1. Multi Point Pacing (MPP)
13. November 2014
Klinikum Luedenscheid
Germany
Multi Point Pacing (MPP)
A new quadripolar pacing technology to improve CRT Response
Dr. Dejan Mijic
Department for
Cardiology and Angiology
Klinikum Luedenscheid
Germany 1

2. more than 20.000 patients in CRT Trials
Mile stone CRT Trials
more than patients in CRT Trials
CRT has expanded enormously over the last 2 decades
It became a very successful therapy for a selected group of HF patients with significant dyssynchrony (LBBB) but ...
Dr. Dejan Mijic 2

3. Birnie, Tang et al., Curr Opin Cardiol 2006
Challange in CRT: Non-responder rate Non-responder rate unchanged (about 30%) 3
Dr. Dejan Mijic
Birnie, Tang et al., Curr Opin Cardiol 2006

4. Potential Reasons for Suboptimal Response4
Dr. Dejan Mijic
Mullens, W. et al. J Am Coll Cardiol 2009;53:

5. Impact of LV lead location
on CRT-response
Significant improvement:
NYHA class
LV reverse remodeling (Δ%LVEDD)
Event-free survival
Data show that LV pacing lead location has a significant effect on CRT response and clinical outcome and non-responder rates may be improved based on pacing location.
Merchant and colleagues assessed the impact of semental LV lead position on CRT outcomes in 155 patients
- In comparison to mid-ventricle / basal LV pacing, patients with apical LV pacing showed less improvement in NYHA class and less LV reverse remodeling as assessed by change in %LVEDD during 6 month f/u 5
Dr. Dejan Mijic
Merchant, F.M. et al. Heart Rhythm May; 7(5):639-44

6. Multipolar LV lead - provides more CRT pacing options -
47mm
Figure 1 View of the quadripolar left ventricular lead with a detailed representation of the multiple pacing vectors. The 3-ring electrodes (M2, M3, P4)
are located 20, 30, and 47 mm from the 4.0-F–tip electrode (D1). Maximum lead body diameter is 4.7-F. In conjunction with an appropriate device, it enables
delivery of pacing stimuli using any of the 4 electrodes in 10 pacing configurations. Bottom: final lead location at implantation from the right anterior oblique
projection. RV right ventricular. 6
Dr. Dejan Mijic

7. Multipolar LV lead MORE-CRT Study Results
MORE-CRT showed a significant reduction in relative risk of 40.8% in the quadripolar CRT group
p=0.0001
85.97%
76.86%
months
N=1069
MORE-CRT was a prospective, randomized parallel open trial that enrolled 1,079 patients with a standard CRT-D indication. Patients were randomized in a 1:2 ratio to either a Control (C, BP CRT system with leads from any manufacturer with 1:2 ratio of St. Jude Medical to non-St. Jude Medical) or Treatment (T, SJM quadripolar CRT system) Arm.
The primary endpoint, freedom from the composite endpoint of intra- and post-operative LV lead-related events at 6 months, was compared between the C and T groups. Intra-operative events included overall lead implant failure in addition to any phrenic nerve stimulation, lead instability or high capture threshold that led to attempting more than one implant location, use of more than one LV lead, or use of a device for lead fixation; post-operative events included LV lead-related serious adverse device effect and abandoned CRT for any reason.
A total of 1,053 out of 1,079 patients (97%) contributed to primary endpoint results.
As shown in the figure on this slide, freedom from LV lead-related events in the intra-operative and post-operative settings was 76.86% in C and 85.97% in T (p =.0001).
Intention-to-treat analysis indicated a significant relative risk reduction of 40.8% in T.
The primary endpoint remained significantly lower in T even after adjusting for differences in the rates of ischemic heart disease (p=0.0027). 7
Dr. Dejan Mijic
Boriani et al., presented at ECS 2014

8. Intraoperative dp/dt measurement
for detection of the hemodynamic optimal pacing vector using the Quartet electrode
R.J. male, , ischemic CM, CAD, EF 20%, SR, LBBB, QRS 180ms.
CRT-D implant (Promote Q).
Pat.1 PA
Pat.1 LAO 40° 8
Dr. Dejan Mijic

9. Results dp/dt Hemodynamics and thresholds of each vector
Vektor 6
Vektor 10
Vektor 1
Vektor 2
Vektor 3
Vektor 4
Vektor 5
Vektor 7
Vektor 8
Vektor 9
Intrinsic dp/dt mmHg
vector 6 dp/dt 850mmHg (+19,3%)
vector 7 dp/dt 930mmHg (+30,6%)
dp/dt mmHg
Stim threshold
vector volt ms
7, ,5
2, ,5
2, ,5
5, ,5
2, ,5
1, ,5
1, ,5
0, ,5
4, ,5
1, ,5
LV stimulation
Stimulation Vector
Figure 1 View of the quadripolar left ventricular lead with a detailed representation of the multiple pacing vectors. The 3-ring electrodes (M2, M3, P4)
are located 20, 30, and 47 mm from the 4.0-F–tip electrode (D1). Maximum lead body diameter is 4.7-F. In conjunction with an appropriate device, it enables
delivery of pacing stimuli using any of the 4 electrodes in 10 pacing configurations. Bottom: final lead location at implantation from the right anterior oblique
projection. RV right ventricular. 9
Dr. Dejan Mijic

10. Distribution of LV pacing vectors:
Best and Bad
bad
best
Intrinsic Bad Best
dp/dt ,7% ,5%
N=18 10
Dr. Dejan Mijic

11. Limitations of conventional BiV CRT
Traditional CRT with one LV stimulation point in heart failure patients could reach resynchronisation by even prolonging the ventricular activation time
Although clinical problems (e.g. PNS, LV lead implantation failure, LV lead dislodgement) can be overcome by a quadripolar lead, the
Non-responder rate remains approximatly 30 %!
Could MultiPoint pacing lead to an additional hemodynamic effect over
conventional BiV CRT pacing ? 11
Dr. Dejan Mijic

12. TRIP-HF - multicenter, single-blind, crossover study
- 40 patients (mean age 70 years, EF 26%)
- Stimulation either 1 RV and 2 LV leads (3-V) or 1 RV and 1 LV lead (2-V)
- primary end point: quality of ventricular resynchronization (Z ratio)
Objectives We compared the effects of triple-site versus dual-site biventricular stimulation in candidates for cardiac resynchronization
Therapy.
Methods This multicenter, single-blind, crossover study enrolled 40 patients (mean age years) with moderate-tosevere heart failure despite optimal drug treatment, a mean LV ejection fraction of %, and permanent atrial fibrillation requiring cardiac pacing for slow ventricular rate. A cardiac resynchronization therapy device
connected to 1 RV and 2 LV leads, inserted in 2 separate coronary sinus tributaries, was successfully implanted in 34 patients. After 3 months of biventricular stimulation, the patients were randomly assigned to stimulation for 3 months with either 1 RV and 2 LV leads (3-V) or to conventional stimulation with 1 RV and 1 LV lead (2-V), then crossed over for 3 months to the alternate configuration. The primary study end point was quality of ventricular resynchronization (Z ratio). Secondary end points included reverse LV remodeling, quality of life, distance covered during 6-min hall walk, and procedure-related morbidity and mortality. Data from the 6- and 9-month
visits were combined to compare end points associated with 2-V versus 3-V.
Results Data eligible for protocol-defined analyses were available in 26 patients. No significant difference in Z ratio, quality of life, and 6-min hall walk was observed between 2-V and 3-V. However, a significantly higher LV ejection fraction (27 11% vs %; p ) and smaller LV end-systolic volume ( cm3 vs cm3; p 0.02) and diameter ( mm vs mm; p 0.02) were observed with 3-V than
with 2-V. There was a single minor procedure-related complication.
Conclusions Cardiac resynchronization therapy with 1 RV and 2 LV leads was safe and associated with significantly more LV reverse remodeling than conventional biventricular stimulation. 12
Dr. Dejan Mijic
Leclercq C, J Am Coll Cardiol 2008;51:1455–62

13. TRIP-HF Leclercq C, J Am Coll Cardiol 2008;51:1455–62
Problem: Y-Port, high energy, PNS-treshold
Results Data eligible for protocol-defined analyses were available in 26 patients. No significant difference in Z ratio, quality of life, and 6-min hall walk was observed between 2-V and 3-V. However, a significantly higher LV ejection fraction (27 11% vs %; p ) and smaller LV end-systolic volume ( cm3 vs cm3; p 0.02) and diameter ( mm vs mm; p 0.02) were observed with 3-V than
with 2-V. There was a single minor procedure-related complication.
Conclusions Cardiac resynchronization therapy with 1 RV and 2 LV leads was safe and associated with significantly more LV reverse remodeling than conventional biventricular stimulation. 13
Dr. Dejan Mijic
Leclercq C, J Am Coll Cardiol 2008;51:1455–62

14. Multipoint Pacing – First studies
Muscle Bundle - Microstimulation
Isolated Tissue Slab 14
Spach MS et al. Circ Res. 1982; 50:
Knisley SB and Hill BC. IEEE Trans Biomed Engineer 1995; 42(10):

15. Selected Site vs. Multipoint Pacing in Healthy Individuals     15
Dr. Dejan Mijic 15

16. Selected Site vs. Multipoint Pacing in Myocardial Scar     16
Dr. Dejan Mijic 16

17. MultiPoint™ Pacing Potential Benefits
Pacing from TWO LV sites (“Multipoint LV stimulation”)
Capture a larger area
Engage areas around scar tissue
Improve pattern of depolarization and repolarization
Improve hemodynamics
Improve resynchronization
LVp
A new technology in pacing for quadripolar systems now allows an additional stimulation vector (MultiPoint) added to the standard quadripolar left ventricular single site pacing. This results in a double LV-stimulation per cardiac cycle. The two stimulation vectors can be chosen from the 10 vectors available in the quadripolar systems.
LVd 17
Dr. Dejan Mijic

18. MultiPoint™ Pacing: Flexible Programming Options Pacing Sequences and Delays
LV First
5-80 ms
5-50 ms
LVp
LV1
LV2 RV
LVd
LVd
LVp RV
LVp
LVd RV RV
Group
LV1
Cathode
Anode A D1 P4 M2
RVc B C M3 D
RV First RV
LV1
LV2 RV
LVd
LVp RV
LVp
LVd 18
Dr. Dejan Mijic

19. Case Report 73-year-old obese female with dilative cardiomyopathy
Hypertension
SR, LBBB, QRS duration = 170 ms
Ejection fraction = 15-20%
Mitral insufficiency II° 19
Dr. Dejan Mijic

20. Case Report Measured dp/dt (mmHg)
Non-biV Pacing Selected biV Site Pacing Multi Point Pacing 20
Dr. Dejan Mijic

21. Case Report 21
Dr. Dejan Mijic

22. Effect of SSP and MPP on dp/dt compared to instrinsic sinus rhythm (n=3)22
Dr. Dejan Mijic

23. Clinical Studies: MultiPoint™ Pacing
MultiPoint Pacing improves acute contractility measurements 1,2
Methods:
N=19
Measurements of acute haemodynamic response (LV-dP/dt) of MPP and biv pacing
Four different MPP configurations with cathode in the LV and RV coil as anode were used
Results:
Most common optimal configuration in MPP was most distal and proximal electrode
In 84% two or more MPP configurations increased significantly LV dp/dt compared with BiV pacing
89% of pts. showed an acute increase of LV dp/dt 23
Dr. Dejan Mijic
Thibault et al. Europace 2013

24. Clinical Studies: MultiPoint™ Pacing
Effects of MPP on mechanical dyssynchrony
Methods:
n=52
Acute pacing protocol consisting of BiV simultaneous pacing and a set of 8 MPP interventions covering a range of LVLV and LVRV delay combinations
Max. VVV-time: 85ms
Results:
In 63% of patients at least one MPP intervention exibited a significant reduction (>20%) of dyssynchrony
Methods:
Acute pacing protocol consisting of BiV simultaneous pacing and a set of 8 MultiPoint Pacing interventions covering a range of LVLV and LVRV delay combinations.
Results:
In 63% of patients, at least one MultiPoint Pacing intervention exhibited a significant reduction (≥20%) in dyssynchrony
Graph 1 (reference 1): Comparison of mean dyssynchrony between BiV and MPP shows that the Yu index (Ts-SD) is more reduced with optimal MPP vs. BiV.
Graph 2 (reference 1): Comparison of mean strain-based early-to-late mechanical delay shows that the delay is more reduced with optimal MPP vs. BiV. 24
Dr. Dejan Mijic
Rinaldi et al. JCF 2013

25. Clinical Studies: MultiPoint™ Pacing
Acute pressure-volume loops in MPP-CRT patients
Methods:
Acute PV loops measurements in n=44 pt
Measurements performed:
Distal BiV (CONV)
Proximal BiV (CONV)
Anatomic MPP (D1-P4)
Electric MPP (conduction delay)
Results:
Compared to the best CONV vector MPP improved (regardless of HF etiology):
LV dP/dtmax (p<0.001)
Stroke volume (p=0.003)
LV EF (p=0,003)
MPP D1/P4 showed the best results
On behalf of Presenter
Patients implanted with the Quartet lead underwent pressure-volume (PV) loop assessment of LV hemodynamics. A pacing protocol with various MPP and conventional BiV configurations was performed, and each configuration was compared to right ventricular pacing (baseline).
Out of 42 patients, the best MPP configuration showed significantly more improvement in acute hemodynamic parameters (dP/dtMax, stroke work, stroke volume, %EF) and diastolic function than the best BiV configuration when compared to baseline, regardless of HF etiology. 25
Dr. Dejan Mijic
Pappone et al., Heart Rhythm 2014; 11:

26. Clinical Studies: MultiPoint™ Pacing
12 months response to MPP compared with conventional BiV Pacing 26
Dr. Dejan Mijic
Pappone et al., Heart Rhythm 2014

27. Clinical Studies: MultiPoint™ Pacing
12 months response to MPP compared with conventional BiV Pacing
Responder Definition:
ESV reduction > 15%
Sustaining the trend observed 2 months post-implant, PV loop guided MultiPoint LV pacing resulted in greater LV reverse remodelling and higher CRT response rate at 12 months compared to PV loop guided conventional CRT
- These findings may have an important implications for heart failure patients and may be valuable for improving CRT outcomes 27
Dr. Dejan Mijic
Pappone et al., Heart Rhythm 2014

28. More CRT MPP Study
MOre REsponse on Cardiac Resynchonization Therapy (CRT) with MultiPoint Pacing
“The purpose of this clinical investigation is to assess the impact of the Multi Point Pacing (MPP) feature at 12 months in the treatment of patients not responding to standard Cardiac Resynchronization Therapy (CRT) after 6 months.”
Type: Prospective, randomized, multicenter design
Enrollment Target: Qualified Patients
Duration: Investigation Timelines: Approx. 42 months
Patient timelines: Participation 6 – 12 months, depending on CRT response 28
Dr. Dejan Mijic

29. Project Flow Chart (follow up of qualified subjects)
More CRT MPP Study
Project Flow Chart (follow up of qualified subjects) 29
Dr. Dejan Mijic

30. Take home messages…
Multi-point pacing using a quadripolar electrode is associated with - high procedural success, lead stability/LV capture, reduction of PNS - numerous programmable configurations which can have an impact on shorter LV activation which can result in better hemodynamics (A-VTI, dp/dt, TDI)
Although only small patient numbers were investigated, there is a certain consistency in the results that multi-point pacing can improve CRT and reduce non-responder rate
Data from multi-point pacing with multipolar LV lead are promising but there is a demand for more automatic adjustment of optimal AV/VV delays
At least patients who do not respond to conventional BIV pacing should be considered for multipoint pacing
Multipoint pacing today is still under continuing investigation, further prospective trials (More-CRT MPP) will show the potential benefit of MPP over conventional BiV pacing in CHF patients 30
Dr. Dejan Mijic

31. Thank you for your attention

32. MPP Programming StrategyV1 V2 V3
Delay 1
Delay 2
NOT Easy…a bit more difficult than programming conventional BiV
More Options…means more flexibility
Now, how do we program?
Two sides: SIMPLE or STRESSED?
Stick with the principles of MPP or consider “optimizing” MPP?
Principles of MPP
Capture larger area, improve resulting homogeneous/uniform propagation
Simple way of programming MPP
Two electrodes with the most anatomical separation with min delays
“Optimization” of MPP
Requires electrical or hemodynamic feedback
Electrical: QRSd, RV-LV conduction
Hemodynamics: non-invasive, invasive
Long-term performance of “optimization” 32
Dr. Dejan Mijic