Catheter Ablation of Atrial Fibrillation Has Become the Prime Therapy for Most Patients with Atrial Fibrillation. Proponent: Roger A.

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1 Catheter Ablation of Atrial Fibrillation Has Become the Prime Therapy for Most Patients with Atrial Fibrillation Proponent: Roger A. Winkle Disclosures Investigator for Cardiorobotics Investigator for CABANA trial Investigator Medtronic MelScheinerone is not FDA approved I have no financial interest in MelScheinerone Questions 1. I believe in Afib ablation and it is my treatment of choice for symptomatic patients 2. I like the idea of Afib ablation but there are too many complications 3. I like the idea of Afib ablation but it does not cure enough patients to make it worthwhile 4. I like the idea of Afib ablation but there are too many complications and it does not cure enough patients 5. I don t like the idea of Afib ablation 1

2 Future Afib Ablator Atrial Fibrillation is Bad! Symptoms are present in almost all patients Worsens most patient s QOL Increases stroke risk substantially Results in multiple hospitalizations and medical encounters Increases mortality Makes patients fatter and wears out their hearts 2

3 Palpitations Chest pain Dyspnea Syncope, dizzy spells Fatigue Other None Lévy et al. Circulation 1999;99: Type of Symptoms Wolf et al: Arch Int Med: 1987: 147; " 3

4 Framingham Heart Study: Percent of Men and Women Dead with and without AF (ages 55-74) Adjusted for age, BP, smoking," diabetes, LVH, MI, CHF, valve disease, " CVA and TIA" (Benjamin et al Circ 1998;98: )" Framingham Heart Study: Percent of Men and Women Dead with and without AF (ages 75-94) Adjusted for age, BP, smoking," diabetes, LVH, MI, CHF, valve disease, " CVA and TIA" (Benjamin et al Circ 1998;98: )" 4

5 Early Termination of Persistent AF and Ablation Outcomes (Winkle et. Al. AJC 1011;108: ) Persistent AF (AF2) AF2a: 179 patients whose physicians always terminated persistent AF by drugs or CV in < 1 week Compared to AF2b: 244 patients left in persistent AF for > 1 week up to 1 year 5

6 Early Termination of Persistent Atrial Fibrillation is Associated with Smaller Left Atrial Size and Better Ablation Outcomes (Winkle et. Al. AJC 1011;108: ) Early Termination of Persistent Atrial Fibrillation is Associated with Smaller Left Atrial Size and Better Ablation Outcomes (Winkle et. Al. AJC 1011;108: ) 6

7 Early Termination of Persistent Atrial Fibrillation: Clinical Variables (Winkle et. Al. AJC 1011;108: ) AF2a AF always terminated AF2b AF >1 week < 1year P Value Number 179 (42.3%) 244 (57.7%) LA size (cm) < * Age (years) =0.194 Females 29.1% 22.5% = DuraNon of AF (years) = * # Drugs Failed = * Average CHADS score = Hypertension 44.1% 50.0% = Diabetes 7.3% 9.0% = BMI = * Cardioversions 65.9% 69.7% = % Redo ablanons 34.1% 30.3% = Coronary artery disease 12.8% 17.2% = Dilated cardiomyopathy 3.9% 11.1% = 0.010* Prior Stroke/TIA 6.1% 6.1% = * StaNsNcally significant Early Termination of Persistent Atrial Fibrillation is Associated with Smaller Left Atrial Size and Better Ablation Outcomes (Winkle et. Al. AJC 1011;108: ) 7

8 Rate control is not the answer! Multiple studies compare rate control to rhythm control using AADs Rate control does nothing to reduce the stroke risk The drugs for rate control cause side effects and even death (digoxin) Due to poor AAD efficacy and crossovers the studies may not really show what they claim AADs may be so toxic that they wipe out any benefit of NSR Atrial Fibrillation Follow-Up Investigation of Rhythm Management-The AFFIRM Study Design (AFFIRM Investigators. NEJM 2002;347: ) Enrolled 4060 patients Patients with atrial fibrillation and high risk of stroke All patients on anticoagulation with target INR = 2.5 (range ) Randomized to initial strategy of rate control or attempts to maintain NSR Primary endpoint: Total Mortality Intention to treat analysis 8

9 Atrial Fibrillation Follow-Up Investigation of Rhythm Management-The AFFIRM Study Design (AFFIRM Investigators. NEJM 2002;347: ) Hypothesis: Antiarrhythmic therapy to maintain NSR has no effect on total mortality compared with therapy that controls the heart rate Enrolled 4060 patients Primary endpoint: Total Mortality Secondary endpoints mortality + CVA s mortality + CVA s + cardiac arrest cost quality of life Intention to treat analysis Atrial Fibrillation Follow-Up Investigation of Rhythm Management-The AFFIRM Study Design (AFFIRM Investigators. NEJM 2002;347: ) Patients with atrial fibrillation and high risk of stroke > 65 years old < 65 years old and > 1 other risk factor (hypertension, diabetes, CHF, TIA, prior CVA, LA > 50mm, fractional shortening < 25%, LVEF< 40%) All patients on anticoagulation with target INR = 2.5 (range ) All patients may have one initial successful cardioversion Randomized to initial strategy of rate control or attempts to maintain NSR 9

10 The Unfortunate Saga of MelScheinerone 5000 patients at high risk of CV death 2500 MelScheinerone Placebo labeled as MelScheinerone 50 % Mortality on MelScheinerone 2500 Placebo MelScheineron labeled as placebo 25% Mortality on Placebo 10

11 The Unfortunate Saga of MelScheinerone 5000 patients at high risk of CV death 2500 MelScheinerone Placebo labeled as MelScheinerone 50 % Mortality on MelScheinerone 2500 Placebo MelScheineron labeled as placebo 25% Mortality on Placebo AFFIRM Trial: Percent of patients Crossing-Over Percent of patients crossing over (%) AFFIRM Investigators. NEJM 2002;347:

12 AFFIRM Trial: Percent of Patients in NSR Percent of patients in NSR (%) Only 28% contributing meaningful data AFFIRM Investigators. NEJM 2002;347: Atrial Fibrillation Follow-Up Investigation of Rhythm Management A subsequent on treatment statistical analysis gives a very different interpretation of the AFFIRM Trial results 12

13 Atrial Fibrillation Follow-Up Investigation of Rhythm Management Due to the large number of cross-overs, the poor efficacy of AADs with many rhythm control patients in AF and the fact that many rate control patients were actually in NSR, Intention to treat analysis may be misleading A subsequent on treatment statistical analysis gives a very different interpretation of the AFFIRM Trial results AFFIRM Trial: Importance of NSR (Circ 2004; 109: ) 13

14 AFFIRM Trial: Importance of NSR (Circ 2004; 109: ) AFFIRM Trial: Importance of NSR (Circ 2004; 109: ) 14

15 AFFIRM Trial: Importance of NSR (Circ 2004; 109: ) Danish Investigators of Arrhythmia and Mortality on Dofetitlde in CHF (DIAMOND- CHF) (NEJM 1999;341: ) 1518 patients with symptomatic CHF and LV dysfunction Double-blind, placebo controlled at 34 Danish centers Inclusion criteria hospitalized patients with new or worsening CHF and at least one episode of SOB on minimal exertion or at rest or PND ECHO with wall motion score of 1.2 or less (EF approx. 35%) Exclusion criteria acute MI within 7 days K + < 3.6 or > 5.5 heart rate < 50 creatinine clearance < 20 cc/min SA or AV block without a pacer recent Class I or III antiarrhythmics history of proarrhythmia planned or recent PTCA/CABG QTc >460msec (>500 if bundle branch block) Aortic stenosis BP > 115 diastolic or < 80 systolic ICD 15

16 Dofetilide in patients with CHF and LV dysfunction (DIAMOND-CHF) (NEJM 1999;341: ) DIAMOND-CHF Sub study of patients in AF at time of enrollment (Pedersen et. al. Circ 2001;104: ) Probability of survival during treatment and follow-up periods in 506 patients with LV dysfunction and AF-AFl at baseline treated with dofetilide or placebo. 16

17 DIAMOND-CHF Sub study of patients in AF at time of enrollment (Pedersen et. al. Circ 2001;104: ) Survival rates of patients treated with or placebo who converted or did not convert to SR. Antiarrhythmic Drugs Cause a lot of side effects Most do not work very well for patients with atrial fibrillation Many cannot be given to patients with poor LV function, CAD, sick sinus etc. All have black box warnings from the FDA which are scary to patients 17

18 Rhythm Control for AF: Antiarrhythmic Drugs Treatment Choices (oral) Class 1A Class 1C Class 3 Flecainide Propafenone Atrial Fibrillation: Prevention of Recurrence after Cardioversion by Quinidine Percent of patients in NSR (%) Coplen SE. Circulation. 1990;82: Time (months) 18

19 Odds Ratio for Total Mortality for Patients Treated with Quinidine Compared to Control RCT n Boissel 212 Byrne-Quinn 92 Hartel 175 Hillestad 100 Lloyd Sodermark ALL STUDIES N = Quinidine Better Coplen SE. Circulation. 1990;82: Quinidine Worse Odds Ratio (Quinidine: Control) Maintenance of Sinus Rhythm with Oral Sotalol in Patients with Symptomatic Atrial Fib / Flutter (Benditt et al AJC 1999;84: ) 253 patients with atrial fibrillation / flutter Multicenter, randomized, double-blind study Evaluated safety and efficacy of 3 fixed doses of d,lsololol (80, 120 or 160 mg bid) Primary endpoint: time to recurrence of AF Treatment continued 1 year or until AF recurred Transtelephonic monitoring used 19

20 Time to documented AF on Sotalol (80, 120, 160 mg bid) or placeb0 Intention to Treat 45%" 40%" 30%" 28%" Sotalol Side Effects Compared to Placebo (Benditt et al AJC 1999;84: ) 20

21 21

22 Dronedarone: Amiodarone Without Side Effects or Just a Different Poison? EURIDIS AND ADONIS (Singh B et al. N Engl J Med 2007;357: ) Age >21 years One episode of Afib in prior 3 months In NSR for one hour before randomization Randomized 2:1 Dronedarone 400mg bid or placebo Endpoint: Time to first documented AF lasting 10 minutes Secondary endpoints Symptoms related to AF Mean Ventricular Rate during first AF recurrence 22

23 EURIDIS and ADONIS Primary Endpoint: Median # Days to First AF Recurrence (Singh et al NEJM 2007;357:987-99) Kaplan-Meier Incidence of First Recurrence of A Fib or Flutter (Singh et al NEJM 2007;357:987-99) 23

24 ANDROMEDA Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe CHF Evaluating Morbidity Decrease Stopped by DSMB January,2003 after 627 patients enrolled due to increased mortality in Dronedarone group PALLUS Trial Age > 65 years with at least one of the following major risk factors systemic arterial embolism myocardial infarction documented coronary artery disease prior stroke symptomatic heart failure Age > 75 years + hypertension and diabetes mellitus. Exclusions: NYHA Class IV or unstable Class III CHF Endpoints Major cardiovascular events (stroke, systemic arterial embolism, myocardial infarction or cardiovascular death) Cardiovascular hospitalization or death from any cause 10,800 patients enrolled in 43 countries at 700 sites Randomized to dronederone 400 mg bid or placebo 24

25 PALLUS Trial Adverse event CV death, MI, stroke, systemic embolism Death, unplanned CV hospitalization* Placebo n=1577 n (%) Dronedarone n=1572, n (%) Hazard ratio 14 (0.9) 32 (2) (5.1) 118 (7.5) Death 7 (0.4) 16 (1) MI 3 (0.2) 3 (0.2) Stroke 7 (0.4) 17 (1.1) HF hospitalization 15 (1) 34 (2.2) p Antiarrhythmic Drugs for Maintaining Sinus Rhythm After Cardioversion of Atrial Fibrillation: A Systematic Review of Randomized Controlled Trials Arch Intern Med. 2006;166: trials were included, with a total of 11,322 pts All drugs increased withdrawals due to adverse effects (NNH, 9-27) All but amiodarone and propafenone increased proarrhythmia (NNH, ) Class IA drugs (disopyramide, quinidine), pooled, were associated with increased mortality compared with controls P =.04; NNH, 109 No other antiarrhythmic showed a significant effect on mortality compared with controls 25

26 Withdrawals and Proarrhythmia Lafuente-Lafuente, C. et al. Arch Intern Med 2006;166: Overall Mortality Lafuente-Lafuente, C. et al. Arch Intern Med 2006;166:

27 Death by Treadmill! 59 year old recently retired lawyer No cardiac or non-cardiac diseases Spring 2007 first Afib while visiting NYC Hospitalized 4 days, spontaneous conversion, echo normal and DC on warfarin and metoprolol California cardiologist changed to ASA Afib got worse, occurring anytime Treated with propafenone but had side effects Flecainide started 100 mg bid, increased to 150 mg bid, still had Afib October, 2007 was at movie and felt lightheaded Went to urgent care where sinus rate in 30s and metoprolol decrease to 25 mg a day Referred for a treadmill 27

28 11/2/11 TM (November 2, 2007) Baseline TM EKG #1 28

29 11/2/11 TM EKG #2 TM EKG #3 Collapse and was unconscious for 15 seconds 29

30 Saw Dr. Winkle on November 15, 2007 Patient declined further antiarrhythmic drugs Metoprolol 25 mg a day (very fatigued on higher doses changed to diltiazem with gradual dose escalation to 240 mg AM and 120 mg PM Still with several episodes of Afib a week lasting for hours at a time during which he could not do much Underwent successful Afib ablation March 21, AF free ever since. Ablation to treat AF: Frequent Negative Comments It takes all day to do It does not work Repeat ablations do not work There are too many complications It works, but almost all patients eventually have a recurrence Most patients still have to stay on anticoagulation even if they are not having AF None of these are true in

31 Sequoia Hospital AF Ablation Results 1504 AF ablations in 1125 patients as of Dec, 31, 2010 All patients symptomatic and most have failed rate control and rhythm control Includes both paroxysmal and persistent AF with and without heart disease 270 (30.9%) AF1 (paroxysmal) 423 (52.8%) AF2 (persistent) 150 (16.3%) AF3 (long-standing persistent) Sequoia Hospital AF Ablation Results Success = no AF off of all drugs Partial success = no AF on AAD Most partial successes and failures offered redo ablation Failure = AF on AAD 3 months after final procedure Both Single Procedure Success rates and final status reported 31

32 AF Ablation Outcome by AF Type (No AF off of drugs) (Winkle et. al. Am Heart J 2011;162: ) Sequoia Hospital: Reasons Why Patients do not have a Redo Ablation Reason for no Redo Redo done or to be done a`er Dec (Last date of panent enrollment) Total Females Males N = 138 N = 49 N (39.9%) 12 (24.5%) 43 (48.3%) Physician or Medical Decision Extensive LA scar AV node ablanon Medical condinons Death/Terminal cancer Prior MAZE or AF ablanon elsewhere Total Physician or Medical Decision 31(22.5%) 9 (18.4%) 22 (24.7%) PaNent Decision Much improved a`er ablanon 7 5 (10.2%) 2 (2.3%) No AF on drugs a`er ininal ablanon (22.4%) 12 (13.5%) PaNent preference (24.5%) 10 (11.2%) Total PaNent Decision 52 (37.7%) 29 (57.1%)* 25 (27.0%)* *P = Females vs. Males 32

33 Freedom from AF at 1,3 and 5 years for those patients Going all the Way 1 year AF free rate 3 year AF free rate 5 year AF free rate Paroxysmal AF1 94.5% 94.5% 94.5% Persistent AF2 87.9% 82.9% 77.3% Long-standing AF3 83% 79.4% 74.4% Long term outcome to almost 7 years for patients cured by the first ablation or who come back for a redo if the first ablation fails 33

34 How to do a faster and safer AF ablation Use only one groin Do only one transseptal puncture (you can put 2 catheters thru the single stick) Use an RF needle for the transseptal No Foley catheter Have dedicated echo machine in EP lab Use general anesthesia Use the open irrigated tip catheter at 50W Mark the location of the esophagus Keep the ACT at 225 and infuse heparin thru the transseptal sheath Reverse heparin and pull sheaths in the EP lab Avoid gadgets : Stereotaxis, Cyroballoons, Robots Zero Gravity: A cheaper way to reduce operator radiation than $2M magnets! 34

35 Comparison of Cryoballoon to RF ablation Cryoballoon Medronic FDA data (n = 163 patients) Radiofrequency at Sequoia Hospital (n = >1800 ablations) Superior outcome Cryo or RF Death 0.6% 0.0% RF Superior Stroke/TIA 4.3% 0.26% RF Superior Heart Attack 1.2% 0.0% RF Superior Pulmonary Vein Stenosis 3.1% 0.07% RF Superior Bleeding Needing Transfusion AV fistula/ Pseudoaneurysms 1.8% 0.13% RF Superior 1.8% 0.93% RF Superior Phrenic Nerve Paralysis 16% 0.0% RF Superior Procedure Time 6 hours 11 minutes 2 hours RF Superior Flouroscopy Time 62.8 minutes 60.2 minutes RF Superior 1Year Cure Rate 69.9% 86.2% RF Superior With OITC Ablate at 50W and Keep the Catheter Moving (Winkle et. al. PACE 2011;34 : ) 35

36 ATRIAL FIBRILLATION ABLATION: PERPETUAL MOTION OF OPEN IRRIGATED TIP CATHETERS AT 50 WATTS IS SAFE AND IMPROVES OUTCOMES (Winkle et. al. PACE 2011;34 : ) Kaplan-Meier Freedom from Afib after initial ablation (n = 843) AF1 = 32% AF2 = 50.2% AF3 = 17.8% Sequoia Hospital Afib Ablations Procedure Times by Catheter and Power (N = 1122) *P<0.041 P< *P<0.001 *P<0.001 * Compared to CTC 36

37 The use of the RF needle for transseptal punctures (Winkle et. al. Heart Rhythm 2011;8: ) Baylis NRG RF Transseptal Needle 37

38 Fewer Complications and better Septal Crossing with the RF Needle (Sequoia Hospital: 1495 AF Ablations) With OITC: Lower Target ACT to 225 Seconds and Reduce Complications (Winkle et. al. AJC 2011;107: ) 38

39 Safety of Lower Activated Clotting Times During Afib Ablation using Open Irrigated Tip Catheters and a Single Transseptal Puncture (Winkle et. al. AJC 2011;107: ) ) Sequoia Hospital AF Ablation Trends over Time (1504 AF ablations in 1125 patients) 39

40 Sequoia Hospital AF Ablation: all Major Complications from in 1504 Ablations Sequoia Hospital AF Ablation Trends over Time (1504 AF ablations in 1125 patients) 40

41 Why Patients Should Skip AADs and Go Directly to Ablation The risk of permanent side effect from ablation is about 1:400 which is the risk of stroke every 2-3 months for the lowest risk AF groups Every drug a patient fails lowers their chance of a successful ablation Every randomized trial of Ablation vs. AAD strongly favors Ablation Sequoia Hospital AF Ablation: Impact of number of AADs failed pre-ablation (Europace in press) 942 patients with paroxysmal AF (n = 348) and persistent AF (n = 594) We examined the impact of number of AADs failed on clinical characteristics and ablation outcomes 41

42 Sequoia Hospital AF Ablation: Change in clinical parameters as patients fail more AADs Number of Drugs Failed No Drugs (n = 195) One Drug (n = 400) Two Drugs (n = 232) 3 or MoreDrugs (n = 115) P Value Le` atrial size (cm) Age (years) * DuraNon of AF (years) * Repeat ablanons 26. 2% 26.8% 31.9% 35.7% 0.045* % Female 27.7% 30.0% 30.1% 40.9% 0.037* Average CHADS 2 score Hypertension 45.6% 47.2% 46.6% 47.8% Diabetes 7.7% 8.5% 10.3% 6.1% Coronary artery disease 11.3% 13.0% 15.5% 16.5% Dilated cardiomyopathy 7.7% 8.5% 10.3% 6.1% Body Mass Index AF1 (paroxysmal AF) 43.1% 64.2% 35.0% 34.7% 0.003* Prior Stroke/TIA 7.2% 5.3% 7.3% 9.6% *StaNsitcally significant, AbbreviaNons: AF = atrial fibrillanon, TIA = transient ischemic agack Sequoia Hospital AF Ablation: Reasons why some patients did not fail AAD before ablation Reason for no prior annarrhythmic drug Total (N = 195) Physician or Medical Decision Sinus node disease/bradycardia 25 ConducNon system disease 1 Coronary artery disease 6 Cardiomyopathy 6 Unexpained syncope 1 Liver or kidney disease 3 Total Physician or Medical Decision 42(21.5%) PaNent Decision PaNent preference 153 Total PaNent Decision 153 (78.5%) 42

43 Sequoia Hospital: AF Ablation Outcome after Initial and Final Ablation by Number of AADs failed Pre-Ablation (Europace in press) Sequoia Hospital AF Ablation: Multivariate analysis of factors predicting failure of initial and final ablations AF recurrence after Initial Ablation AF recurrence after Final Ablation Variable Hazard ratio Hazard ratio 95% CI P Value Hazard ratio Hazard ratio 95% CI P Value Age * Left Atrial size * * BMI (Body Mass Index) Atrial Fibrillation Duration Gender (female vs. male) * * AF type (paroxysmal vs. persistent) * * CAD (absent vs. present) Hypertension (absent vs.present) Diabetes (absent vs. present) Total # of antiarrhythmics failed * * * Statistically Significant, abbreviations: AF = atrial fibrillation, CAD = coronary artery disease, CI = confidence interval 43

44 Summary of Randomized AF Ablation Trials vs. Drugs * Excluding RAAFT ThermoCool AF Trial (Wilber et. Al. JAMA 2010;303(4): ) 44

45 ThermoCool AF Trial (Wilber et. Al. JAMA 2010;303(4): ) Kaplan-Meier Curves of Time to Protocol-Defined Treatment Failure, Recurrence of Symptomatic Atrial Arrhythmia, and Recurrence of Any Atrial Arrhythmia by Treatment Group RF Ablation vs. Antiarrhythmic Drugs as First-Line Treatment of Sx Atrial Fibrillation: A Randomized Trial (Wazni et al. JAMA 2005; 293: ) 45

46 RF Ablation vs. Antiarrhythmic Drugs as First-Line Treatment of Sx Atrial Fibrillation: A Randomized Trial (Wazni et al. JAMA 2005; 293: ) RF Ablation vs. Antiarrhythmic Drugs as First-Line Treatment of Sx Atrial Fibrillation: A Randomized Trial (Wazni et al. JAMA 2005; 293: ) Quality of Life Assessment*. 46

47 2010 European Guidelines:Treatment Recomendations Conclusions Rate control is a poor solution for AF as it only sweeps the dirt under the carpet AADs do not work in a majority of patients and cause a lot of side effects and possibly deaths Ablation can be done safely, in a reasonable amount of time and can restore NSR in a high percentage of patients In randomized trials ablation is vastly superior to AADs The earlier in the AF course ablation is done the greater the chance of eliminating AF The time has come for ablation to be considered as first line treatment for most patients with AF 47

48 Dr. Moss Thank you for all you have done over so many years to help our patients live longer and better quality lives! 48