AF in Patients with Heart Failure Role of AVN Ablation and CRT

AF in Patients with Heart FailureRole of AVN Ablation and CRT

Win K. Shen, MD

Professor of Medicine

Mayo Clinic College of Medicine

Chair, Cardiovascular Diseases

Mayo Clinic Arizona

ACC Florida, 2014

DISCLOSUREDISCLOSUREDISCLOSUREDISCLOSURE

Relevant Financial Relationship(s)None

Off Label UsageNone

Relevant Financial Relationship(s)None

Off Label UsageNone

ObjectivesAtrial Fibrillation and Heart Failure

ObjectivesAtrial Fibrillation and Heart Failure

• Cyclical Relationship: MechanismsAF promotes HFHF promotes AF

• A Case StudyIndications for CRTWhat should be the minimum % of pacing? When to ablate the AVN?

• A review of guidelines and consensus

• Cyclical Relationship: MechanismsAF promotes HFHF promotes AF

• A Case StudyIndications for CRTWhat should be the minimum % of pacing? When to ablate the AVN?

• A review of guidelines and consensus

AFib and CHF – Temporal Relations and MortalityAFib and CHF – Temporal Relations and MortalityFramingham StudyFramingham Study

AFib and CHF – Temporal Relations and MortalityAFib and CHF – Temporal Relations and MortalityFramingham StudyFramingham Study

CP1119361-1

MenMen

Impact of incident CHF Impact of incident CHF on mortality (RR+CI)on mortality (RR+CI)

WomenWomen2.72.7

(1.9-3.7)(1.9-3.7)3.13.1

(2.2-4.2)(2.2-4.2)

MenMen

Impact of incident AFib Impact of incident AFib on mortalityon mortality

WomenWomen1.61.6

(1.2-2.1)(1.2-2.1)2.72.7

(2.0-3.6)(2.0-3.6)

Benjamin: Circ, 2003Benjamin: Circ, 2003

Development of CHF in Pt with AFibDevelopment of CHF in Pt with AFib

YearsYears

Cumulative incidence

of CHF


of CHF

Development of AFib in Pt with CHFDevelopment of AFib in Pt with CHF

YearsYears


of AF


of AF

Atrial Fibrillation and CHF Atrial Fibrillation and CHF Atrial Fibrillation and CHF Atrial Fibrillation and CHF

CHF AFCHF AF• Atrial dilatationAtrial dilatation

• Stretch receptor activationStretch receptor activation

• Neuro-humoral modulationNeuro-humoral modulation

• Signal transduction/bioenergeticsSignal transduction/bioenergetics

• Electropysiologic remodelingElectropysiologic remodeling

• FibrosisFibrosis

AutomaticityAutomaticity RefactorinessRefactorinessConductionConduction

A viciousA viciouscyclecycle

• Loss of atrial contractionLoss of atrial contraction

• Impaired ventricular fillingImpaired ventricular filling

• High heart ratesHigh heart rates

EFEF perfusionperfusionNeurohormonal activationNeurohormonal activationSympathetic stimulationSympathetic stimulation

Use of negative inotropic drugsUse of negative inotropic drugs

TriggeredTriggeredactivityactivity

CHFCHF

AtrialAtrialfibrillationfibrillation

CP1110819-1

AFAF CHFCHF

71 year-old man has mixed CM for 2-3 years. He has permanent AF. Despite medical therapy, he has SOB walking 2-3 blocks and worse at higher altitude. Most recent EF was 28%, LVEDD 59 mm. He has been treated with carvedilol, losartan, lasix, simvastatin, ASA, warfarin. EKG is shown, QRSD 150 msec.

71 year-old man has mixed CM for 2-3 years. He has permanent AF. Despite medical therapy, he has SOB walking 2-3 blocks and worse at higher altitude. Most recent EF was 28%, LVEDD 59 mm. He has been treated with carvedilol, losartan, lasix, simvastatin, ASA, warfarin. EKG is shown, QRSD 150 msec.

Case Study

Case Study Case Study

What would you recommend?

1. CRT is indicated (I)

2. CRT can be useful (IIa)

3. CRT may be reasonable (IIb)

4. CRT is not recommended (III)







If you did implant a CRT, would you recommend AVN ablation?

1. Yes

2. No

If you did implant a CRT, would you recommend AVN ablation?

1. Yes

2. No


If you did not recommend AVN ablation, what would be the desired % of pacing?

1. > 50%

2. > 70%

3. > 90%

4. ~ 100%


1. > 50%

2. > 70%

3. > 90%

4. ~ 100%

CP1313975-1

Recommendations for CRT in Patients With Systolic Heart FailureAHA/ACC/HRS 2012

2012 DBT Focused Update Recommendations Comments

Class I

1. CRT is indicated for patients who have LVEF less than or equal to 35%, sinus rhythm, LBBB with a QRS duration greater than or equal to 150 msec, and NYHA functional class II, III, or ambulatory IV symptoms on GDMT (14- 19). (Level of Evidence: A)

Modified recommendation (specifying CRT in patients with LBBB of !150 msec; expanded to include those with functional class II symptoms).

Class IIa1. CRT can be useful for patients who have LVEF less

than or equal to 35%, sinus rhythm, LBBB with a QRS duration 120 to 149 msec, and NYHA functional class II, III or ambulatory IV symptoms on GDMT. (14-18, 20) (Level of Evidence: A)

New recommendation

(REVERSE, MADIT-CRT, RAFT)

2. CRT can be useful for patients who have LVEF less than or equal to 35%, sinus rhythm, a non-LBBB pattern with a QRS greater than or equal to 150 msec, and NYHA functional class III/ambulatory class IV symptoms on GDMT (14-17). (Level of Evidence: A)

New recommendation

3. CRT can be useful for patients on GDMT who have LVEF less than or equal to 35% and meet CRT indications as above who have atrial fibrillation with adequate rate control allowing for near 100% ventricular pacing (21-24). (Level of Evidence: B)

Modified recommendation (wording changed to indicate benefit based on EF rather than functional class; level of evidence changed from C to B).

(PAVE, APAF, RAFT (15% AF)4. CRT can be useful for patients on GDMT who have

LVEF less than or equal to 35%, and are undergoing device placement with anticipated requirement for significant ventricular pacing (23, 25-27). (Level of Evidence: C)

Modified recommendation (functional class expanded; class changed from IIb to IIa).

Cardiac Resynchronization Therapy Permanent AFib

Cardiac Resynchronization Therapy Permanent AFib

Recommendations Classa Levelb

1) Pt with HF, wide QRS and reduced LVEF1) Pt with HF, wide QRS and reduced LVEF; ; CRT should be considered in chronic HF pt, intrinsic CRT should be considered in chronic HF pt, intrinsic QRS ≥120 ms and LVEF ≤35% who remain in NYHA QRS ≥120 ms and LVEF ≤35% who remain in NYHA functional class III and ambulatory IV despite functional class III and ambulatory IV despite adequate medical treatment, provided that a BiV adequate medical treatment, provided that a BiV pacing as close to 100% as possible can pacing as close to 100% as possible can be achievedbe achieved

IIa B

Brignole et al: EHJ 34:2281, 2013












Variable BV Pacing in AFVariable BV Pacing in AFVariable BV Pacing in AFVariable BV Pacing in AF

VSR/VTR Conducted AF Response(BV)

Pseudo Fusion

Six Studies Reporting Outcome DataSix Studies Reporting Outcome Datafor AF Patients Undergoing CRT for HFfor AF Patients Undergoing CRT for HFSix Studies Reporting Outcome DataSix Studies Reporting Outcome Data

for AF Patients Undergoing CRT for HFfor AF Patients Undergoing CRT for HF

Ganesan et al: J Am Coll Cardiol 2012;59:719–26

First author, yrFirst author, yr Study typeStudy type NN Inclusion criteriaInclusion criteria

Comparator Comparator intervention intervention

groupsgroups NN Age (yrs)Age (yrs)Male Male (%)(%) AF characteristicsAF characteristics Follow-upFollow-up % BVP% BVP

Molhoek, 2004Molhoek, 2004 Prospective Prospective single-center single-center cohortcohort

6060 Drug-refractory Drug-refractory NYHA III-IV heart NYHA III-IV heart failure, LVEF failure, LVEF 35%, QRS 35%, QRS duration duration 120 ms120 ms

CRT-SRCRT-SRCRT-AF-AVNA+CRT-AF-AVNA+CRT-AF-AVNA-CRT-AF-AVNA-

303017171313

68±868±863±10*63±10*

80809090

100% long-100% long-standing persistent standing persistent AFAF(>3 mos)(>3 mos)

6 mos6 mos Not Not reportedreported

100%100%82%82%

Gasparini, 2006Gasparini, 2006 Prospective 2-Prospective 2-center cohortcenter cohort

673673 Drug-refractory Drug-refractory NYHA NYHA 11 heart 11 heart failure, LVEF failure, LVEF QRS durationQRS duration120 ms120 ms


5115111141144848 66*66*

8585 100% permanent 100% permanent AFAF

25.2±18 25.2±18 mosmos

98.5±1.8%98.5±1.8%98.4±2.1%98.4±2.1%88.2±3.1%88.2±3.1%

Ferreira, 2008Ferreira, 2008 Retrospective Retrospective single-center single-center cohortcohort

131131 Drug-refractory Drug-refractory NYHA II-IV heart NYHA II-IV heart failure, LVEF failure, LVEF 35%, QRS 35%, QRS duration duration 120 ms120 ms


787826262727

66±1066±1067±967±970±870±8

747492929696

Not listed for each Not listed for each subgroupsubgroup

6 mos6 mos 95±13%95±13%98±6%98±6%87±19%87±19%

Gasparini, 2008Gasparini, 2008 Retrospective Retrospective multicenter multicenter registry cohortregistry cohort

1,2851,285 Not pre-specifiedNot pre-specified CRT-SRCRT-SRCRT-AF-AVNA+CRT-AF-AVNA+CRt-AF-AVNA-CRt-AF-AVNA-

1,0421,042118118125125

63±1063±1066±966±967±967±9

757578788484

100% permanent 100% permanent AFAF

Median FU Median FU 34 mos34 mos

Not Not reportedreported

98.7±1.8%98.7±1.8%89.4±2.4%89.4±2.4%

Tolosana, 2008Tolosana, 2008 Retrospective Retrospective multicenter multicenter cohortcohort

470470 Drug-refractory Drug-refractory NYHA III-IV heart NYHA III-IV heart failure, LVEF failure, LVEF 35%, QRS 35%, QRS duration duration 120 ms120 ms


3443441919

107107

67±967±970±770±7

68±1068±10

76768181

100% permanent 100% permanent AFAF

12 mos12 mos Not Not reportedreported

100%100%92±7%92±7%

Dong, 2010Dong, 2010 Retrospective Retrospective single-center single-center cohortcohort

154154 Heart failure Heart failure symptoms symptoms despitedespite

CRT-AF-AVNA+CRT-AF-AVNA+CRT-AF-AVNA-CRT-AF-AVNA-

4545109109

72±972±968±1168±11

84848787

88% permanent AF88% permanent AF Median FUMedian FU274 days274 days

Median FUMedian FU222 days222 days††

99.0%99.0%(95% CI: (95% CI: 95-100%)95-100%)

96.5%96.5%(95% CI: (95% CI:

85.5-99%)85.5-99%)

*Represents mean age of CRT-AF patients as a group; †24% lost to follow-up

Mean Difference in NYHA Functional Class for Mean Difference in NYHA Functional Class for CRT-AF Patients Undergoing AVNA vs Medical CRT-AF Patients Undergoing AVNA vs Medical

Therapy with Rate-Controlling DrugsTherapy with Rate-Controlling Drugs

Mean Difference in NYHA Functional Class for Mean Difference in NYHA Functional Class for CRT-AF Patients Undergoing AVNA vs Medical CRT-AF Patients Undergoing AVNA vs Medical

Therapy with Rate-Controlling DrugsTherapy with Rate-Controlling Drugs

Ganesan et al: J Am Coll Cardiol 2012;59:719–26

Difference Difference in meansStudy name in means P and 95% CI

Molhoek 2004 -0.100 0.572

Ferreira 2008 -0.500 0.000

Dong 2010 -0.300 0.009

-0.339 0.002-20-20 -10-10 00 1010 2020

Favors AVNA+

Favors AVNA-



1. > 50%

2. > 70%

3. > 90%

4. ~ 100%


1. > 50%

2. > 70%

3. > 90%

4. ~ 100%

Case Study CRT-D Implanted (05/22/12)

Case Study CRT-D Implanted (05/22/12)

Case Study Post Implantation EKG (5/22/12)

QRSD 138 msec

Case Study Post Implantation EKG (5/22/12)

QRSD 138 msec

Case Study Follow Up (10/22/13)

Case Study Follow Up (10/22/13)

98% BV pacingQRSD 138 msec, LVEDD 55 mmEF 42%, symptoms improved from II to 1-II

Indication for AVJ Ablation in Patients With Symptomatic Permanent AFib and Optimal

Pharmacological Therapy

Indication for AVJ Ablation in Patients With Symptomatic Permanent AFib and Optimal

Pharmacological TherapyHeart Failure, NYHA

class III–IV and EF <35%

CRT

QRS ≥120 ms

Reduced EF anduncontrollable HR, any QRS

AVJ ablationand no CRT No AVJ ablation

IncompleteBiV pacing

CompleteBiV pacing

AVJ ablation

QRS <120 ms

Adequaterate control

Inadequaterate control

No AVJ ablationNo CRT

AVJ ablationand No CRT

Brignole et al: EHJ 34:2281, 2013

AF and HFAF and HF

ACC Florida, 2014ACC Florida, 2014ACC Florida, 2014ACC Florida, 2014

European Survey of Primary Care PhysiciansEuropean Survey of Primary Care Physicians

• 15 countries• 1,363 physicians• 11,062 pt• 1999-2000

• 15 countries• 1,363 physicians• 11,062 pt• 1999-2000

SymptomsSymptoms

Moderate severe41%

Moderate severe41%

Cleland J: Lancet, 2002Cleland J: Lancet, 2002Cleland J: Lancet, 2002Cleland J: Lancet, 2002 CP1090494-1

Stevenson WStevenson WStevenson WStevenson W

Atrial Fibrillation in Heart FailureAtrial Fibrillation in Heart FailureAtrial Fibrillation in Heart FailureAtrial Fibrillation in Heart Failure

Patients (%)Patients (%)

SOLVD, 1992SOLVD, 1992SOLVD, 1992SOLVD, 1992

SOLVD, 1991SOLVD, 1991SOLVD, 1991SOLVD, 1991

V-HeFT, 1991V-HeFT, 1991V-HeFT, 1991V-HeFT, 1991

CHF-STAT, 1991CHF-STAT, 1991CHF-STAT, 1991CHF-STAT, 1991

Stevenson, 1996Stevenson, 1996Stevenson, 1996Stevenson, 1996

GESICA, 1994GESICA, 1994GESICA, 1994GESICA, 1994

Functional classFunctional classFunctional classFunctional class

CONSENSUS, 1987CONSENSUS, 1987CONSENSUS, 1987CONSENSUS, 1987

0 20 40 60 80 100

IIII

II-IIIII-IIIII-IIIII-III

III-IVIII-IVIII-IVIII-IV

IVIVIVIV

Atrial fib22%

CP1068448-51CP1068448-51

0

10

20

30

CC DD

AAAA BBBB

ControlControlControlControl CHFCHFCHFCHFLA

are

a (c

mL

A a

rea

(cm

22 ))L

A a

rea

(cm

LA

are

a (c

m22 ))

0.0

2.5

5.0

7.5

10.0

ControlControlControlControl CHFCHFCHFCHF

Avg

atr

ial %

Avg

atr

ial %

fib

rosi

sfi

bro

sis

Avg

atr

ial %

Avg

atr

ial %

fib

rosi

sfi

bro

sis

**** ****

Cha, AJP 2003Cha, AJP 2003

Heart Failure, Left Atrial Size and Tissue FibrosisHeart Failure, Left Atrial Size and Tissue Fibrosis

80-Year-Old Female80-Year-Old Female

Grogan M: AJC 69:1573, 1992Grogan M: AJC 69:1573, 1992

Serial Changes in EFSerial Changes in EF

*Heart rate 140 one week earlier*Heart rate 140 one week earlier

00

2020

4040

6060

AF 120AF 120 AF 70AF 70 AF 76AF 76 AF 70AF 70

6060 6060

EFEF(%)(%)

4040

Heart rate (bpm)Heart rate (bpm)

3030

CP1000536-4

AF–Adverse Effect of Irregular RateAF–Adverse Effect of Irregular RateAF–Adverse Effect of Irregular RateAF–Adverse Effect of Irregular Rate

VVIVVI VVIVVI VVTVVTVVTVVTVVI = regular rate at mean AF rate

VVT = irregular rate tracking AF

Clark et al: JACC, 1997

L/minL/min

00

22

44

66

88

Cardiac OutputCardiac Output

P<0.01P<0.01

mmmmHgHg

00

55

1010

1515

2020

2525

Wedge PressureWedge Pressure

P<0.002P<0.002

CP942080-15

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AF in Patients with Heart Failure Role of AVN Ablation and CRT

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