Clinical trial NCT04077294: Preoperative BNP: Epidemiological Patterns, Management Strategies and Cost Analysis of Care
Official title: Epidemiological Patterns, Management Strategies and Cost Analysis of Care for the Patient With Perioperative Myocardial Injury When BNP is Used as a Screening Tool for Non-Cardiac Surgery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myocardial Infarction Postoperative
Myocardial Injury
Death, Cardiac
Keywords: Preoperative BNP
Perioperative cardiac risk stratification
Myocardial injury after non-cardiac surgery (MINS)
Canadian Cardiovascular Society (CCS) guidelines
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2019-09-04
Enrollment: 333
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will consist of adult patients undergoing elective non-cardiac surgery with an overnight hospital stay meeting one of the following criteria:

1. age ≥ 65
2. a revised cardiac risk index (RCRI) ≥ 1 (see Appendix 1)
3. age 45 - 64 with significant cardiovascular disease\*

Patients will be identified and recruited in the anesthesia preadmission clinic prior to surgery.

\*Known history of coronary artery disease, cerebral vascular disease, peripheral artery disease, congestive heart failure, severe PHTN or a severe obstructive intracardiac abnormality (eg, severe aortic stenosis, severe mitral stenosis, or severe hypertrophic obstructive cardiomyopathy).

Brief summary: Recently, the use of preoperative BNP as a preoperative risk stratifcation tool was added to the Canadian Cardiovascular Society (CCS) guidelines (4) on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery, based on the prognostic value of preoperative BNP in indentifiy patients at significant risk of 30-day mortality, nonfatal myocardial infarction, or myocardial injury after noncardiac surgery (MINS). While the value of screening for high risk patients through the use of preoperative BNP been demonstrated, the management of postoperative ischemia is less clear. Therefore, this study aims to:

1. Evaluation of the use of BNP as a preoperative screening biomarker; how often is it ordered in Anesthesia Preadmission Clinic and what is the incidence of a positive result (BNP ≥ 92 ng/L)
2. Determine the incidence of myocardial injury after non-cardiac surgery (MINS) at 30 days and myocardial infarction at 1 year at a tertiary care center when BNP is used as a screening tool
3. Record patterns of management of patients with MINS
4. Determine the cost associated with the different patterns of management of MINS
5. Comparison with a cohort group who qualified for BNP screening according to CCS guidelines but did not have it measured. The investigators will attempt to evaluate the cohort group for MINS at 30 days and myocardial infarction at 1 year.

Detailed description: Major cardiac complications are responsible for at least a third of perioperative deaths and are associated with significant morbidity, prolonged hospitalization and increased costs. This number is expected to rise as more surgeries are undertaken in older and frailer patients. The term myocardial injury after noncardiac surgery (MINS) is used to describe all myocardial injury due to ischemia occurring in the first 30 days after surgery. MINS includes:

1. myocardial infarction (cardiac troponin I ≥ 0.04 ug/L) with at least one of: symptoms of ischemia, new ST segment / T wave changes or new left bundle branch block, pathological Q waves, new loss of viable myocardium or regional wall motion abnormality on echocardiogram, intracoronary thrombus identified on angiogram.
2. myocardial injury without MI (elevated troponin without the additional criteria needed to diagnose MI).

The Canadian Cardiovascular Society (CCS) has developed a set of guidelines to help stratify which patients are at higher risk for cardiac mortality. In the latest revision of these guidelines, preoperative B-type natriuretic peptide (BNP) has been identified as a powerful independent predictor of perioperative cardiovascular complications. BNP is a protein released from ventricular cardiomyocytes. It is released in limited amounts during physiological conditions but this is increased significantly in ventricular failure, inflammation, fibrosis, ischemia and hypoxia. Rodseth et al. conducted a systematic review of the prognostic value of preoperative BNP and postoperative BNP in noncardiac surgery and showed that elevated preoperative BNP (i.e. ≥ 92 ng/l) carries a significant risk of 30-day mortality or nonfatal MI (21.8%). This is a significantly lower BNP value compared to what is typically seen in congestive cardiac failure patients. This study has been used to support the most recent CCS guidelines which add preoperative BNP as an important preoperative cardiac risk stratification tool. According to the CCS guidelines, patients with an elevated preoperative BNP should have daily troponins measured for 48 - 72 hours after surgery.

Troponins are components of the myocardial cell involved in contractility, specific subtypes I and T are expressed almost exclusively in the heart. An elevated troponin reflects necrosis of myocardial cells and is extremely useful in the diagnosis of a myocardial infarction. Even a slight elevation in postoperative troponins (TnTi ≥ 0.03ng/ml) without ischemic clinical symptoms can lead to a higher mortality, nonfatal cardiac arrest, nonfatal congestive heart failure, and nonfatal stroke.

While the value of screening for high risk patients through the use of preoperative BNP been demonstrated, the management of postoperative ischemia is less clear. At present, CCS guidelines recommend optimizing aspirin and statin therapy in patients with MINS, but no clear strategy has been elucidated. Evidence to support the use of aspirin and statins comes from the POISE trial. The MANAGE trial recommends starting patients who are not at risk of bleeding on the oral anticoagulant dabigatran for two years. Patients with ST-elevation MI carry a high mortality risk without reperfusion therapy (percutaneous coronary intervention or coronary artery bypass graft) and a high risk of bleeding with it. Patients with non ST-elevation MI may also require revascularization and subsequent dual antiplatelet therapy. It is evident from this brief overview that management of MINS varies from the non-invasive (aspirin and statin administration) to the invasive (PCI or CABG) depending on the extent of myocardial injury, hemodynamic stability and risk of bleeding secondary to the primary surgical procedure.

Screening for patients at risk of MINS by measuring BNP may have a significant impact on health care resources. 80% of patients with MINS are asymptomatic and go unrecognized. Screening for patients who are at risk of postoperative myocardial ischemia will ostensibly uncover a new population of patients i.e. those who, prior to BNP screening, experienced subclinical postoperative ischemia which went undiagnosed until a later juncture by which time potentially worse and irreversible myocardial injury had occurred.

In this study the objectives are to investigate:

1. incidence of qualification for BNP measurement as determined by CCS guidelines
2. incidence of patients with BNP ≥ 92 ng/L
3. incidence of MINS (myocardial infarction and myocardial injury without MI) at 30 days and incidence of myocardial infarction at 1 year after surgery
4. evaluate the management of patients with positive troponin after surgery
5. identify a matched cohort group from the SPOR database
6. compare the incidence and timing of MINS in the BNP group versus that in a matched cohort group who qualified for BNP screening but did not have it done
7. determination of cost of screening, diagnosis and management of MINS and MI for up to 1 year after surgery when BNP is used as a screening tool

In this study, elective patients deemed at risk of a postoperative cardiac event will be monitored, as determined by preoperative BNP measurement, up to 1 year postoperatively. BNP positive patients will be monitored for myocardial injury postoperatively by measuring troponin daily for 72 hours. The incidence of MINS (MI and myocardial injury without MI) in BNP positive patients will be determined. Patients with troponin I ≥ 0.04 ug/L will be referred to the cardiology consult service for further evaluation and management. Subsequent management will be categorized as 1) monitor 2) medical management and 3) revascularization. A cost analysis of the management of all three groups will be performed.

Eligibility criteria: Inclusion Criteria:

* All adult patients:

  * ≥ 65 years of age
  * ≥ 18 years of age with a revised cardiac risk index (RCRI) ≥ 1
  * between 45 and 64 years of age with significant cardiovascular disease
* Elective non-cardiac surgery with an overnight hospital stay (minimum 1 day)

Exclusion Criteria:

* Subjects \< 18 years of age
* Patient refusal to participate
* Patients undergoing cardiac surgery
* Patients undergoing day surgery (\< 1day hospital admission)

Primary outcomes:
measure: Preoperative Brain natriuretic peptide (BNP) ≥ 92 ng/L
timeFrame: From date of preoperative consultation up to the day of surgery, assessed up to 6 months.
measure: Postoperative troponin I ≥ 0.04 ug / L
timeFrame: From the end of the surgical procedure to 72 hours postoperatively
measure: Myocardial injury at 30 days after surgery
timeFrame: 30 days after surgery
measure: Myocardial injury 1 year after surgery
timeFrame: 1 year after surgery
Secondary outcomes:
measure: Observation of management patterns 30 days after surgery in patients with myocardial injury after non-cardiac surgery (MINS)
timeFrame: 30 days after surgery
measure: Observation of management patterns 1 year after surgery in patients with myocardial injury after non-cardiac surgery (MINS)
timeFrame: 1 year after surgery
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital Pre-Admission Clinic
state: Alberta
Study officials:
affiliation: University of Alberta
name: Derek Dillane, MD
role: PRINCIPAL_INVESTIGATOR
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