Topic: CRT optimisation based on Left ventricular activation time

 

This is a Report to be present at a PhD meeting.
The report imperatively needs to include:
Background; Research question; Hypothesis and aims
You can find an example of what I am expecting on the “Example Upgrade Report” document.
The data has been collected accordantly to the “Data_Taken Protocol” document so please use this as reference for development of the report
On the study document entitled “Biophysical Modeling to Simulate the Response” – it was discovered that "The only metric to show a consistent correlation with the CRT response was the peak rate of cumulative activation in Left ventricle" – which is basically where my PhD thesis is around.
In the study entitled “Mechanistic insights into the benefits of multisite pacing” it was found that CRT response was more related with the peak rate of cumulative activation in Left ventricle assessed between the 10th and 90th centiles of the activation time – which is what I am assessing for my PhD.
5.
i J

Evaluation of a novel method of non-invasive surface
electrocardiographic mapping in predicting clinical, structural and
neurohormonal responses in patients undergoing cardiac
resynchronization therapy
PROTOCOL
Version 1.3
23rd September 2013
Institutions
Guy’s and St Thomas’ Hospitals NHS foundation Trust
Westminster Bridge Road
London
SE1 7EH
Royal Brompton & Harefield NHS Foundation Trust
Sydney Street
London
SW36NP
Commercial Partner: Cardiolnsight

:f. –
Contents
Study Team : 3 ‘
List of Abbreviations .4
Background 5
Hypothesis ~ 6
Study Design 6
Outcomes ‘” , 6
Inclusion/Exclusion criteria 6
Methodology 7
Screening 7
Day 1 post implant. , ‘” 9
,/
Follow-up 1 1 O~C
Follow-up 2 11
Follow-up 3 11
Statistical analysis 12
References 13
Appendix , ‘” ‘” 15
Flow Charts 19
Time/Event Schedule 21

2

)

St Thomas’ Site
Principal Investigator
Dr Aldo Rinaldi, Consultant
Cardiologist and Reader in Cardiac
Electrophysiology.
Co-Investigators
Prof Reza Razavi, Head of division
of Imaging Sciences and
Biomedical Enqineerinq KCL.
Consultant Paediatric Cardiologist.
Dr Gerry Carr-White, Consultant
Cardiologist, Clinical lead for Heart
Failure
Clinical Research Fellow
Dr Tom Jackson, Cardiovascular
Imaging research group

Royal Brompton Site
Principal Investigator
Dr Rakesh Sharma, Consultant
Cardiologist, Clinical Lead for Heart
Failure
Co-Investigators
Dr Sabine Ernst, Consultant
Cardiologist and Reader in
Cardiology, Lead for
Electrophysiology Research
Dr Alexander Lyon, Senior Lecturer
and Honorary Consultant
Cardiologist, Heart Failure Theme
Lead, Cardiovascular Biomedical
Research Unit
Dr Rajdeep Khattar, Consultant
Cardiologist and Honorary Clinical
Senior Lecturer, Lead for Adult
Echocardiography
Clinical Research Fellow
Dr Dimitrios Konstantinou, Heart
Failure Care Group
3

List of abbreviations
HF= heart failure
LV= left ventricular
CRT-P= cardiac resynchronization therapy-pacemaker
CRT-O= cardiac resynchronization therapy-defibrillator
NYHA= New York Heart Association
6MWT= six-minute walk test
MLHFQ= Minnesota living with heart failure questionnaire
BNP= brain natriuretic peptide
CABG= coronary artery by-pass grafting
PCI= percutaneous coronary intervention
EF= ejection fraction I
LVEOV= left ventricular end-diastolic volume
LVESV left ventricular end-systolic volume
A-V= atrio-ventricular
V-V= inter-ventricular
LVOT= left ventricular outflow tract
VTI= velocity-time integral
BiV= bi-ventricular
EO= Electrical dyssynchrony
SO= Standard deviation

4

Background
Chronic heart failure (HF) is a growing epidemic and carries a significant
socio-economical burden.’ Although the institution of angiotensin-converting
enzyme inhibitors, beta-blockers and mineralocorticoid receptor antagonists
has improved the natural history of the disease, there is a significant morbidity
and mortality associated with the condition.i vA growing insight in HF
pathophysiology and excitation-contraction coupling followed by advantages
in electrophysiology and pacemaker technology introduced cardiac
resynchronization therapy (CRT) as standard of treatment for a subset of
symptomatic HF patients. Based on the results of major HF trials,3,4 CRT
improves symptoms and the quality of life and reduces complications and the
risk of death. However, up to one third of HF patients do not demonstrate a
clinical improvement and/or echocardiographic evidence of reverse
I
remodelinq.” Considering the financial costs as well the low but not-negligible
risks associated with CRT implantation, it is crucial that clinicians are able to
identify those HF patients who are most likely to benefit from CRT therapy.
Current guidelines regarding eligibility for CRT recommend patients with
symptomatic HF with left ventricular (LV) systolic impairment (LVEF <35%)
and a QRS duration of >120 rns.” 7 Over the past years a series of small,
single centre studies have shown promising results by identifying a number of
conventional echocardiographic and tissue Doppler indices that demonstrated
a reasonable correlation with patients’ response to CRT tberapy.”” However,
after the results of the multicenter trial PROSPECT12 were published, the
early enthusiasm about echo-based measurements predictive ability has
diminished. The major drawbacks inherent in echocardiographic techniques
are poor inter- and intra-observer agreement and low reproducibility plus
limitations in imaging due to poor acoustic windows.
Our aim is to investigate whether a novel non-invasive surface
electrocardiographic mapping tool can accurately identify the subset of HF
patients who will favourably respond to CRT.
5

Hypothesis
Our hypothesis is that baseline calculations of inter-ventricular delay, LV total
activation time and LV electrical dyssynchrony index based on ecSYNC data
will correlate with change in patients’ symptoms, exercise tolerance,
neurohormonal activation and echocardiographic evidence of reverse
remodelling after six months post CRT implantation.
Study design
This is a prospective, single-arm study which will recruit thirty consecutive HF
patients with a conventional indication for CRT-P/CRT-D implantation from St
Thomas’ Hospital and Royal Brompton Hospital Heart Failure/Pacing clinics.
Combined Primary outcome:
• Change in distance travelled during six-minute walk test (6MWT)
• Echocardiographic: signs of LV reverse remodelling defined as an
increase by >5% in left ventricular ejection fraction with an associated
decrease in LV end-diastolic (LVEDV) and end-systolic (LVESV)
volumes
Secondary outcomes:
• Symptoms: change in symptoms severity assessed by Minnesota
Living With Heart Failure Questionnaire (MLHFQ)
• Neurohormonal status: change in neurohormonal activation assessed
by brain-natriuretic peptide (BNP)
• Pacing: atrial and ventricular arrhythmic burden, percentage of bi-
ventricular pacing
Inclusion Criteria:
• Able to give written informed consent
• Age >18 years old
• Fulfils established clinical criteria for CRT implantation (with or without
a defibrillator)
6

)

– ——- .. ——–~~~~~~~~~~~~~
• NYHA Class III-IV Heart Failure (or NYHA II with NYHA III/IV
symptoms in the preceding 12 months)
• LVEF <35% (Calculated using echocardiography or Cardiac MR) at the
time of implantation
• QRS duration> 130ms
• Optimal Tolerated Medical Therapy for Heart Failure
Exclusion Criteria:
• Severe, life threatening non cardiac disease
• Active malignant disease and recent «5 years) malignant disease
• Prior Heart Transplant
• Recent history of unstable angina, acute coronary syndrome or
myocardial infarction within three months of enrolment into the study
• Pregnancy
• Failure to participate in consent process
• Heart Failure requiring constant intravenous therapy including diuretics
and/or inotropes
• Recent revascularisation procedure i.e. coronary artery bypass grafting
(CABG) or percutaneous coronary intervention (PCI) within the last
three months
Methodology (see also flow chart in Appendix)
Screening
Thirty consecutive stable, chronic HF patients with a conventional indication of
CRT-P/CRT-O implantation will be prospectively recruited in St Thomas’ and
Royal Brompton’s Heart Failure/Pacing clinics. Screening visit (this may be on
admission for CRT implant) will involve the following:
• Inclusion and exclusion criteria assessment
• Written informed consent
• Physical examination*
• ECG*
• Evaluation of HF related symptoms*
o NYHA functional class
7

o MLHFQ
• Assessment of exercise capacity*
o 6MWT
• Standard laboratory tests*
? complete blood count
? coagulation studies
? serum creatinine and electrolytes
? liver function tests
• Neurohormonal activation status*
o serum BNP
• Standard echocardiography*
o LVEF, LVEDV, LVESV
• Speckle tracking echocardiography for global longitudinal,
circumferential and radial strain*
* – If these tests have been performed within the previous 3 months they may
not need to be repeated.
Echocardiographic dyssynchrony measurements that will be performed
include (part of standard care):
• inter-ventricular mechanical delay (time difference between the two
semilunar valves pre-ejection period, measured from QRS onset until
the opening of the semilunar valves)
• LV septal-lateral delay (delay between the time intervals to peak
systolic velocity of basal septal and basal lateral LV segments
assessed by tissue Doppler)
• total LV isovolumic time [in s/min; calculated as: 60 – (total ejection time
+ total filling time)] Measurement of inter-ventricular mechanical delay has been proposed as
surrogate marker to assess inter-ventricular dyssynchrony while LV septal-
lateral delay as surrogate marker to assess LV intra-ventricular
dyssynchrony.” Total LV isovolumic time represents global LV dyssynchrony
8

and was reported to be an independent predictor of poor exercise capacity in
a cohort of HF patients.”
CRT Implant
Patients will have a CRT implant as per routine practice at each institution.
They will then go on to have a PA and lateral chest radiograph post
procedure, as per routine clinical practice.
Day 1 Post Implant (or earliest available opportunity)
Initially an echo-guided optimization of CRT atrio-ventricular (A-V) and inter-
ventricular (V-V) intervals will be performed using standard clinical
procedures. First the A-V interval optimization will take place. Different A-V
delays will be progressively applied by telemetry in 20 ms increments ranging
from 60ms to 200ms. The optimal A-V delay will be decided upon maximum
separation of E and A waves recorded by PW Doppler of diastolic mitral inflow
and maximal obtained mitral velocity-time integral (VTI). This method has
been described as the iterative method and has been reported to be both
useful and safe in the setting of HF patients undergoing A-V interval
optimization.” Next V-V interval optimization will take place. Beginning from
nominal V-V delay settings (simultaneous V-V pacing i.e. V-V delay Oms)
different V-V delays will be applied progressively increasing LV pre-excitation
by increments of 20ms (maximum 80ms) and then RV pre-excitation by
increments of 20 ms (maximum 60ms). V-V delay will be considered as
optimal when VTI in left ventricular outflow tract (LVOT) will be maximized
(see Table 1 in Appendix). The impact of each applied A-V and V-V delay
setting upon mitral and LVOT VTI will be assessed after ten consecutive
beats. LVOT VTI guided A-V and V-V optimization has been reported to be
the most feasible and reproducible index and was associated with a
substantial improvement in HF patients exercise capacity.”
During this echocardiogram the participants will also undergo standard
echocardiography whilst the CRT device is in back-up, set at the nominal
manufacturer’s settings and set at the echo optimised settings.
9

All patients will then undergo a low-dose (non-contrast, non-ECG gated)
cardiac CT wearing the ecSYNC vest on. This process is necessary in order
to define the spatial anatomical relationship between ecSYNC vest’s
electrodes and each patient’s heart (see Figure 1 in Appendix).
Based on each ecSYNC provided data set, an activation map of both
ventricles will be generated offline (see Figure 2 in Appendix) and the
following parameters will be calculated:
• inter-ventricular delay (defined as the difference between mean RV
activation time and mean LV activation time)
• left ventricular total activation time (defined as the difference in mean
activation time between the last 10% of LV activation sites and the first
10% of LV activation sites)
• Standard deviation of LV epicardial activation times (electrical
dyssynchrony index)(see Figure 3 in Appendix)
The ecSYNC map will be generated for each of the following settings:
1. CRT in Backup
2. CRT in Nominal Settings
3. CRT in Echo Optimised Settings
4. CRT in each of the echo optimisation protocol settings
1 month (follow-up visit 1)
Participants will be re-assessed as outpatients in St Thomas’ and Royal
Brompton Hospitals Heart Failure/Pacing clinics after approximately one
month. During follow-up visit 1 the following will take place:
• Patient’s symptoms and clinical assessment
• Review of medication
• ECG
• Standard echocardiography
10

)

– ./

3 months (follow-up visit 2-interim analysis)
Participants will be re-assessed as outpatients in the St Thomas’ and Royal
Brompton Hospitals Pacing clinics after approximately three months. The
following assessments will take place:
• MLHFQ
• 6MWT
• ECG
• BNP
• Standard echocardiography
o LVEF, LVEDV, LVESV
• Speckle tracking echocardiography for global longitudinal,
circumferential and radial strain
Data collected during follow-up visit 2 will be correlated with baseline data in
an interim analysis.
6 months (follow-up visit 3-study completion-endpoint assessment)
The next scheduled follow-up visit will be at approximately six months post
CRT implantation in the St Thomas’ and Royal Brompton Pacing clinics. In
this last visit the following assessments will take place:
• MLHFQ
• 6MWT
• ECG
• BNP
• Repeat ecSYNC map with prior spatial anatomical determining low
dose CT scan.
• Standard echocardiography
o LVEF, LVEDV, LVESV
• Dyssynchrony echocardiographic measurements
? interventicular mechanical delay
? septal-lateral delay
? total LV isovolumic time
11

• Speckle tracking echocardiography for global longitudinal,
circumferential and radial strain
During follow-up visit 3, evaluation of protocol pre-specified primary and
secondary outcomes will take place.
Statistical analysis
Patients’ baseline demographical and clinical characteristics will be presented
as median ± inter-quartile range or absolute numbers (%). Scatter plots will be
generated depicting the correlation of baseline ecSYNC derived inter-
ventricular delay, LV total activation time and LV ED index with change (Delta)
between six months and baseline values in 6MWT distance, EF, LVEDV,
LVESV, Minnesota Living With Heart Failure Questionnaire score and BNP
levels. A Spearman correlation analysis will be applied to assess statistical
significance. Repeated measures general linear model analysis will be
performed to test whether any significant interaction lies between temporal
variation in ecSYNC values (from baseline until last visit) and clinical
response to CRT. A two-sided p value of less than 0.05 will be considered
statistically significant.
12

)

References
1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone
G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K,
Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland
D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D,
Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P,
Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J. Heart
disease and stroke statistics–201 0 update: a report from the American
Heart Association. Circulation. 121 (7) :e46-e215.
2. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart.
2007;93(9):1137-1146.
3. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T,
Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM.
Cardiac-resynchronization therapy with or without an implantable
defibrillator in advanced chronic heart failure. N Engl J Med.
2004;350(21 ):2140-2150.
4. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D,
Kappenberger L, Tavazzi L. The effect of cardiac resynchronization on
morbidity and mortality in heart failure. N Engl J Med.
2005;352(15):1539-1549.
5. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E,
Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ,
Underwood J, Pickering F, Truex C, McAtee P, Messenger J. Cardiac
resynchronization in chronic heart failure. N Engl J Med.
2002;346(24):1845-1853.
6. Tracy CM, Epstein AE, Darbar D, Dimarco JP, Dunbar SB, Estes NA,
3rd, Ferguson TB, Jr., Hammill SC, Karasik PE, Link MS, Marine JE,
Schoenfeld MH, Shanker AJ, Silka MJ, Stevenson LW, Stevenson WG,
Va rosy PD. 2012 ACCF/AHAlHRS focused update of the 2008
guidelines for device-based therapy of cardiac rhythm abnormalities: a
report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines. J Am Call
Cardiol.60(14): 1297-1313.
7. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M,
Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA,
Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske
BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P,
Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A. ESC
Guidelines for the diagnosis and treatment of acute and chronic heart
failure 2012: The Task Force for the Diagnosis and Treatment of Acute
and Chronic Heart Failure 2012 of the European Society of Cardiology.
Developed in collaboration with the Heart Failure Association (HFA) of
the ESC. EurHeartJ.33(14):1787-1847.
8. Yu CM, Fung WH, Lin H, Zhang Q, Sanderson JE, Lau CPo Predictors
of left ventricular reverse remodeling after cardiac resynchronization
therapy for heart failure secondary to idiopathic dilated or ischemic
cardiomyopathy. Am J Cardia!. 2003;91 (6):684-688.
13

9. Bax JJ, Bleeker GB, Marwick TH, Molhoek SG, Boersma E, Steendijk
P, van der Wall EE, Schalij MJ. Left ventricular dyssynchrony predicts
response and prognosis after cardiac resynchronization therapy. J Am
Coli Certiiot. 2004;44(9):1834-1840.
10. Bax JJ, Marwick TH, Molhoek SG, Bleeker GB, van Erven L, Boersma
E, Steendijk P, van der Wall EE, Schalij MJ. Left ventricular
dyssynchrony predicts benefit of cardiac resynchronization therapy in
patients with end-stage heart failure before pacemaker implantation.
Am J Cardial. 2003;92(10):1238-1240.
11. Sogaard P, Egeblad H, Pedersen AK, Kim WY, Kristensen BO, Hansen
PS, Mortensen PT. Sequential versus simultaneous biventricular
resynchronization for severe heart failure: evaluation by tissue Doppler
imaging. Circulation. 2002; 1 06(16):2078-2084.
12. Chung ES, Leon AR, Tavazzi L, Sun JP, Nihoyannopoulos P, Merlino
J, Abraham WT, Ghio S, Leclercq C, Bax JJ, Yu CM, Gorcsan J, 3rd,
St John Sutton M, De Sutter J, Murillo J. Results of the Predictors of
Response to CRT (PROSPECT) trial. Circulation. 2008;117(20):2608-
2616.
13. Schlosshan D, Barker D, Pepper C, Williams G, Morley C, Tan LB.
CRT improves the exercise capacity and functional reserve of the
failing heart through enhancing the cardiac flow- and pressure-
generating capacity. Eur J Heart Fail. 2006;8(5):515-521.
14. Dreger H, Antonow G, Spethmann S, Bondke H, Baumann G, Melzer
C. Oyssynchrony parameter-guided interventricular delay
programming. Europace.14(5):696-702.
15. Bajraktari G, Batalli A, Poniku A, Ahmeti A, Olloni R, Hyseni V, Vela Z,
Morina B, Tafarshiku R, Vela D, Rashiti P, Haliti E, Henein MY. Left
ventricular markers of global dyssynchrony predict limited exercise
capacity in heart failure, but not in patients with preserved ejection
fraction. Cardiovasc Ultrasound. 1 0(1 ):36.
16. Kedia N, Ng K, Apperson-Hansen C, Wang C, Tchou P, Wilkoff BL,
Grimm RA. Usefulness of atrioventricular delay optimization using
Doppler assessment of mitral inflow in patients undergoing cardiac
resynchronization therapy. Am J Cardiol. 2006;98(6):780-785.
17. Thomas DE, Yousef ZR, Fraser AG. A critical comparison of
echocardiographic measurements used for optimizing cardiac
resynchronization therapy: stroke distance is best. Eur J Heart Fail.
2009;11(8):779-788.
14

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•
J

Appendix
Figure 1. Spatial anatomical relationship between ecSYNC vest electrodes’
and patient’s heart
15

•
Figure 2. Bi-ventricular activation map. Areas colour-encoded red represent
the earliest activation sites while areas colour-encoded blue correspond to the
latest activation sites.
16

•
•
— ————–.–.———–~-

Figure 3. Parameters of inter-ventricular and intra-ventricular dyssynchrony
provided by ecSYNC incorporated software.

InterVentricular Synchrony (InterV): Bi-Ventrlcular Electrical
Synchrony
• Mean(RV) – Mean (LV)

Left Ventricle Total Activation Time (LVTAT): lntra-Lv Electrical
Synchrony
• Mean (Last 10%) – Mean (First 10%) of LV Activation Time

Standard Deviation of Left Ventricular Activation (LVsd):
J)

CUffem (msl ~
~ Inter\! -61 N/A
SOlv 21 N/A

17

Table 1. A-V and V-V delay optimization protocol

A-V delay (ms)
60 80 100 120 140 160 180 200
Mitral VTI (em)
V-V delay (ms)
BiV LV+20 LV+40 LV+60 LV+80 RV+20 RV+40 RV+60
L VOT VTI (em)
During the A-V optimization process, the impact of different A-V intervals upon
mitral VTI will be tested. During the V-V optimization process, the impact of
simultaneous V-V pacing (i.e. V-V delay Oms), LV pre-excitation and RV pre-
excitation upon LVOT VTI will be assessed.
18

)

Flow Chart 1
Inclusion criteria
• Able to give written informed
consent
• Age> 18 years old
• Fulfils established clinical criteria
for CRT implantation (with or
without a defibrillator)
• NYHA Class III-IV Heart Failure
(or NYHA II with NYHA IIIIIV
symptoms in the preceding 12
months)
• LVEF <35% (Calculated using
echocardiography or Cardiac
MR) at the time of implantation
• QRS duration> 130ms
• Optimal Tolerated Medical
Therapy for Heart Failure

Non-invasive epicardial
electrocardiographic mapping
in predicting clinical CRT
response
Screening
CRT-P or CRT-O eligible patients
according to ESC/AHA/ACC
guidelines
Check for inclusion/exclusion criteria
Obtain informed consent*
• QOL Questionnaire (MLHFQ)
•6MWT
• BNP
• Standard echocardiography including
~ interventicular mechanical delay
~ septal-lateral delay
‘;::. +n+~1 I \/ ie-n”nl” •.•..• i,.. +i •.•..• o

Exclusion criteria
• Severe, life threatening non
cardiac disease
• Active malignant disease and
recent «5 years) malignant
disease
• Prior Heart Transplant
• Recent history of unstable
angina, acute coronary syndrome
or myocardial infarction within
three months of enrolment into
the study
• Pregnancy
• Failure to participate in consent
process
• Heart Failure requiring constant
intravenous therapy including
diuretics and/or inotropes
• Recent revascularisation
procedure i.e. coronary artery
bypass grafting (CABG) or
percutaneous coronary
intervention (PC I) within the last

Flow Chart 2

Day 1 post implant’ .> CRT in Back-up mode I . Activation map construction
I ,
Echo optimisation of CRT • Inter-ventricular delay
‘II
ecSYNC vest application I • LV total activation time
CRT in nominal settings ..
Low-dose CT scan I . • SD of LV activation
VI
Echo optimised CRT I .•..
I ,
1 month
Follow up visit 1
3 months
Follow-up visit 2
Interim analysis

• Assess symptoms/medication
•….. -7 • ECG
• Standard echo
–
: 6 months
Follow-up visit 3
)
ecSYNC vest application 1\
Low-dose CT scan
—

• QoL Questionnaire (MLHFQ)
• 6MWT
• BNP
• Standard echocardiography including
? Interventicular mechanical delay
? septal-lateral delay
? total LV isovolumic time
• Speckle tracking echocardiography
• Activation maps construction
? inter-ventricular delay
? LV total activation time
? SD of LV activation
‘Or earliest available opportunity

20

‘—-
Time/Event Schedule

,….,./
\.

Screening CRT Day 1 Post 1 Month 3 Months 6 Months Unscheduled
Implant Implant Post Implant Post Implant Post Implant Visit
Visit 1 2 3 4 5 6
Informed Consent X X
Inclusion/Exclusion Criteria X
Demographics X
Medical Assessment* XOO X X X X
ECG XOO X X X X
NYHA XOO X X X
MLHFQ XOO X X
6MWT XOO X X
Standard Echo XOO X X X X
Dyssynchrony Echo XOO X
Speckle Tracking Echo XOO X X
Bloods XOO X X X
CRT Implant X
Echo Optimisation X
ecSYNC Map Including CT X X
Adverse Events” X X X X X X
End of Study Follow Up X
*Including medical history, physical examination and medication review
§Adverse event reporting as per GCP guidance
OONot necessary if results available from previous 3 months

Guy’s and St Thomas’ ‘~/:bj
NHS Foundation Trust
Cardiothoracic Centre
St Thomas’ Hospital
London, SE1 7EH
Tel 0207 188 9484
Centre Number: a?l
Study Number:
Patient Identification Number for this trial: ’00 t .
CONSENT FORM
Title of Project: Predicting Response to Cardiac Resynchronisation Therapy Using Body
Surface ECG Mapping
Name of Researcher: Prof Aldo Rinaldi
Please initial all boxes
1. I confirm that I have read and understand the information sheet dated 18/Jul/2013
(version 1.1) for the above study. I have had the opportunity to consider the
information, ask questions and have had these answered satisfactorily.
2. I understand that my participation is voluntary and that I am free to withdraw at any time
without giving any reason, without my medical care or legal rights being affected.
3. I understand that relevant sections of my medical notes and data collected during the
study may be looked at by individuals from Cardiolnsight Technologies, from regulatory
authorities or from the NHS Trust, where it is relevant to my taking part in this research.
I give permission for these individuals to have access to my records.
4. I agree to my GP being informed of my participation in the study.
5. I agree to take part in the above study.
Name of Person
taking consent.

Date
Date
Consent form date of issue: 11/Apr/2013
Consent form version number: 1.0

Page 1 of 1

Cardiolnsight ECM for CRT

St Thomas’ Hospital
I
Day One Post implant Follow-up v 1.1 I
——~—–
Screening 10#: SCR- () D +

Subject Initials (First/Last): K C
* F, 0, T: Fused, Optimal, Truncating
I
Overview – Key Echo/CIT Analysis I
~—~~———

Parameters Echo recorded? Echo Analysis CIT CIT Analysis (offline)
(MVI, A4CH, etc.) (LVEF, LVEDV, LVESV) recorded? (VVsync, Wtat, LVtat, LVdisp)
Device in V
Back-up
Nominal Si~ I .J../ lltO/, UJJ
Setting
Echo Optimal Av)1o, lv]o,
Setting
.J
I
A-V Delay Echo/CIT Analysis I
——————
\ \l
To be performed at a pre-defined v-v Delay: \./_ ~ ms
Cu rrent pacing vector: _ 0 ,=-cf\ ‘”‘

A-V Delay Echo recorded? Echo Analysis CIT recorded? CIT Analysis (offline)
(ms) (MVI, A4CH, etc.) (F, 0, T) (VVsync, VVtat, LVtat, LVdisp)
~ V V-
180 \.-‘” V
160 V V
140 V c-:
130 V /’
120 V -J
110 ,/ j
100 V v”
80 V V
60 ‘/ J
1\.] Identified Optimal A-V Delay via Echo: _(so ~ ms
cS)
Page 1 of 3

Cardiolnsight ECM for CRT

St Thomas’ Hospital
1 D_a_Y_O_n_e_p_o_s_t_im_p_la_n_t_F_o_I_IO_W_-_U_P_V_l_ol 1
I V-V Delay Echo/CIT Analysis I
To be performed at Optimal A-V Delay (above)

v-v Delay Echo recorded? Echo Analysis CIT recorded? CIT Offline Analysis
(ms) (MVI, A4CH, etc.) (VTI) (Wsync, VVtat, LVtat, LVdisp)
-W8O” ~
LV40 J I ?’.’~ V
LV30 V J R-. 9 ~.
LV20 V .«.« vi
LV1~ V “r::}- i h V
SIM \/ fA. ‘s \/
RV20 V Ih,9 ~
v’ , J
RV40 I 7-\ S
~VOllty – J

LV only

Identified Optimal V-V Delay via Echo:.!:~ joms
Page 2 of 3

Cardiolnsight ECM for CRT

St Thomas’ Hospital
I
Day One Post implant Follow-up v 1.1 I
——~——-
I
Extra pacing vectors for err Analysis I
—~——–

Vectors (IT recorded? (IT Offline Analysis
(VVsync, VVtat, LVtat, LVdisp)
Dl-RV V
M2-RV ./
M3-RV ~
P4-RV <…– …
1”’ ~ – (1,. . J
/
AJ..?-M., /.
f) .. – f 0- ,/
Investigator signature

—1—1 _
dd/mm/vvyy
. Page 3 of 3
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