Targeted Left Ventricular Lead Placement to Guide
Cardiac Resynchronisation Therapy: A Randomised
Controlled Trial (TARGET study)
Khan FZ1,2, Virdee MS2, Palmer CR3, Pugh PJ1, O’Halloran D1,
Elsik M2, Read PA2, Begley D2, Fynn SP2, Dutka DP1
1Addenbrooke’s
Hospital, Cambridge, UK
2Papworth Hospital, Cambridge, UK
3Centre for Applied Medical Statistics, Cambridge, UK
Disclosures
Disclosures:
None
Sponsorship:
Papworth Hospital,
Cambridge, UK
Funding:
NIHR UK
Papworth Hospital,
Addenbrooke’s Charitable Trust
Trial
Registration:
ISRCTN19717943
Introduction
• Cardiac Resynchronisation Therapy (CRT) has evolved as
established treatment for advanced heart failure
symptoms, impaired LV systolic function and
intraventricular conduction delay
• 30-40% of patients fail to gain significant clinical benefit
• Left ventricular (LV) lead position has emerged as an
important determinant of response
LV Lead Position in CRT
Higher response when pacing
the latest site of contraction1
1
Lower response when pacing
areas of scar2
Ypenburg et al J Am Coll Cardiol.2009;53(6):483-490
et al Circulation 2006;113(7):969-976.
2Bleeker
Hypothesis
• There have been no randomised controlled trials to
investigate the impact of LV lead position
• The TARGET study designed to prospectively assess the
feasibility of a targeted approach to LV lead placement
and the impact of LV lead targeting on CRT outcomes
• We tested the hypothesis that targeted LV lead placement
to the latest site of contraction and away from areas of
scar would enhance CRT response when compared to
usual (unguided) treatment
Study Design
Single blinded, randomised controlled trial, 2 UK centres
Inclusion: Sinus rhythm, NYHA Class III/IV, LVEF<35%, QRS>120ms
Baseline (all patients): LV volumes, EF, NYHA, 6MWT, MLHFLQ
Randomisation
CONTROL Group
Standard CRT
LV Lead Placement without
echocardiographic guidance
TARGET Group
Targeted LV Lead
Speckle Tracking Echocardiography
used to identify optimal site and LV
lead targeted to this site
All CRT devices optimised using echo following implant
Speckle Tracking Echocardiography to
Identify Optimal Site – Latest Site
Speckle Tracking Echocardiography to
Identify Optimal Site – Scar Determination
Speckle tracking radial strain imaging correlates with delayed
enhanced CMR imaging for determination of scar1,2
In CRT patients, a <10% amplitude of radial strain at the LV
pacing site has a high negative predictive value (91%) for
response (LV reverse remodelling)3
1
Becker et al J Am Coll Cardiol 2008 51(15):1473-1481
2Delagado et al Circulation 2011 123 (1):70-8
3Khan et al J Am Soc Echocardiogr. 2010 23(11):1168-1176
LV Lead Targeting – TARGET Group
Step 1: Identify optimal site as the latest site with an amplitude >10% to signify
freedom from scar
Step 2: Coronary sinus venography in steep left anterior oblique (LAO) view
(50-90º) and coronary vein closest to optimal site identified
Step 3: LV lead placed to optimal site (anterior, lateral, posterior or inferior in
LAO view and basal or mid LV in the RAO view)
Step 4: LV lead position correlated with echocardiographic data and described as:
Concordant (pacing the optimal site)
Adjacent (1 segment away)
Remote (≥2 segments away from the optimal site)
Study Endpoints
Primary endpoint
• Comparison of response rates between groups
(≥15% reduction of LVESV at 6 months)
Secondary endpoints
• Clinical response rates (≥1 improvement in NYHA class)
• All cause mortality
• Combined mortality & heart failure hospitalisation
Statistics: 80% power to identify a 20% difference in
response rates between groups (one-sided α value of 0.05)
Assessed for eligibility (n=247)
Excluded (n= 27)
•Inadequate images to perform speckle
tracking echocardiography
Randomized (n= 220)
ALLOCATION
TARGET Group (n=110)
•Died prior to receiving CRT (n=1)*
•Failure to implant an LV Lead (n= 4)
CONTROL Group (n=110)
•Died prior to receiving CRT (n=1) *
•Failure to implant an LV Lead (n= 3)
FOLLOW UP
Lost to follow-up (n=6) *
Died prior to 6 month follow up (n=3)
Lost to follow-up (n=5) *
Died prior to 6 month follow up (n=4)
ANALYSIS
*Excluded from analysis (n=7)
All patients included for long term
endpoints
Total data analysed n=103
for primary and secondary endpoints
*Excluded from analysis (n=6)
All patients included for long term
endpoints
Total data analysed n=104
for primary and secondary endpoints
Baseline Characteristics
Age (mean ± SD) yrs
Male n (%)
NYHA III/IV
Ischemic Cardiomyopathy n (%)
Diabetes Mellitus n (%)
QRS duration (mean ± SD) ms
LVEDV (mean ± SD) ml
LVESV(mean ± SD) ml
LVEF (mean ± SD) %
ACEI or ARB n (%)
B-blockers n (%)
Spironolactone n (%)
IVMD (mean ± SD) ms
AS-P Delay (mean ± SD) ms
Target Group
(n=110)
70 ± 9
85 (77)
95/15
62 (56)
30 (27)
161 ± 21
202 ± 66
157 ± 56
23 ± 6
104 (95)
78 (71)
63 (57)
45 ± 27
190 ± 136
Control Group
(n=110)
71 ± 10
88 (80)
93/17
61 (56)
29 (26)
161 ± 23
200 ± 58
154 ± 52
24 ± 7
103 (94)
77 (70)
59 (54)
44 ± 24
177 ± 148
Latest Site and LV Lead Position
Target Group
(n=103)
Control Group
(n=104)
Latest Site of Activation %
Inferior
Posterior
Lateral
Anterior
Anteroseptal
Inferoseptal
LV Lead Position %
Inferior
Posterior
Lateral
Anterior
Failed Implant
P Value
0.961
13
38
32
9
4
4
14
41
31
7
4
3
0.443
12
35
46
3
4
6
38
47
6
3
LV Lead Targeting
Target
Group
(n=103)
Relationship of LV Lead to Late Site % (n)
Concordant
Adjacent
Remote
Scar at LV Lead Site % (n)
Control
Group
(n=104)
P
Value
0.011
61 (63)
25 (26)
10 (10)
45 (47)
28 (29)
24 (25)
8 (8)
16 (15)
0.133
Procedural Characteristics
Target Group Control Group P
(n=103)
(n=104)
Value
Implant Related Complications
Total % (n)
Failure to implant LV lead
LV Lead Displacement (repositioning)
Phrenic nerve stimulation (reposition)
Device infection (extraction/re-implant)
Pneumothorax
Myocardial perforation
Procedural Characteristics
Procedural Length (mins)
Screening time (mins)
Screening dose (mGy/cm2)
0.991
13 (13)
4 (4)
5 (5)
1 (1)
1 (1)
1 (1)
1 (1)
14 (13)
3 (3)
6 (6)
2 (2)
1 (1)
1 (1)
1 (1)
139 ± 36
25 ± 14
133 ± 107
138 ± 42
19 ± 13
91 ± 69
0.823
0.031
0.024
Primary Endpoint
Response Rates: TARGET vs. Control (70% vs. 55%, p=0.031)
Absolute difference in the primary endpoint of 15% [95% CI (2%, 28%)]
Secondary Endpoint
Clinical Response Rates: TARGET vs. Control (83% vs. 65%, p=0.003)
Target vs. Control
All Patients: Effect of LV Lead Position
All Patients: Effect of Scar
OR
95% CI
P value
Univariate Regression
Analysis
Age
Male Gender
Ischaemic Aetiology
QRS duration
Scar at LV pacing site
Dyssynchrony
Concordant Lead
1.05
2.09
1.74
1.00
2.40
5.51
5.30
1.01-1.08
0.99-4.43
0.97-3.12
0.98-1.01
1.02-5.70
2.9-10.4
2.8 – 9.96
0.007
0.054
0.063
0.47
0.046
<0.01
<0.01
Multivariate Regression
Analysis
Age
Male Gender
Ischaemic Aetiology
QRS duration
Scar at LV pacing site
Dyssynchrony
Concordant Lead
1.06
2.85
1.54
0.99
3.06
5.95
4.43
1.01-1.11
1.02-7.96
0.69-3.43
0.97-1.01
1.01-9.26
2.78-12.7
2.09-9.40
0.018
0.045
0.29
0.22
0.048
<0.01
<0.01
Conclusions
• The TARGET study is the first randomised controlled
trial of LV lead targeting
• Targeted LV lead placement is feasible and associated
with enhanced CRT response
• Concordant LV lead placement, baseline dyssynchrony
and pacing away from areas of scar are strongly related to
improved CRT outcomes