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