A Randomized Multicenter Comparison of Radiofrequency Ablation and Antiarrhythmic Drug Therapy as First Line Treatment in 294 Patients with Paroxysmal Atrial Fibrillation

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

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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 JohnsonJohnson
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Aim

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

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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, a0.05, 1-ß0.80, N150 patients in
  each group
• Follow-up with 7-day Holter recordings after 3,
  6, 12, 18 and 24 months
• Intention-to-treat analysis

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Endpoints

• Primary 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

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294 Patients Randomized
146 Assigned to RFA 140 Underwent RFA (96)
148 Assigned to AAD 146 Started AAD (99)
666 7D Holter recordings
665 7D Holter recordings
69 underwent repeated RFA
Treatment with 1.240.48 AADs
After 24 months N54 87 RFA procedures
(1.60.7) On AAD N100 /137 (73) (IC 86,
III14) Withdrawn N7 Died N4
After 24 months N140 223 RFA procedures
(1.60.7) On AAD N13/138 (9) (IC 10,
III 3) Withdrawn N5 Died N3
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Baseline Characteristics I RFA AAD
N 146 148
Age (years) 569 5410
Male gender 100 (68) 106 (72)
Body Mass Index 274 274
Hypertension 43 (29) 53 (36)
Coronary artery disease 6 (4) 2 (1)
Valvular disease 7 (5) 15 (10)
Previous stroke or TIA 6 (4) 5 (3)
Diabetes 6 (4) 10 (7)
Chronic lung disease 8 (5) 6 (4)
Pacemaker 5 (3) 6 (4)
Thyroid disease 10 (7) 10 (7)
Previous Cardioversions
0 103 100
1 8 17
2 11 6
3 7 4
4 2 6
gt4 15 15
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Baseline Characteristics II RFA AAD
Duration of usual AF episodes
1 hour 27 29
gt1 hour, 7 hours 57 57
gt7 hours, 24 hours 43 45
gt24 hours, 2 days 14 8
gt2 days, 7 days 3 7
Average interval between AF episodes
0-7 days 82 87
gt7 days, 1 month 48 41
gt1 month, 6 months 14 18
gt6 months 1 0
Left atrial size (echo), mm 406 405
Left ventricular ejection fraction
gt60 116 121
40-60 29 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)
plt0.05
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AF Burden
A RFA D AAD
Mann-Whitney Test Mean rank 149 146 145
150 144 151 141 154 141 154
138 157 140 155 P-value
0.72 0.49 0.34 0.08
0.07 0.007 0.10
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AF after 24 Months
P0.004
P0.012
Number of patients
11
Quality of Life (SF-36)
Physical Component Summary (PCS)
Mental Component Summary (MCS)
ns
ns
p0.01
p0.02
Mean values of PCS and MCS
12
Atrial Flutter
P0.25
Number of patients
13
Serious Adverse Events RFA AAD
Death 3 4
Stroke 1 0
Transient ischemic attack 1 1
Pulmonary vein stenosis 1 0
Tamponade 3 0
Pericardial effusion, no puncture 0 1
Suspected perforation at transseptal puncture 1 0
Atrial flutter, 11 AV conduction 0 2
Atrial flutter or atrial tachycardia 3 3
Cardiac incompensation 0 2
Perimyocarditis 1 0
Bradycardia with need of pacemaker 0 1
Ventricular tachycardia and need for ICD 1 0
Hematoma related to anticoagulation 1 0
Retroperitoneal bleeding, coiling of small artery 1 0
Chest discomfort 1 0
Discomfort probably due to medication 0 2
Cancer 6 4
Other (Rotator cuff rupture, Arthroscopy, Gallbladder surgery) 1 2
Total 25 22
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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.

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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.