Strategies for Diagnosis, Risk Stratification and Treatment of the Acutely Decompensated Heart Failure Patient John H. Burton, MD Residency Program Director

Strategies for Diagnosis, Strategies for Diagnosis, Risk Stratification and Treatment Risk Stratification and Treatment

of the Acutely Decompensated of the Acutely Decompensated Heart Failure PatientHeart Failure Patient

John H. Burton, MD

Residency Program Director

Dept. Emergency Medicine

Albany Medical Center

[email protected]

Heart FailureHeart Failure

Approximately 5 million Americans have CHF (male to female ratio 1:1)

Incidence of 10/1000 > 65 years of age 550,000 new cases/year Hospital discharges 1,000,000 (2001) Single largest expense for Medicare Five-year mortality rate as high as 50%

AHA. 2001 Heart and Stroke Statistical Update

Heart Failure HospitalizationsHeart Failure Hospitalizations

0

100,000

200,000

300,000

400,000

500,000

600,000

Dis

char

ges

Women

Men

AHA, 1998 Heart and Statistical UpdateNCHS, National Center for Health Statistics

The number of heart failure hospitalizations is increasing in both men and women

CDC/NCHS: Hospital discharges include patients both living and dead.AHA Heart and Stroke Statistical Update 2001

Hospital Visits for Congestive Heart FailureHospital Visits for Congestive Heart Failure

Initial Episode 21%

Repeat Visit 79%

Rates of Hospital Readmission 2% within 2 days 20% within 1 month 50% within 6 months

Approximately 85% of the ED visits for CHF

result in hospitalizations

Cardiology Roundtable 1998

A brief discussion of the works of this thing...

The Pump:

1. A Mechanical Component

2. An ElectricalComponent

1. A Mechanical Component

2. An ElectricalComponent

65%

PUMPS LESS!!!

FILLS LESS!!!

Filling….Pumping

Problems with Filling...

Problems with Pumping...

PumpingJust how little

pumping can one get away with?

Normal - 65%No Symptoms - 40-65%Lethargy, less exercise tolerance - 30-45%Shortness of breath - 20 - 30%Incompatible with life - <15%

Etiology of Acute Heart Failure

Hypertension Ischemia Sustained Arrhythmias Cardiomyopathy

EtOH, infiltrative Valvular Heart Disease Pericardial Disease

Approximately1/4th

Diastolic Dysfxn

AFTERloadPREload Contractility

PREload

AFTERload

Contractility

DEFINITION CHFDEFINITION CHF

E. BraunwaldE. Braunwald

“The situation when the heart is incapable of maintaining a cardiacoutput adequate to accommodatemetabolic requirements and the venous return.”

Venous

Legs swell

Neck veins distend

Liver congestion

Lung congestion

Arterial

Decreased perfusion….

BrainKidneys

Everything...

CHF: Diagnosis

CHF is a CLINICAL diagnosis

History Physical Exam Chest X Ray EKG Echocardiogram Laboratory testing

How do you know an ED pt has Heart Failure?

CHF: a CLINICAL diagnosis History Physical Exam Chest X Ray Echocardiogram Laboratory testing

…. Shortness of Breath!!! ; Leg edema; weakness

…. Legs: Edema; Lungs: Rales

Accuracy of Diagnosis: CHF

EMS : 50-65%

Emergency Doc: 65-80%

Cardiologist: 80-85%


1

11.1

2.72.2

10.7

2.9

1.9

0

2

4

6

8

10

12

OR

Predictor

AgeHx CHFHx MIRalesCeph XREdemaJVD

NEJM 02;347:161-167

OR’s for differentiating between patients with and those without CHFOR’s for differentiating between patients with and those without CHF

Ask 3 Questions:1. History of Congestive Heart Failure?

2. RALES on Lung Examination?

3. EDEMA to Legs?

IN The Emergency Department: Do a Chest XRay


Emergency Department

Spectrum of Heart Failure

AsymptomaticAsymptomaticCHFCHF

Dyspnea Dyspnea on on

exertionexertion

Cardiogenic Cardiogenic ShockShock

Pulmonary Pulmonary EdemaEdema

PND and PND and orthopneaorthopnea

Dyspnea at restDyspnea at rest

ModerateModerate

Natriuretic Peptides: Origin and Stimulus of ReleaseNatriuretic Peptides: Origin and Stimulus of Release

Peptide Primary Origin Stimulus of Release

ANP Cardiac atria Atrial distension

BNP Ventricular myocardium Ventricular overload

CNP Endothelium Shear stress of endothelium

Adapted from Burnett JC, J Hypertens 2000;17(Suppl 1):S37-S43

ANP = Atrial Natriuretic PeptideBNP = B-type Natriuretic PeptideCNP = C-type Natriuretic Peptide

Adapted from Burnett JC, J Hypertens 1999;17(Suppl 1):S37-S43

RAAS (Renin-Angiotensin Aldosterone System)

Activation of AT1 receptorsby angiotensin II

VasoconstrictionSodium retentionIncreased aldosterone releaseIncreased cellular growthIncreased sympathetic nervous activity

NPS (Natriuretic Peptide System) ANP, BNP Vasodilation

Sodium excretionDecreased aldosterone levelsInhibition of RAASInhibition of sympathetic nervous activity

CNP VasodilationDecreased vascular smooth muscle growthDecreased aldosterone levels

BNP Levels of 250 Patients Presenting with DyspneaBNP Levels of 250 Patients Presenting with Dyspnea

Mea

n B

NP

C

once

ntr

atio

n (

pg/

ml)

AsymptomaticLV Dysfunction

No CHF(n=14)

38 ± 4141 ± 31

1076 ± 138

No CHF(n=139)

CHF(n=97)

0

200

400

600

800

1000

1200

1400

Maisel A. et al. J Am Coll Cardiol 2001;37(2):379-85

P < 0.001

BNP Concentration for the BNP Concentration for the Degree of CHF SeverityDegree of CHF Severity

BN

P C

once

ntr

atio

n (

pg/

ml)

186 ± 22

791 ± 165

2013 ± 266

Mild(n=27)

Moderate(n=34)

Severe(n=36)

0

500

1000

1500

2000

2500

Maisel A. et al. J Am Coll Cardiol 2001;37(2):379-85

BNP Concentration for the BNP Concentration for the Prediction of Clinical EventsPrediction of Clinical Events

Harrison, Maisel Ann Emerg Med 2002;39:131-138

0 20 40 60 80 100 120 140 160 1800%

5%

10%

15%

20%

25%

30%

35%

40%

45%

BNP < 230 pg/ml

BNP 230-480 pg/ml

BNP > 480 pg/ml

Death or Heart Failure Hospitalization

Days

Rapid Measurement of BNP in Emergency Diagnosis of Heart Failure

Multinational study at 7 centers: Baseline BNP-1586 ED dyspnea pts vs clinical judgment

Mea

n B

NP

C

once

ntr

atio

n (

pg/

ml)

Dyspnea due tononcardiac in pt

with hx ofLV dysfunction

(n=72)

No CHF(n=770)

CHF(n=744)

0

200

400

600

800

1000

1200

1400

Maisel A. et al. NEJM 02;347:161-167

1

11.1

2.7 2.2

10.7

2.91.9

29.6

0

5

10

15

20

25

30

OR

Predictor

AgeHx CHFHx MIRalesCeph XREdemaJVDBNP>100

NEJM 02;347:161-167

OR’s for differentiating between patients with and those without CHFOR’s for differentiating between patients with and those without CHF

BNP IntegrationBNP Integration-Diagnostic:-Diagnostic:

CHF vs COPDCHF vs COPD

-CHF Risk -CHF Risk Stratification:Stratification:

mild, mod, severemild, mod, severedispositiondispositionmortalitymortality

-Therapeutic -Therapeutic Decision-MakingDecision-Making

change therapychange therapycease therapycease therapy

0

100

200

300

400

500

600

700

800

900

1000

No Heart Failure, No Ventricle Stretch

400400 400

100 100 100

Mild Ventricle Stretch: HF, PE, CM, ACS, Pulm HTN

Significant Decompensated Heart Failure

Mea

n B

NP

C

once

ntr

atio

n (

pg/

ml)

Interpretation of the BNP Assay in the Dyspneic Patient

BNP Precision Studies (Assigned Value = 103)

60

70

80

90

100

110

120

1 2 3 4 5 6 7 8 9 10

10 Replicates on Two Different DaysDay 1 Mean = 95.8Day 2 Mean = 85.1

Mean + 2 SD = 66 - 115

BNP CorrelationsMMC vs Hartford

0

200

400

600

800

1000

1200

1400

0 200 400 600 800 1000 1200 1400

You’ll also hear about Pro-BNP

Pro-BNP is the BNP precursor. It is

degraded in the liver - bnp is a

product and is ultimately cleaved

by neutral peptidase: no renal or hepatic effects

DR I

MKRG

S SS

SGLG

FC

CS S

GSGQVM

K V L RR

H

KPS



3. EDEMA to Legs?


Shoot a Chest Xray

Run a BNP level

Current Current Treatment of Treatment of Acute Heart Acute Heart

FailureFailure

Current Treatment of Acute Heart FailureCurrent Treatment of Acute Heart Failure

Diuretics

Reducefluid

volume

Vasodilators

DecreasePreload

AndAfterload

Inotropes

AugmentContract-

ility

Heart Failure GuidelinesHeart Failure Guidelines

1. ACC/AHA Task Force on Practice Guidelines. 2001

1. ACC/AHA Task Force on Practice Guidelines. 1995

2. Working Group for Heart Failure of the European Society of Cardiology. 1997

3. Advisory Council To Improve Outcomes Nationwide in Heart Failure. (ACTION – HF) 1999

4. HFSA Guidelines for Management of Patients With Heart Failure Caused by Left Ventricular

Systolic Dysfunction - Pharmacological Approaches. 1999

Focus on… Omit…

Stable outpatients Criteria for admission to hospital

Systolic dysfunction Tailored hemodynamic treatments

Decompensated patients

1. Circulation 1995;92:2764-2784, 2. Eur Heart J 1997;18:736-753, 3. Am J Cardiol 1999;83(2A):1A-38A, 4. Journal of Cardiac Failure 1999;5:357-382

Current Treatment of Acute Heart FailureCurrent Treatment of Acute Heart Failure

Diuretics

Reducefluid

volume

Vasodilators

DecreasePreload

AndAfterload

Inotropes

AugmentContract-

ility

Lasix Dopamine

LasixNtg: sl, top, iv

MSO4ACEi

BiPAP

Expose the Literature...Expose the Literature...

0 6 12 18 24Months

0

10

20

30

40

50

60

Total Mortality Risk%

199

257

PCW > 16 mmHg

PCW < 16 mmHg

P=0.001

0 6 12 18 24Months

0

10

20

30

40

50

60

Total Mortality Risk%

236

220

Cardiac Index > 2.6 L/min-M2

Cardiac Index < 2.6 L/min/M2

Early Response of PCW but not CI Predicts Early Response of PCW but not CI Predicts Subsequent Mortality in Advanced Heart FailureSubsequent Mortality in Advanced Heart Failure

Fonarow Circulation 1994;90:I-488

P=NS

You’ve also got You’ve also got to look at to look at symptom symptom

improvement...improvement...

Let’s Start with the Let’s Start with the Ntg vs. Lasix DebateNtg vs. Lasix Debate

Increasing dose of nitroglycerin

VEINS

Arteries

Historical Comparison for PCWP

-10

-8

-6

-4

-2

0

2

0 30 60 90

Lasix 1mg/kg

Ntg 0.83mcg/kg/minHydrzn 0.15mg/kg

J Cardiovasc Pharmcol 1987. 10(1):38-46

n = 48 “acute severe ht. failure” pts

Historical Comparison for PCWP

-10

-8

-6

-4

-2

0

2

0 30 60 90 Lasix 1mg/kg

Ntg 0.83mcg/kg/minHydrzn 0.15mg/kgPlac VMAC

Ntg VMAC

Nestd VMAC

J Cardiovasc Pharmcol 1987. 10(1):38-46

Conclusion 1:

Ntg better than LasixHi dose Ntg better than lo dose

Morphine?? Hoffman. Chest 1987;92:586-593.

“Adverse effects were found only in patients who received morphine.” (4 tx groups, 57 patients)

Cohen. Am J Emerg Med 2000;18:342-3.“Assertions that the use of MS in the tx of ACPE is appropriate or inappropriate are opinion only and not scientifically established.”

Sacchetti. Am J Emerg Med 1999;17:571-574.

“Morphine sulfate’s use in acute pulmonary edema is difficult to justify based on the data in this and other studies. Its use resulted in higher intubation rates, ….and consequently higher ICU admission rates.”

0

0.5

1

1.5

2

2.5

3

3.5

%

OR for ICU Admit

MIAgeCaptoprilNTGMSDiuretic

95% Conf IAm J Emerg Med 99;17:571-574: 181 pts

0

1

2

3

4

5

6

%

OR for ETI

MIAgeCaptoprilNTGMSDiuretic

95% Conf IAm J Emerg Med 99;17:571-574: 181 pts

Conclusion 2:

Very little data on MSO4

MSO4 likely bad or at least, redundant to preload

Sedation and Resp Failure?

Acute ACE therapy Routes and selected agents are diverse: PO/SL/IV; Captopril,

Lisinopril, Enalapril….etc…..

Barnett: Current Ther Research 1991. 49:274-281. Report of 7 patients with Acute L heart failure given 12.5 or 25 mg SL

Captopril q 30 minutes x 3: Significant PCWP reductions (25 -> 19 in 60 minutes) without large drops in BP, also documented substantial reductions in subjective orthopnea scores: “SL administered captopril provides..rapid serum conc, balanced vasodilation, and inhibition of Angiotensin II…and does not affect systemic BP in a deleterious manner.”

Acute ACE therapy Haude: Intern Jour Cardiol 1990. 27:351-359.

Randomized cross-over design of 25 patients with Acute L heart failure given 25 mg SL Captopril or 0.8 mg SL Ntg: Significant PCWP reductions without large drops in BP: “SL administration of captopril was superior to nitroglycerin for some parameters. The temporal hemodynamic changes revealed an earlier start of action after nitroglycerin, but a later maximum and a longer persistance after captopril.”

Langes: Current Ther Research 1993. 53:167-176. Report of 13 patients with Acute L heart failure given IV continuous

infusion of Captopril: Significant PCWP reductions (more rapid than SL reports) without large drops in BP, also documented substantial reductions in ACE and aldosterone, although plasma renin increased.

Acute ACE: A RCT in the ED!!!

SL Captopril 12.5 mg vs Placebo

Acad EM 1996. 3:205-212

pts with APE Placebo = 25

Captopril = 23

Baseline treatment = 2mg increments MSO4 + 40mg min. lasix + sl Ntg +/- IV Ntg

Primry Outcome: Placebo vs Captpl

0

10

20

30

40

50

60

70

80

90

100

PlaceboCaptopril

APEXScore

Acad EM 1996. 3:205-212

* = Stat Sig

Minutes after Treatment

**

APEX Score (nonvalidated): 1. Deg of orthopnea tolerance2. Pt.-reported dyspnea3. Observer-reported dyspnea4. Observer-reported diaphoresis(conv score as % of time zero)

Acute ACE: Other Outcomes:SL Captopril 12.5 mg vs Placebo

20

36

9

26

0102030405060708090

100

ETI MI

Placebo

Captopril

Acad EM 1996. 3:205-212

%

No Statistical Differences in Any Groups

Conclusion 3:

ACE acute therapy may be good

No reason to see it as harmful

One more One more to go:to go:

the NVS the NVS questionquestion

BiPAP or CPAP?? Multiple small case reports of Noninvasive

Ventilatory Support (NVS) in patients with varying diagnoses of respiratory failure.

No assessment of hemodynamic findings in a controlled fashion.

BiPAP vs CPAP?? Mehta. Crit Care Med 1997;25:620-628.

One small study raising concern for BiPAP-associated AMI in pulmonary edema patients, compared to CPAP. 27 pts randomized with more rapid improvements in dyspnea and oxygenation associated with BiPAP: BiPAP and CPAP good, BiPAP = MI

Kosowsky. Am J Emerg Med 2000;18:91-95. Good review of literature to date on Noninvasive Ventilatory Support (NVS).

Other Evidence for BiPAP-assoc Badness: Isosorb Dinitrate (4 mg IV q 4 min) vs

Isosorb/BiPAP (10mcg/min titrating by 10mcg/min)

0

20

10

25

10

80

55

85

0

10

20

30

40

50

60

70

80

90

Death Mech. Vent AMI Any Event

Hi dose Ntg

LowNtg,BiPAP

JACC 2000. 36:832-837n = pts <90% Hi Ntg = 20BpP/Ntg = 20

%

*

*

*

Baseline treatment = 3mg MSO4 + 80mg Lasix

Sacchetti Letter 2001: Bipap pressures too low, MS bad and CK is artifact of BiPAP

Conclusion 4:

Bipap: we just don’t know…

But – we believe!

Historical CHF Conclusions: The data is weak for all historical therapies MSO4 implicated as a problem in a number of

investigations... IV Ntg appears efficacious and likely important as initial

therapy…hi dose probably best. BiPAP may be injurious at higher pressures but

ineffective at lower… decreased intubation rates, mortality and other outcomes remain unproven.

ACE evidence: some symptom improvement, no mortality/ETI/AMI benefit proven to date..

Acute Heart Failure: New Drugs and Acute Heart Failure: New Drugs and ApproachesApproaches

Mfg byFDA

Nesiritide (h-BNP) is Identical to the Nesiritide (h-BNP) is Identical to the Endogenous Naturally Occurring HormoneEndogenous Naturally Occurring Hormone

Clemens LE, Protter AA, et al. J Pharmacol Exp Ther 1998;287:67-71

Precise amino acid sequence

Identical pharmacological profile

DR I

MKRG

S SS

SGLG

FC

CS S

GSGQVM

K V L RR

H

KPS

More than diuresis...More than diuresis...

It’s a neurohumoral experience...It’s a neurohumoral experience...

Current Treatment of Acute Heart Failure

DiureticsDiuretics

ReduceReducefluidfluidvolumevolume

Natriuretic PeptidesNatriuretic Peptides

DecreaseDecrease PreloadPreload AndAnd AfterloadAfterload

InotropesInotropes

AugmentAugment Contrac-Contrac- tilitytility

DecreaseDecreaseVolumeVolumePreloadPreload Afterload Afterload AndAndNeuro-Neuro-hormoneshormones

VasodilatorsVasodilators

Ntg vsNtg vs NesiritideNesiritide

Hours0

Months

6

Eligible

Patients

(n = 489)

Catheterized

(n = 246)

Non-Catheterized

(n = 243)

Stratified Randomized

Nitroglycerin (n = 60)

Placebo (n = 62)

Nes fixed-dose (n=62)

Nes adjustable dose (n = 62)


Nesiritide fixed-dose (n = 92)

Nesiritide adjustable dose (n = 62)

3-Hour Placebo-Control Period

Active-Control Period

1 2 3


Placebo (n = 80)

Nesiritide fixed-dose (n = 119)


Nes fixed-dose (n = 80)

End of Study Drug

VMAC Study DesignVMAC Study Design

Added to background Rx

VMAC investigators. VMAC investigators. JAMA JAMA 2002; 287:1531-402002; 287:1531-40

# *# *

# *

# #

# p < 0.05 versus placebo* p < 0.05 versus NTG

15 m

30 m

1 hr

2 hr

3 hrBL

Mean observed value (mmHg)

Placebo Nitroglycerin Nesiritide

18

20

22

24

26

28

30

VMAC Primary Endpoint: VMAC Primary Endpoint: PCWP through 3 HoursPCWP through 3 Hours

VMAC investigators. JAMA 2002; 287:1531-40

VMAC: PCWP Effects to 48 HoursC

han

ge f

rom

Bas

elin

e in

PC

WP

(m

mH

g)C

han

ge f

rom

Bas

elin

e in

PC

WP

(m

mH

g)

End of Placebo-Controlled PeriodEnd of Placebo-Controlled Period

Time on Study Drug (Hours)Time on Study Drug (Hours)

† p < 0.05 Vs. IV NTG* p < 0.05 Vs. Placebo

*

†*

VMAC investigators. VMAC investigators. JAMA JAMA 2002; 287:1531-402002; 287:1531-40

0 0.25 0.5 1 2 3 6 9 12 24 36 48

-9

-8

-7

-6

-5

-4

-3

-2

-1

0PCWP - Placebo

PCWP - IV NTG

PCWP - Nesiritide

†*

†* †

** †

* †

†††

*

-10

0

10

20

30

40

50

60

70

80

90

100

Dyspnea at 3 hours

Nesiritide PlaceboNTG

Improved (%)

Worsened (%)

P=0.034

P=0.191

No change

VMAC Primary Endpoint VMAC Primary Endpoint


VMAC: Dyspnea at 24 HoursVMAC: Dyspnea at 24 Hours

Nitroglycerin

(n=123/124)Nesiritide Fixed

(n=118/119)

-30-20-10

0102030405060708090

100p=0.027

Nitroglycerin Nesiritide

Dyspnea

Non-Catheterized Subjects as Randomized


Nesiritide and Six Month Mortality:Nesiritide and Six Month Mortality:Pooled Analysis of 4 StudiesPooled Analysis of 4 Studies

0 30 60 90 120 150 180

10

20

30

40

50

60

70

80

90

100

All Control (n = 443)

All Nesiritide (n = 724)

6 Month Mortality RateNesiritide 21.5% vs. Control 21.7%RR 1.0 (95% CI 0.70 to 1.3) p=0.830

(All Treated Subjects, As Treated)

Time from the Start of Treatment (days)

Cum

ulat

ive

Mor

talit

y R

ate

(%)

FDA Cardio-Renal Advisory Panel

CHF:The Evolving Therapeutic ApproachCHF:The Evolving Therapeutic Approach

Traditional EM Approach

Lasix: Hi Dose

Top/SL Ntg: Lo Dose

IV MSO4

EMS: Ntg + Lasix

Lasix: Lo Dose

Top/SL/IV Ntg: Hi Dose

Recent EM Approach

Intubation

Once the patient is free of congestion, discontinue therapy.

ACEi - BiPAPIntubation

Emergency Department Patients with Acutely Decompensated Congestive Heart Failure: Is

Discharge a Safe Disposition?

Brewer AV, Burton JH, Strout TD

Department of Emergency Medicine

Maine Medical Center Portland, Maine

* 9% admitted to ICU

* 52% admitted to telemetry

* Mean Hospital LOS = 6.1 days

552 HF patients: 2000

Disposition in Acute CHF

552 CHF Patients CY 2000

84%

16%

AdmittedDischarged

552 ED CHF Encounters

90 CHF Patients Went Home...

20

19

51

ED, No admitED AdmitNo Return

30 DaysPost- Discharge:CHF,SOB, CP

2 deaths2 deaths

No rule performed well.

Incidence of death or complication ranged from 7% to 9% in the lowest risk groups.

Comparison of 4 Clinical Prediction Rules for Estimating Risk in Heart Failure

Disposition in Acute CHFAuble, Yealy: Ann EM: 2007



3. EDEMA to Legs?


Shoot a Chest Xray

Run a BNP level

CHF: Therapeutic ApproachCHF: Therapeutic Approach

Lasix: Lo Dose

Top/SL/IV Ntg: Hi Dose

Once the patient is free of congestion, discontinue therapy.

ACEi - BiPAPIntubation

Documents

Strategies for Diagnosis, Risk Stratification and Treatment of the Acutely Decompensated Heart Failure Patient John H. Burton, MD Residency Program Director