Atrial Fibrillation: What s Old, What s New, What s Tried and True

Transcription

1 Atrial Fibrillation: What s Old, What s New, What s Tried and True

2 No Conflict of Interest

3 Daria C. Ruffolo

4 Risk Factors

5

6 Case Vignette A 75 year old woman with PMHx of HTN, HLD and DM, CKD presents to ED for new onset dizziness, shortness of breath and palpitations that began 3 hours ago while patient was gardening in her lawn. She denies any associated chest pain and no loss of consciousness. Vital Signs: T: 37.5 C, BP 90s/60s (Baseline BP 115/80s), HR 140s-160s bpm and RR 24. A&O x3 with some facial grimmace. Cardiac exam is irregulary irregular without murmurs. Lungs CTAB. Remainder of exam unremarkable. She received a 2L bolus in the ED without increase in blood pressure

7 Differential Diagnosis Atrial Fibrillation Multifocal atrial tachycardia Supraventricular tachycardia Pulmonary Embolism Thyrotoxicosis

8 Elderly patient Palpitation Fatigue/weakness Long term hypertension Tachycardia Irregularly irregular rhythm EKG: atrial fibrillation waves, inconsistent R-R intervals, absence P waves. ATRIAL FIBRILLATION

9 Diagnostic Plan EKG Thyroid Function tests Cardiac enzymes Echocardiogram Within Normal limits Normal Normal Ejection fraction, left atrial enlargement ABGa Within Normal limits

10 EKG

11 Incidence Jongnaransin K, et al Cardiovasc Electro physiol, 2012; 23: 9-14

12 AF is a Progressive Disease

13 Subtypes of AF Paroxysmal:recurrent AF ( 2 episodes), that terminates spontaneously within 7days. Persistent: AF sustains >7 days, or lasts less than 7 days but necessitates pharmacologic or electrical cardioversion. Longstanding persistent: AF sustaining greater than 12 months. Permanent AF: Joint decision has been made by the patient and clinician to cease further attempts to restore and/or maintain sinus rhythm.

14 Highlights Prevalence and incidence of AF Risk stratification for stroke and bleeding New oral anticoagulants Guidelines Practical considerations for choosing an anticoagulant

15 Question #1 An 82 year old man is in your office for an annual Medicare physical. What is the chance he has atrial fibrillation? 1. 1% 2. 5% 3. 10% 4. 25%

16 Prevalence of Diagnosed AF Stratified by Age and Sex Women Men < > 85 x-axis = % y-axis = # of men/wo men # Women # Men Go AS, JAMA May 9;285(18): Pub Med PMID:

17 Question #1 An 82 year old man is in your office for an annual Medicare physical. What is the chance he has atrial fibrillation? 1. 1% 2. 5% 3. 10% 4. 25%

18 Noninvasive Approach January, et al AHA/ACC/HRS Guidelines for Management of Patients with Atrial Fibrillation JACC 2014

19 Indications for Urgent Direct Cardioversion Hemodynamic Instability: Patient with decompensated heart failure Active ischemia: if symptomatic with angina or evidence of ischemia/infarction on EKG Evidence of organ hypoperfusion (altered mental status, cold clammy skin, acute kidney injury)

20 Urgent Cardioversion Electrical Cardioversion: sedate patient and place setting on direct synchronization then shock Initial shock setting of 100J 200J 300J 360J until sinus rhythm returns Make sure you perform direct cardioversion with R wave synchronization to prevent an R on T phenomenon which can lead to V fib Restoration of normal sinus rhythm takes precedence over need for protection from thromboembolic risk Would recommend cardiology consult at this time

21 Question #2 What is the next appropriate management for this patient? 1. IV diltiazem 2. Intubation 3. Urgent Cardioversion 4. IV pain control 5. CT pulmonary angiogram

22 If Patient is Hemodynamically Stable Goal is ventricular rate control (<100 bpm) and anticoagulation Resting HR goal should be bpm in symptomatic patient Roughly 50% of patients with new onset AF will spontaneously convert to NSR spontaneously within 48 hours of onset Rate control or Rhythm control? AFFIRM trial and RACE trial No survival advantage in terms of stroke prevention rhythm control over rate control rate control Rate control agents Calcium Channel Blockers Beta blockers (caution in patients with reactive airway disease) Digoxin Amiodarone (for patients intolerant or unresponsive to other agents)

23 Point of Management

24 Rate Control Agents Drug Classes Drug Loading Dose Maintenance Dose Calcium Channel Blockers (non- dihydropyridine)- initial DOC Beta Blockers-initial DOC Other Diltiazem 10 mg IV over 2 minutes Can repeat up to 20 mg IV Metoprolol Digoxin 5 mg IVP q5min x3 doses 0.5 mg IV loading dose 0.25mg IV in 6 hrs 0.25mg IV 6 hrs after Other Amiodarone 150 mg IV/10 min 1mg/minx 6 hrs 0.5 mg/min x 18hrs 30 mg PO q6 hrs (can transition to long acting) Can use 10 mg IV q6 hrs prn 25 mg PO BID, can uptitrate to 100mg PO BID mg PO QD mg PO QD

25 Rate Control Agents Calcium Channel blockers-non-dihydropyridine agents IV diltiazem-initial dose 10 mg IV over 2 minutes Can increase dose to 20mg IV if needed Maintenance diltiazem 30mg PO q6hrs (short acting) or can transition to total long acting diltiazem Can also use 10mg IVP q6 hrs prn Start PO dose at same time as IV dosing, so PO can kick in by time IV dosing wears off

26 Rate Control Agents Beta blockers Metoprolol- Initial dose: 5mg IVP q5 minutes x3 doses and q6hrs prn Maintenance Dose: 25 mg PO BID, can uptitrate to 100mg PO BID max Start PO at same time as IV medication Esmolol Initial dose: 500mcg/kg IV over 1 min, can repeat in 5 minutes Maintenance drip: mcg/kg per min IV continuous infusion Used only in ICU: o Advantage: short duration of action, easy to titrate to heart rate goal

27 Rate Control Agents Amiodarone- both a rate control and rhythm control agent Initial loading dose: 150 mg IV over 10 minutes, then 1 mg/min x 6 hrs, then 0.5mg/min x18 hrs Maintenance dose: can change to oral 100mg-200mg daily Can promote cardioversion-so need to be on anticoagulation Preferred agent in WPW to prevent AF impulses down accessory pathway leading to promotion of VF Amiodarone: most effective, most toxic. Dronaderone:?least effective, most practical. Black box warning for EF<35%. Contraindicated in permanent atrial fibrillation and recent heart failure.

28 IC agents (flecainide and propafenone):?best agents if no contraindications (SHD); pill-in-the-pocket approach. Sotalol: CAD; in-hospital initiation in most patients. Dofetilide: LV dysfunction; in-hospital initiation

29 Rate Control Agents Digoxin can be used in acute setting but rarely as monotherapy Initial loading dose: 0.5mg IV then 0.25mg IV in 6 hrs 0.25 mg IV 6 hours after Maintenance dose: 0.125mg daily PO Caution in elderly patients and those with renal failure (need to renally dose) TREAT-AF study-increased risk in mortality in elderly patients by >20% on digoxin Indicated in patients with LVEF<30% (inotropic agent)

30 Next Step If patient is hemodynamically unstable in setting of atrial fibrillation (with hypotension, angina, decompensated heart failure, AMS) then proceed with direct synchronized cardioversion Rate control is goal for Afib with RVR for symptomatic management Initial rate control agents are diltiazem or metoprolol, then assessment for thrombus via TEE and elective cardioversion and ~ 1 month of AC

31 Not Good

32 Patient completes a 10gm load and undergoes attempt at cardioversion. Three 360J shocks with ERAF Undergoes repeat cardioversion following additional month of amiodarone therapy. 300J shock is now successful.

33 Clinic Follow Up ECG

34 Highlights Prevalence and incidence of AF Risk stratification for stroke and bleeding New oral anticoagulants Guidelines Practical considerations for choosing an anticoagulant

35 Scoring Systems in Stroke Risk A variety of systems have been published Outlined on next slide All use selected clinical characteristics to predict the risk of stroke Most widely used is the CHADS 2 VASc score All scores provide a rough estimate of risk of thrombosis in a population at similar risk as patient being reviewed

36 Atrial Fibrillation Risk Stratification 12 Schemes applied to 1000 patients from SPAF III study High Moderate Low Stroke Risk in Atrial Fibrillation Working Group. Stroke Jun;39(6): Pub Med PMID:

37 Scoring and Risk Lip et al, JAMA

38 Stroke Risk

39 Question #3 78 year old female with atrial fibrillation and HTN. How would you classify her stroke risk? What is her management? 1. Low 2. Moderate 3. High

40 Bleeding Risk Scores Variety of scoring systems developed to predict risk of bleeding in patients initiating anticoagulants, as with stroke risk Less predictive than stroke risk scores, in general Each score incorporates clinical characteristics and provides estimate of risk of bleeding in a population similar to patients being considered Unclear whether to include risk scores in deci sion making for individual patients

41 Bleeding Risk Scores Widely Used in AF HEMORRHAGES HASBLED ATRIA Score

42 Has Bled

43 Bleeding Risk Scores in AF ATRIA HAS-BLED HEMORR 2 HAGES Anemia 1 3 Hypertension 4 1 Severe renal disease 2 3 Abnormal Renal 5 or 1 Liver function 6 1 Hepatic 10 or 1 Renal disease 2 1 Ethanol abuse 1 Age 75 yrs 2 Stroke 1 Malignancy 1 Any prior hemorrhage 1 Bleeding 1 Older Age (>75 yrs) 1 Hypertension 3 1 Labile INR 8 1 Reduced platelet number or function 11 1 Elderly (>65 yrs) 1 Rebleeding 12 2 Drugs 9 or Alcohol 1 1 Hypertension 4 1 Anemia 13 1 Genetic factors 14 1 Excessive fall risk 15 1 Stroke 1 Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. J Am Coll Cardiol 2012;60: Jul 24. [Epub ahead of print] Online Appendix. PMID:

44 Risks of Bleeding with Warfarin or Dabigatran in AF Oldgren J, et al. Ann Intern Med Nov 15;155(10):660-7, W204. Pub Med PMID:

45 Reversal Process for NOACs Mayo Clinic Guidelines 2016

46 Question #4 78 year old male with atrial fibrillation and hypertension (CHADS2 score = 2 [4% stroke rate per year]). What is his major bleeding rate? 1. 1% 2. 2% 3. 3% 4. 5% 5. 10%

47 Highlights Prevalence and incidence of AF Risk stratification for stroke and bleeding New oral anticoagulants Guidelines Practical considerations for choosing an anticoagulant

48 Pharmacokinetics of NOACs Apixaban Dabigatran Rivaroxaban Direct factor inhibition Xa IIa Xa Bioavailability (F rel ) 80% 6% 80% Peak action (t max ) 1 3 hr 1 3 hr 1 3 hr Protein binding 84% 35% 92 95% Renal clearance 25% 80% 33% Elimination half life with creatinine clearance > 80 ml/min Elimination half life with creatinine clearance ml/min Elimination half life with creatinine clearance ml/min Elimination half life with creatinine clearance < 30 ml/min 15.1 hr 13.8 hr 8.3 hr 14.6 hr 16.6 hr 8.7 hr 17.6 hr 18.7 hr 9.0 hr 17.3 hr 27.5 hr 9.5 hr Kaatz S, et al. Am J Hematol May;87 Suppl 1:S Pub Med PMID:

49 Comparing AHA/ACC 2014

50 Dosing and Clearance AHA/ACC 2014

51 Measuring the Effect of NOACs Coagulation Assays Apixaban Rivaroxaban Dabigatran PT -dilute PT -modified PT Not useful Data n/a Qualitative Qualitative Data n/a Data n/a Not useful Data n/a Data n/a aptt Not useful Not useful Qualitative Chromogenic Assays -Anti-Xa -Anti-Iia Quantitative No effect Quantitative No Effect No effect Quantitative n/a = not available Garcia DA, et al. In review.

52 Reversal of NOACs Suggestions for Reversal of New Oral Anticoagulants Apixaban Dabigatran Rivaroxaban Oral activated charcoal Yes Yes Yes Hemodialysis No Yes No Hemoperfusion with activated charcoal Possible Yes Possible Fresh frozen plasma No No No Activated factor VIIa Unclear Unclear Unclear 3-factor PCC Unclear Unclear Unclear 4-factor PCC Possible Possible Possible P R A X B I N D Kaatz S, et al. Am J Hematol May;87 Suppl 1:S Pub Med PMID:

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54 Choice of Agents: Pros and Cons OAC: Warfarin Advantages: cheap, monitoring, reversible, valvular AF. Disadvantage: narrow therapeutic index, non-reversible, drug/food interactions,inconvenience. NOAC: Advantages: LOWER ICH risk, practical, compliance, drug/food interactions Disadvantages: cost, irreversible

55 Case Continued Amiodarone stopped. Patient underwent catheter ablation of atrial fibrillation. Patient remaining in sinus rhythm 1 yr post ablation on ILR monitoring. Stop anticoagulation?

56 Novel Anticoagulants Forever? General intolerance of NOACs resulting in discontinuation is 20%. Bleeding risk with NOACs is not trivial and increased with concomitant use of anti-platelet agents. NOACs are contraindicated with advanced renal disease. Minimal data on long-term use of NOACs. Safety of life-long NOAC use not tested. Serious adverse events in RELY-ABLE 35%.

57 Need for Additional Stroke Prevention Strategies Atrial fibrillation incidence is increasing and it remains the most common cause of embolic stroke in the US. Warfarin has limitations. NOACs are at least comparable if not superior to warfarin; however, whether they are safe as lifelong strategy remains unknown. There are pts who are not candidate for anticoagulation and will require alternate strategies.

58 Case Continued Presents to clinic 2 months following cardioversion. LVEF 55%. NOW WHAT?

59 What Next? Ablate the AV node and place BiV ICD. Ablate the AV node and place a BiV PPM. Cardioversion following amiodarone loading. Schedule AF ablation.

60 General AF Ablation Approach in the Lab PAF: PVs are the most common trigger àpvi at start Isoproterenol infusion to target additional triggers. Persistent Atrial fibrillation: PVI at start. Rotor ablation. Scar ablation. Posterior wall ablation. LARIAT + PVI. Isoproterenol infusion to target additional triggers.

61 Effect of Catheter Ablation on AF Progression Jongnaransin K, et al Cardiovasc Electrophysiol, 2012; 23: 9-14.

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63 CASTLE-AF: Paradigm Shift for AF Management Study the effectiveness of catheter ablation of atrial fibrillation in patients with heart failure in improving hard endpoints of mortality and heart failure progression when compared to conventional standard therapy. Median 38 mo fu ~40% RRR of death from any cause or worsening heart failure. P=0.07 NEJM 2018; 378:417-27

64 CASTLE-AF NEJM 2018; 378:

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66 NEJM 2018; 378:

67 Left Atrial Appendage (LAA) Role in Embolic Stroke Blackshear et al. Ann Thoracic Surg % of LA thrombus in LAA in non-rheumatic AF. Kleeman et al. Eur J Echocardiogr 2009;10: pts with CHADS2 score 0 or 1, had LAA thrombus by TEE of 3% and dense smoke of 8% SPAF Investigators, Ann Int Med 2008;128: LAA smoke nearly triples risk of stroke in atrial fibrillation

68 LAA Occluder Devices A. PLAATO Device: withdrawn for commercial reasons. B. ACP Device: 7% major complication,6 5% relative stroke risk reduction. C. Watchman Device: PROTECT-AF, PRE VAIL, ASAP Registry. FDA approval. D. WaveCrest Device: 58/60 successful implants.

69 Cox-Maze Procedure Considered the gold-standard for treatment of persistent AFib Key component of procedure is mechanical & electrical isolation of t he LAA. 100% freedom from AF and stroke at 10 years (based on symptoms) 20% required pacemakers following the procedure and 27% major complications Damiano RJ, et al. JTCVS Vol126(6)

70 LARIAT Procedure Routine cath-lab imaging and techniques utilized. Enables immediate and complete closure of the LAA (including electrical isolation). Non-implant solution compatible with treatment objectives for AF

71 Complete and Permanent Elimination of the LAA

72 Summary Complex pathophysiology CHADS-Vasc for OAC Cure of AF cessation of OAC Choice of rhythm control agent Ablation therapy: having a strategy is important Clinical trials for persistent atrial fibrillation: REAFFIRM (completed enrollment), REDO-FIRM, DECAAF II, AMAZE.

73 Highlights Prevalence and incidence of AF Risk stratification for stroke and bleeding New oral anticoagulants Guidelines Practical considerations for choosing an anticoagulant

74 Question #5 78 year old female with atrial fibrillation, hypertension and CHF. CHADS 2 = 3 CHA 2 DS 2 -VASc = 5 HAS-BLED = 2 What would you use for stroke prevention? 1. No anti-thrombotics 2. Aspirin 3. Aspirin + clopidogrel 4. VKA antagonist 5. Dabigatran or Rivaroxaban

75 ACCP Guidelines For patients with Nonrheumatic AF, including those with Paroxysmal AF Level of Risk Low Risk (CHADS 2 = 0) Intermediate Risk (CHADS 2 = 1) High Risk (CHADS 2 = 2) ACCP Recommendation Alternative* Not Recommended No Therapy Aspirin Oral anticoagulation or combination therapy with aspirin and clopidogrel Oral anticoagulation Oral anticoagulation (dabigatran 150 mg b.i.d. vs. VKA**) Aspirin with clopidogrel Aspirin with clopidogrel Aspirin Aspirin *For patients with AF unsuitable for, or who refuse, oral anticoagulant (for reasons other than concerns about major bleeding) **VKA = adjusted-dose vitamin K antagonist You JJ, et al. Chest Feb;141(2 Suppl):e531S-75S. Pub Med PMID:

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77 Scoring Systems and Intervention

78 Anticoagulation Management

79 Newly Diagnosed AF

80 pafib

81 Persistent Afib

82 Rate Control

83 Question #5 78 year old female with atrial fibrillation, hypertension and CHF. CHADS 2 = 3 CHA 2 DS 2 -VASc = 5 HAS-BLED = 2 What would you use for stroke prevention? 1. No anti-thrombotics 2. Aspirin 3. Aspirin + clopidogrel 4. VKA antagonist 5. Dabigatran or Rivaroxaban

84 Highlights Prevalence and incidence of AF Risk stratification for stroke and bleeding New oral anticoagulants Guidelines Practical considerations for choosing an anticoagulant

85 Taiwan Mexico Peru Romania India Columbia Russia Brazil China Korea Greece Thailand Malaysia Poland Japan South Africa France Slocakia Portugal Israel Czech Republic Philippines Bulgaria Hungary Hong Kong Turkey Belgium Austria USA Spain Germany Switzerland Singapore Argentina Netherlands Norway Canada Italy Ukraine UK Denmark Austrailia Finland Sweden TTR per Country in RE-LY USA: Improvement Needed Wallentin L, et al. Lancet Sep 18;376(9745): PMID:

86 Optimal Candidates for New Drugs Patients who: Find INR testing burdensome Despite adherence to provider recommendations, have low timein-range Can afford (or arrange to get) the new drugs Have normal renal function

87 Optimal Candidates for Warfarin Patients who: Have (borderline) renal insufficiency Are taking stable dose of warfarin and do not find INR testing burdensome Have access to self-testing machine Are concerned about the lack of an evidence-based reversal strategy

88 Mi Lukin Yu Behin