1. ATRIAL FIBROSIS IMAGING IS CHANIGNG THE WAY WE MANAGE AF
Saman Nazarian, MD, PhD
Associate Professor, CardiaC Electrophysiology
Hospital of the University of Pennsylvania

2. DISCLOSURES Scientific Advisor PI for Industry Study Research Grants
Biosense Webster, Inc
Siemens, Inc
ImriCor, Inc
CardioSolv, Inc
PI for Industry Study
St Jude Medical, Inc
Research Grants
US NIH
R01s – HL & HL142893
PCORI PaTH Network
Biosense Webster, Inc
Siemens, Inc
ImriCor, Inc
Software Support
QMass Research
ADAS, Galgo
Circle CVI

3. EVIDENCE FOR CARDIAC REMODELING WITH AF
Interstitial Fibrosis
Cardiomyocyte Diameter
Capillary Density
No AF
0-2.75% µm
#/mm2 AF % µm
#/mm2
Architectural Disarray
Interstitial Fibrosis
Diffuse fibrosis perpetuates functional reentry by reducing CV
Cohesive scar anchors and stabilizes functional reentry
Virchows Arch 2004; 445:
Hum Pathol 2005; 36:1080-9
Hum Pathol 2008; 39:
JCEP 2012; 23: 271-9
Cardiovascular Pathology. 23; 2014: 71-84

4. Spragg, Nazarian et al. Heart Rhythm. 2012 Dec;9(12):2003-9
LEFT ATRIAL LGE
Late Gadolinium
Enhancement
No LGE
LGE
Blood Pool
Intensity
Normal
Scar
10-20 minutes
Contrast
Injection
Time
Positive predictive value
0.80 (95% CI: 0.77 to 0.83)
Negative predictive value
0.73 (95% CI: 0.68 to 0.78)
Sensitivity
0.84 (95% CI: 0.80 to 0.87)
Specificity
0.68 (95% CI: to 0.73)
Spragg, Nazarian et al. Heart Rhythm Dec;9(12):2003-9

5. IMAGE INTENSITY NORMALIZATION
Image Intensity on MRI is measured in Arbitrary Units
Variable magnitude and scale across exams
IIR: A normalized measure of image intensity
The signal intensity of myocardium is divided by the mean blood pool image intensity
Khurram, Nazarian, et al. Heart Rhythm Jan;11(1):85-92

6. IMAGE INTENSITY NORMALIZATION
Khurram, Nazarian, et al. Heart Rhythm Jan;11(1):85-92

7. IMAGE INTENSITY NORMALIZATION
Threshold for <0.5 mV
Number of Subjects
IIR Threshold
Threshold for <0.1 mV
Khurram, Nazarian, et al. Heart Rhythm Jan;11(1):85-92

8. Feature Tracking MRI
Quantification of myocardial mechanics from cine MRI
Similar to speckle tracking echocardiography
Habibi, Nazarian, et al. Circ Cardiovasc Imaging Feb;8(2):e002769

9. ASSOCIATION OF LA FUNCTION WITH AF TYPE: MEDIATION BY FIBROSIS
LA Parameters (per SD change in fibrosis extent)
for Fibrosis* P
LAVImin (ml/m2)
9.0
0.013
LA Passive EF (%)
-4.1
0.032
LA Active EF (%)
-3.2
0.052
Peak Global LA Longitudinal Strain (%)
-4.9
0.002
Systolic Strain Rate (s-1)
-5.2
Early Diastolic Strain Rate (s-1)
-3.9
0.030
Late Diastolic Strain Rate (s-1)
-5.3
0.001
Volume (ml)
1.6
1.2
0.8
0.6
PGLAS (%)
Strain Rate (%/ms)
* Models adjusted for history of hypertension, CHF, LVEF, AF type, LAVImax, and LA wall thickness
* From 90 patients with paroxysmal (54) and persistent (36) AF
LA dysfunction is closely associated with increased LGE
The chronic haemodynamic burden of LA dysfunction leads to LA enlargement and further structural/electrical remodeling
Habibi, Nazarian, et al. Circ Cardiovasc Imaging Feb;8(2):e002769

10. WHY WOULD CREATION OF MORE SCAR PREVENT AF?
* Data from 20 patients with 3 month post initial PVI CMR
Ablation induced LGE exhibits higher intensity and thinner myocardium suggesting greater scar density
Reduced tissue heterogeneity reduces the likelihood for sustenance of functional reentry
Fukumato, Nazarian et al. Heart Rhythm Apr;12(4):668-72

11. Khurram, Nazarian et al. JACC Cardiovasc Imaging. 2016 Feb;9(2):142-8
ASSOCIATION OF BASELINE LGE EXTENT AND AF RECURRENCE AFTER CATHETER ABLATION
* Data from 165 patients (57% paroxysmal) undergoing a single initial PV isolation procedure
Regardless of AF persistence at baseline, participants with LGE ≤ 35% have a favorable outcome, whereas those with LGE > 35% have a higher rate of AF recurrence in the first year after ablation
Khurram, Nazarian et al. JACC Cardiovasc Imaging Feb;9(2):142-8

12. Association of LA LGE with EGM Abnormalities Beyond Voltage in AF
40 AF patients
age 63.2 ± 9.2 years
77% paroxysmal
± EGM points per pt
Lower bipolar voltage is associated with SI-Z
Only among pts with prior ablation
Coefficient=-0.049, p<0.001
Activation delay was associated with SI-Z
Only among pts with prior ablation
Coefficient=0.004, p<0.001
LA EGM fractionation was associated with SI-Z
only among ablation-naïve patients
Coefficient=0.012, p=0.03
Kuo, Nazarian, Desjardins et al. Under Preparation

13. CONDUCTION VELOCITY AND LGE
1.0
2.0
3.0
Conduction Velocity (m/s)
Paroxysmal AF
Persistent AF
IIR
Conduction Velocity (m/s)
Thickness (mm)
* Data from 22 patients with activation mapping during sinus rhythm
Increased LGE extent and intensity is associated with lower conduction velocity
Conduction velocity is lower in patients with persistent AF
Atrial scar may result in AF sustenance by promoting slow and non-uniform conduction
Fukumoto, Nazarian et al. Circ Arrhythm Electrophysiol Mar;9(3):e002897

14. SUMMARY
Image based AF substrate assessment is a promising tool for arrhythmia management in the era of “precision medicine”
Regardless of AF persistence at baseline, participants with low baseline LGE burden have a favorable outcome, whereas those with high LGE burden have a higher rate of AF recurrence in the first year after ablation
LGE corresponds to
Low voltage regions in patients with prior ablation
EGM fractionation and reduced CV in ablation naïve patients
Patients with persistent AF exhibit increased LGE compared to those with paroxysmal AF

15. ACKNOWLEDGEMENTS Penn EP / Cardiology Radiology JHU Fellows Funding
Frank Marchlinski, MD
Cory Tschabrunn, PhD
Yuchi Han, MD
Radiology
Benoit Desjardins, MD PhD
Harold Litt, MD
JHU
Hugh Calkins, MD
Henry Halperin, MD, MA
Ronald D. Berger, MD, PhD
Natalya Trayanova, PhD
Stefan Zimmerman, MD
Fellows
Shuanglun Xie, MD
Ling Kuo, MD
Jaeseok Park, MD
Tuna Ustunskaya, MD
Dragana Rujic, MD
Funding
PCORI
NIH NHLBI
R01HL & R01HL142893
Biosense Webster
Siemens
Imricor
Software Support
Qmass MR Research
Circle CVI
Galgo, Adas