Clinical management of crt non responders

1. 1
Clinical Management of CRT
Non-Responders
心臟 科內
葉冠宏醫師

2. CRT Is Highly Beneficial
Mortality
HF or CV
hospitalizations
Cardiac Function/
Structure
QoL or NYHA
CARE-HF1,2
+ + + NA
COMPANION3
+ + NA NA
MIRACLE4 NA NA + +
MIRACLE ICD5 NA NA NA +
REVERSE6 NA +* + =
RAFT7
+ + NA NA
MADIT CRT8
+* + +* NA
CRT is an effective treatment for heart failure patients with:
systolic dysfunction
ventricular electrical conduction delays
1
Cleland J, et al. N Engl J Med. 2005;352:1539-1549.
2
Cleland J, et al. Eur Heart J. 2006;27:1928-1932.
3
Bristow M, et al. J Card Fail. 2000;6:276-285.
4
Abraham W, et al. N Engl J Med. 2002;346:1845-1853.
5
Young J, et al. JAMA. 2003;289:2685-2694.
6
Linde C, et al. JACC. 2008;52:1834-1843.
7
Tang A, et al. N Engl J Med. 2010;363:2385-2395.
8
Moss A, et al. N Engl J Med. 2009;361:1329-1338.
NA = Not powered, not collected, or not blinded for specific end point. * Post-hoc analysis.

3. CRT Response Rates
One-third of patients do not experience the full benefit of CRT
1
Abraham WT, et al. N Engl J Med. 2002;346:1845-1853. 4
Chung ES, et al. Circulation. 2008;117:2608-2616.
2
Young JB, et al. JAMA. 2003;289:2685-2694. 5
Abraham WT, et al. Heart Rhythm. 2005;2:S65.
3
Abraham WT, et al. Circulation. 2004;110:2864-2868. 6
Abraham WT, et al. Late-Breaking Clinical Trials, HRS 2010. Denver, CO.

4. Commonly Used Response Criteria in
Publications
Echocardiographic
↑ LVEF > 5 units
↑ LVEF > 15% relative
↓ LVESV ≥ 10%, no HF death
↓ LVESV ≥ 15%
LVESV < 115% of baseline
↓ LVEDV > 15%
↑ Stroke volume ≥ 15%
Combined
↑ LVEF > 5 units or ↑ 6MWD
≥ 50m AND ↓ NYHA ≥ 1 or ↓
QOL ≥ 10
Clinical
↓ NYHA ≥ 1
↓ NYHA ≥ 1, no HF death
↓ NYHA ≥ 1 and ↑ 6MWD ≥ 25%
↓ NYHA ≥ 1 and ↑ 6MWD ≥ 25%, no HF
death
↑ 6MWD ≥ 10%, no HF death, no
transplant
Two of the following 3: ↓ NYHA ≥ 1, ↑
6MWD ≥ 50 m, ↓ QOL ≥ 15
Clinical composite score improved
1
Fornwalt BK, et al. Circ 2010;121:1985-1991.

5. Clinical Composite Score for CRT Response
Assessment
Patient Death
Hospitalization for Worsening HF
Crossover due to Worsening HF
Worsening NYHA Classification
Moderately or markedly worse on
Patient Global Assessment
Answer
Yes to
Any
Patient
classified as
worsened
Improved NYHA Classification
Moderately or markedly improved
on Patient Global Assessment
Answer
Yes to
Any
Patient
classified as
improved
Patient classified as unchanged
1
Packer, M. Jl of Card Fail 2001;7:176-82

6. CRT Response is Dependent on Multiple
Factors
• Dyssynchrony
• Transmural scar
• Mitral
regurgitation
• “Fetal genes”
• Calcium handling
• LBBB >> RBBB
• QRS > 150 msec
• Female gender
• Non-ischemic CM
Vanderheyden M, et al. JACC 2008;51
Moss AJ et. al. NEJM 2009;361

7. Potential Reasons for Suboptimal CRT
Response
1
Mullens W, et al. JACC. 2009;53:765-773.
SuboptLVLeadPosition
SuboptAVTiming
Arrhythmia
Anemia
<90%
BiVPacingSuboptMedicalTherapyPersistentMech
DyssynchNarrowIntrinsicQRS
CompliancePrim
RVDysfunct

8. Approach to Improving Response
to CRT
Select the
appropriate
patient
Achieve a
stable and
effective LV
lead location
Deliver optimal
therapy
Provide device
diagnostic data
that enhances
device and
disease
management
At Every Stage of Care

12. 12
Am J Cardiol
2011;108:409–415
 114
consecutive
patients
with CRT
 Protocol-
driven care
vs. usual
care

13. 13
 uptitration of neurohormonal blockers (64%), echo-guided AV
optimization (50%), heart failure education (42%), arrhythmia
management (19%), and LV lead repositioning (7%).

14. Exercise Training After CRT Implant Results
in Further Improvement
Patwala AY, et al. J Am Coll Cardiol 2009;53:2332–9
Three months after implantation, exercise group had 30
minute supervised sessions 3x per week
Percentage Change at 6 Months

15. Echo-guided A-V optimization
 Adjusts AV intervals to produce the best LV
filling
15

16. Echo-guided V-V optimization
 Adjusts sequence & timing of LV & RV pacing, to make
the LV as efficient as possible, and to produce an
optimal stroke volume
 Either M-mode or VTI can be used for V-V optimization.
16

17. Device – Based Optimization
17
AdaptivCRT™ Algorithm

18. 18
Heart Rhythm 2011;8:1469 –1475
Every effort should be
made to reduce native
atrioventricular
conduction with cardiac
resynchronization therapy
systems in an attempt to
achieve biventricular
pacing as close to
100% as possible.

19. A Significant Percentage of Patients Do Not
Achieve Optimal BiV Pacing %
Reasons for < 100% pacing
Atrial fibrillation
PVCs
Competitive AV nodal
conduction
In a cohort of >80,000 patients, 40.7% exhibited
less than 98% BiV pacing
Cheng A, et al. Circ Arrhythm Electrophysiol. 2012;5:884-888

20. 20
Long-term survival after CRT among patients with AF+AVJA
is similar to that observed among patients in SR.
Mortality is higher for AF patients treated with rate-slowing
drugs.
J Am Coll Cardiol HF 2013;1:500–7

21. 21
Cardiac resynchronization therapy with 1 RV and 2 LV leads was
safe and associated with significantly more LV reverse remodeling
than conventional biventricular stimulation.
J Am Coll Cardiol 2008;51:1455–62

22. Experiments using a canine model of LBBB
22
By increasing the number of LV pacing electrodes up to seven, LV activation
time was substantially reduced. However, compared with single-site LV pacing,
the LVdP/dtmax increased only if the hemodynamic benefit with single-site
pacing was small.

23. MultiPoint™ Pacing Potential Benefits
 Pacing from TWO LV sites (“Multipoint LV stimulation”)
 Capture a larger area
 Improve pattern of depolarization/repolarization
 Improve hemodynamics
 Improve resynchronization
 Improve CRT response

24. 24
110 HF pts treated for 1 year, conventional CRT (STD, N=54), CRT with
hemodynamic and electrical optimization of LV pacing site (OPT, N=36),
optimization of LV pacing site + MPP (OPT-MPP, N=20)
2016 HRS
Abstract

25. 507 patients, Aug2013 – May 2015, 76 Italian centers
Europace, doi:10.1093/europace/euw094

26. Europace (2015) 17, 148–151
48 European Centers

27. Heart Failure Management Strategies
ResponseOptimize Medical
Treatment
Monitor and
Optimize Device
Ongoing Patient
Education
Regular
Follow-up
Following a regimen for CRT management can
increase the likelihood of a positive CRT response

28. Take Home Messages
 CRT response can be affected by the patient’s disease
state, device implant, device settings, medical therapy
and patient compliance.
 Heart failure management strategies which can
enhance CRT patient care include optimizing medical
treatment, monitoring and optimizing the device,
educating the patient, and performing regular follow-
up.
 A structured evaluation of non-responders can help to
document tests and interventions to determine causes
for CRT non-response.

29. 29
感恩聆聽
敬請指教