Spinal Cord Stimulation for Heart FailureStuart P. Rosenberg, M.S.Senior Manager, Neuromodulation ResearchImplantable Electronic Systems DivisionSt. Jude Medical

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Disclosures

I am an employee of St. Jude Medical.I will be discussing unapproved and/or investigational uses of medical devices.

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Cardiac Dysfunction

Increased Sympathetic

Outflow

RAAS Activation

Fluid Overload

Heart failure is a progressive syndrome

HFSA Guidelines: Lindenfeld, J Card Fail, 2010Schrier, NEJM, 1999

Shortness of breath

Fatigue

Susceptibility to arrhythmias

Myocardial remodeling

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Modern HF treatment paradigm: drugs ± device

AHA/ACC HF Guidelines: Hunt, Circ, 2009

Anti-Sympathetic RxImplantable Cardioverter-Defibrillator (ICD)

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Can we treat patients with heart failure using electrical

neuromodulation?

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SCS for refractory angina pectoris

Promising clinical evidencefrom feasibility studies in man

Decreased frequency of anginal attacks1-3

Decreased nitrate & morphine consumption4-5

Improved functional class6-7 and QoL8,

Increased exercise capacity9-

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Stabilization of intrinsic cardiac nerves during ischemia in canine

Foreman, Cardiovasc Res, 2000

1 Greco, PACE, 19992 Hautvast, Clin Cardiol, 19983 De Jongste H, BHJ, 19944 Murphy, Pain, 19875 Andersen, Pain Clinic, 19956 TenVaarwerk. Heart, 1999

7 Sanderson, BMJ, 19928 Vulink, Intl Neurom, 19999 DeJongste, JACC, 199410 Hautvast, AHJ, 199811 Sanderson, EHJ, 1994

NOTE: SCS is not currently approved in the U.S. for use in treating angina pectoris

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SCS directly affects the heart’s electrical propertiesin healthy canine

Increasing Sympathetic Stimulation

Increasing Vagal Stimulation

Effect of SCS on Sinus Cycle Length

Olgin, J Cardiovasc Electrophysiol, 2002Bernstein, Heart Rhythm, 2012

No SCS

During SCS

Effect of SCS on Atrial Effective Refractory Period

(S1=400 ms)

NOTE: SCS is not currently approved in the U.S. for use in treating cardiac arrhythmia

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SCS improves LV function and reverse remodelingin canine HF

SCSSCS+MEDSMEDSCTRL

Lopshire, Circ, 2009

LVE

DD

(cm

)

BSLN After 2Wk 5Wk 10Wk HF

LVE

SD

(cm

)

BSLN After 2Wk 5Wk 10Wk HF

LVE

DD

(cm

)

BSLN After 2Wk 5Wk 10Wk HF

LVE

SD

(cm

)

BSLN After 2Wk 5Wk 10Wk HF

LV E

ject

ion

Frac

tion

(%)

BSLN After 2Wk 5Wk 10Wk HF

Ser

um B

NP

(pg/

ml)

Systolic function

Reverse remodeling

Neurohormonal biomarkers

BSLN After 2Wk 5Wk 10Wk HF

Ser

um N

orep

inep

herin

e (p

g/m

l)

BSLN After 2Wk 5Wk 10Wk HF

Ser

um B

NP

(pg/

ml)

BSLN After 2Wk 5Wk 10Wk HF

Ser

um N

orep

inep

herin

e (p

g/m

l)

Spo

ntan

eous

arr

hyth

mia

s (n

)S

pont

aneo

us a

rrhy

thm

ias

(n)

Ventricular tachyarrhythmias

NOTE: SCS is not currently approved in the U.S. for use in treating heart failure

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SCS improves LV contractility at reduced O2 demandin porcine HF

HF (No SCS)During SCS

Liu,J Cardiovasc Electrophysiol, 2012

NOTE: SCS is not currently approved in the U.S. for use in treating heart failure

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SCS is promising at different stimulation durationsin porcine HF

BSLN MI MI+HF 2 Wk 6 Wk 10 Wk

Systolic function Serum Norepinephrine

Tse, ESC Congress (abstract presentation), Aug 2012

LVE

F (%

)

BS

LN MI

MI+

HF

10 W

k

BS

LN MI

MI+

HF

10 W

k

BS

LN MI

MI+

HF

10 W

k

Noe

repi

neph

erin

e (p

g/m

L)

Control SCS 12 hr SCS 24 hr

NOTE: SCS is not currently approved in the U.S. for use in treating heart failure

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Neurostimulation of Spinal Nerves that Affect the Heart

SCS-HEART DEFEAT-HF TAME-HF

Sponsor The Methodist Hospital System(collaboration with SJM)

SJM MDT SJM

Principal Invest-igator

Guillermo Torre-Amione

Hung-Fat Tse Doug Zipes, Heinz Theres

Pierre Bordachar

Sites Houston Methodist, USA

~5 sites: Hong Kong & Australia

~30 sites: USA and EU

Bordeaux, FR

# Patients 10 20 250 20Clinical Trial ID

NCT01124136 NCT01362725 NCT01112579 not yet registered

Several clinical trials are underway for SCS in HF

Neurostimulation of Spinal Nerves that Affect the Heart

SCS-HEART DEFEAT-HF TAME-HF

Sponsor The Methodist Hospital System(collaboration with SJM)

SJM MDT SJM

Principal Invest-igator

Guillermo Torre-Amione

Hung-Fat Tse Doug Zipes, Heinz Theres

Pierre Bordachar

Sites Houston Methodist, USA

~5 sites: Hong Kong & Australia

~30 sites: USA and EU

Bordeaux, FR

# Patients 10 20 250 20Clinical Trial ID

NCT01124136 NCT01362725 NCT01112579 not yet registered

ClinicalTrials.gov and internal data

CAUTION Investigational device. Limited by Federal (or United States) law to investigational use.

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Promising early experience with SCS in HF patients

Torre, Heart Failure Society of America (poster presentation), Sep 2012

CAUTION Investigational device. Limited by Federal (or United States) law to investigational use.

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SCS for HF: What else do we need to know?

Mechanism of action

Target patient population and subgroup analyses

Duration, dosage, and other treatment parameters

Possible side effects and interactions with background therapies

NOTE: SCS is not currently approved in the U.S. for use in treating heart failure