maor presentation 2016
TRANSCRIPT
Novel Transcatheter
Device to Treat
Hypertrophic Obstructive
Cardiomyopathy
Elad Maor MD PHD
Zachi Berger PhD MBA
Sheba Medical Center, Israel
2016
The clinical need:
Hypertrophic Obstructive
Cardiomyopathy
Dynamic left ventricular outflow tract obstruction
The most common cardiac genetic disorder
Prevalence 1:500 adults (600,000 in the US)
A major cause of sudden death and heart failure in young people
HCM Can Cause
Outflow Track Obstruction
Characterized by a thickened but nondilated left ventricle
Cause increased intraventricular pressures that may be detrimental to LV function
Increased myocardial wall stress and oxygen demand
In histopathology specimens of HCM, cardiac muscle cells (myocytes) in both ventricular septum and left ventricle (LV) free wall show increased transverse diameter and bizarre shapes
Clinical diagnosis of HCM is usually made with two-dimensional echocardiography
A 14 years old boy with sudden death and
septal thickness of 65 mm. Ao - aorta, LVFW
– left ventricular free wall, VS – ventricular
septum
Clinical Course and
Medical Treatment 1 HCM can lead to sudden cardiac death or progressive heart failure with
exertional dyspnea and functional limitation
Current medical treatments: Myectomy Surgery, Alcohol Ablation, Anticoagulation Drugs
Surgical septal reduction therapy - Myectomy - is the gold standard as the results for, are unmatched for early, long term benefit
However, Myectomy has generally been confined to selected major centers having substantial experience with this procedure and is not suitable for all patients
Clinical Course and
Medical Treatment 2, 3 Percutaneous alcohol septal ablation, is alternative to Myectomy only in
selected patients and is a sub-optimal solution
The use of Beta Blockers, Calcium Channel Blockers and anticoagulation in patients who develop atrial fibrillation with a lot of side effects
There is clinical need for novel minimally invasive
non-surgical approach
Our Device and Method:
Non Thermal Irreversible
Electroporation - NTIRE Our novel transcatheter endovascular device and method will be
able to attenuate left ventricular obstruction and heart failure in patients with HCM, without the need for open heart surgery
Our approach is based on a novel non thermal ablation approach that can damage only cellular components within seconds and with no damage to the extra cellular components
Irreversible Electroporation (IRE) is
an emerging ablation approach
Medical Use of Irreversible
Electroporation
It can induce significant ablation of biological tissue, and is
currently under evaluation in clinical trials for the treatment
of solid tumors utilizing 1,500V
Irreversible electroporation with voltages of up to 3,000V is
CE and FDA approved for solid tumors. It is being used
clinically all over the world
There are currently more than 90 clinical trials running but
not in Cardiology
Summary of NTIRE Preclinical
Studies Non-thermal Irreversible Electroporation (NTIRE) is an
emerging cell ablation approach
NTIRE induces cell death by creating pores in cell membranes
In contrast to all other available ablation modalities, it induces
ablation within microseconds and with no heat generation
Due to its non-thermal nature, NTIRE does not damage extra
cellular components
Our preliminary in vivo results show that endovascular NTIRE
has the potential to ablate hypertrophic myocardium, without
the need for open heart surgery
Our results demonstrate the efficacy and safety of in-vivo non
thermal ablation of cellular components in the beating heart
Preliminary Animal Model
In vivo IRE is achieved using two needle
electrodes inserted into the anterior
myocardium of SD rat through the 4th
inter-costal space
Ablation effect due to different NTIRE protocols
on vascular smooth muscle cells (VSMC). The
figure summarizes and compares NTIRE
ablation efficiency of eight different
electroporation protocols. Ablation effect is
shown as the percentage of vascular smooth
muscle cells in the treated carotid artery
compared with the right carotid artery of the
same animal. The reduction in five of the groups
was statistically significant (P<0.001, bars)
marked with an asterisk)
Arterial Wall Ablation with
In-Vivo IRE
In-Vivo IRE Safety Studies
(Sheba 2012)
In-Vivo Myocardial Ablation
Cellular Environment Rich in
Collagen (Masson Trichrome Stain)
Elastic Stain Shows Sparing of
Blood Vessels Structure
Device Prototype Concept
Endovascular NTIRE Prototype:
Disposable Flexible Nitinol Cage
Real picture of the prototype in its
inflated state. The four legs are 2
cm in length. (Assembled by Jim
Mitchell, Angiodynamics Inc.,
Queensbury , NY - subcontractor)
Electric field distribution (∆V = 600 Volts) -.
Color-Scale is in units of V/cm. This potential
difference electric field is relatively uniform and
high enough throughout the vessel wall
Scientific and Medical
Recognition Peer Reviewed Journal Articles:
Maor E, Ivorra A, Leor J, Rubinsky B. The Effect of Irreversible Electroporation on Blood Vessels. Technol
Cancer Res Treat. 2007 Aug; 6(4): 307-312. Cited in PubMed; PMID: 17668938.
Maor E, Ivorra A, Leor J, Rubinsky B. Irreversible Electroporation Attenuates Neointimal Formation after
Angioplasty. IEEE transactions on bio-medical engineering. IEEE Trans Biomed Eng. 2008 Sep;55(9):2268-
74. Cited in PubMed; PMID: 18713696
Maor E, Ivorra A, Rubinsky B. Non Thermal Irreversible Electroporation - Novel Technology For Vascular
Smooth Muscle Cells Ablation. PLoS One. 2009;4(3):e4757. Epub 2009 Mar 9. Cited in PubMed; PMID:
19270746.
Granot Y, Ivorra A, Maor E, Rubinsky B. In vivo imaging of irreversible electroporation by means of electrical
impedance tomography. Phys Med Biol. 2009 Aug 21;54(16):4927-43. Epub 2009 Jul 30. PMID: 19641242
Maor E, Rubinsky B. Endovascular Nonthermal Irreversible Electroporation: A Finite Element Analysis.
Journal of Biomechanical Engineering 2010;132(3): 031008. Cited in PubMed; PMID: 20459196.
Maor E, Ivorra A, Mitchell JJ, Rubinsky B. Vascular smooth muscle cells ablation with endovascular
nonthermal irreversible electroporation. J Vasc Interv Radiol. 2010. 21(11):1708-15.
Phillips M, Maor E, Rubinsky B. Nonthermal irreversible electroporation for tissue decellularization. J
Biomech Eng. 2010. 132(9):091003.
Peer Reviewed Book Chapter
Maor E, Nagler A, Leor J (November 2008). Umbilical Cord Blood Cells for Cardiac Repair. In Ioannis
Dimarakis (Ed.), Handbook of Cardiac Stem Cell Therapy (chapter 4). London, United Kingdom. Imperial
College Press. ISBN: 9781848162563
Summary of Results
NTIRE damages cell membrane only
NTIRE has a non thermal nature
Treatment duration of less than 10 sec !
Efficient and precise
Sparing of extra cellular components
IP
PCT/IL2014/050219
MYOCARDIAL ABLATION BY IRREVERSIBLE
ELECTROPORATION
BY TEL HASHOMER MEDICAL RESEARCH
INFRASTRUCTURE AND SERVICES LTD
INVENTOR – ELAD MAOR
PRIORITY DATE 05/06/2013
Regulation
FDA - PMA based on utilizing IRE in cancer treatment
Market potential Business model – selling disposables
Prevalence of HCM within the general population is ~0.5%
2.5 Million individual worldwide with HCM
10% will benefit intervention
Estimated price target 5K-10K USD
1-2 B USD potential market
Future Clinical Applications
Septal ablation for HOCM
Tissue scaffolding
Cardiac arrhythmias
Endovascular drug delivery
2 years Development Plan
Activity Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8
1 Design of possible endovascular prototypes X X
2Finish element simulation of the heat transfer
problemX X
3 Assembly of the selected endovascular prototype X X
4 In Vivo experiments – Safety X X
5 In Vivo experiments – Efficacy X X
6 Analysis of histopathology specimens X
The Team
Elad Maor, MD – Inventor and Consultant
Zachi Berger, Ph.D. MBA – CEO/Founder
Clinical development – Sheba Medical Center
Summary
Large market with limited medical solutions
Novel minimally invasive procedure
IP in PCT stage
Regulation will be based on other procedures
Short development time
Leading team and Medical Center
