Strategies for Diagnosis, Risk Stratification and Treatment of the Acutely Decompensated Heart Failure Patient

John H. Burton, MD Residency Program Director Dept. Emergency Medicine Albany Medical Center

burtonj@ mail.amc.edu

Heart 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 Hospitalizations

The number of heart failure hospitalizations is increasing in both men and women 600,000 500,000 400,000 300,000 200,000 100,000 0 '7 9 Women Men '8 1 '8 3 '8 5 '8 7 '8 9 '9 1 '9 3 '9 5 '9 7

CDC/NCHS: Hospital discharges include patients both living and dead.

AHA Heart and Stroke Statistical Update 2001

Hospital Visits for Congestive Heart Failure

Initial Episode 21%

Approximately 85% of the ED visits for CHF result in hospitalizations

Repeat Visit 79%

Rates of Hospital Readmission



2% within 2 days



20% within 1 month



50% within 6 months

Cardiology Roundtable 1998

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

The Pump: 1. A Mechanical Component 2. An Electrical Component

1. A Mechanical Component 2. An Electrical Component 65%

PUMPS LESS!!!

FILLS LESS!!!

Filling….

Pumping

Problems with Filling...

Problems with Pumping...

Pumping

Just how little pumping can one get away with?

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

Etiology of Acute Heart Failure



Hypertension



Ischemia



Sustained Arrhythmias



Cardiomyopathy



EtOH, infiltrative



Valvular Heart Disease



Pericardial Disease

Approximately 1/4th Diastolic Dysfxn

PREload AFTERload Contractility

PREload

AFTERload

Contractility

DEFINITION CHF

“The situation when the heart is incapable of maintaining a cardiac output adequate to accommodate metabolic requirements and the venous return.” E. Braunwald

Venous Legs swell Neck veins distend Liver congestion Lung congestion Arterial Decreased perfusion….

Brain Kidneys 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

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

Physical Exam

…. Legs: Edema; Lungs: Rales

 Chest X Ray  Echocardiogram  Laboratory testing

How do you know an ED pt has Heart Failure?

Accuracy of Diagnosis: CHF EMS : 50-65% Emergency Doc: 65-80% Cardiologist: 80-85%

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

12 11.1

10.7

10 8 OR 6 4 2 0

NEJM 02;347:161-167

1 2.7

2.2

Predictor 2.9

1.9

Age Hx CHF Hx MI Rales Ceph XR Edema JVD

How do you know an ED pt has Heart Failure?

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

PND and orthopnea Dyspnea at rest Dyspnea on exertion Pulmonary Edema Moderate Asymptomatic CHF Cardiogenic Shock

Natriuretic Peptides: Origin and Stimulus of Release Peptide ANP BNP CNP Primary Origin Cardiac atria Stimulus of Release Atrial distension Ventricular myocardium Ventricular overload Endothelium Shear stress of endothelium ANP = Atrial Natriuretic Peptide BNP = B-type Natriuretic Peptide CNP = C-type Natriuretic Peptide

Adapted from Burnett JC,

J Hypertens

2000;17(Suppl 1):S37-S43

RAAS (Renin-Angiotensin Aldosterone System)

Activation of AT 1 by angiotensin II receptors Vasoconstriction Sodium retention Increased aldosterone release Increased cellular growth Increased sympathetic nervous activity

NPS (Natriuretic Peptide System)

ANP, BNP Vasodilation Sodium excretion Decreased aldosterone levels Inhibition of RAAS Inhibition of sympathetic nervous activity CNP Vasodilation Decreased vascular smooth muscle growth Decreased aldosterone levels Adapted from Burnett JC,

J Hypertens

1999;17(Suppl 1):S37-S43

BNP Levels of 250 Patients Presenting with Dyspnea 1400 1200 1000

P < 0.001

800 600 400 141

±

31 200 38

±

4 0 No CHF (n=139) Asymptomatic LV Dysfunction No CHF (n=14)

Maisel A. et al.

J Am Coll Cardiol

2001;37(2):379-85

1076

±

138 CHF (n=97)

BNP Concentration for the Degree of CHF Severity

2013

±

266 2500 2000 1500 1000 500 186

±

22 0 Mild (n=27)

Maisel A. et al.

J Am Coll Cardiol

2001;37(2):379-85

791

±

165 Moderate (n=34) Severe (n=36)

BNP Concentration for the Prediction of Clinical Events

45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 0 Death or Heart Failure Hospitalization 20 BNP > 480 pg/ml BNP 230-480 pg/ml 40 60 BNP < 230 pg/ml 80 Days 100 120 Harrison, Maisel

Ann Emerg Med

2002;39:131-138 140 160 180

Rapid Measurement of BNP in Emergency Diagnosis of Heart Failure Multinational study at 7 centers: Baseline BNP-1586 ED dyspnea pts vs clinical judgment

1400 1200 1000 800 600 400 200 0 No CHF (n=770)

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

Dyspnea due to noncardiac in pt with hx of LV dysfunction (n=72) CHF (n=744)

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

29.6

30 25 20 OR 15 10 5 0

NEJM 02;347:161-167

1 11.1

10.7

2.7

2.2

Predictor 2.9

1.9

Age Hx CHF Hx MI Rales Ceph XR Edema JVD BNP>100

BNP Integration -Diagnostic: CHF vs COPD -CHF Risk Stratification: mild, mod, severe disposition mortality -Therapeutic Decision-Making change therapy cease therapy

Interpretation of the BNP Assay in the Dyspneic Patient 1000 900 800 700 600 500 400 300 200 100 0

Significant Decompensated Heart Failure

400 400 400

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

100 100

No Heart Failure, No Ventricle Stretch

100

BNP Precision Studies (Assigned Value = 103)

120 110 100 90 80 70 60 1 2 3 4 5 6 7

10 Replicates on Two Different Days Day 1 Mean = 95.8

Day 2 Mean = 85.1

Mean + 2 SD = 66 - 115

8 9 10

BNP Correlations MMC vs Hartford

1400 1200 1000 800 600 400 200 0 0 200 400 600 800 1000 1200 1400

You’ll also hear about Pro-BNP S P K M V Q M D R G K R G F C G S I S S S S S S G C L G K V L R R H 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

How do you know an ED pt has Heart Failure?

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

2. RALES on Lung Examination?

3. EDEMA to Legs?

Shoot a Chest Xray Run a BNP level

Current Treatment of Acute Heart Failure

Current Treatment of Acute Heart Failure Diuretics

Reduce fluid volume

Vasodilators

Decrease Preload And Afterload

Inotropes

Augment Contract ility

Heart 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…

Stable outpatients Systolic dysfunction

Omit…

Criteria for admission to hospital 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 Failure Vasodilators Diuretics Inotropes

Reduce fluid volume Decrease Preload And Afterload Augment Contract ility Lasix Lasix Ntg: sl, top, iv MSO4 ACEi BiPAP Dopamine

Expose the Literature...

Early Response of PCW but not CI Predicts Subsequent Mortality in Advanced Heart Failure 60 Total Mortality Risk% 50 40 30 20 10 0 0 199 257 6 12 Months PCW > 16 mmHg PCW < 16 mmHg 18 P=0.001

24 60 Total Mortality Risk% 50 40 30 20 Cardiac Index > 2.6 L/min-M 2 236 Cardiac Index < 2.6 L/min/M 2 10 0 0 220 6 12 Months 18 P=NS 24

Fonarow

Circulation

1994;90:I-488

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

Let’s Start with the Ntg vs. Lasix Debate

Arteries VEINS Increasing dose of nitroglycerin

-2 -4 -6 -8 -10 2 0

Historical Comparison for PCWP

0 30 60 90

n = 48 “acute severe ht. failure” pts

Lasix 1mg/kg Ntg 0.83

mcg/kg/min Hydrzn 0.15

mg/kg

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

-2 -4 -6 -8 -10 2 0

Historical Comparison for PCWP

0 30 60 90 Lasix 1mg/kg Ntg 0.83

mcg/kg/min Hydrzn 0.15

mg/kg Plac VMAC Ntg VMAC Nestd VMAC

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

Conclusion 1: Ntg better than Lasix Hi 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.”

3.5

3 2.5

2 % 1.5

1 0.5

0

Am J Emerg Med 99;17:571-574: 181 pts

OR for ICU Admit MI Age Captopril NTG MS Diuretic

95% Conf I

6 5 4 % 3 2 1 0

Am J Emerg Med 99;17:571-574: 181 pts

OR for ETI MI Age Captopril NTG MS Diuretic

95% Conf I

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 Baseline treatment = 2mg increments MSO4 + 40mg min. lasix + sl Ntg +/- IV Ntg pts with APE Placebo = 25 Captopril = 23 Acad EM 1996. 3:205-212

APEX Score

50 40 30 20 10 0

Primry Outcome: Placebo vs Captpl

100 90 80 70 60 Placebo Captopril

* = Stat Sig * * APEX Score (nonvalidated): 1. Deg of orthopnea tolerance 2. Pt.-reported dyspnea 3. Observer-reported dyspnea 4. Observer-reported diaphoresis (conv score as % of time zero)

0 20 40 60 80

Minutes after Treatment

100 120

Acad EM 1996. 3:205-212

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

100 90 80 70 60 50 40 30 20 10 0 Placebo Captopril 36 20 26 9 ETI

No Statistical Differences in Any Groups

MI

Acad EM 1996. 3:205-212

Conclusion 3: ACE acute therapy may be good No reason to see it as harmful

One more to go: the NVS question

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) Baseline treatment = 3mg MSO4 + 80mg Lasix

90 85 80 80 70 60 50 55 Hi dose Ntg 40 30 25

*

Low Ntg,BiPAP 20

*

20 10 10

*

10 0 0 Death Mech. Vent AMI Any Event

n = pts <90% Hi Ntg = 20 BpP/Ntg = 20 Sacchetti Letter 2001: Bipap pressures too low, MS bad and CK is artifact of BiPAP JACC 2000. 36:832-837

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 Approaches

Mfg byFDA

Nesiritide (h-BNP) is Identical to the Endogenous Naturally Occurring Hormone S P K M V Q M D R G K R G F C G S I S S S S S S G C L G K V L R R H Precise amino acid sequence Identical pharmacological profile

Clemens LE, Protter AA, et al.

J Pharmacol Exp Ther

1998;287:67-71

More than diuresis...

It’s a neurohumoral experience...

Current Treatment of Acute Heart Failure

Diuretics Vasodilators Inotropes Natriuretic Peptides Reduce fluid volume Decrease Preload And Afterload Augment Contrac tility Decrease Volume Preload Afterload And Neuro hormones

Ntg vs Nesiritide

VMAC Study Design

Eligible Patients (n = 489) Catheterized (n = 246)

3-Hour Placebo Control Period Active Control Period

Nitroglycerin (n = 60) Placebo (n = 62) Nes fixed-dose (n=62) Nes adjustable dose (n = 62) Nitroglycerin (n = 92) Nesiritide fixed-dose (n = 92) Nesiritide adjustable dose (n = 62) Nitroglycerin (n = 83) Non-Catheterized (n = 243) Placebo (n = 80) Nes fixed-dose (n = 80) Nitroglycerin (n = 124) Nesiritide fixed-dose (n = 119) Stratified Randomized End of Study Drug Added to background Rx 0 1 Hours 2 3 6 Months

VMAC investigators. JAMA 2002; 287:1531-40

VMAC Primary Endpoint:

PCWP through 3 Hours

Nesiritide Placebo 30 Mean observed value (mmHg) Nitroglycerin 28 26 24 # * # * 22 # * # # # p < 0.05 versus placebo * p < 0.05 versus NTG 20 18 VMAC investigators.

JAMA

2002; 287:1531-40

VMAC: PCWP Effects to 48 Hours 0 -1 -2 -3 -4 -5 † * † * -6 -7 -8 -9 0 0.25 0.5

1 † * † * * * † * 2 3 † * 6 † 9 12 24 36 48 † † End of Placebo-Controlled Period

VMAC investigators. JAMA 2002; 287:1531-40

PCWP - Placebo PCWP - IV NTG PCWP - Nesiritide † p < 0.05 Vs. IV NTG * p < 0.05 Vs. Placebo

VMAC Primary Endpoint

Improved (%) Worsened (%) 100 90 80 70 60 50 40 30 20 10 0 -10 Nesiritide

Dyspnea at 3 hours

P=0.034

P=0.191

NTG No change Placebo VMAC investigators.

JAMA

2002; 287:1531-40

VMAC: Dyspnea at 24 Hours

Non-Catheterized Subjects as Randomized

100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30

Nitroglycerin Dyspnea

100 90 80 70 60 0 -10 -20 -30 50 40 30 20 10 -40 -50 Nitroglycerin -60 (n=123/124) -70

p=0.027

Nesiritide Fixed (n=118/119) #

Nesiritide

Markedly Better Moderately Better Minimally Better Minimally Worse Minimally Worse VMAC investigators.

JAMA

2002; 287:1531-40 15 Mins 1 Hour # p<0.05 Natrecor® or nitroglycerin compared to placebo * p<0.05 compared to nitroglycerin 3 Hours

100 90 80 70 60 50 40 30 20 10 Nesiritide and Six Month Mortality: Pooled Analysis of 4 Studies

(All Treated Subjects, As Treated)

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

All Control (n = 443) All Nesiritide (n = 724)

0 30 FDA Cardio-Renal Advisory Panel 60 90 120

Time from the Start of Treatment (days)

150 180

CHF:The Evolving Therapeutic Approach

EMS: Ntg + Lasix Traditional EM Approach Lasix: Hi Dose Top/SL Ntg: Lo Dose IV MSO4 Recent EM Approach Lasix: Lo Dose Top/SL/IV Ntg: Hi Dose Intubation ACEi - BiPAP Intubation Once the patient is free of congestion, discontinue therapy.

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

Disposition in Acute CHF

552 HF patients: 2000 * 9% admitted to ICU * 52% admitted to telemetry * Mean Hospital LOS = 6.1 days

552 CHF Patients CY 2000

16% 552 ED CHF Encounters 84% Admitted Discharged

90 CHF Patients Went Home...

51 20 30 Days Post- Discharge: CHF,SOB, CP 19 2 deaths ED, No admit ED Admit No Return

Disposition in Acute CHF Auble, Yealy: Ann EM: 2007 Comparison of 4 Clinical Prediction Rules for Estimating Risk in Heart Failure  No rule performed well.

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

How do you know an ED pt has Heart Failure?

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

2. RALES on Lung Examination?

3. EDEMA to Legs?

Shoot a Chest Xray Run a BNP level

CHF: Therapeutic Approach

Lasix: Lo Dose Top/SL/IV Ntg: Hi Dose ACEi - BiPAP Intubation Once the patient is free of congestion, discontinue therapy.