A Guide to Proper Utilization of Biomarkers

Transcription

1 A Guide to Proper Utilization of Biomarkers DR. ABEER BAKHSH CONSULTANT CARDIOLOGIST, ADVANCE HEART FAILURE KING FAHD ARMED FORCES HOSPITAL JEDDAH, SAUDI ARABIA

2 Objective: Mechanism of myocardial injury and Characteristics of Biomarkers Evidence on B-Natriuretic Peptides (BNP) Clinical Pearls and Guidelines on The Use of Biomarkers

3 Definition of a Biomarker: National Institutes of Health (NIH): a biological marker that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes, or pharmacological responses to therapeutic interventions. World Health Organization (WHO): a substance, structure, or process that can be measured in the body or its products and influences or predicts the incidence of outcome or disease.

4 Criteria of a Clinically Useful Biomarker: Reproducible Accurate Rapid turnaround time Cost is reasonable Assist decision making Provide novel information that are not available by other tests

5 Mechanism and Response to Injury in Heart Failure AHA Scienticfic Statement Circulation. 2017;135:e1054 e1091

6 Mechanism and Response to Injury in Heart Failure Natriuretic Peptides (Myocardial stress) Troponin (Myocardial necrosis) CRP (inflammation) Copeptin (Neurohormonal activation) MRproADM (Vascular stress) sst2 (Myocardial remodeling and fibrosis) galactin-3 (Myocardial remodeling and fibrosis)

7 B-Natriuretic Peptide B- natriuretic peptide is released in the circulation in burst in response to myocardial stress. Pre-ProBNP breaks into ProBNP, cleaved by proteolytic enzymes to BNP and NTproBNP. NTproBNP is the amino acid equivalent of BNP. BNP is excreted by the kidney while NT probnp by the Kidney, liver and muscles. BNP half-life 20min, Half-life NT probnp 120min.

8 B-Natriuretic Peptide BNP sensitivity 90% and specificity 76% at value of > 100pg/ml. NTproBNP has a similar value of sensitivity and specificity at a cut off of > 300pg/ml. Age variation NTproBNP < 50y: 450 pg.ml 50-75y: 900 pg/ml > 75y: 1800 pg/ml

9 B-Natriuretic Peptide Level Confounders AHA Scienticfic Statement Circulation. 2017

10 Evidence on The Use of BNP At risk of HF Acute HF Hospitalization Pre- Discharge Chronic Ambulatory HF Guided Therapy Diagnosis In hospital events Readmission Prognosis Decompensatio n OMT STOP HF PRIDE ADHERE CORONA OPTIMIZE HF TIME-HF PROTECT BATTLESCARRED GUIDE-IT

11 AHF In hospital mortality correlated with level of BNP. ADHERE study there was 1.9% vs 6% mortality in low vs high quartiles of BNP. In ADHERE BNP level > 840 ng/ml was associated with more ICU admission, prolonged ventilation and increased length of stay. Pre-discharge BNP at discharge is a predictor of 1 year mortality and hospitalization. BNP < 430 ng/ml was associated with less likelihood of readmission at 30 days. Mortality Each 100 pg/ml in BNP is associated with 35% increase in relative risk of death in chronic ambulatory HF.

12 Evidence on The Use of BNP Optimizing medical therapy is the main objective of heart failure clinic. The target dose of OMT and response to treatment is currently based on clinical assessment, NYHA and Qol. Since biomarkers can identify patient at risk/in decompensated HF then it can be used in guiding treatment. Is there enough evidence on this?

13 Evidence on The Use of BNP PROTECT trial: Single center prospective randomized trial, included LVEF 40% with NYHA II-IV. Excluded patients with renal impairment. Target NT-proBNP 1000 ng/ml. Endpoints were cardiovascular events ( decompensated HF, arrhythmia, ACS, CVA, death). The Study was stopped at 150 patients with target being 300 patients. Januzzi et.al JACC, 2011

14 Evidence on The Use of BNP PROTECT TRIAL Januzzi et.al JACC, 2011

15 THE MEAN CHANGE IN DOSAGE OF GUIDELINE DIRECTED MEDICAL THERAPY PROTECT TRIAL Januzzi et.al JACC Vol. 58, No. 18, 2011.

16 Evidence on The Use of BNP STAR-BNP: Multicenter trail, randomized trial, included HF patients with LVEF 45%, NYHA II-IV, stable dosage of therapy for 1 month prior to inclusion. Excluded patients with chronic renal impairment, recent ACS or hepatic dysfunction. Patients were randomized to Clinical Group and BNP Group with BNP cut off set at BNP < 100 pg/ml. Primary end point was HF related Hospitalization, HF related death. Jourdain et al. JACC Vol. 49, No. 16, 2007

17 STAR- BNP Primary end point was HF related Hospitalization, HF related death. BNP group 25/110 (24%). Clinical group 57/110 (52%) p Jourdain et al. JACC Vol. 49, No. 16, 2007

18 Jourdain et al. JACC Vol. 49, No. 16, 2007

19 GUIDE-IT RCT 1100 stopped at 894 Higher risk HF patients HFrEF EF < 40% Hospitalization within 12 month ER visit within 12 month Treated with IV diuretic within 12 month BNP > 400 ng/ml, NT ProBNP > 2000 within 30 days of randomization Intervention BNP or NT ProBNP guided treatment compared with standard of care Target level of NTProBNP < 1000 Endpoint The composite of time-to-first HF hospitalization or cardiovascular mortality. Felker et al JAMA 2017

20 Felker et al JAMA 2017

21 Felker et al JAMA 2017

22 Felker et al JAMA 2017

23 HEART FAILURE SOCIETIES RECOMMENDATION ON BIOMARKERS UTILIZATION

24 2017 ACC/AHA/HFSA HF guideline update,jacc

25 2017 Canadian HF guideline, CJC

26 Clinical Pearls Chronic HF in ambulatory care: Check biomarkers when it supports your clinical decision making. Rise of > 30% from baseline supports decompensated HF. The most benefit is for patients < 75years. Hospitalized HF Care: Pre-discharge BNP reduction < 30% from admission Pre-discharge BNP strong predictor of mortality