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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