Hospital Management of
Decompensated Heart Failure
Wilson S. Colucci, MDChief, Cardiovascular Medicine
Acute Heart Failure Syndromes
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
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
17%Other19%
Failure to SeekCare
16%Inappropriate Rx
Rx Noncompliance
24%
Diet Noncompliance24%
HFSA Research 2000
Overall Goals in Management of AHFS
Immediate relief of symptoms and hemodynamic stabilization
Identification and correction of underlying / precipitating factors
Optimize fluid status (optimal weight, renal function, edema)
Establishment of effective ambulatory regimen prior to discharge
Discharge planning and follow-up
Precipitants of AHFS
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. 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
A - Normal B
C D
Dry Wet
Warm
Cold
PerfusionDyspneaRalesCVPEdema
Cold extremitiesHypotensionNarrow PPRenal insuff.
Acute HF: Clinical Signs
Intracardiac Filling Pressures– 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
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 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
Three best predictors of mortality in hospitalized patients– BUN > 43 mg/dL– SBP < 115 m Hg– Creatinine > 2.75 mg/dL
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.
? Inc Morbidityand Mortality
Diuretic Therapy
Worse renalfunction
Diuretic & NatriureticResistance
Diuretics can worsen renal function in HF
Decreased preload
NeurohormonalActivation
DiminishedRenal blood flow
Diuretics can improve renal function in HF
0.5
0.8
1.1
1.4
0 2 4 6 8
0 6 12 19 25 0
GFR
(m
l/m
in)
CVP, mm Hg
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
48 hours
1) Change to oral diuretics2) continue current strategy3) 50% increase in dose
Co-primary endpoints
High Dose (2.5 x oral)Q12 IV bolus
Low Dose (1 x oral)Continuous infusion
High Dose (2.5 x oral)Continuous infusion
72 hours
Clinical endpoints
60 days
Conclusions
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)
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
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
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
Stable weight (for at least 2 days) on stable doses of oral diuretics
Pre-discharge education (i.e., diet, weight, medications, activity level and what to do when problems arise)
Discharge planning with CMP nurse
Follow-up visits with CMP Clinic and primary physicians, etc
Patient: Not diuresing 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?
1. Dobutamine2. Dopamine3. Nitroglycerin4. Milrinone5. Nitroprusside6. Nesiritide
A - Normal B
C D
Dry Wet
Warm
Cold
“Typical” management of patients with ADHF who fail continuous furosemide
No/Partial Response to Lasix Bolus
No/Partial Response to Lasix Bolus
50%
Continuous IV Lasix
Continuous IV Lasix
76%
DischargeDischarge 50%
“Typical” management of patients with ADHF who fail continuous furosemide
No/Partial Response to Lasix Bolus
No/Partial Response to Lasix Bolus
Other 50%(750,000)
Continuous IV Lasix
Continuous IV Lasix
NatrecorNatrecor
InotropesInotropes
Die/Mech Assist/TxDie/Mech Assist/Tx
76%
4%
18%
2%Die/Mech Assist/TxDie/Mech Assist/Tx
30%DischargeDischarge
70%
InotropesInotropes20%
DischargeDischarge80%
NatrecorNatrecor20%
DischargeDischarge50%
InotropesInotropes30%
Die/Mech Assist/TxDie/Mech Assist/Tx
5%
DischargeDischarge 95%
InotropesInotropes10%
DischargeDischarge
90%
Die/Mech Assist/TxDie/Mech Assist/Tx 10%
DischargeDischarge 90%
Die/Mech Assist/TxDie/Mech Assist/Tx 20%
DischargeDischarge 80%
Inotropes: Beta-Agonists
Gs
ACase
1AR
Agonist
cAMP
PKA
Ca+
+
Dobutamine: beta1-Adrenergic Agonist
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
Vascular
1 1
Renal
dopaminergic
Dobutamine +++ ++ ++ 0
Dopamine (low dose) 0 0 0 +++
Dopamine (high dose) +++ +++ 0 +++
Dobutamine vs. Dopamine
70
80
90
2.5 3.0 3.5
HR
1418222630
2.5 3.0 3.5
PCWP
1000
1200
1400
1600
2.5 3.0 3.5SVR
Leier et al., Circulation 1978
Dob: 2.5-10 g/kg/minDopa: 2-8 g/kg/min
CI
CI
CI
Inotropes: PDE Inhibitors
Gs
ACase
1AR
Agonist
PDEinh.
PDE3
AMP
cAMP
PKA
Ca+
+
Milrinone: PDE Inhibitor
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
Venous
Arterial
VenousNitrates
Vasodilator Classification
MixedNitroprusside
NesiritideACEIARBs
ArterialHydralazine
Nitroprusside
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
Fe -NOCN
CN
CN
CN
CN
--
2Na+
Nitroprusside: Toxicity
Liver dysfunctionCyanide toxicity
Renal dysfunctionThiocyanate toxicity
Hemodynamic Effects of Hydralazine and Isosorbide Dinitrate
Baseline
HZ
HZ + ISO
As per Chatterjee K, Parmley WW, Massie B, et al. Circulation 1976; 54: 879-883.
Stroke Volume
Pulmonary Capillary wedge Pressure
NO-mediated vasodilation: Natriuretic peptides
Vascular Smooth Muscle Cell
SolubleGuanylate
cyclase
NO
cGMP
EndotheliumNO-donating Drugs
Vasodilation
NP ReceptorParticulate Guanylate
Cyclase
ANPBNP (nesiritide)
Nesiritide: A gentler nitroprusside
Time (hours)
1.5
2
2.5CI
BL 1.5 3 4.5 6
(L/min/m2)
15
20
25
30
35PCWP
** *
(mm Hg)
Colucci, et al. NEJM 2000; 343:246-53
0.03 µg/kg/min
placebo
0.015 µg/kg/min
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 Low Low LowPCWP High High High
SVR High Normal LowBNP BNP DobSNP SNP DopaTNG Dob +/- VDMilrinone Milrinone
Modified from Stevenson and Colucci, Cardiovascular Therapeutics