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MicroRNA signatures of perioperative myocardial injury after elective noncardiac surgery: a prospective observational mechanistic cohort study.

ABSTRACT: BACKGROUND:Elevated 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. METHODS:We 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). RESULTS:MicroRNAs 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. CONCLUSIONS:Circulating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury.

SUBMITTER: May SM

PROVIDER: S-EPMC7678162 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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MicroRNA signatures of perioperative myocardial injury after elective noncardiac surgery: a prospective observational mechanistic cohort study.

May Shaun M SM Abbott Tom E F TEF Del Arroyo Ana G AG Reyes Anna A Martir Gladys G Stephens Robert C M RCM Brealey David D Cuthbertson Brian H BH Wijeysundera Duminda N DN Pearse Rupert M RM Ackland Gareth L GL

British journal of anaesthesia 20200724 5

<h4>Background</h4>Elevated 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.<h4>Methods</h4>We performed a nested case contr ...[more]

PMID: 32718726

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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:BackgroundPerioperative myocardial infarction is frequently attributed to type 2 myocardial infarction, a mismatch in myocardial oxygen supply-demand without unstable coronary artery disease. Our aim was to identify characteristics, management, and outcomes of perioperative type 1 versus type 2 myocardial infarction among surgical inpatients.MethodsAdults age ≥45 years hospitalized for noncardiac surgery were identified in the United States. Perioperative myocardial infarction were identified using International Classification of Diseases, 10th revision (ICD-10) codes. Clinical characteristics, invasive myocardial infarction management, mortality, and readmissions were assessed by myocardial infarction subtype.ResultsAmong 4,755,382 surgical hospitalizations, we identified 38,975 perioperative myocardial infarctions (0.82%), with type 2 infarction in 42%. Patients with type 2 myocardial infarction were older, more likely to be women, and less likely to have cardiovascular comorbidities compared with type 1 myocardial infarction. Fewer patients with type 2 myocardial infarction underwent invasive management than type 1 myocardial infarction (6.7% vs 28.8%, P < .001). Type 2 myocardial infarction mortality was lower than type 1 myocardial infarction mortality (12.1% vs 17.4%, P < .001; adjusted odds ratio [aOR] 0.51, 95% confidence interval [CI] 0.45-0.59). Invasive management of perioperative myocardial infarction was associated with lower mortality in type 1 (aOR 0.56, 95% CI 0.49-0.74) but not type 2 (aOR 1.19, 95% CI 0.77-1.85) myocardial infarction. Among survivors, there was no difference in 90-day hospital readmission between type 2 and type 1 perioperative myocardial infarction (36.5% vs 36.1%, P = .72).ConclusionsType 2 myocardial infarctions account for approximately 40% of perioperative myocardial infarctions. Patients with type 2 perioperative myocardial infarction are less likely to undergo invasive management and have lower mortality compared with those with type 1 perioperative myocardial infarction.

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.

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MicroRNA signatures of perioperative myocardial injury after elective noncardiac surgery: a prospective observational mechanistic cohort study.

Publications

MicroRNA signatures of perioperative myocardial injury after elective noncardiac surgery: a prospective observational mechanistic cohort study.

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