Heart Function in Patients Assessed for Sleep Disordered Breathing (SDB)
Conditions: Heart Failure With Preserved Ejection Fraction, Sleep Disordered Breathing, Heart Failure With Normal Ejection Fraction, Obstructive Sleep Apnea, Central Sleep Apnea, Heart Failure
Sponsor: Imperial College London

 
Prevalence & Prognosis of HFpEF in patients assessed for Sleep Apnoea 
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Heart Function in patients assessed for Sleep Disordered Breathing 
(SDB) 
 
NCT 03226652 
Date: 20/11/2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Prevalence & Prognosis of HFpEF in patients assessed for Sleep Apnoea 
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‘A Study of Heart Function in patients assessed for Sleep Disordered Breathing (SDB)’ 
 
 
 
Prevalence and Prognosis of Heart Failure with Preserved 
Ejection Fraction (HFpEF) in patients assessed for Sleep 
Disordered Breathing (SDB) 
 
 
 
Version 3.1 20/11/2017 
 
 
 
 
MAIN SPONSOR: Imperial College London 
STUDY COORDINATION CENTRE: Royal Brompton Hospital     
NRES reference: 17/SC/0320 
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Prevalence & Prognosis of HFpEF in patients assessed for Sleep Apnoea 
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Study Management Group 
 
Chief Investigator:  
Professor Martin Cowie 
    
Co-investigators:  
Professor Anita Simonds 
Dr Angela Gallagher 
 
Statistician:  
 
Mr Winston Banyan 
 
 
Study Coordination Centre  
 
For general queries, supply of study documentation, and collection of data, please contact: 
 
Study Coordinator:  
Dr A Gallagher 
Address:  
 
Royal Brompton Hospital, Sydney Street, London SW3 6NP  
Tel:  
 
 
020 7352 8121 ext. 2003 
 
 
 
 
 
Fax:   
 
02073518148  
E-mail:   
 
angela.gallagher02@imperial.ac.uk 
 
 
 
 
 
 
 
 
 
Clinical Queries 
 
Clinical queries should be directed to Dr A Gallagher who will direct the query to the 
appropriate person. 
 
 
Sponsor 
 
Imperial College London is the main research Sponsor for this study.  For further information 
regarding the sponsorship conditions, please contact the Head of Regulatory Compliance at: 
 
 
 
Joint Research Compliance Office 
Imperial College London & Imperial College Healthcare NHS Trust 
2nd Floor Medical School Building 
St Mary’s Hospital 
Praed Street 
London 
W2 1NY 
Tel: 020 7594 1862 
 
 
 
This protocol describes the ‘Prevalence and Prognosis of Heart Failure with Preserved Ejection Fraction 
(HFpEF) in patients assessed for Sleep Disordered Breathing (SDB)’ study and provides information 
about procedures for entering participants.  Every care was taken in its drafting, but corrections or 
amendments may be necessary. These will be circulated to investigators in the study.  Problems relating 
to this study should be referred, in the first instance, to the Chief Investigator.  
 
This study will adhere to the principles outlined in the NHS Research Governance Framework for Health 
and Social Care (2nd edition). It will be conducted in compliance with the protocol, the Data Protection 
Act and other regulatory requirements as appropriate. 

 
Prevalence & Prognosis of HFpEF in patients assessed for Sleep Apnoea 
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Table of Contents 
1. 
INTRODUCTION 
6 
1.1 BACKGROUND 
6 
2.  STUDY OBJECTIVES 
7 
3.  STUDY DESIGN 
7 
3.1 STUDY OUTCOME MEASURES 
7 
4. 
PARTICIPANT ENTRY 
8 
4.2 INCLUSION CRITERIA 
8 
4.3 EXCLUSION CRITERIA 
8 
5. 
ADVERSE EVENTS 
8 
5.1 DEFINITIONS 
8 
5.3 REPORTING PROCEDURES 
8 
6. 
ASSESSMENT AND FOLLOW-UP 
9 
7. 
STATISTICS AND DATA ANALYSIS 
9 
8. 
REGULATORY ISSUES 
9 
8.1 ETHICS APPROVAL 
9 
8.2 CONSENT 
9 
8.3 CONFIDENTIALITY 
9 
8.4 INDEMNITY 
9 
8.5 SPONSOR 
9 
8.6 AUDITS AND INSPECTIONS 
9 
9. 
STUDY MANAGEMENT 
10 
10. 
PUBLICATION POLICY 
10 
11. 
REFERENCES 
10 
APPENDIX 1. 
SCHEDULE OF ASSESSMENTS 
12 
APPENDIX 2. 
PARTICPANT INFORMATION SHEET (PIS) 
13 
APPENDIX 3. 
PARTICPANT INVITATION LETTER 
18 
APPENDIX 4. 
GP LETTER 
20 
APPENDIX 5. 
CONSENT FORM 
22 
 
 
 
 
 
 

 
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GLOSSARY OF ABBREVIATIONS 
SDB 
Sleep Disordered Breathing 
OSA 
Obstructive sleep apnoea 
CSA 
Central sleep apnoea 
HFpEF 
Heart Failure with preserved ejection fraction 
HFrEF 
Heart Failure with reduced ejection fraction 
AHI 
Apnoea-hypopnoea index 
LVEF 
Left ventricular ejection fraction 
 
 
STUDY SUMMARY 
 
TITLE Prevalence and Prognosis of Heart Failure with Preserved Ejection 
Fraction (HFpEF) in patients assessed for Sleep Disordered 
Breathing (SDB) 
DESIGN Prospective observational study 
AIMS 
1. To establish the prevalence of HFpEF among patients being 
investigated for SDB. 
2. To examine the type and severity of SDB in patients identified 
with HFpEF.  
3. To characterise the phenotype of the patients that are identified 
with HFpEF  
4. To determine the prognosis of patients with HFpEF based on 
hospitalisation and mortality data.  
OUTCOME MEASURES Primary Outcome measure:  
1) Number of patients with diagnostic criteria for HFpEF 
 
Secondary outcome measures:  
1) The number of patients with SDB and the proportion of OSA 
and CSA. 
2) Apnoea-hypopnoea index (AHI) as an indicator of SBD 
severity. 
3) The 
frequency 
of 
cardiac 
co-morbidities 
including 
hypertension, coronary artery disease, diabetes and atrial 
fibrillation. 
4) Rate of hospitalisation and mortality over 12 months.  
 
POPULATION Patients referred for respiratory polygraphy at the Royal Brompton 
Hospital 
ELIGIBILITY Patients ≥40 years without pre-existing treated SDB or heart failure  
DURATION 20 months 
 

 
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1. 
INTRODUCTION  
 
1.1 
BACKGROUND 
 
Daytime somnolence, fatigue and feeling unrefreshed on waking are typical symptoms of 
sleep disordered breathing (SDB). Respiratory polygraphy, performed either in hospital or at 
home, readily allows confirmation of the diagnosis. Obstructive sleep apnoea (OSA) and 
central sleep apnoea (CSA) are two types of SDB. In OSA there is collapse of the pharynx 
leading to partial or complete airway obstruction, whilst in CSA there is abnormality in the 
neural brainstem control of breathing. Although the mechanisms of obstructive and central 
apnoea differ, they both result in in repetitive reduction (hypopnoea) or cessation of 
breathing (apnoea). This in turn can cause sleep fragmentation, exaggerated negative intra-
thoracic pressure swings, intermittent hypoxia and sympathetic nervous system activation, 
which can have detrimental effects on the cardiovascular system [1].   
 
Whilst performing a respiratory polygraphy allows accurate diagnosis of SDB it does not 
address potential underlying cardiovascular disease in the same patient. It is well –
established that SDB is common among patients with heart failure, both with reduced 
(HFrEF) and preserved ejection fraction (HFpEF) [2]. SDB may occur as a consequence of 
heart failure, but has also been implicated in its progression. Bitter et al studied SDB in 
patients with heart failure with normal ejection fraction identifying its prevalence in 69% of 
individuals [3]. Central sleep apnoea, which is principally linked with heart failure, is 
independently associated with a worse prognosis, including mortality. 
 
Heart failure with preserved ejection fraction (HFpEF) accounts for up to half of all heart 
failure cases and is associated with significant morbidity and mortality [4]. It can be 
challenging to diagnose as it can present with non-specific symptoms, be obscured by 
concomitant diseases and there is a lack of a simplified diagnostic test. Unrecognised heart 
failure, predominately with preserved ejection fraction, was shown to be present in 1 in 6 
primary care patients with breathlessness on exertion [5]. In 2016 the European Society of 
Cardiology (ESC) set out updated diagnostic criteria for HFpEF. This combined the signs 
and symptoms of heart failure, left ventricular ejection fraction (LVEF) ≥50%, elevated 
natriuretic peptide levels, and relevant structural disease or diastolic dysfunction [6]. 
 
The phenotype of patients with SDB and those with heart failure with preserved ejection 
fraction (HFpEF) share similar characteristics [7]. Increasing age, hypertension, obesity, 
diabetes mellitus and atrial fibrillation are well recognised links in both groups. It has been 
shown that in patients with similar co-existent diseases, the added presence of heart failure 
with preserved ejection fraction results in higher morbidity and mortality rates [8]. 
 
 
1.2 
RATIONALE FOR CURRENT STUDY 
 
Previous studies have evaluated the prevalence of SDB in patients known to have HFpEF, 
but not vice versa. Given the relationship between the two conditions and their similar 
phenotypes, we hypothesise that a subset of patients with unrecognised HFpEF can be 
identified in the population being investigated for SDB. We aim to determine the prevalence 
of patients with diagnostic criteria for HFpEF and examine the relationship with SDB. We will 
also collect prognostic data on hospitalisations and mortality over a 12 month period. This will 
allow inferences to be made as to whether this population should be targeted for screening for 
HFpEF. 

 
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2.  STUDY OBJECTIVES 
 
2.1 
PRIMARY OBJECTIVE 
 
• 
To identify patients with diagnostic criteria for HFpEF and establish the prevalence. 
 
2.2 
SECONDARY OBJECTIVES 
 
• 
To examine the type and severity of SDB in patients identified with HFpEF.  
• 
To characterise the phenotype of the patients that are identified with HFpEF. 
• 
To determine the prognosis of patients with HFpEF based on hospitalisation and 
mortality data.  
 
 
3.  STUDY DESIGN 
 
This is a prospective, observational study. The aim will be to recruit 155 patients and to 
collect prognostic data over a 12 month period from the participant’s enrolment.  
 
We will recruit patients referred for respiratory polygraphy, as part of their standard clinical 
care, at the Royal Brompton Hospital Sleep Centre. These patients would be symptomatic or 
be at moderate or high risk for SDB. Patients eligible will be ≥ 40 years with no history of 
pre-existing heart failure with reduced ejection fraction or treated sleep disordered breathing.  
 
The patients will have a respiratory polygraphy (Embletta MPR) performed either in-hospital 
or at home as part of their usual care. The respiratory polygraphy involves recording nasal 
air flow, snore sensor, pulse oximetry, chest and abdominal movement. It is a validated for 
screening for sleep disordered breathing, distinguishing between obstructive sleep apnoea 
(OSA) and central sleep apnoea (CSA). Hypopnoea will be defined as a 30% reduction in 
airflow in combination with at least 3% oxygen desaturation. Apnoea will be defined as a 
cessation of airflow for >10 s, and in case of CSA without any thoracic or abdominal 
breathing effort. The apnoea-hypopnoea index (AHI) will be used to assess the severity of 
SDB with the following classification: Mild 5-14/h, moderate 15-30/h and severe >30/h. 
Patients will be classified as OSA or CSA depending on the majority of events.  
 
On attendance for respiratory polygraphy the following investigations will be performed: 
 
1. Each patient will have documentation of their symptoms, medical diagnoses, 
medications and social history. A clinical cardiovascular examination will be 
performed.   
 
2. Two symptom questionnaires will be completed. The Epworth Sleepiness 
questionnaire will assess daytime somnolence and is standard practice in SDB 
assessment. The SF-36 Questionnaire will assess indices of quality of life.  
 
3. Biomarker assessment of heart failure will be performed by taking a single venous 
blood sample for plasma N-terminal-pro BNP (NT-proBNP) level and Growth 
Differentiation Factor-15 (GDF-15).  
 
4. An electrocardiogram (ECG) will be carried out for documentation of cardiac rhythm. 
 

 
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5. Echocardiography will be performed for assessment of structural heart disease and 
diastolic function in accordance to standard techniques. Parameters assessed will 
include: Left ventricular ejection fraction (LVEF), left ventricular diastolic function 
(E/A, DT, E’ septal. E’ lateral, E/E’), left ventricular wall thickness/mass, left atrial size 
and right ventricular (RV) function. 
 
The criteria for heart failure with preserved ejection fraction will be in accordance to 
European Society of Cardiology guidelines as set out:  Presence of symptoms and/or signs 
of heart failure, LVEF ≥50%, elevated levels of natriuretic peptides, and relevant structural 
disease or diastolic dysfunction. 
 
All recruited patients will be contacted by telephone at 3 monthly intervals over the next 12 
months. Information recorded will include symptoms, new diagnoses, medication changes 
and hospitalisations. Additional data from hospital records and GP records will be used to 
verify the number of hospitalisations, the reason for admission and the outcome.  This 
method will also be used to collect mortality data and if required certification information will 
be sought from the General Register Office.  
 
4. 
PARTICIPANT ENTRY  
 
4.1 
INCLUSION CRITERIA 
 
Patients aged ≥ 40 years referred for a respiratory polygraphy at the Sleep Centre at the 
Royal Brompton Hospital.   
 
4.2 
EXCLUSION CRITERIA 
 
Patients with known heart failure and those receiving treatment for pre-existing sleep 
disordered breathing.  
 
 
5. 
ADVERSE EVENTS 
 
5.1 
DEFINITIONS   
 
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject.   
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect 
that: 
• 
Results in death 
• 
Is life-threatening – refers to an event in which the subject was at risk of death at 
the time of the event; it does not refer to an event which hypothetically might have 
caused death if it were more severe 
• 
Requires hospitalisation, or prolongation of existing inpatients’ hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly or birth defect 
 
Important AEs that are not immediately life-threatening or do not result in death or 
hospitalisation but may jeopardise the subject or may require intervention to prevent one of 
the other outcomes listed in the definition above, will also be considered serious. 
 

 
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5.3 
REPORTING PROCEDURES 
All adverse events should be reported.  Depending on the nature of the event the reporting 
procedures below should be followed.  Any questions concerning adverse event reporting 
should be directed to the Chief Investigator in the first instance.  
 
5.3.1 Non serious AEs 
All such events, whether expected or not, should be recorded.   
 
5.3.2 Serious AEs 
An SAE form should be completed and faxed to the Chief Investigator within 24 hours.  
However, relapse and death due to pre-existing conditions, and hospitalisations for elective 
treatment of a pre-existing condition do not need reporting as SAEs. 
 
All SAEs should be reported to the South Central-Oxford B REC where in the opinion of the 
Chief Investigator, the event was: 
• 
‘related’, i.e. resulted from the administration of any of the research procedures; 
and 
• 
‘unexpected’, i.e. an event that is not listed in the protocol as an expected 
occurrence 
 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief 
Investigator becoming aware of the event, using the NRES SAE form for non-IMP studies.  
The Chief Investigator must also notify the Sponsor of all SAEs. 
 
Local investigators should report any SAEs as required by their Local Research Ethics 
Committee, Sponsor and/or Research & Development Office. 
 
Contact details for reporting SAEs 
 
Please send SAE forms to:  
 
Professor Cowie 
Imperial College London 
National Heart & Lung Institute 
Dovehouse Street  
London 
SW3 6LY 
 
Fax: 020 7351 8148, F.A.O. Professor Cowie 
 
Tel: 020 73518856 (Mon to Fri 09.00 – 17.00) 
  
 
6. 
ASSESSMENT AND FOLLOW-UP  
 
We will be conducting telephone calls at 3 monthly intervals following the patient’s enrolment 
to collect information related to the patient’s health and hospitalisation history. The patient’s 
involvement in the study will be concluded following the final telephone contact at month 12.  
 
Any cardiovascular findings requiring follow-up will be reported to the patient’s usual clinical 
care team and General Practitioner.  

 
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The follow-up of patients from a sleep disordered breathing perspective will be directed by 
their usual clinical care team.  
 
7. 
STATISTICS AND DATA ANALYSIS 
 
The prevalence of HFpEF in this population has not previously been defined. In this study if 
we assume the prevalence of HFpEF to be 10% and if the precision of this estimate is within 
5% then for a 95% confidence interval, the required sample size will be 139 subjects. 
Assuming a 10% drop out, we would require a final sample size of 155. 
 
The primary outcome will be presented as a proportion. For the prognostic data, categorical 
data will be presented as frequency (percentage) and the survival pattern described using 
the log rank test and Kaplan-Meier survival plots. 
 
Data and all appropriate documentation will be stored for a minimum of 10 years after the 
completion of the study, including the follow-up period.   
 
 
8. 
REGULATORY ISSUES 
 
8.1 
ETHICS APPROVAL 
The Chief Investigator has obtained approval from the South Central Oxford B Research 
Ethics Committee.  The study must be submitted for Site Specific Assessment (SSA) at each 
participating NHS Trust.  The Chief Investigator will require a copy of the Trust R&D approval 
letter before accepting participants into the study.  The study will be conducted in accordance 
with the recommendations for physicians involved in research on human subjects adopted by 
the 18th World Medical Assembly, Helsinki 1964 and later revisions. 
 
8.2 
CONSENT  
Consent to enter the study must be sought from each participant only after a full explanation 
has been given, an information leaflet offered and time allowed for consideration.  Signed 
participant consent should be obtained.  The right of the participant to refuse to participate 
without giving reasons must be respected.  After the participant has entered the study the 
clinician remains free to give alternative treatment to that specified in the protocol at any stage 
if he/she feels it is in the participant’s best interest, but the reasons for doing so should be 
recorded.  In these cases the participants remain within the study for the purposes of follow-
up and data analysis.  All participants are free to withdraw at any time from the protocol 
treatment without giving reasons and without prejudicing further treatment. 
 
8.3 
CONFIDENTIALITY 
The Chief Investigator will preserve the confidentiality of participants taking part in the study 
and is registered under the Data Protection Act. 
 
8.4 
INDEMNITY 
Imperial College London holds negligent harm and non-negligent harm insurance policies 
which apply to this study. 
 
8.5 
SPONSOR 
Imperial College London will act as the main Sponsor for this study.  Delegated responsibilities 
will be assigned to the NHS trusts taking part in this study.   
 
. 

 
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8.6 
AUDITS  
The study may be subject to inspection and audit by Imperial College London under their remit 
as sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research 
Governance Framework for Health and Social Care (2nd edition).  
 
 
9. 
STUDY MANAGEMENT 
 
The study will be co-ordinated by Dr Angela Gallagher, Clinical Research Fellow, Royal 
Brompton Hospital, Sydney Street, London, SW3 6NP. Tel: 0207 3528151 ext. 2003; Fax: 
02073518148.  
 
 
10. 
PUBLICATION POLICY 
 
It is anticipated that the study’s results will be published in peer-reviewed journals, presented 
at scientific meetings and submitted as part of MD (Res) thesis. 
 
 
11. 
REFERENCES 
 
1. Cowie, M. R. (2017) Sleep apnea: State of the art. Trends in Cardiovascular 
Medicine. 27 (4), 280-289 
 
2. Pearse SG, Cowie MR. Sleep-disordered breathing in heart failure. Eur J Heart Fail. 
2016;18(4):353-61 
 
3. Bitter, T., Faber, L., Hering, D., Langer, C., Horstkotte, D. & Oldenburg, O. (2009) 
Sleep-disordered breathing in heart failure with normal left ventricular ejection 
fraction. European Journal of Heart Failure. 11 (6), 602-608.  
 
4. Owan, T. E., Hodge, D. O., Herges, R. M., Jacobsen, S. J., Roger, V. L. & Redfield, 
M. M. (2006) Trends in prevalence and outcome of heart failure with preserved 
ejection fraction. The New England Journal of Medicine. 355 (3), 251-259.  
 
5. van Riet, E. E., Hoes, A. W., Limburg, A., Landman, M. A., van der Hoeven, H. & 
Rutten, F. H. (2014) Prevalence of unrecognized heart failure in older persons with 
shortness of breath on exertion. European Journal of Heart Failure. 16 (7), 772-777. 
 
6. Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G., Coats, A. J., 
Falk, V., Gonzalez-Juanatey, J. R., Harjola, V. P., Jankowska, E. A., Jessup, M., 
Linde, C., Nihoyannopoulos, P., Parissis, J. T., Pieske, B., Riley, J. P., Rosano, G. 
M., Ruilope, L. M., Ruschitzka, F., Rutten, F. H., van der Meer, P., Authors/Task 
Force Members & Document Reviewers. (2016) 2016 ESC Guidelines for the 
diagnosis and treatment of acute and chronic heart failure: The Task Force for the 
diagnosis and treatment of acute and chronic heart failure of the European Society of 
Cardiology (ESC). Developed with the special contribution of the Heart Failure 
Association (HFA) of the ESC. European Journal of Heart Failure. 18 (8), 891-975.  
 
7. Triposkiadis, F., Giamouzis, G., Parissis, J., Starling, R. C., Boudoulas, H., 
Skoularigis, J., Butler, J. & Filippatos, G. (2016) Reframing the association and 

 
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significance of co-morbidities in heart failure. European Journal of Heart Failure. 18 
(7), 744-758.  
 
8. Campbell RT, Jhund PS, Castagno D, Hawkins NM, Petrie MC, McMurray JJ. What 
have we learned about patients with heart failure and preserved ejection fraction from 
DIG-PEF, CHARM-preserved, and I-PRESERVE? J Am Coll Cardiol. 
2012;60(23):2349-56. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix 1. Schedule of events table 
 
 
 
Month 
Baseline 
Visit 
3 
6 
9 
12 
Informed consent 
X 
 
 
 
 
History & Examination 
X 
 
 
 
 
Symptom Questionnaires 
X 
 
 
 
 
Blood test (NT-proBNP & GDF-15) 
X 
 
 
 
 
ECG 
X 
 
 
 
 
Echocardiogram 
X 
 
 
 
 
Sleep Study Test 
X 
 
 
 
 
Telephone Call 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix 2. Patient Information Sheet (PIS) 
 
                  
 
IRAS ID Number: 228728 
 
 
Participant Information Sheet (PIS) 
 
A study of Heart Function in patients assessed for Sleep Disordered Breathing 
(SDB) 
 
 
Invitation to participate in the above study: 
 
We would like to invite you to take part in a research study. Before you decide we would like 
you to understand why the research is being done and what it will involve for you. Please 
take time to read the following carefully and discuss it with others if you wish. Ask us if 
there is anything that is not clear or if you would like more information.  Take time to decide 
whether or not you wish to take part.   
 
Thank you for reading this. 
 
What is the purpose of the study? 
 
The purpose of this study is to find out about the heart function of patients who have been 
referred for a sleep study test as part of their normal clinical care.  
 
Sleep disordered breathing (SDB), also known as sleep apnoea, causes typical symptoms of 
daytime sleepiness, fatigue and feeling unrefreshed on waking. SDB results in brief pauses 
or reduced airflow during breathing. This can have potential negative effects on the heart 
and the body’s blood supply. Sleep study tests performed either in hospital or at home 
readily allow the diagnosis of SDB to be made. However, they do not provide information on 
the heart function. 
 
In this study we would like to screen the heart function of patients referred for a sleep study 
test. In particular this will focus on a condition called heart failure. This is a common heart 
condition in the older population and can cause symptoms of breathless, tiredness and 
sometimes disturbed sleep. The aim will be to find out if this condition is present in patients 
being investigated for SDB.  The goal will be to find out how often it occurs, investigate its 
relationship with SDB and to collect information on the outcomes of patients.  
 
This study will be part of an educational project linked to an MD research programme.  
 
 

 
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What will happen if I am diagnosed with abnormal Heart Function? 
 
If any abnormality of your heart function is detected, or diagnostic criteria for heart failure is 
met, your usual doctor or GP will be informed. This will allow appropriate follow-up and 
management for your heart function to be put in place.  
 
Why have I been invited? 
 
You are being asked to take part as you have been referred for a sleep study test and are 
aged 40 years or older. This study will involve 155 participants.  
 
Do I have to take part?  
 
It is up to you to decide whether or not to take part.  If you do decide to take part you will 
be given this information sheet to keep and be asked to sign a consent form to show you 
have agreed to take part. You may choose not to participate in this study or you may leave 
the study at any time without giving a reason.  This would not affect the standard of care 
you receive. 
 
What will happen to me if I take part? 
 
You have been referred for a sleep study test by your doctor to investigate sleep-disordered 
breathing. Taking part in the study will not affect the management of this.  
 
In addition to your sleep study test we will organise the following when you attend for your 
appointments: 
 
1. Meet a member of the research team to discuss the study and consent form in more 
detail. If you chose to participate you will be asked to sign the consent form.  
 
2. Discuss your medical history, medications and perform a routine medical examination 
which will take around 20 minutes.  
 
3. You will be asked to complete two symptom questionnaires, one of which is standard 
when having a sleep study test. Together these will take about 15 minutes. 
 
4. You will be requested to have a blood test to look for two protein markers of heart 
failure. Only a small sample will be required. 
 
5. You will be requested to have an electrocardiogram (ECG), which is a painless, non-
invasive test to check your heart rhythm, taking about 5 minutes. 
 
6. You will be requested to have an echocardiogram, which is a non-invasive ultrasound 
scan of the heart taking about 40 minutes 
 
After your sleep study test we will phone you every 3 months over the next year to find out 
how you are. We would like to record if you started any new medications, had any new 
diagnoses or admissions to hospital. In total this will be 4 phone calls, each taking about 10 
minutes.  We may also need to contact your GP, access your hospital records or seek 

 
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information from the General Register Office to gain a complete picture of how you have 
been over the year.  
 
Expenses and payments 
 
You will not receive any payment for taking part in this study. 
 
What do I have to do?  
 
Involvement in this study should not impose any restrictions to your current lifestyle.  There 
are no specific dietary restrictions.  You can drive, drink, take part in sport or indeed do 
anything that follows the advice given to you by your doctor, taking into consideration any 
medical conditions.  Your treatment will not be altered. 
 
What are the alternatives for diagnosis or treatment? 
 
You do not have to participate in this study for diagnosis and treatment of sleep apnoea. 
 
What are the possible disadvantages and risks of taking part? 
 
There are no disadvantages of taking part. The ECG and echocardiogram are both non-
invasive and safe tests. The blood test will be taken by a trained professional using standard 
safety precautions.  
 
What are the possible benefits of taking part?  
 
You will have an assessment of your heart function. As mentioned before, if this shows any 
significant abnormalities your doctor will be informed. This will allow any appropriate follow-
up appointments to be put in place.  
 
What happens when the research study stops? 
 
At the end of the research, your care will continue as usual. 
 
What if relevant new information becomes available? 
 
Sometimes during the course of a research study, new information becomes available about 
the condition that is being studied.  If this happens, we will tell you about it and discuss with 
you whether you want to continue in the study.  If you decide not to carry on we will make 
arrangements for your care to continue.  If you decide to continue in the study you may be 
asked to sign an updated consent form.  Also, on receiving new information we might 
consider it to be in your best interests to withdraw you from the study.  We will explain the 
reasons and arrange for your care to continue. 
 
What will happen if I don’t want to carry on with this study? 
 
If you do not want to take part in this study, you will receive standard care as determined 
by your doctor. Your participation in this study is voluntary and you may withdraw from the 
study at any time without prejudice to your future medical care. Should you decide to 
withdraw from the study for any reason, you are asked to contact Dr Angela Gallagher 

 
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immediately. Should your participation in the study be terminated, regardless of the reason, 
you will not suffer any penalties or loss of benefits to which you are otherwise entitled. 
 
What if there is a problem? 
 
If you have a concern about any aspect of this study, you should ask to speak to the 
researchers who will do their best to answer your questions (Dr Angela Gallagher 0207 352 
8121 ext. 2003).  If you remain unhappy and wish to complain formally, you can do this 
through the NHS Complaints Procedure (and also by speaking with the Patient Advice and 
Liaison Service (PALS) at the Royal Brompton Hospital on 0207 349 7715). 
 
Harm: 
 
Imperial College holds Public Liability (“negligent harm”) and Clinical Trial (“non-negligent 
harm”) insurance policies which apply to this trial.  If you can demonstrate that you 
experienced harm or injury as a result of your participation in this study, you will be eligible 
to claim compensation without having to prove that Imperial College is at fault.  If the injury 
resulted from any procedure which is not part of the trial, Imperial College will not be 
required to compensate you in this way. Your legal rights to claim compensation for injury 
where you can prove negligence are not affected 
 
Will my taking part in the study be kept confidential? 
 
All information which is collected about you during the course of the research will be kept 
strictly confidential.  Any information about you which leaves the hospital will have your 
name, address and personal details removed so that you cannot be recognised from it.  The 
data collected and analysed will be anonymised meaning that no names will be used. Any 
documents with personal details will be destroyed after 12 months i.e. following your final 
contact with the research team.  
 
Will my General Practitioner (GP) / Family Doctor be informed of my 
involvement? 
 
Provided you consent to this, your GP will be informed that you are participating in the study 
and will be updated of your medical progress. We will also request information from your GP 
about any hospital admissions or other health problems that you have had. 
 
What will happen to any samples I give? 
 
A blood sample will be taken to look for two markers of heart failure. The sample will be 
processed at the Royal Brompton & Harefield NHS Trust laboratory. The sample will not be 
kept for future research and will be destroyed as per the usual Royal Brompton & Harefield 
Laboratory procedure.  
 
Will any genetic tests be done? 
 
No 
 
 
 

 
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What will happen to the results of the research study? 
 
Your medical records will be made available for review by the study investigators and 
regulatory authorities (who periodically check that the studies are being carried out 
correctly). This information will be kept confidential. At the end of the project all the 
research results are gathered together and analysed.  The researchers have a professional 
responsibility to publish their findings, however your identity will not be revealed.  Most 
research is published in the medical press – if you are interested in knowing the overall 
results of the study, ask the researchers about this.  You are entitled to see any results or 
information about you under the Freedom of Information Act.  
 
Who is organising and funding the research? 
 
Imperial College London is sponsoring the research. The doctors conducting the research 
are not being paid for including you in the study. 
 
Who has reviewed the study? 
 
All research in the NHS is looked at by an Independent group of people, called a Research 
Ethics Committee (REC) to protect your safety, rights, wellbeing and dignity.  This study has 
been reviewed and given favorable opinion by the South Central Oxford B Research Ethics 
Committee. In addition approval has been gained from local Research & Development (R&D) 
Offices. 
 
Further Information and Contact Details 
 
If you would like any further information about the study, either now or at time during the 
course of the study, please ask a member of the Research Team: Dr. Angela Gallagher, 
Clinical Research Fellow, Department of Cardiology, Royal Brompton Hospital, Sydney 
Street, London, SW3 6NP. 0207 3528151 ext. 2003. 
 
 
 
Thank you for taking the time to consider this study.  If you do choose to participate, you 
will be given a copy of this information sheet to keep and also a copy of the consent form 
that you will be asked to sign. 
    
 
 
                  
 
 
 
 

 
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Appendix 3. Patient Invitation Letter 
 
 
                 
 
IRAS ID Number: 228728 
 
 
 
PATIENT LETTER 
 
 
Dr <name> 
<address>  
<address>  
<address>  
 
<date> 
 
 
Dear <name>, 
 
A study of Heart Function in patients assessed for Sleep Disordered Breathing (SDB) 
 
We are writing to invite you to consider taking part in the above research study at the Royal 
Brompton & Harefield NHS Foundation Trust. You have been identified as a possible 
participant for this study as you have been referred by your doctor for a sleep study test. 
Taking part in the study is completely voluntary. If you do not wish to be involved, this will 
have no effect on your medical care.  
 
The purpose of this study is to find about the heart function of patients who have been 
referred a sleep study test as part of their normal clinical care. 
 
I have enclosed an information leaflet that explains the study in more depth. If you are 
interested in participating or would like to be contacted with more details please complete 
the tear-off form below and return the letter in the stamped addressed envelope provided or 
contact the research fellow Angela Gallagher on tel. no: 0207 352 8121 ext. 2003. On 
receipt of this form, one of the study team will contact you and provide you with further 
information. 
 
Completion and return of this form does not oblige you in any way to take part in the study 
if you decide you do not wish to. 
 
 
 
 
 
 

 
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Yours sincerely, 
 
 
 
Dr Angela Gallagher 
Clinical Research Fellow 
 
 
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 
- -  
 
I………………………………, am interested and would like member of the study team 
to contact me. 
 
My phone number is…………………………   
 
I understand that this expression of interest places me under no obligation to take part 
in the trial.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix 4. GP Letter 
 
                  
 
 
 
 
Royal Brompton Hospital 
Sydney Street 
London 
SW3 6NP 
 
 
 
IRAS ID Number: 228728 
 
 
GP LETTER 
 
 
Dr <name> 
<address>  
<address>  
<address>  
 
<date> 
 
 
Dear Dr <name>, 
 
Re: Patient Forename SURNAME, DOB, Address 
 
A study of Heart Function in patients assessed for Sleep Disordered Breathing (SDB) 
 
We are writing to inform you that your patient has kindly agreed to participate in the above 
research study at the Royal Brompton & Harefield NHS Foundation Trust. Your patient was 
enrolled into the study on <date>.  We plan to recruit 155 patients into the study and 
collect data over a 12 month period. Ethical approval for this study has been granted by 
South Central Oxford B Research Ethics Committee. 
 
The aim of this study is to determine the prevalence of heart failure with preserved ejection 
fraction (HFpEF) in the cohort of patients being investigated for sleep disordered breathing. 
The patients will be assessed with symptom questionnaires, an ECG, echocardiogram and N-
Terminal Pro-BNP (NT-proBNP) and Growth Differentiation Factor-15 (GDF-15) level when 
attending for their sleep study test. You will be informed of any significant diagnostic 
findings from these tests. We would also like to collect prognostic data on hospitalisation 
and mortality. We will arrange telephone consultations with the patients at 3 monthly 
intervals and may contact you to ask for information about significant medical events that 
may occur during the course of the study.   
 
We shall inform you of any relevant medical changes in the patients’ status that may occur 
during the course of the study.   

 
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If you want any further details about the study, the involvement of your patient, or you wish 
to see a more detailed description of the study, please contact a member of the Research 
team. 
 
Enclosed with this letter is the study Participant Information Sheet (PIS) for your reference.  
 
 
 
Yours sincerely, 
 
 
Dr Angela Gallagher 
Clinical Research Fellow 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix 5. Consent Form 
 
                  
 
IRAS ID Number: 228728 
 
 
 
      
REC Reference Number: 17/SC/0320  
 
Patient Identification Number for this trial: ________ 
                                       
 
 
INFORMED CONSENT FORM 
 
Study Title: A study of Heart Function in patients assessed for Sleep Disordered 
Breathing (SDB) 
 
 
Name of Researcher:  
 
 
Please initial box 
 
1. I confirm that I have read and understand the information sheet dated Day Month Year 
(Version x.x) for the above study and have had the opportunity to consider the 
information, ask questions and have 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 any of my medical notes and data collected during 
the study may be looked at by responsible individuals from Royal Brompton & Harefield 
NHS Foundation Trust, Imperial College London or from regulatory authorities where it is 
relevant to my taking part in 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. 
 
 
 
 
 
 
 
 
 
 

 
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________________________ 
________________ 
____________________ 
Name of Patient 
 
 
Date 
Signature
 
 
 
 
 
 
_________________________ 
________________ 
____________________ 
Name of person taking consent 
Date 
 
Signature 
 
 
 
 
 
When completed 1 copy for patient; 1 copy for researcher; 1 (original) copy to be kept with 
hospital