SREE CHITRA TIRUNAL INSTITUTE FOR
MEDICAL SCIENCES AND TECHNOLOGY THIRUVANANTHAPURAM, KERALA, INDIA – 695011
Prevalence and Determinants of Myocardial
Damage after Occluder Implantation in Patients
with Atrial Septal Defect (ASD)
PROJECT REPORT
Submitted during the course of
DM Cardiology
Dr. MAHIM SARAN DM Trainee
DEPARTMENT OF CARDIOLOGY Jan 2014 – Dec 2016
DECLARATION
I, Dr. Mahim Saran, hereby declare that the project in this book, titled
“Prevalence and Determinants of Myocardial Damage after Occluder
Implantation in Patients with Atrial Septal Defect (ASD)” was undertaken
by me under the supervision of the faculty, Department of Cardiology, Sree
Chitra Tirunal Institute for Medical Sciences and Technology.
Thiruvananthapuram Dr. Mahim Saran
Date: DM Cardiology Trainee
Forwarded
The candidate, Dr Mahim Saran, has carried out the minimum required
project.
Thiruvananthapuram
Date:
Dr. Ajit Kumar V.K.
Professor and Head
Dept. of Cardiology, SCTIMST
TITLE
“Prevalence and Determinants of Myocardial
Damage after Occluder Implantation in Patients
with Atrial Septal Defect (ASD)”
Primary Investigator:
Dr. Mahim Saran,
Senior Resident,
Department of Cardiology, SCTIMST
Guide:
Dr. Sivasankaran Sivasubramonian,
Senior Professor,
Department of Cardiology, SCTIMST
Co-guide:
Dr.Sanjay G.,
Additional Professor,
Department of Cardiology, SCTIMST
ACKNOWLEDGEMENT
In the course of this dissertation I have been benefited greatly from the assistance of
many people, without whose help this study would not have been possible. I would
like to convey my heartfelt thanks to all of them for their kind support.
I am indebted to my guide and teacher Dr. Sivasankaran Sivasubramonian,
Senior Professor, Department of Cardiology, SCTIMST for his constant support,
enthusiasm, guidance and personal attention throughout this study and training.
I thank my co-guide Dr. Sanjay G., Additional Professor, Department of
Cardiology, SCTIMST for his constant guidance, encouragement and immense
support throughout the project.
I am extremely thankful to Dr. Ajit Kumar V.K., Professor and Head, Dept. of
Cardiology, SCTIMST for his valuable suggestions, support and encouragement.
I am equally indebted to the Faculty of Cardiology department for having permitted
me to include their patients in this study.
I also thank all my colleagues for their support and suggestions, my juniors and
seniors for helping me in the study. I express my deep felt gratitude to my family and
my friends whose blessings and well wishes have always been a strong support during
my entire career. And lastly, I am grateful to all the patients, patient's informants, who
willingly participated in my study.
Dr. Mahim Saran
CONTENTS
Page No.
1. INTRODUCTION 1
2. AIMS AND OBJECTIVES 3
3. REVIEW OF LITERATURE 5
4. MATERIAL AND METHODS 18
5. RESULTS 22
6. DISCUSSION 33
7. CONCLUSION 37
8. REFERENCES 39
APPENDIX i 45
Abbreviations
ASD Atrial septal defect
ASDDC Atrial septal defect device closure
cTnI Cardiac troponin I
cTnT Cardiac troponin T
ICE Intracardiac echocardiography
IVC Inferior vena cava
PFO Patent foramen ovale
TEE Transesophageal echocardiography
TRF Time resolved fluorometry
TTE Transthoracic echocardiography
Introduction
Page 1
introduction
Introduction
Page 2
Manipulation of the heart to treat various congenital malformations could result in
myocardial damage which could be minimized by the less invasive interventional procedures
by avoiding cardiotomy and cardiopulmonary bypass. (1, 2) Interventional Atrial Septal
defect (ASD) occlusion produces much lower myocardial damage (1) than surgical ASD
closure. (2) However, little is known about myocardial lesions after occluder implantation in
children. There are indications that the sensitivity of the myocardium to surgical trauma is
inversely related to the patient’s age, with higher vulnerability among children. (3) Cardiac
troponin I (cTnI) is a sensitive and specific marker for myocardial damage. It is detectable
only in traces in the peripheral blood of healthy people. (3, 4) Cardiac troponin I increase is
widely used for the diagnosis of myocardial infarction (4, 5) and its concentration is
increased after cardiac surgery (3, 6, 7) with maximum values 6–10 hours after surgery. (3, 7)
Catheter intervention and radiofrequency ablation also lead to myocardial injury with
increased cTnI. (8, 9) The specific mechanism of myocardial injury in interventional ASD
closure in not fully understood. The influence of the size of the defect and of the closure
device has not been studied. It is not clear whether the size of the septal defect also
contributes to myocardial damage. So, the purpose of our study is to study the incidence and
extent of myocardial damage after occluder implantation in patients with ASD and to
determine its relationship with age, device size and size of the ASD.
Aims And Objectives
Page 3
AIMS
AND
OBJECTIVES
Aims And Objectives
Page 4
To study the incidence and extent of myocardial damage following occluder implantation in
patients with atrial septal defects (ASD) and to correlate the same with baseline parameters
like
1. Age
2. Atrial septal defect size and
3. Device / occluder size
Review of Literature
Page 5
REVIEW
OF
LITERATURE
Review of Literature
Page 6
Atrial septal defect (ASD) accounts for 8-10% of congenital heart defects with an incidence
of 56 per 100,000 live births. (10) Although the total prevalence was 46 per 100,000 births
from 1968-1997, it showed an approximately 9-fold increase to 100 per 100,000 live births in
1995-1997. (11) This recent trend may be attributed to the increasing use of
echocardiography, compared to earlier studies where ASDs were diagnosed using autopsy
reports, death certificates, physical examination, x-rays, catheterization, and surgical reports.
(12)
Etiology:
Atrial septal defect is a congenital defect arising from malformation of the interatrial septum
allowing pulmonary venous return from left atrium to directly enter the right atrium. The
interatrial septum starts developing by 5th week of gestation and descends from the roof of the
atrium to the endocardial cushion. Before the septum primum fuses with the endocardial
cushion, the cephalad portion develops small perforation which coalesce to form a larger
defect. The septum secundum which starts forming as a fold from the atrial roof stops
growing by the seventh week of gestation leaving a flap like foramen ovale which closes at
birth due to higher left atrial pressures. (13)
Ostium secundum ASD, the commonest form of atrial septal defect results from incomplete
formation of septum secundum or excessive apoptosis of the cephalad portion of septum
primum. Incomplete fusion of the septum primum with endocardial cushion on the other
hand, leads to ostium primum ASD. (13) Sinus venosus ASD occurs due to lack of septation
between right upper pulmonary vein and right atrium. (14) And, a rare occurrence of a defect
between coronary sinus and left atrium is referred to as the coronary sinus ASD. (15)
Review of Literature
Page 7
Echocardiographic assessment:
Before planning for defect closure, the size and residual rims of the ASD should be properly
assessed as some of the deficient rims (pulmonary vein, inferior vena cava or posterior rims)
may preclude ASD device closure and deficiency of aortic rim may be the reason for erosion
later. Echocardiographic assessment remains the gold standard for evaluation of ASD. (16)
Transthoracic echo (TTE) is helpful in children for complete evaluation as the window is
good however, in adults transesophageal echo (TEE) may be required.
Transthoracic echocardiography:
Subcostal frontal view is the best view to visualise the defect as the atrial septum is
perpendicular to the ultrasound beam, visualising the septum in its antero-posterior axis. (17)
Placing the beam perpendicular to the septum helps differentiate a true ASD from an echo
drop out.
Analysis of the septum in supero-inferior axis via subcostal sagittal view is the best technique
for sinus venosus ASDs. It also helps in assessment of the inferior vena cava (IVC) rim and
shape of the ASD. (16)
Apical four chamber view is used to assess the mitral and the pulmonary venous rims and the
size and pressures of the right sided chambers. (16)
Parasternal short axis view helps visualise the aortic and posterior rims. It also aids
assessment of pulmonary artery hypertension, by measuring the pulmonary regurgitationjet.
(16)
Review of Literature
Page 8
Transesophageal echocardiography:
Transesophageal echocardiography is used for complete assessment of the defect and during
ASD closure. Multiple views have been suggested (16):
Mid esophageal four chamber view:
This view helps in assessment of mitral rim and detection of device impingement over
the atrioventricular valves in case of a larger device. The multiplane probe is kept at
zero degree and swept up to 15-30 degrees.
Mid esophageal Aortic valve short axis view:
This view is used to assess the aortic and posterior rims. The probe is kept at 30
degrees and swept 15-30 degrees.
Mid esophageal bicaval view:
This view aids in assessment of sinus venosus ASD and the IVC rim. It also helps in
guiding the wire into left atrium through the septum. The probe is kept at 90 degrees
and swept through 105 and 120 degrees.
Other modalities like 3-dimensional echocardiography and intra cardiac echocardiography
have been used but not commonly available. Computerised tomography (CT) or magnetic
resonance imaging (MRI) may be helpful in complex or sinus venosus ASDs and in
delineating the pulmonary vein anatomy if not clear by echo.
Review of Literature
Page 9
Figure 1 demonstrates different morphological variations of atrial septal defects on
transesophageal echocardiography.
Figure 1: Different Morphological Variations of Atrial Septal Defects onTEE; A: Centrally
located ASD imaged at zero degree; the posterior (Post) and the mitral rims are demonstrated
(arrows). B: ASD with deficient Aortic rim (arrow) imaged at 45 degrees. Both of these types
of ASDs can be easily closed using the trans catheter technique. C: A large ASD with
deficient posterior and aortic rims (arrows). These ASDs are technically challenging for
device closure and are associated with complications. D: Multiple ASDs; there is a larger
anterior defect (block arrow) and a smaller posterior defect (thin arrow).Post=posterior,
Ant=anterior, Ao=aortic
Closure of the Atrial septal defect
The gold standard in the treatment of atrial septal defect (ASD) is direct surgical closure of
the defect. (18) Although surgical closure is associated with low morbidity and mortality and
excellent long-term results, sternotomy and cardiopulmonary bypass are required. Hence, in
recent times, secundum ASD are being increasingly closed by trans catheter implantation of
occluder devices
Review of Literature
Page 10
Percutaneous transcatheter closure
Overall utilisation rates of atrial septal defect (ASD) and patent foramen ovale (PFO) repair
have increased over time. This has mainly been due to the dramatic rise in the percutaneous
closure rates. (19) The fact that surgical mortality rates for ASD closure are similar or higher
than transcatheter mortality rates even when accounting for erosion-related mortality might
have led to this substantial increase in its utilisation. (20, 21) In addition lower cost, better
medical outcome, avoidance of unnecessary blood transfusions and the complications that
accompany extracorporeal circulation make transcatheter closure a better option. (22, 23)The
absence of skin scars and a shorter hospital stay are also more appreciated.
American college of cardiology/American heart association guideline published in 2008 have
clearly outlined the guidelines for secundum ASD closure (Table 1). (24) However, even if
the criteria are met, concurrent data may preclude closure in some cases, like a defect larger
that 40mm or a concomitant cardiac lesion that requires surgery. Also, ASD closure should
not be attempted in irreversible pulmonary hypertension where the defect act as a “pop-off”
mechanism decompressing the right heart during pulmonary hypertensive crisis. (25)
Major contra-indications to device placement in secundum ASD are summarised in table 2.
Review of Literature
Page 11
Table 1: Indications for Atrial Septal Defect(ASD) device closure,(24)
Indications for closure of ASD Class
Right atrial and right ventricular enlargement by echocardiography with or
without symptoms.
Class I
Minimum diameter > 5 mm and < 40 mm on echo.
Adequate rims of tissue (> 5 mm) from the defect to surrounding structures
such as the coronary sinus, SVC, IVC, and AV valves, as well as the
pulmonary veins.
Presence of an ASD with documented or verified paradoxical embolization
and/or documented orthodeoxia-platypnea.
Class IIa
Net left-to-right shunting, pulmonary artery pressures less than two-thirds
systemic levels, pulmonary vascular resistance less than two-thirds systemic
vascular resistance, when either is responsive to pulmonary vasodilators, or
test occlusion of the defect is successful.
Class IIb
Review of Literature
Page 12
Table 2: Contraindications to Atrial Septal Defect (ASD) device closure (25)
Contraindications to ASD closure
Aortic rim absence or severe deficiency confirmed in multiple TEE views. Absence
of rims documented in multiple views of 30º, 40º, 50º+.
IVC rim absence or severe deficiency.
Pulmonary vascular resistance > 15 Woods units is an absolute contraindication.
Coronary sinus rim absence with evidence of coronary sinus impingement by the
device in the catheterization laboratory.
Mitral valve impingement by the device with evidence of new-onset or increasing
mitral insufficiency. Try a smaller device, if feasible.
Development of AV block after device deployment.
ASD closure devices
There are two devices approved by the US Food and Drug Administration (FDA) to close
ASDs—the Amplatzer septal occluder and the Helex septal occluder. While the Helex septal
occluder has a non-self-centering design requiring the disc size to be twice the size of the
defect for effective closure, the Amplatzer septal occluder is a self-centering device. The
waist of the device sits in the ASD not leaving much wiggle room after placement. The
requirement of device size to be as close to the defect size as possible makes Amplatzer
septal occlude suitable for defects as large as 40mm.
Various complications of percutaneous occluder implantation have been reported including
device embolization and malpositioning, arrhythmias, thrombus formation, erosion and
residual shunts. (26) While, device embolization is the most common complication requiring
Review of Literature
Page 13
surgical intervention, (27) little is known about myocardial lesions after occluder
implantation in children.
Device related myocardial injury
Device-related erosion or device-related cardiac tissue injury is quite rare in the cardiac
catheterization laboratory (0.1%-0.3%). (28)
In a review of registry of complication the incidence of device erosion in the United States
was 0.1%. All erosions occurred at the dome of the atria, near the aortic root. Deficient aortic
rim, superior rim and larger device to unstretched ASD ratio were considered risk factors for
device erosion, on follow up. It was suggested not to overstretch the defect during balloon
sizing. Patients with small pericardial effusion at 24 hr required closer follow-up.(28)
Cardiac troponin I (cTnI) is a very specific and sensitive marker of myocardial
injury.(29,30)Cardiac surgery in known to cause a transient increase in cTnI serum
concentration.(6,7) However, in a study by Tarnok et al. (31) transient mild elevations of
cTnI concentration were also observed after occluder implantation. These changes lasted for
up to 1 day after the procedure and were more pronounced in children than adults. Mere
diagnostic cardiac catheterisation did not contribute to these results. They considered these
changes to be the result of transient, clinically silent myocardial damage caused by the
procedure. Similar post procedure cTnI elevation were also reported by Pees and colleagues.
(1) They regarded transient, reversible myocardial membrane instability caused by the device
as the cause. Their study focused on older patients (mean age 43.5 years) and did not examine
correlations with age or device size. The specific mechanism of myocardial injury in
interventional ASD closure in not yet fully understood.
Review of Literature
Page 14
Taggart et al. demonstrated that the sensitivity of the myocardium to surgical trauma is
inversely related to the patient’s age, with higher vulnerability among children. (3) cTnI at +1
hour, +4 hours, and +1 day, and the cTnI-AUCs after occluder implantation also correlated
negatively with the patient’s age in a study by Tarnok and company. However, the total
amount of released cTnI was not age related in this study. It is suggested that child’s
myocardium is more susceptible to trauma than adults. (3)
Few studies have also demonstrated that myocardial damage after ASD device closure
(ASDDC) depends upon the occluder size (31) and occluder size/body surface area ratio. (32)
These studies failed to show any influence of body weight and duration of the procedure on
cTnI levels.
The rim of the atrial septum is formed by various vital cardiac structure – the ascending aorta
and aortic sinuses anteriorly (towards the sternum), superior vena cava superiorly and slightly
posterior, pulmonary veins posteriorly, inferior vena cava inferiorly and atrioventricular
valves antero-inferiorly. (Figure 2)
Since the discs of the device lie on these rims, deficiency or absence of these rims effect the
safety and efficacy of the closure. Although other rims are also important the aortic rim is the
most important rim when it comes to device-related complications such as erosion. (28)If 5
mm is considered to be an adequate rim size, more than 40% of patients with ASD have an
aortic rim that is < 5 mm. However, aortic rim deficiency is not a generalised contra-
indication for device closure (table 2). (33)
Review of Literature
Page 15
The absence or deficiency of the IVC rim may cause the device edge to impinge upon the
conduction system causing arrhythmias. Risk of device embolization is also increased in
these situations. In case of deficiency of the atrioventricular valve rim the device may
impinge on mitral or tricuspid valve leaflet resulting in restriction and/or regurgitation. (34)
The atrial septum being a three-dimensional structure, a defect may result in malalignment of
the rims, especially the aortic and posterior rims. In an eccentric and leftward displaced aortic
rim the right atrial disc will be slightly tilted, not straddling the aorta evenly and its edge will
dig into the adjacent atria. Thus, increasing the chances of atrial free wall injury by the right
atrial disc. (35)
Hyperdynamic defect, where the ASD size changes by more than 50% between atrial systole
and diastole poses an increased risk of atrial wall trauma as the device is too large during
systole and appropriately sized during diastole. (35)
Figure 2: Classification of atrial
septal rims. (25)
SVC = Superior vena cava,
IVC = Inferior vena cava,
AV = Atrioventricular,
Ao = Aorta,
TV = Tricuspid valve
Review of Literature
Page 16
An eccentric ASD located high in the atrial septum will be closer to the aorta and hence,
device closure may increase the risk of tissue trauma. (35)
In a study by Amin Z, pre-procedural, intra-procedural and/or post-procedural
echocardiograms of 12 device erosions from 2005 through 2012 were reviewed. Aortic rim
absence in multiple views, poor posterior rim consistency, septal mal-alignment, and dynamic
ASD were found to increase the risk of erosion significantly. In cases of bloody pericardial
effusion with device in place, thorough assessment of the device edge by echocardiography in
short-axis view showed tenting of the atrial free was into the transverse sinus by the device.
(35)
Echocardiography being the primary modality on which the interventionists depend to
determine whether a particular defect is suitable for transcatheter closure or not, in 2011,
Bell-Cheddar and Amin (25) published criteria for effective echocardiographic evaluation of
ASD.
Although transthoracic echocardiography is a useful tool in paediatric age group, adults
generally have a poor acoustic window. In these patients, trans-esophageal echocardiography
(TEE) provides a better delineation of the anatomy of the atrial septum, its nearby structures
and pulmonary venous drainage. Intracardiac echocardiography (ICE) provides very similar
information. Apart from the logistic issues, ICE has a disadvantage of not being able to form
a four-chamber view. But, it has a greater ability to clearly delineate IVC and superior rims.
Bell-Cheddar and Amin (25) recommended that if using TEE, the defect should be evaluated
in three views: aortic short-axis view, four-chamber view, and bicaval view. The aortic short-
Review of Literature
Page 17
axis view should be further evaluated sequentially from 30º through 80º in 10º- to 15º-
increment. This evaluation is crucial as the aortic rim spans approximately 20% to 25% of the
circumference of the ASD. If using ICE, evaluation in two views (shot axis and bicaval) was
recommended. (25) Thorough evaluation should be done to ensure absence of any obstruction
to surrounding structures such as AV valves, the right upper pulmonary vein, and coronary
sinus after placement of the device.
TEE has also been used to successfully guide transcatheter closure of secundum ASD and
PFO. (25, 36) ICE is thought superior to TEE in some centers (37). However, at this time,
TEE remains the gold standard for ASD closure. (38)
Device closure being a technically simple procedure, morbidity and mortality rates associated
with the procedure should be as low as possible. The importance of detailed clinical and
echocardiographic evaluation, anticipation of hemodynamic consequences of ASD closure, a
better understanding of the structure and limitations of the available devices and expertise of
the interventionist in unquestionable. However, we lack enough data to lay down definite
criteria to determine the type of defects where surgical closure should be preferred and to rule
out the defects where closure should not be attempted.
In the absence of meaningful benchmarks, larger studies are needed to compare the outcome
of surgical versus trans-catheter approaches based on defect type and patient characteristics,
determine the high risk patients and identify the defects where closure should not be
attempted.
Material and Methods
Page 18
Material
And
methods
Material and Methods
Page 19
This study is a retrospective observational study on consecutive patients with atrial septal
defect (ASD) admitted ASDDC (ASD device closure) from May 2015 to June 2016.
Standard procedure was adopted to close the defect in the catheterization laboratory by
experienced operators under general anaesthesia and transesophageal echocardiography
guidance, assisted by fluoroscopy after informed consent.
In all patients, device was implanted under general anaesthesia. Before starting the cardiac
catheterization a detailed TEE examination was done using a multiplane probe. Standard
technique for right heart catheterization was then performed via the right femoral vein,
recording the pressures and blood samples to calculate the pulmonary to systemic blood flow
(Qp/Qs) ratio. Antibiotic prophylaxis and unfractionated heparin (100U/kg) were given
routinely. Implantation was performed under fluoroscopic and echocardiographic guidance.
Mullin’s sheath was positioned in the left atrium after which the device was connected to its
delivery system and advanced within the sheath until the left atrial disc was deployed. The
complete system was then slowly withdrawn towards the atrial septum and proper positioning
of the disc was confirmed on TEE. Then the proximal disc was deployed under TEE and
fluoroscopic control in the right atrium. Appropriate device position was confirmed before
releasing the device.
All patients were kept on dual antiplatelets for 6 months post procedure. Cardiac troponin T
(cTnT) was measured 1 day before or at the time of sheath insertion (T1) and 4-6 hrs after the
procedure (T2).Cardiac troponin T was measured using Radiometer's AQT90 FLEX bench-
top immunoassay analyser(which has a cut off value of 0.017ng/ml) in all cases. Troponin T
Material and Methods
Page 20
assay is done automatically by the machine which contains an assay solution and a cartridge
containing a cup with assay specific reagents. The blood sample is collected in an EDTA
sample bottle (minimum 2ml) and set in the introducer panel. In the assay process, the sample
and the assay solution are automatically added to the cup containing the assay-specific
reagents. During the incubation period, the tracer and capture antibodies form sandwich
complexes with the Troponin T present in the sample. After the incubation, the assay cup is
washed with the assay solution and dried. The signal from the tracer antibody is then
measured by means of time-resolved fluorometry (TRF), directly from the dry surface of the
assay cup. The concentration of the analyte in the blood is directly proportional to the
measured signal. The measured signal is converted to concentration using the calibration
curve stored in the memory of the instrument.
Case sheets of all patients who underwent ASD device closure between May 2015 and July
2016 and had negative T1 and positive T2, who did not meet the exclusion criteria were
studied using a pre-specified proforma for the study (appendix i). The data thus collected was
analysed using SPSS.
Statistical analysis
Multivariate linear regression was used to determine the significance of relationship between
the baseline parameters and Trop T elevation. In the group with Trop T > 50ng/L, linear
regression was used to determine the relationship between baseline parameters and Trop T
values. Association was considered significant if p < 0.05.
Material and Methods
Page 21
Exclusion criteria
All patients with other causes of Troponin T elevation were excluded from the study:
– Acute coronary syndrome
– Pre-procedure Renal failure (acute or chronic)
– Pericarditis/myocarditis
– Acute or chronic heart failure
– Cardiotoxic chemotherapy
– Current cardioversion defibrillation
This retrospective study on myocardial troponin elevation was approved by the ethical
committee on 27th May, 2016.
Results
Page 22
results
Results
Page 23
A total of 200 ASD device closures were done from May 2015 to June 2016 with a median
age of 12years. Females constituted 64.5% of the patients. Baseline characteristics of the
patients is mentioned in table 3.
Table 3: Baseline characteristics of the patients undergoing ASD device closure from May
2015 to June 2016 (n=200)
Mean(standard deviation)
Age 18.42+/-16.57
Male [nos. (%)] 71(35.5)
Female [nos. (%)] 129(64.5)
BSA 1.46+/-1
Height 136.1+/-24.8
Weight 35.65+/-1.99
Device size 21.31+/-7.5
ASD Size 17.51+/-17.31
Device Size/BSA 21.70+/-13.9
ASD Size/BSA 17.66+/-12.05
Complex ASD [nos.(%)] 61(30.5)
Results
Page 24
Of these patients 32 (16%) developed Trop T value ≥ 50ng/L6 hours after the procedure.
Baseline characteristics of the two groups (Trop T ≥ 50ng/L = Group 1; Trop T < 50ng/L =
Group 2) were studied (Table 4).
Table 4: Baseline characteristics patients with Trop T ≥ 50ng/L and Trop T < 50ng/L
Trop T>=50 Trop T<50 Significance
Age 17.03+/-14.1 18.68+/-16.93 0.602
≤18years 23 110 0.517
>18years 9 58
Sex- Male 13 58 0.86
Female 19 110
BSA 1.41+/-0.8 1.48+/-1.05 0.631
Height 138+/-25.179 135.68+/-24.78 0.302
Weight 34.36+/-1.56 35.90+/-2.07 0.846
Device size 23.25+/-7.83 20.94+/-7.43 0.70
ASD Size 19.66+/-8.28 17.11+/-7.06 0.089
Device Size/BSA 22.10+/-12.84 21.63+/-14.16 0.189
ASD Size/BSA 18.22+/-11.87 17.57+/-12.12 0.112
Complex ASD 17/32 44/168 0.004
After multivariate logistic regression analysis complex ASDs were found to be significantly
associated with positive Trop T values. Of the 32 patients with evidence of myocardial injury
17(53.1%) had complex ASD. Of the complex ASDs, multiple ASDs and deficient posterior
rim were significantly associated with myocardial injury (Table 5).
Results
Page 25
Table 5: Subsets of complex ASDs
Trop T>=50 Trop T<50 Total Odds ratio
Deficient rim 3 8 11 0.96
Floppy rim 3 13 16 0.51
Multiple ASD 4 1 5 13.23
Deficient Aortic
rim
2 7 9 0.70
Deficient posterior
rim
4 1 5 13.23
Malaligned ASD 1 8 9 0.28
Large ASD 0 2 2 0
IAS aneurysm 0 4 4 0
Total 17 44 61
Results
Page 26
Correlation of myocardial damage with baseline parameters was assessed by linear regression
analysis (Figures3-8)
Figure 3: Correlation of myocardial damage with ASD size
P=0.185, R2 = 0.058
Results
Page 27
Figure 4: Correlation of myocardial damage with Device size
P=0.047, R2 = 0.125
Results
Page 28
Figure 5: Correlation of myocardial damage with Device size/BSA
P=0.819, R2 = 0.002
Results
Page 29
Figure 6: Correlation of myocardial damage with ASD size/BSA
P=0.472, R2 = 0.017
Results
Page 30
Figure 7: Correlation of myocardial damage with age
P=0.394, R2 = 0.024
Results
Page 31
Figure 8: Correlation of myocardial damage with BSA
P=0.45, R2 = 0.019
Results
Page 32
The relationship between the baseline parameters and extent of myocardial damage was
analysed separately in the paediatric population as well. (Table 6)
Table 6: Correlation between extent of myocardial damage and baseline parameters in
paediatric population (≤18years) via linear regression analysis
Parameters studied R sq P value
Device size 0.018 0.04
ASD size 0.053 0.291
Device size/BSA 0.008 0.68
ASD/BSA 0.043 0.34
BSA 0.077 0.19
Age 0.044 0.337
Discussion
Page 33
discussion
Discussion
Page 34
Surgical closure of ASDs had been the traditional method of treatment till 1976 when King
et. al. first documented successful device closure of fossa ovalis ASD. (39) This technique
has gradually been widely accepted and practiced in most centres. Various complications
have been reported with the procedure, the most common being device embolization. Device
related erosion on the other hand is relatively rare and usually a late complication. (35) The
risk is less in cardiac catheterisation laboratory but tends to increase during the first 96 hours
and decreases thereafter. (35) Our centre had only one documented erosion of the mitral
valve out of 2000 device implantations for atrial septal defect over the last 15 years.
Cases of erosion started to emerge after the Amplatzer device received premarket approval.
Unfortunately, we do not have the exact data on the total number of devices placed. In the
absence of sufficient data the risk of erosion may be lower or higher than that demonstrated
by Amin et al. in their review of registry of complications (0.1%-0.3%). (28) Hung-Tao
Chung et al. in their study took cardiac troponin I (cTnI) as a marker of myocardial injury.
(32) In their study, out of the 71 successful transcatheter closures, 50 children (70.4%) had
cTnI elevation greater than the WHO criterion for myocardial cell damage (>0.4 mg/L)
within 12 hours after the procedure. (40) In our study 16% patients had evidence of
myocardial injury following device closure as demonstrated by cardiac troponin T (cTnT)
values >50ng/L. Lack of adequate data, failure of initial studies to use cardiac biomarkers to
determine myocardial injury and observation that a child’s myocardium is more susceptible
to trauma(3) explains the disparities in the results.
Various studies have attempted to identify the risk factors associated with myocardial injury
secondary to percutaneous device closure. These studies have taken cardiac troponins as
markers of myocardial injury. Chung et al. (32) in their study observed that positive cTnI
(>40ng/L) after transcatheter ASD closure depends upon device size/BSA, device size and
Discussion
Page 35
patients height. However, this study was limited to the paediatric population. We found a
positive association between complex ASDs and a positive cTnT value (>50ng/L). There was
no significant association between device size and positive troponin values in our study. The
mean device size in patients with negative troponin values in our study was 20.94mm which
was much higher than 14.24mm in Chung’s study.
Amin Z et al. studied echocardiographic parameters of 12 patients with device related erosion
and found that absence of the aortic rim in multiple views, poor posterior rim consistency,
septal malalignment, and dynamic ASDs, significantly increased the risk of erosions. (35)
However, in the absence of a control group a significant association could not be established.
We observed a significant association of multiple ASDs and deficient posteriors rims with
myocardial injury. Definite criteria to determine which ASDs should be directly taken up for
surgical closure still need to be established.
We also analysed the determinants of the extent of myocardial injury (in terms of cTnT
values) and found that larger device size was significantly associated with greater cTnT
release (p=0.048). The results were similar to those obtained by Tarnok et al. (31). Similar to
their observation we also observed that cardiac troponin release does not depend upon the
patient’s age. We did not find any correlation between cTnT release and ratio of device size
to BSA as observed by Chung et al. (32) However, in their study they used overall troponin
release rather than a single value as in our study.
Embolization or hemodynamic instability during the procedure can be another reason for
troponin release. However, none of our patients had any episode of hypotension or ST-T
changes during the procedure as an evidence for the same. Duration of anesthesia and drugs
Discussion
Page 36
used were standard in all subjects and hence we do not consider any of the factors could have
contributed to inadvertent myocardial damage and troponin release. None of the subjects had
any evidence for any adverse drug reaction and hence it is also not likely to have caused the
troponin release.
The need for thorough echocardiographic evaluation, assessment of the ASD anatomy and
anticipation of the hemodynamic changes occurring on its closure is of paramount importance
in our attempt to reduce the morbidity associated with this relatively simple procedure. Not
only will it reduce the risk associated with device closure to a minimum, but will also help in
ruling out ASDs where percutaneous closure should not be attempted.
Our retrospective study failed to capture the finer procedural details like duration of
procedure, no of attempts and whether right pulmonary vein deployment was associated with
higher troponin release. The need for more prospective studies and the importance of a good
surgical backup cannot be stressed enough.
Conclusion
Page 37
Conclusion
Conclusion
Page 38
Incidence of myocardial injury is more in patients with complex ASDs. Of the complex
ASDs, multiple ASDs and deficient posterior rim are more likely to produce myocardial
damage.
The extent of myocardial damage as reflected by larger cTnT release depends on occluder
size.
Myocardial injury following ASD device closure does not depend on patient’s age or ASD
size.
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Page 39
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Appendix i
PROFORMA
• NAME
• AGE
• SEX
• HOSP NO
• HISTORY
– SYMPTOMS
– PREMORBIDITIES
– SIGNIFICANT FAMILY HISTORY
• EXAMINATION
– PR
– BP
– RR
– CARDIOVASCULAR EXAMINATION FINDINGS
– RESPIRATORY SYSTEM FINDING (SIGNS OF CONGESTION AND
CONSOLIDATION)
– SIGNIFICANT PERABDOMEN FINDING
– FOCAL NEUROLOGICAL DEFICITS
• ASD SIZE BY TEE
Page 46
• COMPLEXITY OF ASD
• Qp/Qs
• ASD DEVICE SIZE
• DURATION OF PROCEDURE
• ADDITIONAL PROCEDURES
• BASELINE TROP T
• POST PROCEDURE TROP T
• Other Lab investigations
– Urea
– Creatinine
– Hemoglobin
– Others
• ECG
• Imaging
– CXR
– Other significant ECHO findings
– Others
• Complications