Heart rate recovery and morbidity after noncardiac surgery: Planned secondary analysis of two prospective, multi-centre, blinded observational studies

Abstract

Background: Impaired cardiac vagal function, quantified preoperatively as slower heart rate recovery (HRR) after exercise, is independently associated with perioperative myocardial injury. Parasympathetic (vagal) dysfunction may also promote (extra-cardiac) multi-organ dysfunction, although perioperative data are lacking. Assuming that cardiac vagal activity, and therefore heart rate recovery response, is a marker of brainstem parasympathetic dysfunction, we hypothesized that impaired HRR would be associated with a higher incidence of morbidity after noncardiac surgery.

Methods: In two prospective, blinded, observational cohort studies, we established the definition of impaired vagal function in terms of the HRR threshold that is associated with perioperative myocardial injury (HRR ≤ 12 beats min-1 (bpm), 60 seconds after cessation of cardiopulmonary exercise testing. The primary outcome of this secondary analysis was all-cause morbidity three and five days after surgery, defined using the Post-Operative Morbidity Survey. Secondary outcomes of this analysis were type of morbidity and time to become morbidity-free. Logistic regression and Cox regression tested for the association between HRR and morbidity. Results are presented as odds/hazard ratios [OR or HR; (95% confidence intervals).

Results: 882/1941 (45.4%) patients had HRR≤12bpm. All-cause morbidity within 5 days of surgery was more common in 585/822 (71.2%) patients with HRR≤12bpm, compared to 718/1119 (64.2%) patients with HRR>12bpm (OR:1.38 (1.14-1.67); p = 0.001). HRR≤12bpm was associated with more frequent episodes of pulmonary (OR:1.31 (1.05-1.62);p = 0.02)), infective (OR:1.38 (1.10-1.72); p = 0.006), renal (OR:1.91 (1.30-2.79); p = 0.02)), cardiovascular (OR:1.39 (1.15-1.69); p<0.001)), neurological (OR:1.73 (1.11-2.70); p = 0.02)) and pain morbidity (OR:1.38 (1.14-1.68); p = 0.001) within 5 days of surgery.

Conclusions: Multi-organ dysfunction is more common in surgical patients with cardiac vagal dysfunction, defined as HRR ≤ 12 bpm after preoperative cardiopulmonary exercise testing.

Clinical trial registry: ISRCTN88456378.

Conflict of interest statement

The METS Study and POM-HR funding sources had no role in the design and conduct of these studies; collection, management, analysis, and interpretation of the data; and preparation or approval of the article. RP holds research grants, and has given lectures and/or performed consultancy work for Nestle Health Sciences, BBraun, Medtronic, GlaxoSmithKline and Edwards Lifesciences, and is a member of the Associate editorial board of the British Journal of Anaesthesia; GLA is a member of the editorial advisory board for Intensive Care Medicine Experimental, is an Editor for the British Journal of Anaesthesia and has undertaken consultancy work for GlaxoSmithKline; TEFA is a committee member of the Perioperative Exercise Testing and Training Society. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Analysis plan.

Fig 2. Exercise-evoked heart rate dynamics and distribution of heart rate recovery.

A. Exercise-evoked changes in heart rate from baseline to peak, and 60s after recovery from the end of exercise in patients with delayed, or normal, heart rate recovery >12beats.min-1. Red colour indicate values below which are associated with increased risk of all-cause mortality obtained in large epidemiological studies.[13, 14] Median (25-75th centile values shown; p values determined by ANCOVA, controlling for age. B. Distribution of heart rate recovery (left axis) plotted against all-cause morbidity (right axis) within 5 days of surgery. Red bars indicate values below which are associated with increased risk of all-cause mortality obtained in large epidemiological studies.[13, 14].

Fig 3. Delayed heart rate and postoperative outcome.

Unadjusted Kaplan-Meier estimator for all surgery types showed that delayed heart rate recovery was associated with prolonged hospital stay (HR: 1.15 (95%CI:1.05–1.26); p = 0.0008).