La stimulation vagaleNouveau traitement électrique de

l’insuffisance cardiaque ?

Philippe Mabo, CHU de Rennes

CARDIORUN 2014Boucan Canot, 3 octobre 2014

Mes relations avec l’industrieBourses de recherche:

Boston, Biotronik, Medtronic, St Jude Medical, Sorin Group

Lectures:Bayer, BMS, Boehringer, Boston, Meda-Pharma, Medtronic,St Jude Medical, Servier, Sorin Group

Consultant:Bayer, BMS, Boehringer, Boston, Biotronik, Daiichi-Sankyo,Meda-Pharma, Medtronic, Sorin Group

Le parcours thérapeutique de l’insuffisance cardiaque

TerminaleSévèreSymptomatiqueAsymptomatiquevérité de nsuffisance rdiaque

aitement

3,1 millions

10,2 millions

7,3 millions

1,5 millions

Nombre de personnes atteintes

22 millions de personnes au

Traitement médical

Défibrillateur resynchronisateur **

Revascularisation, chirurgie

Assistance circulatoireTransplantation

Autonomic Activity in Heart FailureSome Basics

mpathetic nerve hyperactivity• Consequently reduced

sympathetic neuronal density and responsiveness

• Abnormal Ca handling

• Apoptosis

duced Parasympathetic activity• Increased HR, Decreased HRV,

etc.

bnormal cardiac reflexes• Suppressed arterial baroreceptor

reflex

BBS?

sympatheticModulators

wer Devicesdostigmine

Sympathetic Tone Modulators

- Beta-blockers- RAAS- Aldosterone - Newer Devices

Sympathovagal Balance and the Heart

gets for Emerging Neuromodulation Therapies

agal Nerve Stimulation for Heart FailureIntegrated care between HF, Neurosurgery and EP)

Fit®

atorFit®

ator

•Selective Nerve Cuff Electrode

•Standard Bipolar RV Lead

for Sensing

•Standard Bipolar RV Lead

for Sensing

CardioFit Pilot Protocol

32-patient, multi-center study in Europe

Patient population:– NYHA Class II-IV; LVEF 35%; – Medically stable for 3 months, including -blockers

Primary endpoints: device safety and side effects

Secondary endpoints:• Functional: NYHA, 6 MW, Quality Of Life (MN Living with Heart Failure ) • Structural: EF, EDV, ESV• Heart rate variability

23 patients with 12 month extended follow-up

Clinical Impact of VNS6 month follow up

LVEF

Randomization and Follow-up

Randomized, parallel controlled (n=650)Intention to treat from randomizationClinic contact with Control group to balance CardioFit titration visitsPrimary endpoint: HF hospitalization and all cause mortality

Boston VNS System

NYHA class change

The Baroreflex Activation System

•Impl nt la abe•Impl nt la abe

•B ror l xa efe

•A t v t on L sci ai ead

•B ror l xa efe

•A t v t on L sci ai ead

Pro r mm nga i g

Syst me

Pro r mm nga i g

Syst me

euromodulation with Spinal Cord Stimulation

Stimulation leads in epidural space; 2 hours TID of stimulationDevice in lumbar region

•T4

•T5

•RV lead

•RA lead •SCS

lead

Renal denervationProcedure:- Low energy RF- Full circumferential- 4-6 lesions- Catheter or balloon based procedure

evolving

Clinical Impact:- Deceased SNS activity- Restores impaired natriuresis- Decreased LV filling pressures- Increased LV function

Physiology Studies: PRESERVE Study (HF Network)

teforme de neurostimulation implantable évoluée

RFommunication

Analog cardiacsensing &

pacing

RAM/ROM

MEMSSensors

High voltageDefibrillation

Titaniumpackage

Hermetic package

MultichannelNeuro sensing

Neurostimulation

Vagal nerve

Low powerCPU

Projet INTENSE

Académiques

Hospitaliers

Industriels

tense – Premier prototype chez l’animal

Conclusion

Voies thérapeutiques nouvelles

Concepts et approches techniques multiples

Premiers résultats divergeant

Développements en cours

Etape clé: résultats de l’étude INOVATE-HF