Current Approach to Ablation of Atrial Fibrillation



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Current Approach to Ablation of Atrial Fibrillation American College of Osteopathic Internists Unified Osteopathic Convention October 23, 2010 Eric D. Good, D.O., F.A.C.O.I. Assistant Professor, University of Michigan

GOALS OF PRESENTATION Define atrial fibrillation from EP perspective; Distinguish atrial flutter from atrial fibrillation Discuss patient selection, indications, and expected outcomes for ablation of Afib, casecentered approach Identify issues related to follow-up from AF ablation Convince pundits that t catheter t ablation is an effective alternative to anti-arrhythmic drug therapy in the treatment of AFib

Case KE: 60 y/o C M w/ dx afib-flutter x 2 yrs; 4 ED visits Sx: CP, SOB, diaphoresis, flushing PMHx: HTN, GERD, OSA CPAP No CHF, DM, CVA Cath1 yr ago: nl cors, nl LVEF Echo: LA=38 mm Exam: NSR, unremarkable Meds: Toprol XL 50 mg daily (HTN), ASA 81 mg daily, lisinopril, omeperazole

Case KE: EKG prior ED visit

Case KE: Initial Iitil Management Strategy? t 1. Start t amiodarone, continue BBl, ASA 2. 21 day event monitor 3. 48 hr Holter 4. Refer for Aflutter ablation 5. Refer for combined Afib, AFlutter ablation

Distinguishing Aflutter from Afib:

Cavo-tricuspid-isthmus-dependent (Typical) Atrial Flutter:

Atrial Flutter: Electro-Anatomy

Catheter Catheter Ablation Ablation: Aflutter: 98% Efficacy CTI 1% Complication rate Predefined ablation end-points Tricuspid Valve Tricuspid Valve Inferior Vena Cava Inferior Vena Cava

Freedom From Recurrent Atrial Flutter ABLATION (52 patients) AMIODARONE (52 patients) Da Costa et al. Circulation 2006

Case KE: 1. Start amiodarone, continue BBl, ASA 2. 21 day event monitor 3. 48 hr Holter 4. Refer for Aflutter ablation 5. Refer for Afib ablation

CTI Atrial Flutter: What about in context of pt who also has Afib in addition to Aflutter? Staged ablation: Target flutter first; see impact on AF burden Then AARx or LA ablation if AFib Hybrid ablation: Isolate PVs (Left=AFib) & ablate CTI (Right=Aflutter)

Rationale for staged approach: PV triggers can initiate both AF & AFl Fib-flutter is observed clinically & AARx AF often organizes to AFl AARx easier after CTI-RFA CTI-RFA high success (98%); low complication rate (<1%); defined end-point Do not alter LA substrate; risk pro-arrhythmia (Atypical LA flutter); anticoagulation Shorter procedure time

Rationale for hybrid approach: Significant % pts with AFl will have AF in long- term f/u One vs. two procedures Shorter-term anticoagulation (?) Use cooler EP tools; more challenging case

Late Occurrence AF following CTI-RFA AFl: Recurrence CTI-FL 3-5% 25-50% 50% new-af Ellis 82% AF 68% new AF w/o AFl 94% refractory 2 ± 2 AARx Retrospective study Exclusions Callans (2007) 1. Ellis K. JCE. 2007; 18: 799-802 Lara de Melo (2009) 2. Lara de Melo S. Arq Bras Cardiol 2009; 93(5):448-453

Predictors of AF following CTI RFA: LA > 40 mm 1 Mitral Regurgitation 2 LV EF <50% 2 Inducibility sustained AF after RFA 3 Persistent CTI-AFL 4 Duration CTI-AFL > 3yrs 4 1. Ellis K. JCE. 2007; 18: 799-802 2. Da Costa A. Eur Heart J 2002; 23:498-506 3. Phillippon F. Circ 1995;92:430-43592 435 4. Lara de Melo S. Arq Bras Cardiol 2009; 93(5):448-453

Take-home points: AF & AFl are interrelated, but distinct arrhythmias with functionally different mechanisms of propagation Incidence of AF following CTI-RFA significant, even in absence of prior hx AF & increases with time Post CTI-RFA pts need close rhythm surveillance & anticipatory anti-thrombotic thrombotic prophylaxis

Defining Atrial Fibrillation: Electrophsiologic Perspective Paroxysmal Afib Recurrent episodes Terminate spontaneously w/in 7 days Persistent Afib Continuing episodes > 7 days Requiring chemical or electrical CV Long-standing Afib Continuous episodes > 1 year Move away from chronic or permanent

PROJECTED AF PREVALENCE: OLMSTED COUNTY DATA Miyasaka et al, Circulation 2005; 114:119

Atrial Fibrillation Demographics by Age U.S. population x 1000 Population with AF x 1000 30,000 Population with 500 atrial fibrillation 20,000 U.S. population 400 300 10,000 200 100 0 0 <5 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 >95 Age, yr Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-473. 0.1% @ 55 9% @ 80

Poor Prognosis with AF long-term risk of stroke Increased risk of CHF Increase in all-cause mortality Risks especially prominent in women

Afib Promotes Atrial Fibrosis: Collagen & Matrixmetalloproteinases (MMPs) 146 RAA excised at OHS Grouped: SR; CPAF 6 mos; CAF >6, >24, >60 mos Hydroxyproline and MMP content measured Gramley. JCE. 2007(18); 1076-1082

Afib Promotes Atrial Fibrosis: Collagen & Matrixmetalloproteinases (MMPs) Atrial fibrosis irreversible May beget more AF: Impaired atrial conduction Atrial anisotropy atrial micro-reentry Gramley. JCE. 2007(18); 1076-1082

Afib Promotes Atrial Hypoxia: Hypoxia-inducible inducible Factor (HIF) vascular endothelial growth factor (VEGF) 158 RAA excised at OHS Grouped SR or AF Immunostained to detect hypoxia & angiogenesis-related proteins Degree fibrosis & microvessel density determined morphometrically Gramley. Cardiovascular Pathology 2010(19):102 111

No difference between AF & SR? Corey et al, Circulation 2004;109:1509

Important Points Regarding gaffirm Comparison of rate- and rhythm- control management strategies NOT a comparison of NSR vs. AF Elderly ypopulation p (mean age 71) Pts with severe sx s excluded Many pts had recurrent AF in rhythmcontrol group

CAN SINUS RHYTHM IMPROVE SURVIVAL? Predictors of Mortality in AFFIRM Corey et al, Circulation 2004;109:1509

Summary Drug Efficacy in Persistant AF: 70 60 50 40 30 20 10 0 % NSR after CV 6 mos Naccarelli et al. Cardiology. 2004;8:112-115

Efficacy AARx: Meta-analysis analysis Calkins et al. Circ Arrhythm Electrophysiol 2009;2;349-361 361 Overall = 52% (95% CI, 47% to 57%) Placebo studies = 24.9% (95% CI, 15% to 34%) Complication Rate = 30%

Meta-Analysis Distribution of Drugs: Number Studies AA-RX Amiodarone Propafenone Sotalol Flecainide Dofetilide

Mortality, Morbidity, and Quality of Life After Circumferential Pulmonary Vein Ablation for Atrial Fibrillation Compared to drug therapy, LA ablation significantly reduced the risk of: 0.5 0.4 Hazard Ratio AF 0.3 Mortality 0.2 0.1 CHF/CVA Improved QOL 0 AF Mort. HF/CVA Pappone et al. JACC 2003;42:185-97

Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial 66% 16% Wilber et al. JAMA 2010;303(4)333-40

Catheter Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation The A4 Study Randomized, multicenter comparison RFA vs. additional AADs PAF failed 1 AAD Allowed up to 3 ablation procedures Follow-up 90-365 days, 3 mo. Blanking AF recurrence >3 min No restrictions on AADs alone, combo Haissaguerre. Circ 2008; 188(24):2498-505

AF: Ablation vs. Drugs 89% 23% Haissaguerre. Circ 2008; 188(24):2498-505

Efficacy Afib RFA: Meta-analysisanalysis Calkins et al. Circ Arrhythm Electrophysiol py 2009;2;349-361 ;; 361

Ablation is an Effective Alternative to Anti- arrhythmic Drug Therapy in the Treatment of AFib 3.7-fold higher probability of maintaining NSR with RFA than AARx

CASE: CL 44 y/o C, M Fire Captain Holiday heart 6 yrs ago @ti time of fdivorce; dx lone AFib w/ isolated recurrence card game 3 yrs ago Recent admit OSH AFib/RVR, no etoh IV amiodarone NSR d/c Cartia XT 120mg daily Now with weekly episodes 5 min-hrs, though rates 80s bpm Sx=Palp, SOB/DOE, fatigue

Symptomatic Presentation

CASE: CL Cardiolite stress nuclear NEG 11 METS/ 90% HR Echo: LA=37 mm, nl IVS/LPW/EF PMHx= GERD No CVA/TIA, HTN, DM

CASE: CL Therapeutic approach? 1. AV nodal blocking agent (BBl, CaChBl) 2. AARX (Flecainide, Propafenone) 3. Both 1 & 2 4. LA ablation Anti-thrombotic strategy? 1. ASA 2. Wafarin

CASE: CL Event monitor: 6% AFib Sleep Study (snoring & apnea per wife) Apnea-hypopnea index 1.4; SaO2=88% primary snoring, no OSA Excess periodic limb movements with arousals, no restless limb syndrome Shift-work sleep disturbance

CASE: CL Metoprolol succinate 25mg BID Flecainide 100mg BID ASA 325mg Qday Nexium 40mg Qday Fish Oil 1200mg Qday Significant improvement: few, short episodes next 3 yrs

CASE: CL Now with breakthrough episodes, despite increasing flecainide to 150mg BID Therapeutic Strategy: 1. Switch anti-arrhythmicarrhythmic 2. Suck it up, be a man & learn to live with it 3. Schedule LA ablation 4. Repeat event monitor

Candidates for RF Ablation of AF Paroxysmal or persistent Symptomatic, with impaired QOL Inadequate response to meds Less Ideal Candidates LA >55-60 mm Prosthetic mitral valve Persistent t AF > 5 years

Who should perform Afib RFA? Operator performing 30-50 ablations during training & yearly this number underestimates the experience required for a high degree of proficiency. Outcomes better at centers performing more than 100 procedures

AF Initiated By A Premature Depolarization Arising in the RSPV V1 Abl d Abl p CS d CS p

Cornerstone of AF Ablation: Pulmonary Vein Isolation To eliminate premature depolarizations that trigger AF To eliminate bursts of tachycardia that contribute to the perpetuation of AF Accounts for mechanism in 90%-plus PAF

Continuous PV Tachycardia, CL 80 ms, RSPV

Spiral-CT of the Pulmonary Veins LSPV LIPV LA RSPV RIPV

Superficial Myocardial Fibers of the LA * Nathan et al, Circ, 1966

Mechanisms That Contribute to Atrial Fibrillation PV s SVC Autonomic Innervation * * Rotors/ Wavelets VOM CS

Current Ablation Techniques: PV Isolation (PVI) Haissaguerre Anatomic, antral, lasso CFAEs Nadamanee 2 deflections, continuous activity, short CLs Ganglionic i Plexii Pappone, 1/3 have vagal reflex Linear Ablation (avoided)

RF Ablation of a Pulmonary Vein Fascicle

LSPV I V 5 PV d PV m PV p L 1-2 L 2-3 L 3-4 L 4-5 L 5-6 L 6-7 L 7-8 L 8-9 L 9-10 CS d CS m CS p 200 msec Pre-RF During RF Post-RF

Evolution of AF Ablation at the U of M Linear ablation in RA Focal PV ablation Segmental Ostial PV isolation Circumferential PV ablation Ablation of complex atrial electrograms Tailored ablation: Selective PV isolation + widespread RFA of CFAEs Antral Ablation of all PV s ± limited RFA of CFAEs

Basic Premises of the Tailored Approach to Ablation of Paroxysmal AF The less ablation the better PVs play a central role PAF is often but not always only PV-dependent Termination of AF and noninducibility are reliable indicators of end point of RFA

PV Ostium vs. Antrum

Peri-operative issues: Performed with INR 2.0-3.0 Warfarin naïve start t few weeks before procedure Baseline ACT, IV Heparin, ACT goal 350 Protamine reversal at conclusion Continue warfarin minimum 3 mos post procedure TEE to exclude LA/LAA thrombus if persistent atrial fibrillation d/c Rx 5 half-lives li (unless hx/o RVR)

Pre-Procedure Procedure CT or MRI:

58 y y/o M w/ PAF & 3 RIPVs: Copyright 2007 by the American Roentgen Ray Society Cronin, P. et al. Am. J. Roentgenol. 2004;183:767-778

Transseptal Puncture with ICE RA LA

PV Venogram: 12 mg Adenosine

CT Before e& 4 Months After Segmental Ostial Ablation Before Ablation After Ablation LI LS LA RS RI LI LS LA RS RI

Cummings, Ann Intern Med. 2006;144:572-574.

Barium Swallow:

Atrio-Esophageal Fistula: Pappone. Circulation: 2004;109.

CT FINDINGS (Axial): AE Fistula A) Pre-CT: Normal, smooth B) STAT-CT: Narrowed, contour of posterior LA wall irregular, ulcerated LCPV Malamis, A. J Thorac Imaging 2007 (22);2:188-191.

Induction of AF By Isoproterenol, 15 mcg/min

Antral LA Ablation for PAF:

>4 sec

Termination during antral isolation

I II V 1 Complex Electrograms Targeted For Ablation I II III Rapid Egms Fractionated Egms V 5 V 1 Abl d Abl p CS d CS p V 5 Abl d Abl p CSd CS p

Termination of AF During RFA of CFAEs at tbase of flaa

No PAC s/af or PV Conduction During 20 mcg/min of Isoproterenol

Tailored RFA of Paroxysmal AF: End Points Conversion to sinus rhythm No spontaneous AF No AF or frequent ectopy induced by isoproterenol, 20 mcg/min

Tailored Approach to Ablation of PAF 80% 70% 60% Freedom From AF/AFlutter University of Michigan 90% Mean f/u 11 mo. after last procedure 50% 40% 30% 20% 10% 0% AF Noninducible AF Inducible N=88 N=65

Procedure Duration, Post-opop Procedure time varies by operator Average 3-4 hours RF; additional 1-2 prep, recovery Overnight (23-hour) in-patient stay Typically restart AARx Proton-pump inhibitor 1-3 mos Pericarditis usually resolves 1-2 weeks SOB/ catch breath at deep inspiration

Follow-up from Ablation Procedure & When to Consider it a Failure: 3 months following RFA is blanking period Defining AF recurrence: 30 sec May under-represent true benefit of AF Pts seen in f/u min of three months following the ablation procedure, then every six months for at least two years 24-hour ambulatory ecg monitoring (Holter, event) recommended at three to six month intervals for one to two years following ablation or if c/o palpitations during f/u interval

Anticoagulation after Afib RFA: Continue wafarin x 3 mos after RFA 3 mo visit: Low risk: CHADS 0,1 change to ASA Higher risk: CHADS 2 21 event monitor CHADS 2 or prior CVA/TIA?I Indefinite it anticoagulation

LAA Occlusion Device

Cross-section section of appendage. 45 day post-implant. Atrial facing view. 45 day ypost-implant. p

CASE: CL 3 month follow-up Palpitations, short bursts AF first couple weeks after ablation; nothing since Metoprolol succinate, flecainide & wafarin discontinued

No sx CASE: CL 6 month follow-up 28 day auto-triggered event monitor negative

No sx CASE: CL 1 year follow-up Pulmonary CT (nodule protocol)

Efficacy of RF Ablation of AFib 1 Procedure at 12 mos: Paroxysmal: 65-85% Persitent: 50-60% > 1 Procedures at 12 mos: Paroxysmal: 85-95% Persistent: 70-85% Late Recurrences (more than 1 year) 3-5% per year

Complications of Catheter Ablation % Complications 6 5 4 3 2 1 WW Survey UMMC 0

When is Catheter Ablation Appropriate 1 st -Line Therapy for AF? Young patient with idiopathic AF who is averse to long-term drug therapy When only feasible rhythm control agent is amiodarone In patients with low resting HR or sinus node dysfunction, when drug therapy would necessitate pacemaker implant

Special Populations Elderly Heart Failure Mechanical Valves Prior CVA Not good anticoagulation candidates

CASE: FC 46 y/o C F with persistent AF refractory to sotalol s/p MI & CABG NYHA Class II-III III CHF on optimal medical Rx Exam-BP110/80, HR 90, no overt CHF Nuclear stress- no ischemia, EF 28% Echo- LA 44 mm, EF 30%

CASE: FC 1. Rhythm control strategy 2. Rate control strategy 3. Rhythm control strategy + ICD 4. Rate-control strategy + ICD

Heart Failure & AFib 10-50% of pts with CHF have AF AF may be the cause of HF Even when HF is the cause of AF, AF often aggravates the HF further Mechanisms: RVRs Irregularity Ventricular Dysynchrony Loss of AV synchrony AF is independent d predictor of death in HF

Rhythm Control vs. Rate Control for AF 1, 376 pts with AF & CHF (CAD in 48%) Mean age 67 yr, LVEF 27% AF persistent t in 68% Randomized Rhythm control: 682 Rate control : 694 Mean f/u 37 mos Roy et al. NEJM 2008;358:2667-77

Rhythm Control vs. Rate Control for AF Roy et al. NEJM 2008;358:2667-77

Outcomes with Rhythm Control vs. Rate Control Strategies No Significant Differences in: Cardiovascular Mortality y( (8%/yr) y) All-Cause mortality (10%/yr) Stroke (1-2%/yr) Worsening CHF (7-8%/yr) Roy et al. NEJM 2008;358:2667-77

Rhythm Control vs. Rate Control for AF in CHF Conclusions: A rhythm-control strategy does not improve outcomes compared to a ratecontrol strategy in pts with AF & CHF A rate-control strategy reduces the need for DCCV & hospitalization and should be the primary approach for pts with AF & CHF Roy et al. NEJM 2008;358:2667-77

WAIT A MINUTE! Many ypts in rhythm control arm had AF Some pts in rate control arm had no AF Benefits of NSR may have been negated by harmful effects of AADs End-points of LVEF, LVIDd & functional capacity not examined

Maintenance of sinus rhythm with antiarrhythmic drug therapy (AARx) is associated with an improvement in survival and morbidity. CHF-STAT Kaplan-Meier analysis of survival curves in heart failure patients with AF who converted (n=16) and did not convert (n=35) to sinus rhythm on treatment with amiodarone SR AF Deedwania, P. C. et al. Circulation 1998;98:2574-2579

Catheter Ablation for Atrial Fibrillation in CHF Hsu et al, NEJM 2004 58 patients with CHF & LVEF <45% 58 age matched controls with no CHF Persistent/permanent AF in 91% 78% had NSR at 1 year after RF ablation (69% in NSR off Antiarrhythmic Rx) NSR associated with improved LVEF and dimensions, symptoms score, exercise capacity, & QOL

Baseline Characteristics of the Patients with and without Congestive Heart Failure CHF No CHF Hsu et al. NEJM 2004

Improvement after Ablation in Patients with Congestive Heart Failure LV EF LV FS 21±13% 11±7% LV EDD 6±6mm LV ESD 8±7mm Hsu et al. NEJM 2004

Benefit of RFA of AF With & Without Adequate Rate Contol Pre-RFA among Patients with Congestive Heart Failure Inadequate Rate Control Adequate Rate Control Hsu et al. NEJM 2004

RFCA of AF in CHF: Effect on LVEF 81 pts with AF, CHF, EF 40% Randomized: PV isolation ± ablation lines, CFAE ablation AV node ablation + BiV ICD Followed for 6 months after last procedure w/ weekly event monitor transmissions Endpoints: EF, 6-min walk test, QoL Khan MN, et al. N Engl J Med. 2008;359:1778-1785.

CASE: FC 1. Rhythm control strategy 2. Rate control strategy 3. Rhythm control strategy + ICD 4. Rate-control strategy + ICD

CASE: FC Trial of amiodarone (6 wks) and DCCV Recurrence after 1 week NSR Reported significant ifi improvement in CHF Sx Now what? ICD? RFA?

CASE: FC D/C amiodarone NSR 3 mo f/u NYHA Class I Echo LVEF 50% 6 mo event monitor no AF Continued on wafarin

SVT after AFib RFA:

Atypical Atrial Tachycardias/Flutters Following RFA P-AFib Complicates 10-30% ablations PAF Macroreentrant, microreentrant, or focal Difficult to manage medically, require repeat ablation Micro-re-entryentry (14%) FAT (12%) Macro-re-entryentry (75%)

Future Goals in Catheter Ablation Therapy Improve efficacy (single procedure) Shorter procedure times Improved safety Widespread availability

Technology The Great Equalizer Current ablation technologies require a high level of technical skill:

Emerging g Ablation Technologies: Remote Navigation: Niobe (Stereotaxis) Sensei-X (Hansen Medical)

Emerging g Ablation Technologies: Balloon Catheters HIFU Laser Cryothermy

Emerging Ablation Technologies: Multipolar Ablation Catheters: High-density Mesh Ablation:

Summary Afib is a challenging arrhythmia to manage for the PCP, cardiologist and electrophysiologist Ablation is a realizable cure for many patients, but the process is a journey, not just a procedure The ablation journey is bumpy, with need for more than one procedure & post-ablation, proarrhythmia particularly difficult stumbling blocks Challenge of AFib best met by alliance of care with EP and referring practitioner

Thank You!

Eric D. Good, DO D.O.,., FACOI F.A.C.O.I Assistant Professor, Interventional Cardiac Electrophysiology Department of Internal Medicine Division of Cardiovascular Medicine University of Michigan Contact t information: Office: 734-936-6858 Fax: 734-936-7026 Email: dogood@umich.edu