ATRIAL FIBRILLATION CONTINUUM OF CARE Welcome audience, introduce topic of presentation as discussion about atrial fibrillation, new clinical data and recent advances in procedure technology to treat this disease Background: This presentation was developed to provide you with important clinical information on atrial fibrillation and provide you with an overview of radiofrequency (RF) catheter ablation for AF as a treatment option for patients with paroxysmal AF who are refractory or intolerant to drug therapy. Both PC and Mac powerpoint versions of this slide presentation are included on the USB flash drive in this kit. This section of the kit displays each slide in the presentation along with suggestions of how to present the slide in orange, background information for more detailed information on the slide topic and the sources for the information on the slide. While each person has their own presentation style and talking points, we hope that this presentation deck provides you with a framework to enhance your meetings with other healthcare professionals. ATRIAL FIBRILLATION CONTINUUM OF CARE

AF WILL HAVE AN INCREASING IMPACT ON HEALTHCARE Accounts for 1/3 of hospital admissions for cardiac rhythm disturbances Highly symptomatic and affects quality of life Accounts for 15% of all stroke in US Over 100,000 strokes in the US alone attributable to AF Increasing prevalence due to aging population 1 Friberg L, Hammar N, Rosenqvist M (2010) Stroke in paroxysmal atrial fibrillation: report from the Stockholm Cohort of Atrial Fibrillation. Eur Heart J 31 (8):967-975. 2 Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S (2006) ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of 3 Patients with Atrial Fibrillation). Eur Heart J 27 (16):1979-2030. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE (2001) Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 285 (18):2370-2375. 4Gersh B, Tsang T, Bames M, Seward J (2005). The changing epidemiology of non-valvular atrial fibrillation: the role of novel risk factorsGersh B, Tsang T, Bames M, Seward J (2005). Eur Heart J. Supplements 7: C5-C11. Discuss the high level effects of atrial fibrillation Background information: Atrial fibrillation (AF) is the most common heart arrhythmia, affecting 2.3 million people in the US, but left untreated it can adversely affect your patient’s quality of life, and possibly lead to serious complications, even death.1 As a progressive disease, the earlier the intervention, the better the outcome. While AF has a lifetime risk of 20%, it increases with age. Due to the aging of the population, AF is expected to grow more than 2.5 fold over the next 50 years. AF significantly increases the risk for stroke, heart failure, myocardial infarction and death. 2 Stoke is considered the most severe complication of AF. Patients with AF have a four- to five-fold increased risk of stoke compared to those without AF and accounts for approximately 45% of all embolic strokes. AF has the greatest prevalence of any heart arrhythmia (~40%)3. AF significantly affects patients’ quality of life and risk factors for other diseases, is a burden to the healthcare system and is difficult to manage for physicians. Engage the audience in a discussion about the effects of atrial fibrillation on their patients’ quality of life and issues with management of this disease. Sources:  1 Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE (2001) Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 285 (18):2370-2375. 2 Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S (2006) ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Eur Heart J 27 (16):1979-2030. Kannel WB, Benjamin EJ (2008) Status of the epidemiology of atrial fibrillation. Med Clin North Am 92 (1):17-40, ix. 3Millenium Research Group, Global Markets for Atrial Fibrillation Devices (Dec 2008) THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

AF AFFECTS ATRIAL MECHANICAL FUNCTION Atrial fibrillation (AF) is characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function Normal Heart Function and AF Heart Rhythm Vol. 4, No 6, June 2007 Atrial fibrillation. (2009, July 30). In Wikipedia, The Free Encyclopedia. Retrieved 20:50, July 30, 2009, from http://en.wikipedia.org/w/index.php?title=Atrial_fibrillation&oldid=305148284 Source: Adapted from the Mayo Clinic (website). Comparison of Normal Heart Function and Atrial Fibrillation. Updated August 18, 2010. (http://www.mayoclinic.org/atrial- fibrillation/enlargeimage837.html). Accessed December 10, 2010. Review the characteristics of atrial fibrillation and engage the audience in a discussion about diagnosing atrial fibrillation. Background information: AF characteristics include: Rapid and irregular activity in the atria Absence of a p-wave and irregular R waves In AF, structural changes in the atria occur in addition to electrical changes. Atrial fibrosis and loss of muscle mass are the most frequent histological changes in AF. The electrical and structural changes (or “remodeling”) that occur in the atria further perpetuates the existence and maintenance of AF (i.e., “AF begets AF”) 1. It has been previously reported that electrical remodeling occurs during a few hours following the onset of AF, whereas the structural changes begin to develop after several weeks. 2 Due to the structural changes caused by AF that occur over time, therapeutic interventions such as cardioversion, become increasingly difficult as the condition progresses. Sources: 1 Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA (1995) Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation 92 (7):1954-1968. 2 Korantzopoulos P, Kolettis T, Siogas K, Goudevenos J (2003) Atrial fibrillation and electrical remodeling: the potential role of inflammation and oxidative stress. Med Sci Monit 9 (9):RA225-229. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

VARIOUS MECHANISMS CONTRIBUTE TO AF Evidence suggests that AF can be attributed to three mechanisms: Multiple, random propagating wavelets Focal electrical discharges Localized reentrant activity with fibrillatory conduction Structure and Mechanism of AF SOURCE: Jalife J, Berenfeld O, Mansour M (2002) Mother rotors and fibrillatory conduction: a mechanism of atrial fibrillation. Cardiovasc Res 54 (2):204-216. Review the theory regarding mechanisms of AF. Background information: Recent data supports the idea that a focal triggering mechanism involving automaticity or multiple reentrant wavelets is involved in AF, although focal triggers and multiple reentrant mechanisms are not mutually exclusive and may coexist. The observation that the mechanism of AF could be attributed to a focal source and ablation (involves the use of energy to create a lesion in the cardiac tissue) could eliminate AF, reinforced the idea that AF requires a trigger and an anatomic substrate capable of both initiation and perpetuation. 1 Sources: 1 Haissaguerre M, Marcus FI, Fischer B, Clementy J (1994) Radiofrequency catheter ablation in unusual mechanisms of atrial fibrillation: report of three cases. J Cardiovasc Electrophysiol 5 743-751. Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le MA, Le MP, Clementy J (1998) Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 339 659-666. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

AF IS CLASSIFIED INTO SUB-TYPES Paroxysmal: recurrent AF (≥2 episodes), that terminates spontaneously within 7days Persistent: AF sustains >7 days, or lasts less than 7 days but necessitates pharmacologic or electrical cardioversion Longstanding persistent (permanent): continuous AF of greater than 1 year duration ACC/AHA/ESC Classification of AF Heart Rhythm Vol. 4, No 6, June 2007 Review the AF classifications in the American College of Cardiology (ACC), American Heart Association (AHA) Guidelines on the management of atrial fibrillation. Depending on your audience, you may want to define the recent definitions (re-classifications) as compared to chronic and permanent definitions prior to 2006 Guidelines Background info: Two primary systems exist for classification of AF: one based on the duration of AF and the second based on the presence of comorbid cardiovascular disease. Atrial fibrillation is most commonly classified according to the duration of AF occurrence as outlined in guidelines produced by the American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC). Under this classification system, a patient who exhibits AF for the first time is considered a patient with first diagnosed AF. Paroxysmal AF is defined by recurrent, self-terminating episodes, usually lasting <48 hours to 7 days whereas persistent AF is defined by recurrent episodes lasting >7 days or requiring cardioversion. AF is considered long-standing persistent when lasting ≥1 yr. The term permanent AF is used when AF is accepted and normal sinus rhythm has not been achieved either because cardioversion was unsuccessful or was not tried. Patients may have AF episodes that fall into one of more of these categories, in these cases it has been recommended that patients are categorized by their most frequent AF pattern. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

AF TREATMENT GUIDELINES 2007 US Population (301M) AF Prevalence (3.1M) Recurrent paroxysmal or persistent AF Permanent AF (longstanding persistent AF) Minimal or no symptoms Disabling symptoms in AF Anticoagulation & rate control as needed Anticoagulation & rate control as needed Anticoagulation & rate control as needed AADs & cardioversion as needed Catheter ablation* if AAD treatment fails (Paroxysmal AF is the only FDA approved Indication for catheter ablation) Review the ACC/AHA/ESC 2006 Guidelines. Depending on the audience you may want to do this at a high level, or discuss in detail how audience participants manage AF in their practice. Background information: The management of AF patients encompasses three primary objectives: rate or rhythm control the prevention of thromboembolis the management of symptoms, if present Management strategies suggested were based on the duration of AF and other factors such as the existence of comorbid conditions, patient age, concomitant medication use, and the presence and severity of symptoms. The primary treatment decision focused on the selection of rate or rhythm control strategy. Regardless of the control strategy, antithrombotic therapy to prevent stroke was recommended in all patients with AF, except for those with lone AF or contraindications. The table in this slide illustrates the ACC/AHA/ESC’s treatment recommendations for recurrent paroxysmal AF, recurrent persistent AF, and permanent AF. Note there is no currently FDA approved catheter for the ablation of persistent AF. Consider the following when reviewing the guidelines: Each patient is different There’s no one panacea First-line treatment is pharmacological therapy1 ~50% of first-time atrial fibrillation patients are drug refractory Causes an additional 12% to have severe side effects Causes another 18% to have moderate side effects Sources: 1Canaccord Adams, A-Fib: Near a Tipping Point (Aug 2008) Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S (2006) ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Eur Heart J 27 (16):1979-2030. * There is currently no FDA approved catheter for ablation of persistent AF ACC/AHA/ESC Guidelines for Management of pts with AF; Circulation 2006;114:257–354 THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

RHYTHM CONTROL IS NOT INFERIOR TO RATE CONTROL Rate control: minimize symptoms and reduce heart rate Rhythm control: restore and/or maintain sinus rhythm Randomized controlled trials have compared the efficacy of rate versus rhythm control treatments for the management of AF No significant differences in mortality, thromboembolism or bleeding, cardiovascular events, or symptomatic improvement. Findings suggest rhythm control is not inferior to rate control Rate vs Rhythm Control Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD (2002) A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 347 (23):1825-1833. Discuss the Rate vs Rhythm Debate. Review the goals of each method and treatments used to achieve each goal. Note that rhythm control is not inferior to rate control and that catheter ablation emerged as a rhythm strategy partly to address the problems with rate control. Background information: Although much debate has taken place regarding the benefits of rate versus rhythm control strategies, clinical evidence has shown that rate control is not inferior to rhythm control for the treatment of AF. Importantly, while the options for achieving these outcomes are diverse, the use of pharmacological therapies in particular, poses a number of significant challenges.  For example, the selection of drug therapy must be highly individualized to address the presence of varying patient co-morbidities and symptoms.  Especially in the case of AADs, patient safety and pre-existing conditions must be carefully considered in order to select an appropriate treatment regimen.  Further, it is not uncommon for patients with AF to fail to respond or become intolerant to the first therapy they receive.  Patients who become refractory to first-line AAD therapy will often be less responsive to subsequent AAD therapy. Catheter ablation procedures emerged as a rhythm control strategy, in part, in response to this latter challenge of AF management.  Sources: Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD (2002) A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 347 (23):1825-1833. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

Sinus Rhythm via ablation: WHEN CONSIDERING RATE VS RHYTHM CONTROL, MANY FACTORS NEED TO BE CONSIDERED THE BIGGER PICTURE Survival is crucial Additional important factors: Effectiveness of the treatment Quality of life for the patient Rate Control: Atrial fibrillation tends to continue to progress Drug failure rates and side effects increase with time Sinus Rhythm via ablation: Most atrial fibrillation will not progress Risk of side effects dissipate Engage the audience in a discussion regarding rate versus. rhythm control of AF. What is their approach and why? Background information: AFFIRM Study (No. Patients = 4060) The study included patients with these characteristics: 65 years or older Severe symptoms not suitable for randomization Exhibit other risk factors for stroke or death The AFFIRM clinical study concluded that there is conclusion no clinical significant advantage (in mortality) of rate over rhythm control (p>0.05) However, maintenance of sinus rhythm has been associated with a significant reduction in mortality, although the use of AADs to maintain sinus rhythm has been reported to increase mortality by 49%. 1 This suggests that the benefits of sinus rhythm may be offset by the adverse events associated with AADs. In a systematic review of AAD therapy for AF, approximately 30% of patients experienced an adverse event.2 In the same publication, a parallel systematic review reported that catheter ablation of AF effectively maintained sinus rhythm and major complications were reported in only 4.9% of patients. 2 As such, catheter ablation of AF is a recommended treatment option for select patient populations. Sources: 1 Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, Josephson RA, Kellen JC, Klein RC, Krahn AD, Mickel M, Mitchell LB, Nelson JD, Rosenberg Y, Schron E, Shemanski L, Waldo AL, Wyse DG (2004) Relationships Between Sinus Rhythm, Treatment, and Survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation 109 (12):1509-1513. 2 Calkins H, Reynolds MR, Spector P, Sondhi M, Xu Y, Martin A, Williams CJ, Sledge I (2009) Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses. Circ Arrhythm Electrophysiol 2 (4):349-361. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

AF IS A PROGRESSIVE DISEASE HATCH Score: Estimates the probability of AF progression in patients with paroxysmal AF The HATCH score contains four categories: Very low (0) Low (1) Moderate (2 to 4) High (5 to 7) Progression of AF Progression to persistent AF occurred in approximately 50% of patients with a HATCH score > 5 and in 6% of patients with a HATCH score of zero Discuss how AF is a progressive disease and becomes more difficult to treat over time. Background information: A risk stratification rule has been developed to estimate the probability of AF progression in patients with paroxysmal AF. This measurement is called the HATCH score. The HATCH score contains four categories: very low (0) low (1) moderate (2 to 4) high (5 to 7) Progression to persistent AF occurred in approximately 50% of patients with a HATCH score >5 and approximately 6% of patients with a HATCH score of zero. Therefore, conversion of AF to normal sinus rhythm becomes increasingly difficult as the condition progresses and becomes more severe in frequency and duration, which is attributed to structural remodeling of the atria. Early restoration of sinus rhythm is thought to minimize structural remodeling and potentially limit the advancement of AF. Since treatment of AF in more permanent, or sustained forms, is difficult, early diagnosis and treatment is important considering the progressive nature of the condition. 1 Sources: 1de Vos CB, Pisters R, Nieuwlaat R et al. (2010) Progression from paroxysmal to persistent atrial fibrillation clinical correlates and prognosis. J Am Coll Cardiol 55 (8):725-731. de Vos CB, Pisters R, Nieuwlaat R, Prins MH, Tieleman RG, Coelen RJ, van den Heijkant AC, Allessie MA, Crijns HJ (2010) Progression from paroxysmal to persistent atrial fibrillation clinical correlates and prognosis. J Am Coll Cardiol 55 (8):725-731.   THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

THE LONGER THE AF DURATION THE MORE DIFFICULT TO RESTORE SINUS RHYTHM Rates of progression from paroxysmal AF to more frequent and intractable forms of AF ranged up to 30% at 5 years, with annual risk estimates generally 3-6% over time Rates of Transition to Persistent or Chronic AF: % Patients by Type of AF at Baseline Review that numerous studies have investigated AF disease progression THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

AF SIGNIFICANTLY AFFECTS QUALITY OF LIFE SF-36 Quality of Life of Patients with AF Compared with the General Population and Patients with Other Cardiovascular Conditions The SF-36 is a Quality of Life measurement which assesses eight concepts: General health perception Physical functioning Social functioning, Role limitations due to physical problems Bodily pain Mental health Role limitations due to emotional problems Vitality AF patients have significantly reduced quality of life as compared to the general population and patients with other cardiovascular conditions Review how AF significantly affects a patient’s quality of life. Background information: Numerous clinical studies demonstrate that QoL is significantly reduced in patients with AF. The reduction of QoL encompasses many domains such as physical, psychological, emotional, and social functioning THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

ADT IS ASSOCIATED WITH ADVERSE EVENTS Commonly Prescribed AADs: Potential Adverse Events and Contraindications The high incidence of adverse events and recurrence rates may outweigh expected quality of life improvements from antiarrhythmic drugs Review side effects associated with anti-arrhythmic drug treatment. Background information: AADs alter the electrophysiological properties of myocardial tissue in order to treat AF or to prevent its recurrence. The drugs are generally administered through a dosing protocol to restore normal sinus rhythm. Once this has been achieved, normal rhythm is maintained through long-term therapy with the same or a different AAD Due to contraindications, selection of an AAD for an individual with AF must be performed with careful consideration of concomitant cardiovascular conditions, especially hypertension, coronary artery disease, and HF. A majority of currently available AADs have been associated with significant adverse events including ventricular proarrhythmia and extracardiac toxicity.1 Two recent meta-analyses have shown that most AADs significantly increase proarrhythmic effects by altering the rate of the arrhythmia or causing new arrhythmias and that approximately 30% of patients treated with AADs have experienced an adverse event.2 Not surprisingly, the considerable frequency of adverse events related to AAD use contributes to a high rate of discontinuation of treatment, estimated at about 25%. 3 Sources: 1 Savelieva I, Paquette M, Dorian P, Luderitz B, Camm AJ (2001) Quality of life in patients with silent atrial fibrillation. Heart 85 (2):216-217. Burashnikov A, Antzelevitch C (2010) New developments in atrial antiarrhythmic drug therapy. Nature Reviews Cardiology 7 (3):139-148. 2Lafuente-Lafuente C, Mouly S, Longas-Tejero MA, Mahe I, Bergmann JF (2006) Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial fibrillation: a systematic review of randomized controlled trials. Arch Intern Med 166 (7):719-728. Calkins H, Reynolds MR, Spector P, Sondhi M, Xu Y, Martin A, Williams CJ, Sledge I (2009) Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses. Circ Arrhythm Electrophysiol 2 (4):349-361. 3Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, Kus T, Lambert J, Dubuc M, Gagne P, Nattel S, Thibault B (2000) Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med 342 (13):913-920. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

ADT HAS A HIGH RATE OF AF RECURRENCE COMPARED WITH CATHETER ABLATION The recurrence rate of patients treated with antiarrhythmic drugs is higher than with RF ablation Kaplan-Meier Curve of Time to Recurrence of Symptomatic Atrial Arrhythmia Following Second Line Antiarrhythmic Drug Therapy (ADT) Review clinical evidence showing that AF recurrence is more likely with antiarrhythmic drug therapy than RF ablation. Background information: A prospective, multicenter, randomized clinical study that compared radiofrequency catheter ablation (RFCA) and antiarrhythmic drug therapy (ADT) in 167 patients with paroxysmal AF. Included were patients that were unresponsive to at least one AAD and experienced at least three AF episodes within the last six months before randomization. The primary endpoint was freedom from protocol-defined treatment failure, which included documented symptomatic paroxysmal AF during the nine-month effectiveness evaluation period. A significantly larger proportion, 66% of patients in the RFCA group remained free from protocol-defined treatment failure compared with 16% of patients treated with ADT. 70% percent of RFCA patients remained free of symptomatic recurrent atrial arrhythmia compared with 19% of ADT patients and 63% of RFCA patients remained free of any atrial arrhythmia compared with only 17% of ADT patients. Fewer adverse events (4.9%) were reported in patients treated with RFCA compared with those patients treated with ADT (8.8%). Sources: Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, Macle L, Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY, Berry SM, Berry DA (2010) Comparison of Antiarrhythmic Drug Therapy and Radiofrequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation: A Randomized Controlled Trial. JAMA 303 (4):333-340. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

META-ANALYSES DEMONSTRATE THAT RF ABLATION IS MORE EFFECTIVE THAN ADT FOR MANAGING AF IN CERTAIN PATIENTS The studies reported that approximately 77% of RFCA treated patients remained free of AF recurrence in comparison to only 19% to 52% of ADT treated patients Meta-Analyses Comparing Catheter Ablation to ADT in Patients with AF Show that that in addition to reducing AF recurrence, RFCA also improves quality of life. Background information: In the same clinical study that was reviewed on the previous slide, quality of life using the the SF-36 was also studied. Patients in the RFCA group displayed improvements in QoL compared with ADT patients: mean SF-36 physical and mental summary scores improved and mean symptom frequency and severity scores were reduced at three months, a pattern that continued without significant change at the six- and nine-month QoL assessments. Sources: Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, Macle L, Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY, Berry SM, Berry DA (2010) Comparison of Antiarrhythmic Drug Therapy and Radiofrequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation: A Randomized Controlled Trial. JAMA 303 (4):333-340. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

RF ABLATION IMPROVES QUALITY OF LIFE A prospective, multicenter, randomized clinical trial compared RFCA and ADT in 167 patients with paroxysmal AF Patients in the RFCA group displayed improvements in QoL compared with ADT patients at 3 months, and without significant change at 6 and 9 months QoL Assessment: Absolute Change from Baseline to Three Months Review the summary of clinical evidence that demonstrates catheter ablation is effective for patients that are refractory / intolerant to antiarrhythmic drugs. Background information: A number of meta-analyses have been conducted comparing catheter ablation to drug therapy. The analyses demonstrate that RFCA is a more effective therapy for managing AF and is associated with a lower rate of adverse events compared with ADT. The studies reported that approximately 77% of RFCA-treated patients remained free of AF recurrence in comparison to only 19% to 52% of patients who received ADT. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

COMPLETE SOLUTION FOR PATIENTS Develop treatment pathway guidelines as a team Treat atrial fibrillation to focus on potential other heart problems Determine a plan for drug refractory patients Objectives differ patient to patient, but our approach matters every time Engage the audience in a discussion about the effects of atrial fibrillation and the complications that can exist with additional heart problems. By looking at the Bigger Picture, both cardiologists/general practitioners and EPs can work as a team to evaluate each case and together make the best decision for the patient. Offer the group to develop treatment guidelines for specific patient cases as a team. If the group is not ready to establish guidelines at the present time, provide an example of a case where a team approach would be beneficial: A symptomatic, paroxysmal AF patient that was drug refractory to at least 2 AADs How do you approach the case and what do you do? How long will it take? How can the treatment affect the patient? At what point do you foresee the patient returning to the referring physician? THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

THE ABLATION PROCEDURE A minimally invasive technique in which radiofrequency (RF) energy is used to neutralize small areas of the heart tissue that generate and conduct abnormal electrical activity, the source of the arrhythmia Map Creation Video Ablation Video Briefly, walk the audience through an ablation procedure to give the audience further insight into the sophistication of the procedure. If there is interest (or, additional questions), click and view a short video on map creation or ablation. Background information: Catheter ablation is a percutaneous procedure in which ablation targets within the LA are accessed from a small incision, usually made in the groin of the patient. This method is minimally invasive, but does carry risks associated with working in the left side of the heart. It is well-established that the development of AF requires both a trigger and a conductive substrate. As a result, the goals of an AF ablation procedure are to prevent AF by eliminating the trigger that initiates AF and/or by altering the conductive substrate to block perpetuation of the signal. This is accomplished through the targeted destruction of myocardial tissue at sites identified through cardiac mapping. Using a catheter, the electrophysiologist applies focal energy to identified sites to create irreversible lesions within the tissue. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

RF ABLATION INVOLVES LESION CREATION TO PREVENT ABNORMAL ACTIVATION RF ablation uses high frequency alternating current to eliminate or alter the arrhythmogenic substrate An ablation catheter is used to apply RF to the endocardium to produce continuous lesions (scars) that prevent the abnormal electrical activation contributing to AF The most common lesion sets include circling of the pulmonary veins (PVs) called circumferential PV isolation Source: Adapted from Calkins H, Brugada J, Packer DL et al. (2007) HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the HRS Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the EHRA and the ECAS; in collaboration with ACC, AHA, and the STS. Endorsed and approved by the governing bodies of the ACC, AHA, ECAS, EHRA, STS, and the HRS. Europace 9(6):335-379. Discuss the method of ablating RF including the common lesion sets used in this procedure Background information: The Expert Consensus Statement recommends the following techniques and endpoints for catheter ablation of AF: -When targeting the PV foci, complete electrical isolation is the goal. -Careful identification of the PV ostia is mandatory to avoid ablation within the PVs. -Any focal triggers identified outside of the PV should be targeted. -For additional linear lesions, line completeness should be demonstrated. -Ablation of the cavotricuspid isthmus is recommended only in patients with history of AFL or inducible cavotricuspid isthmus-dependent AFL. Sources: Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, Damiano RJ, Jr., Davies DW, Haines DE, Haissaguerre M, Iesaka Y, Jackman W, Jais P, Kottkamp H, Kuck KH, Lindsay BD, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Natale A, Pappone C, Prystowsky E, Raviele A, Ruskin JN, Shemin RJ (2007) HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace 9 (6):335-379. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

CASE STUDIES CASE STUDIES #1 Patient characteristics: Age, gender, duration of AF, left atrial size, comorbidities, pharmacological history Ablation procedure utilized: linear, focal, isolation, circumferential, CFAE, combined, etc. Patient Outcomes: AF free, time to AF recurrence, other atrial arrhythmias, quality of life, post-procedure AAD therapy, rhythm control, and stroke risk control Complications: adverse events (PV stenosis, stroke, fistula, other arrhythmias, tamponade, second ablation) Use this slide (and the next slide) as a guideline to discuss specific patient cases with the audience. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

CONCLUSION AF is a progressive disease. The longer the duration of the disease the more difficult it is to restore / maintain sinus rhythm RF catheter ablation for paroxysmal AF has been demonstrated to be safe and effective for patients that are refractory or intolerant to antiarrhythmic drugs RF ablation has been demonstrated to have a less AF recurrences and improves quality of life as compared to antiarrhythmic drugs Referring patients for early intervention, will reduce patient management complexity Make concluding remarks to the presentation. Highlight the key points of the presentation including the fact that AF is a progressive disease and more difficult to treat as time goes on. It is important to intervene early since treatment outcomes are much better for those with early stage disease. RF ablation is an alternative treatment option for those patients who are refractory or intolerant to antiarrhythmic drugs. Open the discussion up to the audience for questions. THERMOCOOL® Navigation Catheters are approved for drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with CARTO® Systems (excluding NAVISTAR® RMT THERMOCOOL® Catheter)

VIDEO FOR “THE ABLATION PROCEDURE” CREATING THE MAP Return

VIDEO FOR “THE ABLATION PROCEDURE” AF ABLATION Return