less than 0.01; plasma viscosity: 1.71 +/- 0.1 vs 1.66 +/- 0.1 mPas, p less than 0.05; red cell aggregation: 9.9 +/- 2 vs 7.8 +/- 2 U, p less than 0.01; platelet aggregation: 22 +/- 15 vs 13 +/- 13%, p less than 0.01); among patients, fibrinogen, plasma viscosity and spontaneous platelet aggregation were higher in mechanical valves than in bioprostheses (fibrinogen: 359 +/- 95 vs 314 +/- 41 mg/dl, p less than 0.01; plasma viscosity: 1.72 +/- 0.1 vs 1.68 +/- 0.1 mPas, p less than 0.1; platelet aggregation: 23 +/- 15 vs 16 +/- 11%; p less than 0.05), whereas no difference could be found for red cell aggregation (9.7 +/- 2 vs 10.5 +/- 2%, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Failure of adjusted doses of subcutaneous heparin to prevent thromboembolic phenomena in pregnant patients with mechanical cardiac valve prostheses

Objectives. This report describes our experience with the use of an anticoagulant regimen of adjusted doses of subcutaneous heparin during pregnancy in women with cardiac valve prostheses.

Background. Gravid patients with prosthetic heart valves require long-term anticoagulant therapy. To avoid the increased incidence of fetal morbidity and mortality associated with the use of coumarin agents in such patients during pregnancy, anticoagulation with subcutaneous heparin has been suggested. Controversy exists concerning the appropriate treatment of these patients.

Methods. Forty pregnancies in 37 women with prosthetic heart valves were prospectively followed up. Subcutaneous heparin was administered from the 6th until the end of the 12th week and in the last 2 weeks of gestation. Heparin was given every 8 h in the first 36 cases and every 6 h in the last 4 cases, and the dose adjusted to maintain the activated partial thromboplastin time at 1.5 to 2.5 times the control level. Acenocoumarol was used at other times.

Results. The incidence rate of spontaneous abortions was 37.5%; there was one neonatal death (2.5%) due to cerebral hemorrhage. No signs of coumarin-induced embryopathy were found in any of the 16 live-born infants studied by the geneticist. One mother died of gastrointestinal bleeding while receiving oral anticoagulant agents. There were two cases of fatal massive thrombosis of a mitral tilting-disk prosthesis during heparin therapy. The study was interrupted after the last of these two cases.

Conclusions. The regimen of adjusted doses of subcutaneous heparin used in this study is not effective to prevent thrombosis of mechanical valve prostheses during pregnancy. The use of heparin from the 6th to the 12th week of gestation does not decrease the high incidence of fetal wastage associated with anticoagulant therapy. Coumarin agents provide adequate protection against thromboembolism during pregnancy in patients with mechanical valve prostheses.     

A 12-year clinical experience of cardiac valve replacement with domestic tilting disc valve prostheses in 1013 cases]

1013 patients with cardiac valve replacement during a 12-year period from 1978 to 1990 were reported. 566 cases were implanted with Shanghai-made tilting disc valve prostheses and 447 with Lanzhou-made (C-L valves). Mitral valve replacement (MVR) in 753 patients, aortic valve replacement (AVR) in 102 and double valves replacement (DVR) in 158. The overall early mortality rate was 6.2% with 4.9%, 7.8% and 11.3% after MVR, AVR and DVR respectively. Follow-up study was made in 3097.43 patient-year (mean 3.26 years). The late death rate was 1.6% patient-years and with 1.4, 1.8 and 3.2 after MVR, AVR and DVR respectively. The incidence of late valve-related complication (% patient-years) were: thromboembolism 0.39, anticoagulant-related hemorrhages 0.77, prostheses failure 0.22, prosthetic valve endocarditis 0.38, periprosthetic leak 0.12, and reoperations 0.38. The domestic tilting disc valve prostheses are considered to be qualified valves with low mortality and satisfactory results.