Cardiac vagal dysfunction and myocardial injury after non-cardiac surgery: a planned secondary analysis of the measurement of Exercise Tolerance before surgery study

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.