Transcript CRT-D Effectiveness by QRS Duration and Morphology in the MADIT-CRT Patients Wojciech Zareba, MD, PhD, Helmut Klein, MD, Iwona Cygankiewicz, MD, PhD, W.

CRT-D Effectiveness by QRS Duration and
Morphology in the MADIT-CRT Patients
Wojciech Zareba, MD, PhD, Helmut Klein, MD, Iwona
Cygankiewicz, MD, PhD, W. Jackson Hall, PhD, Jeffrey
Goldberger, MD, James P. Daubert, MD, Michael R. Gold, MD,
Mayer Rashtian, MD, Sami Viskin, MD, Wlodzimierz Kargul, MD,
Heinz Pitschner, MD, Scott McNitt, MS and Arthur J. Moss, MD.
University of Rochester, Rochester, NY, Northestern University, Chicago, IL,
Duke University, Durham, NC, Medical University of South Carolina, Charlston,
SC, Foothill Cardiology/California Heart Medical Group, Pasadena, CA, Tel Aviv
Sourasky Medical Center, Tela Aviv, Israel, Silesian Medical University,
Katowice, Poland, Kerckhoff Medical University, Ban Neuheim, Germany
Author Disclosure Information:
W. Zareba - Boston Scientific Corp., S,I;
H. Klein - LIFECOR, M,A; Boston Scientific Corp., S,I;
I. Cygankiewicz - None;
W. Hall - None;
J. Goldberger - None;
J.P. Daubert - Boston Scientific Corp., M,A; Medtronic, Corp., M,A;
CV Therapeutics, Inc., M,A; Biosense Webster, Inc., M,A; S,I; St. Jude
Medical, S,I; Biotronik, S,J;
M.R. Gold - None;
M. Rashtian - None;
S. Viskin - None;
W. Kargul - None;
H. Pitschner - None;
S. McNitt - None;
A.J. Moss - Boston Scientific Corp., S,I.
Multicenter Automatic Defibrillator Implantation Trial
– Cardiac Resynchronization Therapy
(MADIT-CRT)
Moss et al. N Engl J Med 2009;361:1329-1338
Entry Criteria:
 Ischemic NYHA I-II
or non-ischemic NYHA class II
 EF<0.30
 QRS >0.13sec
 Sinus Rhythm
 Optimal pharmacologic therapy:
B-b (>3 mo.); ACE/ARB (>1 mo.);
statins in IHD
MADIT-CRT
ICM NYHA I/II and
NICM NYHA II
EF < 0.30; QRS
>0.13sec
Randomization
N=1,820
Exclusions:
 NYHA III-IV <90 days PTE
 Acute MI, CABG, PCI <3 months
 Existing ICD or CRT device
 AF; PR>250ms; 2nd or 3rd degree HB
 BUN >70mg/dl or creatinine
>3.0mg/dl
ICD only
CRT-D
N=731
N=1,089
MADIT-CRT: Baseline Clinical Characteristics
Variable
ICD
(N = 731)
Age (yrs)
64+11
Males
553 (76%)
Ischemic heart disease
NYHA class I
113 (16%)
NYHA class II
288 (39%)
Nonischemic heart disease
NYHA class II
330 (45%)
EF
24+5
Moss AJ et al. N Engl J Med 2009;361:1329-1338
CRT-ICD
(N = 1089)
65+11
814 (75%)
152 (14%)
446 (41%)
491 (45%)
24+5
Kaplan-Meier Estimates of the Probability of
Survival Free of Heart Failure
Moss AJ et al. N Engl J Med 2009;361:1329-1338
Hazard Ratio for CRT-D vs. ICD only in MADIT-CRT
HR
(95% CI)
P Value
Heart failure or Death
0.66
(0.52–0.84)
0.001
Heart failure only
0.59
(0.47–0.74)
<0.001
Death at any time
1.00
(0.69–1.44)
0.99
Changes in Mean Echocardiographic Left Ventricular Volumes and
Ejection Fraction between Baseline and 1-Year Follow-up
Moss AJ et al. N Engl J Med 2009;361:1329-1338
Effects of CRT-D by QRS
Morphology in MADIT-CRT
Non-LBBB
IVCD, 306,
17%
534, 30%
RBBB, 228,
13%
LBBB, 1281,
70%
Baseline Clinical Characteristics of MADIT-CRT Patients
by QRS Morphology
Clinical Characteristics
LBBB
n=1,281
Non-LBBB
n=536
RBBB
n=228
IVCD
n=308
Age (yrs)
64±11
65±10
66±10*
64±10
Females
394 (31%)
59 (11%)†
18 (8%)†
41 (13%)†
Ischemic NYHA class I
143 (11%)
120 (22%)†
47 (21%)†
73 (24%)†
Ischemic NYHA class II
420 (33%)
314 (58%)†
150 (66%)† 164 (53%)†
Nonischemic NYHA class II
718 (56%)
102 (19%)†
31 (14%)†
71 (23%)†
Prior hospitalization
563 (45%)
274 (52%)
112 (50%)
162 (53%)
EF (%)
23.5±5.3
24.5±5.0†
25.2±5.0†
23.9±5.2†
QRS (ms)
163±19
146±15†
153±15†
142±14†
21±9
22±9
22±9
21±9
1.14±0.32
1.23±0.46†
1.28±0.53
1.18±0.40†
BUN (mg/dl)
Creatinine (mg/dl)
* P<0.05; † P<0.01 when comparing with LBBB patients
Baseline Clinical Characteristics of MADIT-CRT Patients
by QRS Morphology
Clinical Characteristics
LBBB
n=1,281
Non-LBBB
n=536
RBBB
n=228
IVCD
n=308
LVEDV (ml)
251±66
242±52*
231±45†
250±54*
LVESV (ml)
180±53
171±41†
162±35†
177±43†
LAV (ml)
94±22
93±21
92±22
94±20
ACE Inhibitors
982 (77%)
418 (78%)
177 (78%)
241 (78%)
Ang. Rec. Blockers
278 (22%)
98 (18%)
42 (18%)
56 (18%)
Beta-blockers
1204 (94%)
490 (91%)*
202 (89%)†
288 (94%)
Diuretics
873 (68%)
353 (66%)
147 (64%)
206 (67%)
Echo Parameters
Medication:
* P<0.05; † P<0.01 when comparing with LBBB patients
Cumulative Probability of Heart Failure (HF) Event or Death by
Treatment (CRT-D vs. ICD only) in patients with LBBB and NonLBBB QRS Pattern in MADIT-CRT Patients
LBBB
Non-LBBB
Cumulative Probability of Heart Failure (HF) Event or Death by
Treatment (CRT-D vs. ICD only) in patients with RBBB and IVCD
QRS Pattern in MADIT-CRT Patients
RBBB
IVCD
Cumulative Probability of VT/VF or Death by Treatment (CRT-D vs.
ICD only) in patients with LBBB and Non-LBBB QRS Pattern
in MADIT-CRT Patients
LBBB
Non-LBBB
Cumulative Probability of Death by Treatment (CRT-D vs. ICD only)
in patients with LBBB and Non-LBBB QRS Pattern
in MADIT-CRT Patients
LBBB
Non-LBBB
Hazard Ratios for Clinical Endpoints by QRS Morphology
Endpoint
Heart Failure Event
or Death
Heart Failure Event
Death
LBBB
n=1,281
Non-LBBB
n=536
P value for
Interaction
HR
95% CI
P value
0.47
0.37,0.61
<0.001
1.24
0.85,1.81
0.257
<0.001
HR
95% CI
P value
0.41
0.31,0.54
<0.001
1.23
0.76,1.68
0.559
<0.001
HR
95% CI
P value
0.75
0.49,1.16
0.196
1.79
0.90,3.57
0.097
0.037
* The model adjusted for sex, ischemic or nonischemic cardiomyopathy, prior
hospitalizations for heart failure, ejection fraction, QRS>150, left ventricular ejection
fraction, left ventricular end-systolic volume.
Hazard Ratios for Clinical Endpoints by QRS Morphology
Endpoint
VT/VF
HR
95% CI
P value
0.67
0.52,0.87
0.002
Non-LBBB P value for
n=536
Interaction
1.11
0.77,1.60
0.574
0.028
VF
HR
95% CI
P value
0.54
0.33,0.87
0.011
1.24
0.58,2.66
0.585
0.070
HR
95% CI
P value
0.69
0.55,0.87
0.002
1.21
0.87,1.69
0.254
0.006
VT/VF/Death
LBBB
n=1,281
* The model adjusted for sex, ischemic or nonischemic cardiomyopathy, prior
hospitalizations for heart failure, ejection fraction, QRS>150, left ventricular ejection
fraction, left ventricular end-systolic volume.
Hazard Ratios for Primary and Secondary
Endpoints by QRS Morphology in MADIT-CRT
2.5
2.0
LBBB
Non-LBBB
RBBB
IVCD
1.5
1.0
*
0.5
*
*
*
*p<0.05
0.0
HF or Death
HF
Death
VT/VF/Death
VF/Death
Hazard Ratios for Primary Endpoint by QRS Morphology
and Duration by Gender
Males
n
P value
Females
n
HR
HR
P value
QRS Duration
<140 ms
140-159 ms
160-179 ms
≥180 ms
240
465
417
242
1.69
0.77
0.51
0.50
0.063
0.164
0.003
0.019
61
178
153
61
0.20
0.31
0.42
0.33
0.008
0.001
0.036
0.100
QRS Morphology
LBBB*
Non-LBBB
RBBB
IVCD
887
477
210
267
0.56
1.25
0.94
1.49
<0.001
0.273
0.841
0.133
394
59
18
41
0.25
1.55
NA
1.31
<0.001
0.516
0.701
* p=0.006 for interaction comparing HR = 0.56 in males vs. HR = 0.25 in females
Mean Change in Echocardiographic Parameters
from Enrollment to 12 months in CRT-D Patients
LBBB
Non-LBBB
20
12
*
10
9
0
-10
LVEDV
-20
-30
-40
LVESV
-16
-23
*
-26
-35
*
EF
* p<0.001 when comparing
LBBB and Non-LBBB patients
(all changes within subgroups
were significant)
Conclusions
1. Heart failure patients with NYHA class I or II and
ejection fraction ≤30% who present with LBBB derive
substantial benefit from CRT-D: reduction in heart
failure progression and reduction in the risk of
ventricular tachyarrhythmias.
2. No evidence of CRT-D benefit was observed in patients
with Non-LBBB QRS pattern: RBBB or IVCD
regardless of their QRS duration.
3. Beneficial effect of CRT-D in LBBB patients was
observed in all studied subjects: males and females,
ischemic and non-ischemic, QRS>150 and QRS<150 ms.