advanced heart failure: patient identification and ... · advanced heart failure: patient...

Advanced Heart Failure: Patient Identification and Treatment

Options

Donald Haas, MD, MPH

Abington - Jefferson Health

Abington, PA

Disclosures

• I have received honoraria from Thoratec Corporation/St. Jude Medical, manufacturer of Heartmate II and Heartmate 3 left ventricular assist devices

• I will not discuss any off label products or devices

Advanced Heart Failure Considerations

• Heart failure is associated with extremely high mortality rates

“Walking Dead”

Among HF outpatients

– One year mortality 20%

– Five year mortality 50%

Among HF inpatients

– One year risk adjusted mortality 30%

Chen J. JAMA 2011;306:1669 Donahoe SM. JAMA 2007;298:765

Among HF outpatients

– One year mortality 20%

– Five year mortality 50%

Among HF inpatients

– One year risk adjusted mortality 30%

Chen J. JAMA 2011;306:1669 Donahoe SM. JAMA 2007;298:765

Heart failure is associated with very high mortality rates

One year mortality among myocardial infarction patients

is only 7%

Five-year Mortality following Hospitalization for ADHF

Shahar E, et al. J Card Fail 2004;10: 2148-59

Perc

en

t su

rviv

al

Survival of Stage D Heart Failure

Patients with Optimal Medical Therapy

Projected Mortality for Advanced Heart Failure

on Par Other Terminal Diseases

0

10

20

30

40

50

60

70

80

90

AIDS Leukemia Lung Cancer Pancreatic Cancer End-stage Heart

Failure with Optimal

Medical Management Diagnosis

Mort

alit

y e

xpecta

tion %

at

One Y

ear

Rose EA, et al. Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J

Med. 2001 Nov 15;345(20):1435-43.

Heart Failure: Scope of the Problem

• Estimated 7 million patients with HF 1

• 50% have HFpEF or diastolic HF 1,2

(1) Miller LW, Circulation. 2011;123:1522-58.

(2) AbouEzzeddine OF, et al. Congest Heart Fail. 2011;17:160-8.

(3) Bhatia RS. N Engl J Med. 2006; 355: 260-9.

Pulmonary Hypertension

J Am Coll Cardiol 2012 Jan 17;59(3):222-31. Heart. 2012; 98(24): 1805–1811.

Advanced Heart Failure Considerations

• Heart failure is associated with extremely high mortality rates

• Generally, advanced heart failure do not receive appropriate therapy

Stages of Heart Failure

Jessup M, Brozena S. N Engl J Med. 2003;348:2007-18.

Functional Class

• NYHA Class

– Class I: no functional impairment

– Class II: SOB at moderate exertion

– Class III: SOB at minimal – mild exertion

– Class IV: SOB at rest

Why stages?

• NYHA Class

– Class I: no functional impairment

– Class II: SOB at moderate exertion

– Class III: SOB at minimal – mild exertion

– Class IV: SOB at rest

Why stages?

• NYHA Class

– Class I: no functional impairment

– Class II: SOB at moderate exertion

– Class III: SOB at minimal – mild exertion

– Class IV: SOB at rest

- NYHA Class changes

- Inadequate as stand

alone descriptor

of natural history

Stages of Heart Failure

Jessup M, Brozena S. N Engl J Med. 2003;348:2007-18.

Stage A: high risk for HF without structural

heart disease or symptoms

– Hypertension

– Atherosclerotic heart disease

– Diabetes

– Obesity

– Metabolic syndrome

– Cardiotoxins (eg, doxorubicin, EtOH)

– Family history of cardiomyopathy

Stages of Heart Failure

Jessup M, Brozena S. N Engl J Med. 2003;348:2007-18.

Stage B: Structural heart disease without the

development of HF

– Prior myocardial infarction

– Depressed LV ejection fraction

– Left ventricular hypertrophy

– Asymptomatic valvular heart disease

Stages of Heart Failure

Jessup M, Brozena S. N Engl J Med. 2003;348:2007-18.

Stage C: Structural heart disease with

current or prior symptoms

“Needs Lasix” Heart Failure

Syndrome

CARDIOMYOPATHY IS NOT

SYNONYMOUS WITH

HEART FAILURE

Stages of Heart Failure

Jessup M, Brozena S. N Engl J Med. 2003;348:2007-18.

Stage D: refractory symptoms requiring

special intervention

• What constitutes refractory symptoms?

– Repeated HF hospitalizations?

– Inability to complete activities of daily living?

– Severe sodium/fluid restriction and high diuretic

requirement?

Stages of Heart Failure

Jessup M, Brozena S. N Engl J Med. 2003;348:2007-18.

• The routine use of inotropes as heart failure therapy is not indicated in either the short- or long-term setting

• The use of inotropes as a treatment of cardiogenic shock, diuretic/ACE inhibitor–refractory heart failure decompensations, or as a short-term bridge to definitive treatment, such as revascularization or cardiac transplantation, is potentially appropriate

• Inotropes may be appropriate as a palliative measure in patients with truly end-stage heart failure as part of hospice care

Guideline Recommendations: Role of Inotropic Therapy in Patients

with Heart Failure

Hershberger RE et al. J Card Fail 2003; 9:188-91.

COSI* Survival

*Continuous Outpatient Support with Inotropes

IV Inotropic Agents During Hospitalization for Decompensated Heart Failure

* without cardiogenic shock

Cuffe MS et al. JAMA. 2002;287:1541–1547.

Treatment Failure From Adverse Event (48 h)

Sustained Hypotension

Acute MI Mortality

Milrinone

Placebo

Afib

P < 0.001 P < 0.001

P = 0.18

P = 0.004 P = 0.19

12.6

2.1

10.7

3.2

1.5 0.4

4.6

1.5

3.8

2.3

0

5

10

15

20

OPTIME-CHF: In-hospital Adverse Events

• The routine use of inotropes as heart failure therapy is not indicated in either the short- or long-term setting

• The use of inotropes as a treatment of cardiogenic shock, diuretic/ACE inhibitor–refractory heart failure decompensations, or as a short-term bridge to definitive treatment, such as revascularization or cardiac transplantation, is potentially appropriate

• Inotropes may be appropriate as a palliative measure in patients with truly end-stage heart failure as part of hospice care

Guideline Recommendations: Role of Inotropic Therapy in Patients

with Heart Failure

Stage D: refractory symptoms requiring

special intervention

– Need for inotropes

– Treatments

• Transplant

• MCS/LVAD

• Hospice

MCS Candidate

Transplant Candidate

Hospice

Treatment Options for Stage D Heart Failure Patients

MCS Candidate

Transplant

Candidate

Hospice

Treatment Options for Stage D

Heart Failure Patients

“Care as usual”

is not an option

Scope of the Problem • Estimated 7 million patients with HF 1

• 50% have HFrEF or systolic HF 1,2

• 10% have stage D HF

– Estimates vary between 5-20% 1,2

• ~2200 transplants in US annually 6

• ~4000 LVAD implants in US 2015 7

• 16% referred to hospice

– Estimates vary between 12-20% (conservative)2,3,4,5

(1) Miller LW, Circulation. 2011;123:1522-58.

(2) AbouEzzeddine OF, et al. Congest Heart Fail. 2011;17:160-8.

(3) Setoguchi S, et al. Am Heart J. 2010;160:139-44.

(4) Connor SR, et al. J Pain Symptom Manage. 2007;34:277-85.

(5) Givens JL, et al. Arch Intern Med. 2010;170:427-32.

(6) Taylor DO, et al. J Heart Lung Transplant. 2009;28:1007-22.

(7) Personal communication, Thoratec, INTERMACS

Scope of the Problem • Estimated 7 million patients with HF 1

• 50% have HFrEF or systolic HF 1,2

• 10% have stage D HF

– Estimates vary between 5-20% 1,2

• ~2200 transplants in US annually 6

• ~4000 LVAD implants in US 2013 7

• 16% referred to hospice

– Estimates vary between 12-20% (conservative)2,3,4,5

(1) Miller LW, Circulation. 2011;123:1522-58.

(2) AbouEzzeddine OF, et al. Congest Heart Fail. 2011;17:160-8.

(3) Setoguchi S, et al. Am Heart J. 2010;160:139-44.

(4) Connor SR, et al. J Pain Symptom Manage. 2007;34:277-85.

(5) Givens JL, et al. Arch Intern Med. 2010;170:427-32.

(6) Taylor DO, et al. J Heart Lung Transplant. 2009;28:1007-22.

(7) Personal communication, Thoratec, INTERMACS

350,000 HFrEF Stage D

Most advanced HF patients do not receive stage D therapies

18% of patients receive advanced HF therapies

Untreated N =288,300

LVAD N = 3,500

Transplant N = 2,200

Hospice N = 56,000

Death with HF

Characteristic All deaths

(n=160)

Outpt

deaths

(n=80)

Inpt deaths

(n=80)

CHF clinic (mos) 24.7 23.1 26.6

CHF duration (yrs) 5.0 4.6 5.4

Age (yrs) 59.9 57.9 61.1

Male (%) 74 75 74

NYHA III (%) 14 13 14

NYHA IV (%) 79 74 83

ICD (%) 37 30 46

CRT (%) 5 7 5

EF (%) 20 22 19

Teuteberg et al. J Card Fail 2006;12:47

Deaths from 1/1/00-10/20/03

HF Patients (%) Cancer Patients (%)

Hospice prior to death 20.4 50.8

Died <3 days after hospice enrollment

22.8 11.0

Opiates < 60 days before death 22.2 45.6

Opiates in those dying in hospital 19.1 43.7

Opiates in those dying outside hospital

26.8 48.0

ER visits <30 days before death 60.1 38.9

Hospitalized <7 days before death

30.3 15.9

Hospitalized <30 days before death

64.2 45.3

ICU <30 days before death 19.0 7.2

Adm SNF before death 60.6 38.3

Death in acute care hospital 39.1 21.0

Setoguchi S, et al. Am Heart J. 2010;160:139-44.

HF Patients (%) Cancer Patients (%)

Hospice prior to death 20.4 50.8

Died <3 days after hospice enrollment

22.8 11.0

Opiates < 60 days before death 22.2 45.6

Opiates in those dying in hospital 19.1 43.7

Opiates in those dying outside hospital

26.8 48.0

ER visits <30 days before death 60.1 38.9

Hospitalized <7 days before death

30.3 15.9

Hospitalized <30 days before death

64.2 45.3

ICU <30 days before death 19.0 7.2

Adm SNF before death 60.6 38.3

Death in acute care hospital 39.1 21.0

Setoguchi S, et al. Am Heart J. 2010;160:139-44.

HF Patients (%) Cancer Patients (%)

Hospice prior to death 20.4 50.8

Died <3 days after hospice enrollment

22.8 11.0

Opiates < 60 days before death 22.2 45.6

Opiates in those dying in hospital 19.1 43.7

Opiates in those dying outside hospital

26.8 48.0

ER visits <30 days before death 60.1 38.9

Hospitalized <7 days before death

30.3 15.9

Hospitalized <30 days before death

64.2 45.3

ICU <30 days before death 19.0 7.2

Adm SNF before death 60.6 38.3

Death in acute care hospital 39.1 21.0

Setoguchi S, et al. Am Heart J. 2010;160:139-44.

Hospitalizations Predict Mortality

Russell SD, et al. Congest Heart Fail 2008;14:316-21

Hospitalizations Predict Mortality

Russell SD, et al. Congest Heart Fail 2008;14:316-21

Any heart failure admission

is a red flag!!

Impact of Hospitalizations on Mortality J Am Coll Cardiol. 2013;61(12):1209-1221. doi:10.1016/j.jacc.2012.08.1029

Median Survival Decreases Progressively After Each Hospitalization for HF

Hospital admissions not only decrease quality of life, but they are also associated with shorter longevity.

Figure Legend:

Presence of JVD

Drazner MH, et al. N Engl J Med 2001; 345:574-581.

Improvement of Congestion Predicts Survival in

Patients With Class IV Symptoms of ADHF

• 146 Patients hospitalized with class IV HF

• Assessed 4 to 6 weeks after hospitalization for congestion

• Patients with persistent orthopnea (n=33)

– 2-year survival: 38%

• Patients with resolution of orthopnea (n=113)

– 2-year survival: 77% (P=.0001)

0

10

20

30

40

50

60

70

80

2 yr survival

Orthop

Noorthop

Lucas C et al. Am Heart J. 2000;140:840-847.

Failure to achieve euvolemia

is a poor prognostic sign

N=46,218

No mention

10%

Asymptomatic

51%

Improved

(but still symptomatic)

39%

1. ADHERE Registry. 3rd Quarter. 2003 National Benchmark Report. http://www.adhereregistry.com/national_BMR/index.html.

2. Fonarow GC, for ADHERE Scientific Advisory Committee. Rev Cardiovasc Med. 2003;4(suppl 7):S21.

ADHERE®1,2: Patients Discharged From September 1, 2002, to October 30, 20031

No change <1%

Not applicable <1%

Worse <1%

Persistent Symptoms of Congestion at Discharge

in Large Fraction of Patients Admitted for HF

Diuretics and Mortality

0%

25%

50%

75%

100%

0 1 2 3

4+ mg/kg

3-4 mg/kg

2-3 mg/kg

1-2 mg/kg

0.5-1 mg/kg

<0.5 mg/kg

Levy W, Mozaffariun D, Linker D, et al. The Seattle heart failure model. Circulation. 2006;113:1424-33.

Years

p<0.0001

KM Survival - Daily Diuretic Dose mg/kg

Predictors of Acute Mortality for

Patients Admitted with Acute CHF

SBP 115 mm Hg

n=7150

15.28%

n=2048

SCr 2.75 mg/dL

n=2045

6.41%

n=5102

12.42%

n=1425

21.94%

n=620

2.14%

n=20,834

5.49 %

n=4099

SBP 115 mm Hg

n=24,933

2.68%

n=25,122

8.98%

n=7202

BUN 43 mg/dL

N=33,046

Less than Greater than

or equal to

Greater than or

equal to

Greater than or

equal to

Greater than

or equal to

Less than

Less than Less than

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

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0 250 500 750 1000 1250

Pro

port

ion s

urv

ival

Pro

po

rtio

n s

urv

ival

Days

4.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

>76 59-76 44-58 <44

>30 26-30 20-25 <20

GFR (mL/min)

LVEF (%)

GFRc=glomerular filtration rate estimated from serum creatinine, LVEF=left ventricular ejection fraction

Hillage HL et al. Circulation 2000; 102:203-210.

Diagnostic Value of Glomerular Filtration Rate in

Patients With Heart Failure

• Two or more HF hospitalizations in 6 months

• Intolerant of ACE-I/ARB/Beta blocker

• Unable to walk 1 block or 1 flight of stairs without

dyspnea – (< 300 m 6MWT)

• Renal insufficiency (especially BUN)

• Increasing diuretic requirement

Clues to Identifying the Potential Stage D Heart Failure Patient

Russell SD, et al. Congest Heart Fail 2008;14:316-21

• Two or more HF hospitalizations in 6 months

• Intolerant of ACE-I/ARB/Beta blocker

• Unable to walk 1 block or 1 flight of stairs without

dyspnea – (< 300 m 6MWT)

• No clinical improvement with CRT or no CRT and QRS > 140ms

Clues to Identifying the Potential Stage D Heart Failure Patient

Russell SD, et al. Congest Heart Fail 2008;14:316-21

AC

E/A

RB

B

eta

Blo

cke

rs

Ald

ost

ero

ne

an

tago

nis

ts

Loo

p d

iuretics

Meto

lazon

e

J Am Coll Cardiol. 2014;63(7):661-671.

Figure Legend:

NYHA III-IV NYHA II

Triggers for Referral to Advanced HF Program

Swedish HF Registry2000-2013

~10000 patients NYHA III-IV (~9000 NYHA II)

Age < 80 years

• SBP <90 mmHg

• Creatinine >1.8mg/dL

• Hemoglobin <12 g/dL

• No beta blocker

• No RAS antagonist

J Am Coll Cardiol. 2014;63(7):661-671.

Figure Legend:

NYHA III-IV NYHA II

Triggers for Referral to Advanced HF Program

Advanced Heart Failure Considerations

• Heart failure is associated with extremely high mortality rates

• Generally, advanced heart failure do not receive appropriate therapy

• The crucial role of RHC in the management of heart failure

Rapid Assessment of Hemodynamic Status

Congestion at Rest

Low

Perfusion

at Rest

No

No Yes

Yes

Warm & Dry Warm & Wet

Cold & Wet Cold & Dry

Signs/symptoms

of congestion

• Orthopnea/PND

• JV distension

• Ascites

• Edema

• Rales (rare in chronic HF)

Possible evidence of low perfusion • Narrow pulse pressure • Sleepy/obtunded • Low serum sodium

• Cool extremities • Hypotension with ACE inhibitor • Renal dysfunction (one cause)

PND = paroxysmal nocturnal dyspnea; JV = jugular venous.

Stevenson LW. Eur J Heart Fail. 1999;1:251–257.

How do you diagnose shock? Who needs an inotrope?

How do you diagnose shock? Who needs an inotrope?

PA catheter

How do you diagnose shock? Who needs an inotrope?

PA catheter

ESCAPE

Clinical Outcomes in ESCAPE

Six-month end points PAC,

n=215

(%)

Clinical,

n=218

(%)

Days dead or

hospitalized (mean)

38 36

Mortality 20.9 17.4

Rehospitalizations/

patient (mean)

2.1 2.1

Days in hospital (median) 11 11

*No significant differences PAC=pulmonary artery catheterization; clinical=clinically guided therapy only

Evaluation Study of Congestive Heart Failure and

Pulmonary Artery Catheterization Effectiveness: The

ESCAPE Trial

– 26 experienced transplant cardiology centers

– Study of decongestion

• Exclusion included

– creatinine >3.5 mg/dl

– Prior use of dobutamine, milrinone

• Inotropes discouraged

– Sick cohort

• BP 105

• EF < 30%

JAMA. 2005;294(13):1625-1633

O2 consumption ----------------------------------- [hgb][13.6][Ao sat – PA sat]

O2 consumption ----------------------------------- [hgb][13.6][Ao sat – PA sat]

Dehmer, GJ, et al. Clin Cardiol 1982; 5: 436-440

What is the O2 consumption?

108 consecutive patients

Mean : 126 ml/min/m2

Wide variability: 65-250ml/min/m2

CO 6, HGB 15, PA sat 70%

CO 6, HGB 15, PA sat 70% CO 6, HGB 10, PA sat 60%

CO 6, HGB 15, PA sat 70% CO 6, HGB 10, PA sat 60% CO 3, HGB 15, PA sat 50%

CO 6, HGB 15, PA sat 70% CO 6, HGB 10, PA sat 60% CO 3, HGB 15, PA sat 50% CO 3, HGB 10, PA sat 40%

Destination Therapy survival improvement

over time1

1. Jorde UP, Khushwaha SS, Tatooles AJ, et al. Two-Year Outcomes in the

Destination Therapy Post-FDA-Approval Study with a Continuous Flow

Left Ventricular Assist Device: A Prospective Study Using the

INTERMACS Registry. Presented at the ISHLT annual meeting, April 25,

2013.

INTERMACS PROFILES

Stevenson LW, Pagani FD, Young JB, et al. INTERMACS profiles of advanced heart failure: the current picture. J Heart Lung Transplant. 2009;28:535-41.

INTERMACS PROFILES AND OTHER CLASSIFICATION SYSTEMS

Profile # Description NYHA Class Time to MCS therapy AHA/ACC

Stage

INTERMACS

1 Crashing and burning IV Within hours D

INTERMACS

2

Progressive decline on inotropic

support IV Within a few days D

INTERMACS

3 Stable but inotrope dependent IV Within a few weeks D

INTERMACS

4

Recurrent advanced heart failure;

resting symptoms at home on oral

therapy

Ambulatory IV Within weeks to

months D

INTERMACS

5 Exertion intolerant Ambulatory IV Variable D

INTERMACS

6 Exertion limited or walking wounded Ambulatory IV Variable C-D

INTERMACS

7 Advanced NYHA III IIIB Variable C

Source: The Journal of Heart and Lung Transplantation 2013; 32:141-156 (DOI:10.1016/j.healun.2012.12.004 )

Copyright © 2013 International Society for Heart and Lung Transplantation Terms and Conditions

Interaction of Age and INTERMACS Level

on Survival following CF-LVAD Implantation

Clinical Outcomes Based on INTERMACS Profile

Less acutely ill, ambulatory patients in INTERMACS profiles 4-7 had better survival and

reduced length of stay compared to patients who were more acutely ill in profiles 1-3.

Length of Stay Post-VAD Actuarial Survival Post-VAD

Boyle, Ascheim, Russo,

et.al. JHLT. 30:4, 2011.

“It’s better to refer a month too early

than a week too late”

Transplant

LVAD

Hospice

End Stage Cancer

End Stage Heart Failure

74% receive ICD shock

within days of death

ADLER ED 2010

75

76

77

78

79

80

81