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

Abstract

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.

Fig 1

Patient flow diagram showing the number of patients included in the analysis. CPET, cardiopulmonary exercise testing.

Fig 2

Heart rate recovery 1 min after the end of exercise. Histogram showing the frequency distribution of heart rate recovery 1 min after the end of exercise in beats min⁻¹.

Fig 3

Heart rate recovery and Revised Cardiac Risk Index (RCRI). Bar charts showing (a) the proportion (%) of participants with heart rate recovery (HRR) less than or equal to 12 beats min⁻¹, and (b) mean heart rate recovery (beats min⁻¹), stratified by the RCRI. Error bars indicate the 95% confidence interval for the mean. Overall, 167/419 patients with RCRI=0 had heart rate recovery ≤12 beats min⁻¹, 355/871 patients with RCRI=1–2 had heart rate recovery ≤12 beats min⁻¹, and 26/36 patients with RCRI ≥3 had heart rate recovery ≤12 beats min⁻¹. The proportion of patients with heart rate recovery ≤12 beats min⁻¹ was significantly greater for RCRI ≥3 compared with the other two groups (P<0.01).

Fig 4

Heart rate recovery and NT Pro-BNP. Bar charts showing (a) the proportion (%) of participants with heart rate recovery ≤12 beats min⁻¹, and (b) mean heart rate recovery (beats min⁻¹), stratified by NT pro-BNP concentration (<100, 100–199, and ≥200 pg ml⁻¹). Error bars indicate the 95% confidence interval for the mean. Overall, 263/719 (36.6%) patients with NT pro-BNP <100 pg ml⁻¹ had heart rate recovery ≤12 beats min⁻¹, 119/291 (40.9%) patients with NT pro-BNP 100–199 pg ml⁻¹ had heart rate recovery ≤12 beats min⁻¹, and 146/263 (55.5%) patients with NT pro-BNP ≥200 pg ml⁻¹ had heart rate recovery ≤12 beats min⁻¹. NT Pro-BNP, N-terminal pro-hormone of brain natriuretic peptide.