Clinical trial NCT01250912
Conditions: Ventricular Tachycardia Arrhythmia
Keywords: Ablation Arrythmia Imaging
Sponsor: University of Maryland, Baltimore
Start date: 2010-03-01; Completion date: 2019-07-01
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Some patients are at risk for life-threatening fast heart rates. These can frequently be treated by using a catheter inside the heart to burn away the cells that create the fast heart rates. The purpose of this study is to image the nerves inside the heart of those patients. The investigators want to find out if abnormalities in the nervous system in the heart can help the physician to find the area that needs to be burnt away.

Detailed description:
Ventricular tachycardia is the next frontier in cardiology. Patients that have scar in the heart (for example after heart attacks) are at an increased risk of developing ventricular tachycardia. In these patients ventricular tachycardia represents an electrical wave front that circulates in the heart muscle using the scar in the heart. An increasing number of patients with ventricular tachycardia require cauterization (burning away) of the tissue to treat this life-threatening condition. The goal of this cauterization or ablation is to destroy "highways of surviving tissue" inside the scar, that allow ventricular tachycardia to exist. However, this can be very lengthy procedure (\>5 hours) that has only a moderate success in the long run. Therefore, new treatment approaches are needed to make this procedure better.

The purpose of this study is to assess if radio tracers showing the nerve distribution in the heart (cardiac innervation) can be used in addition to the current technology ("voltage mapping") to identify the area that needs to be ablated (burnt away) to treat life-threatening fast heart rates (ventricular tachycardia)

Certain patterns of nerve distribution in the heart (sympathetic cardiac innervation) have been shown to predict outcome for different heart diseases, like heart transplant, coronary artery disease, heart failure, arrhythmias. One substance that allows visualization of the cardiac innervation is 123I-metaiodobenzylguanidine (123I-MIBG), which could provide additional information to understand and treat ventricular tachycardia.

Arms: arm 1: No arms, the Radio tracer will be used in all subjects imaging tests.
Interventions: intervention 1: 123I-metaiodobenzylguanidine
Intervention descriptions: intervention 1: FDA Approved for use in Cancer patients. This use is Off Label. For the imaging study, an activity of 370 MBq (10 mCi) 123I-mIBG (GE Healthcare) will be administered intravenously, and a 10-minute planar image of the anterior thorax (128\_128 matrix) will be acquired beginning 15 minutes after tracer injection.

Protocol documents:
Prot_SAP_000.pdf: 
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Three Dimensional Neuro-cardiac Imaging Using 123I-
metaiodobenzylguanidine Single Photon Emission Computed Tomography to
Guide Ventricular Tachycardia Ablations
                     Protocol                    09/16/09
Background
VT is the next frontier in electrophysiology. An increasing number of 
patients require VT ablation despite optimal medical therapy. Myocardial scars are 
present in the majority of patients with ischemic and nonischemic 
cardiomyopathy and usually act as the substrate for reentrant VT. 
According to pathological findings, rather than being homogeneous 
tissue, cardiac scars often contain many “channels” of surviving 
myocardium within the area, which enable electricity to enter, 
traverse, and exit the scar via different connections within this network
and form a “reentry loop” maintaining reentrant VT. Cauterizing the 
myocardial channels along the scar border in order to interrupt those 
loops and clinical VT, therefore, is the aim for most reentrant VT 
ablations. Because of hemodynamic intolerance as well as the pre-
existing alternative channels and exit sites, an approach targeting 
single VT channels identified by their electrical characteristics will not 
be applicable for the majority of patients. A “substrate-guided” 
ablation approach is frequently conducted to treat such arrhythmias 
and involves the placement of linear ablation lesions along the scar 


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border in order to interrupt as many channels as possible. These are 
the most commonly used and accepted treatment strategies. 
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A detailed anatomic knowledge of scar location and exact scar 
borders is necessary to accurately place curative ablation lines. 3D 
mapping systems are currently used to create a “voltage map” of the 
left ventricle (LV) to obtain such anatomic information (current “gold 
standard”). The amplitude of endocardial voltages is measured and 
recorded in real time by a roving mapping catheter moved along the 
endocardial LV surface. However, voltage mapping has several 
important limitations: First, endocardial voltage is limited in 
distinguishing between nonviable and damaged but viable 
myocardium. Second, a single endocardial voltage measurement 
cannot differentiate between endocardial and epicardial scar 
components. Third, suboptimal catheter contact can result in falsely 
low voltage measurements leading to an overestimation of ventricular 
scar and unnecessary ablation lesions. Fourth, the limited spatial 
resolution of the catheter tip and the mapping density of the voltage 
map can make the detection of isolated scar areas or small patches of 
surviving myocardium (which could represent viable VT channels) 


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difficult.12 Finally, detailed voltage mapping is quite time consuming, 
which increases procedure length and complication rates. 
Current research focuses mostly on better defining the myocardial scar with 
metabolic or anatomic imaging. However, this has multiple limitations. Magnetic 
resonance (MR) imaging has been validated to assess anatomic 
information about scar but is currently contraindicated after 
implantable cardioverter-defibrillator placement and thus unavailable 
in nearly all patients requiring VT ablations. Metabolic imaging can 
provide an alternative definition of myocardial scar to voltage 
mapping, but will still rely 
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on the same therapeutic approach of creating linear lesion along 
the scar border, which has only a limited long-term success rate of 
53%.  
Abnormal sympathetic cardiac innervation has been shown to have prognostic 
value for different heart diseases, e.g. heart transplant, coronary artery disease, heart 
failure, arrhythmias, etc. Importantly, there is a clear association with an increased 
cardiac morbidity and mortality in ischemic heart diseases. 123I-metaiodobenzylguanidine 
(123I-MIBG) allows visualization of the cardiac innervation, which could provide 
additional information to understand VT.
Therefore, the clinical need exists for a novel approach, which 
could provide new pathophysiological insights and may provide 


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innovative treatment strategies. Given a well established relationship 
between ventricular arrhythmias/sudden cardiac death and the cardiac
innervation we propose to investigate the relationship between MIBG 
innervation imaging and ventricular ablation procedures. 
Objective of the study
The purpose of this study is to assess if Single Photon Emission Computed 
Tomography (SPECT) demonstrating cardiac innervation can be integrated into current 
electrophysiology voltage mapping system and provide improved guidance for ablation 
of ventricular tachycardia. 
Benefits to the Patient
Direct benefits to the participant would be the possibility of reducing VT ablation 
procedure time.  Indirect benefits include the possibility of reducing VT ablation 
procedure time and increasing the accuracy of the ablation location with an overall 
improvement in the quality of life.
Study Population
Inclusion Criteria:
1. Patients with ventricular arrhythmias requiring VT ablation 
2. Age 18 y and above;
3. Ability to sign informed consent. 
Exclusion criteria: 
1. Younger than 18 y; 
2. Inability to sign informed consent. 
Procedures
123I-MIBG Imaging Acquisition


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All subjects will be pretreated with either perchlorate (potassium or sodium) or an 
iodine solution to block uptake of free iodine (123I) by the thyroid gland. For the imaging 
study, an activity of 370 MBq (10 mCi) 123I-mIBG (GE Healthcare) will be administered 
intravenously, and a 10-minute planar image of the anterior thorax (128_128 matrix) will 
be acquired beginning 15 minutes after tracer injection. A SPECT study will then be 
acquired using either a dual- or triple-head gamma camera (minimum 30 
projections/head, 20 to 30 seconds/ projection, 64_64 matrix). Repeat planar image and 
SPECT studies will be acquired at 4 hours after injection. All camera heads will be 
equipped with low-energy, high-resolution collimators, and all acquisitions will be 
performed with a 20% energy window centered at the 159 keV photopeak of 123I. Images 
will be reacquired 6 months after the ablation. 
123I-MIBG Imaging Reconstruction and Integration
The SPECT dataset will undergo post-procedural DICOM3 formatting analogous to 
the CT or MRI datasets using MATLAB 7.6.0 (The Mathworks Inc.). The formatted 
SPECT dataset will be transferred into the electrophysiology mapping system using the 
CartoMERGE Image Importation algorithm. 
Voltage Map Dataset
All voltage maps will be created by an electrophysiologist using a Carto 3D 
mapping system and a 3.5-mm Navistar cooled-tip catheter. Bipolar electrograms will be 
filtered at 10–30 to 400–500 Hz. Standard clinical voltage criteria will be used to define 
scar (<0.5 mV), abnormal (0.5–1.5 mV), and normal (>1.5 mV) myocardium. Each 
voltage map will be divided into 17 segments according to the AHA LV model to 
conduct visual analysis as well as quantitative analysis. 


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123I-MIBG Imaging Dataset
For the planar images a whole-heart region of interest (ROI) will be drawn manually 
to include both ventricles. A square mediastinal ROI (7x7 pixels) will be drawn in the 
upper mediastinum, using the apices of the lungs as anatomic landmarks. The H/M ratio 
will be calculated as the ratio of the counts per pixel in the two ROIs. H/M data will be 
used to calculate myocardial washout using two formulas. Uncorrected washout will be 
calculated as
H/M (early)–H/M (late)/H/M (early). 
Background corrected washout will be calculated as
H (early)–M (early)–H (late)–M (late)/H (early)–M (early)
Single aggregate values for each washout parameter will be determined as described 
above.
For the SPECT image sets, segmental myocardial activity will be scored using a 17–
segment model. Each segment will be scored using the following scale: 0 normal tracer
uptake, 1 mildly reduced uptake, 2 moderately reduced uptake, 3 severely reduced
uptake, 4 absent tracer uptake, NA not assessable. Accordingly, the summed score (SS)
for each study could range from 0 to 68 (17x4). 
Heart Rate Variability
All the patients will undergo 24-hour ambulatory electrocardiographic monitoring on
entrance into the study in order to investigate the prognostic value of heart rate variability
(HRV). Time and frequency domain HRV parameters will be calculated from those 
recordings. Traditional measurements of HRV will be analyzed according to the Task 
Force of the European Society of Cardiology and the North American society of Pacing 
and Electrophysiology   Time domain analysis of HRV will include the mean duration of 


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all normal-to-normal (NN) intervals (mean RR), standard deviation of all normal-to-
normal intervals (SDNN), standard deviation of the averages of NN intervals in all 5-min 
segments, mean of SDNN in all 5-min segments (SDNN index), square root of the mean 
of the sum of the squares of differences between adjacent NN intervals, number of NN 
intervals differing by more than 50 ms from the adjacent interval divided by the total 
number of NN intervals, and HRV triangular index. HRV parameters will be reacquired 6
months after the ablation. 
Patient Characteristics 
Patient clinical characteristics (gender, age, ejection fraction, comorbidities, anti-
arrhythmia medications) and their clinical VT characteristics (morphology, frequency, 
duration, cycle length, termination strategy, previous ICD shocks) will be collected.
Research Part of the Protocol
Four specific aims were plan to achieved for this research. Specific Aim 1: 
Evaluate if areas of left ventricular (LV) denervation measured by cardiac 123I-
metaiodobenzylguanidine (MIBG) SPECT imaging (innervation map) can be integrated 
into the CartoXP electrophysiology mapping system. Specific Aim 2: Evaluate, in a 
group of 20 patients, if areas of denervation in the 3D maps reconstructed from MIBG 
SPECT imaging correlate with the voltage-map defined scar targeted during VT ablations
Specific Aim 3: Determine the changes of cardiac innervation before and 6 months after 
the VT ablation in 20 patients. Specific Aim 4: Investigate the possible predicting factors 
for VT reoccurrence within six month after the ablation. 
Risks


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Ventricular tachycardia ablation procedures have a definite morbidity and mortality, with 
a major complication rate of endocardial procedures ranging from 2.5 to 6 %. This is to 
due to both patient-related and procedure-related factors. Patients typically suffer from 
congestive heart failure and other comorbidities and the procedures are long, requiring 
the patient to lie flat for up to eight hours at times. It must be emphasized that both 
procedures are currently performed on patients as indicated. 
In addition to the risks of sedation, standard risks of an endocardial procedure include 
bleeding and other vascular access complications, stroke, myocardial infarction and 
rarely myocardial rupture and pericardial tamponade, aortic valve avulsion, and 
entanglement of the catheter in the mitral valve apparatus requiring surgical intervention, 
and death. Attempts to ablate VT using an endocardial-only approach in patients with a 
high likelihood of having an epicardial origin would lead to unnecessarily prolonged 
endocardial procedures and failed ablation. This would lead to a second, epicardial, 
procedure. 
Measures to Reduce Risks
Our approach will be to conduct the cardiac imaging scan and reconstruction for the 
patients first. This will be followed by endocardial mapping. The imaging information 
known before the endocardial procedure will help reduce the mapping time, improve the 
mapping/ablation accuracy and reduce the risk due to the long procedure time. It is our 
belief that, with this imaging guidance approach, we can improve the success rate of VT 
ablation in VT patients. 
Data Analysis
Means and standard deviations will be calculated for each of the four registration 
strategies, i.e. LM, LM and SF, VA, VA and SF, in order to identify the best registration 
method.  


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Differences in scar size, morphology and severity between 3D MIBG innervation 
maps and EP voltage maps will be analyzed using Student T-test. Segments where 
diastolic potentials, fractionated potentials and successful ablation sites are located will 
be investigate in order to indentify the characteristics of the MBIG imaging in those 
segment, e.g heterogeneity, etc. Segmental/regional washout rate, normalized MIBG 
activities as well as SS scores will be compared with segmental/regional voltage values in
order to indentify the relationship between cardiac denervation areas and abnormal 
endocardial voltage areas. 
Differences in size, morphology and severity, regional/global washout from planer 
images, normalized regional intensities, regional activity summed scores between pre and
post ablation 3D MIBG innervation maps will be analyzed using Paired T-test. Global 
wash out rate will be correlated with HRV indexes before and after the ablation to 
investigate the relationship between them. Normalized regional MIGB intensities, 
regional wash out rate and regional SS score both before and after ablations will be 
compared between VT exit sites segments and other segments with independent sample 
T-test in order to identify the innervation characteristics of the exit site segments.
Measurements and results will be reported as mean ± standard deviation if a normal 
distribution can be assumed. P values at a level of <0.05 will be considered as statistically
significant. Pearson correlation will be conducted to investigate the relationship between 
two sets of images. The logistic regression will be conducted to investigate the 
relationship between 3D innervation morphologies, HRV parameters, patient 
characteristics, clinical VT characteristics and the VT recurrence within the six month 


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follow-up period. Receiver operating characteristics (ROC) curves will be used to assess 
best correlation performed with innervation and voltage map. 
C.6.1. Publications
1. Dickfeld T, Lei P, Dilsizian V, et al. Integration of Three-Dimensional Scar Maps
For  Ventricular  Tachycardia  Ablation  Using  Positron  Emission
Tomography/Computed Tomography (PET/CT). JACC Imaging 2008; 1:73-82
2. Tian J, Smith MF, Chinnadurai P et al. Clinical application of PET/CT fusion
imaging  for  three-dimensional  myocardial  scar  and  left  ventricular  anatomy
during ventricular tachycardia ablation. J Cardiovasc Electrophysiol. Published
January 13, 2009; DOI: 10.1111/j.1540-8167.2008.01377.x
3. Tian J, Smith MF, Jeudy J, Dickfeld T. Multi-Modality Fusion Imaging Using
Delayed-Enhanced  Cardiac  Magnetic  Resonance  Imaging,  Computed
Tomography,  Positron  Emission  Tomography  and  Real-Time  Intracardiac
Echocardiography  to  Guide  Ventricular  Tachycardia  Ablation  in Implantable
Cardioverter-Defibrillator Patients. Heart Rhythm 2009; In Press
C.6.2. Published Research Abstracts
1. Tian J, Smith MF, Turgeman A, Dilsizian V, Abbo A, Peters R, Saba M, 
Shorofsky S, Dickfeld T. (2009) Comparison of PET Metabolic Activities among 
Scar, Border Zone and Healthy Myocardium in Patients Undergoing Ischemic VT
Ablation. Heart Rhythm, In press
2. Tian J, Smith MF, Dilsizian V, Abbo A, Peters R, Saba M, Shorofsky S, Dickfeld 
T. (2009) Integration of 3D Scar Maps using SPECT to Guide Ventricular 
Tachycardia Ablation. Heart Rhythm, In press 
3. Dickfeld T, Tian J, O'Donnell T, Anand A, Hussein A, Peters R, Saba M, 
Shorofsky S, Jeudy J. (2009) Integration of Three-dimensional, Delayed 
Enhancement MRI Scar in Patients with ICD for Guidance of Ventricular 
Tachycardia Ablation. Heart Rhythm, In press
4. Tian J, Smith MF, Chinnadurai P, Dilsizian V, Turgeman A, Abbo A, Plotnick 
D, Hood R, Peters R, Saba M, Shorofsky S, Dickfeld T. (2008) First Clinical 
Experience Using PET/CT Fusion Imaging of Three-Dimensional Myocardial 
Scar and Left Ventricular Anatomy for Ventricular Tachycardia Ablation. 
Circulation, 118, 18, (S2) S690
5. Tian J, Smith MF, Turgeman A, Abbo A, Bruce P, Hood R, Peters R, Saba M, 
Shorofsky S, Dickfeld T. (2008) Comparison of Anatomical and Dynamic CT-


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derived Parameters between Scar, Border zone and Healthy Myocardium in 
Patients Undergoing Ischemic VT Ablation. Circulation, 118, 18, (S2) S937
6. Dickfeld TM, Read K, Gotman S, Tian J, Peters R, Hood R, Saba M, Shorofsky 
S, Fleiter T. (2008) Catheter Navigation, Ablation and Lesion Visualization Using
Real-Time Computer Tomography Guidance. Circulation, 118, 18, (S2) S831
7. Dickfeld, TM, Hodefi D, Read K, Plotnick D, Tian J, Akella J, Nillas M, Johnson 
A, Saba M, Shorofsky S and Fleiter T. (2008) Real-Time CT Guided Ablation 
Procedures: Radiation Exposure, Safety and Feasibility. Heart Rhythm 5, (5S), 
S272