August 9, 2006 Joann Lindenfeld, MD

Diagnosis and
Treatment of
Acute Heart
Failure
August 9, 2006
JoAnn Lindenfeld, MD
Hospitalization: The Predominant
Contributor to HF Costs
38.1 billion (5.4% of healthcare)
38.6%
60.6% Outpatient care
Inpatient care (3.4 visits/year
14.7 /patient)
23.1 billion
billion
0.7%
Transplants
$270 million
(O’Connell JB et al. J Heart Lung Transplant. 1994;13:S107-S112)

Similarities Between Acute MI and Acute
Decompensated HF in the US
Acute MI ADHF
Incidence 1 million per year 1 million per year
Mortality
In-hospital 3–4% 3–4%
After discharge (60–90 d) 2% 10%
Pathophysiological target(s) Clearly defined Uncertain

(coronary
thrombosis)
Clinical benefits of Beneficial Minimal/no benefit or
interventions in published deleterious compared with
clinical trials placebo
ACC/AHA recommendations Many None
Level A
(Gheorghiade M, et al. Circulation 2005;112:3958-68)

I pretty much try to stay in a constant state of confusion just
because of the expression it leaves on my face.
- Johnny Depp
Hospital discharges for HF by age:
1990 vs 2000
↑44%
↑32%
↑42% ↑44%
↑53% ↑84%
Natural History of Chronic and Acute
Heart Failure
Normal heart Chronic heart failure Death
5 million in the US
10 million in Europe
Initial
myocardial
injury
What if fluid overload

Heart Viability
causes progressive HF?

First ADHF episode:
Pulmonary edema
ER admission
Later ADHF episodes:

Rescue therapy
ICU admission
Initial phase Last year

Gheorghiade M. Am J Cardiol. 2005;96(suppl 6A):1-4G.
Mechanism of Worsening HF with Renal
Dysfunction
Renal dysfunction
(Schrier RW. JACC

2006;47:1-8)
Current Treatment of Heart Failure
Acutely Decompensated Heart Failure (ADHF)
♥ How to predict mortality?

♥ What do these patients look like?
♥ How do you know how much to diurese?
♥ Is BNP useful in judging diuresis?
♥ How to use diuretics
♥ What do you do when the creatinine
increases?
♥ Is ultrafiltration useful?
♥ ACE-inhibitors or beta-blockers first?
♥ Should beta-blockers be started in hospital?
♥ When should you use intravenous therapy?
Predictors
of In-
Hospital
Mortality
Fonarow, G. C. et al. JAMA

2005;293:572-580.
Copyright restrictions may apply.
Heart Failure Risk Scoring System
Lee, D. S. et al. JAMA 2003;290:2581-2587.

Mortality Rates in Acutely Decompensated
Heart Failure by Risk Score
Lee, D. S. et al. JAMA 2003;290:2581-2587.


increases?
Epidemiology of HF
ADHERE Euro-HF OPTIMIZE-HF
(n=110 000) (n=11 000) (n=48 612)
Important demographic
characteristics
Mean age, y 75 71 73
Women, % 52 47 52
Known heart failure, % 75 65 87
Preserved EF, % 40 54 49
Medical history, %
CHD 57 68 50
Hypertension 72 53 71
Diabetes 44 27 42
Atrial fibrillation 31 43 31
Renal insufficiency 30 17 30
COPD 31 ... 28

Epidemiology of HF
ADHERE Euro-HF OPTIMIZE-HF
(n=110 000) (n=11 000) (n=48 612)
Clinical profile at presentation
Mean systolic blood pressure, mm Hg 145 133 142
Systolic blood pressure >140 mm Hg, % 50 29 48
Dyspnea at rest, % 34 40 44
Dyspnea on exertion, % 89 35 61
Rales, % 67 ... 64
Jugular venous distension, % ... ... 28
Peripheral edema, % 66 20 65
Outpatient medication use before hospitalization, %
Diuretics 70 87 66
ACE inhibitors 40 62 40
Angiotensin receptor blockers 12 5 12
ß-Blockers 48 37 53
Digoxin 28 36 23
Aldosterone antagonists ... 21 7
Hydralazine ... ... 3
Nitrates 26 32 22

Congestion in HF:
Most Admitted Patients are “Wet”
100%
89%
90%
80% 74%
Admitted Patients (%)
70% 67% 65%

60%
50%
40% 34%
30%
20%
10%
0%
Any Dyspnea Pulmonary Rales Peripheral Dyspnea at Rest
Congestion Edema
(CXR)
<
(ADHERE Registry. 3rd Qtr 2003 National Benchmark Report.)

ADHERE: Diuresis During ADHF
Hospitalization
35%
30%
30% N=26,757
Men - 3.5 kg
Women -2.5 kg
Patients Discharged (%)
25% 24%
20%
15%
15% 13%
10%
7%
6%
5% 3%
2%
0%
<-20 -20 to -15 -15 to -10 -10 to -5 -5 to 0 0 to 5 5 to 10 >10
Change in Body Weight During Hospitalization (lbs)
Time Course of Events Preceding
ADHF Hospitalization
ePAD (19) (-89 to -1)
Thoracic
(-25 to -5)
Impedance (15)
SDAAM (16) (-21 to ?)
Dyspnea (8-9)
Edema,
Cough (10) Cough,
Fatigue (7)
Weight gain (11)
Dyspnea (3)
Days Edema (12)
I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
-90 -25 -20 -15 -10 -5 0 5 10
Admission
Rapid Assessment of Hemodynamic Status
Congestion at Rest Signs/Symptoms of
NO YES Congestion:
Orthopnea / PND
JV Distension
N Hepatomegaly
Low O Edema
Rales (rare in chronic
Perfusion heart failure)
at Rest Elevated est. PA
systolic( loud P2
Y and RV lift)
E
Valsalva square wave
S
Abdominojugular
reflux
Possible Evidence of Low Perfusion:
S3
Narrow pulse pressure Cool extremities
Sleepy / obtunded Hypotension with ACE inhibitor
Low serum sodium Renal Dysfunction (one cause)
Elevated LFTs Pulsus alternans
Value of Proportional Pulse Pressure
to predict low cardiac output
• Pulse Presssure
Systolic BP- Diastolic BP
• Proportional Blood Pressure

• Systolic BP – Diastolic BP = ≤ 25%
Systolic BP
= CI ≤ 2.2
L/min/M2
(JAMA 1989;261:884)
Congestion at Rest
NO YES
Warm &
Warm Wet
N
& Dry
Low O
67%
Perfusion
at Rest Cold & Cold &
Y Dry Wet
E
S
5% 28%
Nohria,J Cardiac Failure 2000;6:64

Physical Findings for PCW > 22 mm Hg
at admission in ADHF
Sensitivity Specificity
JVP > 11cm 67% 74%
Edema > trace 48% 69%
Increase P2 37% 75%

inferolalerally
Rales 15% 85%
>4 fingerbreadths liver 15% 92%
S3 63% 40%
Valsalva square 13% 96%

root sign
Valsalva Maneuver
Normal
Abnormal
Potential Endpoints of Therapy in ADHF
• Resting symptoms
• JVD
• Rales
• Edema
• PCW or Cardiac Output
• BNP
• Echo (mitral regurgitation or PA
pressure)
(Drazner M, et al. J Heart Lung Tx 1999;1126. Rosario, et al. JACC 1998;1819-24. Johnson, et
al. Ciruclation 1998 [abstract])
Is the Swan-Ganz Catheter Useful in the
Patient with Acute Decompensated HF?
NO
(Stevenson, et al. JAMA 2005;294:1625-1633)

Clinical outcomes in the ESCAPE trial
Six-month end points PAC, Clinical,
n=215 n=218
(%) (%)
Days dead or 38 36
hospitalized (mean)
Mortality 20.9 17.4
Rehospitalizations/ 2.1 2.1
patient (mean)
Days in hospital 11 11
(median)
p=NS for all
PAC=pulmonary artery catheterization; clinical=clinically
guided therapy only
Shah M. American Heart Association Scientific Sessions 2004.
ESCAPE
In-hospital complications and adverse events
Complications/adverse events PAC, Clinical,

n=215 (%) n=218 (%)
Bleeding 1.0 0
VT >30 sec or VF 0.5 0
PAC infection 1.9 0
Pulmonary infarction/hemorrhage 0.9 0
Cardiogenic shock 2.8 0.9
Myocardial infarction 0 0.5
Pulmonary embolism 0.5 0
Cardiac arrest 4.2 2.3
Antibiotic-requiring infection 13 9.2
Shah M. American Heart Association Scientific Sessions 2004. Nov 7-10, 2004;
Early Response of PCW but not CI Predicts
Subsequent Mortality in Advanced Heart Failure
Total Mortality Risk% Total Mortality Risk%

60 60
50 50
40 PCW > 16 mmHg 40

Cardiac Index > 2.6 L/min-M2
30 30
199 PCW < 16 mmHg
20 20
236 Cardiac Index < 2.6 L/min/M2
10 10
257 P=0.001 220 P=NS
0 0
0 6 12 18 24 0 6 12 18 24
Months Months
Final hemodynamic measurement in 456 advanced HF patients after tailored vasodilator therapy
(Fonarow G Circulation 1994;90:I-488)


increases?
Structure and Cleavage of proBNP
T ½ = 2 hours T ½ = 22 minutes
Both digested by NEPs and cleared renally

BNP is Increased with HF and
Systolic or Diastolic Dysfunction
Maisel AS, et al. JACC 2003;41:2010

BNP Levels Pre-discharge Predict Mortality
and Readmisssion
(Logeart D, et al. JACC 20042;40:976-82)

BNP on admission is a poor predictor of
PCW
(Forfia PR, et al. J Am Cardiol 2005;45:1667-71)

STARBRITE TRIAL

increases?
Sodium Reabsorption Sites in the Nephron
70% Distal Tubule
Proximal Tubule 5% Thiazide
Diuretics
Collecting Tubule
Loop
Diuretics
Glomerulus
20% 1-4%
Loop of Henle
Determinants of Diuretic Response
Maximal Response
Dose A
Bioavailability
Tubular secretory
Sodium Excretion Rate
capacity
Rate of absorption
Time course of delivery
cy
i en
fi c
Ef
B
Altered dose-response
relationship
Threshold Braking phenomenon
Loop Diuretic Excretion Rate

Bioavailability of Loop Diuretics
100% -
80% -
50% -
10% -
furosemide torsemide bumetanide

Ceiling Doses of Loop Diuretics (mg)
Furosemide bumetanide torsemicle

IV po IV po IV po
Renal Insufficiency
moderate 80 80 2-3 2-3 20-50 20-50
severe 200 240 8-10 8-10 50-100 50-100
Cirrhosis with 40 80-160 1 1 10-20 10-20

normal GFR
CHF with normal GFR 40-80 160-240 2-3 2-3 20-50 20-50
(Adapted from Brater C. New Engl J Med 1999)

Bioavailability of Loop Diuretics
100% -
80% -
50% -
10% -
furosemide torsemide bumetanide

Usefulness of Torsemide after Admission
for ADHF
234 pts admitted for ADHF

Randomized on Discharge
torsemide furosemide
52% ↓ HF Hospitalization
(Murray, et al. Am J Med 2000;111:513-521)


increases?
Baseline Renal Dysfunction and Worsening Renal Function
(WRF) are Additive in Predicting Mortality in HF Patients
Predictors of WRF were thiazide

diuretics, increased BUN, and
vascular disease
And a fall in sCr of >

0.3 mg/dL was
associated with
improved mortality
sCreatinine ≤1.2 1.2-2.0 ≥2.0 ≤1.2 1.2-2.0 ≥2.0

WRF (>0.3mg/dL) no no no yes yes yes
(de Silva, R. et al. Eur Heart J 2006 27:569-581)

What to do when the creatinine begins to
increase?
• Check volume status
• Check blood pressure (especially at peak
onset of vasodilators)
• Restrict sodium intake (and water if
hyponatremic)
• Check for renal problems (obstructions,
prooteinuria, interstitial nephritis)
• Consider vasodilators or inotropes
• Consider ultrafiltration
UNLOAD Trial
n = 200 with ADHF
IV Diuretics Ultrafiltration
for 48 hours
Costanzo MR. American College of Cardiology 2006

Scientific Sessions; March 12, 2006; Atlanta, GA.
Ultrafiltration Improved Weight Loss But
Not Symptoms
End points Ultrafiltration Diuresis p

n 83 84
48 hours
•Weight loss, primary end point 5.0 3.1 0.001
(mean kg)
•Dyspnea score, primary end 6.4 6.1 0.35
point (mean)
•Net fluid loss (mean L) 4.6 3.3 0.001
•K<3.5 mEq/L (%) 1 12 0.018
•Need for vasoactive drugs (%) 3 13 0.015
Costanzo MR. American College of Cardiology 2006

Scientific Sessions; March 12, 2006; Atlanta, GA.
Ultrafiltration Decreased Rehospitalization
End points Ultrafiltration Diuresis p

90 days
•Rehospitalization (%) 18 32 0.022
•Rehospitalization days (mean) 1.4 3.8 0.022
•Unscheduled office/ED visits (%) 21 44 0.009
Costanzo MR. American College of Cardiology 2006 Scientific

Sessions; March 12, 2006; Atlanta, GA.

increases?
IMPACT - HF
n = 363 with ADHF
• Symptomatic hypotension
• Recent inotropes
• AV Block or SSS
• Hepatic impairment
Randomized
Pre-discharge Post-discharge
carvedilol carvedilol
(Galtis WA, et al. JACC 2004;43:1534)

IMPACT - HF
(Galtis WA, et al. JACC 2004;43:1534)

ACE-inhibitor or Beta-blocker First?
CIBIS-III
(Willenheimer R, et al. Circulation 2005;112:2426-2435)

CIBIS-III
Bisoprolol first
Enalapril first
(HR 0.94, CI = 077-1.16, = = 0.0.019 for noninferiority)

CIBIS-III
Bisoprolol first
Enalapril first
Survival
(HR 0.88, CI = 0.63-1.22, p = 0.44)

CIBIS-III
Enalapril first
Freedom
from Bisoprolol first
hospitaliz
ation for
worsening
HF
(HR = 1.25, CI = 0.87-1.81, p = 0.23)


increases?
Congestion at Rest
NO YES
Warm &
Warm Wet
N
& Dry
Low O
67%
Perfusion
at Rest Cold & Cold &
Y Dry Wet
E
S
5% 28%
Nohria,J Cardiac Failure 2000;6:64

Goals in the Treatment of the Patient with
Acutely Decompensated HF
Diuretics Nesiritide Milrinone
Improve symptoms yes (+++) yes (+) ?
Decrease mortality ? ?(↑) ?(↑)
Decrease hospitalization
Duration yes no no
Repeat hospitalization ? no no
Decreased costs yes no(↑) no(↑)

Enoximone or Milrinone are preferable to
Dobutamine in Patients on Beta-blockers
Metra M et al; JACC 2002

Enoximone or Milrinone are preferable to
Dobutamine in Patients on Beta-blockers
Metra M et al; JACC 2002

Before I came here I
was confused about
this subject. Having
listened to your
lecture I am still
confused. But on a
higher level.
-Enrico Fermi

August 9, 2006 Joann Lindenfeld, MD

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Diagnosis and

(O’Connell JB et al. J Heart Lung Transplant. 1994;13:S107-S112)

Pathophysiological target(s) Clearly defined Uncertain

(Gheorghiade M, et al. Circulation 2005;112:3958-68)

What if fluid overload

causes progressive HF?

Later ADHF episodes:

Initial phase Last year

(Schrier RW. JACC

♥ How to predict mortality?

Fonarow, G. C. et al. JAMA

Lee, D. S. et al. JAMA 2003;290:2581-2587.

Lee, D. S. et al. JAMA 2003;290:2581-2587.

♥ How to predict mortality?

(Gheorghiade M, et al. Circulation 2005;112:3958-68)

(Gheorghiade M, et al. Circulation 2005;112:3958-68)

70% 67% 65%

(ADHERE Registry. 3rd Qtr 2003 National Benchmark Report.)

SDAAM (16) (-21 to ?)

• Proportional Blood Pressure

Nohria,J Cardiac Failure 2000;6:64

Edema > trace 48% 69%

Increase P2 37% 75%

>4 fingerbreadths liver 15% 92%

Valsalva square 13% 96%

(Stevenson, et al. JAMA 2005;294:1625-1633)

Complications/adverse events PAC, Clinical,

Total Mortality Risk% Total Mortality Risk%

40 PCW > 16 mmHg 40

(Fonarow G Circulation 1994;90:I-488)

♥ How to predict mortality?

Both digested by NEPs and cleared renally

Maisel AS, et al. JACC 2003;41:2010

(Logeart D, et al. JACC 20042;40:976-82)

(Forfia PR, et al. J Am Cardiol 2005;45:1667-71)

♥ How to predict mortality?

Loop Diuretic Excretion Rate

furosemide torsemide bumetanide

Furosemide bumetanide torsemicle

severe 200 240 8-10 8-10 50-100 50-100

Cirrhosis with 40 80-160 1 1 10-20 10-20

(Adapted from Brater C. New Engl J Med 1999)

furosemide torsemide bumetanide

234 pts admitted for ADHF

(Murray, et al. Am J Med 2000;111:513-521)

♥ How to predict mortality?

Predictors of WRF were thiazide

And a fall in sCr of >

sCreatinine ≤1.2 1.2-2.0 ≥2.0 ≤1.2 1.2-2.0 ≥2.0

(de Silva, R. et al. Eur Heart J 2006 27:569-581)

n = 200 with ADHF

Costanzo MR. American College of Cardiology 2006

End points Ultrafiltration Diuresis p

Costanzo MR. American College of Cardiology 2006

End points Ultrafiltration Diuresis p

Costanzo MR. American College of Cardiology 2006 Scientific

♥ How to predict mortality?

(Galtis WA, et al. JACC 2004;43:1534)

(Galtis WA, et al. JACC 2004;43:1534)

(Willenheimer R, et al. Circulation 2005;112:2426-2435)

(HR 0.94, CI = 077-1.16, = = 0.0.019 for noninferiority)

(Willenheimer R, et al. Circulation 2005;112:2426-2435)