Download Limitations of Current Heart Failure Therapies

Limitations of Current Heart Failure
Therapies and The Need for C-Pulse
William T. Abraham, MD, FACP, FACC, FAHA
Professor of Medicine, Physiology, and Cell Biology
Chair of Excellence in Cardiovascular Medicine
Chief, Division of Cardiovascular Medicine
Deputy Director, Davis Heart & Lung Research Institute
The Ohio State University
Columbus, Ohio
Epidemiology of Symptomatic
Heart Failure in the U.S.
• Major public health problem
•  5.8 million Americans with heart failure
•  500,000 new cases diagnosed each year
• Most frequent cause of hospitalization in
patients older than 65 years
• Causes or contributes to 250,000 deaths/year
• 1-Year mortality rate is about 10-15%
• 5-Year mortality rate approaches 50%
Evidence-Based, Guideline-Recommended
Treatment of Symptomatic Heart Failure
Reduce Mortality
Control Volume
Diuretics
ACEI
or ARB
-Blocker
Aldosterone
Antagonist
or ARB
CRT 
an ICD*
Hyd/ISDN*
Treat Residual Symptoms
*For all indicated patients.
Abraham WT, 2005
Digoxin
Despite Current Therapies, Heart Failure
Morbidity and Mortality Remain High
• 30% to 40% of patients are in NYHA
class III or IV
• Re-hospitalization rates
– 2% at 2 days
– 25% at 1 month
– 50% at 6 months
• 5-year mortality ranges from 15% to
more than 50%
– Asymptomatic LVD  15%
– Mild-moderate HF  35%
– Advanced HF >50%
Outcomes in Patients Hospitalized With
Heart Failure
100
Hospital Readmissions
100
Mortality
75
75
50%
50
50%
50
33%
20%
25
0
25
30
Days
6
Months
0
12%
30
12
Days Months
5
Years
Median LOS: 6 days; N = 38,702
Among Medicare beneficiaries, 27% of HF patients are re-hospitalized within 30 days
Aghababian RV. Rev Cardiovasc Med 2002; 3:S3
Jong P et al. Arch Intern Med 2002; 162:1689
Jencks and Williams. NEJM 2009; 360:1418
Economic Burden of Heart Failure in the U.S.
Maintenance ($18 B)
• Medications
• Routine MD visits
• Nonmedical care
Episodes of
decompensation
($36 B)
• Hospital care
• MD visits
• ED visits
• Dx testing
Surgical procedures
to treat HF ($2 B)
• Heart
transplantation
• Mechanical
devices
Total HF cost: $56 billion
O’Connell JB. Clin Cardiol 2000; 23:III-6
Classifications of Heart Failure
ACC/AHA HF Stage1
A At high risk for heart failure but without
structural heart disease or symptoms
of heart failure (eg, patients with
hypertension or coronary artery disease)
B Structural heart disease but without
symptoms of heart failure
NYHA Functional Class2
None
I Asymptomatic
C Structural heart disease with prior or
current symptoms of heart failure
II Symptomatic with moderate exertion
D Refractory heart failure requiring
specialized interventions
IV Symptomatic at rest
1Hunt
2New
III Symptomatic with minimal exertion
et al., Circulation & JACC September 2005
York Heart Association/Little Brown and Company, 1964
Classifications of Heart Failure
ACC/AHA HF Stage1
A At high risk for heart failure but without
structural heart disease or symptoms
of heart failure (eg, patients with
hypertension or coronary artery disease)
NYHA Functional Class2
None
B Structural heart disease but without
symptoms of heart failure
Asymptomatic
Generally doing well onI available
therapies
C Structural heart disease with prior or
current symptoms of heart failure
II Symptomatic with moderate exertion
D Refractory heart failure requiring
specialized interventions
IV Symptomatic at rest
1Hunt
2New
III Symptomatic with minimal exertion
et al., Circulation & JACC September 2005
York Heart Association/Little Brown and Company, 1964
Classifications of Heart Failure
ACC/AHA HF Stage1
A At high risk for heart failure but without
structural heart disease or symptoms
of heart failure (eg, patients with
hypertension or coronary artery disease)
B Structural heart disease but without
symptoms of heart failure
C Structural heart disease with prior or
current symptoms of heart failure
NYHA Functional Class2
None
I Asymptomatic
II Symptomatic with moderate exertion
III Symptomatic with minimal exertion
Require heroic measures (LVAD,
transplantation)
or
IV Symptomatic
at rest
end-of-life care
D Refractory heart failure requiring
specialized interventions
1Hunt
2New
et al., Circulation & JACC September 2005
York Heart Association/Little Brown and Company, 1964
Classifications of Heart Failure
ACC/AHA HF Stage1
A At high risk for heart failure but without
structural heart disease or symptoms
of heart failure (eg, patients with
hypertension or coronary artery disease)
B Structural heart disease but without
symptoms of heart failure
NYHA Functional Class2
None
I Asymptomatic
C Structural heart disease with prior or
current symptoms of heart failure
II Symptomatic with moderate exertion
D Refractory heart failure requiring
specialized interventions
IV Symptomatic at rest
III Symptomatic with
exertion
Desperately need new therapies
– minimal
C-Pulse
1Hunt
2New
et al., Circulation & JACC September 2005
York Heart Association/Little Brown and Company, 1964
Extra-Aortic Counterpulsation
Heart Fills - Cuff Inflates
Heart Ejects - Cuff Deflates
to body
to heart
reduce
workload
Increased Blood Flow: + 60% coronary flow; + 30% cardiac output;
Reduced Heart Workload: - 30% PA pressure; -33% LV wall stress
C-Pulse System
Extra-aortic Cuff
ECG Sense Lead
Interface Lead
Battery Pack
Driver
Goals for a Pilot Study
• Demonstrate feasibility of device/procedure
– Assess learning curve
– Refine technology and implant technique
• Provide reasonable assurance of safety
– Learn how to mitigate risk
• Explore preliminary efficacy signals
– “Totality of data”
• Support conduct of subsequent pivotal trial
Endpoints of C-Pulse Pilot Study
• Safety
–
–
–
–
Death
Neurological events
Infection
Myocardial infarction
• Efficacy
–
–
–
–
Peak VO2
6-minute hall walk distance
Quality of life
NYHA class ranking
Assessing Efficacy in Heart Failure
• Progressors (worse)
• Non-progressors (unchanged)
• Responders (improved)
• Super-responders
The natural history of heart failure is
progression (worsening)!
Results of C-Pulse Pilot Study*
• 20 patients, 8 women and 12 men, with an
average age of 56 years
• 18 patients classified in NYHA Class III; 2 in
Class IV
• 3 patients successfully bridged to transplant,
with 1 patient being supported for 22 months
• All but 1 patient either improved or
maintained NYHA heart failure classification
*To be presented as “featured clinical research” during the Transcatheter Cardiovascular
Therapeutics Meeting on November 8, 2011 in San Francisco, CA
Results of C-Pulse Pilot Study
• Other improvements were observed as
measured by quality of life scores, 6-minute
walk distances, ejection fractions, and
reductions in medications
• 2 patients were disconnected permanently,
due to the absence of heart failure symptoms
(super responders)
• 1 patient death from an aortic disruption*
*as a result of a re-sternotomy surgery to treat a procedure related infection
Next Steps
• Randomized controlled pivotal trial to
confirm safety and efficacy of C-Pulse
• Primary endpoints focused on heart failure
morbidity (hospitalization) and device/
procedure safety
• Secondary endpoints to include measures
of patient functional status, quality of life
and exercise capacity