New Application of Biventricular New Application of Biventricular

PacingPacing- Xiamen, 2010- Xiamen, 2010

Professor Cheuk-Man YUProfessor Cheuk-Man YUMBChB, MRCP, FHKCP, FHKAM, FRACP, MD, FRCP(Edin/London) MBChB, MRCP, FHKCP, FHKAM, FRACP, MD, FRCP(Edin/London)

Professor of MedicineProfessor of MedicineChairman, Department of Medicine & TherapeuticsChairman, Department of Medicine & Therapeutics

Assistant Dean (External Affairs)Assistant Dean (External Affairs)Director (Clinical Science), Institute of Vascular MedicineDirector (Clinical Science), Institute of Vascular Medicine

Head of Division of CardiologyHead of Division of CardiologyPrince of Wales HospitalPrince of Wales Hospital

The Chinese University of Hong KongThe Chinese University of Hong KongHong Kong, ChinaHong Kong, China

Venous system of the heart

Right atrial lead

Right ventricular lead

Left ventricular

lead

Cardiac Resynchronization Therapy (CRT)Cardiac Resynchronization Therapy (CRT)

Patient Considerations for CRTPatient Considerations for CRT

AHA / ACC / ESC Recommendation– Class I (Level of Evidence = A) :

NYHA class III-IV

QRS > 120-130ms

Ejection fraction <35%

LVVd > 5.5cm

Refractory to medical therapy

Exploration of New Indications for CRTExploration of New Indications for CRT

CHF, wide QRS, NYHA Class I / II

CHF, narrow QRS with dyssynchrony

CHF, wide QRS, less severe systolic dysfunction (EF 35-50%)

Diastolic heart failure

Non-CHF, bradycardia indication

Exploration of New Indications for CRTExploration of New Indications for CRT

CHF, wide QRS, NYHA Class I / II

CHF, narrow QRS with dyssynchrony

CHF, wide QRS, less severe systolic dysfunction (EF 35-50%)

Diastolic heart failure

Non-CHF, bradycardia indication

Relationship between RV pacing & HF

Sweeney et al. JACC 2006

Event Rate in DDD Pacing (RV Apical) Population

Death / HF Hospitalization

Study Yr. FU

21% PASE 2.5

33% CTOPP 3.5

23.6% MOST 2.6

22.6% DAVID 1

Dyssynchrony index (Ts-SD) with pacing = 39.7msDyssynchrony index (Ts-SD) with pacing = 39.7ms

Ts-SD without pacing = 14.6msTs-SD without pacing = 14.6ms

Reversible LV Dyssynchrony with RVA pacingFung JWH … Yu CM. Int J Cardiol 2009

Pacing ONPacing ONPacing OFFPacing OFF

Time of Minimal Time of Minimal regional volumeregional volume

Time of Minimal Time of Minimal regional volumeregional volume

RVA Pacing-induced Systolic Dyssynchrony in Patients with Preserved EF - Fang F … Yu CM. Eur J Echo 2010

RVA Pacing-induced Systolic Dyssynchrony in Patients with Preserved EF - Fang F … Yu CM. Eur J Echo 2010

LV End-systolic LV End-systolic Volume Volume

16

20

24

28

32

En

d-s

ysto

lic

volu

me,

ml

Pacing off Pacing on

P=0.04

0

1

2

3

4

5

6T

smv16

-SD

, %P<0.001

TTsmvsmv16-SD16-SD

N = 93 RVA pacing “On” & “Off”

Pacing off Pacing on

55

60

65

70

75

EF

, %

P<0.001

EFEF

Pacing off Pacing on

Dyssynchronous Dyssynchronous electrical activationelectrical activation

LV mechanical dyssynchrony

LV mechanical disadvantage and

↓efficiency: right ward shift of P-V relation

LV adverse remodeling and asymmetrical

hypertrophy

Increase in wall stress

Impaired myocardial perfusion

Neurohormonal and sympathetic activation

Pathophysiology of RV pacing

PPacing to acing to AAvoid void CCardiac ardiac EEnlargement nlargement

(PACE) Study(PACE) Study

1 1 Institute of Vascular Medicine & Division of Cardiology, Department of Medicine & Institute of Vascular Medicine & Division of Cardiology, Department of Medicine &

Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, 2 2 Department of Cardiology, National Heart Institute, Kuala Lumpur, MalaysiaDepartment of Cardiology, National Heart Institute, Kuala Lumpur, Malaysia

11Cheuk-Man YuCheuk-Man Yu, , 11Joseph Yat-Sun Chan, Joseph Yat-Sun Chan, 22Omar Razali, Omar Razali, 22Hussin Azlan, Hussin Azlan, 11Qing Qing

Zhang, Zhang, 11Gabriel Wai-Kwok Yip, Gabriel Wai-Kwok Yip, 11Fang Fang, Fang Fang, 11Anna Chan, Anna Chan, 11Yat-Yin Lam, Yat-Yin Lam,

11Jeffrey Wing-Hong FungJeffrey Wing-Hong Fung

PPacing to acing to AAvoid void CCardiac ardiac EEnlargement (PACE) Studynlargement (PACE) Study

Late-breaking Clinical Science trial in AHA 2009Late-breaking Clinical Science trial in AHA 2009

PACE studyPACE study

Steering Committee: Steering Committee:

C.M. Yu, G.W.K. Yip, Q. Zhang, J.Y.S. Chan, The Chinese University of Hong Kong; C.M. Yu, G.W.K. Yip, Q. Zhang, J.Y.S. Chan, The Chinese University of Hong Kong; J.W.H. Fung, North District Hospital; O. Razali, H. Azlan; National Heart InstituteJ.W.H. Fung, North District Hospital; O. Razali, H. Azlan; National Heart Institute

Echocardiographic Core Laboratory: Echocardiographic Core Laboratory:

G.W.K. Yip, C.M. Yu, Q. Zhang, F. Fang, The Chinese University of Hong KongG.W.K. Yip, C.M. Yu, Q. Zhang, F. Fang, The Chinese University of Hong Kong

Clinical Event Committee: Clinical Event Committee:

W. Chan, A. Chan, The Chinese University of Hong Kong; W.L Chan, Alice Ho Miu Ling W. Chan, A. Chan, The Chinese University of Hong Kong; W.L Chan, Alice Ho Miu Ling Nethersole HospitalNethersole Hospital

Other investigators and institutions that participated in the PACE study: Other investigators and institutions that participated in the PACE study:

Alice Ho Miu Ling Nethersole Hospital, Hong Kong – H.C.K. Chan, W.L. Chan; Prince Alice Ho Miu Ling Nethersole Hospital, Hong Kong – H.C.K. Chan, W.L. Chan; Prince of Wales Hospital, The Chinese University of Hong Kong – J.Y.S. Chan, C.M. Yu, of Wales Hospital, The Chinese University of Hong Kong – J.Y.S. Chan, C.M. Yu, G.W.K. Yip, A.K.Y. Chan; G.C.P. Chan; National Heart Institute, Kuala Lumpur – O. G.W.K. Yip, A.K.Y. Chan; G.C.P. Chan; National Heart Institute, Kuala Lumpur – O. Razali, H. Azlan, K.H. Lam; North District Hospital, Hong Kong – J.W.H. Fung, K.H. YiuRazali, H. Azlan, K.H. Lam; North District Hospital, Hong Kong – J.W.H. Fung, K.H. Yiu

PACE : Hypothesis & Study DesignPACE : Hypothesis & Study Design

A A multicentermulticenter, , prospectiveprospective, , double-blindeddouble-blinded, , randomizedrandomized study to examine if study to examine if

atrial-synchronized BiV pacing is superior to RVA pacing in preserving LV atrial-synchronized BiV pacing is superior to RVA pacing in preserving LV

systolic function & avoiding adverse LV structural remodeling in patients systolic function & avoiding adverse LV structural remodeling in patients

with standard pacing indication and normal LV ejection fractionwith standard pacing indication and normal LV ejection fraction

PACE : PatientsPACE : Patients

Inclusion criteriaInclusion criteria

Patients with normal LV ejection fraction (Patients with normal LV ejection fraction (≥≥45%) who had standard pacing 45%) who had standard pacing

indicationsindications

Exclusion criteriaExclusion criteria

Persistent atrial fibrillationPersistent atrial fibrillation

Acute coronary syndromeAcute coronary syndrome

Percutaneous coronary intervention or CABG <3monthsPercutaneous coronary intervention or CABG <3months

Life expectancy of <6 monthsLife expectancy of <6 months

Heart transplant recipientsHeart transplant recipients

Pregnant womenPregnant women

Study flowchartStudy flowchart

RecruitmentRecruitment

251 Were screened for 251 Were screened for

pacemaker therapypacemaker therapy

238 Fulfilled the study 238 Fulfilled the study

inclusion criteriainclusion criteria

193 Underwent device193 Underwent device

implantationimplantation

Excluded: Excluded: inadequate image inadequate image quality (7), ejection quality (7), ejection fraction<45% (6)fraction<45% (6)

45 declined 45 declined

participationparticipation

177 underwent 177 underwent

randomizationrandomization

67 Had normal 67 Had normal

diastolic functiondiastolic function110 Had diastolic 110 Had diastolic

dysfunctiondysfunction

RVA pacingRVA pacing(n=33)(n=33)

BiV pacingBiV pacing(n=34)(n=34)

RVA pacingRVA pacing(n=55)(n=55)

BiV pacingBiV pacing(n=55)(n=55)

RandomizationRandomization

88 received 88 received

RVA pacing RVA pacing

(97% RVA (97% RVA

pacing)pacing)

89 received 89 received

BiV pacing BiV pacing

(98% BiV (98% BiV

pacing)pacing)

86 completed86 completed

1-yr follow up1-yr follow up88 completed88 completed

1-yr follow up 1-yr follow up

(1 had (1 had

inadequate inadequate

image quality image quality

for analysis)for analysis)

1 declined 1 declined

follow upfollow up

1 died, 1 1 died, 1 declined declined follow upfollow up

Follow upFollow up

PACE : Biventricular Device ImplantationPACE : Biventricular Device Implantation

PACE : Study End-pointsPACE : Study End-points

Primary End-points

LV ejection fraction at 12 months LV ejection fraction at 12 months

LV end-systolic volume at 12 monthsLV end-systolic volume at 12 months

Secondary End-points

LV end-diastolic volumeLV end-diastolic volume

6-min hall walk distance6-min hall walk distance

Quality of life scoresQuality of life scores

Baseline CharacteristicsBaseline Characteristics

ParametersParameters RVA pacing (n=88)RVA pacing (n=88) BiV pacing (n=89)BiV pacing (n=89) P valueP value

Age – years 68±11 69±11 0.76

Male sex – no. (%) 49 (56) 47 (53) 0.70

Systolic blood pressure – mmHg 143±22 148±24 0.14

Diastolic blood pressure – mmHg 69±12 73±12 0.01

Heart rate – bpm 59±18 59±17 0.98

QRS duration – ms 107±30 107±27 0.98

Left ventricular ejection fraction – % 61.5±6.6 61.9±6.7 0.86

Dyssynchrony Index – ms 12.4±8.1 14.0±10.6 0.43

Indication for pacing – no. (%) 0.24

Advanced atrioventricular block 55 (63) 49 (55)

Sinus node dysfunction 33 (37) 40 (45)

Medical history – no. (%)

Hypertension 55 (62) 62 (70) 0.24

Diabetes mellitus 26 (29) 23 (26) 0.70

Coronary heart disease 20 (23) 19 (21) 0.71

Heart failure 12 (14) 10 (11) 0.63

Chronic renal failure 4 (5) 2 (2) 0.44

PACE : Comparison of Primary End-pointsPACE : Comparison of Primary End-points

*P<0.001 vs RVA pacing*P<0.001 vs RVA pacing

RVA pacingRVA pacing

BiV pacingBiV pacing

LV

eje

cti

on

fra

cti

on

(%

)L

V e

jec

tio

n f

rac

tio

n (

%)

50.0

55.0

60.0

65.0P=0.76

P<0.001

*

Baseline 1 yr

20.0

25.0

30.0

35.0

40.0

*

LV

en

d-s

ys

toli

c v

olu

me

(m

l)L

V e

nd

-sy

sto

lic

vo

lum

e (

ml)

Baseline 1 yr

P<0.001

P=0.42

*P<0.001 vs RVA pacing*P<0.001 vs RVA pacing

Absolute difference of EF Absolute difference of EF by 7%by 7%

Absolute difference of LVESV by Absolute difference of LVESV by 8.1ml 8.1ml

Subgroup Analysis Subgroup Analysis – LV Ejection Fraction– LV Ejection Fraction

Subgroup Analysis Subgroup Analysis – LV End-Systolic Volume– LV End-Systolic Volume

PACE Study : RVA PacingPACE Study : RVA Pacing

BaselineBaseline 1 Year1 Year

PACE Study : Biventricular PacingPACE Study : Biventricular Pacing

BaselineBaseline 1 Year1 Year

PACE : ConclusionPACE : Conclusion

The first randomized, controlled study showing that in patients The first randomized, controlled study showing that in patients

with bradycardia and normal EF, the detrimental effect of RVA with bradycardia and normal EF, the detrimental effect of RVA

pacing on LV systolic function & remodelling can be prevented pacing on LV systolic function & remodelling can be prevented

by BiV pacingby BiV pacing

Medical Team, Division of Cardiology

Research Team, Division of Cardiology

CUHK-Mayo Clinic-AsiaCUHK-Mayo Clinic-Asia Cardiovascular Summit 2011Cardiovascular Summit 2011

Congress Secretariat:

Division of Cardiology, Department of Medicine & Therapeutics

The Chinese University of Hong Kong

Tel: (852) 2647-6639

Fax: (852) 2144-5343

Email: cardiology@cuhk.edu.hk

Postgraduate Education Centre, Prince of Wales Hospital, Hong Kong26-27 March 201126-27 March 2011

Organised by:

In collaboration with:

www.mect.cuhk.edu.hk/cardiologywww.mect.cuhk.edu.hk/cardiology