Intravascular hemolysis after mitral and aortic valve replacement with different types of mechanical prostheses

International Journal of Cardiology 69 (1999) 179–183

Intravascular hemolysis after mitral and aortic valve replacement with different types of mechanical prostheses Gennaro Ismeno*, Attilio Renzulli, Antonio Carozza, Marisa De Feo, Michele Iannuzzi, Pasquale Sante, Maurizio Cotrufo Institute of Cardiac Surgery, Second University of Naples, V. Monaldi Hospital, Via L. Bianchi, Naples, Italy Received 11 February 1998; accepted 21 January 1999

Abstract Heart valve replacement with mechanical prosthesis is associated with mild intravascular hemolysis. In this study we evaluated the incidence of hemolysis in patients with different combinations of two mechanical valves. Between 1974 and 1996, 680 patients underwent mitral and aortic valve replacement with mechanical prostheses; we selected 90 patients, divided into six groups according to the prosthetic model (Group A, ball and tilting disc; Group B, ball and bileaflet; Group C, tilting disc and tilting disc; Group D, tilting disc and bileaflet; Group E, bileaflet and tilting disc; Group F, bileaflet and bileaflet; respectively, in mitral and aortic position). Blood tests were performed to check blood hemoglobin, serum lactic dehydrogenase, percent-correlated reticulocyte fraction, serum haptoglobin, and schistocytes. Chi square test was performed for categorical data. ANOVA and Bonferroni tests were performed in order to evaluate significant statistical differences between media and variance of the hematological data. A mild degree of intravascular hemolysis was observed in 30% of patients with double mechanical prostheses. LDH values were above the normal values in all groups, although a significant difference was found only between Group B versus Groups C and D. Reticulocytes and schistocytes and serum haptoglobin values were within the normal range and no differences were found between the groups. Low levels of blood hemoglobin were found in Groups D and F. The difference was statistically significant when compared with Groups A and E. In conclusion, hemolysis is frequent but never severe in patients with mitral and aortic mechanical prostheses. A higher incidence of subclinical hemolysis was found in patients with bileaflet valves regardless of the position of the implant.  1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Heart valve; Hemolysis; Mechanical prostheses

1. Introduction Heart valve replacement with mechanical prostheses is associated with mild intravascular hemolysis [1–3]. Generally, red blood cell damage is more pronounced with malfunctioning than with properly working prostheses [4]. Nevertheless, some degree of *Corresponding author. Correspondence address: Via Vallone Mandria, 2, 80078 Pozzuoli (Naples), Italy. Tel.: 139-81-5268554; fax: 139-815464594. E-mail address: [email protected] (G. Ismeno)

subclinical hemolysis has been demonstrated in patients with normofunctioning mitral or aortic mechanical prostheses [1–3]. Many variables are associated with the frequency and severity of this complication, type and size of prosthesis [1], position [5], intraprosthetic turbulence [6,7] and heart rate [6,7], even though the mechanical trauma on erythrocytes is the common factor responsible for the hemolysis [8]. Many authors have studied the degree of hemolysis in patients with different types of mechanical valves in mitral and / or aortic position [1–7,9]. Nevertheless,

0167-5273 / 99 / $ – see front matter  1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 99 )00024-8

G. Ismeno et al. / International Journal of Cardiology 69 (1999) 179 – 183

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very few studies have been performed in patients with different types of mitral and aortic prostheses, in order to compare the different combinations of prostheses. In our study we evaluated the degree of hemolysis in six groups of patients that underwent implant of different types of valves in the mitral and aortic position.

with Bjork–Shiley and Sorin Standard Model (608 opening). We also studied the following standard models bileaflet prostheses: St Jude Medical, CarboMedics and Sorin Bicarbon Standard. Finally, to obtain an homogeneous group of patients and to minimize patient prosthesis mismatch we limited our study to 29–30 mm mitral prostheses (Starr–Edwards 3M or size 29 for disc valves) or aortic prostheses of size 21 or 23 mm.

2. Material and methods

2.3. Surgical technique

Between 1974 and 1996, 680 patients underwent mitral and aortic heart valve replacement at our institution.

All patients underwent mitral and aortic valve replacement under mild hypothermic cardiopulmonary by-pass and myocardial protection was achieved with intermittent injection of cold crystalloid solution directly into the coronary ostia. Aortic prostheses were implanted using the single stitches technique while mitral prostheses were implanted with single unpledgeted mattres sutures. Tilting disc valve were implanted in the mitral position with the large opening towards the posterior left ventricular wall. In the aortic position the large opening was oriented towards the right coronary ostia. Bileaflet prostheses were implanted in mitral position in the antianatomical position. In aortic position the hinge area was positioned at 908 with the interventricular septum.

2.1. Patient selection Patients with any kind of hematological disorder were excluded from the study. Furthermore, to avoid any interference between hemolysis and other diseases, patients with more than moderate tricuspid regurgitation, hepatic and or renal disease were excluded from the study. Finally, all patients selected for the study underwent clinical examination, ECG, and chest X-ray. Transthoracic colour Doppler echocardiography was performed to rule out the presence of perivalvular leaks and / or any kind of prosthetic malfunction and / or intracardiac shunts.

2.4. Patient characteristics

2.2. Prosthesis selection

Patient data concerning age, sex, incidence of atrial fibrillation, NYHA class and follow-up are reported in Table 1. Patients were divided into six groups according to the combination of prosthetic models implanted. Group A, mitral ball and aortic tilting disc

The only ball valve prosthesis implanted at our institution is Starr–Edwards Model 6120. As far as tilting disc valves are concerned we studied patients Table 1 Patient characteristics a Group A

B

C

D

E

F

Age (years) M/F AF (%) FU (months) Range of FU

5268.5 1 / 2.9 88 61623 6–125

5164 1 / 3.1 84 58618 6–120

5063 1.5 / 1 79 54626 6–39

5061.5 2.4 / 1 83 25612 6–30

4963 1 / 3.8 75 3068 6–40

5269.5 1 / 1.5 90 18614 6–29

NYHA (%) I II

90 10

85 15

95 5

90 10

100

100

a

M, male; F, female; AF, atrial fibrillation; FU, follow-up.

G. Ismeno et al. / International Journal of Cardiology 69 (1999) 179 – 183

2.7. Statistical analysis

prosthesis; Group B, mitral ball and aortic bileaflet prosthesis; Group C, tilting disc prostheses in mitral and aortic position; Group D, mitral tilting disc and aortic bileaflet prosthesis; Group E, mitral bileaflet and aortic tilting disc prosthesis; Group F, bileaflet prostheses in mitral and aortic position

Chi square and Fischer’s exact test were performed to analyse categorical data. To evaluate significant statistical differences between media and variance of the hematological data, ANOVA (analysis of variance) test and the Bonferroni test for multiple comparisons in the case of affirmative results were performed. P,0.05 was considered statistically significant (aptoglobine P,0.01).

2.5. Hematological studies All patients were informed about the purpose of the study and all gave written consent. Blood (20 ml) was taken every week for 3 weeks to perform the following tests: 1. 2. 3. 4. 5.

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3. Results Data are reported in Table 2.

blood hemoglobin (g / dl), serum lactic dehydrogenase (U / l), percent-correlated reticulocyte fraction (%), serum haptoglobin (g / l), schistocytes (%).

3.1. Evaluation of percentage of hemolysis According to the criteria previously reported, 29 / 90 (32.2%) of patients showed some degree of hemolysis. Group F (double bileaflet prostheses) reported the highest number (7 / 15; 46.7%) of patients with hemolysis. Nevertheless, no statistically significant difference was found between the groups (P.0.05).

The data were recorded and the final results were expressed as the mean value of the three blood tests.

2.6. Criteria for hemolysis The criteria proposed by Skoularigis et al. [9] were employed. Patients were considered as having intravascular hemolysis when serum LDH levels were elevated (.460 U / l) (major criteria) and at least two of the following minor criteria were observed:

3.2. Seric haptoglobin Mean seric haptoglobin dosage was low in all groups and no statistical differences (P50.044) between the groups were found.

Blood hemoglobin, ,13.8 g / dl (male) ,12.4 g / dl (female) Reticulocyte fraction .2%, Presence of schistocytes in the blood, Serum haptoglobin ,0.5 g / l.

3.3. Reticulocyte No statistical difference was observed after analysis of the percent-corrected reticulocyte fraction between the groups (P.0.05).

Table 2 Hematological data for patients with different types of mechanical prostheses in aortic and mitral position Group

LDH (U / l) Hemoglobin (g / dl) Haptoglobin (g / l) Reticulocytes (%) Schistocytes (%) Hemolysis (%) * P,0.05.

Significance

A

B

C

D

E

F

645.3685.9 14.461.7 * 0.0760.05 0.9360.5 1.861.2 3 / 15 (20%)

705.7688.6 * 13.761.6 0.1360.09 0.9160.6 2.260.8 5 / 15 (33.3%)

504.8657.8 * 13.461.4 0.2060.18 0.9960.6 1.460.5 3 / 15 (20%)

549.5663.5 * 12.060.9 * 0.1360.08 1.4760.9 0.860.4 6 / 15 (40%)

605.8691.2 14.361.4 * 0.1760.05 1.6560.8 0.560.3 5 / 15 (33.3%)

665.3684.2 12.360.9 * 0.1360.05 1.4560.8 0.860.2 7 / 15 (46.7%)

* B versus C and D * A and E versus D and F P.0.01 P.0.05 P.0.05 P.0.05

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3.4. Presence of schistocytes A few schistocytes were occasionally found in the peripheral blood smear, regardless of model and position of the prostheses (P.0.05).

3.5. Serum lactic dehydrogenase The mean LDH value was high (.460 U / l) in all groups; in patients with mitral ball valve and bileaflet prosthesis in aortic position (Group B) we observed a mean LDH value of 705.73 U / l, statistically (P, 0.05) higher than in patients with tilting disc valve in mitral position (Groups C and D).

3.6. Blood hemoglobin Low levels of blood hemoglobin were found in Groups D and F. The difference was statistically significant (P,0.05; Bonferroni test) when compared with Groups A and E. No other correlation between the groups showed any statistical difference (P.0.05; ANOVA).

4. Discussion Although in the early days of cardiac surgery some prostheses were associated with significant degrees of intravascular hemolysis [5], nowadays hemolysis is no longer a complication of heart valve replacement with mechanical prostheses. The advent of new mechanical valves has demonstrated the concept that clinically relevant hemolysis is more pronounced with malfunctioning than with normofunctioning valves [4]. Nevertheless, many authors are still reporting some degree of subclinical hemolysis in patients with left sided heart valve replacement with mechanical prostheses [2,9]. The chronic intravascular hemolysis in patients with the currently implanted mechanical valves is mild, subclinical and decompensed hemolytic anemia is a rare finding. Many factors have been found to influence the degree of hemolysis: site of implant, prosthetic design, size of prosthesis, number of prostheses implanted, presence of atrial fibrillation [1]. Comparative studies have been performed between different prosthetic models either in aortic and / or in mitral position to evaluate

the degree of hemolysis according to the prosthetic model. In the past a greater severity of hemolysis was found in patients with ball valve [5,7]. A recent study performed by Skoularigis found a higher degree of hemolysis in patients with bileaflet valves versus tilting disc valves, in double versus single valve replacement and in mitral versus aortic valve replacement [9]. Although many studies investigating the severity of hemolysis in patients with double valve replacement have been performed, the degree of hemolysis in patients with different combinations of mechanical valves (bileaflet–ball–tilting disc) has not been studied. In the present study some degree of subclinical hemolysis was found in 30% of our patients with double valve replacement and, according to the criteria proposed by Skoularigis et al., the incidence of hemolysis was higher whenever a bileaflet valve was implanted either in aortic and / or in mitral position. The Starr–Edwards ball valve has a high incidence of clinically relevant hemolysis, especially in cloth-covered models [7]; 6120 model has rarely been associated with hemolysis in properly working prostheses. Nevertheless, turbulence caused by lateral flow causes some degree of compensated hemolysis. In our study a ball valve in mitral position did not increase the incidence of hemolysis unless it was associated with a bileaflet valve in the aortic position. The finding that bileaflet valves produce more hemolysis than tilting disc valves has already been demonstrated by others [9]. Concern is raised by the fact that bileaflet valves, which have the lowest profile among the mechanical prostheses, probably have the highest closing reflux [10,11]. The total amount of reflux across bileaflet valves varies between 4 and 15% of the forward flow depending on valve size, pressure gradient across the closed valve, cardiac rhythm, stroke volume, heart rate and the method used for assessment [10,11]. It could well be suggested that hemolysis associated with bileaflet valves is another consequence of the regurgitation. It has been hypothesized [8,12] that, as a mechanism of hemolysis, the early asyncronous and diastolic closure of the posterior lying leaflet of a mitral bileaflet prosthesis may be responsible. This theory cannot be applied to our patients, all being bileaflet mitral prostheses in our series, implanted in antianatomical position (hinge area at 908 with left ventricular free wall).

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In conclusion, subclinical hemolysis was detected in a large number of patients with mechanical prostheses in mitral and aortic position. Whenever bileaflet valves were employed either in mitral and / or in aortic position a higher incidence of hemolysis was found. Nevertheless, the advantages of bileaflet valves in terms of durability, thrombogenicity, and hemodynamic performance support their use as valve substitutes [13–20]. Further studies are necessary in patients with bileaflet valves to establish the relations between closing reflux, physiological conditions such as exercise, prosthetic size and subclinical hemolysis.

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