Chronotropic incompetence and myocardial injury after noncardiac surgery: planned secondary analysis of a prospective observational international cohort study

Background: Physiological measures of heart failure are common in surgical patients, despite the absence of a diagnosis. Heart rate (HR) increases during exercise are frequently blunted in heart failure (termed chronotropic incompetence), which primarily reflects beta-adrenoreceptor dysfunction. We examined whether chronotropic incompetence was associated with myocardial injury after noncardiac surgery. Methods: This was a predefined analysis of an international cohort study where participants aged >= 40 yr underwent symptom-limited cardiopulmonary exercise testing before noncardiac surgery. Chronotropic incompetence was defined as the ratio of increase in HR during exercise to age-predicted maximal increase in HR <0.6. The primary outcome was myocardial injury within 3 days after surgery, defined by high-sensitivity troponin assays >99th centile. Explanatory variables were biomarkers for heart failure (ventilatory efficiency slope [minute ventilation/carbon dioxide production] >= 34; peak oxygen consumption <= 14 ml kg(-1) min(-1) ; HR recovery <= 6 beats min(-1) decrease 1 min post-exercise; preoperative N-terminal pro-B-type natriuretic peptide [NT pro-BNP] >300 pg ml(-1)). Myocardial injury was compared in the presence or absence of sympathetic (i.e. chronotropic incompetence) or parasympathetic (i.e. impaired HR recovery after exercise) thresholds indicative of dysfunction. Data are presented as odds ratios (ORs) (95% confidence intervals). Results: Chronotropic incompetence occurred in 396/1325 (29.9%) participants; only 16/1325 (1.2%) had a heart failure diagnosis. Myocardial injury was sustained by 162/1325 (12.2%) patients. Raised preoperative NT pro-BNP was more common when chronotropic incompetence was <0.6 (OR: 1.57 [1.11-2.23]; P=0.011). Chronotropic incompetence was not significantly associated with myocardial injury (OR: 1.05 [0.74-1.50]; P=0.78), independent of rate-limiting therapy. HR recovery <12 beats min(-1) decrease after exercise was associated with myocardial injury in the presence (OR: 1.62 [1.05-2.51]; P=0.03) or absence (OR: 1.60 [1.06-2.39]; P=0.02) of chronotropic incompetence. Conclusions: Chronotropic incompetence is common in surgical patients. In contrast to parasympathetic dysfunction which was associated with myocardial injury, preoperative chronotropic incompetence (suggestive of sympathetic dysfunction) was not associated with postoperative myocardial injury.