Online Appendix
TABLE OF CONTENTS
1.
WEIGHT MANAGEMENT:
3
2.
OTHER RISK FACTOR MANAGEMENT STRATEGIES
3
2.1.
2.2.
2.3.
2.4.
2.5.
2.6.
2.7.
BLOOD PRESSURE CONTROL:
LIPID MANAGEMENT:
GLYCEMIC CONTROL:
SLEEP DISORDERED BREATHING MANAGEMENT:
SMOKING:
ALCOHOL:
INFLAMMATION:
4
4
4
5
5
5
5
3.
7 DAYS HOLTER
5
4.
ECHOCARDIOGRAPHY
6
4.1. LA VOLUME
4.2. LEFT VENTRICULAR END-DIASTOLIC DIAMETER AND VOLUME
4.3. LEFT VENTRICULAR DIASTOLIC FUNCTION
6
6
6
5.
7
ABLATION STRATEGIES
5.1. REDO ABLATION
5.2. ANTICOAGULATION MANAGEMENT
7
7
6.
8
6.1.
6.2.
6.3.
6.4.
7.
7.1.
7.2.
7.3.
7.4.
8.
OUTCOMES FOR COST-EFFECTIVENESS
QUALITY-ADJUSTED LIFE YEARS
COMPARISON WITH OTHER STUDIES
DISCOUNT RATE
MODEL STRUCTURE AND MODELING FRAMEWORK
COSTS:
SHORT TERM COST CALCULATION
LONG TERM COST MODELLING
ASSUMPTIONS
COST CALCULATION
REFERENCES
8
9
10
11
12
12
12
13
13
23
1
List of Tables
Table 1: Total Costs by Individual Element ................................................................ 15
Table 2: Cost of Medications ......................................................................................16
Table 3: Utility and Cost Calculations from Decision Tree.........................................17
Table 4: ICER Calculations – Short Term Decision Tree .............................................18
Table 5: ICER Calculations - Markov Model ............................................................... 18
Table 6: Markov Model Annual Costs ........................................................................19
Table 7: Markov Modelling .........................................................................................20
List of Figures
Figure 1:Complete Decision Tree ................................................................................21
Figure 2: Annual Transition Probabilities – Markov Model.......................................22
Investigators
Rajeev K. Pathak, MBBS; Michelle L. Evans; Melissa E. Middeldorp; Megan
Meredith; Abhinav B. Mehta, M Act St; Rajiv Mahajan, MD, PhD; Christopher X.
Wong MBBS; Darragh Twomey, MBBS; Adrian D. Elliott, PhD; Jonathan M. Kalman,
MBBS, PhD; Walter P. Abhayaratna, MBBS, PhD; Dennis H. Lau, MBBS, PhD;
Prashanthan Sanders, MBBS, PhD.
2
1. Weight Management:
A structured motivational and goal-directed program using face-to-face counseling was used
for weight reduction. Our weight loss clinic is run by a dedicated Physician responsible for
delivering risk factor management to the patient with the help of a research assistant.
Patients were encouraged to utilize support counselling and schedule more frequent reviews
as required. Initial weight reduction was attempted by a meal plan and behavior modification.
Meals consisted of high protein and low glycemic index, calorie controlled foods. If patients
lost <3% of weight after 3-months they were then prescribed very-low-calorie meal
replacement sachets (Nestle Health Science) for 1-2 meals/day. The initial goal was to reduce
body weight by 10%. After patients achieved the initial goal, meal replacement was
substituted to high protein and low glycemic index, calorie-controlled foods to achieve a
target BMI of ≤25kg/m2. Low intensity exercise was prescribed initially for 20-minutes thriceweekly increasing to at least 200-minutes of moderate-intensity activity/week. The patients
are advised to maintain a lifestyle journal in which patients log the daily food intake, weight,
blood pressure and exercise duration. This journal is utilized for giving necessary dietary
advice and it works as an effective behavioral tool for the patients to self-reflect and monitor
the eating habits. This technique has been utilized successfully in past.(1)
2. Other risk Factor Management Strategies
Patients participating in RFM attended a physician-directed RFM clinic (in addition to their
arrhythmia follow up) every 3-months and were managed according to ACC/AHA
guidelines.(2-4)
3
2.1. Blood Pressure Control:
Blood pressure (BP) was measured thrice-daily using home-based automated monitor and an
appropriate-sized cuff. In addition, exercise stress testing was performed to determine the
presence of exercise-induced hypertension with BP>200/100 mmHg considered as evidence
to optimize therapy. Lifestyle advice constituted dietary salt restriction. Pharmacotherapy
was initiated using renin-angiotensin-aldosterone system antagonists with other agents used
where necessary to achieve a target BP of <130/80 mmHg at least 80% of the time. These
were corroborated by in-office and 24-hour ambulatory BP measurements, as required.
Echocardiography was monitored to ensure resolution of left ventricular hypertrophy.
2.2. Lipid Management:
Initially managed with lifestyle measures. If patients were unable to achieve LDL-Cholesterol
<100 mg/dL after 3-months then a HMG-CoA reductase inhibitor was initiated. Fibrates were
used for isolated hypertriglyceridemia (TG>500 mg/dL) or added to statin therapy if TG>200
mg/dL and non-HDL cholesterol was >130 mg/dL.
2.3. Glycemic Control:
If fasting glucose was 100-125 mg/dL, a glucose tolerance test was performed. Impaired
glucose tolerance (IGT) or DM was initially managed with lifestyle measures. If patients were
unable to maintain glycosylated hemoglobin ≤6.5% after 3-months, metformin was started.
Patients in both groups with suboptimal glycemic control (HbA1c>7%) were referred to a
specialized diabetes clinic. Fasting Insulin levels are checked at baseline and at follow up.
4
2.4. Sleep Disordered Breathing Management:
In-laboratory overnight polysommnography (PSG) was scored by qualified sleep technicians
and reviewed with follow-up by a sleep physician. PSG scoring was according to the AASM
alternate PSG scoring criteria. Patients were offered therapy if the Apnea-Hypopnea Index
(AHI) was ≥30/hour or if it was >20/hour with resistant hypertension or problematic daytime
sleepiness. Treatment included positional therapy and continuous positive airway pressure
(CPAP).
2.5. Smoking:
The “5A” (Ask, Advice, Assess, Assist and Arrange follow-up) structured smoking cessation
framework was adopted.(5) Smokers were offered behavioral support through a
multidisciplinary clinic with the aim of cessation.
2.6. Alcohol:
Written and verbal counseling was provided with regular supportive follow-up for alcohol
reduction to ≤30 gm/week.
2.7. Inflammation:
To assess the inflammatory status, hsCRP levels are tested at baseline and each follow-up.
3. 7 days Holter
Multi-channel 7 day Holter (ambulatory) ECG data from each patient were acquired digitally
and transferred for computerized analysis. The individual event traces and digital analysis
were analyzed by cardiac technician and reported by an electrophysiologist blinded to the
5
clinical outcome. In accordance with the Heart Rhythm Society consensus statement, any
atrial arrhythmia ≥30 seconds was considered AF and contributed to the determination of AF
burden.(6)
4. Echocardiography
All patients underwent transthoracic echocardiography (Vivid 7, GE Healthcare, Horten,
Norway) at baseline and follow up. All echocardiographic assessments were performed by
experienced cardiac sonographers and reported by investigator blinded to the patient’s
details.
4.1. LA volume
Left atrial (LA) volume was measured using standard apical two- and four-chamber views on
the frame just prior to mitral valve opening and as specified by current American Society of
Echocardiography guidelines.(7) LA volume was indexed to body surface area.
4.2. Left Ventricular end-diastolic diameter and volume
LV end diastolic diameter was measured at the level of the LV minor axis approximately at the
mitral valve leaflet tips. The measurements were made directly from the 2D image. LV enddiastolic volume was measured at the start of the QRS complex using the modified biplane
Simpson method (method of disks) using the apical four-chamber and two-chamber views.(8)
4.3. Left Ventricular Diastolic Function
Mitral inflow velocity was obtained in the apical four-chamber view by placing a pulsedDoppler sample volume between the tips of the mitral leaflets. Mitral annular velocity was
6
assessed during the early phase of diastole (e’) using pulsed-wave Doppler sampling of lateral
mitral annular motion from the four-chamber view. LV diastolic filling pressure was estimated
by the ratio of mitral inflow peak E velocity to e’.(9)
5. Ablation Strategies
The ablation procedure was performed with the operator blinded to the patient’s study
group. The ablation technique utilized at our institution has been previously described.(10)
The ablation strategy included wide-encircling pulmonary vein ablation with an endpoint of
electrical isolation (PVI) in all patients. Further substrate modification was performed for
patients with AF episodes ≥48-hours or if the largest left atrial dimension exceeded 57mm.
This included linear ablation (roofline and/or mitral isthmus) with an endpoint of bidirectional
block and/or electrogram-guided ablation of fractionated sites.
5.1. Redo Ablation
If patients developed recurrent arrhythmia after the blanking period (3-months), repeat
ablation was offered. Individual operators decided on the extent of additional ablation
undertaken beyond re-isolation of the pulmonary veins. In patients undergoing AF ablation,
in the absence of any arrhythmia, antiarrhythmic drugs were stopped at 3 months.
5.2. Anticoagulation management
All patients were anticoagulated on the basis of current guidelines using the CHADS 2 score.
All patients undergoing ablation were anticoagulated using warfarin for 3-months following
ablation. After 3 months, patients were advised to continue anticoagulation only if their
CHADS2 score was ≥1.
7
6. Outcomes for Cost-Effectiveness
6.1. Quality-Adjusted Life Years
At each annual follow up, freedom from AF was recorded and converted into a utility value in
accordance with previously validated and published data. Reynolds et.al estimated utilities
using raw item responses to the SF-36 and SF-12 general health surveys from three
populations of AF patients – one treated almost exclusively with drug therapy, and two
involving AF ablation. Results of these analyses were plotted. They then transformed Quality
of Life questionnaire data to utilities for patients enrolled in the A4 study, a randomized trial
comparing antiarrhythmic drugs with catheter ablation for patients with paroxysmal AF
despite ≥ 2 attempts at drug therapy. Baseline mean utility scores were 0.725 in the ablation
group and 0.71 in the AAD group. At 6 and 12 months, mean utility scores in the ablation
group had increased significantly, by 0.053 and 0.064 respectively, in paired comparisons
(p<0.001 by signed rank test). Based on the above data, we used a baseline utility value 0.725
for ‘Not AF Free’ in our model. We set the increase in utility with successful AF treatment at
0.065, which was approximately equal to the 12-month change in the A4 study population.
(11-13) With the utility value for ‘Not AF Free’ set at 0.725 and an increase in utility value of
0.065 for the successful treatment for AF, we generated a utility value of 0.79 for the health
state ‘AF Free’. We acknowledge that the studies utilized for utility value calculation are not
a complete match for our study cohort and intervention. However, we think utility values for
the health states ‘Not AF Free’ and ‘AF Free’ can still be utilized, as they remain relevant
irrespective of the type of intervention utilized to achieve them. Moreover, with the type of
intervention (RFM) leading to AF free state in this study, the gain in utility value may even be
a conservative estimate when compared to AF free state achieved with drug therapy or
ablation.
8
6.2. Comparison with Other Studies
There is paucity of data regarding utility values for AF and AF Free health states. Various
different quality of life questionnaires have been utilized for different cohorts and for
different innovations.
1: Reynolds et.al transformed SF-12 (Quality of Life questionnaire) responses to utilities for
patients enrolled in the FRACTAL registry, a population of 1,000 subjects enrolled at the time
for first AF diagnosis. In order to estimate the change in utility achieved with successful
pharmacologic rhythm control of AF, they compared baseline utilities with follow-up values
from 3, 6, and 12 months in patients with no documented recurrences of AF during the first
year of registry follow-up (N=507, see Figure 1). Baseline mean utility was 0.76 ± 0.13. In
paired comparisons at 6 and 12 months, the mean increase in utilities in this group were 0.042
and 0.046, respectively (p<.0001 ).(12,13)
2: Reynolds et.al also performed a similar transformation of SF-36 (Quality of Life
questionnaire) data to utilities for patients enrolled in the A4 study, a randomized trial
comparing antiarrhythmic drugs with catheter ablation for patients with paroxysmal AF
despite ≥ 2 attempts at drug therapy (N=112). Baseline mean utility scores were 0.72 in the
ablation group and 0.71 the Anti-Arrhythmic drug (AAD) group. In a paired comparison, they
found, at 6 and 12 months, mean utility scores in the ablation group increased by 0.053 and
0.064, respectively (p<0.001).(11)
3: In a different cohort, Reynolds et.al transformed SF-36 data on 78 consecutive patients
undergoing catheter ablation for paroxysmal or persistent AF to utilities. Mean baseline
utilities in this population were 0.74 ± 0.13. Utility scores significantly increased in this
population after ablation. The interim analysis showed that the mean change of from “Not
9
AF free” to “AF Free” state was 0.064 and 0.059 in paired comparisons at 6 and 12 months,
respectively (p<0.01).(12,13)
4: Hendriks et.al did a cost effectiveness analysis of the nurse-led integrated chronic care
approach vs. usual care in patients with AF. In this study, health status was assessed with the
Short Form 36 questionnaire (SF-36), which was administered at baseline and at 1-year
follow-up converted to a single utility score by means of the Short Form 6D (SF-6D). Although
the study population and the interventions applied were different but they found the mean
Utility for patients with “Not AF Free’ state, based on SF-6D was 0.627. (14)
5: Blackhouse et.al evaluated the cost-effectiveness of catheter ablation for rhythm control
compared to AAD therapy in patients with AF who have previously failed on an AAD. In this
study they utilized same utility value derived from Reynolds et.al for “Not AF Free State” as
utilized in our study for cost effective analysis. (12,13,15)
6.3. Discount Rate
The Discount Rate for Australia for April 2013 of 3%, published by the FRED Economic Data,
was applied to all Costs.(16) The International Monetary Fund (IMF) rate, published a discount
rate effective in the US as of September 2012 of 3%.(17) The same 3% was used to discount
Benefits, to recognize that the health benefits gained in the future may not have the same
value to society as those gained today. It is generally acknowledged that the same rate should
be used for both benefits and costs.(18) The University of York’s Technical Series paper
“Discounting for Health Effects in Cost Benefit and Cost Effectiveness Analysis” discusses using
the reasons for using the same and different discount rates between costs and benefits.(19)
Based on this, we utilized the same discount rate for both costs and benefits.
10
6.4. Model structure and modeling framework
Short-term analysis was undertaken using a decision tree (Manuscript: Figure-2: RFM Group
& Supplement: Figure-1: for both groups). Study data provided the probabilities of patients
undergoing ablation procedures and the likelihood that, for each pathway, the patient would
achieve “AF Freedom” at Year 4. Incremental cost-effectiveness ratios (ICER) were calculated
for ‘Cost per QALY gained’ (Manuscript: Figure-3), however as RFM provided a saving per
QALY gained, it is not appropriate to quote an ICER figure. Sensitivity analyses were
performed and plotted in a “tornado” diagram (Manuscript: Figure-4). Bootstrapping of 1,000
pair-wise comparisons improved estimates of the sampling distribution and provided data for
the cost-effectiveness utility plane.
A Markov model estimated the long-term cost-effectiveness of RFM over 10 years,
corresponding to the longest follow-up of ablation outcomes available.(19) The health states
used were ‘AF Free’ and ‘Not AF Free’. There were no deaths or strokes in patients, and the
health state ‘Dead’ was not included. All patients entered the Markov model in the health
state ‘Not AF Free’. Using the Markovian assumption, annual transition probabilities were
calculated using an average of recorded results in the study for each cohort. In each annual
cycle, patients could remain ‘Not AF Free’ (with transition probabilities of RFM 48%, Control
72%), or transition to ‘AF Free’ (RFM 52%, Control 28%). Once ‘AF Free’ patients could remain
in this state (RFM 75%, Control 34%) or transition back to ‘Not AF Free’ (RFM 25%, Control
66%).
11
7. Costs:
7.1. Short-Term Cost Calculation
Using a bottom-up costing method, all costs were calculated in year 2010 Australian dollars.
Costs were classified into five categories: interventional procedures, diagnostic procedures,
inpatient care, outpatient visits and medication (Supplementary Table 1). Hospitalization
costs were calculated using ‘Average Length of Stay’ for AF with the standard price per
Occupied Bed Day, provided by the South Australian Department of Health and Ageing. For
each patient, the total number of drugs prescribed for arrhythmia, hypertension and lipid
disorder was recorded at baseline and at follow up. The price of specific brands of
medications, at standard dosages, was averaged to provide an average annual cost for each
drug (Supplementary Table 2). These costs were input into the short-term decision tree
(Supplementary Figure 1) with the probabilities of each chance node, to create the average
total cost and average total utility for each arm of the study. (Supplementary Table 3). The
short-term ICER was derived from the Marginal Utility and Marginal Cost created by the
outcomes of the decision tree (Supplementary Table 4).
7.2. Long-Term Cost modelling
The Markov model looked at the projected costs of the two health states that patients could
be expected to be in at the end of the study – ‘AF Free’ (232 patients) and ‘Not AF Free’ (123
patients). These costs were then modelled over a 10-year period. To create an annual cost for
a health state, a list was compiled of all cost-inducing episodes in the study. Filtered by the
patient’s health state at the end of study, the total number of actual occasions for individuals
in each cohort was summed, then divided over four years, to create an average number of
12
episodes per year for that Health state. This annual figure was then multiplied by the cost of
that episode to provide an ‘annual average cost’ (Supplementary Table 5).
7.3. Assumptions

Patients who were ‘AF Free’ would not require cardioversion, unplanned hospital and
specialist visits, or ablation procedures. The annual costs for these episodes were set to
$0 in the Markov Model.

Patients who were ‘AF Free’ would still attend two planned specialist visits per year.

All patients would remain on their medications.

Patient who were ‘Not AF Free’ were expected to undergo an AF Ablation at a 20% annual
rate (one per five years) and had a 40% chance of undergoing a Cardioversion annually.
7.4. Cost Calculation
The expected costs were then summed to create an Average Annual Cost of $5,209 for being
‘Not AF Free’ and $1,137 for being ‘AF Free’ (Supplementary Table 6). Starting with all patients
being in the health state ‘Not AF Free’ the 10-year cycle for both Control and RFM was
modelled, with patients remaining in, or moving in and out of, the two health states as per
the transition probabilities previously documented (Supplementary Figure 2). A half-cycle
correction was included to adjust for the uncertainty of the transition point between the
consecutive follow ups. The annual costs of each health states were applied to the percentage
population in each health state in that year, and discounted at a 3% annual rate. This
projected a total cost and total utility for both RFM and Control over 10 years (Supplementary
Table 7), allowing marginal Utility and marginal Cost to be calculated. The long-term ICER
13
figure was derived from the marginal Utility and marginal Cost from the Markov Model
(Supplementary Table 5).
14
Online Table 1: Total Costs by Individual Element
Unit
Price
Interventional Procedures
Ablation
ATachy Ablation
Cardioversion
Sub-Total
Diagnostic Procedures
Exercise Stress Test
Glucose Tolerance Test
Holter Monitor
TransThoracic Echo
Blood Pressure Machine
Polysomnography
CPAP Machine
Sub-Total
Inpatient Care
ED Presentation
Hospital Admission for
AF
Sub-Total
Outpatient Visits
Specialist Visit - Initial
Specialist Visit - Planned
Specialist Visit - RFM
Clinic
Specialist Visit Unplanned
Sub-Total
Medications (Change in)
Anti-Arrhythmic
Hypertensive
Statin
Sub-Total
Control
Volume
Cost
RFM
Volume Cost
Total
Variance
$13,847
$2,891
$1,075
0.72
0
1.51
$9,985
$0
$1,624
$11,609
0.46
0.14
0.89
$6,325
$417
$957
$7,698
$3,660
-$417
$667
$3,911
$152
$19
$164
$231
$125
$588
$1,100
4
1
12
5
0
0
0.48
$609
$19
$1,972
$1,153
$0
$0
$531
$4,284
4
1
12
5
1
0.53
0.53
$609
$19
$1,972
$1,153
$125
$314
$587
$4,779
$0
$0
$0
$0
-$125
-$314
-$56
-$495
$545
0.76
$415
0.18
$100
$316
$1,910
1.05
$2,014
0.74
$1,405
$609
$1,505
$924
$2,429
$151
$76
1
16
$151
$1,216
1
16
$151
$1,216
$0
$0
$76
0
$0
16
$1,216
-$1,216
$76
1.94
$14
$133
$1,514
$2,597
-$1,083
-$281
-$10
$94
-$197
-$448
-$106
$4
-$549
$167
$96
$90
$352
$308
$245
$432
$147
0.19
15
Online Table 2: Cost of Medications
Medication Costs
Anti-Arrhythmic
Amiodarone
Sotalol
Flecainide
Anti-Hypertensive
Perindopril
Olmetec
Metoprolol (Tartrate)
Diltiazem
Anti-Glycemic
Metformin
Statin
Atorvastatin
Dose
Pack
Dose
Pack Qty
Max Price
per Pack
Packs
per
Month
Total Cost per
Year
Avg Cost
per Year
200mg /day
80mg twice/day
100mg twice/day
200mg
80mg
100mg
30
60
60
$23.67
$17.29
$36.10
1
1
1
$284.04
$207.48
$433.20
5mg
40mg
50mg
240mg
5mg
40mg
50mg
240mg
30
30
100
30
$19.69
$33.87
$14.89
$23.55
1
1
0.3
1
$236.28
$406.44
$53.60
$282.60
500mg twice/day
500mg
100
$16.01
0.6
$115.27
$115.27
40mg
40mg
30
$35.99
1
$431.88
$431.88
$308.24
$244.73
16
Online Table 3: Utility and Cost Calculations from Decision Tree
Arm
Path
Control Three Ablations
Three Ablations
Two Ablations
Two Ablations
Single Ablation
Single Ablation
No Ablation
No Ablation
End State
AF Free
Not AF Free
AF Free
Not AF Free
AF Free
Not AF Free
AF Free
Not AF Free
TOTAL
Number
of
Pr (%) Patients Avg Utility
0.01
0.03
0.04
0.12
0.18
0.12
0.22
0.29
1.00
1
4
6
18
26
17
32
43
147
2.6929
2.6505
2.7626
2.6487
2.7388
2.6460
2.7098
2.6494
Avg Utility
RFM
Three Ablations
Three Ablations
Two Ablations
Two Ablations
Single Ablation
Single Ablation
No Ablation
No Ablation
AF Free
Not AF Free
AF Free
Not AF Free
AF Free
Not AF Free
AF Free
Not AF Free
TOTAL
0.01
0.00
0.04
0.03
0.30
0.11
0.45
0.05
1.00
2
1
9
6
63
23
93
11
208
2.7533
2.6352
2.7592
2.6655
2.7562
2.6482
2.7650
2.6516
Avg Utility
Total
Utility
Expected
cost per
px
2.6929
10.6020
16.5756
47.6766
71.2088
44.9820
86.7136
113.9242
394.3757
2.6828
$55,185
$55,185
$39,544
$39,544
$24,372
$24,372
$9,655
$9,655
Total Cost
Avg Cost
$55,185
$220,741
$237,264
$711,793
$633,671
$414,324
$308,962
$415,168
$2,997,109
$20,388
5.5066
2.6352
24.8328
15.9930
173.6406
60.9086
257.1450
29.1676
569.8294
2.74
$47,349
$47,349
$35,058
$35,058
$23,135
$23,135
$9,288
$9,288
Total Cost
Avg Cost
$94,697
$47,349
$315,519
$210,346
$1,457,534
$532,116
$863,815
$102,172
$3,623,547
$17,421
Total Cost (all
px)
17
Online Table 4: ICER Calculations – Short Term Decision Tree
Cost
Control Group
Risk Managed
Utility
Control Group
Risk Managed
Avg Cost
$20,388.49
$17,420.90
Avg QALY
2.6828
2.7396
Savings per QALY gained
Marginal Cost
-$2,967.59
Marginal
Utility
0.0567
-$52,305
Online Table 5: ICER Calculations - Markov Model
Cost
Marginal Cost
Control
RFM
Avg Cost
$35,246.22
$23,152.40
Marginal Utility
Control
RFM
Avg QALY
6.4345
6.6275
Utility
Savings per QALY gained
-$12,093.82
0.1930
-$62,653
18
Online Table 6: Markov Model Annual Costs
Health State
Not AF Free
Episode
Specialist Visits
Unplanned Specialist Visits
Hospital
ED Presentation
AF Admission
AF Ablation
Cardioversion
Pharmacy
AA Drugs
HTN Drugs
Cholesterol
Episode Cost
$76.00
$76.00
$545.00
$1,910.00
$13,847.13
$1,075.47
$308.24
$244.73
$431.88
TOTAL
Annual No.
4
0.3659
0.1179
0.2520
0.2093
0.4167
1
1
1
Total Cost
$304.00
$27.80
$64.25
$481.38
$2,898.89
$448.11
$308.24
$244.73
$431.88
$5,207
AF Free
Annual
No.
2
0
0
0
0
0
1
1
1
Total Cost
$152.00
$0.00
$0.00
$0.00
$0.00
$0.00
$308.24
$244.73
$431.88
$1,135
19
Online Table 7: Markov Modelling
RFM
Cycle
AF Free
0
0.0000
1
0.5200
2
0.6396
3
0.6671
4
0.6734
5
0.6749
6
0.6752
7
0.6753
8
0.6753
9
0.6753
10
0.6753
Control
Cycle AF Free
0
1
2
3
4
5
6
7
8
9
10
0.0000
0.2800
0.2968
0.2978
0.2979
0.2979
0.2979
0.2979
0.2979
0.2979
0.2979
Not AF
Free
1.0000
0.4800
0.3604
0.3329
0.3266
0.3251
0.3248
0.3247
0.3247
0.3247
0.3247
Not AF
Free
1.0000
0.7200
0.7032
0.7022
0.7021
0.7021
0.7021
0.7021
0.7021
0.7021
0.7021
Total
1.000
1.000
1.000
1.000
1.000
1.000
1.000
1.000
1.000
1.000
1.000
Total
1.000
1.000
1.000
1.000
1.000
1.000
1.000
1.000
1.000
1.000
1.000
Half cycle corrections
AF Free Not AF
Total
Free
0.0000 0.5000
0.50
0.5798 0.4202
1.00
0.6534 0.3466
1.00
0.6703 0.3297
1.00
0.6742 0.3258
1.00
0.6751 0.3249
1.00
0.6753 0.3247
1.00
0.6753 0.3247
1.00
0.6753 0.3247
1.00
0.6753 0.3247
1.00
0.3377 0.1623
0.50
Half cycle corrections
AF Free Not AF
Total
Free
0.0000 0.5000 0.500
0.2884 0.7116 1.000
0.2973 0.7027 1.000
0.2978 0.7022 1.000
0.2979 0.7021 1.000
0.2979 0.7021 1.000
0.2979 0.7021 1.000
0.2979 0.7021 1.000
0.2979 0.7021 1.000
0.2979 0.7021 1.000
0.1489 0.3511 0.500
Discounted
Cost
$2,605
$2,765
$2,402
$2,269
$2,189
$2,122
$2,060
$1,999
$1,941
$1,885
$915
Discounted
Utility
0.36
0.74
0.72
0.70
0.68
0.66
0.64
0.63
0.61
0.59
0.29
Discounted
Cost
$2,604.64
$3,917.28
$3,769.00
$3,657.24
$3,550.60
$3,447.18
$3,346.77
$3,249.29
$3,154.66
$3,062.77
$1,486.78
Utility
0.36
0.72
0.70
0.68
0.66
0.64
0.62
0.61
0.59
0.57
0.28
Total
Costs
$23,152
Total
Costs
$35,246
Total
Utility
6.63
Total
Utility
6.43
Cost per
Utility
$3,493
Cost per
Utility
$5,478
20
Online Figure 1:Complete Decision Tree
Time = 4 years
Outcome: AF Free
n= 29
Second Ablation
P=
0.40
C=
$15,172
n=
72
First Ablation
P=
C=
n=
Third
P=
C=
AF Free
P= 0.20
5
Ablation
0.17
$15,641
Not AF Free
P= 0.80
AF Free
P= 0.25
n=
24
No Third Ablation
P=
0.83
C=
$0
0.49
$14,717
Not AF Free
P= 0.75
n= 147
Control
C=
$9,655
AF Free
P= 0.60
n= 43
No Second Ablation
P=
0.60
C=
$0
n=
75
No Ablations
P=
C=
0.51
$0
Not AF Free
P= 0.40
n= 32
AF Free
P= 0.43
n=
43
Not AF Free
P= 0.57
Patients with AF
n= 2
AF Free
P= 0.67
n=
3
Third Ablation
P=
C=
n= 18
Second Ablation
P=
0.17
C=
$11,922
n=
104
First Ablation
P=
C=
Not AF Free
P= 0.33
n= 9
AF Free
P= 0.60
n= 15
No Third Ablation
P=
0.83
C=
$0
Not AF Free
P= 0.40
0.50
$13,847
n= 208
n=
86
No Second Ablation
P=
0.83
C=
$0
Risk Factor Mx
C=
$9,288
n=
104
No Ablations
P=
C=
0.17
$12,291
0.50
$0
n=
63
AF Free
P= 0.73
YY
Not AF Free
P= 0.27
n=
93
AF Free
P=
0.89
Not AF Free
P=
0.11
21
Online Figure 2: Annual Transition Probabilities – Markov Model
22
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24