Clinical evidence of autonomic dysfunction due to atrial fibrillation: implications for rhythm control strategy

  • Varun Malik
  • Douglas J. McKitrick
  • Dennis H. Lau
  • Prashanthan Sanders
  • Leonard F. ArnoldaEmail author



The role of the autonomic nervous system in the genesis of atrial fibrillation (AF) has been well studied; however, the converse remains poorly understood. Pulmonary veins (PV) contain receptors important in cardiac reflexes. Here, we evaluated reflex responses in patients with paroxysmal AF (PAF) to lower body negative pressure (LBNP).


Thirty-four PAF patients (including 14 PAF patients post successful PV Isolation; PVI) were compared to 14 age and sex-matched controls. Mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI), cardiac index (CI), and stroke volume index (SVI) were measured continuously during − 0, − 20, and − 40 mmHg LBNP. LBNP reduces venous return, deactivating atrial receptors, thereby eliciting a reflex increase in SVRI to maintain MAP.


AF patients have higher BMI than the controls (p = 0.02). In control subjects, LBNP did not alter MAP as SVRI increased. In PAF patients, LBNP resulted in a reduction in MAP (− 4.8%) with attenuated SVRI response (+ 4.2%) compared to controls (p < 0.05). However, in the post-PVI group, SVRI increase was similar to controls (p = 0.12) although that was insufficient to maintain MAP. In all patients, both reduction in SVI and CI and increase in HR were similar in response to LBNP.


This study provides novel clinical evidence of autonomic dysfunction in PAF patients. Successful PVI results in partial recovery of the cardiac reflex. Therefore, not only does autonomic disturbance predispose to AF but it is also a consequence of AF; potentially contributing to disease progression. This could help explain the dictum “AF begets AF.”


Atrial fibrillation Autonomic nervous system Pulmonary vein isolation Orthostatic reflexes Lower body negative pressure 



Atrial fibrillation


Cardiac index


Heart rate


Mean arterial pressure


Pulmonary vein isolation


Stroke volume


Systemic vascular resistance index


Funding information

Dr. Malik is supported by a Postgraduate Scholarship from The University of Adelaide. Dr. Lau is supported by a Robert J Craig Lectureship from the University of Adelaide. Dr. Sanders is supported by a Practitioner Fellowship from National Health and Medical Research Council of Australia. This work was supported by the Cardiovascular Lipid Grant (Pfizer Inc) and by Edwards Life Sciences who provided the Nexfin continuous monitoring device. Neither party had any role in study design, data collection, interpretation, or preparation of the manuscript.

Compliance with ethical standards

Disclosure of potential conflicts of interest

The University of Adelaide reports receiving on behalf of Dr. Lau lecture and/or consulting fees from Boehlringer Ingelheim, Pfizer, and St Jude Medical. The University of Adelaide reports receiving, on behalf of Dr. Lau, research funding from St Jude Medical. Dr. Sanders reports having served on the advisory board of Biosense-Webster, Medtronic, Abbott, Boston Scientific and CathRx. The University of Adelaide reports receiving on behalf of Dr. Sanders lecture and/or consulting fees from Biosense-Webster, Medtronic, Abbott, and Boston Scientific. The University of Adelaide reports receiving on behalf of Dr. Sanders research funding from Medtronic, Abbott, Boston Scientific, Biotronik and Liva Nova.

Research involving human participants

This study was approved by the institutional human research ethics committees where the work was carried out.

Informed consent

All participants provided written informed consent.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Centre for Heart Rhythm DisordersSouth Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide HospitalAdelaideAustralia
  2. 2.Department of CardiologyRoyal Perth HospitalPerthAustralia
  3. 3.Illawarra Health and Medical Research Institute, Building 32, University of WollongongWollongongAustralia

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