Dataset Information

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.

SUBMITTER: Ackland GL

PROVIDER: S-EPMC6703687 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Ackland Gareth L GL Abbott Tom E F TEF Minto Gary G Clark Martin M Owen Thomas T Prabhu Pradeep P May Shaun M SM Reynolds Joseph A JA Cuthbertson Brian H BH Wijeysundera Duminda D Pearse Rupert M RM

PloS one 20190821 8

<h4>Background</h4>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 ...[more]

PMID: 31433825

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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:Asymptomatic myocardial injury following noncardiac surgery (MINS) is an independent predictor of 30-day mortality and may go unrecognized based on standard diagnostic definition for myocardial infarction (MI). Given lack of published research on MINS in India, our study aims to determine incidence of MINS in patients undergoing noncardiac surgery at our tertiary care hospital, and evaluate the clinical characteristics including 30-day outcome.The prospective observational study included patients >65 years or >45 years with either hypertension (HTN), diabetes mellitus (DM), coronary artery disease (CAD), cerebrovascular accident (CVA), or peripheral arterial disease undergoing noncardiac surgery. MINS was peak troponin level of ?0.03 ng/dL at 12-hour or 24-hour postoperative. All patients were followed for 30 days postoperatively. Predictors of MINS and mortality were analyzed using multivariate logistic regression. Patients categorized based on peak troponin cut-off values determined by receiver operating characteristic curve were analyzed by Kaplan-Meir test to compare the survival of patients between the groups.Among 1075 patients screened during 34-month period, the incidence of MINS was 17.5% (188/1075). Patients with DM, CAD, or who underwent peripheral nerve block anaesthesia were 1.5 (P?<?.01), 2 (P?<?.001), and 12 (P?<?.001) times, respectively, more likely to develop MINS than others. Patients with heart rates ?96 bpm before induction of anesthesia were significantly associated with MINS (P?=?.005) and mortality (P?=?.02). The 30-day mortality in MINS cohort was 11.7% (22/188, 95% CI 7.5%-17.2%) vs 2.5% (23/887, 95% CI 1.7%-3.9%) in patients without MINS (P?<?.001). ECG changes (P?=?.002), peak troponin values >1 ng/mL (P?=?.01) were significantly associated with mortality. A peak troponin cut-off of >0.152 ng/mL predicted mortality among MINS patients at 72% sensitivity and 58% specificity. Lack of antithrombotic therapy following MINS was independent predictor of mortality (P?<?.001), with decreased mortality in patients who took post-op ASA (Aspirin) or Clopidogrel. Mortality among MINS patients with post-op ASA intake is 6.7% vs 12.1% among MINS patients without post-op ASA intake. Mortality among MINS patients with post-op Clopidogrel intake is 10.5% vs 11.8% among MINS patients without post-op Clopidogrel intake.A higher (17.5%, 95% CI 15-19%) incidence of MINS was observed in our patient cohort with significant association with 30-day mortality. Serial postoperative monitoring of troponin following noncardiac surgery as standard of care, would identify "at risk" patients translating to improved outcomes.

Project description:BackgroundElevated plasma or serum troponin, indicating perioperative myocardial injury (PMI), is common after noncardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident.MethodsWe performed a nested case control study of samples obtained before and after noncardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with or without PMI, matched for age, gender, and comorbidity. Real-time polymerase chain reaction quantified (qRT-PCR) relative microRNA expression (cycle quantification [Cq] threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq 500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO).ResultsMicroRNAs were detectable in all 59 patients (median age 67 yr [61-75]; 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, serum microRNA expression increased after surgery (mean fold-change) hsa-miR-1-3p: 3.99 (95% confidence interval [CI: 1.95-8.19]; hsa-miR-133-3p: 5.67 [95% CI: 2.94-10.91]; P<0.001). These changes were not associated with PMI. Bioinformatic analysis of differentially expressed microRNAs from cohorts one (n=48) and two (n=11) identified pathways associated with adrenergic stress and calcium dysregulation, rather than ischaemia.ConclusionsCirculating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury.

Project description:BackgroundRecent studies show that substantial percentage of patients experienced worsening of health related quality of life (HRQoL) 1 year after cardiac surgery. The aim of this study is to identify risk factors that interfere with improvement of HRQoL.MethodsFrom December 2015 till July 2017 a prospective single centre observational study was carried out in 1920 patients participated who underwent non-salvage cardiac surgery. All patients were requested to complete a Short Form 36 (SF-36) questionnaire before and 1 year after surgery. Primary aim of the study was to identify risk factors for non-recovery in the physical domain of the SF-36 in all cardiac surgery patients. Secondary aim was to identify identical risk factors in patients with isolated coronary artery bypass grafting.ResultsAfter cardiac surgery, the questionnaires for physical and mental health were completed by respectively 803 and 807 patients. Median age was 69[62-75] years, and 77% was male. In comparison to the preoperative status, 176 patients (21.9%) did not display an improvement in the SF-36 physical domain score 1 year after cardiac surgery. In a multivariate analysis independent risk factors for non-recovery in the SF-36 physical domain were baseline SF36 physical domain score (OR 0.954[0.942-0.965], P < 0.001), diabetes (OR 0.437 [0.265-0.720], P 0.001), female sex (OR 0.492 [0.307-0.789], P 0.003), post-operative infection (OR 0.240 [0.109-0.525], P < 0.001) and PCI within 1 year (OR 0.113 [0.036-0.349], P < 0.001) For isolated CABG, 23.2% of patients did not display an improvement in the physical domain score and risk factors appeared to be identical.ConclusionsTwenty two percent of all cardiac surgery patients did not show an improvement in the physical domain score of the HRQoL between the preoperative period and 1 year after surgery. Independent risk factors for non-recovery after cardiac surgery were baseline SF-36 physical domain score, diabetes, female sex, any postoperative infection and the need for PCI in the first year. Further research is needed to tailor the patient selection procedure prior to surgery and potentially modify risk factors in the perioperative process.Trial registrationDue to type of study not applicable. https://www.ccmo.nl/metcs/erkende-metcs/regionale-toetsingscommissie-patientgebonden-onderzoek .

Dataset Information

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

Background

Methods

Results

Conclusions

Clinical trial registry

Publications

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

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