Update in Internal Medicine

Atrial Fibrillation: To Treat or Ablate?

Samir Saba, MD, FACC, FHRSProfessor of Medicine

Division Chief, CardiologyCo-Director, Heart and Vascular Institute

Disclosure

Research Support:ØNHLBIØBoston ScientificØMedtronic Inc.

Intellectual Property:ØMedtronic Inc.

OutlineØThromboembolic protectionØAF Management

vRate Control StrategyvRhythm Control Strategy

ØThe past, present, and future of ablation for paroxysmal and persistent AF

ØGuideline Recommendations

Atrial Fibrillation

• Demographics of AFv A heterogeneous population

• General concerns with AF:v Thromboembolismv Symptomsv Myocardial function

• Strategies of Management:v Rate controlv Rhythm control

qAblation

Presentations

Mr. DMØ87 year old manØh/o CAD and LAD stent in 2003ØStroke in 2007ØHad syncope while urinating in

the bathroomØPresenting rhythm is AF with

VRR 70 bpmØNo palpitations, CP, or SOB

Mr. JLØ45 year old manØNegative cardiac historyØWoke-up from sleep with severe

symptoms of palpitations and SOB

ØDrank 6 beers the night beforeØWas in AF with VRR 145 bpmØConverted spontaneously to SR

while in ER

Demographics

Maisel WH et al. Am J Cardiol 2003;91:2D-8D.

Demographics

Lone AFYounger

No heart diseaseNo PVDNo HTNNo DM

No stroke/TIALow CHADS2vasc

AF with Comorbidities

OlderCHF/heart disease

PVDHTNDM

Prior stroke/TIAHigh CHADS2vasc

HIGHER RISK (mortality, stroke, etc…)

LOWER SUCCESS IN MAINTAINING SR

Paroxysmal AF Persistent AF Permanent AF

General Management of Atrial Fibrillation

ØFor decades, the mechanism of AF was perceived to be a chaotic rhythm with no focus to ablate

ØThe main stay of therapy was: vOral anticoagulationvRate control medicationsvRhythm control medicationsvRare ablation of SVT mechanism, possibly implicated in AF

initiation

1. Thromboembolic PreventionØMechanisms of thromboembolism include:

v Stasisv Hyper-coagulable state

Ø Clots form mainly in LAA but can be anywhere in the LAØStroke:

vRisk of stroke increase by 3-5 folds in AFv 15% of all strokes are attributable to AFvRisk higher with higher CHADS2vasc scorev Except for patients at lowest risks (score 0 or 1), or those with

major bleeding complications (brain, retina, massive GI, etc…), anticoagulation is indicated

Thromboembolic PreventionØAnti Platelets (Aspirin, Clopidogrel, Ticaglecor)

ØAnticoagulation

vWarfarin

vDOACs only in NVAF (Dabigatran, Rivaroxaban, Apixaban, Edoxaban, Betrixaban)

ØCHA2DS2-Vasc score

CHA2DS2-VASc Score

Annual Stroke Risk (%)

0

1 1.3

2 2.2

3 3.2

4 4.0

5 6.7

6 9.8

7 9.6

8 12.5

9 15.2

LAA Closure

Reddy VY et al. Circulation. 2013;127:720-729

2. Symptoms

Ø Some patients are asymptomatic Ø Symptoms may include: palpitations, SOB, DOE, CP, dizziness,

fatigue, etc…Ø Attributing symptoms to AF may be difficultØ Symptoms may be due to:

v Irregular ventricular ratev Rapid ventricular ratev Loss of atrial contraction (‘atrial kick’)

3. Tachycardia-Induced Cardiomyopathy

ØIf VRR is persistently fast for long periods of time this may lead low EF

Ø This form of cardiomyopathy is reversible: with good rate control, the EF is expected to normalize

Ø It is often difficult to ascertain whether the rapid AF led to CMP or the CMP resulted in rapid AF (the ‘chicken or egg’ dilemma)

Ø Confirmation is made after few weeks of controlling the ventricular rate of AF or after restoring and maintaining SR

Management of AF: Rate Control Strategy1. Digoxin2. Beta Blockers3. Calcium Channel Blockers4. AVN ablation with Pacemaker

Management of AF: Rhythm Control Strategy

ØSodium Channel BlockersvFlecainidevPropafenone

ØPotassium Channel BlockersvSotalolvDofetilide

ØAmiodaroneØCardioversion +/- DrugØAF Ablation

Choice of Strategy

ØThere is no right or wrong between Rhythm Control and Rate Control

Ø Choice depends on:vClinical factorsvPatient preference

Ø Often, the choice is empiric, i.e. one would try rhythm control initially, but then settles for rate control after rhythm control fails

Ø How hard one needs to try maintaining rhythm control varies by physician, clinical scenario, and patient preference

Choice of StrategyRHYTHM CONTROL

Goal: restore and maintain SRFactors favoring Rhythm Control:1. Symptomatic AF2. Younger age3. Paroxysmal AF4. Normal heart structure5. No prior attempts at SR6. Smaller LA volume7. High odds of maintaining SR8. Patient willing to undergo

procedures (DCCV, AF ablations) or hospitalizations for initiation of AAD

RATE CONTROL

Goal: accept AF but control VRRFactors favoring Rate Control:1. Asymptomatic AF2. Older age3. Persistent AF4. Abnormal heart structure5. Failed prior attempts at SR6. Larger LA volume7. Low odds of maintaining SR8. Patient unwilling to undergo

procedures (except definitive procedures such as AVN RFA/PM) or hospitalizations for initiation of AAD

Choice of StrategyTrial N F/U Endpoint OutcomePIAF 252 1 year Symptoms NS

STAF 200 20mths Death + thromboembolism NS

RACE 526 2-3yrs CompositeNS

Hot Café 205 1-7yrs Death, stroke, hemorrhage NS

AFFIRM 4060 3-5yrs Total mortality NS

AFFIRM Trial

AFFIRM Trial. N Engl J Med 2002; 347:1825-1833

AF Ablation

Haissaguerre M. et al. NEJM 1998;339:659-666

Historical Evolution of Lesion Set for PVI

ØFocal ablationØIsolation of culprit PV at atrial

junctionØIsolation of two ipsilateral PVs at

atrial junctionØWide antral circumferential

ablation of 4 PVs (WACA)

Paroxysmal Atrial Fibrillation

Two approaches:ØPoint-by-point

delivery of lesionsØSingle application

lesions

AF ablation = PVI1-year freedom from AF~75-80%

STOP AF TrialØN=245 patients with PAF failing ≥ 1 AADØRandomized 2:1 to

• Cryoballoon PVI (n=163) • Medical therapy (n=82)

Ø90 day blanking period to adjust AADØ12-month follow-upØPrimary endpoint is freedom from AF

recurrenceResults:Ø4 PV isolated in 97.6% of patientsØSixty five (79%) of Medical therapy

patients crossed over to ablation arm within 12 months

Packer D et al. JACC 2013;61:1713-1723

STOP-AF Post Approval StudyØ39 CentersØ345 patientsØ5.7% complications

o Vascular bleeding – groin or retroperitoneal

o Pseudoaneurysm, AV fistula

o Pericardial effusion or tamponade

o Phrenic nerve injury

o Stroke, thromboembolic event

o Atrio-Esophageal Fistula

Total Major Complications in 450 cases 10 2.2% Persistent Phrenic Nerve Injury 5 1.1%

Symptomatic Pericardial Effusion 3 0.67% Deep Vein Thrombosis 1 0.22%

AV Fistula 1 0.22% Bleed/Hematoma Requiring Transfusion 0 0%

Stroke 0 0% Death 0 0%

Phrenic Nerve Injury 49 10.8% Temporary Phrenic Nerve Injury 44 9.7% Persistent Phrenic Nerve Injury 5 1.1%

Long-Term Phrenic Nerve Injury 0 0%

Guhl E. et al. J Am Heart Assoc. 2016 Jul 21;5(7).

Fire and ICE Trial

Kuck KH et al. N Engl Med J 2016; 374;23:2235-2245

Ø 762 patients with PAF• RFA• Cryo-balloon

Ø Follow-up 1.5 yearsØ Efficacy

• Recurring AF• Aflutter/AT• Use of AAD• Redo Ablation

Ø Safety• Death• CVA• Other serious AE

Persistent Atrial FibrillationWith PVI alone, 1-year freedom from AF~50-60%

PVI + What Other Lesion Set(s)?ØCavo-tricuspid isthmus ablationØRoof line and mitral isthmus lineØGanglionic plexi ablationØRotor mapping and ablationØComplex atrial fractionated electrograms (CAFÉ)ØPosterior LA wall isolation (posterior box)ØHybrid procedures with surgical epicardial and EP endocardial

approach

Ablation of Epicardial Ganglionic Plexi for AF The AFACT Study

ØN=99 with PAF• PVI + GP ablation• PVI

ØN=141 patients with long persistent AF• PVI + lines + GP ablation• PVI + lines

ØPrimary endpoint was 1 year freedom from AF

Driessen AHG et al. JACC 2016;68:1155-1165

STAR-AF II TrialØ589 patients with persistent AF

ØPVI aloneØPVI + CAFÉ ØPVI + Mitral isthmus + Roof lines

Verma A. et al. NEJM 2015;372:1812-1822

Posterior LA wall Isolation

Saad EB et al. J Atr Fib. 2014 ; 7: 1174Kim JS et al. Int J Cardiol 2015;181:277-283

ØN=120 patients with PeAFØRandomized to:• PVI + linear lesions• PVI + linear lesions + PWI

Ø Primary endpoint is AF-free survival

Posterior LA wall Isolation

ØMulticenter study of 390 patients with persistent AF at 6 centers from 2014-2017ØPhase 1: 222 patients underwent PVI+PWI; Phase 2: 168 patients underwent PVI onlyØSame operators performed procedures in both phasesØCryoballoon used for PVI and for PWI

PVI Only PVI + PWI FREEDOM from AF/AFL

Aryana A. et al. Heart Rhythm 2018; 15:1121-1129

PVI + PW Isolation

BEFORE AFTER

AF-FICIENT Trial• Presented at AF Symposium 2017• Multicenter, non-randomized, pilot• Met safety endpoint at 7 and 30 days• 98% PV isolation success rate• Average LA time of 39 min• 80% freedom of AF at 6 months

ØIndividual adjustment of powerØover-the-wire 28mm balloon

with 12 proximal and six distal electrodes to map and ablate.

ØBuilt-in cameras to provide real-time visualization of electrode contact to the tissue

New Technology: Radiofrequency Balloon for AF Ablation

New Technology: HotBalloon Ablation for PAF

ØRandomized (2:1) trial of HBA

vs. AAD

ØRF energy is used to heat the

liquid (saline/contrast) inside

the balloon which transmits

thermal energy to the tissue

ØRF generator automatically

controls the temperature

between 40-70o C

ØA vibratory agitation device

continuously mixes the fluid

to maintain a uniform

temperature in the balloon

Sohara et al. JACC 2016;68:2747-2757

Laser Balloon for PVI

J Cardiovasc Electrophysiology 2013;24:987-994.

The Cabana TrialØN=2,204 patients randomized

to ablation versus medical therapy (2009-2017)

ØAblation• PVI+/-GP, Linear, CAFE• OAC

ØMedical therapy• Rate control • Rhythm control• OAC

ØPrimary endpoint is composite of death, stroke, bleeding, or cardiac arrest

Packer DL et al. JAMA 2019;321:1261

However:Ø ITT analysis negative but with significant crossover

• 9.2% of ablation patient did not receive the ablation• 27.5% of medical therapy patients underwent ablation

Ø On treatment analyses showed significant advantages of ablation• 33% relative reduction in primary composite endpoint• 40% reduction in all-cause mortality

Ø The real goal of AF ablation is to improve AF symptoms

AF Ablation in Heart Failure PatientsCASTLE-AF Trial

ØN=363 HF patients with PAF or persistent failing ≥ 1 AAD

ØAll patients had:• NYHA class II, III, IV• LVEF ≤35%• ICD implanted

ØRandomized 1:1 to• AF ablation (n=179) • Medical therapy (n=184)

ØMedian follow-up 37.8 monthsØPrimary endpoint is death or HF

hospitalization

Marrouche NF et al. N Engl J Med 2018; 378:417-427

Outcomes of AF Ablation ProceduresØImprove patients’ symptoms and QOL

ØIn patients with CHF, AF ablation decreases the composite endpoint of death or hospitalization for heart failure

ØAF ablation does not decrease the risk of stroke or thromboembolic eventsClass III: Harm1. AF catheter ablation should not be performed in patients who cannot be

treated with anticoagulant therapy during and following the procedure. (Level of Evidence: C)

2. AF catheter ablation to restore sinus rhythm should not be performed with the sole intent of obviating the need for anticoagulation. (Level of Evidence: C)

ØAF ablation does not prolong life in all-comers

Rhythm Control for AF

January et al. AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation. JACC 2014: 2246-80.

‡ Based on patient’s preference and institutional experience

Future Directions in AF Ablation Therapies

ØBetter tools for single application ablations (circular and linear) with new energy sources

ØBetter understanding of the value of additional/adjunctive therapies to improve effectiveness of AF ablation

ØHybrid approach to AF ablation endocardially (EP lab) and epicardially (CT surgery)

ØFurther expanding of the ablations to sicker patients who may extract more benefit from it

Questions?