55
A Prospective Study of Ripple Mapping the Post-Infarct Ventricular Scar to guide Substrate Ablation for Ventricular Tachycardia Short title: Ripple Mapping in post-infarct VT Vishal Luther* MRCP; Nick WF Linton* MEng, MRCP, PhD; Shahnaz Jamil-Copley MRCP; Michael Koa-Wing MRCP, PhD; Phang Boon Lim MRCP, PhD; Norman Qureshi MRCP; Fu Siong Ng MRCP, PhD; Sajad Hayat MD, MRCP; Zachary Whinnett MRCP, PhD; D. Wyn Davies MD, FRCP, FHRS; Nicholas S. Peters MD, FRCP, FHRS; Prapa Kanagaratnam FRCP, PhD *contributed equally as first author Institutional Affiliation: Imperial College Healthcare NHS Trust, London, UK Address for correspondence: Dr. Prapa Kanagaratnam 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

  • Upload
    dinhbao

  • View
    218

  • Download
    3

Embed Size (px)

Citation preview

Page 1: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

A Prospective Study of Ripple Mapping the Post-Infarct Ventricular Scar to guide

Substrate Ablation for Ventricular Tachycardia

Short title: Ripple Mapping in post-infarct VT

Vishal Luther* MRCP; Nick WF Linton* MEng, MRCP, PhD; Shahnaz Jamil-Copley MRCP;

Michael Koa-Wing MRCP, PhD; Phang Boon Lim MRCP, PhD; Norman Qureshi MRCP;

Fu Siong Ng MRCP, PhD; Sajad Hayat MD, MRCP; Zachary Whinnett MRCP, PhD; D. Wyn

Davies MD, FRCP, FHRS; Nicholas S. Peters MD, FRCP, FHRS; Prapa Kanagaratnam FRCP,

PhD

*contributed equally as first author

Institutional Affiliation:

Imperial College Healthcare NHS Trust, London, UK

Address for correspondence:

Dr. Prapa Kanagaratnam

St. Marys Hospital, Imperial College Healthcare NHS Trust, London W2 1NY, United Kingdom.

Telephone: +44 (0) 203 312 3783; Fax: +44 (0) 203 312 1657

Email: [email protected]

Word count: 6837

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

Page 2: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Journal Subject Terms

Arrhythmia and Electrophysiology

Arrhythmias

Catheter Ablation and Implantable Cardioverter-Defibrillator

Electrophysiology

Sudden Cardiac Death

Basic, Translational, and Clinical Research

Clinical Studies

Fibrosis

Mechanisms

Funding sources

V. Luther is funded by a British Heart Foundation Clinical Research Training Fellowship award

(no. FS/15/12/31239). We acknowledge the ElectroCardioMaths Programme of the British Heart

Foundation Centre of Research Excellence, BHF Grant RG/10/11/28457, and the National

Institute for Health Research (UK) Biomedical Research Centre.

Disclosures

Imperial Innovations hold Intellectual Property relating to Ripple Mapping on behalf of Drs

Kanagaratnam and Linton, who have also received royalties from Biosense Webster. Drs

Kanagaratnam, Linton, Jamil-Copley, Luther, and Lim have received consulting fees with

respect to Ripple Mapping from Biosense Webster. The other authors report no conflicts.

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

Page 3: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

ABSTRACT

Background: Post-infarct ventricular tachycardia (VT) is associated with channels of surviving

myocardium within scar characterized by fractionated and low amplitude signals usually

occurring late during sinus rhythm. Conventional automated algorithms for 3D electro-

anatomical mapping cannot differentiate the delayed local signal of conduction within the scar

from the initial far-field signal generated by surrounding healthy tissue. Ripple Mapping (RM)

displays every deflection of an electrogram, thereby providing fully informative activation

sequences. We prospectively used CARTO based Ripple Maps to identify conducting channels

(RMCCs) as a target for ablation.

Methods and Results: High density bipolar LV endocardial electrograms were collected using

CARTO3v4™ in sinus rhythm or ventricular pacing and reviewed for RMCC identification. 15

consecutive patients (median age 68yrs, LVEF 30%) were studied (6month pre-procedural ICD

therapies: median 19 ATP events (Q1-Q3=4–93) and 1 shock (Q1-Q3=0–3)). Scar (<1.5mV)

occupied a median 29% of the total surface area (median 540 points collected within scar). A

median of 2 RMCCs were seen within each scar (length 60mm; initial component 0.44mV;

delayed component 0.20mV; conduction 55cm/s). Ablation was performed along all identified

RMCCs (median 18 lesions) and any presumed inter-connected late activating sites (median 6

lesions (Q1-Q3=2-12). The diastolic isthmus in VT was mapped in 3 patients and co-located

within the RMCCs identified. VT was non-inducible in 85% of patients post ablation and 71%

remain free of VT recurrence at 6 month median follow up.

Conclusions: Ripple mapping can be used to identify conduction channels within scar to guide

functional substrate ablation.

3

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

Page 4: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Key Words:

Ventricular Tachycardia

Myocardial Infarction

Implantable Cardioverter Defibrillator

Ablation

Mapping

4

70

71

72

73

74

75

Page 5: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Introduction

Post-infarct re-entrant ventricular tachycardia (VT) is dependent on channels of surviving

myocardium within the infarct scar.1 ‘Substrate-based’ ablation that eliminates all abnormal

electrograms, including fractionated and late potentials within scar can reduce long-term VT

recurrence.2 However, detailed mapping studies of local electrograms can identify paths of

activation within the scar, forming channels that are considered a more specific target for

substrate ablation.3, 4

Ripple Mapping (RM) is a method of 3D activation visualization that displays each electrogram

component as a dynamic bar that protrudes from its 3D location on the surface geometry.5 The

height of each bar correlates with the voltage amplitude of the electrogram at that time point.

When multiple points are collected, activation is visually apparent from the direction of

propagation of bar movement on the map. This is achieved without the need for manual

annotation or setting a window of interest. Ripple activation maps can be superimposed on a

conventional bipolar voltage map, thereby displaying the surface geometry with both voltage and

activation simultaneously.6, 7 RM is incorporated into CARTO3v4™ (Biosense Webster), and has

been applied prospectively to guide atrial tachycardia ablation in the scarred atrium.8

We have previously described how RM is able to visualize “conducting channels” (RMCCs) of

electrogram activation within scar using an off-line system in a retrospective series of ventricular

substrate maps.9 This showed that pacing sites with good pace-maps and where entrainment

mapping confirmed participation in VT co-located with the identified RMCCs. On the basis of

5

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

Page 6: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

these studies, we propose to test the hypothesis that ablating RMCCs within the post-infarct scar

can prevent VT recurrence.

6

23

24

Page 7: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Methods

Study Sample

Consecutive patients referred for VT ablation secondary to documented episodes of sustained VT

or appropriate ICD therapy post distant myocardial infarction were studied. All patients

prospectively enrolled after providing written informed consent to participate in the research

study. This study was approved by a local human research ethics committee.

Ventricular scar mapping

Patients were studied in the post-absorptive state under general anesthesia. Surface ECGs and

bipolar electrograms were monitored continuously on a LabSystem Pro (Bard Electrophysiology,

Lowell, MA), sampled at 1 KHz and bandpass filtered at 30–500 Hz, with the notch filter

switched off. Noise signal in the lab was recorded below 0.05mV. A steerable quadripolar

catheter was positioned in the right ventricular apex. The left ventricle (LV) was accessed via

transeptal approach (BRK Needle, St. Jude Medical) under trans-esophageal guidance or

retrograde from the aorta. Heparin boluses were administered intravenously to target an activated

clotting time >300 seconds. The Hansen Sensei® Robotic System (Hansen Medical Inc.,

Mountain View, CA, USA) was used to support endocardial mapping and ablation as per

operator preference.10 No epicardial mapping was performed.

Detailed maps of the endocardial LV surface were obtained in sinus rhythm (or during right

ventricular pacing if the patient was pacing dependent) using a 3.5-mm tip SmartTouch

Thermocool catheterTM (Biosense Webster). Interpolation was limited to a color threshold ≤5

mm, with an emphasis on fully defining the scar and border zone of the infarcted tissue. Normal

7

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

Page 8: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

bipolar endocardial voltage was defined as a peak-to-peak amplitude ≥1.5 mV, “core scar” as

<0.5 mV, and “border zone” was between 0.5-1.5mV.11 Electro-anatomical data were collected

either point by point, or using an automated point collection facility (ConfiDENSETM Continuous

mapping) as per operator preference. The automated system relied on filters for each beat based

on a series of pre-assigned parameters. Criteria for including points were; (1) a cycle length

stability within a 5% range of the R-R interval; (2) an electrode position stability within 2mm;

(3) gating to end expiration of the respiratory cycle; (4) a contact force above a minimum of 2g

(to avoid sites with insufficient contact).

The multi-electrode PentaRay catheterTM (2-6-2mm spacing) was applied in the latter cases in

this study. To ensure adequate surface contact, a tissue proximity filter which only collected

points in proximity to the endocardial surface based on an impedance measurement algorithm of

either dipole was applied.

VT induction

VT induction was performed at 2 sites with 2 drive trains, with up to 3 extra-stimuli decremented

to ventricular refractoriness or 200ms. If VT was inducible and sustained, a remap of the scar

was performed. If an unstable VT was induced, it was terminated by overdrive pacing or

defibrillation, and no further attempts to induce VT were performed.

Analysis of Ripple Map

Ripple bars of a typical bipolar electrogram from an area of functional myocardium within

ventricular scar is shown in figure 1a. The electrogram is composed of two components: a far-

field component from the bulk of ventricular myocardium surrounding the scar (generally higher

8

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

Page 9: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

amplitude, lower frequency), followed by a delayed component from local tissue. Substrate

mapping relies upon differentiation of the local from far field components. When multiple

electrograms within the scar are reviewed using RM, two wavefronts may be seen: an initial

wavefront occurs in tandem with bars in the surrounding healthy tissue and is presumed far field,

followed by a delayed wavefront of presumed local activation (figure 1b and supplemental video

1).

Whilst the patient underwent VT induction, CARTO Ripple Maps were analyzed for Ripple

Mapping Conducting Channels (RMCCs), defined as channels of sequentially moving adjacent

bars representing local activation within scar, distinct from the initial wavefront (figure 1c). No

pacing maneuvers were performed to confirm the distinction between local and far field

components within the RMCC. Electrogram deflections less than 0.05mV were hidden from the

Ripple Map to reduce background noise, and the bars were clipped at 0.30mV to allow low

voltage signals to be displayed more clearly. These parameters could be adjusted during analysis.

Ripple Maps were studied from the onset of QRS until the end of ventricular activation. Design

lines were drawn on the anatomical shell to encircle the entire RMCC or clusters of late local

activating Ripple bars that activated simultaneously, and adjacent clusters were joined to form

RMCCs. If the initial and delayed wavefronts were difficult to differentiate, maps were analyzed

frame-by-frame or in reverse towards the onset of the QRS. Electrograms along each RMCC

were then analyzed using the CARTO Ripple Viewer, which enabled multiple Ripple bars to be

selected, and the corresponding electrograms to be displayed together. This was used to validate

the RMCC design-lines that had been drawn.

Where VT was mapped, Ripple Maps were studied over the complete tachycardia cycle length to

identify the location of ripple bar activation during the diastolic interval. Design lines were

9

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

Page 10: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

drawn to encircle the boundaries of this diastolic activation to highlight the diastolic pathway

(RMDP).

Radiofrequency Ablation

Ablation was delivered within each RMDP where VT was mapped, followed by all RMCCs

identified. Discrete clusters of late activating ripple bars were also ablated as they were

considered an endocardial component of an epicardial RMCC. Ablation was performed with a

3.5-mm externally irrigated-tip catheter. Each RF delivery was temperature-controlled to 50oC,

with a power limit of 30W for 60secs (17/ml/min) or 50W for 30secs (30ml/min) as per operator

preference, with a target contact force of 10-20g aiming for the local signal to diminish. No other

ablation was performed within this protocol.

Endpoints

a) Post procedural VT inducibility: Post ablation ventricular stimulation was used to assess VT

inducibility as a marker of immediate ablation efficacy. Patients were defined as either “non-

inducible” or “inducible” for VT.

b) Follow-up: ICD interrogations were conducted at 1, 3, 6, and 12 months and arrhythmia logs

were retrieved. Endpoints were defined by time to first VT episode recurrence (first ATP or shock

therapy, or sustained VT captured within a monitor zone or 12 lead ECG) . All patients were offered

remote monitoring, and additional ICDs were interrogated whenever symptoms suggested

delivery of device therapy.

10

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

Page 11: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Statistical Analysis

Categorical variables were expressed as percentages. Continuous variables were expressed as

mean ± 1 standard deviation for normally distributed data and/or median (lower quartile – upper

quartile) for non-normal data. Paired non-normal data were analyzed using the Wilcoxon Signed

Ranks test. A two sided p value ≤0.05 was considered significant.

11

117

118

119

120

121

Page 12: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Results

Study Population: Baseline clinical characteristics of 15 consecutive patients (median age 68yrs

(58-77), LVEF 30% (30-40) studied in this protocol are listed in Table 1. Previous VT ablation

had been performed in 6/15 (40%) patients, and 11/15 (73%) patients were prescribed

Amiodarone. Pre-procedural ICD therapy burden over the previous 6 months or last VT ablation

included 19 ATP events (4–93) and 1 shock (0–3).

Map collection: Details of LV map collection are summarized in Table 2. Ventricular scar maps

in the first 12/15 cases (80%) were collected with a SmartTouch™ catheter supported by the

Hansen Sensei™ Robotic System. The latter 3/15 (20%) maps were collected using the

PentaRay™. Voltage maps were collected in an RV paced rhythm in 9/15 (60%) patients (pacing

dependent/operator preference). Chamber geometry and electro-anatomical data were collected

simultaneously (median chamber area of 258cm2 (235-298), median 714 points per map (55–

1107), median mapping time of 79mins (63–90)). Detailed mapping was performed within scar

((median 540 points per map (365-742); (median 6.6 point per cm2 (5.3-8.7); (median scar area

77cm2 (62-120)). Scar represented median 29% (26–37%) of the total endocardial surface area.

VT induction: VT was non-inducible in 2/15 (13%) patients from the start. In 10/15 patients,

VT was either non-sustained or poorly tolerated requiring termination with overdrive pacing or

defibrillation. VT was mapped in only 3/15 (20%), enabling detailed review as a Ripple Map

(1205±1026 EGMs) to characterize the RMDP. No entrainment was performed in VT, but

12

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

Page 13: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

ablation was delivered within the mapped RMDP. In all patients, after the first VT was induced,

no further attempts to induce VT were performed till after RMCC ablation.

Ripple mapping within ventricular scar:

RMCCs were identified in all patients and 3 patients also had induced VT mapped. Figure 2

Panel I illustrates the RMCCs identified in patient 9 using the raw data shown in supplemental

Video 2a. The two RMCCs (enhanced with design lines) are seen as late activating channels

separate from the initial wavefront. The direction of activation is readily apparent, and the

channel is seen without any manual annotation or point tagging. In this example, the RMCCs are

broad and cover a relatively large area of the scar. In Panel II and Supplemental Video 2b, the

corresponding VT circuit is shown as a Ripple Map and local diastolic activation is clearly

differentiated from systolic activation. The entire RMDP is seen with varying diameter along its

length. Ablation within the RMDP interrupted the VT circuit.

In some cases the RMCCs were difficult to see during forward play and needed step-by step

reverse play. Figure 3 Panel I summarize the three RMCCs identified from supplemental Video

3a in patient 5. The RMCCs were seen closer to the conventional scar border on the bipolar

voltage map. Isolated clusters of very late activating ripple bars that do not appear connected to

the RMCCs identified are also apparent, and it is assumed that these arose from channels that are

deep to the endocardium. In panel II and supplemental Video 3b, the diastolic component of the

induced VT is shown. The complete RMDP was not seen, due to either insufficient point

collection or non-endocardial components to the circuit. Despite this, using the RMDP, there

13

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

Page 14: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

appears to a central refractory core in this circuit within the scar. A single ablation lesion within

the RMDP interrupted VT.

Centripetal pattern of activation into the scar core has also been described previously and

supplemental video 4a from patient 13 demonstrates an example of this with a Ripple Map.12

Figure 4a illustrates how this pattern might occur with regions of functional tissue activated by

any number of RMCCs. This map was collected with the PentaRay™ (2599 points). By playing

the RM backwards and encircling each patch of simultaneously activating tissue, interconnecting

RMCCs were gradually built up. Figure 4b summarizes the final RMCC locations. Remapping of

the scar post RMCC ablation to look for elimination of activation along RMCCs was also

performed in this case, and presented in the video. Supplemental video 4b shows the

corresponding VT map. In this example there was a narrow RMDP which opened into a broad

region of diastolic activation before the systolic activation occurred. Ablation within the RMDP

interrupted VT.

Details of RMCC characterization within all study patients are presented in Table 3. A median of

2 RMCCs were identified within each scar. The median RMCC length was 60mm (40-80).

Electrograms were sampled for analysis every 10mm along each RMCC. The median amplitude

of the initial component (presumed far field) was significantly greater than the delayed

component (presumed local), (initial component 0.44mV (0.25-0.68); delayed component

0.20mV (0.13-0.30); p<0.001). The median conduction velocity within the RMCC was 55cm/s.

RF ablation was delivered along each RMCC (median 18 lesions per RMCC (9-22)). Further

14

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

Page 15: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

ablation (median 6 lesions (2-12)) was performed within isolated clusters of late activating ripple

bars, considered an endocardial component of an epicardial RMCC.

Clinical outcome: This has been summarized in Table 4. At the end of the procedure, no VTs

were inducible in 11/13 (85%) patients where VT was induced from the start (VT occurred in the

remaining 2 cases only with a more aggressive programmed stimulation for induction). There

were no complications during the procedures, but 1 patient died a week later from worsening

heart failure and no ventricular arrhythmic episodes were identified on post mortem device

interrogation. In those patients already on long-term Amiodarone, it was continued. Patients

were followed up for a median of 6 months. 10/14 (71%) patients remain free of VT recurrence.

VT recurred in 4 patients - within 1 month (Pt. 11, Pt. 12), at 2 months (Pt. 13) and 6 months (Pt.

3) post-ablation. Of note, despite VT non-inducibility immediately post procedure, Pt. 12

presented again with ICD storm, and importantly, during redo ablation, the RMCCs identified

during the index case had not been completely eliminated.

Post procedural analysis: By merging the 3 RMDP and RMCC maps, it was possible to

understand the relationship between these. Figure 5 confirms that the RMDP (length 61±17mm,

area 5±0.3cm2, diastolic component 0.27±0.18mV) always appeared within the area of an

RMCC (length 60±23mm, area 5.4±3cm2, delayed component 0.21±0.17mV). Interestingly,

figure 6 demonstrates how the lines of block bordering the RMDPs in pt. 9 were formed of

myocardium with no signal during VT but of conducting myocardium during sinus rhythm

(0.22±0.1mV) indicating functional block. These areas of functional block were within the

RMCC borders (20±13% of total RMCC area), not at the scar border-zone.

15

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

Page 16: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Supplemental figure 1 illustrates how the location of most RMCCs did not correlate with

‘voltage channels’ as voltage was usually annotated to the largest electrogram component rather

than the local signal within the RMCC. All remaining ventricular scar maps within this study are

presented as supplemental figure 2, with the location and direction of RMCC activation

highlighted. The location of the scar within the ventricle did not influence the frequency,

location, or size of an RMCC within the scar.

16

211

212

213

214

215

216

Page 17: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Discussion

In this study, we describe our early experience of Ripple Mapping the post-infarct ventricular

scar to identify channels of local activation. These conduction channel (RMCCs) co-located with

the VT diastolic pathway (RMDP) (mapped in 3 patients, with ablation interrupting VT in each

case), and ablation of these RMCCs rendered 85% of patients non-inducible for VT and 70%

free from ICD therapy at 6 months.

All approaches to substrate-based ablation of ventricular scar use 3D mapping to characterize the

likely location of channels that might support VT. Voltage mapping displays scar as areas below

a threshold of 1.5mV, allowing encirclement of the scar border zone or complete scar

“homogenization” to isolate or eliminate all potential channels without defining them

specifically.13, 14 Adjustment of the voltage threshold has been used to identify channels of

preserved myocardium within scar, but as voltage is annotated to the electrogram peak, these

regions are usually formed of far-field signal.15 Manual tagging of abnormal potentials or manual

adjustment of activation time using color-coded isochronal activation maps can highlight local

activation through scar, but are challenging with high density point collection, and annotation as

a single activation time is suboptimal at sites with fractionated or multiple late potentials.12

Adjusting the window-of-interest post QRS has been used to highlight sites of late activation but

ignores all local signals within the time-window spanned by the QRS complex.16

In this study, we found that Ripple Mapping overcame some of the practical limitations of

characterizing the VT substrate using conventional 3D mapping techniques. We have previously

17

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

Page 18: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

used CARTO Ripple Map to guide ablation in atrial tachycardia without annotation. The

approach to mapping ventricular scar is quite different because of the extent of far-field

electrograms from the surrounding healthy myocardium. RM preserved all components of the

electrogram, and delayed low-amplitude local activation within scar was seen distinct from an

initial wavefront, presumed far-field, that occurred in tandem with activation in the surrounding

healthy tissue, and evident on the map without any manual annotation or tagging needed. This

was less susceptible to operator variation when played backward frame-by-frame, checking the

electrograms to exclude noise and far-field repolarization. The direction of activation from

clusters of late potentials characterized the scar into RMCCs. Previously, in a retrospective series

we were able to show that sites of entrainment with concealed fusion, excellent pace-maps and

termination co-located to such RMCCs.9 In the current study, we were able to show that where

the VT RMDP could be mapped, it was contained entirely within an RMCC, though this was

limited to only 3 cases. In certain areas, it was formed by functional block within the RMCC

borders. The RMDPs did not always co-locate to the latest late potentials within scar, nor did

they locate to the infarct-border zone as defined by conventional bipolar voltage mapping.

Therefore, neither the ‘lateness’ of the local electrogram, nor the scar-border zone determined

the arrhythmic potential. It is possible that at shorter pacing intervals the local electrograms of

the RMCCs may become more delayed and exhibit functional block resulting in smaller RMCCs

that are more specific for diastolic pathways, but this was beyond the scope of the current study.

All channels identified on a Ripple Map are based on electrogram amplitude and hence a

function of the electrode size and spacing. Mapping with multipolar catheters employing narrow

spacing and smaller electrodes, as in the PentaRay, has demonstrated increased comparative

18

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

259

260

261

262

Page 19: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

amplitude in local signal compared to a large tip and widely spaced electrodes.17 The influence of

electrode type in RMCC identification requires further study.

The optimal approach to use this information to guide ablation is yet to be determined. It was

clear that only a portion of the RMCC was needed to produce an RMDP, and that the connection

between the RMCC and healthy tissue was not easily determined. Therefore, in this study, we

opted to deliver a series of lesions along the RMCC to disrupt the RMCC without

‘homogenizing’ it and using VT inducibility as the endpoint. Our medium term results are

consistent with other studies using this endpoint.2 In the current study, Pt. 12 was non inducible

at the end but had recurrence. Importantly, the RMCCs identified during the index case were still

apparent at restudy. However, there may be discrepancy between the region of mapping and the

ablation lesion location which limits the use of ablation strategies to comment on the mechanism

of tachycardias. It was feasible to remap the scar post ablation to demonstrate RMCC elimination

post ablation and this may offer an alternative endpoint for substrate ablation which requires

further study.

19

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

Page 20: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Limitations: This was a small, single-center and non-randomized feasibility study where we

describe our early experience using Ripple Mapping to guide substrate ablation. This study

allows for several future potential studies as outlined in the discussion. This study was not

designed to compare the Ripple Mapping technique to other methods of VT substrate ablation.

Ripple maps were collected in sinus rhythm in some patients and RV pacing in others, and was

not standardized from the start. Defining the RMCC up to the scar border was difficult as early

local activating signals were hidden within the far field wavefront. This technique is limited in

scars closer to the conducting system, where local signal is seen earlier within the QRS, and the

latest activating site can be a far field signal.

20

278

279

280

281

282

283

284

285

286

Page 21: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Conclusions

We describe a technique using CARTO Ripple Map for mapping the functional substrate of post-

infarct scar. We were able to identify conduction channels that contain the diastolic isthmus of

ventricular tachycardia. Further studies are needed to elucidate if Ripple Mapping can be used to

target alternative endpoint such as channel abolition to improve outcomes.

21

287

288

289

290

291

Page 22: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

References

1. Stevenson WG, Khan H, Sager P, Saxon LA, Middlekauff HR, Natterson PD, Wiener I. Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction. Circulation. 1993;88:1647-1670

2. Jais P, Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia R, Shah A, Derval N, Cochet H, Knecht S, Miyazaki S, Linton N, Rivard L, Wright M, Wilton SB, Scherr D, Pascale P, Roten L, Pederson M, Bordachar P, Laurent F, Kim SJ, Ritter P, Clementy J, Haissaguerre M. Elimination of local abnormal ventricular activities: A new end point for substrate modification in patients with scar-related ventricular tachycardia. Circulation. 2012;125:2184-2196

3. Tung R, Mathuria NS, Nagel R, Mandapati R, Buch EF, Bradfield JS, Vaseghi M, Boyle NG, Shivkumar K. Impact of local ablation on interconnected channels within ventricular scar: Mechanistic implications for substrate modification. Circ Arrhythm Electrophysiol. 2013;6:1131-1138

4. Berruezo A, Fernandez-Armenta J, Andreu D, Penela D, Herczku C, Evertz R, Cipolletta L, Acosta J, Borras R, Arbelo E, Tolosana JM, Brugada J, Mont L. Scar dechanneling: New method for scar-related left ventricular tachycardia substrate ablation. Circ Arrhythm Electrophysiol. 2015;8:326-336

5. Linton NW, Koa-Wing M, Francis DP, Kojodjojo P, Lim PB, Salukhe TV, Whinnett Z, Davies DW, Peters NS, O'Neill MD, Kanagaratnam P. Cardiac ripple mapping: A novel three-dimensional visualization method for use with electroanatomic mapping of cardiac arrhythmias. Heart rhythm. 2009;6:1754-1762

6. Jamil-Copley S, Linton N, Koa-Wing M, Kojodjojo P, Lim PB, Malcolme-Lawes L, Whinnett Z, Wright I, Davies W, Peters N, Francis DP, Kanagaratnam P. Application of ripple mapping with an electroanatomic mapping system for diagnosis of atrial tachycardias. J Cardiovasc Electrophysiol. 2013;24:1361-1369

7. Koa-Wing M, Nakagawa H, Luther V, Jamil-Copley S, Linton N, Sandler B, Qureshi N, Peters NS, Davies DW, Francis DP, Jackman W, Kanagaratnam P. A diagnostic algorithm to optimize data collection and interpretation of ripple maps in atrial tachycardias. Int J Cardiol. 2015;199:391-400

8. Luther V, Linton NW, Koa-Wing M, Lim PB, Jamil-Copley S, Qureshi N, Ng FS, Hayat S, Whinnett Z, Davies DW, Peters NS, Kanagaratnam P. A prospective study of ripple mapping in atrial tachycardias: A novel approach to interpreting activation in low-voltage areas. Circ Arrhythm Electrophysiol. 2016;9:e003582

9. Jamil-Copley S, Vergara P, Carbucicchio C, Linton N, Koa-Wing M, Luther V, Francis DP, Peters NS, Davies DW, Tondo C, Della Bella P, Kanagaratnam P. Application of ripple mapping to visualize slow conduction channels within the infarct-related left ventricular scar. Circ Arrhythm Electrophysiol. 2015;8:76-86

10. Luther V, Jamil-Copley S, Koa-Wing M, Shun-Shin M, Hayat S, Linton NW, Lim PB, Whinnett Z, Wright IJ, Lefroy D, Peters NS, Davies DW, Kanagaratnam P. Non-randomised comparison of acute and long-term outcomes of robotic versus manual ventricular tachycardia ablation in a single centre ischemic cohort. J Interv Card Electrophysiol. 2015;43:175-85

11. Marchlinski FE, Callans DJ, Gottlieb CD, Zado E. Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation. 2000;101:1288-1296

12. Irie T, Yu R, Bradfield JS, Vaseghi M, Buch EF, Ajijola O, Macias C, Fujimura O, Mandapati R, Boyle NG, Shivkumar K, Tung R. Relationship between sinus rhythm late activation zones and critical

22

292293294295296297298299300301302303304305306307308309310311312313314315316317318319320321322323324325326327328329330331332333334335336337338339

Page 23: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

sites for scar-related ventricular tachycardia: Systematic analysis of isochronal late activation mapping. Circ Arrhythm Electrophysiol. 2015;8:390-399

13. Di Biase L, Santangeli P, Burkhardt DJ, Bai R, Mohanty P, Carbucicchio C, Dello Russo A, Casella M, Mohanty S, Pump A, Hongo R, Beheiry S, Pelargonio G, Santarelli P, Zucchetti M, Horton R, Sanchez JE, Elayi CS, Lakkireddy D, Tondo C, Natale A. Endo-epicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy. J Am Coll Cardiol. 2012;60:132-141

14. Tilz RR, Makimoto H, Lin T, Rillig A, Deiss S, Wissner E, Mathew S, Metzner A, Rausch P, Kuck KH, Ouyang F. Electrical isolation of a substrate after myocardial infarction: A novel ablation strategy for unmappable ventricular tachycardias--feasibility and clinical outcome. Europace. 2014;16:1040-1052

15. Arenal A, del Castillo S, Gonzalez-Torrecilla E, Atienza F, Ortiz M, Jimenez J, Puchol A, Garcia J, Almendral J. Tachycardia-related channel in the scar tissue in patients with sustained monomorphic ventricular tachycardias: Influence of the voltage scar definition. Circulation. 2004;110:2568-2574

16. Vergara P, Trevisi N, Ricco A, Petracca F, Baratto F, Cireddu M, Bisceglia C, Maccabelli G, Della Bella P. Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation. J Cardiovasc Electrophysiol. 2012;23:621-627

17. Berte B, Relan J, Sacher F, Pillois X, Appetiti A, Yamashita S, Mahida S, Casassus F, Hooks D, Sellal JM, Amraoui S, Denis A, Derval N, Cochet H, Hocini M, Haissaguerre M, Weerasooriya R, Jais P. Impact of electrode type on mapping of scar-related VT. J Cardiovasc Electrophysiol. 2015

23

340341342343344345346347348349350351352353354355356357358359360361

362

Page 24: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Table 1: Patient Demographics

Patient No

Age (yrs)

Revascularisationapproach

LVEF(%)

Amiodarone Device Previous ablations

Pre-procedural ATP

Pre-procedural shocks

1 71 Medical 42 N ICD 0 167 262 79 CABG 38 Y CRT-D 1 1325 133 78 CABG 22 Y ICD 3 7 24 57 PCI 30 Y ICD 1 0 05 67 CABG 35 Y ICD 1 0 86 89 Medical 20 Y CRT-D 0 57 07 75 Medical 30 Y ICD 0 12 48 78 CABG 20 Y ICD 0 1 19 49 PCI 35 Y ICD 0 52 110 46 CABG 42 N ICD 0 99 011 64 CABG 30 N ICD 1 87 012 38 PCI 45 Y ICD 0 19 213 75 PCI 30 Y ICD 1 201 114 68 CABG 45 Y ICD 0 7 015 58 CABG 30 N ICD 0 0 1

Median 68 30 19 1LQ 58 30 4 0UQ 77 40 93 3

24

363364365

366

Page 25: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Table 2: Mapping and scar characteristics

25

Patient No

Rhythm MappingCatheter

Total LV area/cm2

EA points

Scar Location Total scar area (cm2)

Scar Proportion

(%)

Scar points

Scar points/ cm2

Mapping time

(mins)1 Sinus SmartTouch 206 556 Basal: Septum 58 28 340 5.9 892 RV Paced SmartTouch 211 1180 Basal: Septum/posterior 55.5 26 760 13.7 763 RV Paced SmartTouch 258 1573 Basal: Inferior/posterior 184 71 1101 6.0 374 Sinus SmartTouch 320 552 Apex: Anterior 240 75 385 1.6 795 Sinus SmartTouch 166 390 Apex: Anterior 66 40 301 4.6 926 RV Paced SmartTouch 501 714 Apex: Anterior 125 25 535 4.3 607 RV Paced SmartTouch 299 1321 Basal Inferior/posterior 70 23 925 13.2 998 Sinus SmartTouch 282 1034 Basal: Inferior/posterior 123 47 724 5.9 1059 RV Paced SmartTouch 255 691 Mid: Anterior 83 33 550 6.6 7510 RV Paced SmartTouch 229 520 Basal: Inferior 32 14 300 9.4 8211 Sinus SmartTouch 240 891 Apical 79 33 630 8.0 9012 Sinus SmartTouch 246 720 Basal-Mid infero-septal 75 30 540 7.2 6513 RV Paced PentaRay 265 2599 Basal-Mid posterior 77 29 1689 21.9 8014 RV Paced PentaRay 296 531 Basal Infero-posterior 44 15 345 7.8 4515 RV Paced PentaRay 432 630 Basal-Mid infero-posterior 117 27 510 4.4 52

Median 258 714 77 29 540 6.6 79

LQ 235 554 62 26 365 5.3 63

UQ 298 1107 120 37 742 8.7 90

367368369

Page 26: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Table 3: RMCC characteristics

PatientNo.

No. of RMCCs

Length (mm)

Median amplitudeinitial component

(mV)

Median amplitudedelayed component

(mV)

Conduction Velocity (cm/s)

RMCC ablation lesions

Isolated late cluster

ablation lesions1 1 25 0.25 0.09 34 2 02 2 30 0.76 0.17 26 7 4

30 1.16 0.38 34 93 1 70 0.64 0.15 55 18 124 1 90 0.91 0.5 67 21 175 3 40 0.65 0.11 50 8 3

35 0.41 0.11 44 690 0.33 0.2 60 22

6 2 70 0.22 0.13 67 13 2660 0.25 0.1 55 11

7 1 60 0.30 0.22 38 29 148 1 70 1.09 0.3 70 21 69 2 85 0.37 0.13 71 21 12

85 0.22 0.1 85 1910 1 95 0.96 0.37 37 30 011 2 55 0.68 0.25 46 25 0

55 0.67 0.18 35 1512 2 80 1.03 0.32 55 28 4

40 0.62 0.29 62 813 3 40 0.44 0.17 57 5 0

30 0.1 0.18 50 2555 0.18 0.22 69 10

14 2 60 0.34 0.2 34 17 860 0.11 0.55 52 19

15 1 85 0.51 0.54 81 30 8

Median 2 60 0.44 0.20 55 18 6LQ 1 40 0.25 0.13 38 9 2UQ 2 80 0.68 0.30 67 22 12

26

370371

Page 27: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Table 4: Acute and long term outcomes

Patient No

Post procedural VT Stim Follow-Up(months)

1 Non inducible 142 Non inducible 143 Inducible for VT 6*4 Non inducible 125 Non inducible 126 Non inducible 127 Non inducible <1†8 Not performed 89 Non inducible 610 Not performed 611 Non inducible 1*12 Non inducible 1*13 Non inducible 2*14 Non inducible 215 Inducible for VT 1

Median 6

* – VT recurrence noted at follow up † – Patient died at day 7 from heart failure; no ventricular arrhythmia detected on post mortem device interrogation.

27

372373

374375376377378379380381382

Page 28: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 1a: Ventricular EGM

A bipolar EGM (400m/sec sweep speed) collected within ventricular scar is displayed. The EGM

contains 2 components. The initial component is a likely far field signal (either epicardial or

surrounding healthy tissue). The second component likely represents delayed local activation

(late potential). Six time frames from the Ripple Map are displayed (1-3 occur during far field

signal; 5-6 occur during the local signal). The Ripple bar for each time point is seen, overlying a

CARTO voltage isochrone. The height of the bar reflects the voltage amplitude at that time

point. Negative deflections are displayed as an upward moving bar such that no component of

the electrogram is lost.

Figure 1b and supplemental video 1: RMCC

Five adjacent points sampled within scar are displayed. Panel I: The Ripple map demonstrates

bars (9ms, 24ms, 29ms, 47ms, and 58ms) associated with the initial wavefront (green arrows)

ascending up the anatomy. This may represent far field from either epicardial activation or

activation from the surrounding healthy tissue.

Panel II: The Ripple map shows bars (73ms, 79ms, 91ms, 106ms, and 115ms) representing

delayed activation (black arrows) ascending up the anatomy, forming a Ripple Mapping

Conduction Channel. Importantly, the initial activation is still occurring in the dense scar when

delayed activation commences at the border zone. Once the delayed activation has reached the

scar core, the signal is clearly late and hence separated from the initial wavefront.

Figure 1c: Algorithm for identifying RMCCs within a scar

28

383

384

385

386

387

388

389

390

391

392

393

394

395

396

397

398

399

400

401

402

403

404

Page 29: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 2 (and supplemental video 2a+b): Clear direction of RMCC activation (pt. 9)

The map was collected in a paced rhythm. Scar (<1.5mV) was identified on the anterior wall

(83cm2, 550 points). Panel I: Design lines have outlined the path of RMCC activation. The

terminal end of the first wavefront of Ripple bars (orange arrow) is seen at +160ms and +180ms

post QRS onset. These bars are concurrent with activation from the surrounding healthy tissue

and likely correspond with far field activation. At +160ms, a second cluster of Ripple bars is

noted in the mid-lateral wall (yellow arrow). At +180ms, these bars have ascended up towards

the base of the LV corresponding with late potentials ascending up the scar with increasing

activation delay; this represents RMCC1. At +210ms, a further cluster of very late activating

ripple bars is now seen on the mid-septal side (blue arrow). By +240ms, these bars have

ascended up the scar towards the base of the LV. Sampled electrograms along the blue arrow

path again demonstrate late potentials ascending up the scar with increasing activation delay;

representing RMCC2.

Panel II: VT was induced (CL 450ms) and mapped. 4 time points during the diastolic period are

presented. A channel of Ripple bars reflecting mid diastolic potentials ascends from apex to base

through scar. Electrograms sampled along this path cover the diastolic interval. An outline of this

path is drawn on the map and represents the RMDP.

29

405

406

407

408

409

410

411

412

413

414

415

416

417

418

419

420

421

422

Page 30: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 3 (and supplemental video 3a+b): Analysis of RM within ventricular scar to guide

substrate ablation (pt. 5)

The map was collected in sinus rhythm. Scar (<1.5mV) was identified on the anterior wall

(66cm2, 300 points). Panel I: Ripple bars were seen to propagate from the septum to the lateral

wall. The map is presented in reverse. A cluster of late activating bars approximately +130ms

post QRS onset is seen within basal scar, and corresponds to late potentials travelling from the

lateral wall to the septum, representing RMCC1. RMCC2 is encountered +115ms post QRS

onset, this time travelling mid scar from septal-lateral LV. RMCC3 is seen +80ms post QRS

onset travelling down the lateral wall from base-apex. In the presented time frame, bars are seen

along each RMCC as the corresponding late signals are at different time points away from the

iso-electric line. Our approach to substrate ablation is presented, with ablation delivered along all

RMCCs and at late activating clusters.

Panel II: VT was induced (CL 440ms) and mapped. 3 time points within the diastolic period are

presented. RM tracked diastolic signals travelling around a counter-clockwise loop within the

scar.

30

423

424

425

426

427

428

429

430

431

432

433

434

435

436

437

438

Page 31: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 4a: An illustration of centripetal channel activation towards the center of the scar.

A diagrammatic representation of post infarct endocardial ventricular scar is presented (blue

islands) which includes areas of residual surviving myocardium within the scar (uncolored white

areas). An activation wavefront (red) is seen progressing from left to right through 4 time frames

within the scar (mid QRS - very late post QRS). Whilst the wavefront in healthy tissue

progresses in a linear direction, the wavefront enters the scar from multiple sites, and zig-zags

slowly towards channels of active tissue towards the center of the scar. Regions of active tissue

could have been activated by any number of pathways.

Beneath each time frame is an illustration of how this might be depicted on a Ripple Map

overlying a display of bipolar voltage (purple represents healthy tissue, and red represents scar).

A wavefront of Ripple bars rapidly travels within the healthy tissue around the scar border-zone

in a linear direction. Within the scar, ripple bars enter from all directions towards the scar core.

31

439

440

441

442

443

444

445

446

447

448

449

450

Page 32: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 4b (and supplemental video 4a+b): RMCCs in close proximity with probable path of

activation towards the center of the scar (pt. 13)

Panel I: The map was collected in a paced rhythm using a PentaRayTM catheter. Scar (<1.5mV)

was identified on the infero-posterior wall (77cm2, 1689 points). Each cluster of ripple bar

activation has been encircled. Adjacent circles have been connected in order of time to form the

outline of each RMCC. Ripple bars enters the scar at a mid septal site (brown arrow) +150ms

post QRS onset. At +170ms, this activation has ascended towards the LV base. Adjacent EGMs

analyzed along the brown arrow path are shown and demonstrate increasing local activation

delay and are labeled RMCC1. Also at +170ms, Ripple bars enter the scar at a mid-lateral site

(yellow arrow). By +210ms, this activation ascends up the scar. At +220ms, Ripple bars again

enter the scar from a mid-lateral site (pink arrow). At the same time, activation designated by the

yellow arrow has now ascended towards the scar core. EGMs analyzed along the yellow arrow

path demonstrate increasing local activation delay and are labeled RMCC2. Activation

designated by the pink arrow slowly ascends up the scar (+250ms), reaching the site of latest

activation at +270ms within the scar core. EGMs analyzed along the pink arrow path

demonstrate increasing local activation delay and are labeled RMCC3.

Panel II: VT was induced (CL 500ms) and mapped. 3 time points within the diastolic interval are

presented. Mid diastolic potentials were identified in the scar core. RM clearly tracked diastolic

signals towards the lateral wall within the scar. Design lines have outlined the RMDP on the

map.

32

451

452

453

454

455

456

457

458

459

460

461

462

463

464

465

466

467

468

469

470

471

Page 33: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 5: RMCC and VT isthmus co-localization

Panel I: The RMCC substrate map (left) and VT map (right) from Figure 2 (Pt. 9) are displayed

in identical orientations (“sync views”). In order to demonstrate the location of the VT isthmus in

relation to the RMCCs, the VT map has been opened directly on the RMCC map. The CARTO

system merges the colors represented by the voltage map. The VT isthmus is seen to co-localize

within the RMCC.

Panel II: VT was mapped in the 3 cases presented (Pts. 9, 5, 13). The VT map was opened on its

corresponding RMCC map and the VT isthmus is outlined in blue and the RMCC in white. The

VT isthmuses collocate within the corresponding RMCCs, reinforcing the functional significance

of the RMCCs identified.

33

472

473

474

475

476

477

478

479

480

481

482

Page 34: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 6: Functional lines of block border the RMDP

The lines of block bordering the RMDP (white outline) mapped in VT from Pt. 9 (described in

figure 2 and figure 5) were analyzed in greater detail. The area of the RMDP is contained within

the edge of the RMCC (blue outline) mapped in paced rhythm. The area immediately outside the

RMDP border, but contained within the RMCC was formed of myocardium that has signal

during pacing but without any diastolic potentials during VT confirming this is an area of

functional block.

34

483

484

485

486

487

488

489

Page 35: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 1a:

Figure 1b

35

490

491

492

493

494

Page 36: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 1c:

36

495

496

497

498

499

Page 37: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 2:

37

500

501

502

Page 38: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 3:

38

503

504

505

Page 39: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 4a:

39

506

507

508

Page 40: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 4b:

40

509

510

511

Page 41: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 5:

41

512

513

514

515

Page 42: Study Sample - Imperial College London Web viewWord count: 6837. Journal Subject Terms. ... Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia

Figure 6:

42

516

517

518

519

520