ESCBM meeting 2018, Prague Utility of Cardiac Biomarkers in Clinical Heart Failure Care Md. Shahidul Islam, M.D., Ph.D shaisl@me.com
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Circulating Biomarkers in Heart Failure. Berezin AE. Adv. Exp. Med. Biol. 2018 Evolving Role of Natriuretic Peptides from Diagnostic Tool to Therapeutic Modality. Pagel- Langenickel I. Adv. Exp. Med. Biol. 2018 4
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Plasma BNP concentration in patients with and without left ventricular systolic dysfunction. McDonagh TA et al, 1998, Lancet 351:9
BNP and NT-pBNP Similar concentration in normal people In LV dysfunction NT-pBNP is about four times higher than BNP
Variations in the concentrations of BNP and NT-pBNP Age: Sex: BMI: Normal values increase with age Higher in women Lower in obese people 10
Cutoffs of NT-pBNP for diagnosis of HF Age < 50 years: 450 ng/l Age 50-75 years: 900 ng/l Age > 75 years: 18000 ng/l 11
Rapid measurement of BNP in rapid diagnosis of heart failure Maisel AS et al, NEJM, 2002; 347:161
Usefuleness of NT-pBNP in primary care settings Wright SP et al J Am Coll Cardiol 2003; 42:1793
Kaplan-Meier analysis of cumulative rates of survival in CHF patients with eft ventricular dysfunction stratified into two groups on the basis of median plasma concentration (73 pg/ml) of BNP. Takayoshi Tsutamoto et al. Circulation. 1997;96:509-516 Copyright American Heart Association, Inc. All rights reserved.
Plasma BNP concentration predicts survival in Heart failure patients. Anand IS et al 2003, Circulation, 107:1278
One year mortality 7% One year mortality 21.6% Hartmann F et al 2004 Circulation 110:1780
2.5 fold higher risk of death or hospitalization Hartmann F et al 2004 Circulation 110:1780
BNP or NT-pBNP? No accepted conversion factor BNP >100 ng/l is roughly equivalent to NT-pBNP > 900 ng/l for HF diagnosis NT-pBNP has greater prognostic value NT-pBNP is more sensitive to renal function NT-pBNP is useful during treatment with ARNI or neseritide NT-pBNP and BNP assays probably detect probnp
Variability of BNP and NT-pBNP Intraindividual biologic variatian and analytic assay variation Significant difference in results over time depends on the total variability (RCV percentage change, or Relative Change Value) Significant change for NT-pBNP: 11% decrease in day do day values, or 47% decrease in week to week values Significant change for BNP: 25% decrease in day do day values, or 72% decrease in week to week values Wu AH et al, Am Heart J 2006; 152:828 19
Disadvantages of BNP / NT-pBNP A high NP doesn not exclude other co-exixting diseases NPs do not increase in some acute HF Some patients with severe chronic HF have high NP Right heart failure due to lung disease or left ventricular disease have high NPs NP measurement must be combined with clinical assessment Special case for people treated with nesiritide or sacubritil 20
NT-pBNP in patients with renal failure NT-pBNP is excreted by the kidney Cut-off values in patients with GFR <60 ml/min: >1200 ng/l Cut-off values in patients with GFR >60 ml/min: >450 ng/l for patients < 50 years >900 ng/l for patients > 50 years In patients with GFR > 60, sensitivity 85%, specificity 88%; In patients with GFR <60 sensitivity 89%, specificity 72% Anwaruddin, S et al, J Am Coll Cardiol 2006; 47:91 21
Value of serial NT-pBNP guided therapy Not useful in acute HF In chronic HF the results are mixed NT-pBNP guided therapy reduces mortality in patients < 75 years. NT-pBNP guided therapy helps achieving target dose of ACE-I and beta blockers in patients < 75 years Porapakkham P et al Arch Intern Med 2010; 170:507 22
BNP (ng/l) 3000 2500 HF hospitalization 2000 1500 Worsening HF Worsening HF 1000 500 0 2010 201 3 We t Dry 201 4 201 5 201 6 201 7 Time-course of B-type natriuretic peptide levels in a patient with heart failure with reduced left ventricular ejection fraction.
Cum. Survival 1,8 Low BNP and low E/e,6,4,2 0 P < 0.0001 0 25 50 75 100 125 150 175 200 Time (months) Low BNP and High E/e High BNP and Low E/e High BNP and high E/e All-cause mortality in patients with chronic heart failure categorized according to B- type natriuretic peptide (BNP) levels and the ratio of transmitral blood flow to myocardial early diastolic velocities (E/e ). Simioniuc A et al, Int J Cardiol 2016;224:416-423
PARADIGM Study. McMurray JJ et al. NEJM 2014, 371:993 26