1. Atrial Fibrillation: New Ways to Treat an Old Rhythm
Critical Care Nurses Fall Symposium, November 7, 2014
Kristopher Krueger, MD, PhD
Cardiac Electrophysiology
Park Nicollet Heart and Vascular Center

2. Atrial Fibrillation: New Ways to Treat an Old Rhythm
Disclosures: None

3. Objectives *: “New Treatments” Scope of atrial fibrillation problem?
General information.
Negative effects?
Stroke Risk Reduction.
Oral anticoagulation*.
Device options*.
Rate vs. Rhythm Control.
Rate Control*.
Rhythm Control.
Cardioversion.
Medications*.
Ablation*.
Practical Management.
*: “New Treatments”

4. Epidemiology and Prognosis
Most common sustained arrhythmia
2.2 million in US
Last 20 years, 66% increase in admissions for a-fib
0.4-1% prevalence (up to 8% in those older than 80)
Incidence:
0.1% per year <40 y/o
1.5-2% per year >80 y/o
Prognosis:
Increased risk of stroke (5-fold).
Increased risk of heart failure (3-fold).
Double mortality rate.
Diminished quality of life.
Possible increased risk of dementia.

5. Dementia Risk AF indepenently associated with all forms of dementia
37025 consecutive patients from large database followed prospectively.
10161 (27%) developed AF
1535 (4.1%) developed dementia
5 years follow-up.
Mean age 60.6±17.9 years

6. Dementia Risk cont. AF independently associated with all dementia.
Highest risk of AD was in younger AF group
Dementia patients had higher rates of HTN, CAD, CRI, heart failure and strokes.
After dementia Dx, presence of AF = higher mortality (HR= )
Bunch et al., Heart Rhythm, 2010, 7: 433.

7. Stroke Risk Reduction

8. Oral Anticoagulation Aspirin. Clopidogrel. Coumadin.
Novel Oral Anticoagulants.
Dabigatran (Pradaxa).
Rivaroxaban (Xarelto).
Apixaban (Eliquis).

9. Procedure/Device Therapy for Stroke Risk Reduction.
Surgical LAA amputation.
Watchman LAA occlude.
Amplatzer Cardiac Plug.
Lariat LAA amputation.

10. Lariat LAA Ligation

11. LAA Occlusion: Amplatzer Cardiac Plug
Jain AK, Gallagher S. Percutaneous occlusion of the left atrial appendage in non-valvular atrial fibrillation for the prevention of thromboembolism: NICE guidance. Heart 2011; 97:762.

12. LAA Occlusion: Watchman
Jain AK, Gallagher S. Technology and guidelines Percutaneous occlusion of the left atrial appendage in non-valvular atrial fibrillation for the prevention of thromboembolism: NICE guidance. Heart 2011; 97:762.

13. LAA Occlusion/Amputation.
Surgical LAA Amputation (Garcia-Fernandez et al., Role of left atrial appendage obliteration in stroke reduction in patients with mitral valve prosthesis: a transesophageal echocardiographic study, JACC, 2003, 42: 1253)
205 patient’s studied retrospectively after mitral valve replacement + LAA amputation.
Stroke after 6 years was 3% (vs. 17% for those without LAA amputation.
For the most part, standard of care at time of mitral valve surgery in patient with h/o atrial fibrillation.
Limited data on stand-alone surgery.

14. LAA Occlusion/Amputation.
Watchman: Protect AF trial
Non-inferiority, 700 patients randomized 2:1.
CHADS score of 1 or greater.
Primary efficacy and primary safety endpoints.
Concerns about safety. Not yet FDA approved.
Amplatzer Cardiac Plug
Lariat LAA amputation: some safety data, limited efficacy data.

15. Rate and Rhythm Control

16. What should be driver for deciding between rhythm control and rate control strategy?
Desire to avoid anticoagulation.
Alter long-term prognosis of atrial fibrillation.
Control of symptoms related to atrial fibrillation.
All of the above.

17. What should be main driver for deciding between rhythm control and rate control strategy?
Desire to avoid anticoagulation.
Alter long-term prognosis of atrial fibrillation.
Control of symptoms related to atrial fibrillation.
All of the above.
-no good data that rhythm control strategies prevent stroke: very common to have asymptomatic “silent” episodes of atrial fibrillation.

18. AFFIRM: Randomized, prospective 4060 patients.
Rate control (≤80, ≤110 bpm)
Rhythm control
Age: 69.7±9.9
1° endpoint: overall mortality
Mean f/u 3.5 years
Rhythm control associated with more ADRxs, hospitalizations.
Young patients:
-650 pts (16%) <60 y/o
-101 (2.5%) <50 y/o

19. Other Rate vs. Rhythm Trials
RACE (Hagens et al., JACC, 2004, 43: 241)
522 patients, 68±9, no difference in composite 1° endpoint.
PIAF (Hohnloser et al, Lancet, 2000, 356: 1789)
252 patients, 61±10, no difference in symptoms.
STAF (Carlsson et al., JACC, 2003, 41: 1690)
200 patients, 66±8, no difference in composite 1° endpoint.
HOT CAFÉ (Opolski et al., Chest, 2004, 126: 476)
205 patients, 61±11, no difference in composite 1° endpoint.
Study names: AFFIRM: Atrial fibrillation follow-up investigation of rhythm management.
RACE: Rate control versus electrical cardioversion for persistent atrial fibrillation.
PIAF: Pharmacological intervention in atrial fibrillation.
STAF: Strategies of treatment of atrial fibrillation.
HOT CAFÉ: How to treat chronic atrial fibrillation.
Primary Endpoints:
AFFIRM: all-cause mortality.
RACE composite endpoint: CV death, CHF, severe bleeding, PM implantation, thromboembolic events, severe adverse drug effects of antiarrhythmic drugs.
PIAF: symptomatic improvement.
STAF: composite endpoint: overall mortality, cerebrovascular complications, CPR, embolic events.
HOT CAFÉ: composite endpoint: death, thromboembolic complications, intracranial or other major hemorrhage.
Patients in NSR in Rhythm control: %

20. AF and CHF: 1376 pts (682 vs. 694) 67±1 years old (34 pts <65 y/o)
EF ≤35%
CHF symptoms
h/o atrial fibrillation
67±1 years old (34 pts <65 y/o)
1° outcome: time to CV death.
2° outcomes similar
All cause death
Stroke
Worsening CHF
Number of patients:
-682 in rhythm control.
-694 in rate control

21. Exceptions to Rate vs. Rhythm Studies?
Symptoms, Symptoms, Symptoms
Patient preference.
Patient expectation.
Atrial fibrillation contributing/in-setting of other process
CHF especially tachycardia-mediated cardimyopathy.
COPD, pneumonia.
Younger age?
Average age of previous studies was
What is appropriate strategy in younger (<50-60) patients?
Patients with difficult to control heart rates.
Future studies to determine any additional benefits of ablation.
-Patient preference is probably most important decision making factor.
Exclusion criteria CHF: decompensated heart failure within 48 hours before intended randomization

22. Other Driver for Determination of Strategy?
Vignette #1
54 y/o male with a-fib diagnosed after presentation for mild palpitations.
Initially felt no other new symptoms.
Now is pre-occupied with a-fib, can’t stop thinking about it.
Vignette #2
74 y/o male with new a-fib.
DOE, palpitations, exertional intolerance.
Patient Choice

23. Quick clinical case 62 y/o male with atrial fibrillation and no Sx.
CHADSVASC of 0.
Recent cardioversion failure x3.
1st w/o AAD.
2nd on 50 mg bid flecainide.
3rd on 100 mg bid flecainide.
What is next most appropriate management strategy?
1. Accepting a-fib, rate control strategy.
2. EP study and ablation for PVI.
3. Repeat trial of cardioversion on amiodarone.
4. Repeat trial of cardioversion on non-amio AAD.

24. Rate Control

25. Rate Control Beta-blockers:
Metoprolol generally preferred.
Don’t like atenolol in older patients with CRI
Carvedilol preferred in LV dysfunction.
Calcium channel blockers (diltiazem, verapamil):
Should not be used with LV dysfunction.
Less of an issue with sinus rate slowing.
Digoxin: I do not generally use.

26. HR Target? Lenient vs. Strict Rate Control. 614 patients
Lenient: resting HR <110 bpm.
Strict: resting HR <80 bpm, moderate exercise: <110 bpm.
Primary outcome: composite of CV deaths, CHF hospitalization, stroke or SE, bleeding and life threatening arrhythmias.
2-3 year follow-up.

27. Lenient vs. Strict Rate Control
P<0.001 for pre-specified non-inferiority margin.
More patient’s to target in lenient group.
97.7% vs. 67%
Fewer total visits
75 vs. 684.
Similar frequency of Sx and Aes
Exceptions?

28. Rhythm Control

29. Rhythm Control Cardioversion. Medications (Anti-arrhythmics).
Quick, easy.
Infrequent cardioversion acceptable as sole rhythm control.
Medications (Anti-arrhythmics).
Numerous, can feel like “spinning” your wheels.
Class IIa recommendation: “Infrequent, well-tolerated recurrence of AF is reasonable as a successful outcome of antiarrhythmic drug therapy.”
Ablation.

30. Practice GuidelinesCollege of Cardiology Foundation/American Heart Association Task Force on Atrial Fibrillation (Updating the 2006 Guideline) : A Report of the American 2011 ACCF/AHA/HRS Focused Update on the Management of Patients With
2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline) : A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.

31. Ablation Strategies for Atrial Fibrillation

32. Rationale For A-fib Ablation: PVI

33. What is success rate of ablation for atrial fibrillation (PVI)?
50%
65%
75%
Who knows/Need more information.

34. What is success rate of ablation for atrial fibrillation (PVI)?
50%  most AADs
65%  amiodarone
75%
Who knows/Need more information.
Answer depends on a lot of factors:
-which study you read/quote.
-definition of success.
-follow-up during study

35. Ablation vs. AADs Meta-analysis 6 studies. Prospective studies.
Mainly paroxysmal/persiste nt.
693 total patients.
65% RRR of a-fib with ablation
Nair et al., JCE, 2009, 20: 138.

36. Ablation Success/Risks
Questionnaire study (Cappato et al., Circ Arrhyth Elect, 2010, 3(1): 32.
Worldwide survey (521 centers)
Results: ablations (16309 patients, )
Mean f/u: 18 months (3-24 months)
10488 asymptomatic w/o AADs
2047 asymptomatic w/ AADs
Conclusions:
Effective in 80% of patients after 1.3 procedures/pt
Effective w/o AAD in 70%
Major complications: 4.5%

37. Atrial Fibrillation Ablation
In general, ablation has better success rates.
Ongoing trials.
Technology/strategies continue to evolve.
Appropriate candidates for ablation:
Significant symptoms to warrant rhythm control.
Failure/intolerance of anti-arrhythmics.
Desire to not take anti-arrhythmics.
Ongoing Trials:
-CABANA
-Better determine success rate.
-Determine other benefits to ablation.

38. Guidelines: 2011 ACCF/AHA/HRS Focused Update on the Management of A-fib (Update of 2006 Guidelines)
Class I: Catheter ablation performed in experienced centers (>50/year) is useful in maintaining sinus rhythm in selected patient with significantly symptomatic, paroxysmal AF who have failed treatment with an AAD and have normal-mildly dilated LA, normal-mildly reduced LV function and no severe pulmonary disease.

39. Guidelines: 2011 ACCF/AHA/HRS Focused Update on the Management of A-fib (Update of 2006 Guidelines)
Class IIa: Catheter ablation is resonable to treat symptomatic persistent AF.
Class Iib: Catheter ablation may be reasonable to treat symptomatic paroxysmal AF in patients with significant left atrial dilation or with significant LV dysfunction.

40. Future of Rhythm Control
Do results of Affirm and other rate vs. rhythm control studies apply to atrial fibrillation ablation?
On-treatment analysis of Affirm.
Independent studies looking at benefits of a-fib ablation.
Ongoing and future trials of a-fib ablation: CABANA

41. Exceptions to Trials On-treatment analysis of AFFIRM
SR and warfarin use associated with lower risk of death.
AADs use associated with increased mortality
AADs no longer associated with mortality after adjustment for SR
Corley et al., Circulation, 2004, 109:

42. Effects of A-fib Ablation on Risk of Stroke and Death
International multicentre registry
7 countries in UK and Australia.
Consecutive patients undergoing catheter ablation of AF.
1273 pts, 58±11 years
Long-term outcomes compared to:
Cohort with AF treated medically in Euro Heart Survey.
Hypothetical cohort without AF but age and gender.
Analysis after 1st procedure regardless of success, intention-to-treat basis.

43. Effects of A-fib Ablation on Risk of Stroke and Death
Success rates:
Paroxysmal: 85% (76% off AAD).
Persistent: 72% (60% off AAD).
Lower rates of stroke and death in cohort compared to medical treatment.
Rates of events no different compared to general population.
Hunter et al., Heart, 2012; 98: 48.

44. Practical Management

45. Triage: 1st presentation.
Admit/ER evaluation vs. outpatient management.
Unstable patient?—think of other cause! PE
CHF
ACS, etc.
Heart rate unacceptably high?
What is cut-off for “too high”?
Generally make decision based on symptoms.
-”Unstable” patient/symptoms:
-unacceptable heart rate

46. Outpatient Management
Decision on OAC.
Long-term management: CHADSVASC score vs. Risks of OAC.
If above risk is low, plan for rhythm control in future?
Routine tests:
Echo, TSH, CBC, chemistry panel.
Need evaluation for OSA.
Are other symptoms present requiring further work-up.
Rate vs. Rhythm control.
I always offer a trial of rhythm control.
Referral?

47. Thank You.