1. New Application of Biventricular Pacing - Xiamen, 2010
Professor Cheuk-Man YU
MBChB, MRCP, FHKCP, FHKAM, FRACP, MD, FRCP(Edin/London)
Professor of Medicine
Chairman, Department of Medicine & Therapeutics
Assistant Dean (External Affairs)
Director (Clinical Science), Institute of Vascular Medicine
Head of Division of Cardiology
Prince of Wales Hospital
The Chinese University of Hong Kong
Hong Kong, China

2. Cardiac Resynchronization Therapy (CRT)
Right atrial lead
Left ventricular lead
Right ventricular lead
Venous system of the heart

3. Patient Considerations for CRT
AHA / ACC / ESC Recommendation– Class I (Level of Evidence = A) :
NYHA class III-IV
QRS > ms
Ejection fraction <35%
LVVd > 5.5cm
Refractory to medical therapy

4. Exploration 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

5. Exploration 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

6. Relationship between RV pacing & HF
Sweeney et al. JACC 2006

7. 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

8. Reversible LV Dyssynchrony with RVA pacing
Fung JWH … Yu CM. Int J Cardiol 2009
Dyssynchrony index (Ts-SD) with pacing = 39.7ms
Ts-SD without pacing = 14.6ms

9. RVA Pacing-induced Systolic Dyssynchrony in Patients with Preserved EF - Fang F … Yu CM. Eur J Echo 2010
Pacing OFF
Pacing ON
Time of Minimal regional volume
Time of Minimal regional volume

10. LV End-systolic Volume End-systolic volume, ml
RVA Pacing-induced Systolic Dyssynchrony in Patients with Preserved EF - Fang F … Yu CM. Eur J Echo 2010 EF
EF, %
P<0.001
Tsmv16-SD
Tsmv16-SD, %
P<0.001
Pacing off
Pacing on
LV End-systolic Volume
End-systolic volume, ml
Pacing off
Pacing on
P=0.04
N = 93
RVA pacing “On” & “Off”
Pacing off
Pacing on

11. Pathophysiology of RV pacing
Dyssynchronous electrical activation
LV mechanical dyssynchrony
LV mechanical disadvantage and ↓efficiency: right ward shift of P-V relation
Impaired myocardial perfusion
Increase in wall stress
LV adverse remodeling and asymmetrical hypertrophy
Neurohormonal and sympathetic activation

12. Pacing to Avoid Cardiac Enlargement (PACE) Study
1Cheuk-Man Yu, 1Joseph Yat-Sun Chan, 2Omar Razali, 2Hussin Azlan, 1Qing Zhang, 1Gabriel Wai-Kwok Yip, 1Fang Fang, 1Anna Chan, 1Yat-Yin Lam, 1Jeffrey Wing-Hong Fung
1 Institute of Vascular Medicine & Division of Cardiology, Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong,
2 Department of Cardiology, National Heart Institute, Kuala Lumpur, Malaysia 12

13. Pacing to Avoid Cardiac Enlargement (PACE) Study
Late-breaking Clinical Science trial in AHA 2009 13

14. PACE study Steering Committee:
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 Institute
Echocardiographic Core Laboratory:
G.W.K. Yip, C.M. Yu, Q. Zhang, F. Fang, The Chinese University of Hong Kong
Clinical Event Committee:
W. Chan, A. Chan, The Chinese University of Hong Kong; W.L Chan, Alice Ho Miu Ling Nethersole Hospital
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 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. Razali, H. Azlan, K.H. Lam; North District Hospital, Hong Kong – J.W.H. Fung, K.H. Yiu 14

15. PACE : Hypothesis & Study Design
A multicenter, prospective, double-blinded, randomized study to examine if atrial-synchronized BiV pacing is superior to RVA pacing in preserving LV systolic function & avoiding adverse LV structural remodeling in patients with standard pacing indication and normal LV ejection fraction 15

16. PACE : Patients Inclusion criteria
Patients with normal LV ejection fraction (≥45%) who had standard pacing indications
Exclusion criteria
Persistent atrial fibrillation
Acute coronary syndrome
Percutaneous coronary intervention or CABG <3months
Life expectancy of <6 months
Heart transplant recipients
Pregnant women 16

17. Study flowchart Recruitment Randomization Follow up 17
251 Were screened for pacemaker therapy
238 Fulfilled the study inclusion criteria
193 Underwent device
implantation
Excluded: inadequate image quality (7), ejection fraction<45% (6)
45 declined participation
177 underwent randomization
67 Had normal diastolic function
110 Had diastolic dysfunction
RVA pacing
(n=33)
BiV pacing
(n=34)
(n=55)
Randomization
88 received
RVA pacing (97% RVA pacing)
89 received
BiV pacing (98% BiV pacing)
86 completed
1-yr follow up
88 completed
1-yr follow up (1 had inadequate image quality for analysis)
1 declined follow up
1 died, 1 declined follow up
Follow up 17

18. PACE : Biventricular Device Implantation18

19. PACE : Study End-points
Primary End-points
LV ejection fraction at 12 months
LV end-systolic volume at 12 months
Secondary End-points
LV end-diastolic volume
6-min hall walk distance
Quality of life scores 19

20. Baseline Characteristics
Parameters
RVA pacing (n=88)
BiV pacing (n=89)
P 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
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)
Diabetes mellitus
26 (29)
23 (26)
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 20

21. PACE : Comparison of Primary End-points
BiV pacing
RVA pacing
LV ejection fraction (%)
P=0.76
P<0.001 *
Baseline
1 yr *
LV end-systolic volume (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
by 7%
Absolute difference of LVESV by 8.1ml 21

22. Subgroup Analysis – LV Ejection Fraction22

23. Subgroup Analysis – LV End-Systolic Volume23

24. PACE Study : RVA Pacing
Baseline
1 Year 24

25. PACE Study : Biventricular Pacing
Baseline
1 Year 25

26. PACE : Conclusion
The first randomized, controlled study showing that in patients with bradycardia and normal EF, the detrimental effect of RVA pacing on LV systolic function & remodelling can be prevented by BiV pacing 26

27. Medical Team, Division of Cardiology

28. Research Team, Division of Cardiology

29. CUHK-Mayo Clinic-Asia
Cardiovascular Summit 2011
26-27 March 2011
Postgraduate Education Centre, Prince of Wales Hospital, Hong Kong
Organised by:
In collaboration with:
Congress Secretariat:
Division of Cardiology, Department of Medicine & Therapeutics
The Chinese University of Hong Kong
Tel: (852)
Fax: (852)