Download Congestion in Heart Failure

How Well is Chronic Heart
Failure Being Managed?
Gregg C. Fonarow, MD
Eliot Corday Professor of
Cardiovascular Medicine and Science
UCLA Division of Cardiology
Director, Ahmanson-UCLA Cardiomyopathy Center
Director, UCLA Cardiology
Fellowship Training Program
Los Angeles, California
Chronic Heart Failure
 Approximately 5 million Americans have Chronic HF
 550,000 new cases annually
 Hospital discharges 1,100,000 (2003)
 Accounts for 12 million office visits/year
 One of the largest expenses for Medicare
 Five-year mortality rate as high as 50%
HF, heart failure.
AHA. 2006 Heart and Stroke Statistical Update.
2
Burdens of Heart Failure
Congestive Symptoms
Activity Limitation
Dysrrhythmias
Hospitalizations
Reduced Survival
3
Decompensated Heart Failure:
The Major Contributor to Cost of Care
Health Care
Professionals
$2.0 Billion
(7%)
Nursing Home/
Home Health Care
$6.3 Billion
(21%)
Indirect
$2.8 Billion
(9.5%)
Drugs/Other
Medical Durables
$3.1 Billion
(10.5%)
American Heart Association. 2006 Heart and Stroke Statistical Update.
Hospitalization for
Decompensation
$15.4 Billion
(52%)
Total 2006
$29.6 Billion
4
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
100,000
Women
Men
0
CDC/NCHS: Hospital discharges include patients both living and dead.
AHA, 1998 Heart and Stroke Statistical Update.
NCHS, National Center for Health Statistics.
AHA, Heart Disease and Stroke Statistics -- 2005 Update.
5
Hospital Admissions for HF
Remain on the Increase Due to…
 Inevitable progression of disease
 Rising incidence of chronic heart failure
(population aging, improved survival with
AMI/revascularization)
 Incomplete treatment during hospitalization
 Poor application of chronic heart failure management
 Noncompliance with diet and drugs
 Difficulty in assessing volume status and closely
monitoring patients
AMI, acute myocardial infarction.
Fonarow GC, et al. Rev Cardiovasc Med. 2000;1:25-33.
6
6-Month Readmission Rates
Among 17,448 Survivors of
Hospitalization for CHF
60
Patients (%)
44
40
20
16
0
Rehospitalized
at least once
CHF, congestive heart failure.
17,448 Medicare patients who survived hospitalization for HF.
Krumholtz HM. Arch Intern Med. 1997;157:99-104.
Rehospitalized
at least twice
7
Outcomes During and
After HF Hospitalization
 In-hospital
– Length of stay (mean) 6.2 days
– Mortality rate 4.1%
 Hospital readmissions
– 20% at 30 days
– 50% at 6 months
 Longer-term mortality
– 11.6% at 30 days
– 33.1% at 12 months
Fonarow GC, et al. J Card Failure. 2003;9:S79.
Jong P, et al. Arch Intern Med. 2002;162:1689-1694.
8
Long-Term Trends in Mortality
With Heart Failure
Temporal Trends in Age-Adjusted Mortality
After the Onset of Heart Failure*
Period
30-Day Mortality,
1-Year Mortality,
5-Year Mortality,
% (95% CI)
% (95% CI)
% (95% CI)
Men
Women
Men
Women
Men
Women
1950–1969
12 (4-19)
18 (7-27)
30 (18-40)
28 (16-39)
70 (57-79)
57 (43-67)
1970–1979
15 (7-23)
16 (6-24)
41 (29-51)
28 (17-38)
75 (65-83)
59 (45-69)
1980–1989
12 (5-18)
10 (4-16)
33 (23-42)
27 (17-35)
65 (54-73)
51 (39-60)
1990–1999
11 (4-17)
10 (3-15)
28 (18-36)
24 (14-33)
59 (47-68)
45 (33-55)
*All values were adjusted for age (<55, 55-64, 65-74, 75-84, and ≥85 years).
Levy D, et al. N Engl J Med. 2002;347:1397-1402.
9
Evidence-Based Treatment
For Stage C Heart Failure
Reduce Mortality
ACEI
or ARB
ICD*
-Blocker
CRT 
an ICD*
Aldosterone
Antagonist
Hyd/ISDN*
Enhance Adherence
Education
Disease Management
Performance Improvement Systems
Control Volume
Salt Restriction*
Diuretics*
Treat Residual
Symptoms
Digoxin*
Treat
Comorbidities
Aspirin*
Warfarin*
Statin*
*For select indicated patients.
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ICD,
implantable cardioverter defibrillator; CRT, cardiac resynchronization therapy; Hyd/ISDN,
hydralazine and isosorbide dinitrate.
10
Utilization of Evidence-Based
Therapies in Heart Failure
History of HF and LVEF Documented and 0.40*
100
Enrolled Discharges (%)
90
80.8
80
70
60
57.4
50.8
50
41
40
30
20
12.8
10
0
ACE Inhibitor
ARB
-Blocker
Diuretic
Digoxin
*Excludes patients with documented contraindications.
LVEF, left ventricular ejection fraction.
2300/7883 patients hospitalized with HF; prior known dx of systolic dysfunction HF; outpatient medical regimen.
ADHERE Registry Report Q1 2002 (4/01-3/02) of 180 US Hospitals.
Presented by GC Fonarow at the Heart Failure Society of America Satellite Symposium, September 23, 2002.
11
Utilization of Evidence-Based HF
Therapies: IMPROVEMENT International
Survey
100
90
Patients (%)
80
70
60
60
50
40
34
30
20
20
12
10
0
ACE Inhibitors
(ACEI)
-Blockers
(BB)
ACEI + BB
Aldosterone
Antagonists
International survey: 15 countries, 1363 physicians, 11,062 patients: Year 2000.
Outpatient regimen in patients with Stage C HF, documented systolic dysfunction.
Cleland JG, et al. Lancet. 2002;360:1631-1639.
12
ADHERE Quality of Care Conformity
to JCAHO HF Performance Indicators
Lagging Centers
120%
Leading Centers
97%
100%
Utilization (%)
88%
80%
70%
85%
72%
58%
60%
40%
20%
8%
1%
0%
Discharge
Instructions
LV Function
Measurement
ACEI use
All P<0.0001.
81 142 admissions between 6/2002-12/2003 at 223 hospitals
Grouped by Leading (90th percentile) and Lagging (10th percentile).
JCAHO, Joint Commission on Accreditation of Healthcare Organizations.
Fonarow GC, et al. Arch Intern Med. 2005;165:1469-1477.
Smoking
Cessation
13
“Failure” of Usual Care
in Heart Failure
 Failure to prescribe evidence-based medications
 Failure to discontinue medication that may exacerbate HF
 Failure to titrate medications to target doses
 Failure to adequately address co-morbidities
 Failure to adhere to prescribed medications
 Failure to comply with dietary regimen
 Failure to adequately assess congestion
 Failure to seek early care with escalating symptoms
 Failure of adequate discharge planning
 Failure of adequate follow-up
 Failure of adequate monitoring
 Failure of patient social support systems
 Failure to address patient and caregiver needs
14
Congestion in Heart Failure
 Congestion is the primary cause of heart failure
symptoms, hospital admissions, and hospital
readmissions
 Congestion is an important predictor of mortality
and morbidity
 Clinical congestion often lags behind rising filling
pressures (hemodynamic congestion)
 Congestion is often difficult to recognize, delaying
appropriate interventions
15
Clinical Presentation of Patients
Hospitalized with Heart Failure
150,000 Hospitalization Episodes in ADHERE
Any dyspnea (%)
89
Dyspnea at rest (%)
34
Fatigue (%)
32
Rales (%)
68
Peripheral edema (%)
66
Pulmonary congestion (%)
75
SBP <90 mm Hg (%)
ADHERE, Acute Decompensated Heart Failure National Registry.
Adapted from Fonarow GC. Rev Cardiovasc Med. 2003;4(Suppl 7):S21-S30.
2
16
Congestion Often Does not
Translate into Signs/Symptoms
 Among patients with severe heart failure1
– PCWP 33 ± 6 mm Hg, CI 1.8 ± 0.5, LVEF 0.18 ± 0.06
– CXR: 27% no congestion, 41% minimal congestion
 Among patients with moderate to severe heart failure2
– PCWP 30 ± 9 mm Hg, CI 2.1 ± 0.8, LVEF 0.18 ± 0.06
– No rales: 84%, No edema: 80%, No JVP 50%, No
orthopnea: 22%
 Hemodynamic congestion may not be recognized clinically
(doesn’t translate into symptoms/signs until late)
PCWP, pulmonary capillary wedge pressure; CI, cardiac index; CXR, chest X-ray; JVP, jugular venous pressure.
1. Mahdyoon H, et al. Am J Card. 2003;63:625-627.
2. Stevenson LW, et al. JAMA. 1989;261:884-888.
17
Hemodynamic vs Clinical Congestion
Obvious
Congestive
Symptoms
Stevenson LW, et al. Circulation. 2006;113:1020-1033.
18
Congestion Precedes
Hospitalization
Pressure Change
Hospitalization
40
Change (%)
30
20
10
RV Systolic Pressure
Estimated PA Diastolic
Pressure
0
Heart Rate
-10
Baseline
-7
-6
-5
-4
-3
-2
-1
Recovery
Days Relative to the Event
RV, right ventricular; PA, pulmonary artery.
Adamson PB, et al. J Am Coll Cardiol. 2003;41:565-571.
19
Importance of
Recognizing Congestion
 In chronic heart failure,  LV filling pressures
(even severe) infrequently cause rales and acute
pulmonary edema1,2
 Recognizing hemodynamic congestion is challenging
 Identifying congestion early will lead to early
treatment, and possibly prevent progression of heart
failure and hospitalizations
1. Mahdyoon H, et al. Am J Card. 1989;63:625-627.
2. Stevenson LW, et al. JAMA. 1989;261:884-888.
20
Common Signs and
Symptoms of Congestion
 Signs
– Jugular venous
distention/elevation
– Peripheral edema
– Pulmonary congestion/
rales
– Pleural effusions
– S3 gallop
 Symptoms
– Dyspnea on exertion
– Orthopnea
– Paroxysmal nocturnal
dyspnea
– Fatigue
– Abdominal fullness
– Anorexia, nausea,
vomiting
21
Conventional Methods Used
in the Assessment of Congestive
in Patients with Heart Failure
 Symptoms
 Change in weight
 Physical examination
 Chest X-ray
 Echocardiogram
 Right heart catheterization (Swan-Ganz)
 Left heart catheterization
22
The Challenge of Diagnosing
Heart Failure: Physical Examination
 JVP on Physical Exam
– Great if well seen
– In OPTIMIZE-HF and
ADHERE, in the majority
of hospitalized HF
patients, initial exam
missed it
– Obesity epidemic:
good luck
 S3 on physical exam
– Great if heard
– Missed 4/5 times
OPTIMIZE-HF, Organized Program to Initiate Life-Saving Treatment in Hospitalized Patients with Heart Failure.
23
How Good Is the Physical Examination
for Estimating Hemodynamics?
Variable
Sensitivity (%)
Specificity (%)
PPA (%)
NPA (%)
RAP
JVP
48
78
60
69
Edema
10
94
55
60
27
69
52
44
S3
36
81
69
54
Dyspnea
50
73
67
57
Rales
13
90
60
48
Cardiac Index
Pulse Pres
PCWP
RAP, right atrial pressure.
366 patients with heart failure undergoing examination and right heart catheterization.
Capomolla S, et al. Eur J Heart Fail. 2005;7:624-630.
24
The Limited Reliability of the Physical
Examination in Heart Failure
 Prospectively compared physical signs with
hemodynamic measurement in 50 hospitalized
patients
 Rales, edema, JVP elevation absent in 18 of 43
patients with PCWP >24 mm Hg
 Sensitivity 58%, specificity 100%
Stevenson LW, et al. JAMA. 1989;261:884-888.
25
Phonocardiographic Analysis of S3 and S4
in Patients Undergoing Catheterization
Heart sound
Elevated LVEDP
S3 sensitivity (%)
41
S4 sensitivity (%)
46
S3 specificity (%)
92
S4 specificity (%)
80
LVEDP, left ventricular end-diastolic pressure.
Marcus GM, et al. JAMA. 2005;293:2238-2244.
26
Chest X-Ray in Heart Failure
27
How Good Is Chest X-ray
in Diagnosing Heart Failure?
 CXR blows
– Misses 20% of echoproven cardiomegaly
– Detection of pleural
effusion if supine
• 67% sensitivity
• 70% specificity
– Even worse
if done portable
Kono T, et al. Jpn Circ J. 1992;56(4):359-365.
Ruskin JA, et al. Am J Roentgenol. 1987;148(4):681-683.
28
Hospitalizations for Heart Failure
 Congestion is the primary reason for heart failure
admissions
 Low cardiac output and associated signs/symptoms
are uncommon
 Suboptimal weight reduction during hospitalization
 Although appear improved clinically, many patients
are discharged with signs and symptoms (related
to pulmonary congestion that is not being identified
clinically)
29
More than 50% of Patients Have Little or
No Weight Loss During Hospitalization
35
33%
Patients (%)
30
24%
25
20
13%
15
10
15%
7%
6%
3%
5
2%
0
(<-20)
(-20 to -15) (-15 to -10) (-10 to -5)
(-5 to 0)
(0 to 5)
(5 to 10)
(>10)
Change in Weight (lbs)
Fonarow GC. Rev Cardiovasc Med. 2003;4(Suppl 7):S21-S30.
30
Change in Heart Failure Signs and
Symptoms (Admission to Discharge)
Admission
Discharge
79
42
50
33
53
58
5
12
4
57
33
57
20
50
6
13
6
13
Symptoms (%)
Dyspnea on exertion
Dyspnea at rest
Orthopnea
PND
Fatigue
Signs (%)
JVP >6cm
Rales
S3 gallop
Edema >2+
PND, paroxysmal nocturnal dyspnea.
Gattis WA, et al. J Am Coll Cardiol. 2004;43:1534-1541.
31
Hospitalization Outcomes
ADHERE
OPTIMIZE-HF
(107,920 patients) (34,059 patients)
>2.5 kg weight loss (%)
50
50
Unchanged/worse
Better (symptomatic)
Better (asymptomatic)
Length of stay (mean days)
In-hospital mortality (%)
Mortality at 2-3 months (%)
<1
40
50
6.1
4.0
N/A
<3
40
51
6.4
3.8
9
Readmissions at 2-3 months (%)
N/A
31
HF symptoms
Adams KF, et al. Am Heart J. 2005;149:209-216.
Fonarow GC, et al. J Am Coll Cardiol. 2004;844-4A.
32
Outpatient Monitoring
of Congestion
 Signs and symptoms
 Daily weights
 Natriuretic peptides (BNP and NT-pro BNP)
 Noninvasive bioimpedence monitors
BNP, brain (B-type) natriuretic peptide; NT, N-terminal.
33
Limited Reliability of Daily Weights
Over Time
 Daily weights are helpful but not always reliable
predictors of heart failure status
 Many patients have difficulty operating/reading
scales or remember to weigh themselves
 Weight gain may reflect normal fluctuations,
variation in time/conditions of weights, or
improved appetite with improved heart failure
 Weight loss due to loss of muscle/fat (cachexia)
may obscure increased fluid retention
34
Interventions to
Relieve Congestion
 Increase dietary sodium restriction
 Fluid restriction
 Increase dose, frequency, or mode of administration
of loop diuretics
 Add/adjust dose of aldosterone antagonist
 Thiazide diuretics
 Metolazone
 Vasopressin antagonists*
 Ultrafiltration*
*Still investigational.
35
Key Therapeutic Goal in HF:
Maintain Optivolemic State
Hypervolemia: Increased symptoms,
increased risk of hospitalization,
increased risk of arrhythmias, increased
mortality
Optivolemia: Low risk
Hypovolemia: Is over-diuresis a problem?
36
Loop Diuretics and Heart Failure
 There have been no outcome studies of diuretic
therapy for the treatment of heart failure and, thus,
it’s effects on morbidity and mortality are not known
 Diuretic therapy administered as monotherapy
results in all of the following:
– Further activation of renin-angiotensin-aldosterone
system
– Further activation of sympathetic nervous system
– Reflex vasoconstriction, increased afterload
– Decrease in stroke volume and cardiac output
– Substantial reduction in glomerular filtration rate (GFR)
Ravnan SL, et al. Congest Heart Fail. 2002;8:80-85.
Brater DC. Drugs. 1985;30:427-443.
37
Marked Activation of the ReninAngiotensin-Aldosterone
System By IV Loop Diuretics
1000
Mean
(95% CI)
10
2.5
0.5
Plasma aldosterone (pmol/L)
Plasma renin activity (ng/mL/h)
50
Mean
(95% CI)
600
200
100
Before Diuretic
(n=12)
After Diuretic
(n=11)
Bayliss J, et al. Br Heart J. 1987;57:17-22.
Before Diuretic
(n=12)
After Diuretic
(n=11)
38
Acute Vasoconstrictor Response to IV
Furosemide in Congestive Heart Failure
Hemodynamic
Variable
Baseline
20 mins after IV
Furosemide 40 mg
P Value
PAWP (mm Hg)
33 ± 9
28 ± 7
<0.01
SVI (mL/min/m2)
27 ± 8
24 ± 7
<0.01
HR (bpm)
87 ± 13
91 ± 16
<0.01
BP (mm Hg)
90 ± 15
96 ± 15
<0.01
SVR (dyn-s-cm-5)
1454 ± 384
1676 ± 415
<0.01
PRA (ng/mL)
9.9 ± 8.5
17.8 ± 16
<0.05
PNE (pg/mL)
667 ± 390
839 ± 368
<0.01
SVI, stroke volume index; HR, heart rate; BP, blood pressure; SVR, systemic vascular resistance;
PRA, plasma renin activity; PNE, plasma norepinephrine.
Kubo SH, et al. Am J Cardiol. 1987;60:1322-1328.
39
Furosemide Monotherapy Causes a
Significant Decline in Renal Function
15
GFR (% change)
10
Placebo
5
0
-5
IV Furosemide
-10
-15
-20
-25
0
500
1000
1500
2000
2500
Urine Output (mL) 0 - 8 hours
Change in GFR after furosemide 80 mg IV, Class III HF n=16 age 61, LVEF 0.28, CAD 63%,
Gottlieb SS, et al. Circulation. 2002;105:1348-1353.
40
Higher Doses of Loop Diuretic
is Associated with Increased
Mortality in Severe HF
1.0
 Retrospective analysis of 1153
patients with advanced HF from
PRAISE study
0.8
Group
Diuretic dose
A
B
C
D
High
High
Low
Low
ACE inhibitor dose
Low
High
Low
High
n=240
n=160
n=526
n=224
 High diuretic use independent
predictor of:
–
Total mortality (HR 1.37;
P=0.018)
–
SCD (HR 1.39; P=0.042)
–
Pump failure death (HR 1.51;
P=0.034)
 Metolozone use also independent
predictor of mortality
Total mortality
 Loop diuretic above and below
median compared
A
0.6
B
C
0.4
D
0.2
Chi-square=33.83
P=0.0001
0
0
6
12
18
24
30
36
Months from Randomization
PRAISE, Prospective Randomized Amlodipine Survival Evaluation; SCD, sudden cardiac death.
Neuberg GW, et al. Am Heart J. 2002;144:31-38.
41
Difficulty Assessing
Volume Status
 May contribute to over diuresis and higher dose
than necessary loop diuretic use
 Over diuresis contributes to adverse symptoms
such as dizziness and headache
 Over diuresis contributes to renal dysfunction
and increased risk of acute renal failure
 Excess diuretic use is associated with further
neurohumoral activation
 Excess diuretic use is associated with increased
mortality
42
Key Therapeutic Goal in HF:
Maintain Optivolemic State
Hypervolemia: Increased symptoms,
increased risk of hospitalization,
increased risk of arrhythmias, increased
mortality
Optivolemia: Low risk
Hypovolemia: Increased symptoms,
increased risk of hospitalization,
increased risk of renal failure, increased
mortality
43
Conventional View: Pathophysiological
Differentiation of Symptoms and
Progression in Heart Failure

What produces heart failure symptoms?
– Hemodynamic abnormalities (e.g., changes
in cardiac function and peripheral
hemodynamics)

What produces disease progression?
– Neurohormonal abnormalities (e.g.,
activation of renin-angiotensin-aldosterone
and sympathetic nervous systems)
Time-Dependent Mortality
Risk in Heart Failure
Weekly Mortality Risk
5
HR=20
AHF Hospitalization
4
Mortality %
4
3
Stage C Outpatient
HR=10
3
2
2
HR=4
2
1
1
1
1
0.8
0.8
0.8
0.8
0.8
0.5
0.5
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
0.5
0.2
0.5
0.5
0.2
0.2
16
17
0.4 0.4 0.4
0.4 0.4 0.4 0.4
0.2 0.2 0.2
0.2 0.2 0.2 0.2
0
15
18
19
20
21
22
23
24
Time (weeks)
AHF, acute heart failure.
45
Mechanisms by Which Elevated LV Filling
Pressures Could Contribute to Mortality in HF
 Stretch induced angiotensin II release
 Mechanically induced myocardial structural remodeling
 Progressive atrioventricular valvular regurgitation
 Subendocardial ischemia/cell death by necrosis/apoptosis
 Changes in extra cellular matrix structure and function
 Myocardial stretch induced increase in intracellular cAMP and calcium
 Desensitization of low pressure ventricular mechanoreceptors

What produces disease progression?
– Neurohormonal abnormalities
– Persistent elevation in ventricular filling pressures
– Acute decompensation of heart failure
Implantable Devices May Offer
Unique Means to Monitor Fluid Status
 Objectively track fluid accumulation and/or
hemodynamics longitudinally over time
 Multiple measurements per day are averaged to
give a truer picture of that day’s trends
 Acute changes are compared to the patient’s
own expected baseline
 Intrathoracic impedance is not affected by respiration
or any complicating factors such as electrode
placement that impact external systems
 No compliance issues as with patient weights
47
Information from Implanted Devices
to Assist in HF Disease Management
48
Congestion in Heart Failure:
Conclusions
 Congestion is the primary cause of heart failure symptoms,
hospital admissions, and hospital readmissions
 Congestion is an important predictor of mortality and
morbidity
 Congestion contributes to progression of heart failure
 Clinical congestion often lags behind rising filling pressures
 Congestion is often difficult to recognize, delaying
appropriate interventions
 Improved methods to monitoring congestion may improve
clinical management and outcomes
49
Optimal Care of Heart Failure:
How to Improve Outcomes
 Optimize survival enhancing oral medications
(ACE inhibitors and/or ARB, beta-blockers,
aldosterone antagonists)
 Optimize survival-enhancing heart failure device
therapies (ICD, CRT)
 Optimize patient education and heart failure disease
management
 Maintain optimal volume status
50