1. A Randomized Multicenter Comparison of Radiofrequency Ablation and Antiarrhythmic Drug Therapy as First Line Treatment in 294 Patients with Paroxysmal Atrial Fibrillation
Jens Cosedis Nielsen, Professor, MD, DMSc,
Aarhus, Denmark
on behalf of the MANTRA-PAF investigators 1

2. MANTRA-PAF Investigators
Arne Johannessen Gentofte University Hospital, CPH, Denmark
Pekka Raatikainen Oulu University Hospital, Finland
Gerhard Hindricks Leipzig University Hospital, Germany
Håkan Walfridsson University Hospital Linköping, Sweden
Ole Kongstad Lund University Hospital, Sweden
Steen Pehrson Rigshospitalet, Copenhagen, Denmark
Anders Englund University Hospital, Örebro, Sweden
Juha Hartikainen Kuipio University Hospital, Finland
Leif Spange Mortensen UNI-C, Denmark (Datamanagement and statistics)
Peter Steen Hansen Aarhus University Hospital, Skejby, Denmark
(Chair, investigator committee)
Jens Cosedis Nielsen Aarhus University Hospital, Skejby, Denmark
(Coordinating investigator)
Funding: The trial was supported by unrestricted grants from the Danish Heart Foundation and from Biosense Webster and Johnson&Johnson 2

3. Aim
To compare radiofrequency ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment in patients with paroxysmal atrial fibrillation (AF). 3

4. Methods Randomized controlled multicenter trial
Antiarrhythmic drug therapy (Class IC or III) (AAD) versus pulmonary vein isolation (RFA)
Power calculation: Assumed freedom from AF after 24 months in 75% (RFA) versus 60% (AAD) of the patients, α=0.05, 1-β=0.80, N=150 patients in each group
Follow-up with 7-day Holter recordings after 3, 6, 12, 18 and 24 months
Intention-to-treat analysis 4

5. Endpoints Primary endpoints: Secondary endpoints:
Cumulative burden of AF
AF-burden at each 7-day Holter recording
Secondary endpoints:
Freedom from any AF after 24 months
Freedom from symptomatic AF after 24 months
Burden of symptomatic AF after 3, 6, 12, 18, and 24 months
Atrial flutter
Quality of Life after 12 and 24 months
Serious adverse events 5

6. On AAD: N=13/138 (9%) (IC: 10, III: 3) Withdrawn N=5 Died N=3
294 Patients Randomized
146 Assigned to RFA
140 Underwent RFA (96%)
148 Assigned to AAD
146 Started AAD (99%)
69 underwent
repeated RFA
665 7D Holter
recordings
666 7D Holter
recordings
Treatment with
1.24±0.48 AAD’s
After 24 months
N=140; 223 RFA procedures (1.6±0.7)
On AAD: N=13/138 (9%) (IC: 10, III: 3)
Withdrawn N=5
Died N=3
After 24 months
N=54; 87 RFA procedures (1.6±0.7)
On AAD: N=100 /137 (73%) (IC: 86, III:14)
Withdrawn N=7
Died N=4 6

7. Baseline Characteristics I RFA AAD
146
148
Age (years)
56±9
54±10
Male gender
100 (68%)
106 (72%)
Body Mass Index
27±4
Hypertension
43 (29%)
53 (36%)
Coronary artery disease
6 (4%)
2 (1%)
Valvular disease
7 (5%)
15 (10%)
Previous stroke or TIA
5 (3%)
Diabetes
10 (7%)
Chronic lung disease
8 (5%)
Pacemaker
Thyroid disease
Previous Cardioversions
103
100 1 8 17 2 11 6 3 7 4
>4 15 7

8. Baseline Characteristics II RFA AAD
Duration of usual AF episodes
≤1 hour 27 29
>1 hour, ≤7 hours 57
>7 hours, ≤24 hours 43 45
>24 hours, ≤2 days 14 8
>2 days, ≤7 days 3 7
Average interval between AF episodes
0-7 days 82 87
>7 days, ≤1 month 48 41
>1 month, ≤6 months 18
>6 months 1
Left atrial size (echo), mm
40±6
40±5
Left ventricular ejection fraction
>60%
116
121
40-60% 26
Medication last week before randomization
Warfarin
69 (47%)
65 (44%)
Betablocker
106 (73%)
107 (72%)
Calcium channel blocker
28 (19%)
16 (11%) *
Digoxin
17 (12%)
13 (9%)
* p<0.05 8

9. AF Burden A: RFA D: AAD 9 Mann-Whitney Test
Mean rank
P-value 9

10. AF after 24 Months
P=0.004
P=0.012
Number of patients 10

11. Quality of Life (SF-36) Physical Component Summary (PCS)
Mental Component Summary (MCS) ns ns
p=0.01
p=0.02
Mean values of PCS and MCS 11

12. Atrial Flutter
P=0.25
Number of patients 12

13. Serious Adverse Events
RFA
AAD
Death 3 4
Stroke 1
Transient ischemic attack
Pulmonary vein stenosis
Tamponade
Pericardial effusion, no puncture
Suspected perforation at transseptal puncture
Atrial flutter, 1:1 AV conduction 2
Atrial flutter or atrial tachycardia
Cardiac incompensation
Perimyocarditis
Bradycardia with need of pacemaker
Ventricular tachycardia and need for ICD
Hematoma related to anticoagulation
Retroperitoneal bleeding, coiling of small artery
Chest discomfort
Discomfort probably due to medication
Cancer 6
Other (Rotator cuff rupture, Arthroscopy, Gallbladder surgery)
Total 25 22 13

14. Conclusions
At 24 months AF-burden and occurrence of any and symptomatic AF were significantly lower in the RFA group than in the AAD group.
No significant difference was observed in the cumulative burden of AF between AAD and RFA.
QOL (PCS) better in the RFA group after 12 and 24 months.
These data support RFA as a first-line treatment in patients with paroxysmal AF. 14

15. Discussion Selected patient population.
Not an argument for offering all patients with paroxysmal AF radiofrequency ablation!
Both strategies should be discussed with the patients and considered by patients and physicians when rhythm control for symptomatic paroxysmal AF is indicated.
The results of the MANTRA-PAF trial support the idea of early ablation for AF to avoid progression of AF on the long term. 15