Clinical Research in Cardiology

, Volume 107, Issue 7, pp 539–547 | Cite as

Treatment of atrial fibrillation in patients with enhanced sympathetic tone by pulmonary vein isolation or pulmonary vein isolation and renal artery denervation: clinical background and study design

The ASAF trial: ablation of sympathetic atrial fibrillation
  • Mark R. de Jong
  • Annemiek F. Hoogerwaard
  • Ahmet Adiyaman
  • Jaap Jan J. Smit
  • Anand R. Ramdat Misier
  • Jan-Evert Heeg
  • Boudewijn A. A. M. van Hasselt
  • Isabelle C. Van Gelder
  • Harry J. G. M. Crijns
  • Ignacio Fernández Lozano
  • Jorge E. Toquero Ramos
  • F. Javier Alzueta
  • Borja Ibañez
  • José M. Rubio
  • Fernando Arribas
  • José M. Porres Aracama
  • Josep Brugada
  • Lluís Mont
  • Arif Elvan
Original Paper



Hypertension is an important, modifiable risk factor for the development of atrial fibrillation (AF). Even after pulmonary vein isolation (PVI), 20–40% experience recurrent AF. Animal studies have shown that renal denervation (RDN) reduces AF inducibility. One clinical study with important limitations suggested that RDN additional to PVI could reduce recurrent AF.


The goal of this multicenter randomized controlled study is to investigate whether RDN added to PVI reduces AF recurrence.


The main end point is the time until first AF recurrence according to EHRA guidelines after a blanking period of 3 months. Assuming a 12-month accrual period and 12 months of follow-up, a power of 0.80, a two-sided alpha of 0.05 and an expected drop-out of 10% per group, 69 patients per group are required. We plan to randomize a total of 138 hypertensive patients with AF and signs of sympathetic overdrive in a 1:1 fashion. Patients should use at least two antihypertensive drugs. Sympathetic overdrive includes obesity, exercise-induced excessive blood pressure (BP) increase, significant white coat hypertension, hospital admission or fever induced AF, tachycardia induced AF and diabetes mellitus. The interventional group will undergo PVI + RDN and the control group will undergo PVI.


Patients will have follow-up for 1 year, and continuous loop monitoring is advocated.


This randomized, controlled study will elucidate if RDN on top of PVI reduces AF recurrence.


RDN PVI AF Hypertension Sympathetic overdrive 


Compliance with ethical standards

Conflict of interest

The study receives sponsoring from the Medtronic External Research Program. Dr. J. Toquero Ramos reports his membership of the Medtronic European Advisory Board. The other authors declare no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Mark R. de Jong
    • 1
  • Annemiek F. Hoogerwaard
    • 1
  • Ahmet Adiyaman
    • 1
  • Jaap Jan J. Smit
    • 1
  • Anand R. Ramdat Misier
    • 1
  • Jan-Evert Heeg
    • 2
  • Boudewijn A. A. M. van Hasselt
    • 3
  • Isabelle C. Van Gelder
    • 4
  • Harry J. G. M. Crijns
    • 5
  • Ignacio Fernández Lozano
    • 6
  • Jorge E. Toquero Ramos
    • 6
  • F. Javier Alzueta
    • 7
  • Borja Ibañez
    • 8
  • José M. Rubio
    • 8
  • Fernando Arribas
    • 9
  • José M. Porres Aracama
    • 10
  • Josep Brugada
    • 11
  • Lluís Mont
    • 11
  • Arif Elvan
    • 1
  1. 1.Department of CardiologyIsala HospitalZwolleThe Netherlands
  2. 2.Department of Internal MedicineIsala HospitalZwolleThe Netherlands
  3. 3.Department of RadiologyIsala HospitalZwolleThe Netherlands
  4. 4.Department of CardiologyUniversity of GroningenGroningenThe Netherlands
  5. 5.Department of CardiologyMaastricht Universitair Medisch CentrumMaastrichtThe Netherlands
  6. 6.Department of Arrhythmia UnitHospital Universitario Puerta de HierroMadridSpain
  7. 7.Department of Arrhythmia UnitHospital Universitario Virgen de la VictoriaMálagaSpain
  8. 8.Department of CardiologyHospital Fundación Jimenez DíazMadridSpain
  9. 9.Department of CardiologyHospital Universitario 12 de OctubreMadridSpain
  10. 10.Department of CardiologyHospital DonostiaSan SebastianSpain
  11. 11.Arrhythmia Unit, Cardiovascular Institute, Hospital ClínicUniversity of BarcelonaBarcelonaSpain

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