Transcript CHF - VeoMed

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
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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
Discharges
500,000
400,000
300,000
200,000
Women
Men
100,000
AHA, 1998
Heart and
Statistical include
Update patients both living and dead.
CDC/NCHS:
Hospital
discharges
NCHS, National Center for Health Statistics
AHA Heart and Stroke Statistical Update 2001
7
'9
5
'9
3
'9
1
'9
9
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7
'8
5
'8
3
'8
1
'8
'7
9
0
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
65%
1. A Mechanical
Component
2. An Electrical
Component
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
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Hypertension
Ischemia
Sustained Arrhythmias
Cardiomyopathy
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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
Arterial
Legs swell
Decreased
perfusion….
Neck veins distend
Liver congestion
Brain
Kidneys
Lung congestion
Everything...
CHF: Diagnosis
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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?
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CHF: a CLINICAL diagnosis
…. Shortness of Breath!!! ; Leg edema; weakness
History
…. Legs: Edema; Lungs: Rales
Physical Exam
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
Age
Hx CHF
Hx MI
Rales
Ceph XR
Edema
JVD
OR 6
4
2.9
2.7
2.2
2
1
0
NEJM 02;347:161-167
Predictor
1.9
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
Dyspnea at rest
PND and
orthopnea
Dyspnea on
exertion
Pulmonary
Edema
Moderate
Asymptomatic
CHF
Cardiogenic
Shock
Natriuretic 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
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 AT1 receptors
by angiotensin II
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
P < 0.001
Mean BNP
Concentration (pg/ml)
1400
1076 ± 138
1200
1000
800
600
400
200
0
38 ± 4
No CHF
(n=139)
141 ± 31
Asymptomatic
LV Dysfunction
No CHF
(n=14)
Maisel A. et al. J Am Coll Cardiol 2001;37(2):379-85
CHF
(n=97)
BNP Concentration (pg/ml)
BNP Concentration for the
Degree of CHF Severity
2013 ± 266
2500
2000
1500
791 ± 165
1000
500
0
186 ± 22
Mild
(n=27)
Maisel A. et al. J Am Coll Cardiol
2001;37(2):379-85
Moderate
(n=34)
Severe
(n=36)
BNP Concentration for the
Prediction of Clinical Events
Death or Heart Failure Hospitalization
45%
40%
35%
30%
BNP > 480 pg/ml
25%
20%
15%
10%
BNP 230-480 pg/ml
5%
BNP < 230 pg/ml
0%
0
20
40
60
Harrison, Maisel Ann Emerg Med 2002;39:131-138
80 100
Days
120
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
Mean BNP
Concentration (pg/ml)
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
Age
Hx CHF
Hx MI
Rales
Ceph XR
Edema
JVD
BNP>100
20
OR 15
11.1
10.7
10
5
2.7
2.2
1
0
NEJM 02;347:161-167
Predictor
2.9
1.9
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
Mean BNP
Concentration (pg/ml)
900
800
Significant Decompensated Heart Failure
700
600
500
400
400
400
400
300
Mild Ventricle Stretch: HF, PE, CM, ACS, Pulm HTN
200
100
100
0
100
100
No Heart Failure, No Ventricle Stretch
BNP Precision Studies (Assigned Value = 103)
120
110
100
90
80
70
60
1
2
3
4
5
6
7
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10 Replicates on Two Different Days
Day 1 Mean = 95.8
Day 2 Mean = 85.1
Mean + 2 SD = 66 - 115
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
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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
Vasodilators
Reduce
fluid
volume
Decrease
Preload
And
Afterload
Inotropes
Augment
Contractility
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
Reduce
fluid
volume
Lasix
Decrease
Preload
And
Afterload
Lasix
Ntg: sl, top, iv
MSO4
ACEi
BiPAP
Inotropes
Augment
Contractility
Dopamine
Expose the Literature...
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 > 16 mmHg
40
40
30
Cardiac Index > 2.6 L/min-M2
30
199
PCW < 16 mmHg
20
20
Cardiac Index < 2.6 L/min/M2
236
10
257
0
0
6
10
P=0.001
12
Months
18
24
0
220
0
6
P=NS
12
Months
18
Fonarow Circulation 1994;90:I-488
24
You’ve also got
to look at
symptom
improvement...
Let’s Start with the
Ntg vs. Lasix Debate
Arteries
VEINS
Increasing dose of nitroglycerin
Historical Comparison for PCWP
2
0
30
60
90
0
Lasix 1mg/kg
-2
Ntg 0.83
mcg/kg/min
Hydrzn 0.15
mg/kg
-4
-6
-8
n = 48 “acute severe ht. failure” pts
-10
J Cardiovasc Pharmcol 1987. 10(1):38-46
Historical Comparison for PCWP
2
0
30
60
90
Lasix 1mg/kg
0
-2
-4
Ntg 0.83
mcg/kg/min
Hydrzn 0.15
mg/kg
Plac VMAC
-6
Ntg VMAC
-8
Nestd VMAC
-10
J Cardiovasc Pharmcol 1987. 10(1):38-46
Conclusion 1:
Ntg better than Lasix
Hi dose Ntg better than lo dose
Morphine??
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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.”
OR for ICU Admit
3.5
3
2.5
2
%
1.5
1
MI
Age
Captopril
NTG
MS
Diuretic
0.5
0
Am J Emerg Med 99;17:571-574: 181 pts
95% Conf I
OR for ETI
6
5
4
%
3
2
MI
Age
Captopril
NTG
MS
Diuretic
1
0
Am J Emerg Med 99;17:571-574: 181 pts
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
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Routes and selected agents are diverse: PO/SL/IV; Captopril,
Lisinopril, Enalapril….etc…..
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Barnett: Current Ther Research 1991. 49:274-281.
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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
n
Haude: Intern Jour Cardiol 1990. 27:351-359.
o
n
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.
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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
Primry Outcome: Placebo vs Captpl
100
90
80
70
60
* = Stat Sig
*
50
40
*
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)
30
20
0
12
0
10
80
60
40
20
10
0
0
APEX
Score
Placebo
Captopril
Minutes after Treatment
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
26
20
9
ETI
MI
No Statistical Differences in Any Groups
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??
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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??
n
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
n
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
%
55
60
Hi dose Ntg
50
40
*
30
20
10
0
10
*
10
0
Death
n = pts <90%
Hi Ntg = 20
BpP/Ntg = 20
25
*
20
Low
Ntg,BiPAP
Mech. Vent
AMI
Sacchetti Letter 2001: Bipap pressures
too low, MS bad and CK is artifact of BiPAP
Any Event
JACC 2000. 36:832-837
Conclusion 4:
Bipap: we just don’t know…
But – we believe!
Historical CHF Conclusions:
n
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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
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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
Reduce
fluid
volume
Vasodilators
Decrease
Preload
And
Afterload
Inotropes
Natriuretic Peptides
Decrease
Augment
Contractility
Volume
Preload
Afterload
And
Neurohormones
Ntg vs
Nesiritide
VMAC Study Design
ActiveControl Period
3-Hour PlaceboControl Period
Nitroglycerin (n = 60)
Eligible
Patients
(n = 489)
Catheterized
(n = 246)
Nitroglycerin (n = 92)
Placebo (n = 62)
Nes fixed-dose (n=62)
Nesiritide fixed-dose (n = 92)
Nes adjustable dose (n = 62) Nesiritide adjustable dose (n = 62)
Nitroglycerin (n = 83)
Nitroglycerin (n = 124)
Non-Catheterized Placebo (n = 80)
(n = 243)
Nes fixed-dose (n = 80)
Stratified
Added to background Rx
Nesiritide fixed-dose (n = 119)
Randomized
0
End of Study Drug
2
1
Hours
3
6
Months
VMAC investigators. JAMA 2002; 287:1531-40
VMAC Primary Endpoint:
PCWP through 3 Hours
Nitroglycerin
Placebo
Nesiritide
Mean observed value (mmHg)
30
28
26
22
# *
#
#
3 hr
#*
2 hr
24
# p < 0.05 versus placebo
* p < 0.05 versus NTG
# *
20
1 hr
BL
15 m
30 m
18
VMAC investigators. JAMA 2002; 287:1531-40
VMAC: PCWP Effects to 48 Hours
Time on Study Drug (Hours)
0 0.25 0.5
1
2
3
*
6
9
12 24 36 48
0
PCWP - Placebo
-1
PCWP - IV NTG
-2
PCWP - Nesiritide
-3
*
-4 †
†
*
-5 *
-6
-7
-8
†
*
†
*
*
†
*
†
†
†
-9
†
End of Placebo-Controlled Period
VMAC investigators. JAMA 2002; 287:1531-40
† p < 0.05 Vs. IV NTG
* p < 0.05 Vs. Placebo
VMAC Primary Endpoint
Dyspnea at 3 hours
100
90
Improved (%)
Worsened (%)
P=0.034
80
70
60
50
40
30
20
10
0
-10
P=0.191
No change
Nesiritide
NTG
Placebo
VMAC investigators. JAMA 2002; 287:1531-40
VMAC: Dyspnea at 24 Hours
Non-Catheterized Subjects as Randomized
Nitroglycerin
Nesiritide
Dyspnea
100
100
90
80
70
60
50
40
30
20
10
0
-10
-20
-30
p=0.027
90
#
80
Markedly
Better
70
60
Moderately
Better
50
40
30
Minimally
Better
20
10
0
MinimallyMarkedly
No Change
Worse
-10
-20
-30
-40
-50Nitroglycerin
-60
(n=123/124)
Nesiritide Fixed
MinimallyMarkedly
No Change
Worse
(n=118/119)
-70
VMAC investigators. JAMA 2002; 287:1531-40
Nesiritide and Six Month Mortality:
Pooled Analysis of 4 Studies
Cumulative Mortality Rate (%)
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) p=0.830
90
80
70
All Control (n = 443)
60
All Nesiritide (n = 724)
50
40
30
20
10
0
30
60
90
120
Time from the Start of Treatment (days)
FDA Cardio-Renal Advisory Panel
150
180
CHF:The Evolving Therapeutic Approach
EMS: Ntg + Lasix
Traditional EM Approach
Lasix: Hi Dose
Top/SL Ntg: Lo Dose
IV MSO4
Intubation
Recent EM Approach
Lasix: Lo Dose
Top/SL/IV Ntg: Hi
Dose
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...
20
51
30 Days
PostDischarge:
CHF,SOB, CP
ED, No admit
ED Admit
No Return
19
2 deaths
Disposition in Acute CHF
Auble, Yealy: Ann EM: 2007
Comparison of 4 Clinical Prediction Rules for
Estimating Risk in Heart Failure
n
No rule performed well.
n
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.