Transcript Case 1: W.C.

Hospital Management
of
Decompensated Heart Failure
Wilson S. Colucci, MD
Chief, Cardiovascular Medicine
Acute Heart Failure Syndromes
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Acute (i.e., new) onset of HF in patient without prior
episodes or history of HF (e.g., acute MI, myocarditis)
Worsening (“decompensation”) of existing chronic,
“compensated” heart failure
Persistently decompensated HF despite optimal
medical management (often referred to as advanced or
end-stage HF)
Natural History of HF Progression
AHFS
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About 900,000 admissions per year
Average LOS 6-7 days
$23 billion annual costs
Affects most patients with chronic HF
Admissions for Heart Failure: Frequent Flyers
Initial Admission 21%
Readmission 79%
Rates of readmission
• 2% in 2 days
• 20+% in 30 days
• 50% in 6 months
Causes of Readmission for HF
Rx Noncompliance
24%
Diet Noncompliance
24%
16%
Inappropriate Rx
19%
Failure to Seek
Care
17%
Other
HFSA Research 2000
Overall Goals in Management of AHFS

Immediate relief of symptoms and hemodynamic stabilization
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Identification and correction of underlying / precipitating factors
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Optimize fluid status (optimal weight, renal function, edema)
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Establishment of effective ambulatory regimen prior to discharge
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Discharge planning and follow-up
Precipitants of AHFS
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Diet indiscretion
Medication non-compliance
Uncontrolled hypertension
Myocardial ischemia/infarction
Cardiac arrhythmia (rapid heart beats, loss
of atrial kicks)
Exacerbation of COPD
Medications (NSAID, glitazones, diltiazem
verapamil)
Patient: W.C.
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67 year old man, ischemic CMP admitted with
progressive DOE and fatigue
HR 98, tachypnea, BP 100/84, CVP 16 cm,
bibasilar rales, 3+ edema to knees, cold feet
Labs: BUN 50, creat 2.5, BNP 1,500
Hemodynamic Profiles
Volume Status
Dry
Warm A - Normal
Perfusion
Cold
C
Wet
B
D
Cold extremities
Hypotension
Narrow PP
Renal insuff.
Dyspnea
Rales
CVP
Edema
Acute HF: Clinical Signs

Intracardiac Filling Pressures
–
–
–
–
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orthopnea, dyspnea on exertion
rales, jugular vein distention
bedside Valsalva maneuver
chest x-ray
Adequacy of Perfusion
–
–
–
–
narrow pulse pressure
cool extremities
mental obtundation
renal insufficiency, oliguria
LV Failure Easily Missed on
Exam and/or CXR
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By exam - rales, edema, and JVD often absent (e.g., 42%
in Stevenson et al., JAMA 1989;261:884)
By CXR – congestion often absent (e.g., 27% had no
congestion and 41% had minimal congestion in Mahdyoon
et al., AJC 1989)
PA Catheter
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Gold standard, but usually/often not needed
Adds little to management of uncomplicated case
– ESCAPE Trial
Indicated/valuable in patient with known LV failure if:
– Suspected low output / hypoperfusion
– Unclear volume status
– Ischemia, renal insufficiency, ARDS
– Poor / unclear response to IV therapy / to optimize
oral therapy
Predictors of In-Hospital Mortality
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Three best predictors of mortality in hospitalized
patients
– BUN > 43 mg/dL
– SBP < 115 m Hg
– Creatinine > 2.75 mg/dL
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But, information mainly retrospective from registry
data (e.g., ADHERE Registry)
Therefore, not that useful in individual patient, but
identifies patients to worry about
Fonarow GC et al. JAMA 2005;293:572-80.
Diuretics can worsen renal function in HF
? Inc Morbidity
and Mortality
Diuretic &
Natriuretic
Resistance
Worse renal
function
Diuretic Therapy
Decreased
preload
Neurohormonal
Activation
Diminished
Renal blood flow
Diuretics can improve renal function in HF
GFR (ml/min)
1.4
1.1
0.8
0.5
0
0
6
2
12
19
25
CVP, 4mm Hg
0
6
8
Firth et al Lancet 5/7/88
Intensification of diuretic regimen
When diuresis is inadequate to relieve congestion, as
evidenced by clinical evaluation, the diuretic regimen should
be intensified, using either:
1) higher doses of loop diuretics;
2) addition of a second diuretic (e.g. metolazone,
spironolactone, or chlorothiazide); or
3) continuous infusion of a loop diuretic (Level of
Evidence: C)
NIH “Dose” Trial: How to Diurese
To evaluate the safety and efficacy of various initial
strategies of furosemide therapy in patients with ADHF
– Route
» Q12 hours bolus
» Continuous infusion
–
Dose
» Low intensification (1 x oral dose)
» High intensification (2.5 x oral dose)
Dose: Study Design
Acute Heart Failure (1 symptom AND 1 sign)
<24 hours after admission
2x2 factorial randomization
Low Dose (1 x oral)
Q12 IV bolus
Low Dose (1 x oral)
Continuous infusion
High Dose (2.5 x oral)
Q12 IV bolus
48 hours
1) Change to oral diuretics
2) continue current strategy
3) 50% increase in dose
72 hours
Co-primary endpoints
60 days
Clinical endpoints
High Dose (2.5 x oral)
Continuous infusion
Conclusions
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There was no statistically significant difference in global
symptom relief or change in renal function at 72 hours for
either:
– Q12 bolus vs. Continuous infusion
– Low intensification vs. High intensification
Conclusions (2)
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There was no evidence of benefit for continuous infusion
compared to Q12 hour bolus on any secondary endpoint
Despite transient changes in renal function, there was no
evidence for higher risk of clinical events at 60 days associated
with the high intensification strategy
High intensification (2.5 x oral dose) was associated
with trends towards greater improvement in multiple
domains:
–
–
–
–
Symptom relief (global assessment and dyspnea)
Weight loss and net volume loss
Proportion free from signs of congestion
Reduction in NT-proBNP
Diuretic Resistance: Other
Approaches to Consider
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Addition of inotrope (e.g., dobutamine)
– and / or vasodilator (e.g., nesiritide),
– or inodilator (e.g., milrinone) to improve cardiac output,
and hopefullly, renal perfusion
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Addition of low-dose dopamine to increase renal
perfusion
Vasopressin antagonists if hyponatremic (tolvaptan,i.v.,
lixivaptan, p.o.)
Ultrafiltration
Pre- and Post-Discharge Management
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Stable weight (for at least 2 days) on stable doses of oral
diuretics
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Pre-discharge education (i.e., diet, weight, medications, activity
level and what to do when problems arise)
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Discharge planning with CMP nurse
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Follow-up visits with CMP Clinic and primary physicians, etc
Patient: Not diuresing
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67 year old man, ischemic CMP admitted with progressive DOE and
fatigue
Modest response to diuretics, still very sob
BP 100/84, HR 98, bibasilar rales, pedal edema, cool feet
Labs: BUN 50, creat 2.5, BNP 1,500
Poor response to continuous infusion furosemide
PA catheter: RA 17, PCWP 34, CO 2.7 (CI 1.6), SVR 1870
Which drug would you use next?
Dry
Wet
1. Dobutamine
2. Dopamine
Warm A - Normal
B
3. Nitroglycerin
4. Milrinone
D
5. Nitroprusside
C
Cold
6. Nesiritide
“Typical” management of patients with ADHF
who fail continuous furosemide
Discharge
76%
Continuous
IV Lasix
50%
No/Partial
Response to
Lasix Bolus
50%
“Typical” management of patients with ADHF
who fail continuous furosemide
50%
Discharge
76%
Continuous
IV Lasix
30%
Inotropes
Other 50%
(750,000)
No/Partial
Response to
Lasix Bolus
20%
Natrecor
4%
Natrecor
18%
Inotropes
2%
Die/Mech
Assist/Tx
80%
Discharge
20%
Inotropes
70%
Discharge
30%
Die/Mech
Assist/Tx
90%
Discharge
10%
Inotropes
Discharge
Die/Mech
Assist/Tx
Discharge
Die/Mech
Assist/Tx
Discharge
Die/Mech
Assist/Tx
80%
20%
90%
10%
95%
5%
Inotropes: Beta-Agonists
Agonist
1AR
Gs
Ca++
ACase
cAMP
PKA
Dobutamine: beta1-Adrenergic Agonist
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Stimulates cAMP
Inotrope, weak vasodilator
Titrated to cardiac index
Side effects: Tachycardia,
arrhythmias, ischemia
Hypo-responsiveness
Variable inotropic response,
needs to be titrated
Colucci et al., Circulation 1986;73:III175
Low-dose Dopamine
Myocardial
1/2
Dobutamine
Vascular
1
Renal
1
dopaminergic
+++
++
++
0
Dopamine (low dose)
0
0
0
+++
Dopamine (high dose)
+++
+++
0
+++
Dobutamine vs. Dopamine
Dob: 2.5-10 g/kg/min
Dopa: 2-8 g/kg/min
HR
90
80
70
2.5
3.0
3.5
30
26
22
18
14
SVR
PCWP
CI
2.5
3.0
CI
3.5
1600
1400
1200
1000
2.5
3.0
3.5
CI
Leier et al., Circulation 1978
Inotropes: PDE Inhibitors
Agonist
1AR
Gs
Ca++
ACase
cAMP
PKA
PDE3
AMP
PDEinh.
Milrinone: PDE Inhibitor
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Inhibits phosphodiesterase, thereby increasing
cAMP in myocardium and vasculature
Potent inotrope
Potent vasodilator
Side effects similar to dobutamine (tachycardia,
arrhythmias, ischemia) plus hypotension
Simplified dosing
Hemodynamic effect of arterial dilation
BP = CO X SVR
Normal
 SVR
 CO
 BP
HF
 SVR
 CO
 BP
Vasodilator Classification
Venous
Nitrates
Mixed
Nitroprusside
Nesiritide
ACEI
ARBs
Arterial
Arterial
Hydralazine
Venous
Nitroprusside
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Very potent, balanced, direct-acting vasodilator
Very rapid action
Requires central monitoring
Effects highly variable patient-to-patient
Cyanide and thiocyanide toxicity
Rebound after withdrawal
Nitroprusside: Toxicity
CN
2Na+
CN
CN Fe -NO
CN
CN
Liver dysfunction
Cyanide toxicity
--
Renal dysfunction
Thiocyanate toxicity
Hemodynamic Effects of Hydralazine
and Isosorbide Dinitrate
HZ + ISO
HZ
Stroke Volume
Baseline
Pulmonary Capillary wedge Pressure
As per Chatterjee K, Parmley WW, Massie B, et al.
Circulation 1976; 54: 879-883.
NO-mediated vasodilation: Natriuretic peptides
Endothelium
NO-donating Drugs
NO
Soluble
Guanylate
cyclase
ANP
BNP (nesiritide)
Vascular Smooth Muscle Cell
cGMP
Vasodilation
NP Receptor
Particulate
Guanylate
Cyclase
Nesiritide: A gentler nitroprusside
35
PCWP
(mm Hg)

placebo
30
25
*
20
0.015 µg/kg/min
*
*
0.03 µg/kg/min
15
2.5
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CI (L/min/m2)
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2
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1.5
BL
1.5
3
Time (hours)
4.5 6
Colucci, et al. NEJM 2000; 343:246-53
Direct-acting balanced vasodilator
Less potent and rapid than NTP
But, does not require central monitoring
and no direct toxicity
However, not a diuretic
Dose-related hypotension
Concerns about renal effects
Concerns about adverse outcomes
ASCEND Trial – neutral outcomes
Use as needed for symptoms and
hemodynamics, not outcomes
Updated Guide to Initial Therapy
CO
PCWP
Low
High
Low
High
Low
High
SVR
High
BNP
SNP
TNG
Milrinone
Normal
BNP
SNP
Dob +/- VD
Milrinone
Low
Dob
Dopa
Modified from Stevenson and Colucci, Cardiovascular Therapeutics