Validation of B-type Natriuretic Peptide With N-terminal Pro B-type Natriuretic Peptide in Perioperative Risk Assessment

Study Overview
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Brief Summary
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This is a single-centre, prospective study to determine the correlation and comparative thresholds between N-terminal pro-brain natriuretic peptide (NT ProBNP, Roche) and brain natriuretic peptide (BNP, Abbott) tests. The study population will include patients assessed in presurgical screening (PSS) or on the day of surgery (DOS) who are presenting for elective surgery requiring a minimum of one-night admission, and are a) >65 years old, b) RCRI ≥1 or c) >45 years old with significant cardiovascular disease (coronary artery disease, peripheral arterial disease, cerebral vascular disease, congestive heart failure, obstructive intracardiac disease such as severe aortic stenosis, severe mitral stenosis or severe hypertrophic obstructive cardiomyopathy). Informed consent will be obtained at PSS or on the DOS by study staff. High sensitivity troponin I measurements will be taken on postoperative day (POD) 0, 1 and 2, and the outcome of MINS (high sensitivity troponin > 30 ng/L) or vascular death will be determined by an assessor blinded to BNP/NT ProBNP results at postoperative day (POD) 30. Given a sample size of 431 patients and based upon previous local data that found approximately 500 patients qualifying for BNP testing in a six month period, the investigators predict data collection to be completed in approximately six months.

Detailed Description
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This is a single-centre, prospective study to determine the correlation and comparative thresholds between NT ProBNP (Roche) and BNP (Abbott) tests. This will involve simultaneous serum sampling for both BNP and NT ProBNP at pre-surgical screening (PSS) or on the day of surgery (DOS). Serum sampling of BNP in this patient population is standard of care in our institution, thus only the additional blood required for the NT ProBNP test requires additional consent. Informed consent will be obtained at PSS or on the DOS by study staff. High sensitivity troponin I (Abbott) measurements will be taken on postoperative day (POD) 0, 1 and 2, as per local standard of care and the outcome of MINS (myocardial injury after non-cardiac surgery as indicated by high sensitivity troponin > 30 ng/L) or vascular death will be determined by an assessor blinded to BNP/NT ProBNP results at postoperative day (POD) 30. The primary outcome is correlation of POC NT ProBNP with BNP levels and validation of appropriate thresholds. The secondary outcome is combined MINS and vascular death at POD 30. The study population will include patients assessed in PSS or on the DOS who are presenting for elective surgery requiring a minimum of one-night admission following and are a) >65 years old, b) revised cardiac risk index (RCRI) ≥1 or c) >45 years old with significant cardiovascular disease (coronary artery disease, peripheral arterial disease, cerebral vascular disease, congestive heart failure, obstructive intracardiac disease such as severe aortic stenosis, severe mitral stenosis or severe hypertrophic obstructive cardiomyopathy). The required sample size of 431 patients was calculated to adequately perform a power assessment of the primary outcome of correlating BNP and NT ProBNP thresholds. Historically, Presurgical Screening (PSS) at Kingston Health Sciences Centre (KHSC) collects BNP serum samples from approximately 500 patients at PSS in a six month time frame, as reported by a local, retrospective quality assurance study (McMullen/Cook). This sample size will not likely be sufficient to determine significance regarding the secondary outcome of MINS or vascular death by POD 30. Nonetheless, the trend observed may be informative in the context of correlating the risk prediction provided by BNP screening at our centre to that from larger studies.

Official Title
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Validation of B-type Natriuretic Peptide With N-terminal Pro B-type Natriuretic Peptide in Perioperative Risk Assessment

Conditions
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Perioperative Care

Intervention / Treatment
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* Diagnostic Test: NT ProBNP (Roche)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient consents to study and is undergoing non-cardiac surgery and is one of: Age > 65 years Revised cardiac risk index (RCRI) >=1 Age > 45 years old with significant cardiovascular disease (coronary artery disease, peripheral arterial disease, cerebral vascular disease, congestive heart failure, obstructive intracardiac disease such as severe aortic stenosis, severe mitral stenosis or severe hypertrophic obstructive cardiomyopathy) Exclusion Criteria: Age < 18 years Patient undergoing cardiac surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-Cardiac Surgery Patient<br>Our study population will be comprised of any patient undergoing non-cardiac surgery who meets standard of care criteria for BNP testing. This includes patients who are a) >65 years old, b) revised cardiac risk index (RCRI) ≥1 or c) >45 years old with significant cardiovascular disease (coronary artery disease, peripheral arterial disease, cerebral vascular disease, congestive heart failure, obstructive intracardiac disease such as severe aortic stenosis, severe mitral stenosis or severe hypertrophic obstructive cardiomyopathy) | Diagnostic Test: NT ProBNP (Roche)<br>* This NT ProBNP assay is a point-of-care (POC) test that will be conducted on a 2 mL sample of whole blood collected in a non-heparinized tube. NT ProBNP results are used in this setting to predict perioperative cardiovascular risk.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BNP/NT ProBNP Conversion Formula | The primary objective of this study is to determine external validation of the BNP (Abbott)/NT ProBNP conversion formula (Kasahara et al., 2019) and to provide recalibration, if necessary, for the POC NT ProBNP results. | Within three months before surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| POD30 Myocardial injury after non-cardiac surgery (MINS) | Incidence of thirty-day post-operative myocardial injury after non-cardiac surgery (MINS) as determined by high-sensitivity troponin I (Abbott) > 30 ng/L | 30 days after surgery | 
| POD30 Vascular Death | Thirty day vascular death is defined as death from the composite of these vascular diseases: hypertensive disease, ischemic heart disease, cerebrovascular disease, pulmonary vascular disease, renal failure, artery/arteriole/capillary disease. | 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BNP, NT ProBNP, MINS, myocardial injury after non-cardiac surgery, perioperative risk, risk stratification, perioperative care