Multiparametric assessment of apical versus septal pacing study using Cardiac Magnetic Imaging ...

355 Pages·2016·4.98 MB·English

Multiparametric assessment of apical
versus septal pacing study using Cardiac
Magnetic Imaging

A thesis submitted for the degree of Doctor of
Philosophy (PhD) in the Faculty of Medical
and Human Sciences at the University of
Manchester

2015

Dr Mark Peter Ainslie
BSc (hons) MBChB (hons) MRCP
PGDipMedEd

School of Medicine, University of Manchester

1
Contents

Contents ......................................................................................................... 2
List of Figures ................................................................................................ 7
List of tables ................................................................................................. 11
Abbreviations ............................................................................................... 13
Abstract ........................................................................................................ 17
Declaration ................................................................................................... 18
Copyright ...................................................................................................... 18
My contribution to the work ........................................................................ 19
Publications related to this thesis .............................................................. 20
Papers ................................................................................................................ 20
Abstracts ............................................................................................................ 20
Dedication .................................................................................................... 21
Chapter 1: Introduction ............................................................................... 23
1.1 Normal Cardiac Conduction system ........................................................ 23
1.2.1 Atrial Fibrillation ....................................................................................... 26
1.2.2 Type of AF ................................................................................................. 26
1.2.3 Clinical presentation of AF ....................................................................... 26
1.2.3 Pathophysiology ....................................................................................... 27
1.2.4 Treatment of AF ........................................................................................ 28
1.2.5 Catheter ablation....................................................................................... 30
1.2.6 AV node ablation and Pacing ................................................................... 30
1.2.7 Pacemakers and AF .................................................................................. 30
1.3.1 Cardiac Pacing .......................................................................................... 32
1.3.2 Right ventricular pacing ........................................................................... 34
1.3.3 Early clinical trials and RV pacing ........................................................... 34
1.3.4 Animal models of pacing .......................................................................... 35
1.3.5 Acute RV pacing in humans ..................................................................... 38
1.3.6 Longer-term effects of RV pacing in humans ......................................... 40
1.3.7 Alternative pacing sites ............................................................................ 42
1.3.8 Biventricular pacing versus RV apical pacing ........................................ 43
1.3.9 Alternative right ventricular sites ............................................................ 44
His pacing ........................................................................................................ 44
Right ventricular outflow tract ........................................................................... 45
RV septal pacing .............................................................................................. 46
Conflicting results between alternate pacing sites ............................................ 47
1.4 RVOT anatomy ............................................................................................. 57
1.5.1 Cardiac dyssynchrony and imaging methods to measure it. ................ 62
1.5.2 Inter-ventricular dyssynchrony ................................................................ 62
2
1.5.2.1 Echocardiography ................................................................................ 62
1.5.3 Intra-ventricular dyssynchrony ................................................................ 64
1.5.3.1 Echocardiography ................................................................................ 64
1.5.3.2 Nuclear Imaging ................................................................................... 68
1.5.3.3 Cardiovascular Magnetic Resonance Imaging ...................................... 68
1.6 Cardiac MRI and pacemakers ..................................................................... 73
1.6.1 Implantable pulse generators in the MR environment ........................... 73
1.6.2 MRI safety terminology............................................................................. 74
1.6.3 Safety issues concerning IPGs and ICDs in the MRI environment........ 75
1.6.3.1 Tissue heating ...................................................................................... 76
1.6.3.2 Force and Torque ................................................................................. 77
1.6.3.3 Inappropriate pacing, shocks, inhibition of therapies............................. 77
1.6.3.4 Electrical reset ...................................................................................... 78
1.6.3.5 Reed switches ...................................................................................... 78
1.6.4 MRI in conventional (i.e. MR unsafe) systems ........................................ 79
1.6.5 MR conditional devices ............................................................................ 80
1.6.6 Scanning an IPG patient ........................................................................... 85
1.6.7 CMR Imaging ............................................................................................. 89
1.6.8 Issues concerning patient selection ........................................................ 92
CHAPTER 2: Methods .................................................................................. 94
2.0 Methods ........................................................................................................ 94
2.1 Patient Selection .......................................................................................... 94
2.1.1 Inclusion Criteria ...................................................................................... 95
2.1.2 Exclusion Criteria .................................................................................... 95
2.2. Study Outline .............................................................................................. 97
2.2.1. Study design .......................................................................................... 97
2.2.2 Consent procedures .............................................................................. 100
2.2.3 Withdrawal of patients ........................................................................... 100
2.2.4 Sample size ........................................................................................... 100
2.2.5 Potential risks to patient ........................................................................ 101
2.2.6. Adverse event and Serious Adverse Event reporting ............................ 101
2.2.7 Data Collection and record keeping ....................................................... 102
2.3 Pacemaker implantation ............................................................................ 103
2.3.1 Pacemaker implantation ........................................................................ 103
2.3.2 Lead positioning .................................................................................... 104
2.4 AV node ablation ....................................................................................... 108
2.4.1 Antegrade approach (Right-sided approach) ......................................... 108
2.4.2 Retrograde (Left sided) approach .......................................................... 109
2.5. Medical outcomes study Short Form 36 (SF36) health survey .............. 111
2.6. Cardiac Magnetic resonance ................................................................... 112
2.6.1. LV Volumes and function ...................................................................... 113
2.6.2. LV Strain and strain rate ....................................................................... 114
2.6.3. LV twist, normalised twist and torsion ................................................... 115
2.7.4. RV TAPSE ........................................................................................... 117
2.7.5. Dyssynchrony indices ........................................................................... 117
2.7.6. LV myocardial fibrosis .......................................................................... 118
2.7.7. Aortic and Pulmonary flow .................................................................... 120
3
2.8. Cardiopulmonary exercise testing (CPEX).............................................. 123
2.8.1. Bicycle CPEX ....................................................................................... 124
2.8.2. Treadmill CPEX .................................................................................... 124
2.8.3. Indications for termination of exercise testing ....................................... 125
2.9. Six minute walk testing ............................................................................ 125
Chapter 3. Sub-Studies ............................................................................. 128
Study 1. Aortic and pulmonary flow measurements validation ............. 129
3.1 Aortic and pulmonary flow measurements validation ...................... 129
3.1.2 Aim ........................................................................................................... 129
3.1.3 Introduction ............................................................................................. 129
3.1.4 Method ..................................................................................................... 130
3.1.5 Results ..................................................................................................... 130
3.1.6 Discussion............................................................................................... 133
Study 2. Which is the most suitable method for CPEX testing in a pacing
dependent patient? .................................................................................... 134
3.2 Which is the most suitable method for CPEX testing in a pacing
dependent patient? .................................................................................... 134
3.2.1 Aim ........................................................................................................... 134
3.2.2 Introduction ............................................................................................. 134
3.2.3 Hypothesis .............................................................................................. 135
3.2.4 Method ..................................................................................................... 135
3.2.5 Results ..................................................................................................... 135
3.2.6 Discussion............................................................................................... 137
3.2.7 Conclusion .............................................................................................. 139
Study 3. Any training effect of CPEX testing ........................................... 140
3.3. Any training effect of CPEX testing ................................................... 140
3.3.1 Introduction ............................................................................................. 140
3.3.2 Method ..................................................................................................... 140
3.3.3 Results ..................................................................................................... 140
3.3.4 Discussion............................................................................................... 142
Study 4. Phantom studies ......................................................................... 143
3.4 Phantom studies .................................................................................. 143
3.4a The Gel Phantom ............................................................................... 143
3.4a.1 Introduction ........................................................................................... 143
3.4a.2 Aim ......................................................................................................... 144
3.4a.3 Methods ................................................................................................. 144
3.4a.4 Results ................................................................................................... 152
3.4a.5 Discussion ............................................................................................. 157
Study 4b. Effect of Metal Susceptibility artefact on T1 mapping and
velocity phase encoding using an agarose phantom model. ................ 158
3.4b.1 Introduction ........................................................................................... 158
3.4b.2 Methods ................................................................................................. 160
4
3.4b.2.1 Phantom ........................................................................................... 160
3.4b.2.2 T1 mapping ...................................................................................... 163
3.4b.2.3 Velocity phase encoding ................................................................... 163
3.4b.2.4 Experiments ..................................................................................... 163
3.4b.2.5 Analysis ............................................................................................ 164
3.4b.3 Results .................................................................................................. 165
3.4b.3.1 T1 Mapping ...................................................................................... 165
3.4b.3.2 T1 values over time in gel phantom .................................................. 168
3.4b.3.3 Effect of Pacemaker on T1 mapping ................................................. 170
3.4b.3.4 Effect of pacemaker leads on T1 mapping ........................................ 177
3.4b.3.5 Effect of metal susceptibility artefact on velocity phase encoding ..... 179
3.4b.4 Discussion ........................................................................................... 184
3.4b.5 Conclusion .......................................................................................... 187
Study 5. Image optimization in the presence of an Implantable pulse
generator .................................................................................................... 188
Study 5. Image optimization in the presence of an IPG. ......................... 188
3.5.1 Introduction ............................................................................................. 188
3.5.2 Method ..................................................................................................... 189
3.5.3 Results ..................................................................................................... 189
3.5.4 Discussion............................................................................................... 193
3.5.5 Conclusions ............................................................................................ 194
Study 6.Evaluation of left ventricular torsion using cardiac MRI.
Validation of tagging and feature tracking. ............................................. 196
Study 6. Evaluation of left ventricular torsion using cardiac MRI.
Validation of tagging and feature tracking. ............................................. 197
3.6.1 Introduction ............................................................................................. 197
LV torsion ....................................................................................................... 197
3.6.2 Study Population .................................................................................... 199
3.6.3 Hypothesis .............................................................................................. 199
3.6.4 Methods ................................................................................................... 199
Twist .............................................................................................................. 200
Normalised Twist ............................................................................................ 200
Circumferential shear angle (Torsion) ............................................................ 201
3.6.5 Results ..................................................................................................... 204
Effect of dobutamine on strain ........................................................................ 205
Effect of dobutamine on Twist and Torsion ..................................................... 213
3.6.6 Discussion............................................................................................... 221
3.6.7 Conclusions ............................................................................................ 223
Chapter 4. Septal versus Apical pacing- Acute Study ............................ 225
4.1 Patient Cohort ............................................................................................ 225
4.2 Baseline exercise capacity ........................................................................ 228
4.3 Quality of life .............................................................................................. 230
4.4 RV Lead positions...................................................................................... 232
4.4.1 Fluoroscopy ........................................................................................... 232
4.4.2 Cardiac MRI .......................................................................................... 233
5
4.5 ECG ............................................................................................................. 238
4.5.1 Can the ECG determine lead positions .................................................. 240
4.6 Image quality .............................................................................................. 242
4.7 Acute Safety data ....................................................................................... 251
4.7.1 Pacing thresholds, impedance and battery voltage ................................ 251
4.7.2 Specific absorption rate ......................................................................... 254
4.8 Effect of acute pacing position on heamodynamics ............................... 255
4.8.1 Blood pressure ...................................................................................... 255
4.8.2 Aortic and Pulmonary flows ................................................................... 256
4.8.3 Cardiac dimensions, LV volumes and ejection fraction .......................... 259
4.8.4 Right Ventricular function ...................................................................... 263
4.8.5. Left ventricular Strain............................................................................ 263
4.8.6 Intra-ventricular dyssynchrony ............................................................... 272
4.8.7. Twist and Torsion ................................................................................. 275
4.9. Discussion ................................................................................................ 278
4.9.1 Baseline demographics ......................................................................... 278
4.9.2 Right ventricular lead positions .............................................................. 278
4.9.3 ECG parameters ................................................................................... 280
4.9.4 Imaging artefacts ................................................................................... 281
4.9.5 Safety data ............................................................................................ 283
4.9.6 Haemodynamics .................................................................................... 284
4.9.7 Right ventricular function ....................................................................... 286
4.9.8 Deformational measures of left ventricle- Strain, twist, torsion ............... 286
4.9.9 Dyssynchrony ........................................................................................ 289
5.1 Septal versus apical pacing- medium term study. ............................ 291
5.2 Safety data ................................................................................................. 291
5.2 Quality of life SF36..................................................................................... 293
5.4 Exercise capacity ....................................................................................... 295
5.5 Left ventricular function ............................................................................ 296
5.6 Discussion ................................................................................................. 299
6. Conclusions and future directions ....................................................... 303
6.1 Conclusions ............................................................................................... 303
6.2 Future directions ....................................................................................... 305
Appendix .................................................................................................... 308
Borg Scale of perceived exertion ................................................................... 308
Worksheet for 6MWT ....................................................................................... 310
Health Survey for Pacemaker Study Patients (SF36) .................................... 311
Radiation dose risk assessment by medical physics ................................... 316
Consent form ................................................................................................... 320
Patient information sheet ................................................................................ 321
GP Sheet ........................................................................................................... 331
MAPS protocol ................................................................................................. 332
Protocol for effect of metal susceptibility artefact on T1 mapping and
velocity phase encoding ................................................................................. 334
Evaluation of left ventricular torsion using cardiac MRI. Validation of tagging
and feature tracking. ....................................................................................... 335
6
Inclusion and exclusion criteria ..................................................................... 336
References ................................................................................................. 338

List of Figures
Figure 1. The cardiac conduction system ................................................................ 24
Figure 2. RVOT anatomy ........................................................................................ 60
Figure 3. Cross sectional anatomy of the RVOT. ..................................................... 61
Figure 4. Schematic representations of Inter-ventricular (A) and Intra-ventricular (B)
dyssynchrony during RV apical pacing assessed by doppler echocardiography. ..... 67
Figure 5. Tagging of the left ventricle in short axis in diastole and systole. .............. 69
Figure 6. Example of LV dyssynchrony assessment in a patient ............................. 71
Figure 7. Radiopaque markers on a St Jude Medical, Medtronic and Boston Scientific
MR conditional pacemakers and leads. ................................................................... 85
Figure 8. Algorithm for safe scanning of an IPG patient. .......................................... 88
Figure 9. Images of CMR in a patient with a cardiac device. ................................... 91
Figure 10. Study timeline for MAPS trial. ................................................................. 99
Figure 11. Mond stylet. A secondary curve is posteriorly directed to get onto the
RVOT septum. ...................................................................................................... 105
Figure 12. Fluoroscopy PA view- Lower RVOT border marked. Lead is placed within
the RVOT in the PA view. ...................................................................................... 105
Figure 13. LAO 40-degree view. The Septum and Pulmonary valve are marked.
Using the Mond stylet the RVOT lead is pulled down into a suitable septal position
.............................................................................................................................. 106
Figure 14. RAO 40 degree view. This is used to confirm apical lead position. ....... 106
Figure 15. Pacemaker generator at fluoroscopy in PA projection. ......................... 107
Figure 16. PA CXR illustrating RVOT and Apical lead positions in a study patient. 107
Figure 17. Intracardiac signals seen on the Map distal catheter when planning an
AVN ablation ......................................................................................................... 109
Figure 18. Triangle of Koch with compact AV node at apex. .................................. 110
Figure 19. LV torsion. Circumferential shear angle. ............................................... 116
Figure 20. Magnitude (left) and phase encoded (right) maps of aorta. ................... 122
Figure 21. Contour drawn around aorta for analysis. ............................................. 122
Figure 22. Modified Bruce protocol for CPEX testing. ............................................ 124
Figure 23. Bland Altman plot comparing rater A and B for aortic flow measurements.
.............................................................................................................................. 131
Figure 24. Bland Altman plot comparing rater A and B for pulmonary flow
measurements. ..................................................................................................... 131
Figure 25. Bland Altman plot comparing rater B on two occasions for aortic flow
measurements. ..................................................................................................... 132
Figure 26. Bland Altman plot comparing rater B on two occasions for pulmonary flow
measurements. ..................................................................................................... 132
Figure 27. Bland Altman plot for VO2 max between the two CPEX tests performed.
.............................................................................................................................. 142
7
Figure 28. The gel phantoms within the MR scanner. ............................................ 151
Figure 29. Scatterplot showing relationship between agarose concentrations and the
measured T1 and T2 values in the gel phantom. ................................................... 156
Figure 30. Scatterplot showing relationship between Copper Sulphate concentration
and the measured T1 and T2 values in the gel phantom. ...................................... 156
Figure 31. Phantom B. PPM within container on rig............................................... 161
Figure 32. Phantom A (right) and B (left) filled with agarose gel. ........................... 162
Figure 33. Grid placed on coronal projection for T1 mapping analysis. .................. 164
Figure 34. T1 map of the gel only phantom in coronal plane (phantom A). ............ 165
Figure 35. Coronal localiser and corresponding T1 map in the PPM phantom. Marked
artefact is observed see spreading out from the centre of the device. ................... 166
Figure 36. T1 values across the two phantom models. The gel only phantom
(phantom A) is relatively homogenous with only a small variation in T1 values across
the phantom centrally (shaded). In phantom B the heterogeneity introduced by the
device can be seen. .............................................................................................. 167
Figure 37. T1 time drift. T1 measured over a 2-week period. Every 3 scans represent
a single day. .......................................................................................................... 169
Figure 38. The relationship between the distance from the PPM and the measured
T1 value in the coronal plane, using a scatter plot. ................................................ 171
Figure 39. The relationship between the distance from the PPM and the measured
T1 value in the sagittal plane, using a scatter plot. ................................................ 172
Figure 40. Mean T1 values in PPM phantom compared to gel only phantom in the
sagittal plane. The T1 value within the gel phantom remains constant. ................. 173
Figure 41. The relationship between the distance from the PPM and the measured
value in the axial plane, using a scatter plot. ......................................................... 174
Figure 42. The relationship between the distance from the PPM and the measured
T1 value in the axial plane adjusted to cross the PPM, using a scatter plot (see text
for explanation) ..................................................................................................... 175
Figure 43. The mean T1 values of PPM phantom compared to gel phantom in axial
plane. .................................................................................................................... 176
Figure 44. Plot of distance from lead body and mean T1 values in PPM phantom
compared to the gel only phantom. ....................................................................... 177
Figure 45. Plot of distance from lead tip and mean T1 values in PPM phantom
compared to the gel only phantom. ....................................................................... 178
Figure 46. Scatterplot showing the effect of moving the isocentre towards and away
from the PPM on the flow measured in the phantoms, in the sagittal projection for 18
scans. ................................................................................................................... 180
Figure 47. The effect of distance from the PPM on the total flow measured in the gel
only and PPM phantom in the axial plane. ............................................................. 182
Figure 48. Total flow measured at four regions of interest at different isocentres for
both phantoms. ROI closest and ROI 4 furthest from PPM. ................................... 183
Figure 49. A) SpGr B) SSFP C) T1 BB TSE D) T2 BB TSE images in the axial
projection for the PPM phantom. ........................................................................... 190
Figure 50. SSFP sequences in the axial projection with the following local centre
frequency shifts A) 0Hz B) 25Hz C) 50Hz D) 75Hz E) 100Hz F) 125Hz G) 150Hz F)
175Hz.................................................................................................................... 191
Figure 51. bSSFP in axial plane with the following bandwidths A) 251 B) 496 C) 744
and D) 1488Hz. ..................................................................................................... 192
8
Figure 52. bSSFP and inhomogeneities in the magnetic field. ............................... 195
Figure 53. Bland Altman plot of left ventricular ejection fraction between two raters.
.............................................................................................................................. 204
Figure 54. Longitudinal strain in 4-chamber view at 0, 7.5 and 15mcg dobutamine
measured by CMR-FT. .......................................................................................... 205
Figure 55. Circumferential strain for the mid-ventricular short axis slice, at 0, 7.5 and
15mcg dobutamine concentrations measured by CMR-FT. ................................... 206
Figure 56. Radial strain in short axis at 0, 7.5 and 15mcg dobutamine concentrations
measured by CMR-FT. .......................................................................................... 206
Figure 57. Circumferential strain in short axis at 0, 7.5 and 15 mcg dobutamine
concentrations measured by Intag. ........................................................................ 207
Figure 58. Radial strain in short axis at 0, 7.5 and 15mcg dobutamine concentrations
measured by CMR-FT. .......................................................................................... 207
Figure 59. Bland Altman plot of the peak circumferential strain measured by Intag
compared to CMR-FT at 0mcg dobutamine. .......................................................... 211
Figure 60. Bland Altman plot of the peak circumferential strain measured by Intag
compared to CMR-FT at 7.5mcg dobutamine. ....................................................... 212
Figure 61. Bland Altman plot of the peak circumferential strain measured by Intag
compared to CMR-FT at 15mcg dobutamine. ........................................................ 212
Figure 62. Effect of increasing dobutamine concentration on twist measured by CMR-
FT and Intag. ......................................................................................................... 214
Figure 63. Effect of increasing dobutamine concentration on torsion measured by
CMR-FT and Intag ................................................................................................ 215
Figure 64. Bland Altman for Twist at 0mcg dobutamine ......................................... 217
Figure 65. Bland Altman plot for twist at 7.5mcg dobutamine ................................ 217
Figure 66. Bland Altman plot for twist at 15mcg dobutamine ................................. 218
Figure 67. Bland Altman plot for torsion at 0mcg dobutamine ................................ 219
Figure 68. Bland Altman plot for torsion at 7.5mcg dobutamine. ............................ 219
Figure 69. Bland Altman plot for torsion at 15mcg dobutamine. ............................. 220
Figure 70. Right ventricular 2-chamber view (RV apical lead position) 1 ideal position,
2 reasonable position, 3 not ideal position. ............................................................ 234
Figure 71. 4-chamber view (RV apical lead position). ............................................ 234
Figure 72. Right ventricular in/out view (RVOT lead position). ............................... 235
Figure 73. RVOT view (RVOT lead position). ........................................................ 235
Figure 74. Quantification of artefact in the bSSFP short-axis basal slice. .............. 243
Figure 75. Quantification of artefact in the bSSFP short-axis mid slice. ................. 244
Figure 76. Quantification of artefact in the bSSFP short-axis apical slice. ............. 244
Figure 77. Comparison of artefact observed on bSSFP and SpGr sequences in the 4-
chamber view at basal, mid and apical levels. ....................................................... 245
Figure 78. Graph of the 16-segment model of the left ventricle illustrating the
distribution of artefact in the bSSFP sequences. ................................................... 246
Figure 79. Comparison of artefact seen in the mid short-axis slice for the different
imaging sequences. .............................................................................................. 249
Figure 80. Scatterplot of distance of pacemaker from the left ventricle and the mean
artefact on bSSFP images. .................................................................................... 250
Figure 81. Total body SAR measured for each image sequence. .......................... 254
Figure 82. Aortic and pulmonary flows for the RVOT septal and RV apical positions.
N=50. .................................................................................................................... 256
9
Figure 83. Aortic and pulmonary VTI measured by echocardiography for RVOT
septal and RV apical positions. ............................................................................. 258
Figure 84. Longitudinal strain measured for apical and RVOT lead. Note strain is a
negative value but has been represented as positive for the graph. N=50. ............ 266
Figure 85. Longitudinal strain measured for apical and RVOT lead in 3 cardiac views,
for optimal lead combination. N=25.. ..................................................................... 266
Figure 86. Maximum opposing wall delay between the septal and lateral walls at
basal, mid and apical ventricular levels. N=50. Error bars are +/- SEM. ................ 274
Figure 87. Maximum opposing wall delay between the septal and lateral walls at
basal, mid and apical ventricular levels for optimal lead pairings . N=25. Error bars
are +/- SEM. .......................................................................................................... 274
Figure 88. SF36 scores for 0 and 9 months following the AV node ablation. ......... 294
Figure 89. Exercise capacity assessed by CPEX at 0 and 9 months. .................... 295

10