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Atrial Fibrillation The Last Big Hurdle in Treating SVT

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Presentation on theme: "Atrial Fibrillation The Last Big Hurdle in Treating SVT"— Presentation transcript:

1 Atrial Fibrillation The Last Big Hurdle in Treating SVT
Esam Baryun, MD, FACC, FHRS

2 Ever Felt Like This?

3 AF: an age related condition
Go et al JAMA 2001;285:

4 AF: a growing problem Doubling of patients with AF from 1995 to 2030
Reasons for epidemic: Aging population, Improved longevity from CAD, Improved detection, Rising obesity rate Doubling of patients with AF from 1995 to 2030 Go et al JAMA 2001;285:

5 Risk Factors Clinical: Subclinical:
Non-modifiable: Age, Sex, Ethnicity, Genetic Modifiable: Htn, DM, CAD, Obesity, OSA, Tob Subclinical: LVH, Systolic/Diastolic dysfunction, LA size/function BNP, CRP

6 Obesity and AF Risk Adjusted HR 1.5 with obesity, attributable to increased LA size Wang et al, JAMA 2004; 292:2471

7 Causes of AF Anything that damages or stretches the atria: Htn, Aging
Obstructive Sleep Apnea, Pulm Dz Ischemia, CHF, Myocarditis, Valvular Dz (MS, MR), CABG Thyrotoxicosis, Ethanol (Holiday Heart) Obesity BMI>30 Accessory Pathway Genetics

8 Classifications of AF 1. Paroxysmal: “self terminating” 2. Persistent
Episodes of AF <7days. 2. Persistent Episodes of AF >7days 3. Permanent Rhythm control failed 4. “Lone” Describes any of the classifications above that occur in individuals without structural cardiac or pulmonary disease.

Once AF begins, there are multiple adverse outcomes and therefore prevention is imperative. There are currently several potentially modifiable risk factors for AF that may provide strategies for population based interventions.

10 AF begets AF Electrical Remodeling: Reversible
Tachy  Cellular Ca load Decrease ARP and WCL Triggered Activity Structural Remodeling: Not reversible Fibrous tissue deposition  Local conduction abnormality Reentry This is sufficient for AF maintenance Preventable but not reversible Irreversibility may necessitate early intervention AF is a moving target: if SR maintenance is the intention, earlier intervention may be particularly effective and important.

11 The longer we wait to control rhythm the harder it is to regain SR
Pts Converted to SR in 3 Mo of Onset Are More Likely to Remain in SR Dittrich HC et al. Am J Cardiol. 1989;63: 82% 67% Patients in sinus rhythm (%) 36% 27% 1 month P<.02 6 months P<.07 The longer we wait to control rhythm the harder it is to regain SR

12 AF causes Histologic Remodeling of Atria as Early as 4 Months
Sinus Rhythm AF Enlarged atrial cells Severe myolysis Glycogen accumulation Reduction in Connexin 40 expression

13 Gap Junctions In heart cells the signal to contract is passed efficiently through gap junctions

14 Stroke and AF Framingham data: 4-5 fold increased risk
Risk may be higher if silent multi-infarction cognitive impairment included Chronic AF and paroxysmal AF carry same risk Stroke associated with AF: more severe with higher mortality Coumadin only prevents 65% of strokes.

15 Prevention of AF AF Genetics (Chromosome 4q25)
Predictors (Who is at higher risk?) Sex, Age, BMI, Syst BP, PR interval, Murmur LA size, LV wall thickness Risk Prediction Models may help identify patients for primary prevention.

16 AF Genetics Wolff described three brothers with AF in 1943.
Increasing evidence of a heritable component of lone AF. Presence of AF in 1st degree relatives was associated with an increased risk of developing AF. Positive F/H of AF in 1/3 of pts with lone AF indicating that familial AF is more common than previously recognized.

17 Having at least 1 affected parent approximately doubled the risk of predicted AF Fox…Benjamin JAMA 2004;291:2851

18 Therapeutic Options

19 Management Medical therapy Ablation Rate control: AVN blockers
Rhythm control: Anti-arrhythmics CVA prevention: Warfarin New antithrombotics LAA occlusion vs resection. PROTECT-AF (Watchman) Ablation Catheter Ablation: AF ablation: PVAI, Substrate modification AVN ablation and PPM Surgical Ablation

20 Other Anticoagulants Xa inhibitor Direct Thrombin Inhibitors: Apixaban
ARISTOTLE: Apixaban vs Warfarin AVERROES: Apixaban vs ASA in pts who can’t take coumadin Rivaroxaban – RECORD (Canada, Europe 9/08) Direct Thrombin Inhibitors: Dabigatran – PETRO phase III, RE-LY Study Very few drug-drug interaction (PPIs). No antidote. 110mg same CVA but less hge 150mg less CVA but same hge Ximelagatran – SPORTIF – as good as Warfarin but not FDA approved due to Liver Toxicities Ideal: no drug interactions, no monitoring levels, and has an antidote.

21 Dabigatran Direct Thrombin Inhibitor
Approved by the FDA in October 19, 2010 for prevention of CVA in AF Dose: 150 mg twice daily If severe renal impairment (CrCl 15-30): 75 mg twice daily (dose Not studied in RELY!!) No specific antidote. Due to its short duration of effect drug discontinuation is usually sufficient to reverse any excessive anticoagulant activity. In life-threatening bleeding: recombinant activated factor VII and prothrombin complex concentrates can be considered.

22 Anti-arrhythmic Choice

23 New Antiarrhythmic Drugs
Dronedarone Similar to Amiodarone but less lipophilic, no iodine, & half life 24hr. No significant organ toxicities Ranolazine (Na channel blocker) Alters the trans-cellular late Na current, indirectly prevents the Ca overload, inhibits triggered activity Approved as anti-anginal. Vernakalant (K channel blocker) Atria selective Accepted for review by the FDA The ideal anti-arrhythmic is atria selective.

24 Rate Control vs Rhythm Control
AFFIRM (AF f/u Investigation of Rhythm Management) , NEJM 2002 RACE (Rate Control vs. cardioversion for persistent AF) – NEJM 2002 PIAF (Pharmacologic Intervention in Atrial Fibrillation) – Lancet 2000 STAF (Strategies of Treatment of Atrial Fibrillation) – JACC 2003 HOT CAFÉ ( How to Treat Chronic Atrial Fibrillation) – Chest 2004

25 Rate Control vs Rhythm Control
Favor attempts to maintain SR: First or infrequent episodes of persistent AF Young active patient Significant symptoms Difficult rate control Contraindication to long term warfarin Favor rate control: Asymptomatic sedentary elderly patient Contraindication to anti-arrhythmics or ablation

26 AFFIRM TRIAL 4060 patients Persistent AF Age >65, Mean 70 Other risk factors for stroke Patients with contraindications for anticoagulant therapy were excluded Primary endpoint: all-cause mortality. Mean 3.5 years follow up. For rhythm control group anticoagulant encouraged but could be discontinued

27 AFFIRM TRIAL No difference in mortality Similar incidence
of stroke: 1% per year in each group Most strokes occurred in pts off warfarin or subtherapeutic INR AFFIRM Investigators NEJM 2002;347:

Optimal management for: Pts with mod-severe disabling AF symptoms Younger pts with paroxysmal AF Outcome if better tools to maintain sinus rhythm were available Long-term implications of rate vs rhythm control (mean duration of follow-up only 3.5 years)

29 What DOES AFFIRM tell us?
Do not stop coumadin in rhythm control pts. Elderly pts with asymptomatic persistent AF are less likely to benefit from antiarrhythmics. Unfortunately we don’t have good antiarrhythmic agents.

30 Limitations of the AFFIRM Study
May not be applicable to all pts with AF. Results cannot be generalized to : Younger patients Pts without other RF for stroke Paroxysmal AF Pts with severe symptoms might have been considered unsuitable for a rate control strategy and may not have been enrolled (Selection Bias). In the rhythm control group, continuous anticoagulation was encouraged but could be stopped at the physician’s discretion if SR had been maintained for at least 4-12 weeks Most strokes occurred in pts in whom warfarin was stopped or were sub-therapeutic Average follow-up was only 3.5 years and treatment of AF is a life-long process A large proportion of pts in the rate control arm remained in SR. Does not reflect typical outcome in pts with AF treated with rate control.

31 Rhythm Control In theory converting someone to NSR should:
Improve cardiac hemodynamics Prevent LV dysfunction Maintain proper cardiac output Reduce risk of thromboembolism -> reduce risk of death

32 AF Adversely Affects Qaulity of Life Dorian P et al. J Am Coll Cardiol

33 Clinical Trials Showed the Survival Advantage of Sinus Rhythm
STAF: The Strategies for Treatment of AF study SR maintained in 30% of rhythm control patients Mortality: 2.5% per year in the rhythm control group 4.9% per year in rate control group Result was NOT statistically significant Framingham Heart Study cohort CHF-STAT SOLVD DIAMOND 

34 AF increases mortality
Framingham Heart Study cohort : Follow-up of the original AF was associated with a 1.5- to 1.9-fold mortality risk after adjustment for preexisting cardiovascular conditions SOLVD: Studies of LV Dysfunction Prevention and Treatment Trial– retrospective analysis Evaluated whether AF in pts with low EF was associated with higher mortality. AF pts had greater: All-cause mortality (34% vs 23%, P < 0.001)

35 SR Decreases Mortality
DIAMOND: The Danish Investigations of Arrhythmia and Mortality ON Dofetilide study  3028 pts with severe CHF or recent MI Presence of SR was associated with a significant reduction in mortality (RR 0.44, 95% CI, , P < ) CHF-STAT : The CHF Survival Trial of Antiarrhythmic Therapy AF pts who converted to SR (n=16) had a lower mortality rate (P = 0.04) than those who did not (n=35) AFFIRM Study Post Hoc Analyses: SR is a Predictor of Survival SR was associated with a lower risk of death (47% reduction) Anticoagulant use associated with a decreased risk of death (50% reduction)

36 Sustaining Sinus Rhythm Is Associated With Decreased Mortality
Reduction in mortality (%) AFFIRM DIAMOND The AFFIRM Investigators. Circulation. 2004;109: ;Circulation. 2001;104: ; Lancet. 2006;367:

Predictors of Mortality in AFFIRM Epstein et al, Circulation 2004; 109:1509

38 CABANA Trial Ablation Vs Anti-Arrhythmic Drug Therapy for AF
Designed to test the hypothesis that the treatment strategy of Afib ablation will be superior to current therapy with either rate control or rhythm control drugs for reducing total mortality. 3000 Pts randomized to Ablation or Pharmacologic Therapy CABANA Trial will disclose: The role of medical and non-pharmacologic therapies for AF Establish the cost and impact of therapy on quality of life Determine if AF is a modifiable risk factor for increased mortality.

39 AVN ablation and Pacemaker Implantation
Advantages: adequate rate control without drugs regularizes ventricular rate Disadvantages requires permanent pacemaker fibrillation continues: anticoagulation needed risk of torsade de pointes early after sudden rate decrease risk of hemodynamic deterioration from RV pacing GN Kay et al Ablate and Pace J Intervent Card Electrophy 1998 Brignole et al Circulation Geelen P, et al. VF and sudden death after AVJ ablation. PACE 1997;20:343–8. Jordaens L, et al. Sudden death and long term survival . Eur J Card EP 1993;21:102–9. Gasparini M, et al. Long-term follow-up after AV ablation…PACE 2000;23:1925–9. Ozcan C, et al. Long-term survival. NEJM 2001;344: 1043–51.

40 A New Idea Came Along Haissguerre et al. NEJM1998;339:659-66

41 Mechanistic Approach to AF Ablation- Some Simplifications
AF is predominantly driven by the LA. AF is predominantly driven by 2 mechanisms: I. Focal Rapid Firing from the PVs (Paroxysmal AF). II. Multiple Reentry Circuits around anatomical obstacles (Chronic AFIB).

42 Ectopic Foci Haissguerre et al. NEJM1998;339:659-66
Chen Circ1999;100:

43 AF ablation

44 Pulmonary Vein Antral Isolation

45 Pulmonary Vein Isolation
Electrophysiological Breakthroughs From the Left Atrium to the Pulmonary Veins Michel Haïssaguerre, MD; Dipen C. Shah, MD; Pierre Jaïs, MD; Mélèze Hocini, MD; Teiichi Yamane, MD; Isabel Deisenhofer, MD; Michel Chauvin, MD; Stéphane Garrigue, MD; Jacques Clémenty, MD Going… Going… Gone ! Haïssaguerre, M. et al., Circulation. 2000;102:2463–2465.


47 Lt Inferior Pulmonary Vein

48 Side-by-Side Geometry Electroanatomic Map & 3-D CT: Cranial View
Esophagus Left PVs Right PVs LA Roof LAA ESI Nav-X 3-D Geometry 3-D CT via CardEP (Cranial View)

49 AF ablation How is procedure performed?
Out pt, 3-5hr, moderate-heavy sedation Discharged home next am Coumadin mandatory 6-8 weeks after Four vein sheaths: 2 RFV (Lasso, Ablation) LFV (ICE) RIJ (Duo-deca)

50 Visualization: Intracardiac Ultrasound
Facilitate trans-septal access to LA Visual guidance of catheters at PV ostium Direct visualization of: PV ostial size Anatomic abnormalities Pericardial effusion Thrombus Facilitate safe and rapid transeptal LA access Visual guidance for placement of diagnostic loop catheter at PV ostium Optimization of RF energy delivery via “bubble” monitoring Doppler flow assessment of PV flow to assess for stenosis Visualization of PV ostial size, anatomic abnormalities, pericardial effusion, thrombus

51 Left Atrial Mapping and Catheter Ablation Visualization: Intracardiac Ultrasound
Tenting of the intra-atrial septum during transeptal catheterization An 8 Fr model also was announced in June 2004 (?release date?) Transeptal Access to LA AcuNav 10 Fr Phased Array Diagnostic Ultrasound Catheter (by Acuson)

52 Left Atrial Mapping and Catheter Ablation Visualization : Intracardiac Ultrasound
Optimizing Catheter Placement at PV Os Intracardiac echo facilitates PV isolation by: 1. Rendering transseptal access easier and safer. 2. Helping in proper placement of the circular mapping catheter at the vein ostium. 3. Optimizing power titration during radiofrequency energy delivery through detection of bubbles at the catheter-tissue interface. Prompt detection of dense bubbles (type 2 bubbles) could also prevent impedance rise and avoid the milieu for thrombus formation. In addition, monitoring PV flow velocity offers the potential to prevent excessive swelling at the PV ostium, which could lead to chronic PV stenosis. In this respect, ablation at the PV ostium should be aborted when the PV diastolic flow velocity exceeds 1 m/s.

53 Trans-septal Puncture with LA entry

54 Intracardiac Echo Tenting of Interatrial septum
Esophagus posterior to LA

55 Lasso on Lt Inf PV

56 Lasso on Lt Sup PV


58 So why ablate? Our best drugs are: Only moderately effective (30-50%)
Have side effects/toxicities Many patients despite adequate rate control remain symptomatic in AF Sustaining SR may be associated with decreased mortality

59 AF ablation Pappone, JACC, 2003

60 Risks vs Benefits Potential benefits Potential harm
Symptomatic benefit No need for AADs Thromboembolic benefit Mortality benefit? Potential harm Stroke LA flutters Tamponade TE fistula PV stenosis

61 Post Ablation Care Early AF recurrence (not uncommon)
20-50% of patients More than half will resolve within 3 mos Antiarrhythmic drugs usually continued for first 2-6 months Atrial tachycardias post ablation Anticoagulation High risk of CVA in first month post RFA Redo procedures in 20% of pts (after 3 mo)

62 AF case 1 67y old female, school teacher
Recurrent symptomatic AF with RVR Admitted to hospital several times, twice in 10/08 Tachypalpitations several times a week Failed amiodarone and sotalol AFib RFA 11/08 Post RFA: One AF episode 2 days after ablation (blanking period) No tachypalpitations since then A 2 wk MCOT 2 & 6 months later shows no AF Off amiodarone and coumadin

63 MCOT 2mo after ablatioin

64 AF case 2 Middle age female, Nurse
Paroxysmal AF with RVR, once/1-2months Failed anti-arrhythmics A fib ablation in 12/08 Follow up: No episodes since ablation MCOT 2/16-2/24 showed 0% AF Tikosyn was stopped four months after ablation

65 Case 3 50y old female Frequent tachypalpitations, with significant symptoms Propafenone helped a little Dose increased but still significantly symptomatic Palpitations occur if one dose is delayed 2hr Max dose of AA caused metallic taste

66 Baseline MCOT

67 Higher dose only decreased episodes
Propafenone 225mg Propafenone 150mg

68 A fib ablation 3/09 Follow up:
No more palpitations immediately after ablation 2 month: No palpitations even when misses AA dose Feels great and more energetic 3 months: Propafenone was discontinued three months after ablation Repeat MCOT showed no AF

69 Case 4 51y old man with symptomatic persistent AF
On amiodarone for >6 mo Amiodarone stopped given his age, and 2 mo later started on tikosyn AF ablation 3/09

70 MCOT 2 months post RFA

71 Remains AF free 5 months after

72 Case 5 66y old female Persistent symptomatic AF for >1 year
Failed multiple AA therapy Success rate with ablation less than paroxysmal AF

73 AF Ablation on 5.28.09 AF burden decreased gradually weeks after PVAI

74 Case 6 60 y old man with persistent AF. Amiodarone started 7. 28. 09
Case 6 60 y old man with persistent AF. Amiodarone started DC CV AF ablation

75 Case 7 65y old man failed two anti-arrhythmics AF ablation in 5.09

76 MCOT 4 months later Propafenone was discontinued

77 Conclusion These advances may yet tip the balance back in favor of a rhythm control strategy. RFA of the PVs has been successful in long-term maintenance of SR, representing a curative strategy that eliminated the need for pharmacotherapy for AF in drug-refractory patients.


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