Clinical trial NCT02573532: Incidence and Outcome of Perioperative Myocardial Injury After Non-cardiac Surgery
Official title: Basel Incidence, Patient Characteristics, Outcome and Possible Strategies to Improve Outcome of Perioperative Myocardial Injury After Non-cardiac Surgery: 1-Year Follow-up
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Perioperative Myocardial Injury
Keywords: myocardial ischemia/diagnosis
myocardial ischemia/epidemiology
perioperative
perioperative complications/diagnosis
prognosis
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Cantonal Hospital of Aarau, Switzerland
First posted: 2015-10-09
Enrollment: 16204
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Consecutive patients that underwent a systematic approach to PMI detection at the participating hospitals as clinical routine will be included.

The screening consists of a pre-operative "baseline" measurement of hs-cTnT within 30 days prior to surgery, and two post-operative measurements taken on the first and second day after surgery. Screening is done in patients requiring hospitalization \>24 hours after surgery AND (aged ≥ 65 years OR history of coronary artery disease OR peripheral artery occlusive disease OR cerebrovascular disease). Patients are seen by a cardiologist in case of detection of a PMI.

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.

Eligibility criteria: Inclusion criteria

* Patients received a perioperative hs-cTnT screening for PMI
* Patient consent available Exclusion criteria
* Patient's refusal

Primary outcomes:
measure: Deaths in one year after non-cardiac surgery in patients with and without PMI
timeFrame: 1 year
Secondary outcomes:
measure: MACE in one year after non-cardiac surgery in patients with and without PMI
timeFrame: 1 year
measure: Incidence of PMI within a screening program in high-risk patients undergoing major non-cardiac surgery
timeFrame: 3 days after surgery
measure: Number of patients with PMI with ischemic symptoms and signs detected in a screening program in high-risk patients undergoing major non-cardiac surgery
timeFrame: 3 days after surgery
measure: Number of patients with PMI with management changes after screening-induced consultation
timeFrame: 3 days after surgery, followed for 1 year
measure: Generate a pre- and an immediate postoperative prediction score for occurrence of major adverse cardiac events including PMI
timeFrame: 1 year
measure: Costs related to the introduction of perioperative hs-cTnT screening.
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
measure: Derive and validate an improved diagnostic screening approach for detection of PMI.
timeFrame: 3 days after surgery
measure: Evaluate the effect of pre-operative medication use.
timeFrame: 3 days after surgery
measure: Evaluate the effect of post-PMI medication on outcome of PMI.
timeFrame: 1 year
measure: Description of PMI subtypes and potential diagnostic criteria available at time of PMI detection.
timeFrame: 3 days after surgery
measure: Validate the diagnosis of PMI within a screening program in high-risk patients undergoing major non-cardiac sur-gery with other troponin assays.
timeFrame: 3 days after surgery
Other outcomes:
measure: Estimate potential effect of detection and management of PMI on major adverse cardiac events by a screening program implemented within clinical routine
timeFrame: 1 year
measure: Compare cardiac troponin T and I in the detection of PMI
timeFrame: 3 days after surgery
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: BS
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Christian Müller, MD, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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