Admission B-Type Natriuretic Peptide Levels and In-Hospital Mortality in Acute Decompensated Heart Failure Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

Admission B-Type Natriuretic Peptide Levels and In-Hospital Mortality in Acute Decompensated Heart Failure

Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

Gregg C. Fonarow MD, FACC, William F. Peacock MD, Christopher O. Phillips MD, MPH, Michael M. Givertz MD, FACC, Margarita Lopatin MS and ADHERE Scientific Advisory Committee and Investigators

Admission BNP and In-HospitalAdmission BNP and In-HospitalMortality in ADHF Mortality in ADHF

• Levels of BNP and NT-proBNP have been shown to be elevated Levels of BNP and NT-proBNP have been shown to be elevated in patients with left ventricular (LV) dysfunction and correlate in patients with left ventricular (LV) dysfunction and correlate with the New York Heart Association functional class with the New York Heart Association functional class

• Clinical investigations of natriuretic peptides have focused on Clinical investigations of natriuretic peptides have focused on the diagnostic usefulness for heart failure (HF) and LV the diagnostic usefulness for heart failure (HF) and LV dysfunction and their prognostic usefulness in chronic HF, acute dysfunction and their prognostic usefulness in chronic HF, acute coronary syndromes, stable coronary artery disease, other coronary syndromes, stable coronary artery disease, other medical conditions, and community cohorts medical conditions, and community cohorts

• Whether plasma levels of BNP are predictive of in-hospital Whether plasma levels of BNP are predictive of in-hospital mortality risk in patients hospitalized with acute decompensated mortality risk in patients hospitalized with acute decompensated HF has not been well studiedHF has not been well studied


The ADHERE (Acute Decompensated Heart Failure National Registry) Registry

Multicenter Observational Open labelElectronic web-based

Registry of the management of patients treated in hospitals for acutely decompensated heart failure in the US

The ADHERE Registry


Initial BNP Levels in ADHERE

• Time Period: Q2 2003 – Q4 2004

• 191 out of 229 ADHERE hospitals (176 BNP only, 15 BNP and pro-BNP, 14 pro-BNP only, 24 none)

• First BNP result, within 24 hours of admission

• Results as documented in medical record

• 48,629 (63%) out of 77,467 pt episodes had BNP assessment

• Analysis by BNP quartiles, continuous, and log transformed BNP


Admission BNP and In-Hospital Mortality in ADHF

Distribution of BNP Values

(pg/mL)

48,629 (63%) out of 77,467 pt episodes had BNP assessment at initial evaluation.Only 3.3% of patients in ADHERE with initial BNP < 100 pg/mL


Admission BNP and In-Hospital Mortality in ADHF Admission BNP and In-Hospital Mortality in ADHF

• BNP QuartilesBNP Quartiles

–Quartile I: Quartile I: < 430 pg/mL< 430 pg/mL

–Quartile II: Quartile II: 430 – 839 pg/mL430 – 839 pg/mL

–Quartile III: Quartile III: 840 – 1729 pg/mL840 – 1729 pg/mL

–Quartile IV: Quartile IV: >> 1730 pg/mL 1730 pg/mL


Patient Characteristics by Quartiles of BNP Levels in the ADHERE Registry

Q1

(<430)

N=12,161N=12,161

Q2

(430-839)

N=12,146N=12,146

Q3

(840-1730)

N=12,156N=12,156

Q4

(>1730)

N=12,166N=12,166

P Value

Age 72.2 73.9 74.1 73.9 P<0.0001

Male (%) 44.5 47.2 49.3 50.6 P<0.0001

White (%) 79.5 79.4 77.5 72.4 P<0.0001

Hx HF 71.3 73.4 77.3 81.7 P<0.0001

CAD 51.8 58.7 62.3 63.4 P<0.0001

Prior MI 24.0 28.9 33.4 34.5 P<0.0001

HTN 76.1 75.6 74.7 75.1 P=0.0908

Diabetes 50.0 44.5 41.3 40.0 P<0.0001

AFib 33.8 36.2 32.5 27.8 P<0.0001

CRI Hx 20.2 26.4 32.5 44.5 P<0.0001

Dialysis 0.6 1.2 2.8 9.7 P<0.0001


Patient Characteristics by Quartiles of BNP Levels in the ADHERE Registry

Q1

(<430)

Q2

(430-839)

Q3

(840-1730)

Q4

(>1730)

P Value

SOB rest 30.3 33.9 35.0 35.1 P<0.0001

Rales 63.0 68.7 70.5 72.4 P<0.0001

SBP 145.5 145.4 142.9 141.2 P<0.0001

HR 87.2 88.0 87.9 87.3 P=0.0023

Sodium 138.2 138.1 137.8 137.6 P<0.0001

BUN 26.5 29.4 32.7 38.7 P<0.0001

Cr 1.3 1.5 1.7 2.3 P<0.0001

CXR cong 67.8 74.9 77.7 79.2 P<0.0001

LVEF 46.6 41.4 36.0 31.4 P<0.0001

% LVEF <40 29.4 42.5 57.1 69.7 P<0.0001


Patient IV Treatments by Quartiles of BNP Levels in the ADHERE Registry

Q1

(<430)

Q2

(430-839)

Q3

(840-1730)

Q4

(>1730)

P Value

Diuretic 89.8 93.5 93.9 90.3 P<0.0001

Time to Rx 7.0 hrs 6.9 hrs 6.6 hrs 6.9 hrs P=0.5311

Vasoactive 20.6 28.1 36.2 42.0 P<0.0001

Inotrope 6.2 8.3 11.6 15.1 P<0.0001

Vasodilator 16.8 23.3 29.5 33.9 P<0.0001

NTG 6.4 7.6 8.7 8.4 P<0.0001

Nesiritide 11.1 17.1 22.8 27.9 P<0.0001


Q1Q1

<430<430

N=12,161N=12,161

Q2Q2

430-839430-839

N=12,146N=12,146

Q3Q3

840-1729840-1729

N=12,156N=12,156

Q4Q4

>>17301730

N=12,166N=12,166PP Value Value

Oral MedicationsOral Medications

ACE Inhibitors (%) 53.6 56.7 57.9 55.4 <.0001

ARBs (%) 17.4 16.1 14.7 13.4 <.0001

Beta Blockers (%) 60.8 69.3 71.8 73.6 <.0001

Calcium Blockers (%) 28.8 26.8 22.3 19.8 <.0001

Digoxin (%) 28.8 33.6 35.0 34.4 <.0001

Diuretics (%) 76.3 78.6 78.0 74.6 <.0001

Peripheral Vasodilators (%) 4.7 6.7 8.1 10.5 <.0001

Warfarin (%) 29.7 31.0 26.5 23.8 <.0001


In-hospital MedicationsIn-hospital Medications


In-Hospital Mortality Risk by Initial BNP Levels in the ADHERE Registry

1.9

2.8

3.8

6

0

1

2

3

4

5

6

InH

ospi

tal M

orta

lity

Q1 (<430) Q2 (430-839) Q3 (840-1730) Q4 (>1730)

P<0.0001



BNP Quartiles

Category II vs. I III vs. I IV vs. I

Total N 12,146 vs. 12,161 12,156 vs. 12,161 12,166 vs. 12,161

Unadjusted0 1.50 (1.27-1.79) p<.0001

2.11 (1.80-2.48) p<.0001

3.41 (2.93-3.97) p<.0001

Adjusted1 1.40 (1.18-1.66) p=.0001

1.94 (1.65-2.29) p<.0001

3.17 (2.72-3.69) p<.0001

Adjusted2 1.33 (1.12-1.58) p=.0015

1.65 (1.40-1.94) p<.0001

2.34 (2.00-2.74) p<.0001

Adjusted3 1.46 (1.19-1.78) p=.0003

1.84 (1.51-2.23) p<.0001

2.74 (2.26-3.31) p<.0001

Adjusted4 1.28 (1.08-1.53) p=.0057

1.58 (1.34-1.86) p<.0001

2.23 (1.91-2.62) p<.0001

0 Area under the ROC curve (AUC)=0.62.1 Age, gender. AUC=0.66.2 Age, gender, BUN, systolic BP, creatinine. AUC=0.75.3 Age, gender, BUN, systolic BP, creatinine, LVEF<.40 or Mod./Sev. AUC=0.75.4 Age, gender, BUN, systolic BP, creatinine, sodium, pulse, dyspnea at rest. AUC=0.77.

Odds Ratios (95% CI), p-value

In-Hospital Mortality Risk by Initial BNP Levels Reduced vs. Preserved Systolic Function HF

1.4

2.8

3.8

6.4

0

1

2

3

4

5

6

7

InH

ospi

tal M

orta

lity

Q1 (<622) Q2 (622-1210) Q3 (1210-2310)

Q4 (>2310)

P<0.0001

1.5

2.7 2.8

5

0

1

2

3

4

5

InH

ospi

tal M

orta

lity

Q1 (<336) Q2 (336-630) Q3 (630-1230) Q4 (>1230)

P<0.0001

LVEF < 0.40 LVEF > 0.40


0 1000 2000 3000 4000 5000

BNP (pg/mL)

0.02

0.04

0.06

0.08

Mor

talit

y R

ate



ADMISSION TO THE ICUADMISSION TO THE ICUSTRATIFIED BY BNP QUARTILESTRATIFIED BY BNP QUARTILE

12.8

15.416.6

19.6

0

5

10

15

20

25

QI QII QIII QIV

%

P<.0001


TOTAL HOSPITAL LENGTH OF STAY TOTAL HOSPITAL LENGTH OF STAY STRATIFIED BY BNP QUARTILESTRATIFIED BY BNP QUARTILE

4.04.3 4.5

4.9

0

1

2

3

4

5

6

QI QII QIII QIV

Med

ian

Day

s

P<.0001


Patient Outcomes by Quartiles of BNP Levels in the ADHERE Registry

Q1

(<430)

Q2

(430-839)

Q3

(840-1730)

Q4

(>1730)

P Value

Ventilation 3.1 3.7 3.9 4.1 P=0.0002

CPR 0.6 0.9 1.2 1.7 P<0.0001

Ultrafiltrat 0.6 0.8 1.6 5.0 P<0.0001

LOS (days) 5.2 5.7 5.9 6.3 P<0.0001

ICU admit % 12.8 15.4 16.6 19.6 P<0.0001

ASx at DC 48.8 49.6 48.0 43.6 P<0.0001



Study LimitationsStudy Limitations

• Data collected from chart review which is dependent on Data collected from chart review which is dependent on the accuracy and completeness of documentation and the accuracy and completeness of documentation and abstractionabstraction

• This “real world” study used results of various This “real world” study used results of various commercially available BNP assays vs. results from commercially available BNP assays vs. results from single central core laboratorysingle central core laboratory

• Individual hospitalization episodes vs. individual unique Individual hospitalization episodes vs. individual unique patients patients

– Each hospitalization represents unique opportunity to either Each hospitalization represents unique opportunity to either survive or not survive.survive or not survive.


Admission BNP and In-HospitalAdmission BNP and In-HospitalMortality in ADHF Mortality in ADHF

• Elevated admission BNP is a significant predictor of in-Elevated admission BNP is a significant predictor of in-hospital mortality in ADHF, independent of other risk hospital mortality in ADHF, independent of other risk factorsfactors

• BNP is predictive of mortality in both patients with reduced BNP is predictive of mortality in both patients with reduced and those with preserved LVEFand those with preserved LVEF

• Further research necessary to determine whether pts with Further research necessary to determine whether pts with higher admission BNP would benefit from more intensive higher admission BNP would benefit from more intensive monitoring and/or aggressive treatment strategiesmonitoring and/or aggressive treatment strategies


AcknowledgmentsAcknowledgments

The ADHERE Scientific Advisory The ADHERE Scientific Advisory Committee and InvestigatorsCommittee and Investigators

Documents

Admission B-Type Natriuretic Peptide Levels and In-Hospital Mortality in Acute Decompensated Heart Failure Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950