Recent Successes in Heart Failure -...

Recent Successes in Heart Failure

Samer S. Najjar, M.D.Medical Director, Heart Failure and Heart Transplantation

MedStar Heart and Vascular Institute

MedStar Washington Hospital Center

May 30, 2015

Presenter Disclosure Information

FINANCIAL DISCLOSURE:

Research Support: HeartWare Inc, Gambro

Advisory Board: HeartWare Inc

Samer S. Najjar, MD

UNLABELED/UNAPPROVED USES DISCLOSURE:

None

Recent Sucesses in Heart Failure

Chronic Heart Failure

Acute Decompensated Heart failure

Heart Failure with Preserved Ejection Fraction

Stage D Heart Failure

Heart FailureEpidemiology/Facts

Prevalence: ~ 7 million in US (2.5%)

Incidence: ~ 550,000/year

Mortality: ~ 300,000/year

Office visits: ~ 3.4 million (2004)

Hospital discharges: ~ 1,000,000 (2001)

Health care costs exceed $30 billion/year

Single largest expense for Medicare

0.3 0.30.5 0.4

1.81.5

5.8

2.3

6.2

4.1

9.8

10.9

0

2

4

6

8

10

12

20-34 35-44 45-54 55-64 65-74 75+

Male Female

Heart FailurePrevalence

Perc

en

t o

f P

op

ula

tio

n

Age

References: American Heart Association. Heart Disease and Stroke Statistics – 2005 Update.

NHANES: 1999-2002.

Heart FailureDemographic Trends

Elderly U.S. population will double in the next decade

0

25

50

75

1990 2000 2010 2020 2030

Pro

jecte

d E

lderly

Popula

tion

>65 y

ears

(m

illio

ns)

12.6% total US

population

31.5 million

65.6 million

21.8% total US

population

7NATRECOR® (nesiritide) P0512500

Estimated Direct and Indirect Costs of Heart

Failure in the USLow productivity/

mortality*

$2.6Home healthcare

$2.2

Drugs/other

medical durables

$2.9

Physicians/other

professionals

$1.9

Nursing home

$3.6

Hospitalization

$14.7

Total cost:

$27.9 Billion

* Lost future earnings of persons who will die in 2005, discounted by 3%.

Reference: American Heart Association. Heart Disease and Stroke Statistics – 2005 Update.

Heart Failure Hospitalizations

The Number of Heart Failure Hospitalizations Is Increasing in Both Men and Women

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

AHA. 2002 Heart and Stroke Statistical Update. 2001.

An

nu

al

Dis

ch

arg

es

0

100,000

200,000

300,000

400,000

500,000

600,000

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

Women

Men

Year

'99

Heart Failure Pathophysiology

Myocardial Injury Fall in LV Performance

Activation of RAAS, SNS, ET,

and Others

Myocardial ToxicityPeripheral Vasoconstriction

Hemodynamic Alterations

Remodeling and

Progressive

Worsening of

LV Function Heart Failure SymptomsMorbidity and Mortality

ANP

BNP

Shah M, et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2-S6.

Therapies for Chronic HF by NYHA Class

Diuretics

Digoxin

ACE inhibitors

ARBs

Beta blockers

Aldactone

Hydralazine/nitrates

ICD

CRT

Therapy Class I Class II Class III Class IV

Adapted from Almeda FQ, Hollenberg SM. Postgrad Med. 2003;113:41

MADIT-IIICD vs. Conventional Rx

N Engl J Med. 2002;346:877-882

0.78

0.69

P=0.007

0 1 2 3 4

Defibrillator Group

Conventional Group

Pro

ba

bil

ity o

f S

urv

iva

l

Years

0.5

0.6

0.7

0.8

0.9

1.012% 28% 28%

Ventricular Dyssynchrony

Effects of CRTon LV Performance

45

40

35

30

25

20

Ejection Fraction (%)

Baseline 1wk 1mo 3mo off-immed

off-1wk

off-4wk

1000

900

800

700

600

500

400

Baseline 1wk 1mo 3mo off-immed

off-1wk

off-4wk

dP/dtmax (mmHg/sec)

Yu CM, et al. Circulation. 2002;105:438-445

Systolic Heart failure treatment with

the If

inhibitor ivabradine Trial

Mean heart rate reduction

70% of patients on ivabradine 7.5 mg bid

0 2 weeks 1 4 8 12 16 20 24 28 32

Months

90

80

70

60

50

67

7575

80

64

Heart rate (bpm)

Placebo

Ivabradine

www.shift-study.comSwedberg K, et al. Lancet. 2010;376(9744):875-885

0 6 12 18 24 30

40

30

20

10

0

Primary composite endpoint(CV death or hospital admission for worsening HF)

18%

Cumulative frequency (%)

Placebo

Ivabradine

HR = 0.82 (0.75–0.90)

P < 0.0001

Months


0 6 12 18 24 30

30

20

10

0

Hospitalization for HF

26%

Placebo

Ivabradine

HR = 0.74 (0.66–0.83)

P < 0.0001

Months



Death from heart failure

26%

0 6 12 18 24 30

10

5

0

HR = 0.74 (0.58–0.94)

P = 0.014

Placebo

Ivabradine

Months



McMurray JJ et al. N Engl J Med 2014;371:993-1004

Angiotensin-Neprilysin Inhibition vs. Enalapril in HF (PARADIGM-HF)

McMurray JJV et al. N Engl J Med 2014;371:993-1004


Heart FailureOutcomes of Hospitalized Patients

References: Aghababian RV. Rev Cardiovasc Med. 2002;3(suppl 4):S3-S9.

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

0

25

50

75

100

20%

50%

30Days

6Months

Hospital Readmissions

0

25

50

75

100

12%

60%

30Days

12Months

Mortality

33%

5Years

Median length of hospital stay: 6 days

N = 38,702 N = 38,702

Incomplete Relief of Congestion

8% 7%

13%

24%

32%

15%

3% 2%

0

5

10

15

20

25

30

35

En

roll

ed

Dis

ch

arg

es

(%)

20% of ADHF patients

discharged with weight

gain or no change in weight

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

Change in Weight (lbs)

DOSE trialBolus vs. Continuous Diuretics

Felker et al. N Engl J Med 2011; 364:797-805

ASCEND-HFNesiritide in patients with ADHF

O’Connor et al. N Engl J Med 2011; 365:32-43

Mechanical Fluid Removal by Ultrafiltration

Vascular

Space

UF

Vascular

Space

Interstitial

Space (edema)

Na

Na

Na

Na

K

P

H2O

K

P

PR

APS

Primary End PointWeight Loss at 48 Hr

Primary End PointWeight Loss at 48 Hr

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

Bart BA et al. N Engl J Med 2012;367:2296-2304

CARRESS-HFUF in ADHF with Cardiorenal Syndrome

CARRESS-HF – UF v. Diuretics

May 19, 2015

29

Bart NEJM 2012

Prevalence of HFPEF vs. SHF

by Age Groups

Tribouilloy Eur Heart J 2007; 29:339

Heart FailureSecular Trends in Survival

Owan, N Engl J Med 2006; 355; 251

Reduced EF Preserved EF

ACC/AHA Heart Failure Stages

Jessup N Engl J Med 2003;348:2007-2018

Therapies for End-Stage HF

Hospice/Palliation

Inotropes

IABP

Heart Transplantation

Mechanical Assist Devices

NUMBER OF HEART TRANSPLANTS

REPORTED BY YEAR

0

500

1000

1500

2000

2500

3000

3500

4000

4500

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

Nu

mb

er

of

Tra

ns

pla

nts

Other

EuropeNorth America

2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

ADULT HEART TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: 1/1982 – 6/2006)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Years

1982-1991 (N=18,854)

1992-2001 (N=35,146)

2002-6/2006 (N=12,369)

All comparisons significant at p < 0.0001

HALF-LIFE 1982-1991: 8.8 years; 1992-2001: 10.5 years; 2002-6/2006: NA

Su

rviv

al (%

)

ISHLT 2008J Heart Lung Transplant 2008;27: 937-983

Ventricular Assist Devices

REMATCH Trial

Rose E et al NEJM 2001:345;1435-43.

- 48%

p=0.001

LVAD

Medical Rx

Ventricular Assist Devices

HeartMate II HeartWare

Months

0 6 12 18 24

Perc

en

t S

urv

ival

0

10

20

30

40

50

60

70

80

90

100

CF LVAD

68%

58%

OMM REMATCH 8%

25%

* N Engl J Med 2001; 345:1435-43

Outcomes with LVAD vs. OMM

N Engl J Med. 2009;361:2241-51

Months

0 6 12

Pe

rcen

t S

urv

iva

l

0

10

20

30

40

50

60

70

80

90

100

Early Triale

Implant dates n 30 d 6 Mo 12 mo

a Apr ’08 - Oct ‘10 1496 95% 89% 85% b Apr ’08 - Aug ‘08 169 96% 90% 85%

c Mar ’07 - Apr ‘08 205 95% 86% 80% d Mar ’05 - Mar ‘07 281 92% 82% 73%

e Mar ’05 - May ’06 133 89% 75% 68%

Early-mid Triald

Late Trialc

Post-Triala

Post-Approval Studyb

a John et al STS 2011b Starling et al JACC (in press)d Pagani et al JACC 2009e Miller et al NEJM 2007

John, Naka, Smedira et al: Presented at STS 2011

HeartMate IISurvival by Era

Improvement in Functional Class

Rogers, J Am Coll Cardiol. 2010 27;55(17):1826-34

Baseline 1 mth 3 mth 6 mth

Improvement in QOL (KCCQ)

Rogers, J Am Coll Cardiol. 2010 27;55(17):1826-34

ThoratecNext Generation Pumps

HeartMate III HeartMate X

Investigational Devices

HeartWare HVAD & MVAD

Investigational Devices

Partial SupportCirculite

Investigational Device

LVAD Offered on ebay!

Advances in Heart Failure Therapy

Chronic Heart Failure √ √

Acute Decompensated Heart failure X


X X

Stage D Heart Failure √ √ √ √

PrognosisHeart Failure vs. Cancer Mortality

Coronary heart disease statistics: heart failure supplement., BHF 2002, http://www.heartstats.org, accessed 25.02.04.

Based on Quinn M et al. ONS 2001 & Cowie MR et al. Heart 2000; 83: 505-510.

0 20 40 60 80 100

Melanoma

Uterus

Prostate

Colon

Ovarian

Leukaemia

Oesophagus

Pancreas

One year survival rate (%)

The one-year survival rate for heart failure is worse than that

for cancer of the breast, uterus, prostate & bladder

NHL= Non-Hodgkins lymphoma

http://www.heartstats.org/

PrognosisHeart Failure vs. Cancer Mortality

1 Rose, Gelijns, Moskowitz, et al. NEJM. 345:1435-43, 2001. 2 Rogers, Butler, Lansman, et al. J Am Coll Cardiol. 50:741-47, 2007.

3 Hershberger, Nauman, Walker, et al. J Card Fail. 22:616-24, 2003.4 Gorodeski, Chu, Reese, et al. Circ Heart Fail. 2:320-24, 2009


Back-Up Slides


Hemodynamic Profile Assessment

Congestion at Rest

Low

Perfusion

at Rest

No

No Yes

Yes

Warm & Dry Warm & Wet

Cold & WetCold & Dry

Signs/symptoms of congestion

• Orthopnea/PND

• JVD

• Ascites

• Edema

• Rales (rare in HF)

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

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

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


Patient Selection and TreatmentCongestion at Rest

YesNo

Warm & Dry

PCWP normal

CI normal(compensated)

Cold & Wet

PCWP elevated

CI decreased

Cold & Dry

PCWP low/normal

CI decreased

Vasodilators

Nitroprusside

Nitroglycerin

Inotropic Drugs

Dobutamine

Milrinone

Normal

SVRHigh

SVR

Low

Perfusion

at Rest

No

Yes

Warm & Wet

PCWP elevated

CI normal

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

Similarities Between Acute MI and

Acute Decompensated HF

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

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

(coronary

thrombosis)

Uncertain

Clinical benefits of

interventions in published

clinical trials

Beneficial

Minimal/no benefit or

deleterious compared with

placebo

ACC/AHA recommendationsMany

Level ANone***

Cost of End-Stage HF

REMATCH Trial (OMM)

– Mean cost last 2 yrs: $156,169

$78,880 (50% last 6 mos)

– 1 in 4 days in last 6 months spent in the hospital

– 79% of all costs were for inpatient costs

• 28% for ICU care,

• 18% for outpatient care,

• 3.5% for MD professional fees

Russo, M, et al. JCF. 2008;14(8): 651-658.

B165-0411

LVAD costs compared with other life-

saving therapies

$91,093

$53,000

$160,000

$128,000

$0

$50,000

$100,000

$150,000

$200,000

Heart

Transplantation

(1995)

Kidney Dialysis

(2000)

Chemotherapy

for Colon

Cancer (2004)

LVAD for DT

(2004)

Total One Year Costs Per Initial Hospitalization

Annual Medicare budget per heart transplant ($175,000) from deLissovoy, Health Affairs, 1998

Annual Medicare payment for kidney dialysis ($53,000) from CMS, 2002

Twelve month cost of mAb-based chemotherapy based on AWP for colon cancer ($161,000) from Schrag, NEJM, 2004

Average LVAD hospitalization costs ($128,084) for two of the highest-volume DT-accredited facilities (Miller et al, 2006)

LVAD

implantation is

both life-saving

and resource-

intensive.

Costs are very

similar to other

high-tech

interventions

that society

pays

Natural History of Systolic HF

Survival After Hospitalization

Miller, Guglin J Am Coll Cardiol. 2013;61(12):1209-21

Heart FailureRisk Stratification

Cardiopulmonary

Exercise Testing

Prognostic Significance of

Oxygen Consumption

Albouaini Heart 2007;93:1285-1292 Mancini Circulation 1991;83:778-786

Ivabradine significantly reduces major risks associated

with heart failure:

18% reduction in CV death or hospital admission for worsening HF

26% reduction in death from heart failure

26% reduction in hospital admission for worsening heart failure

Benefits are apparent early, are consistent in

predefined subgroups, and have been

demonstrated on top of recommended therapy

Treatment is well tolerated

Conclusion


Continuous Flow Physiology

No PULSE

Measurement of

Blood Pressure

McMurray JJV et al. N Engl J Med 2014;371:993-1004


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