Introduction: A second look at the autonomic nervous system: Repurposing our lessons learned

The key function of the autonomic nervous system (ANS) in normal cardiac physiology has been known for more than 50 years. Early studies in the 1960s and 1970s by Braunwald and colleagues demonstrated the ANS’ role in the maintenance of cardiac output at rest and in response to exercise through modulation of heart rate, contractility, preload, and afterload [1, 2]. Abnormal hyperactivity of the sympathetic nervous system (SNS) and simultaneous dysfunction of the parasympathetic nervous system in heart disease were also recognized during this time period [1-4]. Additional population studies in heart failure (HF) patients showed an association of SNS activation with exercise capacity, hemodynamics, degree of left ventricular dysfunction, as well as mortality, establishing the critical impact of the ANS in cardiovascular dysregulation in the heart failure syndrome [5-9]. However it remained unclear if ANS activation played a truly causative role in myocardial deterioration rather than serving as a marker of the body’s attempt to maintain homeostasis in the face of a failing heart.