SHA24/006002

Managing Atrial Fibrillation In the office: Rate versus Rhythm control GHA10-SHA24, Feb. 13-16, 2013, Riyadh, Saudi Arabia

Raed Sweidan, MD, FACC Consultant Cardiac Electrophysiologist King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia

Clinical Case (1) • 46 year old male smoker with HTN and type II DM who presented to the PCC with 3 week history of palpitations, and dyspnea with mild exertion. He has been under a lot of stress lately and was consuming large amounts of caffeine.

• Medications: ASA, Natrilix SR, and Glucophage

• BP: 156/88, HR 121 (irregular). PE otherwise unremarkable • ECG: AF. Ventricular response was 118 bpm

• The PCC MD stopped Natrilix, started Valsartan /HCTZ (160/12.5), Bisoprolol 5mg daily, ASA, ordered labs and echo and appointment with cardiology in 2 weeks

Clinical Case (1) • I sow the patients after 2 months. He was doing much better. Only minimal DOE, no palpitations, no chest pains.

He continued to smoke but eliminated caffeine and was compliant with his new medications • BP: 123/72, Pulse: 68 (irregular)

• ECG: AF. Ventricular response of 78 bpm • Routine labs and TSH were normal.

• Echo: Normal LV systolic function, grade I diastolic dysfunction. Mild LVH (1.3cm), Normal LA size. No valvular disease

Clinical Case (1) What would you recommend: • Continue rate control and initiate AC because of his TE risk • Admit. Initiate AC. TEE to R/O LAA clot. If negative proceed with DCCV to NSR and AA therapy to maintain sinus rhythm.

• Admit. Initiate AC. TEE to R/O LAA clot. If negative proceed with DCCV to NSR. Do not start AA drugs • Initiate AC. Once INR is therapeutic for 3 weeks, DC Bisoprolol, start Sotalol 80 BID in clinic. Admit for DCCV if still in AF after 3-4days.

• Initiate AC and refer for AF ablation

AF: Definitions • First detected episode of AF • Paroxysmal AF: Recurrent AF (2 episodes) that terminates spontaneously within 7 days.

• Persistent AF: AF which is sustained beyond seven days, or lasting less than seven days but necessitating pharmacologic or electrical cardioversion.

• Longstanding persistent AF: is defined as continuous AF of greater than one-year duration.

• Permanent AF: Sinus rhythm could not be restored and a decision has been made not to pursue restoration of sinus rhythm by any means, including catheter or surgical ablation.

Management of Atrial Fibrillation Aims of therapy: Relieve symptoms Reduce morbidity (strokes) Preserve cardiac function Improve mortality Management strategy will depend on: Duration and pattern of AF Severity of symptoms Associated cardiovascular disease Potential effects on cardiac function over time

Managing Atrial Fibrillation AF practice guidelines Your patient unique characteristics Access to care and availability of drugs Local resources and expertise (ablation)

THE ART OF MANAGING AF PATIENTS

Newly diagnosed AF in the office: Assessment: Careful assessment of symptoms (Duration, frequency, severity‌‌) Basic laboratory data and rule out reversible causes Cardiac assessment (by echo): Is there structural heart disease ?

Management: Initiate rate control and anticoagulation (AC) based on TE risk Decide on the strategy: Rhythm or rate control Maintain AC regardless of strategy according to TE risk

2012 Focused Update of the ESC Guidelines for Management of Atrial Fibrillation

Recommendation for Prevention of Thromboembolism in Non-Valvular Atrial Fibrillation CHA2DS2A-VASc score Risk Factor

Score

Congestive heart failure / LV dysfunction

1

Hypertension

1

Age ≼ 75

2

Diabetes Mellitus

1

Stroke / TIA / Thromboembolism

2

Vascular disease

1

Age: 65 - 74

1

Sex category (female sex)

1

Maximum score

9

2012 Focused Update of the ESC Guidelines for Management of Atrial Fibrillation Recommendation for Prevention of Thromboembolism in Non-Valvular Atrial Fibrillation

Newly diagnosed AF in the office: For rate control strategy: Achieve control at rest and with exercise to relieve symptoms, and no evidence for significant deterioration in LV function AVN blocking agents (BB, CA channel blockers, Digoxin) Digoxin reduces only resting heart rate and not during activity Amiodarone can be used for rate control when others fail (severe LV dysfunction and CHF) AV junction ablation and PPM only as a last resort

Should assess rate control by exercise test or holter monitor

AF: Rate Control How much control, or how lenient?

RACE II Trial : • No difference between strict rate control (<80 at rest, <110 with exercise) and lenient strategy ( < 110)

• However, the mean HR in the strict control group was 75 and was 86 in the lenient group • Few patients had HR over 100 bpm • The trial was not that lenient

Newly diagnosed AF in the office: For Rhythm control strategy: Restore sinus rhythm (DCCV or chemical) after adequate AC (therapeutic INR for 3 weeks before CV or R/O LAA thrombus by TEE if over 48 h duration)

May not need to initiate AA therapy following the first episode Pill in the pocket for infrequent episodes in lone AF AA therapy to maintain SR when episodes are frequent Type of AA is based on the presence and severity of SHD Assess the role of ablation: Who is a good candidate?

Rhythm vs Rate Control in AF Evidence Base 5 prospective, controlled, randomized trials comparing 2 different treatment strategies

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 in Atrial Fibrillation

HOT CAFĂ&#x2030;

HOw to Treat Chronic Atrial Fibrillation

Fuster et al. J Am Coll Cardiol. 2006;48:854-906.

14

Percent

Rhythm vs Rate Control: Stroke and Mortality 20 18 16 14 12 10 8 6 4 2 0

Stroke

Death

Rate

Rhythm

Fuster et al. J Am Coll Cardiol. 2006;48:854-906.

15

AF: Rhythm vs. Rate Control AFFIRM Trial • • • • • • •

A total of 4060 were enrolled Mean age was 70 years 70% had HTN 39% had CAD Mean LVEF: 54% Both groups received anticoagulation Patients had to tolerate AF and had no contraindications for anticoagulation

AF: Strategies of Rate vs. Rhythm Control What did the clinical trials show ?

• No difference in mortality • No difference in quality of life • No difference in morbidity (strokes)

Mortality results for AFFIRM

AF: Rate vs. Rhythm Control Trial

Patients (n) Follow-up (y)

Age

Patients in SR

AFFIRM*

4060

3.5

70±9

35% vs. 63% ( at 5 y)

RACE

522

2.3

68±9

10% vs. 39% ( at 2.3 y)

PIAF

252

1

61±10

10% vs. 56% (at 1 y)

STAF

200

1.6

66±8

11% vs. 26% (at 2 y)

*Mean LVEF in AFFIRM was 54%

Reduction in mortality (%)

Sustaining Sinus Rhythm Is Associated With Decreased Mortality 60 50

44%

47%

40 30 20

95% CI, 0.30–0.64

99% CI, 28–61

P<.0001

P<.0001

DIAMOND*

AFFIRM†

10 0

*Danish Investigations of Arrhythmia and Mortality ON Dofetilide. †Atrial Fibrillation Follow-up Investigation of Rhythm Management.

The AFFIRM Investigators. Circulation. 2004;109:1509-1513; Pedersen OD et al. Circulation. 2001;104:292-296; Nattel S et al. Lancet. 2006;367:262-272.

Rate vs. Rhythm Control What is the verdict?

• The randomized clinical trials did not demonstrate mortality or morbidity differences between rate and rhythm control strategies • The patients randomized were elderly and tolerated rate control well (asymptomatic) • Anti-arrhythmic drug therapy was ineffective in maintaining sinus rhythm • Toxicity and pro-arrhythmic effects of these drugs may have offset any benefits from sinus rhythm • Patients who truly maintained sinus rhythm have better survival, symptoms, and quality of life.

• Symptoms –driven decisions should be taken when recommending management strategies

Rate vs. Rhythm Control Candidates for rate control • Asymptomatic or minimally symptomatic

Candidates for rhythm control • Symptomatic, LVF worsening due to AF • Young

• Elderly • Persistent • Prior failure of AA drugs

• Paroxysmal • Newly detected • No prior use of AA drugs

Dronedarone • Benzofuran derivative. Similar to amiodarone but without iodine moiety . (Lacks thyroid and pulmonary toxicity).

• Multichannel blocker with anti-adrenergic properties • Rate control properties: Reduces VR during AF by 11-13 bpm.

• • • • •

Metabolized by the liver (CYP3A4). Elimination HL: 19 hours Prolongs the QT interval. However, TdP is rare Increases Digoxin levels (by 1.7, 2.5 folds) Does not alter the INR 400 mg twice daily dose

ATHENA Trial: Study Design 4,628 patients >75 years with AF or 70-75 years with AF and at least one additional cardiovascular risk factor R

Dronedarone 400 mg BID

Placebo

Follow-up: 12-30 mos. (mean: 21 mos.)

Primary Endpoint: Composite of all-cause mortality and cardiovascular hospitalization

Secondary Endpoint: Death from any cause, cardiovascular death, CV hospitalizations JCE 2008; 19.1/Heart Rhythm 2008

ATHENA Trial: Hazard ratios for outcomes, dronedarone vs placebo groups (mean follow-up: 21 months) End point

HR (95% CI)

p

Death or CV hospitalization*

0.76 (0.69–0.84) <0.001

Death from any cause 0.84 (0.66–1.08) 0.18

CV death

0.71 (0.51–0.98) 0.03

CV hospitalization

0.74 (0.67–0.82) <0.001

*Primary end point

Hohnloser SH et al. N Engl J Med 2009; 360:668-678.

Amiodarone vs. Dronedarone for Prevention of Recurrent AF Amiodarone Dronedarone Sotalol Class IC Placebo

Patients in sinus rhythm at 1 year (%) 80 70 60 50 40 30 20 10 0

DIONYSOS: Amiodarone (58%) DIONYSOS: Dronedarone (36%)

CTAF

SAFE-T

AFFIRM

DAFNE

EURIDIS

ADONIS

Dronedarone in patients with CHF ANDROMEDA: â&#x20AC;˘ Increased mortality (8.1% vs. 3.8%) and worsening heart failure in pts. hospitalized with CHF and severe LV dysfunction Kober et al., NEJM 2008

Dronedarone should not be used in patients with LV dysfunction who have: 1. Recent CHF decompensation 2. patients with NYHA class III - IV

Dronedarone in Permanent Atrial Fibrillation PALLAS Trial – Dronedarone vs. placebo – Patients (≥65years) in permanent atrial fibrillation – And one other cardiovascular disease risk factor – Was stopped prematurely after median f/u of 3.5 months due to: – Significant increase in CV events (stroke, MI, systemic embolism, CV death) in the Dronedarone group Presented at AHA Nov. 2011

Dronedarone Summary • First AA drug to decrease CV mortality and hospitalizations • Can be used as a second line therapy (after BB) in most patients without structural heart disease • Should not be used in patients with acute or history of CHF • Should not be used in patients with LVEF< 35% • Should not be used in patients with chronic AF • Should not be used concomitantly with Dabigatran • Better side effect profile than amiodarone but less effective.

This drugnis not a replacement for amiodarone • Hepatic toxicity is rare, but careful monitoring is needed

AF: Rhythm Control Out-patient initiation of antiarrhythmic therapy Assessment of risk(pro-arrhythmic risk): Patients with structural heart disease Old patients Renal impairment History of pro-arrhythmia Conduction abnormalities or bradycardia on ECG

Out-patient initiation of AA therapy is reasonable for AF patients without structural heart disease. Class IIa (C)

2012 Focused Update of the ESC Guidelines for Management of Atrial Fibrillation Recommendation for AA drug therapy

AF: The Role of Ablation Focal Rapid firing from the pulmonary veins initiates and maintains AF in patients with PAF

Muscle sleeves extending into the pulmonary veins (source of ectopy)

Ablation of AF

Paroxysmal AF Elimination of main triggers: (circumferential PV isolation)

Persistent & long standing persistent AF Modifying the Arrhythmogenic substrate (additional linear lesions)

Ablation of AF • Results for paroxysmal are better than persistent AF (60-70% vs. 30-50%) • Many pts. will require more than one procedure • Recurrences are frequent even very late recurrences • Several single center and non-randomized studies showed superiority of ablation over AA medication MANTRA-PAF: Randomized, multicenter, 294 pts.

AA vs. catheter ablation as first line therapy. More pts. Were free of any AF or symptomatic AF in the ablation group but total AF burden was not significantly different.

(Similar results with RAAFT II and other studies are undergoing like CABANA…)

2012 HRS/EHRA/ECAS Expert Consensus Statement on AF ablation Indications for catheter ablation of Symptomatic AF

Indications for catheter ablation of Symptomatic AF Class

LoE

Paroxysmal AF

I

A

Persistent AF

IIa

Long standing persistent AF

IIb

Refractory to at least one class 1 or 3 antiarrhythmic

Class

LoE

Paroxysmal AF

IIa

B

B

Persistent AF

IIb

C

B

Long standing persistent AF

IIb

C

Prior to initiation of class 1 or 3 antiarrhythmic

2012 Focused update of ESC guidelines for AF management Catheter ablation of paroxysmal symptomatic AF refractory to antiarrhythmic therapy: Class I, (A)

Catheter ablation of paroxysmal symptomatic AF as first line therapy: Class IIa, (B)

Management of Atrial Fibrillation Summary (1) Accurate assessment of symptoms, identification of reversible causes, and evaluation of cardiac function are essential Rate control and AC according to TE risk should be achieved in all patients, and AC should continue even when SR seem to have been restored The choice of AA drug used is significantly influenced by the presence and severity of structural heart disease Lake of benefit of rhythm control strategy in reducing morbidity or mortality in AF is largely due to limited efficacy of AA, their side effects, and mainly their pro-arrhythmic effects

Management of Atrial Fibrillation Summary (2) Increasing evidence of superiority of catheter ablation over AA drugs in maintaining SR, improving symptoms and quality of life Large multi-center prospective randomized trials comparing AA drug therapy to catheter ablation are underway Catheter ablation is more effective in paroxysmal than in persistent AF, and is now a class I indication when AAs fail or as first line therapy in some cases

Thank You