i
Prospective single blinded observational study to
compare TTK ChitraTM
with St Jude MedicalTM
heart valve prostheses in terms of haemolysis
PROJECT REPORT
Submitted during the course of
DM Cardiology
Dr. Mukund A Prabhu
DM Trainee
DEPARTMENT OF CARDIOLOGY
Jan 2011 – Dec 2013
ii
DECLARATION
I, Dr. Mukund A Prabhu hereby declare that the project in this book was
undertaken by me under the supervision of the faculty, Department of Cardiology,
Sree Chitra Tirunal Institute for Medical Sciences and Technology.
Thiruvananthapuram Dr Mukund A Prabhu
Date DM Trainee
Forwarded
The candidate, Dr Mukund A Prabhu, has carried out the minimum required
project.
Thiruvananthapuram Prof. Dr Thomas Titus
Date Head of Department of Cardiology
iii
ACKNOWLEDGEMENTS
Dr. Jaganmohan Tharakan, a teacher par excellence, who has been a constant source
of inspiration.
Dr. K K Narayanan Namboodiri who was the guide not only in this study, but also in
many other aspects of my life.
Dr. Simran Kundan, the never tiring co-investigator of this study.
Dr. Kavitha Ravi, Associate professor of Pathology at Medical college Trivandrum,
who extended her unconditional help in analysis of peripheral smears.
Dr. Manu Bhasker and Dr. Jithesh Balan whose help was constant and crucial.
Dr. Shanmugasundaram P, and Dr. Kiron S who helped with and taught the statistical
analysis.
My colleagues, seniors and juniors for all the support they extended.
The staff nurses at cardiology department who were helpful in every way during my
residency and during this study.
My parents and family for their unsurpassable guidance, blessings, support and help.
I deeply thank the patients who were a part of this study.
iv
ABBREVIATIONS
A Fib - Atrial fibrillation
AVR - Aortic valve replacement
CE - Carpentier Edwards prosthesis
CHVP - TTK-Chitra valve prosthesis
CM - Carbomedics prosthesis
DVR - Double valve replacement
EOA - Effective valve orifice area
Hb - Hemoglobin
LDA - Laser Doppler Anemometry
LDV - Laser Doppler Velocimetry
LDH - Lactate Dehydrogenase
MVR - Mitral Valve replacement
MH - Medtronic Hall prosthesis
SJM - St Jude medicals prosthesis
v
INDEX
PAGE NO.
INTRODUCTION 1
HYPOTHESIS 5
OBJECTIVES 6
REVIEW OF LITERATURE 7
MATERIALS AND METHODS 16
RESULTS 19
DISCUSSION 35
LIMITATIONS 41
CONCLUSIONS 42
REFERENCES 43
Introduction
Background
1
BACKGROUND
Mechanical heart valve prostheses are associated with hemolytic anemia due to
several mechanisms including trauma to red blood cells induced by shear stress,
abnormal jet flow through the prostheses, direct mechanical damage to red blood
cells and thrombocytes as well as complement fixation to red blood cells or
exogenous toxins (1). Generally, red blood cell damage is more pronounced with
malfunctioning than with properly working prostheses (2).Increased destruction of
red blood cells is a known complication in patients after insertion of aortic valve
prostheses (3).Incidence of hemolysis is less in tilting disc valves compared to ball
and cage prosthesis (4). 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 (5) where as other authors have done it at a 1
year follow up period or more (6).
The increased destruction of erythrocytes with haemolysis after insertion of
prosthetic heart valves has been related to an increase in shearing stress developed
from turbulent jets and from increased diastolic or systolic gradients(7) The disc
valve models (Bjork-Shiley and Lillehei-Kaster prostheses) are characterized by a
central flow pattern with little turbulence. The peak systolic gradients measured after
operation have been found significantly lower than usually reported in patients with
ball valve prostheses (8).
The degree of rise in SLDH levels correlates with the degree of shortening of the 51-
Cr labeled red cell survival time (9). TTK Chitra valve is a tilting disc model of heart
valve (vide infra).
The American College of Cardiology/American Heart Association (ACC/AHA)
proposes the determination of LDH in patients after prosthetic heart valve
implantation for detection of prosthetic valve dysfunction (10).
Background
2
The mitral valve is situated in a relatively low pressure system and is less likely to
produce the shearing stress required to damage red cells. But mild haemolysis,
however, was present in the majority of patients with tilting disc prosthesis (Bjork-
Shiley and Lillehei-Kaster prostheses). Increased concentrations of serum lactate
dehydrogenase (LDH) showed no significant correlation with either the peak
diastolic gradient across the valve or the flow through the valve. There was no
significant difference between the incidence and severity of haemolysis after
insertion of Bjork-Shiley or Lillehei-Kaster prosthesis in the mitral position (11) or
aortic position (12).
Previous studies investigating St. Jude Medical (SJM) Standard, Omniscience and
Medtronic Hall prostheses reported normal to slightly elevated LDH values for
normal functioning prostheses (13,14). Moderate hemolysis is known to occur with
new generation bileaflet valves SJM HPR and SJM RegentR in aortic position (15).
The only mechanical bileaflet valve on the market that does not show LDH elevation
in aortic position is the ON-XR Valve. The design of this valve hides the hinges of
the bileaflets to avoid blood contact with the hinges (16).
A sensitive method for measuring intravascular haemolysis is to determine serum
lactic dehydrogenase activity since the erythrocytes have a high concentration of this
enzyme which is released into plasma by haemolysis (4). Other indices of hemolysis
due to red cell destruction are serum Haptoglobin, red cell count and hemoglobin and
reticulocyte counts. Measurements of reticulocyte counts have been shown of minor
value, except in cases with more severe haemolysis. The serum haptoglobin was
usually absent or much reduced, in most studies on prosthetic valve related
hemolysis, but is probably a variable too sensitive to be used as reliable index for
intravascular haemolysis in this connection(4). Degree of hemolysis may be assessed
by serum LDH levels, Hemoglobin and Bilirubin levels after prosthetic valve
implantation. Various studies use different time intervals for these measurements.
Background
3
Gennaro et al measured it weekly for 3 weeks following surgery to determine the
incidence and severity of prosthetic valve induced hemolysis.
A study performed by Skoularigis et al 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 (17).
The TTK Chitra heart valve prosthesis is unique in design, materials of construction
and fabrication. It is the most extensively researched, tested, and premarket clinically
evaluated device in India .TTK Chitra Valve has been in use for more than 20 yrs .Its
clinical performance evaluation has revealed that overall it is an excellent substitute,
and cost effective for other standard valves (18). In vitro test have demonstrated that
the low negative pressure gradients and absence of ‘cavitation effect’ with TTK
Chitra valve might be of importance in reducing blood damage and thrombosis, as
compared to valve with rigid occluders (19). No data is available on prevalence or
severity of hemolysis in TTK-Chitra valve. This study aims to find out the same and
compare with similar data on St.Jude prosthesis.
DESIGN OF TTK CHITRA VALVE
The valve incorporates a Tilting Disc, pivoted eccentrically in the metallic frame.
The sewing ring is fitted snugly around the frame and is used to suture the valve in
the intended position in the heart. The frame and the disc are hydro dynamically
designed to reduce drag and inertia and polished to minimize the chances of clotting.
(20).
Background
4
Fig: 1 Design of TTK Chitra valve
It has some attractive features like Complete Structural Integrity, Absence of
cavitation related damage, Silent operation, Rotatable within the sewing ring
to assure its freedom to rotate if repositioning is required and low profile.
Hypothesis
Hypothesis
5
HYPOTHESIS
TTK-Chitra valve is non-inferior to St.jude valve with respect to
intravascular hemolysis and red cell damage
Aims & Objectives of the Study
Objectives
6
OBJECTIVES
To determine the prevalence and severity of hemolysis in patients with
TTK-Chitra valve prosthesis and compare with that in St.jude prosthesis.
Review of Literature
Review of Literature
7
REVIEW OF LITERATURE
Ellis et al.(1) classified the causes of prosthesis induced hemolysis into 3 factors —
(a) blood impact with valve supra structures, (b) turbulent shear stress in disturbed
forward flow, and (c) shear stress due to transvalvular leakage—reporting that the
effects of leakage were greater than those of the other causes.
Leakage jets arise mainly from small gaps between leaflet edges and housings in
Medtronic Hall (MH)valves, but from hinges in St. Jude (SJM ) and Carbomedics
(CM) valves. High-pressure regurgitant flow through complicated hinge structures is
considered the main cause of bileaflet valves having a greater degree of hemolysis
than tilting disc valves, as reported by several studies,(17, 21) even though bileaflet
valves were superior to tilting disc valves in shear stress in forward flow (22, 23)
Platelets can become hyper activated due to shear forces and they present a risk for
the development of a thrombotic event. This risk of platelet over activity may be
viewed as the result of an imbalance in the homeostatic system, due,
in large part, to chronic blood damage and the destruction of formed blood elements.
As early as 1970, Harker and Slichter (24) showed that patients with first-generation
mechanical valves such as the ball-and-cage and tilting disc had a shortened platelet
half-life due to increased incidence of platelet destruction and activation. Direct
mechanical trauma by impact with the valve supra structure and shearing forces
induced by turbulent flow are the two possible mechanisms accounting for this
destruction. In a later study, Dale et al. (49) found a correlation between elevated
levels of the enzyme lactate dehydrogenase (LDH) and decreased red cell half-life in
patients with first-generation prosthetic heart valves.
The same fluid stresses which can lead to the damage and/or destruction of red cells
and platelets can also affect the endothelial cells, which line the walls of the
vasculature. When endothelial cells are stripped from their biological substrates by
Review of Literature
8
high fluid stresses, the exposure of the extra cellular matrix proteins lining the
surfaces can lead to the subsequent adherence, activation, and aggregation of
platelets. (25, 26)
Laser Doppler Anemometry (LDA), also known as Laser Doppler Velocimetry
(LDV), is an optical technique ideal for non-intrusive 1D, 2D and 3D point
measurement of velocity and turbulence distribution in both free flows and internal
flows. Science and industry LDA systems to gain a clearer understanding of fluid
mechanics Yoganathan et al. (22) employed 2D LDV to conduct the first detailed
investigations of the pulsatile forward flow fields of the SJM bileaflet valve in the
aortic position and the Medtronic-Hall and Bjork–Shiley tilting-disc valves.
They reported maximum turbulent shear stresses downstream of the leaflets ranging
from 1200 dyne per sq.cm for the SJM valve to 2000 dyne per sq.cm for the
Medtronic-Hall valve. Using 1D LDV, Chandran et al. (27) investigated the flow
pattern for different caged ball and tilting disc aortic valve prostheses. The study
showed that the velocity profiles and turbulent shear stress magnitudes downstream
from the tilting disc prostheses are dependent upon the opening of the disc and that
the turbulent normal stresses downstream from the ball caged prostheses were smaller
than those behind tilting disc valves. Fontaine et al. (28) were the first to study the
Bjork–Shiley and SJM aortic valve flow fields with a 3D LDV. They reported
relatively small differences between Reynolds stresses calculated by three-component
vs. two component LDV—within 10 to 20 percent. They also found that the Reynolds
shear stresses calculated along the velocity measurement axes can underestimate the
principle Reynolds shear stress by as much as 100%.
The design of mechanical heart valves deliberately includes some degree of leakage,
or retrograde, flow upon valve closure. This reverse flow is intended to scour critical
areas of the valve, such as the hinges and the areas between the leaflet edges and the
housing. With the advent of high performance computers and advances in
computational fluid dynamics algorithms, more detailed three-dimensional unsteady
laminar and disturbed flow simulations are becoming a reality today. Development of
Review of Literature
9
high resolution fluid-structure interaction algorithms, inclusion of detailed structural
analysis of biological leaflet valves during the valve function, and particle dynamics
analysis with the fluid dynamic analysis to simulate the platelet and red blood cell
motion in the crevices with mechanical valve function are crucial for our further
understanding of the valve function mechanics. However, complementary
experimental studies to validate the simulations are also essential to gain confidence
in the results of the complicated numerical simulations. The results from such
simulations will provide valuable information towards design improvements to
minimize the problems associated with implanted valve prostheses towards the goal
of developing an ideal valve replacement (29).
More hemolysis has been reported with bileaflet prosthesis in many studies (17, 22,
30, and 31). More degree of hemolysis in bileaflet valve as compared to tilting disc
valve may be due to a greater reflux volume and multiple peripherally regurgitant jets
demonstrated in the former on transesophageal echo (17,22).
A greater severity of hemolysis was found in patients with ball valve in the past
literature (32). Sezai et al (33) performed valvar replacement in 86 cases with St. Jude
Medical valves which utilize two discs made of pyrolytic carbon and employ a
bileaflet central opening system. With regard to postoperative clinical evaluation on
valve function and chronic hemolysis, they compared the cases of St. Jude Medical
valves with those of Starr-Edwards (S.E.) valves Carpentier-Edwards (C.E.) valves
and cases of open mitral commissurotomy. As for valve function such as left
atrioventricular diastolic pressure gradient, mitral effective orifice area both at rest
and on exercise, the St. Jude Medical valve yielded best results. Next was the C.E.
and third was the S.E. The results of the St. Jude Medical valve group and those of
the open mitral commissurotomy group were equivalent. In comparison with ball type
cardiac valve prostheses and bioprostheses, the St. Jude Medical valve has excellent
hemodynamic characteristic. Concerning hemolysis, the St. Jude Medical was below
only the C.E., however the degree of hemolysis was so low that the St. Jude Medical
valve holds great promise as central flow mechanical valve prostheses.
Review of Literature
10
Modifications of the artificial valve design may contribute to minimize shear stress
and direct trauma, and may enhance hemodynamic performance of new bi-leaflet
heart valves. In patients with SJM HPR and SJM Regent R prosthetic valves in aortic
position, mean LDH values were slightly above normal. The values for haptoglobin
were below detection limits in more than 75% of patients. No valve-related anemia or
valve-related elevated bilirubin values were reported. These observations match with
the data for the SJM Standard prosthesis (33).These findings are supported by the fact
that no relationship between LDH values and valve size or transvalvular gradient was
found. Therefore, the moderate hemolysis in patients with bileaflet mechanical SJM
heart valves of the HPR and RegentR series are due to other reasons. The design
improvement from SJM Standard to HPR or RegentR was achieved by constructing a
supra annular cuff configuration resulting in a gain in orifice area over for any given
outer diameter. However, the blood contacting components of both the HPR and the
RegentR valve have the same design as the Standard valve without compromising
structural integrity by a shift in the cuff retaining orifice rims [16]. This is probably
the reason for similar biochemical parameters for the SJM Standard, HPR or RegentR
valves. The only mechanical bileaflet valve on the market that does not show LDH
elevation in aortic position is the ON-XR valve [34]. In contrast to the SJM prosthetic
valves, the design of this valve hides the hinges of the bileaflets to avoid blood
contact with the hinges [34]. Other investigators found various causes for blood cell
damage by prosthetic heart valves like direct blood-to-foreign surface contact,
upstream shear stress and—even more important—regurgitation-induced blood cell
damage depending on valve type, valve size (the greater, the larger) and mean aortic
pressure [1,21,34,35,36]. These data indicate that the mild hemolysis of mechanical
SJM valves is design related (flow profile, regurgitation volume and hinge
construction with blood contact), but independent from valve size and transvalvular
gradient
The Chitra tilting disc valve was developed in India to meet the need for a low-cost
cardiac valve. The valve has an integrally machined cobalt-based alloy cage, an ultra-
high molecular-weight polyethylene disc, and a polyester suture ring. An important
Review of Literature
11
feature of this valve is its soft closing sound, by virtue of a plastic occluder (37). The
high prevalence of rheumatic valvular disease in the young population and the high
cost of imports necessitated the development of an Indian valve. The development of
the tilting disc prosthesis was successfully concluded in February 1995, when the
third model completed its clinical trial. The tilting disc valve has an integrally
machined cobalt alloy cage, an ultra high molecular weight polyethylene disc and a
polyester suture ring. The choice of design was based on its superior hydrodynamics
and the age distribution of patients, the majority of whom were below 30 years. The
polymer-metal combination was selected for its extremely low wear rate and proven
durability in the human body (38). The hydrodynamic performance was comparable
to that of proven clinical models. The accelerated testing indicated lifetimes in excess
of 50 years and the animal trials showed the valve to be safe. In the clinical trial, there
was no incidence of structural failure or paravalvular leak. The linearized rate of late
thromboembolism was 6.2%/patient-year (pty), anticoagulant related hemorrhage
0.54%/patient year, and infective endocarditis 0.54% per patient year.
Less data is available on the hemolytic parameters of TTK –Chitra valve.
In a prospective study of 78 patients, with normally functioning mitral prosthetic
valves of various makes, hemolysis was evaluated post-operatively on 7th, 30th and
180th days by clinical evaluation, transthoracic echocardiography, hemoglobin,
serum lactic dehydrogenase (LDH), and reticulocyte count (39).
LDH was elevated in almost all the patients with mechanical valve replacement.
None had significant anemia. All the evidence of hemolysis was not observed in any
of the recipients. There was no statistically significant difference in the degree of
hemolysis among the recipients of various tilting disc valves. There was no
significant correlation between the severity of hemolysis and cardiac rhythm and the
size of valve. The recipients of bileaflet valve had significantly more severe
hemolysis than those of tilting disc valves. LDH was consistently elevated in most of
the recipients of the mechanical valves at postoperative follow up. Nearly half the
patients received prosthesis. Recipients of TTK Chitra valve prosthesis showed least
Review of Literature
12
hemolysis. The severity of hemolysis among the recipients of various tilting disc
valves at 7th postoperative day was not significantly different. However the severity
of hemolysis in the recipients of Medtronic Hall valves was more than those of the
others at 30th and 180th day and the difference was statistically significant. Similarly
the hemolysis was statistically more significant at 180 days follow up in the recipients
of bileaflet prosthesis. There was no significant correlation between the severity of
hemolysis and the size of the prosthesis.
More LDH elevation was observed in patients with bileaflet (Mira Edwards) valve
prosthesis than those with tilting disc valve prosthesis (Sorin Carbocast and Chitra
TTK) in mitral position. (19)
The severity of hemolysis is reported to be related to the type, position and size of
prostheses used, as well as the presence of valve malfunction. Hemolysis was
evaluated in 170 patients with St. Jude Medical (SJM) and 80 patients with Medtronic
Hall (MH) prostheses, with normal mechanical function. Overall, patients with SJM
prostheses had greater frequency and severity of hemolysis than patients with MH
prostheses, irrespective of position and size. No patient had decompensated anemia.
The frequency of hemolysis was similar in both groups with double-valve
replacement, whereas severity was greater with SJM than MH prostheses. The
number and position of the prostheses were correlated with severity of hemolysis:
Double-valve replacement and mitral position were correlated with greater hemolysis
than single-valve replacement and aortic position. Valve size, cardiac rhythm and
time from operation did not correlate either with frequency or severity of hemolysis.
Authors concluded that in normally functioning SJM and MH prostheses hemolysis is
frequent but never severe; SJM demonstrates greater frequency and severity when
compared with MH valve; and that the number, position, but not size, significantly
affect the severity of hemolysis (17)
Meccozi et al, studied intravascular hemolysis in newer generation prosthetic valves
and found that subclinical hemolysis is a frequent finding. A low incidence of
hemolysis was found in stented biologic prostheses, and it was absent in stentless
Review of Literature
13
aortic valves. Frequency of hemolysis in patients with stented aortic bioprostheses
was 3%, whereas it was absent in those with stentless valves. Among mechanical
valve recipients, double versus single valve replacement and mitral versus aortic
valve replacement were correlated with the presence of hemolysis; double valve
recipients also showed a more severe degree of hemolysis. Modifications of valve
design may contribute to minimize the occurrence of hemolysis in mechanical
prostheses (14)
Criteria for Hemolysis
As suggested by Skoularigis et al, patients were considered to have intravascular
hemolysis under the following conditions:
1. Serum LDH levels were greater than 460 U/L (normal, 230-460 U/L). (Major
criteria)
2. Any 2 of the following 4 criteria were present: (Minor criteria)
(1) blood hemoglobin level of less than 13.8 g/dL for male patients (normal, 3.8-17.9
g/dL) and less than 12.4 g/dL for female patients (normal, 12.4-15.5 g/dL);
(2) Serum haptoglobin levels of less than 0.5 g/L (normal, 0.5-3.2 g/L);
(3) Reticulocyte count of greater than 2% (normal, <2%); or
(4) presence of Schistocytes in the peripheral blood smear (normally absent).
According to Skoularigis and coworkers [17], hemolysis is present if serum LDH, as
major criteria, is above normal and two other minor criteria are present. Horstkotte’s
criteria [21] establish hemolysis severity based on the serum levels of LDH and
haptoglobin.
Review of Literature
14
Horstkotte criteria LDH (U/L) Haptoglobin (mg%)
No hemolysis <220 >37
Mild hemoysis 220–400 <37
Moderate hemolysis 400–800 <10
Severe compensate
hemolysis
>800 0
Decompensated
hemolysis
>1000 0
Normal LDH values are different when measured by Horstkotte (>220 U/L) than by
Skoularigis and associates (>450 U/L). This difference is attributable to measuring
LDH at two different ends of a reversible enzymatic reaction: formation of lactate
from pyruvate (L) or pyruvate from lactate (P), and it is usually converted using a
0.483 factor. However, indiscriminate use of a standard conversion factor is not
advisable because assay conditions of analyzers and reagents are different (47).
However the upper limit of LDH at our biochemical lab at Sree chitra tirunal institute
of medical sciences and technology was 190 U /dL.
Due to these differences in definition of hemolysis among different studies, we chose
a different method to define hemolysis.
Review of Literature
15
Definition for our:
We considered a rise in LDH by more than 2 standard deviations above the
preoperative LDH accompanied by a drop in Hemoglobin levels by 2 standard
deviations compared to pre-operative levels as an indicator of hemolysis, if other
causes of LDH rise or hemoglobin levels are excluded. Presence of shistocytes was
considered to be a supportive evidence for hemolysis.
Khandeparkar et al (39) in their study, defined hemolysis based on LDH and
hemoglobin levels.
1. Serum LDH levels were greater than 190 U/L (normal, 100-190 U/L).
2. Blood hemoglobin level of less than 13.0 g/dl for male patients (normal, 13.0-15.0
g/dl) and less than 12.0 g/dl for female patients (normal, 12.0- 14.0 g/dl)
3. Reticulocyte count of greater than 2% (normal, <2%)
Howe ever mean reticulocyte count was <2% in all the subgroups in their study and
only LDH values were considered for identifying hemolysis.
Materials & Methods
Materials and Methods
16
MATERIALS AND METHODS
Study design, Materials and methods
It is a prospective study to determine the incidence and severity of hemolysis in
patients undergoing Prosthetic valve replacement with TTK-Chitra Valve in the
aortic/mitral or both positions, and also to compare the similar data for St.Jude valves
in similar positions. It is designed as a prospective, comparative, observational study
with about 30 patients each in 2 groups-TTK-Chitra and St.Jude valves
AIMS AND OBJECTIVES
To determine the prevalence and severity of hemolysis in patients with TTK-Chitra
valve prosthesis and compare with that in St.jude prosthesis
INCLUSION CRITERIA
All patients with valvar heart disease, who have undergo valve replacement surgery
with either TTK-Chitra valve or St.Jude valve in aortic or mitral positions
EXCLUSION CRITERIA
. 1. Patients with prosthetic valve dysfunction
2. Patients with patient-prosthesis mismatch
3. Patients having other causes of hemolysis or raised LDH/Bilirubin
4. Non-consenting patients
5. Patients undergoing double valve replacement
6. Patients having other types of prosthetic valves implanted
Materials and Methods
17
PROTOCOL
All patients who underwent Single valve replacement with either TTK-Chitra valve
(CHVP) or St.Jude valve (SJM) at SCTIMST between November 2011 and
December 2012 were enrolled in this study.
Those satisfying inclusion and not having the exclusion criteria were explained the
details of the study and a detailed informed consent was taken. In addition to the
initial cardiac evaluation, these patients underwent a LDH level, Hemoglobin levels,
and Bilirubin levels during preoperative evaluation and these same parameters along
with reticulocyte count and peripheral smear during the putative post operative visit.
Electrocardiogram and echocardiogram were also taken and prosthetic valve function
meticulously evaluated.
Hemoglobin was measured in the standard way be Cyan meth hemoglobin technique.
Peripheral smear was analyzed by an experienced pathologist in a blinded of the
details of the cohort.
S.LDH was analyzed by measuring enzyme activity and our lab range was 100-190
IU/dL. This was different from cut offs used in other similar studies. Hence we
defined the occurrence of hemolysis in a different way.
Normal LDH values are different when measured by Horstkotte (>220 U/L) than by
Skoularigis and associates (>450 U/L). This difference is attributable to measuring
LDH at two different ends of a reversible enzymatic reaction: formation of lactate
from pyruvate (L) or pyruvate from lactate (P), and it is usually converted using a
0.483 factor. However, indiscriminate use of a standard conversion factor is not
advisable because assay conditions of analyzers and reagents are different (47).
However the upper limit of LDH at our biochemical lab at Sree chitra tirunal institute
of medical sciences and technology was 190 U /dL.
Due to these differences in definition of hemolysis among different studies, we chose
a different method to define hemolysis.
Materials and Methods
18
Definition of hemolysis for our study:
We considered a rise in LDH by more than 2 standard deviations above the
preoperative LDH accompanied by a drop in Hemoglobin levels by 2 standard
deviations compared to pre-operative levels as an indicator of hemolysis, if other
causes of LDH rise or hemoglobin levels are excluded. Presences of shistocytes were
considered to be a supportive evidence for hemolysis.
STATISTICAL ANALYSIS
• Data are presented as means ± SD and as simple percentages. A separate
analysis was performed to identify the variables associated with the presence
of subclinical hemolysis in the overall population, in aortic valve recipients,
in mitral valve recipients, in mechanical valve recipients, and in bioprosthesis
recipients. The variables analyzed were the following: sex; age; heart rhythm;
prosthetic model, size, and site of implantation; aortic and mitral peak and
mean transprosthetic gradients and different biochemical and hematological
parameters. SPSS 16 version software was used. Chi square test was
performed for qualitative variables. Fischer test used whenever sample size is
small (Subgroup analysis).Independent T test for quantitative variables and
Pearson equation for correlation.
Analysis of Results
19
RESULTS
123 patients who underwent AVR or MVR during November 2011 to December
2012 were screened for the study. Of these, 15 excluded because complete
investigations were not available (lysed sample, suboptimal peripheral smear etc.) 54
patients in each group (Total 108) were recruited for the final analysis.
They were age and sex matched. Rhythm, etiology and NYHA class was also found
to be comparable but Lesion and hence valve position were not matched. In the TTK
Chitra valve cohort, aortic valve disease was more common (Aortic stenosis 40.7%,
Aortic regurgitation 16.7%) than Mitral valve disease (Mitral stenosis 33.3%, Mitral
regurgitation 9.3%).Compared to St Jude valve cohort, (Aortic stenosis 25.9%,
Aortic regurgitation 16.7% , Mitral stenosis 42.6%, Mitral regurgitation 24.1%) ,this
difference was statistically significant (P=0.04) (Table :1)
20
CHITRA ST.JUDE
TABLE 1: Baseline characteristics N=54
% (n)
N=54
% (n)
P
(2-tail)
Sex Male 51.8% (29) 48.2% (27)
.7 Female 48.2% (25) 51.8% (27)
NYHA
class
I 1.9% (1) 3.7% (2)
.31 II 79.6% (43) 66.7% (36)
III 18.5% (10) 29.6% (16)
Rhythm Sinus 37% (40) 28.7%(31)
.06 A Fib 13% (14) 21.3% (23)
Etiology
Rheumatic 48.1% (26) 63.0% (34)
.09 MVP 3.7% (2) 9.3% (5)
Sclerocalcific 24.1% (13) 18.5% (10)
Others 24.1% (13) 9.3% (5)
Lesion
AS 40.7% (22) 25.9% (14)
.04 AR 16.7% (9) 7.4% (4)
MS 33.3% (18) 42.6% (23)
MR 9.3% (5) 24.1% (13)
Valve Mitral 46.3% (25) 64.8% (35)
.05 Aortic 53.7% (29) 35.2% (19)
Valve
Size
17,19,21,23 29.7% (16) 35.2% (19)
.45
25,27,29,33 70.4% (38) 65% (33)
21
The baseline biochemical and hematological parameters were all matched among the
two cohorts (Table: 2)
Table 2:Baseline parameters Mean Std.
Deviation
P
Age TTK 41.13 11.01 .09
SJM 44.46 9.31
Hemoglobin TTK 12.44 1.85 .69
SJM 12.57 1.57
PCV TTK 40.74 3.64 .39
SJM 40.11 3.9
Total Bilirubin TTK .85 .34 .18
SJM .95 .45
Indirect TTK .67 .25 .13
SJM .78 .42
Direct TTK .17 .16 .94
SJM .17 .11
SGOT TTK 32.96 12.6 .85
SJM 32.44 15.89
SGPT TTK 49.00 27.05 .89
SJM 48.31 21.07
LDH TTK 221.67 43.79
.56 SJM 227.54 59.92
22
The mean duration of follow up after surgery was 8.3 ± 1.73 months. No patients in
any of the cohorts had clinically significant hemolysis.
Serum LDH levels after valve replacement, in TTK Chitra Cohort (CHVP) was
lower than that in St. Jude (SJM) cohort (284.17 ± 81.82 vs 333.28 ± 78.09, p=0.002)
(Table: 3).
The total bilirubin - (CHVP 0.66 ± 0.35, SJM 0.87, ± 0.55 p=0.025) and indirect
bilirubin (CHVP-0.57±0.33, SJM mean 0.77 ± 0.51, p=0.02) were also lower in the
TTK-Chitra cohort compared to St. Jude cohort. Other parameters like Hemoglobin,
Packed cell volume and Reticulocyte count showed no significant difference.
(Table:3)
Two patients in SJM group had fragmented cells and one had elevated reticulocyte
counts. But this was not found to be significant on statistical analysis
23
Table 3: Post –surgery Make Mean Std.
Deviation
P
Duration of follow up TTK-Chitra 8.37 1.73 .83
St. Jude 8.30 1.74
Hemoglobin TTK-Chitra 10.92 1.16 .58
St. Jude 10.8 1.23
PCV TTK-Chitra 37.04 3.99 .22
St. Jude 36.07 4.15
LDH TTK-Chitra 284.17 81.82 .002
St. Jude 333.28 78.09
SGOT TTK-Chitra 31.59 13.89 .75
St. Jude 30.85 10.28
SGPT TTK-Chitra 46.59 23.00 .54
St. Jude 44.23 16.37
Total Bilirubin TTK-Chitra .66 .35 .025
St. Jude .87 .55
Indirect Bilirubin TTK-Chitra .57 .33 .02
St. Jude .77 .51
Direct Bilirubin TTK-Chitra .09 .08 .64
St. Jude .10 .06
Reticulocyte count TTK-Chitra .74 .41
.24 St. Jude
.88 .78
24
The difference in LDH levels was similar i.e., SJM had higher values of LDH than
for CHVP (343.91 ± 87.91 vs. 269.60 ± 63.85, p=0.001). Neither total and indirect
Bilirubin values nor the other parameters showed significant differance among the
groups when compared with respect to mitral valve position. (Table: 4)
Table 4: Comparison of
parameters for Mitral valve
Make(N=
TTK-25 SJM-35)
Mean Std.
Deviation
P
Age TTK-Chitra 39.56 10.38 .10
St. Jude 43.63 8.57
Hemoglobin TTK-Chitra 10.73 1.12 .93
St. Jude 10.76 1.21
PCV TTK-Chitra 36.18 3.88 .96
St. Jude 36.23 4.28
LDH TTK-Chitra 269.60 63.85 .001
St. Jude 343.91 87.91
SGOT TTK-Chitra 30.88 11.24 .93
St. Jude 31.11 9.02
SGPT TTK-Chitra 46.48 21.09 .34
St. Jude 41.91 15.29
Total Bilirubin TTK-Chitra .67 .40 .11
St. Jude .87 .49
Indirect Bilirubin TTK-Chitra .58 .35 .10
St. Jude .76 .45
Direct Bilirubin TTK-Chitra .08 .05 .27
St. Jude .10 .06
Reticulocyte count TTK-Chitra .75 .38 .24
St. Jude .98 .90
25
Interestingly there was no significant difference in any of the parameters among the
two groups when compared with respect to Aortic valve replacement (AVR) alone.
Table 5: Comparison of parameters
for Aortic valve
Make(N=
TTK-29 SJM-
19)
Mean Std.
Deviation
P
Age TTK-Chitra 42.48 11.54 .29
St. Jude 46.00 10.62
Hemoglobin TTK-Chitra 11.09 1.18 .54
St. Jude 10.87 1.29
PCV TTK-Chitra 37.79 4.01 .10
St. Jude 35.79 3.99
LDH TTK-Chitra 296.72 93.94 .48
St. Jude 313.68 52.25
SGOT TTK-Chitra 32.21 15.99 .67
St. Jude 30.37 12.54
SGPT TTK-Chitra 46.69 24.90 .80
St. Jude 48.37 17.80
Total Bilirubin TTK-Chitra .66 .30 .15
St. Jude .86 .65
Indirect Bilirubin TTK-Chitra .55 .31 .13
St. Jude .76 .62
Direct Bilirubin TTK-Chitra .10 .10 .83
St. Jude .09 .05
Reticulocyte count TTK-Chitra .73 .43 .80
St. Jude .69 .44
26
When the change in Serum LDH levels before and after valve replacement were
compared among CHVP and SJM groups it was found that SJM cohort has a higher
rise in LDH levels compared to CHVP cohort.
This held true when analyzed with respect to Mitral position alone
But there was no significant difference when compared with respect to Aortic
position alone. (Table: 6)
Table:6 Change in LDH
post surgery
N Mean Standard
deviation
Standard
error
P (2
tailed)
Chitra 54
62.50 85.854 11.683 .014
St .Jude 54
105.74 93.098 12.669 .014
Mitral Chitra
25 47.68 73.038 14.608 .008
SJM 35 114.63 106.047 17.925 .005
Aortic Chitra
29 75.28 94.945 17.631 .571
SJM 19 89.37 61.978 14.219 .537
27
Mean
LDH
Mean post-op LDH and Change in LDH
28
No significant difference was found among the parameters between MVR and AVR
with in the same group (Both for CHVP and SJM cohorts) (Table: 7 and 8)
Table7:Comparision of parameters in
CHVP
N=
MVR-
25
AVR-29
Mean Std.
Deviation
P
Age Mitral 39.56 10.38 .33
Aortic 42.48 11.54
Hemoglobin Mitral 10.73 1.12 .255
Aortic 11.09 1.18
PCV Mitral 36.18 3.88 .14
Aortic 37.79 4.01
LDH Mitral 269.60 63.85 .22
Aortic 296.72 93.94
SGOT Mitral 30.88 11.24 .73
Aortic 32.21 15.99
SGPT Mitral 46.48 21.09 .97
Aortic 46.69 24.90
Total Bilirubin Mitral .67 .40 .90
Aortic .66 .30
Indirect Bilirubin Mitral .58 .35 .75
Aortic .55 .31
Direct Bilirubin Mitral .08 .05 .46
Aortic .10 .10
Reticulocyte count Mitral .75 .38 .83
Aortic .73 .43
29
Table 8:Comparision of parameters in SJM N=
MVR-35
AVR-19
Mean Std. Deviation P
Age Mitral 43.63 8.57 .37
Aortic 46.00 10.62
Hemoglobin Mitral 10.760 1.21 .75
Aortic 10.874 1.29
PCV Mitral 36.23 4.28 .71
Aortic 35.79 3.99
LDH Mitral 343.91 87.91 .17
Aortic 313.68 52.258
SGOT Mitral 31.11 9.02 .80
Aortic 30.37 12.54
SGPT Mitral 41.91 15.29 .17
Aortic 48.37 17.80
Total Bilirubin Mitral .87 .49 .97
Aortic .86 .65
Indirect Bilirubin Mitral .76 .45 .99
Aortic .76 .62
Direct Bilirubin Mitral .10 .06 .70
Aortic .09 .05
Reticulocyte count Mitral .98 .90 .19
Aortic .69 .45
30
No significant difference was found when analysis of hemolytic parameters was done
with respect to rhythm (Table: 9)
Table 9:Comparision of parameters for
Rhythm
N=
Sinus71
A fib 37
Mean Std.
Deviation
P
Age Sinus 41.65 10.57 . 11
A Fib 45.00 9.46
Hemoglobin Sinus 10.979 1.19 .17
A Fib 10.643 1.18
PCV Sinus 36.74 4.19
.53 A Fib 36.21 3.90
LDH Sinus 308.56 82.77 .98
A Fib 309.03 85.56
SGOT Sinus 31.00 13.06 0.75
A Fib 31.65 10.39
SGPT Sinus 46.14 21.29 .79
A Fib 44.00 17.13
Total Bilirubin Sinus .7315 .47 .60
A Fib .8441 .47
Indirect Bilirubin Sinus .6369 .44 .24
A Fib .7332 .43
Direct Bilirubin Sinus .0946 .07 .28
A Fib .1108 .06
Reticulocyte count Sinus .78 .46 .43
A Fib .88 .85
31
There was a weak but statistically significant correlation between LDH and SGOT
(spearman correlation co-efficient-0.35, p=0.00)
No correlation between Bilirubin and SGOT or LDH levels was found
A rise in LDH by more than 2 standard deviations from pre-operative levels, and a
drop in Hemoglobin by more than 2 standard deviations from preoperative levels
were compared and analyzed. Those who had both a rise in LDH levels and a fall in
Hemoglobin levels were considered to have hemolysis. A rise in post operative LDH
levels occurred in 25.9% subjects in CHVP cohort and 59.3% in SJM cohort
(p=0.001). (Fig :2)
A drop in hemoglobin occurred in 14 (25.9%) subjects in CHVP group compared to
23 (42.6%) in CHVP group (p=0.06). Hemolysis occurred in 7.4% of subjects in
CHVP group versus 32.5% in SJM group (p=0.002) (Table: 10)
The odds ratio for hemolysis was 5.74 (95% Confidence interval 1.784 – 18.94)
Table 10:
Prevalence of
hemolysis
Rise in LDH Fall in Hb Hemolysis
CHVP 14 (25.9)% 14 (25.9%) 4 (7.4%)
SJM 32 (59.3%) 23 (42.6%) 17 (31.5%)
P Value .001 .06 .002
32
Fig: 2 Number of patients with LDH rise and
hemolysis
0
10
20
30
40
50
60
70
LDH rise Hemolysis
CHVP
SJM
When analysis was carried out for prevalence of hemolysis with respect to mitral and
aortic positions, the rise in LDH levels were significantly lower in CHVP cohort vs.
SJM cohort (p=0.008 for mitral position and p=0.01 in aortic position ) (Table: 11)
However when presence of hemolysis was compared, a statistical significance was
observed only with respect to aortic position (20% in CHVP cohort vs. 31% in SJM
cohort p=0.001). In CHVP group, hemolysis is more at Mitral than aortic position.
But in SJM group, more hemolysis was observed in aortic position. But it should be
the numbers were small and subgroups were unequal, to carry out a reliable subgroup
analysis.
Similarly, analysis to compare the parameters for Aortic vs. Mitral positions within
the given make (CHVP Vs SJM cohorts) showed that there was no significant
difference in the parameters in between these two positions (Table: 12).
Results
33
Table: 11
Hemolysis Rise in LDH Fall in Hemoglobin
CHVP (n=54) n SJM(n=54) n P CHVP SJM p CHVP SJM p
Mitral 3(12%) 25 9(25.7%) 35 0.19 5 (20%) 19(54.3%) 0.008 4(16%) 15 (42.9%) 0.03
Aortic 1
(3.4%)
29 8 (42.1%) 19 0.001 9 (31%) 13 (68.4%) 0.01 10(34.5%) 8 (42.1%) 0.6
0
10
20
30
40
50
Percentage
having
hemolysis
Mitral Aortic
Fig:3 Hemolysis depending on valve position
CHVP
SJM
Results
34
Table: 12 Hemolysis Rise in LDH Fall in Hemoglobin
Mitral n Aortic n P Mitral Aortic p Mitral Aortic p
CHVP 3(12%) 25 1 (3.4%) 29 0.12 5 (20%) 9 (31%) 0.36 4(16%) 10(34.5%) 0.12
SJM 9(25.7%) 35 8 (42.1%) 19 0.96 19(54.3%) 13 (8.4%) 0.31 15 (42.9%) 8 (42.1%) 0.96
Discussion
Discussion
35
DISCUSSION
This prospective, single blinded, observational, single centre case- control study
compared the prevalence of subclinical hemolysis in Chitra valve and compared its
severity with that in St. Jude prosthesis.
54 patients who were age and sex matched were studied. But valve position was not
matched (p=0.04). (Fig:4)
0
5
10
15
20
25
30
35
Numbers
MVR AVR
Fig 4: Propotion of mitral and aortic valves
CHVP
SJM
Intermediate term follow up (The mean duration of follow up after surgery was 8.3 ±
1.73 months) results showed that TTK chitra (CHVP) cohort had less elevation of
LDH levels compared to St. Jude (SJM) cohort.
LDH, Total bilirubin and indirect Bilirubin showed significant difference between
the two groups
• LDH - P=0.002 (CHVP mean 284.17, ±81.82, SJM-mean 333.28, ±78.09)
• BIT- P=0.025 (CHVP mean 0.66±0.35, SJM mean 0.87±0.55)
• BII-P=0.02 (CHVP-mean 0.57 ±0.33, SJM mean 0.77±0.51)
Discussion
36
Khandeparkar et al (39) studied short term (up to 3 months) prevalence of normally
functioning mitral valve prosthesis of 4 different makes. This included both Bileaflet
and tilting disc designs, but St.Jude prosthesis was not studied. They also found a
lower incidence of hemolysis in tilting disc designs and TTK Chitra prosthesis had
the least prevalence at 30 and 180 days post surgery. Similar to this study, hemolysis
was diagnosed by rise in LDH and low Hemoglobin, but absolute cut offs were used
unlike standard deviation in our study. Though the authors proposed reticulocyte
count >2% as a diagnostic marker of hemolysis, all the subgroups had mean
reticulocyte counts <2% at 7, 30 and 180 days post surgery. This is consistent with
our study where reticulocyte count was found to be <2% in most patients. The reason
for this is not clear, but may be due to coexisting iron deficiency (iron or
micronutrient deficiency) and blood loss (anticoagulation related, and perhaps
surgery related), commonly prevalent in Indian population.
More hemolysis has been reported with bileaflet prosthesis in this and other studies
also (17,22, 30, 31). More degree of hemolysis in bileaflet valve as compared to
tilting disc valve may be due to a greater reflux volume and multiple peripherally
regurgitant jets demonstrated in the former on transesophageal echo (17).
When the change in S.LDH levels before and after valve replacement were compared
among CHVP and SJM groups it was found that SJM (105.74± 93.098) has a higher
rise in LDH levels compared to CHVP (62.50 ± 85.854 ), (p=0.04). Similarly SJM
group (333.28 ± 78.09) had higher absolute mean post operative LDH levels
compared to CHVP group (284.17 ± 81.82), (p=0.002).
Discussion
37
0
20
40
60
80
Percentage
rise in
LDH
No rise
in LDH
Fig:4 Propotion having Rise in LDH levels
CHVP
SJM
Fig:5 Absolute LDH rise
0
20
40
60
80
100
120
140
CHVP SJM
Ris
e in
LD
H MVR
AVR
Bothcombined
This held true when analyzed with respect to Mitral valve replacement (MVR) alone
(CHVP 269.60 ±63.85 Vs SJM 343.91 ± 87.91, p=0.001). There was no significant
difference when compared with respect to aortic valve replacement (AVR) alone
(CHVP 296.72 ±93.94 Vs SJM 313.68± 52.25, p=.48).
Miguel Josa et al (47) showed a greater degree of blood damage in the presence of a
mitral valve, with serum LDH levels significantly higher in patients with Mitral or
Double valve than in those with Aortic valve position. Neither valve size nor the
indexed Effective valve orifice area (EOA) influenced hemolysis. In their study, it
held true even in those patients in whom a prosthesis-to-body surface area mismatch
Discussion
38
was present. Their findings are consistent with those of other investigators and are
similar to results with other bileaflet and disc prostheses (16, 17)
Apart from Serum LDH, when analysis was done to detect the prevalence of
hemolysis as per the definition used, it was observed that Hemolysis occurred in
7.4% of subjects in CHVP group versus 32.5% in SJM group (p=0.002). (Fig: 2).
The odds ratio for hemolysis was 5.743 (95% Confidence interval 1.784 – 18.94).
Though rise in LDH values and higher absolute values occurred in Mitral valve
subgroup of SJM cohort, the incidence of hemolysis was more in the AVR subgroup
of SJM cohort (Fig: 3). This analysis may be unreliable as the subgroups largely
differ in number. There was no statistically significant difference in LDH values
between mitral and aortic subgroups with in either the CHVP cohort or the SJM
cohort.
Since the clinical introduction of the St. Jude valve in 1977 and the publication of the
excellent results of performance of bileaflet valves (40,41), these prostheses have
become the mechanical heart valve substitute of choice for many surgeons. However,
design of this new generation of valve prostheses has not eliminated the problem of
flow separation and stagnation and high degree of turbulent shear stresses associated
with potential damage to blood elements, particularly to red blood cells and platelet
activation (36). Red blood cell destruction and platelet damage and activation lead to
hemolysis and thrombotic phenomena [25, 36]. Regurgitant stresses are more severe
in the mitral position than in the aortic position. Forward turbulent flow and
cavitation phenomena have also been associated with hemolysis (42).
Various studies have used different parameters as a marker of subclinical hemolysis.
Ninomiya et al (30) studied S.LDH levels early and late post postoperative period as
the main marker of hemolysis.
They found that late postoperative hemolysis was higher in the SJM and
Carbomedics (CM) groups than in the Medtronic Hall (MH) group because
hemolysis in the SJM and Carbomedics (CM) groups was more severe in the late
Discussion
39
postoperative period than in the early postoperative period. Since the MH valve uses
a Teflon sewing ring, which is fine-textured and minimally covered by the
endocardium, the decrease in late postoperative hemolysis is thought to have
occurred because artificial material such as pledgets and stitches was covered by
endocardium. Although the SJM valve is thought to result in less late than early
postoperative hemolysis because its Dacron sewing ring is loose-textured and
covered by endocardium, their findings were not consistent with this. The CM valve
has a carbon-coated Dacron sewing ring to prevent excessive endocardial
proliferation, but increased hemolysis in the late postoperative period was still not
consistent with general belief. Concerning these late postoperative increases in
hemolysis in the SJM and CM groups, they surmised that shear stress against blood
through pivot recesses may be higher in the late postoperative period than in the
early postoperative period because the transvalvular regurgitant flow increases in the
late postoperative period as cardiac function improves. Nevaril et al.(7) reported that,
above a certain level, a small increase in shear stress resulted in hemolysis of many
cells. Rambod et al (43) reported that patients with an ejection fraction > 0.45 had a
higher frequency of micro bubbles, which was reported to be related to hemolysis.
This hypothesis is supported by Ninomiys’s study (30), which showed that the late
postoperative cardiac index was higher than the early postoperative cardiac index.
Although blood pressure and heart rate theoretically affect transvalvular regurgitant
flow, no significant correlation was seen between these parameters and hemolysis.
Many studies have reported no correlation between hemolysis and the size of valve
prostheses (17, 44, 45, and 46). Hence we didn’t attempt to correlate between size of
the prosthesis, heart rate or transvalvar regurgitant flow with hemolysis.
Blood flow through mechanical valves damages red blood cells and activates
platelets. It can be postulated that subclinical hemolysis is also an indicator of the
degree of latent platelet damage and activation and potential for valve thrombotic
phenomena, and should be given a strong consideration in the evaluation of the
performance of any heart valve prosthesis (47). Similar to the speculation described
in this study, we may also postulate that the infrequent thrombotic and
Discussion
40
thromboembolic phenomena observed in TTK-Chitra valve could be related to the
low degree of blood element damage associated with this prosthesis.
Our study too found no correlation between the severity of hemolysis and the heart
rhythm as observed in other studies (17, 39)
Only 3 patients were observed to have evidence of hemolysis in peripheral smear in
our study. Though all of them were from the SJM cohort, this was not found to be
statistically significant.
The lesser prevalence of subclinical hemolysis in TTK Chitra valve may be
attributed to its tilting disk design and also to less cavitation in Chitra TTK heart
valve due to use of ultra high molecular weight polyethylene (48).
Another important observation made in our study was that there was a drop in
hemoglobin level post surgery, compared to preoperative levels. This drop was there
in both the cohorts and was by about 1 standard deviation.
CHVP: 1.7± 1.9 mg/dL vs. SJM 1.7 ± 1.9 mg/dL p<0.05 for hemoglobin drop in both
cohorts, and p=0.36 for comparison of hemoglobin drop between the two cohorts.
This demands the consideration of other causes of anemia in our population like iron
deficiency, other deficiencies like folic acid etc that is essential for hematopoeisis,
occult blood loss due to parasitosis and oral anticoagulation and also delayed
recovery from post operative blood loss.
None of the other similar studies have analyzed the change in post operative
hemoglobin; rather they have chosen an absolute cut off value for hemoglobin that
identifies the occurrence of hemolysis.
Conclusions
Conclusions
41
CONCLUSION
TTK-Chitra valve was non inferior to St.Jude valve with respect to clinical
intravascular hemolysis.
There was no clinically significant hemolysis in either of the groups.
Subclinical hemolysis was lesser with TTK-Chitra valve than in St.Jude valve
especially so in the aortic position.
Red cell damage as indicated by rise in Serum LDH was less with TTK-
Chitra valve in both mitral and aortic positions.
Prevalence of hemolysis didn’t correlate with the cardiac rhythm.
The drop in hemoglobin levels that occurred in both cohorts even when there
was no significant LDH rise suggests that mechanisms other than hemolysis
may be contributing for anemia and mandates a separate focused
investigation.
Limitations
Limitations
42
LIMITATIONS
This is a Single centre study.
Though the sample size in each cohort was comparable to that in other similar
studies, we have no matched the number of subjects in each subgroup with respect to
mitral or aortic positions. When subgroup analysis was done with respect to valve
position, number of samples might be small and unequal. But this is true with most
of other similar studies.
Haptoglobin was not analyzed. Haptoglobin was almost invariably low in all similar
studies and it may be regarded as too sensitive a test for comparing hemolysis.
Criteria used for defining hemolysis were different from other studies. But even
though multiple studies used different criteria, most studies regarded LDH as a
sensitive marker for subclinical hemolysis and comparison between intensity of
hemolysis most often used LDH levels alone.
We didn’t include subjects with double valve replacement (DVR) in our study.
References
43
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