How Well is Chronic Heart Failure Being Managed?

Gregg C. Fonarow, MDEliot Corday Professor of

Cardiovascular Medicine and ScienceUCLA Division of Cardiology

Director, Ahmanson-UCLA Cardiomyopathy CenterDirector, UCLA Cardiology

Fellowship Training ProgramLos Angeles, California

HF, heart failure.AHA. 2006 Heart and Stroke Statistical Update. 2

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%

Burdens of Heart FailureBurdens of Heart Failure

Congestive Symptoms

Activity Limitation

Dysrrhythmias

Reduced Survival

Hospitalizations

3

Decompensated Heart Failure: The Major Contributor to Cost of Care

Hospitalization for Decompensation

$15.4 Billion (52%)

Drugs/Other Medical Durables

$3.1 Billion (10.5%)

Indirect $2.8 Billion

(9.5%)

Nursing Home/ Home Health Care

$6.3 Billion (21%)

Health CareProfessionals $2.0 Billion

(7%)

Total 2006$29.6 Billion

American Heart Association. 2006 Heart and Stroke Statistical Update. 4

Heart Failure Hospitalizations

0

100,000

200,000

300,000

400,000

500,000

600,000

'79 '81 '83 '85 '87 '89 '91 '93 '95 '97 ‘9920

01

Dis

ch

arg

es

Women

Men

AHA, 1998 Heart and Stroke Statistical Update.NCHS, National Center for Health Statistics.AHA, Heart Disease and Stroke Statistics -- 2005 Update.

The number of heart failure hospitalizations is increasing in both men and women

CDC/NCHS: Hospital discharges include patients both living and dead.

5

AMI, acute myocardial infarction.Fonarow GC, et al. Rev Cardiovasc Med. 2000;1:25-33.

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

6

6-Month Readmission Rates Among 17,448 Survivors of

Hospitalization for CHF

CHF, congestive heart failure.17,448 Medicare patients who survived hospitalization for HF.Krumholtz HM. Arch Intern Med. 1997;157:99-104.

Rehospitalizedat least once

Rehospitalizedat least twice

0

20

40

60

Pat

ien

ts (

%)

16

44

7

Fonarow GC, et al. J Card Failure. 2003;9:S79. Jong P, et al. Arch Intern Med. 2002;162:1689-1694.

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

8

45 (33-55)59 (47-68)24 (14-33)28 (18-36)10 (3-15)11 (4-17)1990–1999

51 (39-60)65 (54-73)27 (17-35)33 (23-42)10 (4-16)12 (5-18)1980–1989

59 (45-69)75 (65-83)28 (17-38)41 (29-51)16 (6-24)15 (7-23)1970–1979

57 (43-67)70 (57-79)28 (16-39)30 (18-40)18 (7-27)12 (4-19)1950–1969

WomenMenWomenMen WomenMenPeriod

5-Year Mortality,

% (95% CI)

1-Year Mortality,

% (95% CI)

30-Day Mortality,

% (95% CI)

Temporal Trends in Age-Adjusted Mortality After the Onset of Heart Failure*

*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.

Long-Term Trends in Mortality With Heart Failure

9

*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.

Control VolumeReduce Mortality

Salt Restriction*Diuretics*

Digoxin*

-BlockerACEIor ARB

AldosteroneAntagonist

Treat Residual SymptomsCRT

an ICD*Hyd/ISDN*ICD*

Treat Comorbidities

Aspirin*Warfarin*

Statin*

Enhance Adherence

EducationDisease Management

Performance Improvement Systems

Evidence-Based Treatment For Stage C Heart Failure

10

*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.

50.8

12.8

57.4

80.8

41

0

10

20

30

40

50

60

70

80

90

100

En

roll

ed

Dis

ch

arg

es (

%)

ACE Inhibitor ARB -Blocker Diuretic Digoxin

History of HF and LVEF Documented and 0.40*

Utilization of Evidence-Based Therapies in Heart Failure

11

60

34

2012

0

10

20

30

40

50

60

70

80

90

100

ACE Inhibitors(ACEI)

-Blockers(BB)

ACEI + BB Aldosterone

Antagonists

Pat

ien

ts (

%)

Cleland JG, et al. Lancet. 2002;360:1631-1639.

International survey: 15 countries, 1363 physicians, 11,062 patients: Year 2000.Outpatient regimen in patients with Stage C HF, documented systolic dysfunction.

Utilization of Evidence-Based HF Therapies: IMPROVEMENT International

Survey

12

All P<0.0001.81 142 admissions between 6/2002-12/2003 at 223 hospitalsGrouped 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.

1%

72%

58%

8%

70%

97%

88% 85%

0%

20%

40%

60%

80%

100%

120% Lagging Centers Leading Centers

DischargeInstructions

LV FunctionMeasurement

ACEI use Smoking Cessation

Uti

liza

tio

n (

%)

ADHERE Quality of Care Conformity to JCAHO HF Performance Indicators

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

Any dyspnea (%) 89

Dyspnea at rest (%) 34

Fatigue (%) 32

Rales (%) 68

Peripheral edema (%) 66

Pulmonary congestion (%) 75

SBP <90 mm Hg (%) 2

ADHERE, Acute Decompensated Heart Failure National Registry.Adapted from Fonarow GC. Rev Cardiovasc Med. 2003;4(Suppl 7):S21-S30.

150,000 Hospitalization Episodes in ADHERE

Clinical Presentation of Patients Hospitalized with Heart Failure

16

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.

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)

17

Hemodynamic vs Clinical Congestion

Stevenson LW, et al. Circulation. 2006;113:1020-1033. 18

ObviousCongestiveSymptoms

RV, right ventricular; PA, pulmonary artery.

Adamson PB, et al. J Am Coll Cardiol. 2003;41:565-571.

Congestion Precedes Hospitalization

Pressure Change Hospitalization

Days Relative to the Event

Baseline -7 -6 -5 -4 -3 -2 -1 Recovery

Ch

ang

e (

%)

-10

0

10

20

30

40

RV Systolic Pressure

Estimated PA Diastolic Pressure

Heart Rate

19

1. Mahdyoon H, et al. Am J Card. 1989;63:625-627.2. Stevenson LW, et al. JAMA. 1989;261:884-888.

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

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

22

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

The Challenge of DiagnosingHeart Failure: Physical Examination

JVP on Physical Exam

– Great if well seen

– In OPTIMIZE-HF and ADHERE, in the majority of hospitalized HF patients, initial exammissed 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?

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.

Variable Sensitivity (%) Specificity (%) PPA (%) NPA (%)

RAP

JVP

Edema

48

10

78

94

60

55

69

60

Cardiac Index

Pulse Pres 27 69 52 44

PCWP

S3

Dyspnea

Rales

36

50

13

81

73

90

69

67

60

54

57

48

24

Stevenson LW, et al. JAMA. 1989;261:884-888. 25

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%

LVEDP, left ventricular end-diastolic pressure.Marcus GM, et al. JAMA. 2005;293:2238-2244.

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

26

Chest X-Ray in Heart Failure

27

How Good Is Chest X-ray in Diagnosing Heart Failure?

CXR blows

– Misses 20% of echo- proven 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

2%3%

15%

33%

24%

13%

6%7%

0

5

10

15

20

25

30

35

(<-20) (-20 to -15) (-15 to -10) (-10 to -5) (-5 to 0) (0 to 5) (5 to 10) (>10)

Change in Weight (lbs)

Pa

tie

nts

(%

)

Fonarow GC. Rev Cardiovasc Med. 2003;4(Suppl 7):S21-S30.

More than 50% of Patients Have Little or No Weight Loss During Hospitalization

30

Admission Discharge

Symptoms (%)

Dyspnea on exertion 79 58Dyspnea at rest 42 5Orthopnea 50 12

PND 33 4Fatigue 53 57

Signs (%)

JVP >6cm 33 6Rales 57 13S3 gallop 20 6Edema >2+ 50 13

PND, paroxysmal nocturnal dyspnea.Gattis WA, et al. J Am Coll Cardiol. 2004;43:1534-1541.

Change in Heart Failure Signs and Symptoms (Admission to Discharge)

31

ADHERE OPTIMIZE-HF

(107,920 patients) (34,059 patients)

>2.5 kg weight loss (%) 50 50

HF symptoms

Unchanged/worse <1 <3 Better (symptomatic) 40 40 Better (asymptomatic) 50 51

Length of stay (mean days) 6.1 6.4 In-hospital mortality (%) 4.0 3.8Mortality at 2-3 months (%) N/A 9

Readmissions at 2-3 months (%) N/A 31

Hospitalization Outcomes

Adams KF, et al. Am Heart J. 2005;149:209-216. Fonarow GC, et al. J Am Coll Cardiol. 2004;844-4A. 32

BNP, brain (B-type) natriuretic peptide; NT, N-terminal. 33

Outpatient Monitoring of Congestion

Signs and symptoms

Daily weights

Natriuretic peptides (BNP and NT-pro BNP)

Noninvasive bioimpedence monitors

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

*Still investigational.

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*

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

Ravnan SL, et al. Congest Heart Fail. 2002;8:80-85.Brater DC. Drugs. 1985;30:427-443.

Loop Diuretics and Heart Failure

There have been no outcome studies of diuretictherapy 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)

37

Bayliss J, et al. Br Heart J. 1987;57:17-22.

Pla

sma

ren

in a

ctiv

ity

(ng

/mL

/h)

Before Diuretic(n=12)

After Diuretic(n=11)

50

10

2.5

0.5P

lasm

a a

ldo

ste

ron

e (p

mo

l/L

)

Before Diuretic(n=12)

After Diuretic(n=11)

1000

600

200

100

Mean (95% CI)Mean

(95% CI)

Marked Activation of the Renin- Angiotensin-Aldosterone

System By IV Loop Diuretics

38

Acute Vasoconstrictor Response to IV Acute Vasoconstrictor Response to IV Furosemide in Congestive Heart FailureFurosemide in Congestive Heart Failure

<0.01839 ± 368667 ± 390PNE (pg/mL)

<0.0517.8 ± 169.9 ± 8.5PRA (ng/mL)

<0.011676 ± 4151454 ± 384SVR (dyn-s-cm-5)

<0.0196 ± 1590 ± 15BP (mm Hg)

<0.0191 ± 1687 ± 13HR (bpm)

<0.0124 ± 727 ± 8SVI (mL/min/m2)

<0.0128 ± 733 ± 9

PAWP (mm Hg)

P Value20 mins after IV Furosemide 40 mg

BaselineHemodynamic Variable

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

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.

-25

-20

-15

-10

-5

0

5

10

15

0 500 1000 1500 2000 2500

Urine Output (mL) 0 - 8 hours

GF

R (

% c

ha

ng

e)

Placebo

IV Furosemide

Furosemide Monotherapy Causes a Significant Decline in Renal Function

40

Higher Doses of Loop Diuretic is Associated with Increased

Mortality in Severe HF

Retrospective analysis of 1153 patients with advanced HF from PRAISE study

Loop diuretic above and below median compared

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

PRAISE, Prospective Randomized Amlodipine Survival Evaluation; SCD, sudden cardiac death.Neuberg GW, et al. Am Heart J. 2002;144:31-38.

1.0

0.8

0.6

0.4

0.2

0

To

tal

mo

rta

lity

Months from Randomization

0 6 12 18 24 30 36

Chi-square=33.83P=0.0001

Group Diuretic dose ACE inhibitor dose

A High Low n=240B High High n=160C Low Low n=526D Low High n=224

A

B

C

D

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)

4

3

2 2

1 1 10.8 0.8 0.8 0.8 0.8

0.5 0.5 0.5 0.5 0.50.4 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 0.2 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 0.2 0.2 0.2

0

1

2

3

4

5

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Time (weeks)

Mo

rtal

ity

%

AHF Hospitalization Stage C Outpatient

HR=20

HR=10

HR=4

Weekly Mortality Risk

Time-Dependent Mortality Risk in Heart Failure

AHF, acute heart failure. 45

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

Mechanisms by Which Elevated LV Filling Pressures Could Contribute to Mortality in HF

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

50

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