1 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 What do MEs tell us? New Clinical Insights All cited trademarks are the property of their respective owners. CAUTION: The law restricts these devices to sale by or on the order of a physician. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations.

2 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Review Avitall´s pre-clinicial reasearch 1.What is the focus of Avitall´s preclinical work? 2.Could you summarize results? 3.How have you used this data in front of your customers to highlight the value of IntellaTip MiFi TM technology?

3 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 New Avitall’s article Maximal Electrogram Attenuation Recorded from Mini Electrodes Embedded on 4.5mm Irrigated and 8mm Non-Irrigated Catheters Signifies Lesion Maturation B. Avitall, University of Illinois Chicago, JCE 12568, Oct 2014 One step further into lesion maturation feedback ME EGMs attenuation = Safer transmural lesions ?

4 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Methods: Fixed duration (60s) vs titrated to Max attenuation of MEs 44 secs 24 secs Maximal Electrogram Attenuation Recorded from Mini Electrodes Embedded on 4.5mm Irrigated and 8mm Non-Irrigated Catheters Signifies Lesion Maturation B. Avitall, University of Illinois Chicago, JCE 12568, Oct 2014

5 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Lesion Set Example: SVC/IVC Maximal Electrogram Attenuation Recorded from Mini Electrodes Embedded on 4.5mm Irrigated and 8mm Non-Irrigated Catheters Signifies Lesion Maturation B. Avitall, University of Illinois Chicago, JCE 12568, Oct 2014

6 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Results comparing both methods 60 sec Method vs Max Attenuation Method Rise of Pacing Thresholds post-ablationNS ME EGMs attenuationNS Lesion size (max depth in ventricle 9,3 mm)NS Atrial Lesion TransmuralityNS Atrial Lesion DimensionsAtrial Energy Delivery 4.5mm irrigated 8mm NS= no significant differences B. Avitall, University of Illinois Chicago, JCE 12568, Oct 2014

7 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Safety results METHOD60 secMax Attenuation Lung lesions (depth) 37 4,4+-1mm with IntellaTip MiFi TM XP 19 Shallower, < 1mm IntellaTip MiFi TM XP Esophageal lesions 4non Char7non Safer lesions using Max ME EGM attenuation Method Maximal Electrogram Attenuation Recorded from Mini Electrodes Embedded on 4.5mm Irrigated and 8mm Non-Irrigated Catheters Signifies Lesion Maturation B. Avitall, University of Illinois Chicago, JCE 12568, Oct 2014

8 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Key Observations: 1.IntellaTip MiFi TM is the only ablation catheter in the market that provides information that can allow for shorter ablation times with similar efficacy thanks to ME max EGM attenuation 2.Prolonging RF passed the point of max EGM attenuation can potentially lead to additional extracardiac injuries and char 3.Injuries in this study were created ablating in fixed anatomical landmarks and have been considered superficial and not of a big concern by Dr. Avital. Nevertless, the ME signal attenuation method significantly reduced their occurrence Maximal Electrogram Attenuation Recorded from Mini Electrodes Embedded on 4.5mm Irrigated and 8mm Non-Irrigated Catheters Signifies Lesion Maturation B. Avitall, University of Illinois Chicago, JCE 12568, Oct 2014

9 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 OBJECTION HANDLING

10 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Are both catheters IntellaTip MiFi TM OI and IntellaTip MiFi XP TM prone to create lung damages, esophageal lesions or char? 1.For the propose of the study, lesions were created in anatomic landmarks at fixed settings of time (60sec) /power (30W for IntellaTip MiFi TM OI and 65W for IntellaTip MiFi TM XP) /temperature (max 35 ºC for OI and 65 ºC for IntellaTip MiFi TM XP) to enable comparisons through the study. 2.In clinical practice, these parameters would be adapted (not fixed) to anatomical locations and energy will be titrated. 3.Even in these fixed conditions in the study, maximum ME attenuation method shows dramatically improved results reducing number and depth of lung lesions along with no reported incidence of char or esophageal lesions. 4.In the same conditions of the study, commercially available solid tip/OI catheters are expected to provide similar results in term of extracardiac damages. Differently from them, IntellaTip MiFi TM EGM’s signal clarity helps provide more accurate information as to when to stop RF.

11 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Why even with the Max attenuation method both catheters still present lung lesions? 1.Extracardiac tissue damage may be inherent to creating transmural lesions with all RF catheters, especially in tissue (like lung or oesophagus) that is in direct contact with the outside of the ablated tissue. 2.Dr. Avitall’s commented that “lung lesions were superficial with Max attenuation method and thus, not a large concern. Clinically, lung lesions are probably more common than we know in usual practice, but since they do not present symptomatically, we do not know about real occurrence” 3.The incidence and extent of lung injury as a result of catheter ablation have not been focused upon in the literature, but there are records of clear incidence after RF ablation of AF (Weber R et al. Pulmonary edema after extensive radiofrequency ablation for atrial fibrillation J Cardiovasc Electrophysiol Jul;19(7):748-52). 4.Limiting the RF application to the maximal attenuation of the EGM decreased the number and depth of lung injuries.

12 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 TOOLS Article (on-line version)Article Summary

13 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Extra Clinical tools: GAP identification in redo flutter case Article (on-line version) Conclusion: First reported use of this catheter for recurrent typical right atrial flutter. It demonstrates an efficient and effective means of identifying the critical region of recurrent typical right atrial flutter. The advantage of this technique is that it does not require any additional equipment setup time or medication administration. Rapid Ablation of Recurrent Atrial Flutter Using a Novel Ablation Catheter Gupta, JICRM 5 (2014), 1808–1812

14 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Extra Clinical tools: GAP identification in redo flutter case Rapid Ablation of Recurrent Atrial Flutter Using a Novel Ablation Catheter Gupta, JICRM 5 (2014), 1808–1812

15 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 MEs clinical value Summary by Dr. Murgatroyd Are ME signals better than conventional EGMs? –Improved sensitivity –Resolution of CFEs –Improved discrimination of near/farfield –Sensitive to movement and possibly to propagation Do MEs improve localization? –Define limits of chamber/muscular sleeve, isolated area –Identify gaps Do MEs improve pacing manoeuvres? –Very low thresholds & EGM quality aid entrainment –Avoidance of anodal capture may improve pacemapping Do MEs improve feedback during ablation? –Contact information – electrical rather than force –Signal attenuation easier to see than with conventional EGMs –May improve safety by limiting ablation

16 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Move into PRACTICE Groups of 2 people Choose one of the following objections and prepare your answer to it (ACRC) (10’) 1.Yes, I see the great value of IntellaTip MiFi TM Technology, however, I have the feeling the attenuation of the signal on the MEs during ablation is too fast. Does this mean that the MEs do not read deep into the tissue? 2.Avitall´s pre-clinical work has clarified me a few points to understand better the IntellaTip MiFi TM technology further than the “true location” which is the most intuitive one. However, I am concerned by the number extra tissue damages published in his last paper. Should I expect similar complications in my clinical cases?

17 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Move into PRACTICE 3.I believe the IntellaTip MiFi TM technology has a great value. However, in my flutter cases, I am confident on using irrigated catheters better than solid tips which I have not used anymore for 5 years now. I will wait until you have IntellaTip MiFi TM OI available. To prepare this last Objection fill in the table bellow: Determine which IntellaTip MiFi TM XP benefits could be more relevant to move an OI user into a IntellaTip MiFi TM XP user in flutter and use them while role playing the objection IntellaTip MiFi TM XPConventional OI benefit 1 in flutter cases benefit 2 in flutter cases benefit 3 in flutter cases ……………………………

18 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Move into PRACTICE (cont.) SHARE answers to the objections: 1.Objection 1 (10’) 1.one pair presents 2.The other pairs give feedback and complete the answer if needed 2.Objection 2 (10’) 1.one pair presents 2.The other pairs give feedback and complete the answer if needed 3.Objection 3 (10’) 1.one pair presents 2.The other pairs give feedback and complete the answer if needed

19 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Backup Slides for trainers

20 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Best answers for the objections OBJECTION 1: Yes, I see the great value of Mifi Technology, however, I have the feeling the attenuation of the signal on the Mes during ablation is too fast. Does this mean that the MEs do not read deep into the tissue? A: I understand your concerns. It is difficult to understand and get used to the new information coming from the MEs since we have always had only EGMs coming from the conventional bipoles. C: Why do you have this feeling? Have you used Mifi XP for ablation? If yes, what is your personal experience related to this point? Did you use the ME´s EGM´s attenuation to stop ablation? Have you had the time to read through Avital´s pre-clinical work? In your opinion, How does it clarifies your concerns? R: 1- We do not yet have all the data to provide a conclusive answer. This will require several studies (pre-clinical, clinical, acute and long term) to answer which we cannot have at this point due to the early stage of the technology. 2- The published pre-clinical data indicate that ME EGMS probably provide information from deeper in the tissue (up to 4mm in A tissue and 9mm in V tissue per Avital work). The significance of these data is being studied further. We have in-house pre-clinical R&D work ongoing to clarify this further, with data expected later this year.  One thing we can say for sure is that the MEs provide a very strong negative predictor. This means that if something is seen on the MEs, we should always encourage to stay on with RF, even when other parameters would tell you to come off, because there is viable tissue under the tip.  Another thing we can say, based on the study results, is that lesion depth is similar using the max attenuation method or the 60 second method, so no differences on lesion depth due to longer applications not based on MEs EGMs. Also, no differences in transmurality in atrial lesions with both methods (over 90%). C: Is this information clarifying your concerns?

21 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Best answers for the objections OBJECTION 2: Avitall´s pre-clinical work has clarified me a few points to understand better Mifi technology further than the “true location” which is the most intuitive one. However, I am concerned by the number extra tissue damages published in his last paper. Should I expect similar complications in my clinical cases? A: I understand your concerns. Patient safety is always the first priority for all of us. C: Have you had the time to read through Avital´s pre-clinical work in detail? In your opinion, what are the similarities or differences of the methods on the paper and the real clinical practice? R: 1- Extracardiac tissue damage may be inherent to creating transmural lesions with all RF catheters, especially in tissue (like lung or oesophagus) that is in direct contact with the outside of the ablated tissue. The following study that looked at this (all ablations with thermocool) showed a 10% oesophageal injury rate (22/219): 2- For the propose of the study, lesions were created in anatomic landmarks at fixed settings of time (60sec) /power (30W for OI and 65W for XP) /temperature (max 35 ºC for OI and 65 ºC for XP) to enable comparisons through the study. 3- In clinical practice, these parameters would be adapted (not fixed) to anatomical locations and energy will be titrated. 4- Even in these fixed conditions in the study, maximum ME attenuation method shows dramatically improved results reducing number and depth of lung lesions along with no reported incidence of char or esophageal lesions. 5- In the same conditions of the study, commercially available solid tip/OI catheters are expected to provide similar results in terms of extracardiac damages. Differently from them, MiFi EGM’s signal clarity helps provide more accurate information as to when to stop RF. 6- Furthermore, out of hundreds of patients in EU and thousands in US, Mifi XP has shown no complication related to extra cardiac damages C: Would you agree on this explanations? Would you be willing to try Mifi in your clinical cases?

22 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan 2015 Best answers for the objections OBJECTION 3: I believe the Mifi technology has a great value. However, in my flutter cases, I am confident on using irrigated catheters better than solid tips which I have not used anymore for 5 years now. I will wait until you have Mifi OI available A: I understand your point and I have also seen this in other accounts. C: What were the reasons to move from solid tip to open irrigated cath. in flutter 5 years ago? Why are you more confident on using irrigated tips in flutter? How are you currently performing re-do cases? R: 1- One of the reasons to use OI catheters instead of solid tip ones in flutter is the signal resolution which is low with solid tips. However, Mifi XP will provide MEs EGMs with high signal quality and reduced far field signals compared to conventional tips or irrigated tips. 2- Another reason to use OI catheters is the large tips catheters limitation to deliver high energy in pouches in the ICT. However, poaches are not the main and only reason to create gaps in the CTI ablation line. Maneuvers like perpendicular ablation to improve passive cooling or larger tips (10 mm) which can cover more than the pouch area, will help to achieve high power in those areas. 3- Additionally, the MEs will help you to identify faster and easier the exact point where the gap is and also to ablate it exactly where it is (center of ablation= center of mapping) 4- You can also be more efficient in your flutter cases using the MEs attenuation during ablation to limit RF time. C: Would you agree on these benefits of Mifi technology in flutter? Would you be willing to try Mifi XP in your next case? Mifi XPConventional OI Gap detectionDeliver high energy also in pouches Reduced RF time (MEs EGM attenuation)Possibility to use it for flutter line in Afib case Higher signal resolution, less far field Improved entrainment /validation maneuvers…………………………………………………

23 Boston Scientific Confidential -- For Internal Use Only. Do Not Copy, Display or Distribute Externally – Information not intended for distribution in France EP AA Jan