Online Table 1 : Device implantation criteria for the 13 studies included in the meta-analysis of CRT-D vs
ICD therapy in the incidence of ventricular arrhythmias
Study, Year
Criteria
Study (CRT-D)
Control (ICD)
EF
≤ 35%
≤ 35%
Higgins SL et al, 2003
Young JB et al, 2003
The MIRACLE ICD Trial
Arya A et al, 2005
Ermis C et al, 2005
Voigt A et al, 2005
Linde C et al, 2008 REVERSE
Study
Nordbeck P et al, 2009
Blaschke F et al, 2011
Thijssen J et al, 2011
QRSd
NYHA
EF
QRSd
NYHA
EF
QRSd
NYHA
EF
QRSd
NYHA
EF
QRSd
NYHA
EF
QRSd
NYHA
EF
QRSd
≥ 120ms
II, III, IV
≤ 35%
≥ 130ms
III, IV
≤ 35%
≥ 120ms
II, III, IV
CRT-D Upgrade from ICD
patients
≥ 120ms
II, III, IV
≤ 35%
≥ 130ms
III, IV
≤ 35%
≥ 120ms
II, III, IV
NR - Standard Guidelines for ICD
placement
CRT-D Upgrade from ICD
patients
NR - Standard Guidelines for ICD
placement
≤ 40%
≥ 120ms
I, II
≤ 35%
≥ 120ms
NYHA
II, III, IV
EF
QRSd
NYHA
EF
NR - Standard Guidelines for
CRT-D placement
≤ 40%
≥ 120ms
I, II
≤ 35%
NR - Standard Guidelines for ICD
placement
NR - Standard Guidelines for ICD
placement
NR – Primary prevention Indication for ICD
QRSd
NYHA
Timoteo AT et al, 2011
Ouellet G et al, 2012
Gopalamurugan AB et al, 2014
Gopinathannair R et al, 2014
EF
QRSd
NYHA
EF
QRSd
NYHA
EF
QRSd
NYHA
EF
QRSd
NYHA
≤ 35%
CRT-D Upgrade from ICD
≥ 120ms
CRT-D Upgrade from ICD
II, III, IV
CRT-D Upgrade from ICD
≤ 35%
≥ 120ms
II, III, IV
≤ 30%
≥ 130ms
I, II
NR - Standard Guidelines for
CRT-D placement
≤ 35%
NR - Standard Guidelines for
CRT-D placement
NR - Standard Guidelines for ICD
placement
NR - Standard Guidelines for ICD
placement
NR - Standard Guidelines for ICD
placement
≤ 35%
NR – Primary prevention Indication for ICD
NR – Primary prevention Indication for ICD
≤ 30%
≥ 130ms
I, II
NR - Standard Guidelines for ICD
placement
Note : CRT – Cardiac Resynchronization Therapy – Defibrillator; EF – Ejection Fraction; ICD – Implantable CardioverterDefibrillator; ms – milliseconds; NR – Not Reported; NYHA – New York Heart Association; QRSd –QRS duration
Online Table 2: Ventricular arrhythmia definition and device settings for the 13 studies included in the
meta-analysis of CRT-D vs ICD therapy in the incidence of ventricular arrhythmias
Study, year
Higgins SL et al,
2003
Young JB et al, 2003
The MIRACLE ICD
Trial
Arya A et al, 2005
Ermis C et al, 2005
Voigt A et al, 2005
Linde C et al, 2008
REVERSE Study
Nordbeck P et al,
2009
Blaschke F et al,
2011
Thijssen J et al, 2011
Timoteo AT et al,
2011
Ouellet G et al, 2012
VA Definition
VT/VF episodes requiring appropriate
ATP or shock therapy
VT/VF episodes requiring appropriate
ATP or shock therapy
VT/VF episodes requiring appropriate
ATP or shock therapy
VT/VF episodes requiring appropriate
ATP or shock therapy
VT/VF episodes requiring appropriate
ATP or shock therapy
Sustained VT/VF episodes irrespective of
device therapies - All episodes
adjudicated by events committee (only
10% of all sustained VA not treated)
VT/VF episodes requiring appropriate
ATP or shock therapy
VT/VF episodes requiring appropriate
ATP or shock therapy
VT/VF episodes requiring appropriate
ATP or shock therapy
Device Settings
Not reported
Not reported
Zones not clearly specified. Proportion and cycle length
of VA were comparable and not significantly different
between two groups
VT:<400 ms but ≥320 ms
VF:<320 ms
Not reported
Zones & therapies: left to the discretion of the
implanting physician.
Zones & therapies: left to the discretion of the
implanting physician. .Mean VT detection: 350+/- 24
ms . Mean VF detection: 310+/- 16 ms.
VT :>170–180 bpm
VF :>200 bpm.
VT monitor zone: 150 to 188 beats/min. VT :>188-210
beats/min.
VF>210 beats/min with different therapy settings
Not reported
VT/VF episodes requiring appropriate
ATP or shock therapy
VT/VF episodes requiring appropriate
VT zone>180 beats/min.VF zone >250 beats/min
ATP or shock therapy
VT/VF episodes requiring appropriate
Zones & therapies: left to the discretion of the
Gopalamurugan AB
ATP or shock therapy
implanting physician.
et al, 2014
Gopinathannair R et Sustained VA lasting >30 sec or requiring Not reported
ICD therapy
al, 2014
Note : ATP – Anti-Tachycardia Pacing; bpm – beats per minute; ms – milliseconds; VF – Ventricular Fibrillation; VT –
Ventricular Tachycardia
Online Table 3 : Ventricular arrhythmia definition and device settings for the 13 studies included in the
meta-analysis of CRT responders vs non-responders in the incidence of ventricular arrhythmias
Study, year
VA Definition
Device Settings
Di Biase L et
al, 2008
VT/VF episodes requiring
appropriate ATP or shock therapy
Mean VT detection = 395 +/- 29 ms (atleast 16 consecutive beats)
Mean VF detection = 313 +/- 14 ms (sustained for 12 of 16 beats)
Markowitz SM
et al, 2008
Schaer BA et
al, 2010
Gold MR et al,
2011
Device settings at discretion of implanting physician
ThijssenJ et al,
2011
Eickholt C et
al, 2012
Shahrzad S et
al, 2012
VT/VF episodes requiring
appropriate ATP or shock therapy
VT/VF episodesrequiring
appropriate ATP or shock therapy
Sustained VT/VF episodes
irrespective of device therapies All episodes adjudicated by events
committee (only 10% of all
sustained VA not treated).
VT/VF episodes requiring
appropriate ATP or shock therapy
VT/VF episodes requiring
appropriate ATP or shock therapy
VT/VF episodes requiring
appropriate ATP or shock therapy
Itoh M et al,
2013
VT/VF episodes requiring
appropriate ATP or shock therapy
VT: <350 ms(>171 beats/min)
Primary prevention:VT:175–180 beats/min. Secondary prevention: VT:
20 beats/minlower than the clinically observed VT. VF :210 beats/min.
Device settings at discretion of implanting physician
VT monitor: 150 to 188 beats/min. VT 188 -210 beats/min. VF>210
beats/min
VT: 450 msto 300 ms, VF: < 300 ms
VT :>168/min.VF: >187/min
Manfredi JA et VT/VF episodes requiring
Device settings at discretion of implanting physician
al, 2013
appropriate ATP or shock therapy
Friedman DJ
VT/VF episodes requiring
Device settings at discretion of implanting physicianbut generally VT
et al, 2014
appropriate ATP or shock therapy
zones in range of 160–190 beats/min.
Garcia-Lunar I VT/VF episodes requiring
Device settings at discretion of implanting physician
et al, 2014
appropriate ATP or shock therapy
Ruwald MH et VT/VF episodes requiring
VT :180 to 250 bpm. VF: ≥250 bpm.
al, 2014
appropriate ATP or shock therapy
van der
VT/VF episodes requiring
VT Monitor: 150 to 188-190 beats/min, VT: 188-190 to 220Heijden AC et
appropriate ATP or shock therapy
231beats/min.
al, 2014
VF> 220-231beats/min
Note : ATP – Anti-Tachycardia Pacing; bpm – beats per minute; ms – milliseconds; VF – Ventricular Fibrillation; VT –
Ventricular Tachycardia
Funnel Plot of Standard Error by Log odds ratio
0.0
0.2
Standard Error
0.4
0.6
0.8
1.0
-4
-3
-2
-1
0
1
2
3
Log odds ratio
e-Figure 5: Funnel plot of studies included in the Meta-analysis of CRT-D vs ICD in
the incidence of Ventricular Arrhythmias assuming Random Effect Model
4
Funnel Plot of Standard Error by Log odds ratio
0.0
Standard Error
0.5
1.0
1.5
2.0
-3
-2
-1
0
1
2
Log odds ratio
e-Figure 6: Funnel plot of studies included in the Meta-analysis of CRT responders
vs non-responders in the incidence of Ventricular Arrhythmias assuming Random
Effect Model
3