Heart Failure

A to D

Garrie J. Haas, M.D.

Heart Failure and Cardiac Transplant Program

Division of Cardiovascular Medicine

The Ohio State University

Heart Failure Epidemiology

5.8 million persons in U.S. have HF

> 550,000 diagnoses each year

15 million office visits

Annual number of hospitalizations

> 1 million with primary HF diagnosis

> 3 million primary or secondary diagnosis

Re-hospitalization rates post discharge

25% at one month

50% at 6 months

Estimated direct / indirect cost of HF in U.S.

AHA Heart Disease and Stroke Statistics 2010

Heart Failure Incidence

Similar trends over past several

years

Increased in Men, Blacks, Elderly,

CAD, HTN

Highest in Black Males, lowest in

White Females

Heart Failure:

Prevalence by Stage and Class

Death

CHF

Patients

5MM USNYHA

Class 1

1.75 MM

NYHA

Class 2

1.75MM

NYHA

Class 3

1.25MMNYHA

Class 4

.25MM

Based upon US prevalence of 5MM

Remodeling Progression / Worsening of Cardiac Function

AHA/ACC STAGE CSTAGE B

STAGE D

Stage B - ALVD

One half the mortality rate of those

with symptoms

Risk of death 5-8 x higher than

normal age-matched population.

The transition from Stage B to Stage C heart failure is

associated with in increase in the risk of death by a

factor of 5 **

Ammar et al. Circulation 2007.

Established and Possible Risk

Factors for Heart Failure

Over 100 Risks

identified

Varying degrees of

‘independent’

association

Clinically relevant

VS. Esoteric

Schocken D. Circulation 2008; 117: 2544

Key Messages

From JNC-7

Estimated that 28%

unaware of HTN

39% of those aware are

not on medication

65% treated are not

Controlled

42 million in U.S. with

uncontrolled HTN

Diuretic

Digoxin

Diuretic

Digoxin

ACEI

Diuretic

Digoxin

ACEI

Diuretic

Digoxin

ACEI

-blocker

Diuretic

Digoxin

ACEI

-blocker

Diuretic

Digoxin

ACEI

-blocker

ARB

SOLVD-T (1991)

RRR 21%

CIBIS-2 (1999)

RRR 33%

CHARM-Added (2003)

(-blocker subgroup)

RRR 30%

Improving Survival in CHF

One-Year Mortality

0

5

10

15

20

Perc

en

t (

%)

Hospitalization: The Predominant Contributor to

HF Costs 38.1 billion (5.4% of healthcare)

60.6%

Inpatient care

38.6%

Outpatient care

(3.4 visits/year

/patient)

0.7%

Transplants

$270 million

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

23.1

billion

14.7

billion

Mortality Rates After First Hospitalization for HF

Jong et al. Arch Intern Med. 2002;162:1689-1694.

Age- and Sex-Stratified Case-Fatality Rates 30 Days and 1 Year

After First Hospitalization for HF

Men Women

Mortality, % Mortality, %

Age Group, y No. of Patients 30-Day 1-Year No. of Patients 30-Day 1-Year

20-49

50-64

65-74

≥75

All Ages

655

3048

5923

9310

18,936

4.6

5.5

8.6

15.6

11.4

15.0

20.5

28.8

43.1

34.0

375

1892

4412

13,087

19,766

4.3

5.4

6.8

14.7

11.8

10.9

19.5

23.0

37.9

32.3

Hospitalization for Heart Failure: Symptoms at Rest or

Minimal Exertion

At Rest or with Minimal

Activity

Orthopnea/PND/cough

Resting or immediate

dyspnea

Anorexia, abd. symptoms

Edema

Fatigue

Trouble concentrating

Elevated Filling Pressures Low CO

Left

Due to above symptoms

Due to above symptoms

Right

±

±

90 % in

ADHERE

35% in

ADHERE

66 % in

ADHERE

Courtesy of Dr. Lynne W. Stevenson

Over 90% of All Hospitalizations for

Acutely Decompensated Heart Failure Are

Due to Fluid Overload1

The Majority of These Patients Have

Failed Treatment With Oral Diuretics2

1. Aronson. ACC. 2000.

2. Adams et al. Am Heart J. 2005;149:209-216.

Most Common Intravenous Medications

0

10

20

30

40

50

60

70

80

90

100

Patients

(%

)

IV Diuretic Dobutamine Dopamine Milrinone Nesiritide Nitroglycerin Nitroprusside

IV Vasoactive Meds

88%

6% 6%10%

3% 1%

10%

ADHERE® Registry. Benchmark Report. 2004.

All Enrolled Discharges (n=105,388) October 2001–January 2004

Inadequate Diuresis During ADHF Treatment

Note: For the chart, n represents the number of patients who have both baseline and discharge weight, and

the percentage is calculated based on the total patients in the corresponding population. Patients without

baseline or discharge weight are omitted from the histogram calculations.

ADHERE® Database

All Enrolled Discharges in Over 12 Months (01.01.2003–12.31.2003)

Who Were Discharged Home (including home with additional and/or outpatient care)

The Nationn=26,757, 68%

Change in Weight From Admission to Discharge

7% 6%

13%

24%

30%

15%

3% 2%

0

10

20

30

40

50

Enro

lled D

ischarg

es (

%)

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

Change in Weight (lb)

Increased Morbidity

and Mortality

Diuretic Therapy

Impaired Renal

Function Decreased Renal

Perfusion

Development

of Diuretic and

Natriuretic

Resistance Diminished

Blood Flow

Neurohormonal

Activation

The Cardiorenal Syndrome of HF

ADHERE® CART: Predictors of Mortality

SYS BP 115n=24,933

SYS BP 115n=7150

6.41%

n=5102

15.28%

N=2048

21.94%

n=62012.42%

n=1425

5.49%

n=4099

2.14%

n=20,834

BUN 43N=33,324

Greater thanLess than

2.68%

n=25,122

8.98%

n=7202

Cr 2.752045

Highest to Lowest Risk Cohort

OR 12.9 (95% CI 10.4–15.9)

Fonarow GC et al. JAMA. 2005;293:572-580.

Jaske B. J Card Fail. 2003;9:227-231.

Ultrafiltration for Acute Heart Failure

Removal of excess volume

mechanically

A simplified peripheral ultrafiltration

system including a miniaturized

disposable circuit developed for

patients with volume-overload states

Evaluated in multiple observational

studies and a recently reported

multicenter trial (UNLOAD)

Urine vs UF Electrolytes After Intravenous Diuretics or

Ultrafiltration

Sodium Potassium Magnesium

0

20

40

60

80

100

120

140IVD

UF

P =.000025

P =.000017

P =.017

mg

/dL

Ali et al. J Card Fail. 2006;12(6 suppl):114.

Secondary End Point Net Fluid Loss at 48 H

P =.001

M = 3.3, CI + 0.29 L

(N=82)

M = 4.6, CI + 0.29 L

(N=81)

Net F

luid

Loss (

liters

)

Ultrafiltration Arm Standard Care Arm

5.5

5

4.5

4

3.5

3

2.5

2

Costanzo MR et al. J Am Coll Cardiol. 2007;49:675-683.

Sodium removed644 mEq

198 mEq

Freedom From Rehospitalization for HF

100 -

80 -

60 -

40 -

20 -

-

10 20 30 40 50 60 70 80 90

Days

Pe

rce

nta

ge

of P

atie

nts

Fre

e F

rom

Re

ho

sp

ita

liza

tio

n

No. Patients at Risk

Ultrafiltration Arm 88 85 80 77 75 72 70 66 64 45

Standard Care Arm 86 83 77 74 66 63 59 58 52 41

P=.037

Ultrafiltration Arm (16 Events)

Standard Care Arm (28 Events)

0

Costanzo MR et al. J Am Coll Cardiol. 2007;49:675-683.

Acute HF – Pre-Discharge Phase

Goals at discharge

Improve signs and symptoms

Appropriate management of precipitants

Euvolemia with transition to oral diuretics

Implementation of HF guidelines

Transition to chronic HF therapy

Post discharge planning and education

Weight monitoring

Diet

Telephone and clinic follow-up

Medications

When to call for symptoms

Gheorghiade and Pang. JACC 2009.

Haas GJ, Young JB. Texbook of CV Medicine

2009 ACC/AHA Updated Guidelines

ICD therapy is recommended for primary

prevention of sudden cardiac death to reduce

total mortality in patients with nonischemic

dilated cardiomyopathy or ischemic heart

disease at least 40 days post-myocardial

infarction, have an LVEF less than or equal to

35%, with NYHA functional class II or III

symptoms while receiving chronic optimal

medical therapy, and who have reasonable

expectation of survival with a good functional

status for more than 1 year.

Patients With Reduced Left Ventricular

Ejection Fraction

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Primary Prevention: Implantable Cardioverter-Defibrillator

Does patient have Class IV symptom (most patients hospitalized with HF)?

Does patient have risk profile for heart failure death during next year?

Is prognosis for more than one year survival with good overall

Function status limited by non-cardiac conditions?

Is patient within 40 days of myocardial infarction?

Are there reversible factors for which treatment may improve LVEF?

If all answers “No” : Discuss risk and benefit of ICD in outpatient setting

No ICD now,Re-evaluatefor stabilityand riskafter 1 month

Selecting Patients with Heart Failure for Discussion About ICD as Primary

Prevention of Sudden Death

Stevenson and Desai. J Cardiac Failure 2006

Yes

Yes

High risk HF profile

NoICD

YesNoICD

No ICD now,Re-evaluateafter 3-6 mosof optimalmedical Rx

Yes

Yes

Factors to Consider, e.g.High creat/BUN

HypotensionACEI/ARB intolerance

Low serum sodiumVery high serum BNP

Multiple HF hosps

Less than 3-6 months optimal med RxProlonged tachycardiaExcess alcohol consumptionMedications that can exacerbate HF

ICD Information for Patients

If we put an ICD in 100 patients with heart disease like

yours, over the next 5 years we would expect:

30 patient will die anyway

7-8 patients will be saved

by the ICD

Stevenson and Desai. J Cardiac Failure 2006

10-20 would have a shock

they don’t need

5-15 would have other

complications

The rest of patients will not

experience their devices at

all

Some patients will request to have the device

inactivated to allow natural death.

Cardiac Resynchronization Therapy

1/3 of patients with low LVEF and class III-IV

symptoms manifest QRS > 120 msec.

The ECG representation of abnormal cardiac

conduction has been used to identify patients with

dyssynchronous LV contraction.

While this is imperfect, no other consensus definition

of cardiac dyssynchrony currently exists.

Cardiac Resynchronization Therapy Guidelines

For patients with LVEF ≤ 35%, QRS ≥ 120 ms, NYHA Functional

Class III or ambulatory Class IV, on optimal recommended medical

therapy, and

in sinus rhythm ………… CRT is Recommended

with AF …………………. CRT is Reasonable

with frequent dependence on

ventricular pacing ….. CRT is Reasonable

I IIa IIb III

A

I IIa IIb III

B

I IIa IIb III

CACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac

Rhythm Abnormalities. J Am Coll Cardiol, 2008; 51:2085-2105.

Future Directions in CRT

Expanding the indication to less severe heart failure (asymptomatic LVD and mild HF)

Expanding the indication to narrow QRS patients with ECHO dysynchrony

Expanding the indication to less severe LVD (e.g., LVEF 36% to 50%)

Changing the definition of ventricular dysynchrony (QRS duration ECHO)

Further leveraging CRT devices for monitoring clinical status

Future Directions in CRT

Expanding the indication to less severe heart failure (asymptomatic LVD and mild HF)

Expanding the indication to narrow QRS patients with ECHO dysynchrony

Expanding the indication to less severe LVD (e.g., LVEF 36% to 50%)

Changing the definition of ventricular dysynchrony (QRS duration ECHO)

Further leveraging CRT devices for monitoring clinical status

Moss AJ. NEJM 2009

Moss AJ. NEJM 2009

MADIT-CRT: Results

Impedance Decreases with Increasing Lung

Wetness

Heart Failure Exacerbation

Pulmonary Congestion

Decrease in Intrathoracic Impedance

Physician Programmable Threshold

OptiVol Fluid Index

Daily Impedance

Reference Impedance

40 80 120 160 2000

20

60

100

Days

Flu

id I

ndex

(Wd

ays)

0 40 80 120 160 200

70

80

90

Days

Imp

edance (W

)

Physician Programmable Threshold

OptiVol Fluid Index

Daily Impedance

Reference Impedance

40 80 120 160 2000

20

60

100

Days

Flu

id I

ndex

(Wd

ays)

0 40 80 120 160 200

70

80

90

Days

Imp

edance (W

)Algorithm Developed to Track Fluid

Accumulation

Medtronic data on file

Another Approach to Heart Failure Management

LASIX®

(Furosemide)

40 mg

1 white tablet

Recheck in 12h

LASIX®

40

LARA

HeartPOD™SystemPatient Advisory Module (PAM)

LARA

Modified PDA

Powers through clothing

Atmospheric reference

Stores telemetry

Alerts patient to monitor

‘DynamicRX®’ instructs

Meds

Activity

Clinician contact

based on LAP values and

physician’s prescription

SAVACOR, INC

Advanced HF (StageD)

Progressive symptoms

Resting tachycardia / low BP

Progressive LV remodelling

Intolerance of evidence-based medications

Hyponatremia

Worsening renal function

Diuretic resistance

Increased QRS duration

Anemia

Increased arrhythmia

Refer for advanced HF

Med,Surg, Device treatment

options

Inotrope dep. ??

Yes NoAssess with*CPX, RHC

*NYHA

•HFSS,

•SHFM

*Evaluate forTransplant

*MCS

*Clinical Trial

*Hospice

Evaluation of Advanced HF (Stage D)

Realistic Expectations following Transplant

Referral

1174 Transplant referrals

558 treated medically

418 (36%) listed for transplant

168 received other surgery

Of those Listed …

217 (18% of those referred originally) transplanted

77 de-listed (27 improved, 32 non-tsplt surgery)

74 died

50 waiting

Mahon NG et al. J Card Fail 2004; 10: 273

Factors involved in determining appropriateness of

Transplant or VAD Implantation ( Stage D HF )

Wilson SR, et al. Circulation. 2009; 119: 2225-2232

Hepatic

Function

Neurologic

Function

Multiorgan

Failure

Age

Body Size

Malignancy

Psychological and

Psychiatric Conditions

Arrhythmias

Inotropic

Support

Valvular

Disease

Right Ventricular

Function

Ischemic Heart

DiseaseInfectious

Disease

Nutritional

Status

Renal

Function

Pulmonary

FunctionIntracardiac

Shunt

Non-Cardiovascular

Considerations

Cardiovascular

Considerations

Left Ventricular Assist Device

Heartmate II (long-term) Heartware (long-term)

*investigational

Ventrassist (long-term)

*investigational

Centrimag (short-term)

Slaughter M, et al. NEJM 2009

Continuous Flow LVAD (HM II) vs.

Pulsatile LVAD (HM XVE)

1. The CONSENSUS Trial Study Group. N Engl J Med. 1987;316:1429-1435.

2. Packer M et al. N Engl J Med. 1996;334:1349-1355.

3. Pitt B et al. N Engl J Med. 1999;341:709-717.

4. Moss A et al. N Engl J Med. 1996;335:1933-1940.

5. Abraham WT et al. N Engl J Med. 2002;346:1845-1853.

Therapies Demonstrated to Reduce Mortality in

Heart Failure

ACE Inhibitors / ARB’s (Stage A-D)

Beta Blockers (Metoprolol, Carvedilol) (Stage A-D)

Aldosterone Antagonists (Stage C)

Hydralazine / Nitrates (AA) (Stage C,D)

Transplant / LVAD (Stage D)

ICD

LVEF < 35, Class II or III (Stage C)

Cardiac Resynchronization +/- ICD

LVEF <35, QRS >120 ms, Class III or IV (Stage C)