Transcript Primary Results from the SMART AV DELAY Trial: A Randomized

Primary Results from the SMART AV DELAY
Trial: A Randomized Trial Comparing
Empiric, Echocardiographic Guided and
Algorithmic AV Delay Programming in
Cardiac Resynchronization Therapy (CRT)
Kenneth A. Ellenbogen, MD, Michael R. Gold, PhD, MD, Bernd
Lemke, MD, Ignacio F. Lozano, MD, Timothy E. Meyer, PhD,
Suneet Mittal, MD, Jagmeet P. Singh, MD, Frank G. Spinale, PhD,
MD, Kenneth M. Stein, MD, Jennifer E. Van Eyk, PhD, Alan D.
Waggoner, MHS for The SMART-AV Trial Investigators.
Presenter Disclosure Information
Kenneth A. Ellenbogen, MD
Primary Results from the SMART AV DELAY Trial (Boston Scientific)
FINANCIAL DISCLOSURE:
Research Grants: Boston Scientific, Medtronic, St. Jude Medical,
Biosense Webster, Sanofi
Consulting / Advisory board: Boston Scientific, Biotronik, Medtronic, St.
Jude Medical, Sorin Group, Sanofi, Cardionet, Atricare, EBR
Lectures: Boston Scientific, Biotronik, Medtronic, St. Jude Medical,
Sorin Group, Sanofi
Stock Options: None; Salary Support: None; Speaker Bureau: None
UNLABELED/UNAPPROVED USES DISCLOSURE: None
All devices used in the SMART-AV trial were Boston Scientific
SMART-AV (Background)
• In patients with heart failure and prolonged QRS duration, cardiac
resynchronization therapy (CRT) reduces heart failure hospitalizations
and prolongs survival compared with optimal medical therapy (OMT).
• Achieving the optimal outcome from CRT may be dependent on proper
programming of the optimal atrioventricular (AV) delay.
• However, large scale randomized trials establishing the overall efficacy
of CRT have differed widely in their approach to AV optimization.
• CONTAK CD – No optimization
• CARE-HF and MIRACLE – Doppler echocardiography of transmitral flow
• COMPANION – algorithm based on the intrinsic AV interval and baseline
QRS
• The ASE proposed a mitral inflow method for routine AV optimization
after CRT.
Objectives
• To compare three alternative AV optimization techniques and to
assess the hypotheses that:
1) systematic AV delay optimization using echocardiography
and/or the SD algorithm is superior to a fixed nominal AV
delay as demonstrated by improved LV geometry after 6
months and
2) that programming according to SD is non-inferior to using
echocardiography-determined AV delay optimization.
Methods
SMART-AV Inclusion
Primary Endpoint:
•
•
•
•
• LVESV at 6 months
•
•
NYHA class III or IV
EF < 0.35
QRS >120ms
Expected to be in sinus rhythm at the
time of implant
Willing and capable of undergoing a
device implant and participating in all
testing
Receiving OPT
SMART-AV Exclusion
•
Complete heart block or unable to
tolerate pacing at VVI-40-RV for up to 14
days
•
Previously received CRT
Secondary Endpoints:
• 6 min walk, EF, NYHA Class,
LVEDV, QOL (MLWHF)
Statistics:
• Continuous outcomes: general
linear model - F test
• Categorical outcomes: risk
difference of proportions – Chisquared test
• Applicable to primary,
secondary and subgroup
analyses
SMART-AV – Study Design
Enrollment and Implant CRT-D with SmartDelay
Program device to VVI-40-RV
Post-Implant Visit (1 to 14 days post-implant)
(1:1:1 Randomization, Programmed to DDD(R)60)
SmartDelay
Echo (Iterative)
Fixed (120/0)
3- month Visit
3- month Visit
3- month Visit
6- month Visit
6- month Visit
6- month Visit
Stein KM, et al. Pacing Clin Electrophysiol. 2010;33(1):54-63
Baseline Patient Characteristics
Characteristics
SD
(n=332)
Echo
(n=323)
Fixed
(n=326)
p-value
Age (yrs)
66 ± 11
66 ± 11
66 ± 11
ns
71%
68%
65%
ns
Resting heart rate (bpm)
71 ± 12
72 ± 13
71 ± 13
ns
Ejection fraction (%)
25 ± 7
24 ± 7
25 ± 7
ns
152 ± 21
153 ± 20
153 ± 20
ns
2%
1%
2%
ns
11%
11%
14%
ns
79/11/9
72/16/10
79/11/9
ns
57%
57%
56%
ns
4/92/4%
2/96/2%
2/95/3%
ns
Gender (% male)
QRS duration (ms)
History of ventricular fibrillation
History of paroxysmal atrial fibrillation
LBBB/RBBB/IVCD (%)
Ischemic cardiomyopathy
NYHA FC II/III/IV heart failure
Continuous variables are expressed as mean ± SD
SMART-AV – Patient Flow
Enrolled
n=1060
Implanted
n=1014
Randomized
n=980
SmartDelay
n=332
Echo (Iterative)
n=323
Fixed (120/0)
n=325
Withdrawn, LTFU
or Missing data
n=49
Withdrawn, LTFU
or Missing data
n=41
Withdrawn, LTFU
or Missing data
n=44
Evaluable Data
n=283 (85%)
Evaluable Data
n=282 (87%)
Evaluable Data
n=281 (86%)
Primary Endpoint – LVESV
Secondary Structural Endpoints – LVEDV, LVEF
Secondary Functional Endpoints – Six Min Walk, QOL
Secondary Endpoint – NYHA Class
Distribution of AV Delays at 6-months post-implant
Primary Endpoint Subgroup: Etiology, Atrial Pacing %
Primary Endpoint Subgroup: Bundle Branch Block, QRS Width
Primary Endpoint Subgroup: Gender
Summary & Conclusion
• The change in LVESV for the SD arm was no different than either the
Echo or Fixed arms.
• There were no significant differences in the secondary structural or
functional endpoints by optimization group.
• Patients with a wide QRS duration, LBBB, non-ischemic
cardiomyopathy, and female gender responded more favorably to CRT
therapy.
• In post-hoc analysis, females optimized with SD and Echo responded
more favorably than females randomized to the Fixed arm.
• The routine use of AV optimization techniques as assessed in this trial
is not warranted. However, this data does not exclude possible utility in
selected patients who do not respond to CRT.