BNP in Diastolic Heart Failure Jon Wilson Mercer Pharm D Candidate C/O 2012

What is diastolic heart failure? Ventricles become relatively “stiff” and can not fully relax during diastole. As a result, ventricles may not fill completely and blood can “dam up” in the body’s organs (mainly the lungs).

Diastolic Heart Failure Signs/Symptoms of heart failure but preserved left ventricular systolic function(EF>45%) Maybe asymptomatic too Incidence increases with age 50% of older patients with heart failure may have isolated diastolic dysfunction With early diagnosis and proper management, prognosis of diastolic dysfunction is more favorable than systolic

Diastolic Heart Failure Cardiac catheterization remains preferred method for diagnosis. However, in practice, 2-D echocardiography with Doppler is best noninvasive tool. Doppler identifies abnormal LV diastolic filling dynamics.

Diastolic Heart Failure

Pharmacologic Therapies ACE-inhibitors ARBS Diuretics Beta Blockers

B-type Natriuretic Peptide(BNP) Causes natriuresis and vasodilation Inhibit the renin-angiotensin system BNP is stored in heart tissue Released into the blood in response to increased wall stress caused by ventricular pressure and volume overload

Why BNP released during diastole? Some theories… Patient’s impaired relaxation may have abnormally high loading pressures during stress, resulting in elevated resting BNP levels LV hypertrophy in the absence of ventricular pressure overload. BNP plasma levels increase with age.

BNP LV systolic dysfunction is associated with higher BNP levels than is diastolic dysfunction Patients with isolated LV diastolic dysfunction will usually have BNP levels between 300 and 480 pg per mL, whereas patients with LV systolic dysfunction usually have BNP levels between 550 and 820 pg per mL. BNP by itself does not differentiate between systolic and diastolic heart failure

BNP as a marker of diastolic dysfunction in the general population: Importance of left ventricular hypertrophy T.V. Lukowicz, M.Fischer, H.W. Hense, A. Doring, J. Stritzke, G.Riegger, H. Schunkert, A.Luchner. The European Journal of Heart Failure 7 (2005)

Objective To assess BNP for the detection of diastolic dysfunction in the general population.

Study Data from MONICA Augsburg study Echos performed on 1678 patients BNP measurements on 1438 patients Only subjects with sinus rhythm were evaluated for Doppler of diastolic function 1123 patients had both parameters for diastolic function and BNP

Results

BNP with diastolic dysfunction 20.3+/-4.7pg/ml vs. control 9.6+/-0.5pg/ml BNP with diastolic dysfunction and LV hypertrophy 37.3+/-49.1pg/ml vs. control BNP with LV systolic dysfunction 76.2+/-23.2pg/ml vs. control

Conclusion The increased BNP concentrations in patients with diastolic dysfunction was related to LV hypertrophy. Can not recommend screening for diastolic dysfunction with BNP Normal BNP can possibly rule out diastolic dysfunction and LV hypertrophy

Level of Evidence

BNP and NT-proBNP predict echocardiographic severity of diastolic dysfunction Jasmine Grewal, Robert MCKelvie, Eva Lonn, Peter Tait, Jonas Carlsson, Monica Gianni, Christina Jarnert, Hans Persson. European Journal of Heart Failure 10(2006)

Objective To assess the best combination of clinical parameters and BNP or NT-proBNP to predict diastolic dysfunction in heart failure(HF) with preserved left ventricular ejection fraction(HF- PLEF) as determined by Doppler-Echo.

Study HF patients with EF>40% in the CHARM Echo Substudy were included Patients classified as Normal diastolic function Mild diastolic function(relaxation abnormality) Moderate diastolic function(pseudonormal) Severe diastolic function(Restrictive abnormality)

Results Table 2 Univariate predictors of moderate/severe diastolic dysfunction Variable OR (95% CI) Area under ROC-curve (CI) p NT-proBNP>600 pg/ml 7.4 (3.4-16).74 ( ) < NT-proBNP>300 pg/ml 2.2 ( ).67 ( ) 0.01 BNP>100 pg/ml 4.9 ( ).72 ( ) < LAVI>28 ml/m2 4.4 ( ).68 ( ) History of atrial fibrillation 2.5 ( ).67 ( ) History of diabetes mellitus 2.2 ( ).66 ( ) History of coronary artery disease 1.1 ( ).62 ( ) 0.35 History of hypertension 1.0 ( ).62 ( ) 0.21 BMI>30 kg/m2 0.8 ( ).62 ( ) 0.29 Heart rate (beats/min) 0.99 ( ).55 ( ) 0.30 ACE-Inhibitor therapy 1.1 ( ).51 ( ) 0.79 Beta blocker therapy 0.74 ( ).53 ( ) 0.32 Diuretic therapy 1.6 ( ).55 ( ) 0.17 Creatinine (μmol/L)b 3.8 ( ).63 ( ) 0.004

Conclusion High levels of natriuretic peptides are the most powerful predictors in diagnosing moderate/severe DD in patients with HF-PLEF as compared to other clinical variables. Natriuretic peptides can provide evidence of prognostically important DD in HF-PLEF.

Level of Evidence

Utility of B-Natriuretic Peptide in Detecting Diastolic Dysfunction Emily Lubien, BS; Anthony DeMaria, MD; Padma Krishnaswamy,MD; Paul Clopton, MS; Jen Koon, BSN; Radmila Kazanegra, MD; Nancy Gardetto,NP; Erin Wanner,BS; Alan S. Maisel,MD. Circulation 2002, 105:

Objective To determine if BNP levels can predict diastolic abnormalities in patients with normal systolic function, comparing with Doppler Echo readings.

Study 294 patients referred for echo Cardiologist making assessment of LV function were blinded to BNP levels Classified as Normal Impaired relaxation Pseudonormal Restrictive like filling patterns

Results Mean BNP Levels Normal(n=175) 33+/-3pg/mL Abnormal(n=119) 286+/- 31pg/mL Restrictive like filling patterns had highest levels at 408+/- 66pg/mL Patient’s with symptoms had even higher BNP levels.

Results

Conclusion A rapid assay for BNP can reliably detect the presence of diastolic abnormalities on echocardiography, which may reinforce diagnosis diastolic dysfunction.

Level of Evidence

Agreement between studies BNP can not accurately diagnose diastolic heart failure alone. Measuring of BNP makes a great compliment tool with a Doppler reading to help better predict moderate/severe diastolic heart failure in HF-PLEF.

References T.V. Lukowicz, M.Fischer, H.W. Hense, A. Doring, J. Stritzke, G.Riegger, H. Schunkert, A.Luchner. BNP as a marker of diastolic dysfunction in the general population: Importance of left ventricular hypertrophy. The European Journal of Heart Failure 7 (2005) Jasmine Grewal, Robert MCKelvie, Eva Lonn, Peter Tait, Jonas Carlsson, Monica Gianni, Christina Jarnert, Hans Persson. BNP and NT-proBNP predict echocardiographic severity of diastolic dysfunction. European Journal of Heart Failure 10(2006) Emily Lubien, BS; Anthony DeMaria, MD; Padma Krishnaswamy,MD; Paul Clopton, MS; Jen Koon, BSN; Radmila Kazanegra, MD; Nancy Gardetto,NP; Erin Wanner,BS; Alan S. Maisel,MD. Utility of B- Natriuretic Peptide in Detecting Diastolic Dysfunction. Circulation 2002, 105: CHHABI SATPATHY, M.D., TRINATH K. MISHRA, M.D. Diagnosis and Management of Diastolic Dysfunction and Heart Failure. Am Fam Physician Mar 1;73(5):