recent successes in heart failure -...
TRANSCRIPT
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
www.shift-study.comSwedberg K, et al. Lancet. 2010;376(9744):875-885
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
Cumulative frequency (%)
www.shift-study.comSwedberg K, et al. Lancet. 2010;376(9744):875-885
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
Cumulative frequency (%)
www.shift-study.comSwedberg K, et al. Lancet. 2010;376(9744):875-885
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
Angiotensin-Neprilysin Inhibition vs. Enalapril in HF (PARADIGM-HF)
Recent Successes in Heart Failure
Chronic Heart Failure
Acute Decompensated Heart failure
Heart Failure with Preserved Ejection Fraction
Stage D Heart Failure
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
Recent Successes in Heart Failure
Chronic Heart Failure
Acute Decompensated Heart failure
Heart Failure with Preserved Ejection Fraction
Stage D Heart Failure
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
Recent Successes in Heart Failure
Chronic Heart Failure
Acute Decompensated Heart failure
Heart Failure with Preserved Ejection Fraction
Stage D Heart Failure
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
Heart Failure with Preserved Ejection Fraction
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
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
53NATRECOR® (nesiritide) P0512500
Back-Up Slides
54NATRECOR® (nesiritide) P0512500
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.
55NATRECOR® (nesiritide) P0512500
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
www.shift-study.comSwedberg K, et al. Lancet. 2010;376(9744):875-885
Continuous Flow Physiology
No PULSE
Measurement of
Blood Pressure
McMurray JJV 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
Angiotensin-Neprilysin Inhibition vs. Enalapril in HF (PARADIGM-HF)