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, UK2Papworth 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 CRTHigher response when pacing the latest site of contraction1
Lower response when pacing areas of scar2
1 Ypenburg et al J Am Coll Cardiol.2009;53(6):483-490 2Bleeker et al Circulation 2006;113(7):969-976.
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
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 TARGET Group
Targeted LV LeadSpeckle Tracking Echocardiography used to identify optimal site and LV
lead targeted to this site
Standard CRTLV Lead Placement without echocardiographic guidance
All CRT devices optimised using echo following implant
Study Design
Speckle Tracking Echocardiography to Identify Optimal Site – Latest Site
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
Speckle Tracking Echocardiography to Identify Optimal Site – Scar Determination
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)
LV Lead Targeting – TARGET Group
Study EndpointsPrimary 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)
TARGET Group (n=110)•Died prior to receiving CRT (n=1)*
•Failure to implant an LV Lead (n= 4)
Lost to follow-up (n=6) *Died prior to 6 month follow up (n=3)
*Excluded from analysis (n=7)All patients included for long term
endpointsTotal data analysed n=103
for primary and secondary endpoints
CONTROL Group (n=110)•Died prior to receiving CRT (n=1) *•Failure to implant an LV Lead (n= 3)
ALLOCATION
Lost to follow-up (n=5) *Died prior to 6 month follow up (n=4)
FOLLOW UP
*Excluded from analysis (n=6)All patients included for long term
endpointsTotal data analysed n=104
for primary and secondary endpoints
ANALYSIS
Target Group (n=110)
Control Group (n=110)
Age (mean ± SD) yrs 70 ± 9 71 ± 10Male n (%) 85 (77) 88 (80)NYHA III/IV 95/15 93/17Ischemic Cardiomyopathy n (%) 62 (56) 61 (56)Diabetes Mellitus n (%) 30 (27) 29 (26)QRS duration (mean ± SD) ms 161 ± 21 161 ± 23LVEDV (mean ± SD) ml 202 ± 66 200 ± 58LVESV(mean ± SD) ml 157 ± 56 154 ± 52LVEF (mean ± SD) % 23 ± 6 24 ± 7ACEI or ARB n (%) 104 (95) 103 (94)B-blockers n (%) 78 (71) 77 (70)Spironolactone n (%) 63 (57) 59 (54)IVMD (mean ± SD) ms 45 ± 27 44 ± 24AS-P Delay (mean ± SD) ms 190 ± 136 177 ± 148
Baseline Characteristics
Target Group (n=103)
Control Group (n=104)
P Value
Latest Site of Activation % 0.961
Inferior 13 14 Posterior 38 41Lateral 32 31Anterior 9 7 Anteroseptal 4 4Inferoseptal 4 3
LV Lead Position % 0.443
Inferior 12 6Posterior 35 38Lateral 46 47Anterior 3 6Failed Implant 4 3
Latest Site and LV Lead Position
Target Group (n=103)
Control Group (n=104)
P Valu
eRelationship of LV Lead to Late Site % (n)
0.011
Concordant 61 (63) 45 (47)Adjacent 25 (26) 28 (29)Remote 10 (10) 24 (25)
Scar at LV Lead Site % (n) 8 (8) 16 (15) 0.133
LV Lead Targeting
Target Group (n=103)
Control Group (n=104)
P Value
Implant Related Complications 0.991Total % (n) 13 (13) 14 (13)Failure to implant LV lead 4 (4) 3 (3)LV Lead Displacement (repositioning) 5 (5) 6 (6)Phrenic nerve stimulation (reposition) 1 (1) 2 (2)Device infection (extraction/re-implant) 1 (1) 1 (1)Pneumothorax 1 (1) 1 (1)Myocardial perforation 1 (1) 1 (1)
Procedural CharacteristicsProcedural Length (mins) 139 ± 36 138 ± 42 0.823Screening time (mins) 25 ± 14 19 ± 13 0.031Screening dose (mGy/cm2) 133 ± 107 91 ± 69 0.024
Procedural Characteristics
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 valueUnivariate Regression AnalysisAge 1.05 1.01-1.08 0.007Male Gender 2.09 0.99-4.43 0.054Ischaemic Aetiology 1.74 0.97-3.12 0.063QRS duration 1.00 0.98-1.01 0.47Scar at LV pacing site 2.40 1.02-5.70 0.046Dyssynchrony 5.51 2.9-10.4 <0.01Concordant Lead 5.30 2.8 – 9.96 <0.01
Multivariate Regression AnalysisAge 1.06 1.01-1.11 0.018Male Gender 2.85 1.02-7.96 0.045Ischaemic Aetiology 1.54 0.69-3.43 0.29QRS duration 0.99 0.97-1.01 0.22Scar at LV pacing site 3.06 1.01-9.26 0.048Dyssynchrony 5.95 2.78-12.7 <0.01Concordant Lead 4.43 2.09-9.40 <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