Update on atrial fibrillation management Disclosure Catheter - - PDF document

▶
update on atrial fibrillation management disclosure
SMART_READER_LITE
LIVE PREVIEW

Update on atrial fibrillation management Disclosure Catheter - - PDF document

Jan 02, 2024 164 likes •327 views

12/1/17 Update on atrial fibrillation management Disclosure Catheter Ablation of Atrial Fibrillation: SentreHeart, Inc What Does 2018 Hold? Apama Medical/Boston Scientific Consultant Equity holder 1 12/1/17 AF PAROXYSMAL

slide-1
SLIDE 1

12/1/17 1

Update on atrial fibrillation management Catheter Ablation of Atrial Fibrillation: What Does 2018 Hold? Disclosure

SentreHeart, Inc Apama Medical/Boston Scientific

  • Consultant
  • Equity holder
slide-2
SLIDE 2

12/1/17 2

INTRODUCTION GROWTH MATURITY DECLINE

1 2 3 4

AF PAROXYSMAL Diagnosis PERSISTENT AF LONG STANDING AF. PERMANENT AF. 33.5 Million WW High BP CHD Rheumatic HD Hyperthyroidism Obesity/Diabetes Sleep Apnea HX of AF Behaviors Increase Risk Alcohol and Caffeine High Stress

Restore Maintain Protect

Standard “Historical” Treatment for AF

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. N Engl J Med 2002;347:1825-1833.

AFIRM Trial

Van Gelder IC et al. N Engl J Med 2010;362:1363-1373.

RACE-2 Trial

slide-3
SLIDE 3

12/1/17 3

2017 HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation It’s Not the Answer Too little = Stroke Too much = Hemorrhage

INR 1 2 3 4 5

TARGET

WARFARIN

Risks increase with age Low compliance Contraindications

Dabigatran Rivaroxaban Apixaban

Mechanism Direct Thrombin Inhibitor Factor Xa Inhibitor Factor Xa Inhibitor Dose 110 mg or 150 mg 2x/ day 20 mg/day 5 mg 2x/ day *2.5 mg 2x/day Efficacy in preventing embolic events Superior (150 mg) Noninferior (110 mg) noninferior superior Hemorrhagic stroke Significantly less (110 mfg) More (150 mg) at lesless less GI bleeding Not specified (110mg) Major GI bleeding Epitaxis and hematuria less All bleeding events Less (at 110 mg) Similar (at 150mg) less

*2.5 mg twice daily if two or more: age >80, weight <60 kg or Cr > 1.5 (25% renal excretion). Excluded if Cr > 2.5

Oral Anticoagulants DISCONTINUATION RATES

5 10 15 20 25 RE-LY ARISTOTLE ROCKET-AF

NOAC Warfarin

Rivaroxaban NEJM 2011;365:883-91 Apixaban NEJM 2011;365:981-92 Dabigatran NEJM 2009;361:1139-51

slide-4
SLIDE 4

12/1/17 4

  • 82 year old woman with

paroxsysmol AF

  • History of both ICH and

cardioembolic stroke, hypertension

  • TEE reveals LAA thrombus

Patients with Limited to NO options

Patients with contraindications to OAC therapy

LAA Closure Devices Available in the US

Watchman is FDA approved for stroke prevention Atriclip and LARIAT are FDA approved, but not for stroke prevention Watchman Atriclip LARIAT

AF Risk Factor Modification

  • HTN
  • DM
  • Obesity
  • Sleep Apnea
  • Alcohol
  • Excercise

RACE 3

Risk Factor Driven Upstream Therapy in Early Atrial Fibrillation

The Routine versus Aggressive upstream rhythm Control for prevention of Early persistent atrial fibrillation in heart failure study

Michiel Rienstra, Anne H. Hobbelt, Marco Alings, Jan G.P. Tijssen, Marcelle D. Smit, Johan Brügemann, Bastiaan Geelhoed, Robert G. Tieleman, Hans L. Hillege, Raymond Tukkie, Dirk J. Van Veldhuisen, Harry J.G.M. Crijns, Isabelle C. Van Gelder, for the RACE 3 Investigators Presented at the ESC in Barcelona 2017

slide-5
SLIDE 5

12/1/17 5

Hypothesis and trial design

§ Hypothesis: Risk factor driven upstream therapy is superior to conventional therapy for maintenance of sinus rhythm in patients with early persistent AF and HF § RACE 3 trial design: § Prospective, randomized, open label, superiority trial § Investigator-initiated § Multicenter: 14 sites in The Netherlands and 3 in United Kingdom § Enrolment between 2009 and 2015 § 1 year follow-up

Causal treatment of AF and HF

Risk factor driven upstream Conventional

ECV after 3 weeks

Guideline-recommended rhythm and rate control

Flowchart

Patients with early persistent AF and HF 7-day Holter at 1-year

Upstream therapy consists of: 1) Mineralocorticoid receptor antagonist 2) Statin 3) ACE-inhibitors and/or angiotensin-receptor blockers 4) Cardiac rehabilitation:

  • physical activity
  • dietary restrictions

Primary endpoint

20 40 60 80 100

Sinus rhythm at 1-year

75% 63% Odds ratio 1.765 Lower 95% confidence limit 1.115 Superiority hypothesis was proven (p=0.021)

Upstream Conventional

% of patients

Conclusions

Conclusion and implication

§ The RACE 3 study shows that risk factor driven upstream therapy, including treatment of risk factors and change of lifestyle, is effective and feasible to improve maintenance of sinus rhythm in patients with early persistent AF and HF § The effect of upstream therapy on reduction of risk factors and cardiovascular diseases, instead of atrial remodeling, was favourable

slide-6
SLIDE 6

12/1/17 6

Case History

  • 78 year old male h/o CM, COPD and persistent AF
  • Admitted to hospital with SOB
  • EP consulted to consider PVI vs AVJ and PM
  • Physical exam reveals pt on O2, mildly elevated JVP

, diffuse bilateral rhonchi, minimal pedal edema

  • ECG reveals AF with rate of 126 bpm
  • LVEF of 33% by echo

Treatment Options

  • PVI
  • AVJ with PM
  • Rate control with OAC therapy
  • Restore and maintain sinus rhythm with AADs
  • Cardioversion

The CASTLE-AF Trial

Catheter Ablation versus Standard conventional Treatment in patients with LEft ventricular dysfunction and Atrial Fibrillation

  • Symptomatic PAF or Persistent

AF

  • Failure or intolerance to AAD or

unwillingness to take AAD

  • LVEF < 35%
  • NYHA class > II

Inclusion Criteria Primary Endpoint

  • All-cause mortality
  • Worsening heart failure

admissions

slide-7
SLIDE 7

12/1/17 7

CASTLE-AF

Treatment Protocol

  • ACC/AHA/ESC 2006 guidelines for

treatment of AF in heart failure patients

  • Efforts to maintain sinus rhythm were

recommended

  • In the case of rate control strategy:

– 60 and 80 bpm at rest – 90 and 115 bpm

  • OAC therapy was initiated if not already

strated, and maintained throughout the

  • study. INR between 2.0-3.0

Conventional therapy

  • Pulmonary Vein Isolation
  • Additional lesions
  • At the discretion of the operator
  • Repeat ablation after blanking period

Ablation therapy

slide-8
SLIDE 8

12/1/17 8

Pivotal Trials

  • Catheter Ablation vs Anti-arrhythmic Drug

Therapy for Atrial Fibrillation Trial (CABANA)

  • EAST Trial

Clinical success of various ablation techniques for persistent/long-standing persistent atrial fibrillation

Brooks AG, et al. Outcomes of long standing persistent AF: A systematic review. Heart Rhythm. 2010; 7:835-46

slide-9
SLIDE 9

12/1/17 9

Summary:

  • After the first ablation procedure, sinus rhythm

was documented in 41/202 (20.3%) patients.

  • After multiple procedures, sinus rhythm was

maintained in 91/202 (45.0%) patients.

JACC 2012;60:1921-9

New Technologies

A C D B

Narayan, S. M., Krummen, D. E., Shivkumar, K., Clopton, P., Rappel, W. J., & Miller, J. M. (2012). Journal of the American College of Cardiology, 60(7), 628–636.

Do Rotors Drive Persistent AF?

CONFIRM Trial Ø 107 procedures (76% persistent AF) Ø PVI (n=71) vs. PVI + rotor (n=36) Ø Rotors identified in 98/101 persistent AF cases

STAR AF II Trial

Verma A et al. NEJM 2015; 372: 1812-1822 PVI: Triggers PVI + CFE: Triggers + substrate PVI + lines: Triggers + substrate

slide-10
SLIDE 10

12/1/17 10

* * * * * * * * * * * * * * *

11

* * * ** ** * * * * * * * * * * * *

19 AVNRT

Ø Non PV Triggers (N=83) Initiating AF 68/401 patients (17%) RA LA

1AVRT

* * * * ** * *** * * * ** * * * * * * * * * * *** *

15 4 4 4

Alonso et al. Pace 2003

Non-PV Focal Triggers Initiating AF Cox Maze III Cut and sew Maze

“Gold Standard” for Non- Pharmacological Treatment of AF

Prasad SM. J Thorac Cardiovasc Surg. 2003;126:1822-28.

Benefit of LAA Closure

“Cut and sew” Cox-Maze Cox J., et al. J Thorac Cardiovasc Surg 1999;118:833-840

AF, Hx TE, No OAC AF, No TE, No OAC AF, Hx TE, OAC AF, No TE, OAC AF, No Risk, No TE, No OAC Post maze, No OAC, No LAA

B

UCSF Sub-X MAZE (Epicardial)

slide-11
SLIDE 11

12/1/17 11

LAA

A B C D E F

Fibrillating Areas Isolated within he the Left Atrium after Radiofrequency Linear Catheter Ablation

Rostock…..Haissaguerre JCE 17:807-812, 2006

  • Circulation. 2011;123:1575-1578

LAA Isolation Improves Ablation Outcomes

Left Atrial Appendage : An Underrecognized Trigger Site of Atrial Fibrillation Di Biase et al., Circulation. 2010;122:109-118 15% 68% 74%

slide-12
SLIDE 12

12/1/17 12

Unexpectedly High Incidence of Stroke and Left Atrial Appendage Thrombus Formation after Electrical Isolation of the Left Atrial Appendage for Treatment of Atrial Tachyarrhythmias: An undescribed and under recognized complication of left atrial catheter ablation

Andreas Rillig , MD, Roland R. Tilz, MD, Tina Lin, MD, Christian Heeger, MD, Anita Arya, PHD, Andreas Metzner, MD, Shibu Mathew, MD, Erik Wissner, MD, Hisaki Makimoto, MD, PHD, Peter Wohlmuth, Karl-Heinz Kuck, MD, Feifan Ouyang, MD LAA thrombus

Mechanical standstill Thrombus formation

LAA thrombus in 21%, and three patients had a stroke while on OAC

Sick et al., JACC 2007

Combined PVI and LAA Exclusion

  • Restoration of sinus rhythm with PVI
  • Stroke prevention without need for OAC therapy

after LAA occlusion device

Combined PVI and LAA occlusion

Potential benefits:

PVI should be done before LAA closure with an LAA implant

Dislodgement D

L A WATCH MAN A V Throm bus

Catheter ablation can compromise LAA implant integrity

Leaks

slide-13
SLIDE 13

12/1/17 13

IV C MV SVC

LAA ligation with PVI Cox Maze III

LAA exclusion as adjunctive therapy to PVI for the treatment of AF: What is the rationale?

  • Elimination of atrial arrhythmias arising from the LAA
  • Left atrial debulking/reduction results in decreased left atrial dispersion
  • Allows for a more complete ablation procedure

Restore Maintain Protect

Electrical Isolation LAA Exclusion

Merits of an Epicardial LAA Closure Approach

Pre CT 45D Post CT

LAA No LAA

LAA ligation results in a permanent LAA closure

LA LAA

Bartus et al., Circ AE 7:764-767, 2014

The Effects of LAA Ligation on LAA Electrical Activity

Frederick T. Han M.D.*1, Krzysztof Bartus M.D., Ph.D.* 2, Dhanunjaya Lakkireddy, MD3, Francia Rojas, MD4, Jacek Bednarek, M.D., Ph.D.5, Boguslaw Kapelak, M.D., Ph.D.2, Magdalena Bartus Ph.D. 6, Nitish Badhwar M.B.B.S., FHRS7, Mathew Earnest, MD3, Miguel Valderrabano, M.D4, Randall J. Lee M.D., Ph.D7,8,9,

N = 30 N = 38

Han et al., Heart Rhythm 11:864–870, 2014

slide-14
SLIDE 14

12/1/17 14

Conversion of persistent atrial fibrillation to sinus rhythm after LAA ligation with the LARIAT device

Nitish Badhwar, Suneet Mittal, Abdi Rasekh, Smit Vasaiwala, Dan Musat, Payam S.Naeini, Qi Fang , Karin Nentwich, Thomas Deneke, Jie Chang, Dhanunjaya Lakkireddy, David Wilber, Randall J. Lee Int J Cardiol. 225:120-122, 2016

13 of 162 patients (8%) with pAF converted to SR. 12 patients > 1 year of pAF.

LAA-LA Registry

0% 10% 20% 30% 40% 50% 60% 70% LARIAT + Ablation Ablation Only Total

Recurrence Rate

Lakkireddy, et al.

24/69 42/69 66/13 8

*JACC EP: 2015

  • 69 consecutive patients undergoing LAA

ligation with LARIAT system followed by AF ablation vs ablation only.

  • Primary Outcome: Recurrence of AF @ 12M
  • ff AAD

– Defined as recurring AF episodes >30 sec via 24hr holter monitor

  • AF recurrence was lower in the LARIAT group

(35% vs 61% p=0.028) after the first ablation

  • Fewer patients in the LARIAT group needed

repeat ablation (16% vs 33% p=0.018)

  • Multi-center, prospective randomized trial
  • Comparing LAA ligation and PVI versus PVI in

patients with persistent and longstanding persistent AF

Clinical Hypothesis of amaze

Close the LAA

  • LAA permanently disappears

and no longer a source of thrombus

LAA ligation

  • Leads to LAA electrical isolation
  • Decreases LA mass and

favorable electrical remodeling

  • Allows for more complete PV

ablation

slide-15
SLIDE 15

12/1/17 15

Protocol Synopsis

Principal Purpose Evaluate the additional efficacy of LARIAT LAA ligation to decrease the 12- month rate of AF , and to confirm an acceptable safety profile Patient Population Patients (18-80 y.o.) with documented persistent or longstanding persistent AF (< 3 yrs continuous AF) planned for catheter ablation Design Prospective, multicenter, RCT (2:1) Bayesian Adaptive Design; 400 – 600 subjects total; ~50 sites 2 randomized stages: Stage 1 ≤ 175 subjects; interim safety and performance analysis of first 100 Investigational Tx LARIAT LAA ligation followed by PVI catheter ablation (separated by >4 weeks) Control Tx PVI catheter ablation without LAA ligation

Primary Endpoints

Primary Effectiveness Endpoint (Superiority study) Freedom from episodes of AF > 30 seconds and no requirement for new Class I or III AAD therapy at 12 months post PVI, measured by 24-hr holter

  • r symptomatic event monitoring*

Primary Safety Endpoint The incidence of significant LARIAT device or procedure-related SAEs

  • ccurring within 30 days after the LAA ligation procedure (Performance

Goal) *consistent with HRS 2012 Consensus Guidelines

Summary

  • 100 subject Stage I completed Dec 2016.

– 30d safety data adjudicated by an independent DMC and FDA – FDA recommended continuation of the aMAZE trial based

  • n meeting the pre-defined safety goals and LAA closure

effectiveness

  • 240 subjects enrolled thru October 2017

– 400 subjects required for first assessment of efficacy data

2018 Update for AF

  • Risk factor modification
  • Rhythm vs Rate control
  • OAC therapy
  • LAA exclusion only for patients

intolerant/contraindicated to OAC therapy or LAA thrombus on OAC therapy

  • Consider PVI earlier, especially in patients with HF
  • aMAZE trial for persistent AF patients