Cardiac Vagal Dysfunction and Myocardial Injury After Non-Cardiac Surgery: A Planned Secondary Analysis of the Measurement of Exercise Tolerance Before Surgery Study

Br J Anaesth. 2019 Feb;122(2):188-197. doi: 10.1016/j.bja.2018.10.060. Epub 2018 Dec 17.


Background: The aetiology of perioperative myocardial injury is poorly understood and not clearly linked to pre-existing cardiovascular disease. We hypothesised that loss of cardioprotective vagal tone [defined by impaired heart rate recovery ≤12 beats min-1 (HRR ≤12) 1 min after cessation of preoperative cardiopulmonary exercise testing] was associated with perioperative myocardial injury.

Methods: We conducted a pre-defined, secondary analysis of a multi-centre prospective cohort study of preoperative cardiopulmonary exercise testing. Participants were aged ≥40 yr undergoing non-cardiac surgery. The exposure was impaired HRR (HRR≤12). The primary outcome was postoperative myocardial injury, defined by serum troponin concentration within 72 h after surgery. The analysis accounted for established markers of cardiac risk [Revised Cardiac Risk Index (RCRI), N-terminal pro-brain natriuretic peptide (NT pro-BNP)].

Results: A total of 1326 participants were included [mean age (standard deviation), 64 (10) yr], of whom 816 (61.5%) were male. HRR≤12 occurred in 548 patients (41.3%). Myocardial injury was more frequent amongst patients with HRR≤12 [85/548 (15.5%) vs HRR>12: 83/778 (10.7%); odds ratio (OR), 1.50 (1.08-2.08); P=0.016, adjusted for RCRI). HRR declined progressively in patients with increasing numbers of RCRI factors. Patients with ≥3 RCRI factors were more likely to have HRR≤12 [26/36 (72.2%) vs 0 factors: 167/419 (39.9%); OR, 3.92 (1.84-8.34); P<0.001]. NT pro-BNP greater than a standard prognostic threshold (>300 pg ml-1) was more frequent in patients with HRR≤12 [96/529 (18.1%) vs HRR>12 59/745 (7.9%); OR, 2.58 (1.82-3.64); P<0.001].

Conclusions: Impaired HRR is associated with an increased risk of perioperative cardiac injury. These data suggest a mechanistic role for cardiac vagal dysfunction in promoting perioperative myocardial injury.

Keywords: B-type natriuretic peptide; cardiopulmonary exercise testing; heart rate; myocardial injury after non-cardiac surgery; surgery; troponin; vagal function.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Exercise Test
  • Exercise Tolerance*
  • Female
  • Heart / innervation*
  • Heart Injuries / physiopathology*
  • Heart Rate
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Postoperative Complications / physiopathology*
  • Predictive Value of Tests
  • Preoperative Care
  • Prospective Studies
  • Surgical Procedures, Operative*
  • Treatment Outcome
  • Vagus Nerve / physiopathology*


  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain