Clinical trial NCT03212326
Conditions: Ventricular Tachycardia Ischemic Cardiomyopathy
Sponsor: Weill Medical College of Cornell University
Start date: 2013-03-01; Completion date: 2018-12-01
Enrollment: 24 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
There is a high correlation between scar areas identified by contrast-enhanced ICE and scar areas identified by conventional electroanatomic mapping. Therefore, the investigators will assess the utility of contrast-enhanced ICE to identify and localize myocardial scar real-time during VT ablation procedures.

Detailed description:
Ventricular tachycardia (VT) is a life-threatening arrhythmia which occurs frequently in the setting of structural heart disease, most often as result of myocardial fibrosis or scar. Catheter ablation is often performed to treat recurrent VT, but is predicated on precise localization of myocardial scar, as scar is often the source of VT. Currently during VT ablation procedures the identification of scar is based on electroanatomic mapping where bipolar voltage criteria have been established (i.e., bipolar electrogram voltage \< 1.5 mV is considered scar). However this definition is purely based on electrical signal information and so has significant limitations: 1) there has not been definitive establishment of the sensitivity and specificity of this threshold for defining scar in comparison with tissue; 2) a detailed 3-D map created by time-consuming movement of the mapping catheter must be obtained in order to assess the existence and location of the scar; 3) only scar on the surface in contact with the mapping catheter (most often endocardial) may be definitively identified, whereas there may be intramyocardial or epicardial scar that would not be identified unless the mapping catheter makes direct contact with those areas which may involve additional risky access (epicardial) or even impossible (intramyocardial). For these reasons it would be very helpful to have another method to identify and localize myocardial scar during a VT ablation procedure. Cardiac MRI has been validated for identifying and localizing scar, but would not be recommended for many patients due to presence of ICD (implantable cardioverter-defibrillator) devices in these patients. Contrast-enhanced echocardiography has been validated to identify myocardial scar (Montant 2010), and intracardiac echocardiography (ICE) is standardly used in VT ablation procedures. Therefore, the investigators will assess the utility of contrast enhanced ICE by identifying and localizing myocardial scar real-time during VT ablation procedures.

Arms: arm 1: Perflutren echo contrast is infused to enhance intracardiac echo imaging recorded during catheter ablation of ventricular tachycardia. We will compare areas that appear to be myocardial scar on ultrasound with areas of abnormal electrical signals obtained by direct catheter mapping.
Interventions: intervention 1: Perflutren Lipid Microsphere Intravenous Suspension [DEFINITY]
Intervention descriptions: intervention 1: Perflutren 1.3mL diluted in 50 mL is infused intravenously, and intracardiac echo imaging is recorded to analyze for areas of possible myocardial scar, which is then compared with areas of abnormal electrical signal via direct catheter mapping which is performed during ablation of ventricular tachycardia.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Study Title:  
Contrast-enhanced intracardiac echocardiography for localization of myocardial scar during 
ablation of ventricular tachycardia 
NCT# 03212326 
IRB approval date: January 17, 2013 
Subsequent revised versions: none. 
 
 
 


Objective 
We sought to compare areas of scar marked on 3D-integrated ICE with abnormal electrogram 
sites in patients with cardiomyopathy (CM) and VT. 
Design 
Prospective, single-arm study enrolling 24 subjects. 
Methods 
We prospectively evaluated 24 pts (mean age 67 ± 14, 89% male) with CM (83% ischemic) 
undergoing VT ablation.  ICE contours of the left ventricle were drawn on Carto at baseline and 
again during infusion of echo contrast (perflutren).  Areas of akinesis, thinning, or abnormal 
echogenicity were labeled as scar, and compared with the voltage map (sites <1.5 mV defined 
LVR). 
INCLUSION 
Age > 18 years 
Undergoing catheter ablation of likely reentrant VT 
Planned use of intracardiac echocardiography (ICE) 
 
EXCLUSION 
Contraindication to perflutren (Definity) echo contrast: known right-to-left, bidirectional, or 
transient right-to-left cardiac shunts; known hypersensitivity to perflutren 
 
STUDY PROTOCOL 
Informed consent is to be obtained prior to procedure. 
After initial standard catheters are placed for electrophysiologic study (including ICE catheter), 
ICE imaging is optimized and echo contrast will then be infused: 
Contrast protocol (Fay Lin, M.D.) 
Echocardiographic contrast agents have demonstrated safety and efficacy for enhancement of 
chamber opacification in transthoracic echocardiography (Mulvagh 2008). Intravenous 


echocardiographic contrast has also been utilized for evaluation of left atrial appendage 
thrombus prior to electrophysiologic procedures (von der Recke G 2002, Ruiz-Arango 2008, 
Donal E 2008).  
Definity contrast (0.5 ml of Definity agitated and diluted in a 50-mL bag of normal saline) will be 
administered as a continuous intravenous infusion (12 ml/h) through a large bore peripheral 
intravenous line (20 Fr). The infusion rate will then be adjusted to obtain homogeneous LV 
cavity opacification without attenuation of distal segments. Pulse emission frequency (MHz) 
and mechanical index (MI) will be adjusted to obtain optimal endocardial and myocardial 
definition. Gain control and time-gain compensation will be adjusted at the noise floor during 
contrast imaging. 3D ICE images will be acquired after image optimization. No more than 0.5 ml 
total of Definity will be administered to any patient during one study. 
ICE imaging and localization of myocardial scar (Chris Liu, M.D.) 
With optimized contrast-enhanced ICE, myocardial scar will be localized and marked using the 
3-dimensional mapping system (CartoSound) which is used standardly during these procedures. 
Post-procedure analysis 
Scar areas identified and localized using contrast-enhanced ICD will be compared qualitatively 
(location via the 17-segment model of the left ventricle as well as categorization of endocardial, 
intramyocardial, and epicardial) and quantitatively (measured areas on the 3D maps) with the 
scar areas identified and localized using the conventional 3D electroanatomic map (obtained in 
the same patient per standard of care).  Wilcoxon test will be used to compare paired data for 
each patient. 
Hypothesis 
There is high correlation between scar areas identified by contrast-enhanced ICE and scar areas 
identified by conventional electroanatomic mapping. 
Contrast safety  
A large body of relevant published clinical data establishes the safety of approved and 
experimental ultrasound contrast agents (Herzog CA 2008). Adverse effects have been reported 
for all approved contrast agents; they are usually infrequent and mild and may include 
headache, weakness, fatigue, palpitations, nausea, dizziness, dry mouth, altered sense of smell 
or taste, dyspnea, urticaria, pruritus, back pain, chest pain, or rash, or a combination of these 
effects. However, allergic and potentially life threatening hypersensitivity reactions may occur 
rarely. Therefore, patients should be monitored for hypersensitivity reacitons under the 
direction of a physician experienced in the management of hypersensitivity reactions. 
Echocardiographic contrast consists of micronized bubbles and is unrelated to iodinated 


contrast; as such, renal insufficiency or renal failure is not a contraindication to use of 
echocardiographic contrast. 
 
In 2008, the FDA reviewed the safety of echocardiographic contrast and implemented the 
following contraindications for Definity and other contrast agents: 
 Contraindicated in right-to-left, bidirectional, or transient right-to-left cardiac shunts 
 Contraindicated in hypersensitivity to perflutren 
 Patients with pulmonary hypertension or unstable cardiopulmonary conditions must 
have additional monitoring of vital signs, electrocardiography, and cutaneous oxygen 
saturation for 30 minutes after administration. 
In this study, contrast imaging with intracardiac echocardiography will be performed prior to 
atrial septal puncture. Patients with right to left or bidirectional shunts observed on 
intracardiac echocardiography or who report hypersensitivity will not undergo contrast 
imaging. All patients will be observed for complications in the electrophysiology laboratory 
after contrast administration. 
 
Scientific BACKGROUND 
Ventricular tachycardia (VT) is a life-threatening arrhythmia which occurs frequently in the 
setting of structural heart disease, most often as result of myocardial fibrosis or scar.  Catheter 
ablation is often performed to treat recurrent VT, but is predicated on precise localization of 
myocardial scar, as scar is often the source of VT.  Currently during VT ablation procedures the 
identification of scar is based on electroanatomic mapping where bipolar voltage criteria have 
been established (i.e., bipolar electrogram voltage < 1.5 mV is considered scar).  However this 
definition is purely based on electrical signal information and so has significant limitations: 1) 
there has not been definitive establishment of the sensitivity and specificity of this threshold 
for defining scar in comparison with tissue; 2) a detailed 3-D map created by time-consuming 
movement of the mapping catheter must be obtained in order to assess the existence and 
location of the scar; 3) only scar on the surface in contact with the mapping catheter (most 
often endocardial) may be definitively identified, whereas there may be intramyocardial or 
epicardial scar that would not be identified unless the mapping catheter makes direct contact 
with those areas which may involve additional risky access (epicardial) or even impossible 
(intramyocardial).  For these reasons it would be very helpful to have another method to 
identify and localize myocardial scar during a VT ablation procedure.  Cardiac MRI has been 
validated for identifying and localizing scar, but would not be recommended for many patients 


due to presence of ICD (implantable cardioverter-defibrillator) devices in these patients.  
Contrast-enhanced echocardiography has been validated to identify myocardial scar (Montant 
2010), and intracardiac echocardiography (ICE) is standardly used in VT ablation procedures.  In 
this study, we will assess the utility of contrast-enhanced ICE to identify and localize myocardial 
scar real-time during VT ablation procedures.  The advantage of having scar areas precisely 
identified with ICE would be more expeditious localization of scar without involving the 
fluoroscopy exposure of electroanatomic mapping. 
 
 
Citations 
Ruiz-Arango A, Landolfo C. A novel approach to the diagnosis of left atrial appendage thrombus 
using contrast echocardiography and power Doppler Imaging. Eur J Echocardiogr. 2008 9:329-
33 
Donal E, Sallach JA, Murray RD, Drinko JK, Jasper JE, Thomas JD, Klein AL. Contrast-enhanced 
tissue Doppler imaging of the left atrial appendage is a quantitative measure of spontaneous 
echocardiographic contrast in atrial fibrillation. Eur J Echocardiogr. 2008 9:5-11 
Von der Recke G, Schmit H, Illien S, Luderitz B, Omran H. Use of transesophageal contrast 
echocardiography for excluding left atrial appendage thrombi in patients with atrial fibrillation 
before cardioversion. 
Herzog CA. Incidence of adverse events associated with use of perflutren contrast agents for 
echocardiography. JAMA 2008; 299:2023 
Montant P, Chenot F, Goffinet C, et al.  Detection and quantification of myocardial scars by 
contrast-enhanced 3D echocardiography.  Circ Cardiovasc Imaging. 2010;3:415-423. 
 
 
 


STATISTICAL ANALYSIS PLAN 
The scar locations suggested by ICE were compared to those obtained with traditional 
electroanatomic mapping after completion of the study by an electrophysiologist with training 
in both electrophysiology, intracardiac ultrasound imaging, and transthoracic 
echocardiography.  Scar areas identified and localized using contrast-enhanced echo will be 
compared qualitatively (location via the 17-segment model of the left ventricle as well as 
categorization of endocardial, intramyocardial, and epicardial) with the scar areas identified 
and localized using the conventional 3D electroanatomic map (obtained in the same patient per 
standard of care).   
This is a descriptive study.  We will present percent of subjects with scar as detected by 
intracardiac echo without contrast, with intracardiac echo enhanced with contrast, with voltage 
mapping, and percentage of ventricular tachycardia mapped to the scar segments on echo and 
voltage maps.  We will compare these percentages using the Kruskal-Wallis test in order to 
assess 3 groups with likely non-parametric data.  Data analysis will be performed using MedCalc 
version 13.2.