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Imaging and Modeling in Atrial Fibrillation:

Rob MacLeod, University of UtahCARMA Center, SCI Institute, CVRTI

Bioengineering Department

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CARMA

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What is Atrial Fibrillation?= Afib = AF

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Normal Contraction Atrial Fibrillation

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Miyasaka et al. Circulation. 2006;114:119-125.

0

2

4

6

8

10

12

14

16

2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050

5.1

5.1 5.6

5.96.7

6.16.8

7.78.9

7.58.4

10.2

9.4

11.7

13.1

10.311.1

14.315.2

15.9

11.7 12.1

Proj

ecte

d N

umbe

r of

Per

sons

W

ith A

F (m

illio

ns)

Year

Current age-adjusted AF incidence

Increased age-adjusted AF incidence

AF Prevalence

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We All Get Older

0

3.0

6.0

9.0

12.0

<55 55-59 60-64 65-69 70-74 75-79 80-84 >85

11.110.3

7.3

5.0

3.0

1.70.9

0.2

9.1

7.2

5.0

3.4

1.71.0

0.40.1

Prev

alen

ce (%

)

Age (years)

Women (n=7,801)Men (n=10,173)

Go AS, et al. JAMA. 2001;285:2370-2375.

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So What?

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20% of Strokes

$20 billion/year

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What Causes AFib?

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Substrate

Trigger+

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Subsrate:Fibrosis

Shinagawa K, .... Nattel S. Circ. 2002: 2672-2678.Lee KW, et al. Circ. 2006: 1703-1712.

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Complex Propagation

de Groot, .... Allessie MA. Circ. 2010: 1674-1682.

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LAA

PV

PVLA

Substrate: Extension of muscle sleeves

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*

PulmonaryVeins

Left Atrium

Triggers

**

*

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Nervous System

Dewire et. al. Nat. Rev. Cardiol., 2010: 129–138.

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Clinical Result

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Clinical Result

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Treatment?

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Catheter Ablation

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Electroanatomical Mapping

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Imaging?

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MR Angiography

Pre First Pass Subtraction

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Dark Blood MRI

Ao

LA

2.5mm

RIPV

Ao

LA6.1mm

RIPV

Ao

LA2.3mm

RIPV

Pre-treatment

24 Hrs Post

3 Months Post

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Late Gadolinium Enhancement

Pre-treatment 3 month Post

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Evaluation

Patient Workflow

Treatment Followup

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Fibrosis and Outcome EvaluationPseudo-color

Normal

Low-voltageEnhanced(fibrosis?)

Pseudo-color

Normal

Low-voltageEnhanced(fibrosis?)

Electroanatomical Map

Electroanatomical Map

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Utah Scoring Scheme Evaluation

Akoum et al. J Cardiovasc Electrophysiol, 22:16-22, 2011

< 5% 5-20%

20-35% > 35%

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Fibrosis Imaging Evaluation

Pixel IntensityFr

eque

ncy

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Corview Evaluation

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Corview Evaluation

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Evaluation

Patient Workflow

Treatment Followup

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Ablation Guidance Treatment

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Real Time MRI Treatment

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Real Time MRI Treatment

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Experiments! Treatment

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Experiments!

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Real Time MRI

March, 2011

Treatment

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Evaluation

Patient Workflow

Treatment Followup

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EAM vs. MRI Followup

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Repeat AblationIncomplete Isolation

Complete Isolation

Patient 1

First PVAI - Posterior Left

Second PVAI - Posterior Left

Incomplete Isolation

Complete Isolation

Patient 2

First PVAI - Posterior Left

Second PVAI - Posterior Left

McGann et al. JACC,52(15): 1263-1272, 2008

Followup

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Predicting Success Followup

LGE (pre) T2w (<1hr) LGE (<1 hr) LGE (3 mo)

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Evaluation

Open Challenges

Treatment Followup

Image qualitySignal Acq./Proc.

LA Segmentation

Fibrosis Detection Scar DetectionLesion Imaging

Case Simulation

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Animal Models of AFib

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Utah Cooperative Arrhythmia Program

UCAP

Development of chronic AF animal model

DE-MRI of structural changes

Serum markers of

inflammation

MRI analysis and fibrosis

quantificationPathology and

histology of fibrosis

Electro-physiological

studies

UCAIR, Radiology

SCI

Clinical EP, Cardiology

Utah State University

Hematology

Pathology

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Modeling and Simulations

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18 Journal of Cardiovascular Electrophysiology Vol. 22, No. 1, January 2011

Figure 1. A series of left atrial MRI 3D reconstructions displayed in the RAO and PA projections illustrating areas of fibrosis (bright green) across the 4stages of fibrosis. Utah stage 1: <5% fibrosis, Utah stage 2: 5–20% fibrosis, Utah stage 3: 20–25% fibrosis, Utah stage 4: >35% fibrosis.

Data Analysis

Statistical analysis was performed using STATA 11 (Stata-Corp, College Station, TX, USA). Continuous variables arereported as means and standard deviations and categoricalvariables are reported as percentages of the cohort. Stu-dent’s t-test was used to compare continuous variables andChi-square test to compare proportions. A Cox proportionalhazard multivariate regression model was used to determinesignificant predictors of AF recurrence following ablation.To avoid overfitting, nonsignificant predictor variables wereremoved from the regression model in a stepwise fashion.Two-sided P-values <0.05 were considered significant.

Results

Pre-Ablation Fibrosis/Structural Remodeling BasedStaging

DE-MRI scans were of adequate quality to obtain quan-tification of pre-ablation SRM in 120 of the 144 total patient

TABLE 1Characteristics of 120 Patients with Preablation Quantification of Left Atrial Fibrosis

Utah Stage 1 Utah Stage 2 Utah Stage 3 Utah Stage 4(<5%) (5–20%) (20–35%) (>35%)

(N = 10) (N = 71) (N = 23) (N = 16) P-value

Age (years) 58 ± 14 62 ± 13 67 ± 13 68 ± 8 nsHTN (%) 50.0 53.5 56.5 43.8 nsDiabetes (%) 10 7.0 21.7 6.3 nsCoronary disease (%) 30 12.7 13.0 18.8 nsCHF (%) 10 5.6 4.3 12.5 nsLV EF (%) 57.2 ± 3.5 51.8 ± 9.5 49.7 ± 11.4 44.8 ± 13.2 nsParoxysmal/persistent AF (%) 60/40 45/55 35/65 25/75 ns

ns = nonsignificant.

cohort (85%). Motion artifact often due to AF at the time ofMRI acquisition was the main contributing factor for poorscans quality.

Of the 120 patients successfully quantified, the averagepre-ablation fibrosis was 18.06 ± 13.49% of the LA wallvolume. These patients were then divided into 4 categoriesas follows: Utah stage 1 or minimal fibrosis (at least 1 stan-dard deviation below the cohort mean, i.e., <5% enhance-ment), Utah stage 2 or mild fibrosis (5–20% enhancement),Utah stage 3 or moderate fibrosis (20–35% enhancement)and Utah stage 4 or extensive fibrosis (greater than 35% en-hancement). Figure 1 shows examples of patients in each ofthese stages. Of the patients with successful quantification,10 (7%) were in Utah stage 1, 71 (49%) in Utah stage 2, 23(16%) in Utah stage 3 and 16 (11%) in Utah stage 4. Age at thetime of initial MRI acquisition, prevalence of hypertension,coronary artery disease, congestive heart failure, diabetesand left ventricular ejection fraction were comparable acrossthe 4 groups. The patients’ characteristics are detailed inTable 1.

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Be Brave!!!

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