Should Preoperative Brain Natriuretic Peptide (BNP) Be Measured Routinely?

INTRODUCTION

In addition to its contractile function, the heart is also considered an endocrine organ capable of producing two natriuretic peptide hormones, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Both hormones cause increased renal excretion of water and solute in response to plasma volume overload and hyperosmolality. A variety of pathophysiologic stressors are also known to stimulate BNP release, with myocardial ischemia and cardiomyocyte stretch being principal among these.

BNP was first isolated from porcine brain in 1988. It is a misnomer because it originates in far greater quantities from the ventricular myocardium compared with the brain. BNP is synthesized as a prehormone, proBNP, which, upon release into the circulation, is cleaved into the biologically active BNP and an inactive N-terminal fragment called NT-proBNP. Plasma concentration of NT-proBNP is higher than that of BNP. Even though they are derived from the same precursor protein, they are subject to different metabolic pathways whereby BNP is degraded faster.

Plasma BNP/NT-proBNP is useful in the clinical evaluation and risk stratification of patients with stable coronary artery disease (CAD), acute coronary syndrome, and congestive heart failure (CHF). Its diagnostic and prognostic value in this regard has been evident since the early 1990s. ^, It can also be used as a biomarker for perioperative risk stratification in patients with risk factors for cardiac morbidity and mortality. Preoperative NT-proBNP has been shown to be strongly associated with vascular death and myocardial injury after noncardiac surgery (MINS). MINS is a common cardiovascular complication after surgery and is associated with perioperative death. It is defined as myocardial injury that may result in myocardial necrosis, is caused by myocardial ischemia, and has prognostic relevance. It is independently associated with a 30-day mortality rate of at least 3.0%

MINS, by definition, includes myocardial infarction (MI) and ischemic myocardial injury occurring within 30 days of surgery. It was developed as a concept in 2014 by the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) group of investigators who recognized that patients may experience perioperative myocardial injury that does not satisfy the diagnostic criteria for MI. The diagnostic criteria for perioperative MI are no different from those for MI that occurs outside the surgical setting (as defined by the joint task force of European Society of Cardiology [ESC], American College of Cardiology [ACC] Foundation, American Heart Association [AHA], and World Heart Association), i.e., an elevation in cardiac troponin in combination with one of the following: ischemic symptoms, ischemic electrocardiographic changes, imaging evidence of new loss of viable myocardium, or angiographic evidence of intracoronary thrombus. Large epidemiologic studies have established troponin thresholds, based on iterative processes, for diagnosis of MINS using multivariable analyses to establish association with 30-day mortality ( Table 9.1 ). Although the etiology has not been elucidated to any degree, supply-demand mismatch is thought to significantly exceed thrombus formation as the underlying cause in a preponderance of cases. It is noteworthy, however, that most cases of MINS are thought to occur in patients with underlying atheroma.

OPTIONS/THERAPIES

Accurate cardiovascular risk assessment allows for stratification for further preoperative optimization, intraoperative monitoring and anesthesia technique, and postoperative disposition. The algorithmic approach taken by the ACC/AHA for perioperative cardiac assessment for CAD is useful for obtaining a perspective on screening options and for deciding on the degree of invasiveness required ( Fig. 9.1 ). This stepwise strategy has two critical junctures, the first being classification into low versus elevated risk groups. A number of risk assessment tools can be used for this. The Revised Cardiac Risk Index (RCRI) and the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Surgical Risk Calculator are two of the most frequently used. The RCRI, originally described in 1999, includes six factors, assigned one point each: history of ischemic heart disease, CHF, cerebrovascular disease, preoperative insulin use for diabetes, serum creatinine > 2.0 mg/dL (177 μmol/L), and high-risk surgery ( Table 9.2 ). The RCRI score has been externally validated and its predictive value found to be significant in all types of elective noncardiac surgery except for abdominal aortic aneurysm repair. RCRI score and corresponding pooled risk estimates from external validation studies that used systematically monitored perioperative troponin measurements can be seen in Table 9.3 . The ACS NSQIP is a web-based universal risk calculator that is predictive for 18 disparate complications, including MI and cardiac arrest ( Table 9.4 ). A separate risk calculator, the ACS Myocardial Infarction and Cardiac Arrest Calculator (MICA), looks specifically at perioperative cardiac events. There is no evidence demonstrating superiority of ACS NSQIP or MICA over RCRI. Critics of ACS NSQIP and MICA maintain that cardiac risk may be underestimated because patients in contributing studies did not undergo perioperative troponin testing, nor have the NSQIP surgical risk calculators undergone validation in a study that monitored troponin measurements after noncardiac surgery. A further criticism of the NSQIP calculators relates to the definition of MI in the studies used to derive the NSQIP risk indices, which only included patients with ST-segment elevation MI (STEMI) or a large symptomatic increase in troponin (more than three times the normal level). It is quite likely that many postoperative infarcts are of the non-STEMI (NSTEMI) variety and silent. Advocates for both NSQIP risk calculators point to the large patient numbers and multicenter methodology used in their development: over 200,000 patients from more than 250 hospitals for ACS MICA and over 1.4 million patients from 393 hospitals for ACS NSQIP. The RCRI, conversely, was developed from a prospective single-center cohort of 4315 patients.

The second critical juncture in the ACC/AHA algorithm involves determination of functional capacity. Patients with poor or unknown functional capacity will require further evaluation (e.g., myocardial perfusion imaging or dobutamine stress echocardiography) if surgery is not urgent and the patient is a willing and appropriate candidate for revascularization. The metabolic equivalent (MET) score is frequently used to assess functional capacity. An alternative method for evaluation of functional capacity is the Duke Activity Status Index (DASI), a self-assessment tool consisting of 12 questions related to activities of daily living ( Table 9.5 ). A recent large multicenter, international, prospective cohort study demonstrated the superiority of DASI, compared with the MET score, for prediction of death or MI within 30 days of major elective noncardiac surgery.

BNP/NT-proBNP has been posited as a surrogate measure of functional capacity. Several studies and meta-analyses demonstrate that preoperative BNP/NT-proBNP concentration improves perioperative cardiac risk prediction in patients undergoing noncardiac surgery. There is no indication that one biomarker is superior for perioperative cardiac risk stratification. The following sections are mostly concerned with the elective surgical patient where measurement of preoperative BNP/NT-proBNP can be done in a timely fashion and the results analyzed in a way that may be impactful.