Atrial Fibrillation 2014 Christopher L. Fellows, MD, FACC, FHRS Virginia Mason Medical Center Seattle, Wa.

www.acc.org www.hrsonline.org 2014 AHA/ACC/HRS Guidelines for the Management of AF 2011 Focused Update on the management of AF 2012 Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation www.acc.org www.hrsonline.org

AF is very frustrating Causes strokes…strokes are BAD Makes pts feel BAD Therapy toxic and ineffective

There are 3 reasons to treat AF…

Stroke Risk in Patients With Nonvalvular AF Not Treated With Anticoagulation According to the CHADS2 Index Chads2 scheme best predictor of stroke risk so far (combination of 2 AFI and SPAF schemes) Results from national registry of AF 2001, adaptation of This scheme adopted for guidelines Evidence level C (expert panel opinion) Stroke Rate %per year CHADS2 Score

CHADS2 CHADS2 VASC CHF Hypertension Age > 75 Diabetes Stroke/TIA (2) CHF/LV dysfunction Hypertension Age > 75 (2) Diabetes Stroke/TIA/TE (2) Vasc disease Age > 65 Sex (female) Gage BF JAMA 285:2864-2870,2001 Lyp GYH Chest 137:263-272,2010

Is Sinus Rhythm Important ? AFFIRM (Wyse DG, et.al. NEJM 2002;347:1825-31) RACE (Hagens VE, et.al. JACC 2004;43:241-247.) STAF (Carlsson J, et.al. JACC 2003;41:1690-1696.) All concluded …..that there were no mortality differences between rate control and rhythm control strategies in the treatment of AF

Sinus Rhythm AFFIRM type trials excluded highly symptomatic patients Trials designed to test strategy not therapy Therapy was very ineffective

AFFIRM Substudy On treatment analysis NSR= 47% lower risk of death AAD use = 49% increased risk of death AFFIRM investigators. Circ 2004;109:1509-1413

“…the failure of AFFIRM, RACE, or STAF in showing any differences between rate and rhythm control is not so much a positive statement for rate control but rather a testimony on the ineffectiveness of the rhythm control methods used.” Verma A, Natale A. Circulation 2005;112:1214-1231.

OK, Sinus rhythm is good but at what price ? Drugs Pacer ICD Ablation

Antiarrhythmic Drugs Amiodarone Propafenone Sotalol Time (days) 100 80 60 Sinus Rhythm (%) 40 The efficacy of amiodarone was evaluated in a recent multicenter Canadian study entitled the Canadian Trial of Atrial Fibrillation (CTAF). In this trial, 403 patients, all with symptomatic AF, were randomized to receive either low-dose amiodarone (200 mg/day) or conventional therapy with either propafenone or sotalol. Recurrence rates with sotalol and propafenone were found to be similar and were consistent with the rates reported in previous studies (including Reimold's study shown on the previous slide). Amiodarone, however, was found to be significantly more effective than both propafenone and sotalol in preventing AF recurrence. After 1 year of therapy, for example, 69% of amiodarone-treated patients remained in sinus rhythm compared to 39% of patients treated with sotalol or propafenone (p<0.001).7 _______________ 7. Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, et al. for the Canadian Trial of Atrial Fibrillation (CTAF) Investigators. Amiodarone to prevent recurrence of atrial fibrillation. N Engl J Med 2000;342:913-920. 20 100 200 300 400 500 600 Time (days) Roy et al. NEJM 2000;342:913-920.

AF drugs…my best guess Betablockers Flec/Propaf Sotalol Amio/Dofet Dronedarone Ca blocker Dig Everybody Lone AF Good LV Bad LV Rate control CHF only

OK, Sinus rhythm is good but at what price ? Drugs Pacer ICD Ablation

Haissaguerre et al.NEJM 1998;339:659-66.

Kaplan-Meier Curves of Time to Protocol-Defined Treatment Failure, Recurrence of Symptomatic Atrial Arrhythmia, and Recurrence of Any Atrial Arrhythmia by Treatment Group HR indicates hazard ratio; CI, confidence interval. Wilber, D. J. et al. JAMA 2010;303:333-340

“… the success of Pulmonary Vein Antral Isolation can exceed 90%, sometimes requiring 2 procedures, and there is an associated risk of stroke <1%, cardiac perforation <1%, pulmonary vein stenosis <1%, vascular injury <1%, and atrioesophageal fistula 1/1000.”

Results Worldwide data* (100 centers), 52% efficacy (27% repeats) 6% complications US data** (92 centers) 66% efficacy *Cappato R, Calkins H, Chen S et.al Circ. 2005;111:1100-1105. **Mickelson S, Dudley B, Treat E, et.al. JICE 2005;12:213-220.

Published Catheter Ablation Success Rates N = 63 studies 6936 pts A Meta Analysis of Radiofrequency Ablation and Antiarrhythmic Drug Studies demonstrated catheter ablation success compares favorably to antiarrhythmic drugs Ablation success rates represent a mixed population of paroxysmal (69.8%), persistent (14.9%) and longstanding persistent (13.9%) Adverse events were rarer but more severe for ablation – 5% vs 30% for AAD Note that the numbers on top of each bar represent the number of publications and patients that contributed to the analysis. The Y-Axis shows percent success. Success Rates Catheter Ablation Major complications 4.9% Calkins H, et al. Circulation. 2009;2:349-361.

Cryoablation 1948 (Hass) surgical Cryo lesions in Cardiac surgery using CO2 1963 (Cooper) developed liquid nitrogen surgical cryo tools 1977 (Gallagher) reported AVN ablation using surgical cryoablation 1991 (Gillette) cryoablation catheter in animals 1999 (Dubuc) cryocatheter in humans

Cryoablation Preserves endothelial integrity1 Decreases risk of thrombus formation1 There are some unique advantages to cryo: Cryoadhesion means the catheter sticks to the tissue (like a tongue stuck to a pole in winter). This allows the operator the ability to relax their grip on the catheter, and can minimize the amount of fluoro used. The cryolesion above demonstrates: Minimal thrombus An intact endocardium The well-demarcated nature of cryolesions A lesion in which the process of fibrosis is complete 1 Sarabanda AV, et al. J Am Coll Cardiol. 2005;46:1902-1912. 22 22

Effectiveness Results Freedom from AF after 90 Days Blanked for Detectable AF CRYO 69.9% (114 / 163) Treatment Success OR = 29.5 (12.0 – 72.2) p < 0.001 Effectiveness was defined for cryoablation patients as having both acute procedural success and freedom from chronic treatment failure, which meant no detectable AF post blanking, no use of non-AF study drug and no AF intervention. 69.9% of patients treated with cryoablation achieved the primary endpoint of freedom from AF vs. 7.3% in the AF drug group. Blanked for Detectable AF DRUG 7.3% (6 / 82) 23 23

Cryoballoon results 2/11 – 10/14 (CF) N=595 (male 72%) Ages 29-84 All symtomatic, documented multiple AF episodes, failed drug therapy. 82/410 prior failed procedures (8 surgical Maze, 10 multiple RF failures)

Cryoballoon results 2/11 - 12/13 124 patients >1 yr f/u 90% NSR, (77% 95/124 NSR off drugs).

Advance Balloon f/u > 12 mo 50 pts ablated between 6/12 and 11/12 47/50 f/u data available 39/47 cured (no AF no AAD) (83%) 4/47 brief AF no AAD 2/47 no AF remain on AAD 2/47 failures (4%) 96 %

Immediate Lab Complications (18/595 = 3%) 7 groin hematoma (1.1%) (no intervention required) 2 hypotension/acidosis 1 hyperkalemia 1 phenylepherine IV extravasation 2 hematuria from foley placement 1 ileus 1 temporary pacing overnight for bradycardia 1 cath/stent 2 CHF exacerbation 16/410= 3.9%

Phrenic nerve palsy (N=595) 40 transient with full recovery in lab. 4 persistent at discharge, 3 with full recovery by 3 months, 1 recovery in 12 months.

Late Complications (N=595) 0 CVA ,TIA,MI, or embolism 0 Tamponade 0 EA fistula 0 Deaths 0 persistent phrenic nerve palsy (1 yr) 2/410=0.5%

“… the success of Pulmonary Vein Antral Isolation can exceed 90%, sometimes requiring 2 procedures, and there is an associated risk of stroke <1%, cardiac perforation <1%, pulmonary vein stenosis <1%, vascular injury <1%, and atrioesophageal fistula 1/1000.”

Repeat Procedures 25 %-33% with RF 34/595 (5.7%) with Cryo

Goals Improve efficacy Decrease complications Decrease repeat procedures Minimize iatrogenic arrhythmias ( LA flutter) Decrease lab time or minimize variability 1) 50-60 to 80-90 > 6% to 4.9% 25% to 3% 3 hours to 2 hours

Total Lab Time

Long-term Outcomes N= 605 (579 PAF) 18-48 month f/u ( median 30 month) 61.6% single procedure 74.9% multiple procedure PNP 2% ( last 420 patients 0.7%) Vogt J, et al. JACC 2013;61:1707-12

CRYO Procedure Experience Impacts Treatment Success P < 0.001 by quartile 90% 100% 69% 80% 66% 56% 60% Treatment Success 40% The majority of STOP AF investigators were first-time users of Arctic Front. As with any new technology or technique, there is a learning curve. Procedural effectiveness is linked to the number of procedures completed. This link is evident when displayed by quartiles with each quartile increasing its treatment success in the sequence those procedures were performed. Treatment success is inclusive of both acute procedural success and freedom from chronic treatment failure at 12 months. In the graph above, each bar represents approximately 41 cryoablation procedures (range 38-43). In the first bar, Quartile 1, there are 25 centers and 43 procedures. These procedures represent the 1st and 2nd Arctic Front procedures the 25 centers performed. The success rate for just these procedures was 56%. In the second bar, Quartile 2, there are 14 centers and 38 procedures. These procedures represent the 3rd – 5th Arctic Front procedures the 14 centers performed, for a success rate of 66%. Only 14/25 centers enrolled to this point. In the third bar there are 10 centers and 42 procedures. These procedures represent the 6 – 11th Arctic Front procedures those 10 centers performed, for a success rate of 69%. Finally, the last bar represents four centers and 40 procedures. These four centers performed at least 12 and up to 23 Arctic Front procedures. Only four centers enrolled this many ablation patients. The success rate for these specific procedures was 90%. 25 centers n=43 14 centers n=38 10 Center n=42 4 centers n=40 20% 0% 1st and 2nd procedures 3rd – 5th procedures 6th – 11th procedures 12th – 23rd procedures 35 35

AF Ablation The “Cure”….where are we ? The concepts are good The tools are getting better Current techniques are becoming more practical for widespread application Safety remains a concern

AF ablation remains a second line therapy for highly symptomatic patients who fail medical management or cannot /will not take medications (2006) or first line therapy for selected patients (2011)

Things to consider This is great for symptomatic paroxysmal AF It is a 2 hour procedure under a general anesthetic Requires anticoagulation with warfarin It does not change your CHADS score It doesn’t work in everybody There are serious potential complications