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

1
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

2
burtonj_at_mail.amc.edu
3
Heart Failure

• Approximately 5 million Americans have CHF (male
  to female ratio 11)
• Incidence of 10/1000 gt 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
4
Heart Failure Hospitalizations
The number of heart failure hospitalizations is
increasing in both men and women

AHA, 1998 Heart and Statistical Update NCHS,
National Center for Health Statistics
CDC/NCHS Hospital discharges include patients
both living and dead.
AHA Heart and Stroke Statistical Update 2001
5
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
6
A brief discussion of the works of this thing...
7
The Pump 1. A Mechanical Component 2. An
Electrical Component
8
65
1. A Mechanical Component 2. An
Electrical Component
9
(No Transcript)
10
PUMPS LESS!!!
11
FILLS LESS!!!
12
Filling.Pumping
Problems with Filling...
Problems with Pumping...
13
Pumping
Just 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 - lt15
14
Etiology of Acute Heart Failure

• Hypertension
• Ischemia
• Sustained Arrhythmias
• Cardiomyopathy
• EtOH, infiltrative
• Valvular Heart Disease
• Pericardial Disease

Approximately 1/4th Diastolic Dysfxn
15
AFTERload
PREload
Contractility
16
PREload
17
AFTERload
18
Contractility
19

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
20
Venous Legs swell Neck veins distend Liver
congestion Lung congestion
Arterial Decreased perfusion. Brain Kidneys
Everything...
21
CHF Diagnosis

• CHF is a CLINICAL diagnosis
• History
• Physical Exam
• Chest X Ray
• EKG
• Echocardiogram
• Laboratory testing

22
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
23
How do you know an ED pt has Heart Failure?

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

24
ORs for differentiating between patients with
and those without CHF
NEJM 02347161-167
25
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
26
Emergency Department
27
Spectrum of Heart Failure
Dyspnea on exertion
Pulmonary Edema
Moderate
Asymptomatic CHF
Cardiogenic Shock
Severe
Mild
28
Natriuretic Peptides Origin and Stimulus of
Release
Peptide Primary Origin Stimulus of
Release ANP Cardiac atria Atrial
distension BNP Ventricular myocardium Ventricula
r overload CNP 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
200017(Suppl 1)S37-S43
29
RAAS (Renin-Angiotensin Aldosterone System)
Activation of AT1 receptors
Vasoconstriction
Sodium retention
by angiotensin II
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
199917(Suppl 1)S37-S43
30
BNP Levels of 250 Patients Presenting with Dyspnea
P lt 0.001
1076 138
Mean BNP Concentration (pg/ml)
141 31
38 4
Asymptomatic LV Dysfunction No CHF (n14)
No CHF (n139)
CHF (n97)
Maisel A. et al. J Am Coll Cardiol
200137(2)379-85
31
BNP Concentration for the Degree of CHF Severity
2013 266
BNP Concentration (pg/ml)
791 165
186 22
Moderate (n34)
Mild (n27)
Severe (n36)
Maisel A. et al. J Am Coll Cardiol
200137(2)379-85
32
BNP Concentration for the Prediction of Clinical
Events
Death or Heart Failure Hospitalization
45
40
35
30
BNP gt 480 pg/ml
25
20
15
10
BNP 230-480 pg/ml
5
BNP lt 230 pg/ml
0
0
20
40
60
80
100
120
140
160
180
Days
Harrison, Maisel Ann Emerg Med 200239131-138
33
Rapid Measurement of BNP in Emergency Diagnosis
of Heart FailureMultinational study at 7
centers Baseline BNP-1586 ED dyspnea pts vs
clinical judgment
Mean BNP Concentration (pg/ml)
No CHF (n770)
CHF (n744)
Dyspnea due to noncardiac in pt with hx of LV
dysfunction (n72)
Maisel A. et al. NEJM 02347161-167
34
ORs for differentiating between patients with
and those without CHF
NEJM 02347161-167
35
BNP Integration-Diagnostic CHF vs COPD-CHF
Risk Stratification mild, mod,
severe disposition mortality-Therapeutic
Decision-Making change therapy cease therapy
36
Interpretation of the BNP Assay in the Dyspneic
Patient
Significant Decompensated Heart Failure
Mean BNP Concentration (pg/ml)
400
400
400
Mild Ventricle Stretch HF, PE, CM, ACS, Pulm HTN
100
100
100
No Heart Failure, No Ventricle Stretch
37
(No Transcript)
38
(No Transcript)
39

• Youll 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
40
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
41
Current Treatment of Acute Heart Failure
42
Current Treatment of Acute Heart Failure
Diuretics
Vasodilators
Inotropes
Decrease Preload And Afterload
Augment Contract- ility
Reduce fluid volume
43
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 Omit
• Stable outpatients Criteria for admission to
  hospital
• Systolic dysfunction Tailored hemodynamic
  treatments
• Decompensated
  patients

1. Circulation 1995922764-2784, 2. Eur Heart J
199718736-753, 3. Am J Cardiol
199983(2A)1A-38A, 4. Journal of Cardiac Failure
19995357-382
44
Current Treatment of Acute Heart Failure
Vasodilators
Diuretics
Inotropes
Decrease Preload And Afterload
Augment Contract- ility
Reduce fluid volume
Lasix Ntg sl, top, iv MSO4 ACEi BiPAP
Lasix
Dopamine
45
Expose the Literature...
46
Early Response of PCW but not CI Predicts
Subsequent Mortality in Advanced Heart Failure
Total Mortality Risk
Total Mortality Risk
60
60
50
50
PCW gt 16 mmHg
40
40
Cardiac Index gt 2.6 L/min-M2
30
30
199
PCW lt 16 mmHg
20
20
Cardiac Index lt 2.6 L/min/M2
236
10
10
220
257
P0.001
PNS
0
0
0
6
12
18
24
0
6
12
18
24
Months
Months
Fonarow Circulation 199490I-488
47
Youve also got to look at symptom improvement...
48
Lets Start with the Ntg vs. Lasix Debate
49
Arteries
VEINS
Increasing dose of nitroglycerin
50
(No Transcript)
51
Historical Comparison for PCWP
n 48 acute severe ht. failure pts
J Cardiovasc Pharmcol 1987. 10(1)38-46
52
Historical Comparison for PCWP
J Cardiovasc Pharmcol 1987. 10(1)38-46
53
Conclusion 1Ntg better than LasixHi dose Ntg
better than lo dose
54
Morphine??

• Hoffman. Chest 198792586-593.
• Adverse effects were found only in patients
  who received morphine. (4 tx groups, 57
  patients)
• Cohen. Am J Emerg Med 200018342-3.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 199917571-574.
• Morphine sulfates 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.

55
95 Conf I
Am J Emerg Med 9917571-574 181 pts
56
95 Conf I
Am J Emerg Med 9917571-574 181 pts
57
(No Transcript)
58
Conclusion 2Very little data on MSO4MSO4
likely bad or at least, redundant to
preloadSedation and Resp Failure?
59
Acute ACE therapy

• Routes and selected agents are diverse PO/SL/IV
  Captopril, Lisinopril, Enalapril.etc..
• Barnett Current Ther Research 1991. 49274-281.
• 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 -gt 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
  IIand does not affect systemic BP in a
  deleterious manner.

60
Acute ACE therapy

• Haude Intern Jour Cardiol 1990. 27351-359.
• 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. 53167-176.
• 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.

61
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. 3205-212
62
Primry Outcome Placebo vs Captpl
APEX Score
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)
Minutes after Treatment
Acad EM 1996. 3205-212
63
Acute ACE Other OutcomesSL Captopril 12.5 mg
vs Placebo

No Statistical Differences in Any Groups
Acad EM 1996. 3205-212
64
Conclusion 3ACE acute therapy may be goodNo
reason to see it as harmful
65
One more to gothe NVS question
66
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.

67
BiPAP vs CPAP??

• Mehta. Crit Care Med 199725620-628.
• 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 20001891-95. Good
  review of literature to date on Noninvasive
  Ventilatory Support (NVS).

68
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




n pts lt90 Hi Ntg 20 BpP/Ntg 20
Sacchetti Letter 2001 Bipap pressures too low,
MS bad and CK is artifact of BiPAP
JACC 2000. 36832-837
69
Conclusion 4Bipap we just dont knowBut
we believe!
70
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 therapyhi 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..

71
(No Transcript)
72
Acute Heart Failure New Drugs and Approaches
Mfg byFDA
73

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

Precise amino acid sequence Identical
pharmacological profile
Clemens LE, Protter AA, et al. J Pharmacol Exp
Ther 199828767-71
74

• More than diuresis...

75

• Its a neurohumoral experience...

76
Current Treatment of Acute Heart Failure
Natriuretic Peptides
Inotropes
Vasodilators
Diuretics
Decrease Volume Preload Afterload
And Neuro- hormones
Reduce fluid volume
Decrease Preload And Afterload
Augment Contrac- tility
77

• Ntg vs
• Nesiritide

78
VMAC Study Design
3-Hour Placebo- Control Period
Active- Control Period
Nitroglycerin (n 60)
Nitroglycerin (n 92)
Placebo (n 62)
Catheterized (n 246)
Nes fixed-dose (n62)
Nesiritide fixed-dose (n 92)
Eligible Patients (n 489)
Nes adjustable dose (n 62)
Nesiritide adjustable dose (n 62)
Nitroglycerin (n 83)
Nitroglycerin (n 124)
Non-Catheterized (n 243)
Placebo (n 80)
Nes fixed-dose (n 80)
Nesiritide fixed-dose (n 119)
Stratified
Randomized
End of Study Drug
6
0
1
2
3
Added to background Rx
Hours
Months
VMAC investigators. JAMA 2002 2871531-40
79
VMAC Primary Endpoint PCWP through 3 Hours
Nesiritide
Placebo
Nitroglycerin
Mean observed value (mmHg)
30
28
26

p lt 0.05 versus placebo p lt 0.05 versus NTG

24






22
20
18
BL
1 hr
3 hr
2 hr
15 m
30 m
VMAC investigators. JAMA 2002 2871531-40
80
VMAC PCWP Effects to 48 Hours
Time on Study Drug (Hours)

Change from Baseline in PCWP (mmHg)











End of Placebo-Controlled Period
p lt 0.05 Vs. IV NTG p lt 0.05 Vs. Placebo
VMAC investigators. JAMA 2002 2871531-40
81
VMAC Primary Endpoint
Dyspnea at 3 hours
100
P0.034
90
P0.191
80
70
60
Improved ()
50
40
30
20
10
No change
0
Worsened ()
Placebo
Nesiritide
NTG
-10
VMAC investigators. JAMA 2002 2871531-40
82
VMAC Dyspnea at 24 Hours
Non-Catheterized Subjects as Randomized
Nitroglycerin Nesiritide
Dyspnea
p0.027
100
90
80
70
60
50
40
30
20
10
0
-10
-20
-30
Nitroglycerin
Nesiritide Fixed
(n123/124)
(n118/119)
VMAC investigators. JAMA 2002 2871531-40
83
Nesiritide and Six Month MortalityPooled
Analysis of 4 Studies
100
(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) p0.830
90
80
70
All Control (n 443)
60
Cumulative Mortality Rate ()
All Nesiritide (n 724)
50
40
30
20
10
0
30
60
90
120
150
180
Time from the Start of Treatment (days)
FDA Cardio-Renal Advisory Panel
84
CHFThe 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
ACEi - BiPAP Intubation
Intubation
Once the patient is free of congestion,
discontinue therapy.
85
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
86
Disposition in Acute CHF
552 HF patients 2000

• 9 admitted to ICU
• 52 admitted to telemetry
• Mean Hospital LOS 6.1 days

87
552 CHF Patients CY 2000
88
90 CHF Patients Went Home...
2 deaths
89
Disposition in Acute CHFAuble, 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.

90
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
91
CHF Therapeutic Approach
Lasix Lo Dose Top/SL/IV Ntg Hi Dose
ACEi - BiPAP Intubation
Once the patient is free of congestion,
discontinue therapy.