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Assessing Congestion in HF : Natriuretic Peptides
- 1. Assessing Congestion in HF: Natriuretic Peptides Michael Felker, MD, MHS, FACC, FAHA Professor of Medicine Chief, Heart Failure Section Duke University School of Medicine
- 2. Vicious Cycle of Congestion in AHF Worsening heart failure Elevated LVEDP Increased wall stress Myocardial Oxygen demand Myocardial ischemia Increased functional MR CONGESTION
- 3. “If you wish to converse with me, define your terms.” Voltaire
- 4. Congestion • All agree that it is important • All agree that addressing it is key to success • What is it exactly? – Clinical congestion (rales, JVP, edema)? – Hemodynamic congestion (elevated filling pressures)? – Something else (fluid loss, body weight change, NP’s)?
- 5. Pharmacologic Actions of hBNP Hemodynamic (balanced vasodilation) veins arteries coronary arteries Neurohumoral aldosterone endothelin norepinephrine Renal diuresis natriuresis GFR D R I M K R G S S S S G L G F C CS S G SGQVM K V L R R H KPS Cardiac lusitropic antifibrotic anti-remodeling
- 6. BNP Correlates (Loosely) with LV Filling Pressures Kazanegra J, Cardiac Failure 2001 PAW(mmHg) Hours BNP(pg/ml) 15 17 19 21 23 25 27 29 31 33 baseline4 8 12 16 20 24 600 700 800 900 1000 1100 1200 1300 PAW BNP *Pulmonary artery wedge.
- 7. BNP Reflects Ventricular Wall Stress Iwananga, JACC
- 8. Natriuretic Peptides Represent a “Myocyte Level” View of Congestion Help!
- 9. Maisel AS et al. N Engl J Med. 2002;347:161-167. 1.0 0.8 0.6 0.4 0.2 0.0 0.0 0.2 0.4 0.6 0.8 1.0 1-Specificity Sensitivity Final Diagnosis Heart Failure Final Diagnosis NOT Heart Failure BNP 100 pg/mL “Test positive” 673 227 BNP <100 pg/mL “Test negative” 71 Sensitivity =90% 615 Specificity =73% Positive predictive value=75% Negative predictive value=90% BNP=50 pg/mL BNP=80 pg/mL BNP=100 pg/mL BNP=150 pg/mL BNP=125 pg/mL Natriuretic Peptides for Diagnosis Optimal cut-off point determined @ 100 pg/mL Maisel AS et al. N Engl J Med. 2002;347:161-167.
- 10. Natriuretic Peptides and Prognosis in Chronic HF: Data from Val-HeFT Anand, I. et al, Circ 2003
- 11. Predischarge BNP Is Strong Predictor of Post- Discharge Events 0 25 50 75 100 0 30 60 90 120 150 180 DeathorReadmission,% Follow-up, Days Hazard Ratios 15.2 5.1 1 p<.0001 p<.0001 BNP >700 ng/L* (n = 41, events = 38) BNP 350-700 ng/L* (n = 50, events = 30) BNP <350 ng/L* (n = 111, events = 18) Logeart D, et al. J Am Coll Cardiol. 2004;43:635-641.
- 12. Change in NTproBNP and Outcomes Masson, JACC 2008
- 13. Kociol R et al, Circ HF 2013
- 14. Biomarker Guided Therapy and All-Cause Mortality: Meta-Analysis Combined BATTLESCARRED STARS-BNP STARBRITE Troughton TIME-CHF PRIMA Felker GM. Am Heart J 2009 N = 1627 Adjusted HR = 0.69 (0.55-0.86)
- 15. High Risk Systolic HF Patient LVEF ≤ 40 within 12 months HF event within 12 mos (HF hosp, ER visit, or outpt IV diuretic) NTproBNP > 2000 pg/mL within last 30 days Usual Care N= 550 Primary endpoint: Time to CV death or first HF hospitalization Secondary Endpoints: All-cause mortality Total days alive and out of hospital during follow-up CV mortality or CV hospitalization Safety Health related quality of life Resource utilization, costs, cost-effectiveness Biomarker Guided NTproBNP < 1000 pg/mL N=550 Follow up: 2 wks, 6 wks, 3 months, then Q3 month for 12-24 mos Screening Randomization Follow-up Endpoints Additional 2 week follow up after changes in therapy
- 16. Ambulatory/Outpatient In ambulatory patients with dyspnea, measurement of BNP or N-terminal pro-B-type natriuretic peptide (NT- proBNP) is useful to support clinical decision making regarding the diagnosis of HF, especially in the setting of clinical uncertainty. Measurement of BNP or NT-proBNP is useful for establishing prognosis or disease severity in chronic HF. I IIa IIb III I IIa IIb III
- 17. Hospitalized/Acute Measurement of BNP or NT-proBNP is useful to support clinical judgment for the diagnosis of acutely decompensated HF, especially in the setting of uncertainty for the diagnosis. Measurement of BNP or NT-proBNP and/or cardiac troponin is useful for establishing prognosis or disease severity in acutely decompensated HF. I IIa IIb III I IIa IIb III
- 18. Advantages of Natriuretic Peptides as Measures of Congestion • Quantitative • Reproducible across time and across providers • Does not require high level of expertise • Non-invasive • Cheap (relatively) • Supported by guidelines with highest level of recommendation
- 19. Biomarkers Always Augment Clinical Judgment • Impacted by – Age – Gender – Renal function – Atrial fibrillation – Obesity – HFpEF vs. HFrEF
- 20. Greater Decongestion = Better Outcomes Kociol et al, Circ HF 2013 • Drop in NT- proBNP • Change in weight • Net fluid loss
- 21. Conclusions • Natriuretic peptides represent a quantitative, reproducible assessment of myocyte wall stress – Best marker for making diagnosis of HF – Correlate with symptoms – Correlate with outcomes – Change with favorable change in clinical course – Failure to improve with treatment identifies very high risk patients – ? Potential target for adjusting therapy