Sympathetic autonomic dysfunction and impaired cardiovascular performance in higher risk surgical patients: implications for perioperative sympatholysis

OBJECTIVE: Recent perioperative trials have highlighted the urgent need for a better understanding of why sympatholytic drugs intended to reduce myocardial injury are paradoxically associated with harm (stroke, myocardial infarction). We hypothesised that following a standardised autonomic challenge, a subset of patients may demonstrate excessive sympathetic activation which is associated with exercise-induced ischaemia and impaired cardiac output. METHODS: Heart rate rise during unloaded pedalling (zero workload) prior to the onset of cardiopulmonary exercise testing (CPET) was measured in 2 observation cohorts of elective surgical patients. The primary outcome was exercise-evoked, ECG-defined ischaemia (>1 mm depression; lead II) associated with an exaggerated increase in heart rate (EHRR ≥12 bpm based on prognostic data for all-cause cardiac death in preceding epidemiological studies). Secondary outcomes included cardiopulmonary performance (oxygen pulse (surrogate for left ventricular stroke volume), peak oxygen consumption (VO2peak), anaerobic threshold (AT)) and perioperative heart rate. RESULTS: EHRR was present in 40.4-42.7% in both centres (n=232, n=586 patients). Patients with EHRR had higher heart rates perioperatively (p<0.05). Significant ST segment depression during CPET was more common in EHRR patients (relative risk 1.7 (95% CI 1.3 to 2.1); p<0.001). EHRR was associated with 11% (95%CI 7% to 15%) lower predicted oxygen pulse (p<0.0001), consistent with impaired left ventricular function. CONCLUSIONS: EHRR is common and associated with ECG-defined ischaemia and impaired cardiac performance. Perioperative sympatholysis may further detrimentally affect cardiac output in patients with this phenotype.