Brain Natriuretic Peptide&

Acute Myocardial Infarction

A Review of Literature

Presented by: Jay Hall PA-S II Preceptor: Ali Rahimi MD

Acute Myocardial Infarction

• Chest pain is the reason for over 5 million ER visits a year [1]

• It is the second most common presenting symptom in the ER [1]

• What’s #1?

Myocardial Infarction

Acute Myocardial Infarction

• Nearly 2% of chest pain patients are released from the hospital when in fact they are suffering an AMI [2]

• But admitting a patient without a diagnosis of AMI causes an expensive and invasive workup

• Cardiac markers aid in the early treatment and better results for AMI [3]

Cardiac Markers

Cardiac serum markers are essential to aid in diagnosis of patients who do not present with “classic” symptoms and

signs of AMI

Brain Natriuretic Peptide

• An entire family of natriuretic peptide hormones (NPs) exists whose purpose is to counteract the hormones of the renin-angiotensin-aldosterone system as well as the sympathetic system [4]

• The three NPs most important to the cardiac system are atrial NP, also called A-type NP (ANP); brain NP, also called B-type NP (BNP); and C-type NP (CNP).

Brain Natriuretic Peptide

• Although ANP and BNP are found in the atria and ventricles:– ANP is predominately and rapidly released from atrial

myocardium from increased atrial wall tension

– BNP is predominately released from ventricular myocardium in a slower response to increased ventricular wall tension.

• BNP is initially released as a prohormone, pro-BNP, which is then enzymatically cleaved into BNP and NT-proBNP, the amino-terminal portion of the prohormone.

Markers of Myocardial Injury and Dysfunction.Casey, Patricia; MSN, RN

AACN Clinical Issues: Advanced Practice in Acute & Critical Care. 15(4):547-557, October/December 2004.

TABLE 3 Cardiovascular Effects of Natriuretic Peptides

•NPs are released in response to volume expansion and increased intracardiac pressure, assisting in the regulation of blood pressure, blood volume, and sodium balance (Table 3).

Brain Natriuretic Peptide

• While all three NPs are produced in the brain, ANP and BNP are found in higher concentrations in the myocardium. Therefore, BNP is a misnomer, called as such because it was first isolated from porcine brain tissue. [4]

BNP in Literature

• Several studies have identified BNP as a diagnostic tool, a therapeutic guide, and a prognostic indicator, as well as a therapeutic agent (nesiritide, a recombinant form of BNP) in heart failure. [6] Recent studies have investigated the role of BNP and NT-pro-BNP in ACS. Elevated levels of BNP and NT-proBNP in patients with ACS are indicative of short- and long-term mortality and morbidity (heart failure and AMI). [7-8]

• A recent study of a subset of subjects from the Heart and Soul Study found a positive correlation between BNP levels and risk of inducible ischemia. [10]

BNP

• ANP and BNP are neurohormones released into the circulation in response to altered hemodynamics – exercise or ventricular

dysfunction.

• Guanylyl cyclase-linked NP receptors remove NPs from the circulation. However, because of the receptor’s higher affinity for ANP, as well as degradation by an enzyme that also has a higher affinity for ANP, BNP has a longer half-life compared to ANP (18 minutes compared to 3 minutes)

Our Focus

• We will focus on a few studies specifically looking at the use of BNP in the acute phase of infarction as well as a long term predictor.

Comparison of Usefulness of N-Terminal Pro-Brain Natriuretic Peptide as an Independent Predictor of Cardiac Function Among Admission Cardiac Serum Biomarkers in Patients With Anterior Wall Versus

Nonanterior Wall ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary

Intervention

• Joost D.E. Haeck MD et al. • The American Journal of Cardiology

Volume 105, Issue 8, 15 April 2010, Pages 1065-1069

Purpose • Determine the prognostic value of N-terminal pro-brain natriuretic

peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

• Measured NT-pro-BNP, cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and creatinine on the patients' arrival at the catheterization laboratory in 206 patients with ST-segment elevation myocardial infarction.

Design and Inclusion• All patients included in the present study were participants in the PRoximal Embolic

Protection in Acute myocardial infarction and Resolution of ST-Elevation (PREPARE) trial.

• In this 2-center, randomized, open trial, patients with ST-segment elevation myocardial infarction were randomized to primary percutaneous coronary intervention (PCI) with combined proximal embolic protection and thrombus aspiration (n = 141) or primary PCI alone (n = 143).

• In brief, the patients were eligible for inclusion in the PREPARE trial if– they had experienced an onset of symptoms of myocardial infarction <6 hours before

presentation – had electrocardiographic evidence of persistent ST-segment elevation of ≥200 μV in ≥2

contiguous leads and – Thrombolysis In Myocardial Infarction flow grade 0 to 1 on diagnostic angiography

Results

• Patients with an admission NT-pro-BNP level of ≥260 pg/ml more often had a greater LV end-diastolic volume, a greater LV end-systolic volume, a lower LVEF, a larger infarct size, and a larger number of transmural segments.

• Overall, anterior wall myocardial infarctions were larger, with a larger number of transmural segments.

Conclusion

• Patients with nonanterior wall myocardial infarction and an admission NT-pro-BNP level of <260 pg/ml will have better preserved LV function

N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction

of mortality and subsequent myocardial infarction in patients with unstable coronary

artery disease.

• James, Stefan K et al

• Circulation. 108(3):275-81, 2003 Jul 22.

• NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial.

• Levels of NT-proBNP were correlated independently with:– age, female gender, low body weight, diabetes, renal

dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia

Figure 1. Kaplan-Meier survival curves regarding probability of death during 1 year for patient strata, according to quartiles of NT-proBNP.

James S K et al. Circulation 2003;108:275-281

Copyright © American Heart Association

Figure 2. Mortality at 1-year follow-up among strata of patients, according to deciles of NT-proBNP levels.

James S K et al. Circulation 2003;108:275-281

Copyright © American Heart Association

Figure 4. Mortality at 1-year follow-up among strata of patients, according to quartiles of NT-proBNP and quartiles of creatinine clearance (A), troponin T (B), CRP (C), and heart rate (D).

James S K et al. Circulation 2003;108:275-281

Copyright © American Heart Association

• Increasing NT-proBNP was related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year.

• Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. – In contrast, only troponin T, creatinine clearance, and ST-segment

depression were independently related to future MI.

• The combination of NT-proBNP and creatinine clearance provided the best prediction– 1-year mortality of 25.7% with both markers in the top quartile vs 0.3%

with both markers in the bottom quartile

In other words…

In a study of 7,800 patients with non–ST-segment-elevation ACS, higher levels of NT-proBNP were associated with an increased risk of death as early as 48 hours after AMI and for up to 1 year later. [9]

• CRP and troponin levels were also elevated, but there was a stronger correlation of risk of an event with elevated NT proBNP.

Conclusion

• The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.

• Brain Natriuretic Peptide (BNP) as a Marker of Perioperative Cardiac Damage After Coronary

Artery Bypass Grafting (CABG): Preliminary Study

• Sztefko, Krystyna PhD et al

• Point of Care: The Journal of Near-Patient Testing & TechnologyIssue: Volume 4(1), March 2005, pp 20-23

Purpose

• Evaluation of brain natriuretic peptide (BNP) measurement as an aid in diagnosis of perioperative myocardial infarction (PMI) and as a prognostic factor after coronary artery bypass grafting (CAGB) was conducted. The study included 34 patients who underwent CABG

Brain Natriuretic Peptide (BNP) as a Marker of Perioperative Cardiac Damage After Coronary Artery Bypass Grafting (CABG): Preliminary Study.Sztefko, Krystyna; Kalfas-Paluch, Dorota; Sniezek-Maciejewska, Maria; Sadowski, Jerzy

Point of Care: The Journal of Near-Patient Testing & Technology. 4(1):20-23, March 2005.

FIGURE 1 . The time course of BNP concentration in patients undergoing CABG. The mean +/- SE plasma BNP levels are given. Statistical differences between preoperative value and the values after surgery for each group are provided.

Conclusion

• Acutely and markedly elevated plasma BNP levels after CABG reflect the state of left ventricular function and measurement of BNP after cardiac surgery may be useful in risk stratification for patients after CABG.

• Relation of Plasma Brain Natriuretic Peptide Levels on Admission for ST-Elevation

Myocardial Infarction to Left Ventricular End-Diastolic Volume Six Months Later Measured

by Both Echocardiography and Cardiac Magnetic Resonance

• Ana Garcia-Alvarez MD et al

• The American Journal of CardiologyVolume 104, Issue 7, 1 October 2009, Pages 878-882

Design• Eighthly-two patients with first STEMIs admitted to a tertiary care

hospital and reperfused within 12 hours of symptom onset were prospectively included.

• The diagnosis of STEMI was established: – typical ischemic chest pain lasting ≥30 minutes– electrocardiographic ST-segment elevation ≥0.1 mV in ≥2 leads – Increase in troponin I to ≥2 times higher than the normal range

• Exclusion criteria– history of cardiomyopathy (previous myocardial infarction, hypertensive heart

disease, valvular heart disease, or history of heart failure) – advanced heart failure – impaired renal function (creatinine >1.5 mg/dl)– life-limiting noncardiac diseases, or any contraindication to CMR

Design

• LV dilatation was assessed as the percentage of variation in end-diastolic LV volume compared to baseline measurement, using volumes derived from echocardiography and CMR – Clinically significant LV dilatation at 6-month follow-up was defined

as a >20% increase in LV end-diastolic volume compared to baseline

• All analyses was preformed by blinded practitioners

• There were no statistical differences in baseline characteristics, with the exception of BNP levels

• Patients were treated the same and received the same post-ACS care

• Clinically significant LV dilatation was observed in 26 of patients (32%).

• BNP on admission was statistically higher in patients who subsequently developed clinically significant LV dilatation– (182 ± 117 vs 106 ± 91 pmol/ml, p <0.01). – BNP values also persisted significantly higher at

follow-up in this group of patients

Time course of BNP levels after STEMI in the dilatation group (DG) and the nondilatation group (NDG). *p <0.01 for the comparison of BNP levels between groups.

Conclusion

• In conclusion, high BNP levels on admission and at follow-up predict LV dilatation after STEMI. The early determination of plasma BNP upon admission for STEMI could be helpful in identifying patients at higher risk for LV dilatation, in whom aggressive management is warranted.

Thoughts

• BNP is a useful and effective predictor of future morbidity and mortality in patients who suffer ACS

• Further studies are needed but why not

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and Health Statistics, No 326. 2002.

• 2 -- Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med. 2000;342:1163–1170.

• 3 – Current Medical Diagnosis and Treatment 2010

• 4-- Baines AD, DeBold AJ, Sonnenberg H. Natriuretic effect of atrial extract on isolated perfused rat kidney. Can J Physiol Pharmacol. 1983;61:1462–1466

• 5 --Omland T, Persson A, Ng L, et al. N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes. Circulation. 2002;106:2913–2918

• 6 -- Prahash A, Lunch T. B-type natriuretic peptide: a diagnostic, prognostic, and therapeutic tool in heart failure. Am J Crit Care. 2004; 13:47–55

• 7 -- de Lemos JA, Morrow DA, Bentley JH, et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med.2001;345:1014–1021

• 8-- Sabatine MS, Morrow DA, de Lemos JA, et al. Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide.Circulation. 2002;105:1760–1763.

• 9 -- James SK, Lindahl B, Siegbahn A, et al. N-terminal pro–brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a global utilization of strategies to open occluded arteries (GUSTO)-IV Substudy.Circulation. 2003;108:275–281

• 10 -- Markers of Myocardial Injury and Dysfunction, Casey, Patricia E. MSN, RN, AACN Clinical Issues: Advanced Practice in Acute and Critical Care• Issue: Volume 15(4), October/December 2004, pp 547-557

• 11-- Sabatine MS, Morrow DA, de Lemos JA, et al. Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide.Circulation. 2002;105:1760–1763