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Incidence and Outcome of Perioperative Myocardial Injury After Non-cardiac Surgery

Active, not recruiting
Conditions
Perioperative Myocardial Injury
Registration Number
NCT02573532
Lead Sponsor
University Hospital, Basel, Switzerland
Brief Summary

This observational study includes patients undergoing major non-cardiac surgery, and screens them for the occurrence of perioperative myocardial injuries (PMI). Incidence, patient characteristics, pathophysiology, potential prevention and therapy strategies and 1-year outcomes of PMI will be described.

Detailed Description

Background: Worldwide more than 230 million surgical operations are performed each year. Despite advances in all fields of medicine, there is still a significant risk of death related to major non-cardiac surgical procedures. The observed 30-day mortality depends on patient- as well as procedural factors and ranges between 1% and 10%. Cardiovascular complications, particularly perioperative myocardial injury/infarction (PMI) seem to be major contributors to about a third of all deaths. PMI may differ from spontaneous acute myocardial infarction (AMI). The vast majority of patients experiencing PMI do NOT have acute chest pain or other symptoms typical for AMI likely because they are narcotized or sedated and random ECGs are often not informative. Accordingly, most patients with PMI are currently not detected in routine clinical practice. Missed diagnosis is invariably associated with missed opportunity for the initiation of treatment. As most patients with PMI are missed in routine clinical care, the true incidence of and outcome after PMI are largely unknown. Prior studies have often not obtained a baseline sample and thus have suggested that all cTn elevations are likely due to AMI which may exaggerate the numbers. In addition, usually conventional less sensitive assays have been used. Further, the predominant pathophysiology of PMI is currently unknown. It has been suggested that type II MI characterized by coronary perfusion pressure mismatch and not type I MI characterized by acute thrombotic coronary occlusion is the predominate mechanism. However, autopsy data suggest that plaque rupture is more common. Thus, it may be that type 2 AMI is more common but that the modest incidence of type 1 AMI is not dangerous prognostically.

Aim: To explore the incidence, patient characteristics, pathophysiology, potential prevention and therapy strategies and long-term outcome of PMI after major non-cardiac surgery

Methodology: Consecutive high-risk patients undergoing major non-cardiac surgery will be included and followed for one year for the occurrence of all-cause death and other major adverse cardiac events. Patients receive a standardized assessment of cardiovascular status and systematic perioperative screening for PMI using high sensitivity cardiac troponin T (hs-cTnT) at baseline prior to surgery, as well as on day 1 and day 2 after surgery. Acute cardiac injury will be defined as an absolute increase in h/s-cTn of the 99th percentile of healthy individuals for the respective assay above baseline cTn-value or between two postoperative values if the preoperative value is missing. A search for possible alternative causes for hs-cTnT elevations will be aggressively sought if a rising pattern of values is detected. Two independent experts will adjudicate the most likely cause of PMI using all clinical information pertaining to the individual patient including the 12-lead ECG, peak hs-cTnT blood concentrations, coronary angiography and myocardial perfusion scanning. Influence of PMI on occurrence of all-cause death will be assessed using multivariate Cox-proportional hazards analysis. Further, pre-operative and post-operative prediction models for death, major adverse cardiac events, and PMI shall be derived using a derivation-validation design.

Potential Significance: This study will generate scientific data that have major scientific implications by contributing to closing current knowledge gaps concerning the influence of PMI on long-term mortality as well as the incidence, patient characteristics, and pathophysiology of PMI after non-cardiac surgery. This knowledge will have immediate clinical implications as it could e.g. lead to major changes in perioperative management with reconsiderations of the necessary target blood pressure to avoid coronary perfusion mismatch and consecutive cardiac injury.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
16204
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Deaths in one year after non-cardiac surgery in patients with and without PMI1 year
Secondary Outcome Measures
NameTimeMethod
Number of patients with PMI with ischemic symptoms and signs detected in a screening program in high-risk patients undergoing major non-cardiac surgery3 days after surgery

Patients with PMI are evaluated for: presence of chest pain, atypical symptoms, palpitations, dyspnea, edema, or nausea; ST-changes, Q-waves, T-wave abnormalities, new bundle branch block

Derive and validate an improved diagnostic screening approach for detection of PMI.3 days after surgery

Endpoint: sensitivity and specificity for PMI.

Incidence of PMI within a screening program in high-risk patients undergoing major non-cardiac surgery3 days after surgery

PMI is defined as an absolute increase in h/s-cTn of the 99th percentile of healthy individuals for the respective assay above baseline cTn-value or between two postoperative values if the preoperative value was missing. PMI will be further classified as type I myocardial infarction, type II myocardial infarction, or myocardial injury due to non-cardiac causes.

Number of patients with PMI with management changes after screening-induced consultation3 days after surgery, followed for 1 year

Changes in management can be: changes in medication, intensification of surveillance, call for use of coronary angiography, myocardial stress testing, other, or none

MACE in one year after non-cardiac surgery in patients with and without PMI1 year

MACE is defined as a composite of death, acute myocardial infarction, life-threatening arrhythmia (cardiac arrest, sustained ventricular tachycardia, atrioventricular (AV) -block III), or acute heart failure (requiring admission to a hospital or intra-hospital transfer to the intensive care unit) within one year. Two independent cardiologists or anaesthesiologists will adjudicate all MACE.

Generate a pre- and an immediate postoperative prediction score for occurrence of major adverse cardiac events including PMI1 year
Description of PMI subtypes and potential diagnostic criteria available at time of PMI detection.3 days after surgery
Evaluate the effect of pre-operative medication use.3 days after surgery

Endpoint: number of patients undergoing elective non-cardiac surgery suffering PMI (cardiac origin) after non-cardiac surgery with vs without pre-operative statin/RAAS blocker/β-blocker therapy.

Evaluate the effect of post-PMI medication on outcome of PMI.1 year

Endpoint: death and MACE in patients suffering PMI (cardiac origin) with vs without statin/RAAS blocker/β-blocker therapy.

Validate the diagnosis of PMI within a screening program in high-risk patients undergoing major non-cardiac sur-gery with other troponin assays.3 days after surgery

PMI is defined as an absolute increase in h/s-cTn of the 99th percentile of healthy individuals for the respective assay above baseline cTn-value or between two postoperative values if the preoperative value was missing.

Costs related to the introduction of perioperative hs-cTnT screening.1 year

Health system costs of implementation of screening is calculated as number of interventions initiated additionally to routine care after screening

Derive and validate a risk score in patients with different subtypes of PMI for the occurrence of major cardiac adverse events to inform treatment decisions.1 year

Endpoint: percentage of correctly classified patients in validation cohort.

Trial Locations

Locations (1)

University Hospital Basel

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Basel, BS, Switzerland

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