Measuring Natriuretic Peptides in Acute Coronary Syndromes Peter A. McCullough, MD, MPH, FACC, FACP, FAHA, FCCP Consultant Cardiologist Chief Academic and Scientific Officer St. John Providence Health System Providence Park Heart Institute, Novi, MI USA e-mail: peteramccullough@gmail.com
Measuring Natriuretic Peptides in Acute Coronary Syndromes Participant Poll
Confidential Training Materials - Internal Use Only 3
Unstable Plaque Inflammation and repair Cap thickness Core size Lumen VULNERABLE PLAQUE Fibrous cap Lipid-rich core Cap disruption - Vulnerability - Triggers Fibrous tissue Atheromatous material (lipid-rich) Thrombus Plaque hemorrhage Macrophage Smooth muscle cell Théroux P, Fuster V. Circulation. 1998;97:1195-1206. Thrombolysis D Y N A M I C Thrombosis Myocardial Infarction UNSTABLE CORONARY ARTERY DISEASE DETERMINANTS OF THROMBOSIS - Local factors - Systemic factors Downstream embolization
Annual Admissions for Acute Coronary Syndrome (ACS) ~ 2.0 MM Patients Admitted to CCU or Telemetry Annually 600,000 ST-Segment Elevation MI 1.4 Million Non-ST-Segment Elevation ACS Antman EM, et al. Circulation. 2004;110:588-636. Braunwald E, et al. Circulation. 2000;102:1193-1209.
Acute Evaluation of ACS Presentation Chest Pain or Short of Breath ECG Normal ST-Segment Depression ST-Segment Elevation Blood Marker Panel + + + Diagnosis Rule-Out Unstable Angina Acute MI Adapted from Braunwald E, et al. Available at: http://www.americanheart.org/downloadable/heart/1022188973899unstable_may8.pdf. Adapted from Antman EM, et al. Circulation.2004 Aug 31;110(9):e82-292.
NACB Guidelines Class IIA recommendation for use of biomarkers in risk stratification for ACS Measurement of BNP or NT pro BNP may be useful in addition to a cardiac troponin for risk assessment in patients with a clinical syndrome consistent with ACS. Class IIB recommendation for use of biomarkers in risk stratification for ACS A multimarker strategy that includes measurement of 2 or more pathobiologically diverse biomarkers in addition to a cardiac troponin may aid in enhancing risk stratification in patients with a clinical syndrome consistent with ACS. Confidential Training Materials - Internal Use Only 8
Early Risk Stratification I IIa IIb III Cardiac biomarkers should be measured in all patients who present with chest discomfort consistent with ACS. I IIa IIb III A cardiac-specific troponin is the preferred marker, and if available, it should be measured in all patients who present with chest discomfort consistent with ACS.
Troponin
Troponin and Mortality in NSTE ACS Changes in Focus on Heart Failure UA/NSTEMI 9/00 Mortality at 42 Days (% of patients) 8 6 4 2 0 1.0 1.7 3.4 831 174 148 134 50 67 0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 >9.0 Cardiac Troponin I (ng/ml) Risk Ratio 1.0 1.8 3.5 3.9 6.2 7.8 Antman N Engl J Med. 335:1342, 1996 3.7 McCullough, Cardiac Biomarkers, 2008 6.0 7.5
Ultrasensitive Troponins
Acute Coronary Syndrome Guidelines Biomarker data be available to the physician within 30 60 minutes following the patient s arrival in the ED Braunwald E, Antman EM, Beasely JW, et al. Circulation. 2002;106:1893 1900. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Biomarkers of Acute Coronary Syndrome and Heart Failure, Draft 2004 in print 2006, Recommendation Level for POCT Testing when TAT > 1 hr, IIB.
St. Francis Hospital, Evanston, IL
St. Francis Hospital, Evanston, IL Cardiac CTA Where? When?
Weber M, Hamm C. Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine. Heart. 2006 Jun;92(6):843-9.
BNP Secretion Induced by Ischemia
Results of BNP Testing in ACS Frequency of Baseline BNP > 80 pg/ml 30 25 25.2 % 20 15 10 19.1 15.6 10.1 5 0 All Pts NSTEMI UA ctni Neg Morrow DA JACC 2003; 41:1264-72
Probability of Death Through 30 Days Stratified by B-Type Natriuretic Peptide (BNP) Mortality (%) 20 15 10 5 7 Days 15.2% vs. 1.3% P<0.0001 48 Hours 8.7% vs. 1.3% P=0.001 BNP >80 pg/ml 30 Days P<0.0001 BNP 80 pg/ml 0 0 10 20 30 Follow-Up (Days) Mega J. et al., J Am Coll Cardiol 2004; 44:335-9.
BNP BNP In the as a Prediction Predictor of In-Hospital In-hospital Death Mortality Confidential Training Materials - Internal Use 20
Cumulative Incidence of Subsequent Death or New or Worsening CHF Percentage 22 20 18 16 14 12 10 8 6 4 2 0 B-Type Natriuretic Peptide Levels Baseline-Month 4 High-High Low-High High-Low Low-Low 120 240 360 480 600 Days After Month 4 Visit No. at Risk High-High 137 128 121 91 59 35 Low-High 77 77 70 65 43 17 High-Low 330 322 292 225 161 97 Low-Low 2929 2877 2777 2539 2232 1649 Morrow, D. et al., JAMA 2005;294:2866-71.
BNP and Multivariate Risk Scores
Association of B-Type Natriuretic Peptide, in Conjunction With Cardiac Troponin, and Mortality at 30 Days Positive Results Elevated BNP in ACS Large zones of ischemia Left main lesions Severe 3-vessel disease Large infarctions Pre-existing LV impairment Systolic Diastolic N=5 N=41 N=33 Renal dysfunction McCullough PA, ACC, 2007; Neyou A, O'Neil B, Berman AD, Boura JA, McCullough PA. Determinants of markedly increased B-type natriuretic peptide in patients with ST-segment elevation myocardial infarction. Am J Emerg Med. 2010 Mar 24. Negative Results Mega J. et al., J Am Coll Cardiol 2004; 44:335-9.
Markedly Elevated BNP in ACS and Multivessel Disease BNP and the number of vessels with significant stenoses (at least one lesion >75%), p=0.0006. Neyou A, O'Neil B, Berman AD, Boura JA, McCullough PA. Determinants of markedly increased B-type natriuretic peptide in patients with ST-segment elevation myocardial infarction. Am J Emerg Med. 2010 Mar 24.
Markedly Elevated BNP in ACS and Multivessel Disease 30 BNP (pg/ml) level and mortality, p=0.004 for trend. 25 Mortality (%) 20 15 10 5 0 <500 501-1000 1001-1500 >1500 BNP (pg/ml) Neyou A, O'Neil B, Berman AD, Boura JA, McCullough PA. Determinants of markedly increased B-type natriuretic peptide in patients with ST-segment elevation myocardial infarction. Am J Emerg Med. 2010 Mar 24.
BNP at Markedly Elevated Levels and In-Hospital Mortality Why Draw BNP in the ED? Powerful Tool.
Class IIb: Measurement of B-type natriuretic peptide (BNP) or NT-pro-BNP may be considered to supplement assessment of global risk in patients with suspected ACS. (Level of Evidence: B)
Teachable Algorithm: BNP and NT-proBNP pg/ml 4000 3500 3000 2500 2000 1500 1000 500 Grey Zone egfr < 60 ml/min Cardiac Ischemia RV Source (PE/Cor Pulmonale) Sepsis McCullough, Cardiac Biomarkers, 2008 Elevated Clinical Grey Zone Age Grey Zone Normal 0 BNP NT-proBNP McCullough PA, AACC 2006
Chest Pain or Short of Breath: ACS Considered BNP Risk Stratification Algorithm ECG Normal No ischemic changes ST-segment depression ischemic T-wave changes ST-segment elevation Troponin, CK-MB (neg) Troponin, CK-MB (pos) Confirm AMI BNP Testing BNP <100 pg/ml No ACS CTA/GXT-MPI/2DE Outpatient risk Factor modification BNP <100 pg/ml Moderate Risk Usual UA/NSTEMI/STEMI Care Expect favorable outcome BNP 100-500 pg/ml High Risk Higher TIMI/GRACE score Prox LAD Plaque Rupture Older Pre-existing LV Dysfxn CKD BNP 6-12 weeks. 6-12 mos. Late HF or death BNP >500 pg/ml Very High Risk LM or 3VD Large ischemic zone Complicated PCI expected No reflow Shock Heart Failure In hospital Death BNP 6-8 weeks, 6-12 mos. Late HF or death McCullough PA, Peacock WF, O'Neil B, de Lemos JA, Lepor NE, Berkowitz R. An evidence-based algorithm for the use of B-type natriuretic testing in acute coronary syndromes Rev Cardiovasc Med. 2010;11 Suppl 2:S51-65.
Triage BNP Indications Aid in the diagnosis of heart failure Assess the severity of heart failure Risk stratification of patients with acute coronary syndromes Prognostic aid in patients with heart failure Only Triage BNP was awarded FDA clearance for risk 30 stratification in ACS.