Transcript The Resynchronization Therapy in Normal QRS (RethinQ) Study

Presenter Disclosure Information
John F. Beshai, MD
RethinQ Trial Results
Disclosures Information:
The following relationships exist related to this presentation:
Consultant - St. Jude Medical, Atricure
Research Grant - St. Jude Medical
R Grimm : Speaker - St. Jude, Medtronic, GE
Research Grant - GE
S Nagueh: Speaker - Medtronic
Consultant - St. Jude
J Baker : no disclosures
S Beau: no disclosures
S Greenberg: Consultant - Medtronic, St. Jude, Boston Scientific
L Pires: Consultant - St. Jude
P Tchou: no disclosures
The Resynchronization Therapy in
Normal QRS (RethinQ) Study
John F. Beshai, MD, Richard A. Grimm, DO,
Sherif F. Nagueh, MD, James H. Baker II, MD,
Scott L. Beau, MD, Steven M. Greenberg, MD,
Luis A. Pires, MD, Patrick J. Tchou, MD
for the RethinQ study investigators
Study Sponsored by St. Jude Medical
Background
• Currently, indications for cardiac resynchronization therapy (CRT)
include QRS duration > 120ms, LVEF < 35% and NYHA
Class III-IV.
• 20-30% of patients do not respond to CRT despite application of
established selection criteria.
• Patients with normal conduction or a slightly prolonged QRS
duration also exhibit mechanical abnormalities due to
intraventricular dyssynchrony.
• Myocardial Tissue Doppler Imaging (TDI) allows both the velocity
and timing of regional longitudinal motion to be measured.
• LV dyssynchrony may also be useful in predicting the benefit of
CRT before implantation of the pulse generator.
Hypothesis
• We hypothesized that patients with NYHA class III, left
ventricular ejection fraction less than or equal to 35%,
narrow QRS duration < 130 ms, and evidence of
mechanical dyssynchrony on echocardiography may
benefit from cardiac resynchronization therapy.
Study Design
Overall Objective
Determine CRT safety and efficacy in patients who are
candidates for an ICD with NYHA Class III, narrow QRS
duration (<130 ms) and evidence of mechanical
dyssynchrony as measured by echocardiography/Tissue
Doppler Imaging
Primary Endpoint
Improvement in Peak VO2 during CPET of at least
1.0ml/kg/min at 6 months.
Secondary Endpoints
Improvement in quality of life score at 6-months
Improvement in NYHA classification at 6-months
Inclusion and Exclusion Criteria
Inclusion Criteria
Exclusion Criteria
• NYHA class III HF
• NYHA class I, II, or IV
• LVEF ≤ 35%
• Permanent Atrial
Fibrillation
• Evidence of
mechanical
dyssynchrony
• Recent MI, unstable
angina or cardiac
revascularization
• QRS duration < 130ms
• Prior cardiac
resynchronization
therapy
Echo Criteria for LV Dyssynchrony
Mechanical dyssynchrony considered present if either
• M-Mode
- Septal posterior wall mechanical delay (SPWMD) ≥ 130 ms
OR
• Tissue Doppler Imaging (TDI) of the basal ventricular
segments in apical 4/2/3 chamber views
- Septal to lateral delay ≥ 65ms
OR
- Antero-septal to posterior delay ≥ 65ms
Study Design
172 patients
randomized in 34
centers
Randomized to
CONTROL or CRT
Stratified by
QRS < 120 ms or ≥ 120 ms
And
Ischemic or Non-ischemic CM
CONTROL
Followed for 6-months
CRT
Followed for 6-months
Results
Baseline Characteristics
Control
(n = 85)
CRT
(n = 87)
Age (yr), Mean ± SD
58 ± 14
60 ± 12
Male sex, n(%)
49 (58%)
62 (71%)
NYHA III, n(%)
84 (99%)
87 (100%)
QRS Duration (ms), Mean ± SD
106 ± 13
107 ± 12
Ischemic Cardiomyopathy, n(%)
43 (51%)
47 (54%)
26 ± 6
25 ± 5
77 (91%)
79 (93%)
74 (87%)
10 (12%)
77 (89%)
84 (97%)
73 (84%)
7 (8%)
Left ventricular ejection fraction (%)
Medications, n(%)
ACE inhibitor or substitute§
Beta-Blocker
Diuretic
§ Antiarrhythmic
Includes ARBs and other ACE substitutes, including Hydralazine
Baseline Mechanical Dyssynchrony
Mechanical Dyssynchrony Control
CRT
Parameters
ms
ms
SPWMD - M-Mode
n = 12
n=9
Mean ± SD
165 ± 27 151 ± 22
Septal to lateral - TDI
n = 69
n = 67
Mean ± SD
99 ± 29 96 ± 28
Antero-septal to posterior
n = 55
n = 59
- TDI
106 ± 29 94 ± 23
Mean ± SD
Baseline Echocardiographic Data
LV end systolic diameter (mm)
Mean +/- 1 SD
p = 0.06
40
40
60
60
p = 0.29
80
80
LV end diastolic diameter (mm)
Mean +/- 1 SD
n = 87
20
n = 85
Control
CRT
0
0
20
Control
n = 85
CRT
n = 87
Baseline Echocardiographic Data (Cont)
LV end systolic volume (mL)
Mean +/- 1 SD
300
300
LV end diastolic volume (mL)
Mean +/- 1 SD
Control
n = 87
50
50
0
Control
0
n = 85
CRT
100
200
100
p = 0.43
200
p = 0.61
n = 85
CRT
n = 87
Baseline Evaluations
Peak VO2(ml/kg/min)
Exercise Duration (min)
15
Mean +/- 1 SD
p = 0.85
p = 0.85
5
5
10
15
10
20
25
Mean +/- 1 SD
Control
n = 85
n = 87
0
0
n = 85
Control
CRT
CRT
n = 87
Baseline Evaluations (Cont)
Six-minute Hall Walk Distance (m)
Mean +/- 1 SD
400
p = 0.43
p = 0.95
40
200
60
300
80
100
Quality of Life Score
Mean +/- 1 SD
20
Control
n = 85
n = 87
0
0
n = 85
CRT
100
Control
CRT
n = 87
Patient Flow Analysis
• 172 patients randomized (87 CRT and 85
control)
• 11 patients in CRT group and 5 patients in
control group not included in endpoint analysis
–< 6 months of follow up (7 patients)
–Unable to complete CPET at 6 month visit for
reason other than worsening HF (3 patients)
–Death not due to worsening HF (3 patients)
–Withdrawal prior to 6 month visit (3 patients)
• 156 patients (76 CRT and 80 control) were
available for efficacy analysis
Results - Primary Endpoint
Peak VO2 (ml/kg/min)
Median & 95% CI
p = 0.63
41%
46%
0
8
p = 0.75
20
10
40
60
12
80
14
100
% Improved in Peak VO2
Baseline
6-months
Control (n = 80)
CRT (n = 76)
Control
n = 80
CRT
n = 76
Results - Secondary Endpoints
Quality of Life
NYHA Class
70
100
Median & 95% CI
p = 0.006
64%
54%
50
60
60
80
p = 0.91
40
41%
20
40
29%
0
30
8%5%
Baseline
6-months
Control (n = 80)
CRT (n = 76)
Improved
No Change
Worsened
Control (n = 80)
CRT (n = 76)
LV Volumes and Dimensions
Change in LVEDD/ LVESD
Median & 95% CI
p = 0.71
p = 0.81
LVEDV
LVESV
p = 0.49
p = 0.34
LVEDD
LVESD
-40
-4
-2
-20
0
0
2
10
4
Change in LVEDV/ LVESV
Median & 95% CI
Control
CRT
Peak VO2 by sub-group
Peak VO2
(% improved from baseline)
(% improved from baseline)
100
100
Peak VO2
p = 0.82
p = 0.45
p = 0.25
40
40
60
60
80
80
p = 0.02
n = 55
CRT
n = 41
n = 59
CRT
n = 40
Control
n = 36
n = 39
0
n = 25
Control
0
20
Control
n = 17
Control
20
CRT
CRT
QRS ≥ 120 ms QRS < 120 ms
Ischemic
Non-ischemic
Summary
• This prospective, multi-center, randomized trial was
designed to evaluate the effectiveness of CRT therapy
in a HF population with narrow QRS duration and
evidence of mechanical dyssynchrony.
• There was no statistical significant difference in the
change in Peak VO2 between the treatment and control
group during cardiopulmonary exercise testing.
• No improvement in other objective parameters including
6-minute walk test, LV reverse remodeling, and
secondary endpoint - quality of life score .
Summary
• NYHA class improved to a greater extent in the
treatment group than in the control group.
• Although numbers were small in the sub-group analysis,
there was no statistically significant difference in the
primary endpoint between ischemic and non-ischemic
patients.
• Patients with QRS duration 120 - 130 ms demonstrated
an improvement in peak VO2.
Conclusion
• CRT did not improve Peak VO2 during exercise in patients with
NYHA Class III heart failure, QRS duration <130ms, EF ≤ 35% and
mechanical dyssynchrony as specified in this trial.
• While there was a statistically significant improvement of NYHA
class, a secondary endpoint, there was no improvement in qualityof-life, 6-minute walking test, or echocardiographic measures of
reverse LV remodeling
• A subgroup of patients with QRS duration between
120 ms and 130 ms demonstrated an improvement from CRT,
however patients with QRS duration < 120 ms did not demonstrate
improvement
• The subgroup of patients stratified on the basis of cardiomyopathy
etiology did not demonstrate an improvement in peak VO2.