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

Perioperative Myocardial Injury Clinical Trial

— BASEL-PMI  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02573532
• Other study ID #: BASEL-PMI
• Status: Recruiting
• Start date: October 2015
• Est. completion date: December 2025

Study information

• Verified date: May 2023
• Source: University Hospital, Basel, Switzerland
• Contact: Christian Müller, MD, Prof
• Phone: +41 61 328 6549
• Email: christian.mueller[@]usb.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 20000
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion criteria

• Patients received a perioperative hs-cTnT screening for PMI

• Patient consent available Exclusion criteria

• Patient's refusal

Related Conditions & MeSH terms

• Perioperative Myocardial Injury
• Wounds and Injuries

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel	BS

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Cantonal Hospital of Aarau, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Estimate potential effect of detection and management of PMI on major adverse cardiac events by a screening program implemented within clinical routine		1 year
Other	Compare cardiac troponin T and I in the detection of PMI		3 days after surgery
Primary	Deaths in one year after non-cardiac surgery in patients with and without PMI		1 year
Secondary	MACE in one year after non-cardiac surgery in patients with and without PMI	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.	1 year
Secondary	Incidence of PMI within a screening program in high-risk patients undergoing major non-cardiac 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.	3 days after surgery
Secondary	Number of patients with PMI with ischemic symptoms and signs detected in a screening program in high-risk patients undergoing major non-cardiac 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	3 days after surgery
Secondary	Number of patients with PMI with management changes after screening-induced consultation	Changes in management can be: changes in medication, intensification of surveillance, call for use of coronary angiography, myocardial stress testing, other, or none	3 days after surgery, followed for 1 year
Secondary	Generate a pre- and an immediate postoperative prediction score for occurrence of major adverse cardiac events including PMI		1 year
Secondary	Costs related to the introduction of perioperative hs-cTnT screening.	Health system costs of implementation of screening is calculated as number of interventions initiated additionally to routine care after screening	1 year
Secondary	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.	Endpoint: percentage of correctly classified patients in validation cohort.	1 year
Secondary	Derive and validate an improved diagnostic screening approach for detection of PMI.	Endpoint: sensitivity and specificity for PMI.	3 days after surgery
Secondary	Evaluate the effect of pre-operative medication use.	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/ß-blocker therapy.	3 days after surgery
Secondary	Evaluate the effect of post-PMI medication on outcome of PMI.	Endpoint: death and MACE in patients suffering PMI (cardiac origin) with vs without statin/RAAS blocker/ß-blocker therapy.	1 year
Secondary	Description of PMI subtypes and potential diagnostic criteria available at time of PMI detection.		3 days after surgery
Secondary	Validate the diagnosis of PMI within a screening program in high-risk patients undergoing major non-cardiac sur-gery with other troponin assays.	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.	3 days after surgery