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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.

SUBMITTER: Abbott TEF

PROVIDER: S-EPMC6354047 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Abbott T E F TEF Pearse R M RM Cuthbertson B H BH Wijeysundera D N DN Ackland G L GL

British journal of anaesthesia 20181217 2

<h4>Background</h4>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<sup>-1</sup> (HRR ≤12) 1 min after cessation of preoperative cardiopulmonary exercise testing] was associated with perioperative myocardial injury.<h4>Methods</h4>We conducted a pre-defined, secondary analysis of a multi-centre prospect ...[more]

PMID: 30686304

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Project description:Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors' subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia.The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1 year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30 days after surgery, and the secondary outcome is all-cause death within 1 year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration.The METS Study has received research ethics board approval at all sites. Participant recruitment began in March 2013, and 1-year follow-up is expected to finish in 2016. Publication of the results of the METS Study is anticipated to occur in 2017.

Project description:BackgroundPreoperative anaemia is associated with elevated risks of postoperative complications. This association may be explained by confounding related to poor cardiopulmonary fitness. We conducted a pre-specified substudy of the Measurement of Exercise Tolerance before Surgery (METS) study to examine the associations of preoperative haemoglobin concentration with preoperative cardiopulmonary exercise testing performance (peak oxygen consumption, anaerobic threshold) and postoperative complications.MethodsThe substudy included a nested cross-sectional analysis and nested cohort analysis. In the cross-sectional study (1279 participants), multivariate linear regression modelling was used to determine the adjusted association of haemoglobin concentration with peak oxygen consumption and anaerobic threshold. In the nested cohort study (1256 participants), multivariable logistic regression modelling was used to determine the adjusted association of haemoglobin concentration, peak oxygen consumption, and anaerobic threshold with the primary endpoint (composite outcome of death, cardiovascular complications, acute kidney injury, or surgical site infection) and secondary endpoint (moderate or severe complications).ResultsHaemoglobin concentration explained 3.8% of the variation in peak oxygen consumption and anaerobic threshold (P<0.001). Although not associated with the primary endpoint, haemoglobin concentration was associated with moderate or severe complications after adjustment for peak oxygen consumption (odds ratio=0.86 per 10 g L-1 increase; 95% confidence interval, 0.77-0.96) or anaerobic threshold (odds ratio=0.86; 95% confidence interval, 0.77-0.97). Lower peak oxygen consumption was associated with moderate or severe complications without effect modification by haemoglobin concentration (P=0.12).ConclusionHaemoglobin concentration explains a small proportion of variation in exercise capacity. Both anaemia and poor functional capacity are associated with postoperative complications and may therefore be modifiable targets for preoperative optimisation.

Project description:BackgroundPhysiological 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.MethodsThis 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).ResultsChronotropic 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.ConclusionsChronotropic 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.

Project description:OBJECTIVES:Redox regulation plays a crucial role in balancing the cardiovascular system. In this prospective study we aimed to identify currently unknown correlations valuable to cardiovascular research and patient management. METHODS:Blood samples from 500 patients were collected directly before cardiosurgical interventions (Ethics Committee reference number 85/11). Four central redox parameters were determined together with about 30 clinical, anthropometric, and metabolic parameters. RESULTS:Creatinine levels and pulmonary hypertension were significant predictors of the total antioxidant status (TAOS) in the patients; total glutathione levels were linked to C-peptide, and creatinine, gender, and ventricular arrhythmia influenced nitrate/nitrite levels. Notably, significant interactions were found between medication and redox parameters. Calcium channel blockers (CCBs) were positive predictors of total glutathione levels, whereas angiotensin-converting enzyme inhibitors and CCBs were negative predictors of NOx levels. Age showed the highest correlation with the duration of the intensive care stay, followed by NOx levels, creatinine, TAOS, and C-reactive protein. DISCUSSION:In this prospective study we determined multiple correlations between redox markers and parameters linked to cardiovascular diseases. The data point towards so far unknown interdependencies, particularly between antihypertensive drugs and redox metabolism. A thorough follow-up to these data has the potential to improve patient management. ABBREVIATIONS:A: absorption; ?A: absorption difference; ABTS: 2,2'-azino-di(3-ethylbenzothiazoline sulfonate); ACE: angiotensin-converting enzyme; AO: antioxidant; ARB: angiotensin receptor blocker; BMI: body mass index; CAD: coronary artery disease; CCB: calcium channel blocker; CDC: coronary heart diseases; COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; CVD: cardiovascular diseases; Cu-OOH: cumene hydroperoxide; D: dilution factor; DAN: 2,3-diaminonaphtalene; DMSO: dimethylsulfoxide; DNA: deoxyribonucleic acid; DTNB: 5,5-dithiobis(2-nitrobenzoate); ?: extinction coefficient; EDRF: endothelium-derived relaxing factor; fc: final concentration; GPx: glutathione peroxidases; (h)GR: (human) glutathione reductase; GSH: (reduced) glutathione; GSSG: glutathione disulfide; GST: glutathione-S-transferase; Hb: hemoglobin; HDL: high-density lipoprotein; Hk: hematocrit; H2O2: hydrogen peroxide; ICS: intensive care stay; LDH: lactate dehydrogenase; LDL: low-density lipoprotein; MI: myocardial infarction; NED: N-(1-naphthyl)-ethylendiamine-dihydrochloride; NOS: nitric oxide synthase; NOx: nitrate/nitrite; NR: nitrate reductase; PBS: phosphate buffered saline; PCA: principle component analysis; PH: pulmonary hypertension; ROS: reactive oxygen species; RNS: reactive nitrogen species; RT: room temperature (25°C); SA: sulfanilamide; SOD: superoxide dismutase; SSA: sulfosalicylic acid; TAC: total antioxidant capacity; TAOS: total antioxidant status; TEAC: trolox equivalent antioxidative capacity; TG: triglycerides; tGSH: total glutathione; TNB-: 2-nitro-5-thiobenzoate; U: unit; UV: ultraviolet; VA: volume activity; Wc: working concentration; WHR: waist-hip ratio.

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

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

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