A Retrospective Observational Analysis of a Cohort With Heart Failure With Preserved Ejection Fraction From a BNP Pathway Clinic
Conditions: Heart Failure With Preserved Ejection Fraction
Sponsor: Portsmouth Hospitals NHS Trust

 
 
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Study Title:  A retrospective observational analysis of a cohort with Heart 
Failure with Preserved Ejection Fraction from a BNP pathway clinic 
IRAS ID: 262060 
Date and Version No: 04/10/2019 Version: 1.0 
              
Chief Investigator: 
Dr Kaushik Guha  
Consultant Cardiologist 
Cardiology, Level C, Queen Alexandra Hospital 
Southwick Hill Road, Cosham, PO6 3LY 
Kaushik.Guha@porthosp.nhs.uk 
Investigators:  
P. Evans – Trainee Clinical Scientist 
Dr P. Kalra – Consultant Cardiologist 
E. Lane – Chief Cardiac Physiologist 
Martin Stout – Clinical Academic Senior Lecturer 
Sponsor:  
Portsmouth Hospitals NHS Trust  
Funder (if applicable): 
This study is funded through The Scientist Training Programme 
(STP) as part of Mr Paul Evans’s Clinical Scientist training. 
Signatures:  
The approved protocol should be signed by author(s) and/or 
person(s) authorised to sign the protocol 
 
 
 
  
Protocol 
Development 
Team: 
Co-Investigators 
as 
listed 
above, 
Jamie 
Sergeant 
(Biostatistician at University of Manchester) and patient representative team (Sharon Court, 
Anna Glanville-Hearson, Chris Staples, Joleen Tobias, Noreen Cole, Bill Ware and Darren 
Jenkinson). 
 
 
 
 
 
 
 

 
 
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TABLE OF CONTENTS 
1. Amendment History ……………………………………………………………….4 
2. Synopsis …………………………………………………………………………….5 
3. Abbreviations ………………………………………………………………………7 
4. Lay Summary ……………………………………………………………………….8 
5. Background & Rationale …………………………………………………………9 
6. Preliminary Studies ……………………………………………………………...11 
7. Aims & Objectives ……………………………………………………………….11 
7.1 Primary Objective ……………………………………………………………11 
7.2 Secondary Objectives ………………………………………………………11 
8. Study Design ……………………………………………………………………...11 
8.1 Summary of Study Design …………………………………………………11 
8.2 Primary and Secondary Outcome Measures …………………………...11 
9. Study Participants …………………………………………………………….....12 
9.1 Study Setting …………………………………………………………………12 
9.2 Overall Description of Study Participants ………………………………12 
9.3 Eligibility Criteria …………………………………………………………….12 
10. Sampling …………………………………………………………………………..12 
11. Study Procedures ………………………………………………………………..12 
11.1 Recruitment ……………………………………………………………….13 
11.2 Screening and Enrolment ………………………………………………13 
11.3 Randomisation ……………………………………………………………13 
11.4 Study Assessments ……………………………………………………..13 
12. Data Handling and Record Keeping …………………………………………..14 
12.1 Data Collection Forms …………………………………………………..14 
12.2 Data Managements ………………………………………………………14 

 
 
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13. Data Analysis ……………………………………………………………………..14 
13.1 Description of Analysis Populations …………………………………14 
13.2 Analysis of Endpoints …………………………………………………..14 
13.3 Procedure for Dealing with Missing, Unused and Spurious Data.15 
13.4 Procedure for Reporting any Deaviation(s) from the Original 
Statistical Analysis Plan ……………………………………………………15 
13.5 Interim Analysis and Criteria for Early Study Termination ……….15 
14. Ethics ……………………………………………………………………………….15 
14.1 Participant Confidentiality ……………………………………………...15 
14.2 Other Ethical Considerations ………………………………………….15 
14.3 Declaration of Helsinki ………………………………………………….15 
14.4 ICH Guidelines for Good Clinical Practice …………………………..15 
15. Patient Public Involvement (PPI) ………………………………………………16 
15.1 Study Design ……………………………………………………………...16 
15.2 Study Implementation …………………………………………………...16 
15.3 Dissemination …………………………………………………………….16 
16. Financing and Insurance ……………………………………………………….16 
17. Timetable and Organisational Chart ………………………………………….17 
18. Resources, Equipment and Physical Facilties ……………………………..17 
19. Dissemination and outcome …………………………………………………...17 
20. References ………………………………………………………………………...18 

 
 
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1. 
AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes 
made 
 
 
 
 
 

 
 
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2. 
SYNOPSIS 
 
Study Title 
A retrospective observational analysis of a cohort with Heart Failure 
with Preserved Ejection Fraction from a BNP pathway clinic 
Problem statement 
Heart failure with preserved ejection fraction (HFpEF) is a complex 
condition with various causes that is not yet fully understood. Most 
significantly there is no single method of diagnosing or treating the 
condition. Recently a novel non-invasive diagnostic criterion to predict 
the likelihood of HFpEF was proposed by Reddy et al. (2018) called 
H2FPEF. The main limitation of this study was the use of a single 
centre population from the Mayo clinic in Rochester, US. Another 
limitation is that the H2FPEF diagnostic criterion consists of common 
and often co-existing conditions which could as a result overestimate 
HFpEF probability. The aim of the investigators is to retrospectively test 
the H2FPEF criteria on the population at Queen Alexandra Hospital 
(QAH) in Portsmouth, which is of a lower socio-economic status and 
greater ethnic diversity. Implications of the project if H2FPEF is proved 
to be generalizable to the population is that it can be used within the 
Trust and rolled out to others. This would allow diagnosis to be made 
quicker and more cost effectively using echocardiography and without 
the need for invasive cardiac catheterisation. On the other hand if 
H2FPEF is found not to be applicable to the population then further 
research would be required to find the ideal diagnostic tool. 
Research question / 
hypothesis 
The investigator’s hypothesis is that when H2FPEF criteria is compared 
against retrospectively held data for the patient population at QAH that 
this will overestimate the probability of HFpEF 
Study Design 
The study is a single-centre retrospective observational analysis 
Study Participants 
Patients who attended heart failure clinics at Queen Alexandra Hospital 
between January 1st 2016 – December 31st 2016 
Planned Sample Size 
2000 
Follow-up duration 
1 year 
Planned Study 
Period 
04/10/2019 – 30/04/2020 
Primary Objective 
The primary objective of the investigator’s project is to test if the 
H2FPEF score accurately predicts HFpEF on the population at Queen 
Alexandra Hospital. 
Secondary 
Objectives 
•Investigate if H2FPEF overestimates HFpEF diagnosis on the patient 
population when compared against known BNP levels. 
•To evaluate if H2FPEF can be validated on the patient population and 
be utilised to improve patient pathway for HFpEF. 
•To monitor patient responses to treatments and care for one year. 
Primary Outcome 
Measure 
To assess the predictive accuracy of H2FPEF at predicting HFpEF on 
the patient population as calculated by logistic regression, with 
diagnostic accuracy being assessed by sensitivity and specificity 
calculations. 
Secondary Outcome 
Measures 
• ANOVA will be performed to provide one simultaneous evaluation of 
the data to determine if there is a significant difference between 

 
 
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H2FPEF score and diagnosis of HFpEF. 
•To assess number of hospital admissions and any changes in 
treatment/ care after one year for the population. 

 
 
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3. 
ABBREVIATIONS 
List all abbreviations / acronyms in alphabetical order, for example: 
AF 
Atrial Fibrillation 
ANOVA 
Analysis of Variance 
BMI 
Body Mass Index 
BNP 
B-type natriuretic peptide 
BSE 
British Society of Echocardiography 
ECG 
12 lead Electrocardiogram 
E/e’ 
Echocardiographic measure of ventricular filling pressures 
EF 
Ejection Fraction 
GCP 
Good Clinical Practise 
H2FPEF 
New diagnostic criteria for HFpEF (Heavy, ≥2 Hypertensive medications, atrial 
fibrillation, pulmonary hypertension, elderly, elevated filling pressure 
HFmrEF 
Heart Failure with Mid-Range Ejection Fraction 
HFpEF  
Heart Failure with Preserved Ejection Fraction 
HFrEF  
Heart Failure with Reduced Ejection Fraction 
LV 
 
Left Ventricle 
NHS 
 
National Health Service 
NIHR  
National Institute for Health Research 
NT-proBNP 
N-Terminal pro-B-type Naturetic Peptide 
PASP  
Pulmonary Artery Systolic Pressure 
PPI 
 
Patient Public Involvement 
QAH 
 
Queen Alexandra Hospital 
STP 
            Scientist Training Programme 

 
 
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4. 
LAY SUMMARY  
 
Heart failure with preserved ejection fraction (HFpEF) is a complex condition with various 
causes that is not yet fully understood. Heart failure is a long-term condition where the heart 
is unable to pump enough blood to meet the demands of the body. Heart failure is then 
categorised based on ejection fraction, which is the percentage of how much blood the heart 
pumps out each beat. HFpEF is a form of heart failure were the heart still pumps >50% of its 
volume each heart beat. Most significantly there is no method of diagnosing or treating the 
condition. A recent project proposed non-invasive criteria using routinely collected data to 
predict the likelihood of HFpEF. This was termed H2FPEF and uses: weight, number of 
hypertensive medications prescribed, age, presence of atrial fibrillation, ventricular filling 
pressures and pulmonary hypertension. The main limitation of this study is the use of a 
single centre population from the Mayo clinic in Rochester, US. Another limitation is that the 
H2FPEF criterion consists of common conditions which could as a result overestimate 
HFpEF probability. The aim of the investigators is to test the H2FPEF criteria on previous 
data already held from heart failure clinic database at Queen Alexandra Hospital (QAH) in 
Portsmouth. Implications of the project if H2FPEF is proved to be accurate on the population 
is that it can be used within the Trust and other trusts. This would allow HFpEF to be 
identified quicker at a reduced cost for the trust and reduced risk for the patient avoiding 
invasive investigations. On the other hand if H2FPEF is found not to be applicable to the 
population then further research would be required to find the ideal tool or method to identify 
HFpEF. A follow-up of patients is also proposed to monitor any long-term outcomes and how 
they respond to treatments. 

 
 
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5. 
BACKGROUND AND RATIONALE 
 
Epidemiology: 
In the UK heart failure is the biggest cause of hospital admissions in people aged over 65, 
and is associated with poor morbidity and mortality outcomes if not managed effectively 
(National Institute for Health Care and Excellence [NICE], 2015). Heart failure is a complex 
heterogeneous condition characterised by typical symptoms and signs indicative of structural 
or functional cardiac abnormalities which despite normal filling pressures results in failure to 
deliver oxygen at a rate proportionate to the demands of metabolizing tissues (Ponikowski et 
al., 2016). Typical symptoms of heart failure include shortness of breath, reduced exercise 
tolerance, fatigue, orthopnoea and paroxysmal nocturnal dyspnoea; with signs such as 
peripheral oedema, functional mitral regurgitation, murmur and elevated jugular venous 
pressure (Allen et al., 2015). All of these signs and symptoms are however not specific to 
heart failure and could be caused by alternative conditions which makes diagnosis difficult 
(Oren and Goldberg, 2017).   
 
Heart failure is categorised based on ejection fraction (EF);  
• 
EF <40% - Heart failure with reduced ejection fraction (HFrEF) 
• 
EF 40-49% - Heart failure with mid-range ejection fraction (HFmrEF) 
• 
EF ≥50% - Heart failure with preserved ejection fraction (HFpEF) 
 
The aetiology of HFpEF is less well understood compared to HFrEF because it is not a 
uniform disease and patients usually have a combination of morbidities, but there is now a 
greater focus on it as it is just as prevalent (Lam et al., 2011; Dunlay et al., 2017; van Empel 
and Rocca, 2018). No effective therapies have as yet been found for management of HFpEF, 
with therapies that have proven effective in reducing mortality and morbidity in HFrEF 
patients not having the same effect for HFpEF patients, making this an important research 
focus (O’Gallagher and Shah, 2018). Approximately half of heart failure patients are now 
believed to have HFpEF, with the prevalence increasing and set to become the dominant 
form of heart failure as the condition becomes better understood and diagnosed (Banerjee, 
2016; Deaton et al., 2018). 
 
Background: 
  
HFpEF was previously characterised as ‘diastolic dysfunction’ but this terminology was 
changed as it was found that diastolic dysfunction was also seen in patients with ‘systolic 
dysfunction’ (Borlaug and Paulus, 2011). Myocardial stiffness which leads to increased filling 
pressures is a common pathophysiologic attribute of HFpEF despite its multifactorial 
aetiology (Telles and Marwick, 2018). Other common conditions associated with HFpEF 
include: atrial fibrillation (AF), chronotropic incompetence, pulmonary hypertension, right 
ventricular dysfunction and endothelial dysfunction; with common non-specific risk factors 
such as: age, gender, hypertension, obesity, diabetes, metabolic syndrome and renal failure 
(Borlaug, 2014; Ferrari et al., 2015; Harper et al., 2018). This complex heterogeneity of 
HFpEF which is not yet fully understood highlights the difficulty that clinicians have in being 
able to diagnose the condition. 
Diagnosis of HFpEF is difficult and as of yet there is no test to confirm diagnosis, with current 
guidelines saying initial diagnosis should include the presence of typical signs and 
symptoms, an elevated B-type natriuretic peptide (BNP) (>35 pg/mL and/or N-Terminal pro-

 
 
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B-type Natriuretic Peptide [NT-proBNP] >125 pg/mL) and ejection fraction ≥50% (Lekavich et 
al., 2015; Ponikowski et al., 2016). Echocardiography is the preferred method of assessing 
for HFpEF due to it being widely available, non-invasive, and able to provide immediate 
results (Ponikowski et al., 2016). Recent studies comparing the use of echocardiography 
against ‘gold standard’ invasive cardiac catheterisation to assess cardiac filling pressures 
found echocardiography to be just as accurate and reliable (Anderson et al., 2017; Lancellotti 
et al., 2017). Implications of this research would be that patients could be assessed as 
outpatients by focus echocardiography rather than invasively in the cardiac catheterisation 
lab, which would improve patient experience, enhance patient outcomes and prove cost-
effective for trusts. 
 
In response Reddy et al (2018) recently proposed non-invasive diagnostic criteria called 
H2FPEF which assesses patients based on body mass index (BMI), the number of 
hypertensive medications they take, presence of AF, pulmonary pressure, age and filling 
pressure. The advantage of the H2FPEF score is that it uses only non-invasive 
echocardiography data alongside routine clinical data making it easy to derive. However one 
key limitation of their study is the population they used was all from the Mayo clinic and so 
the generalisability of their results has not been tested for other populations, such as those of 
lower socioeconomic status like in Portsmouth. A further limitation is the parameters chosen 
to create H2FPEF are all relatively common morbidities and usually co-exist, making it likely 
that it will over diagnose HFpEF.  
 
Research questions:  
The main research question the investigators are investigating is whether the H2FPEF 
criteria proposed by Reddy et al. (2018) is an accurate predictor of HFpEF on the patient 
population at QAH. In the original paper by Reddy et al. (2018) they created and tested 
H2FPEF criteria on their study population from the Mayo clinic, Rochester, US. This 
population is predominantly Caucasian and of a high socioeconomic status and so lacks 
generalisability. In response the investigators are testing the H2FPEF criteria on the 
population at QAH which is of a lower socioeconomic status, to investigate if it remains an 
accurate predictor of HFpEF. 
 
Risks:  
As the investigators study is a retrospective observational study there are no risks to 
participants, and all data obtained will be anonymised with no personally identifiable data 
being analysed. 
 
Impact:  
The main outcome of this project will be whether the H2FPEF score is able to accurately 
predict HFpEF on the patient population of QAH, Portsmouth or if it overestimates diagnosis. 
If the investigator’s research hypothesis is accepted then future research will be required to 
either optimise H2FPEF score or to develop new HFpEF diagnostic criteria. The enigma of 
HFpEF would continue to be the focus of research with the aim of developing an applicable 
clinical diagnostic tool. Alternatively if the investigators accept the null hypothesis then the 
H2FPEF score will have been validated on the population and would have the potential to be 
used by QAH and other trusts. Future research would then be required on other populations 
to further assess the generalisability of H2FPEF. The implications of this would be that 
patients are able to be diagnosed with HFpEF quicker and non-invasively requiring just an 
ECG, a focus echocardiogram and a routine clinical examination. Consequently invasive 

 
 
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cardiac catheterisation would not be required for diagnosis which would improve patient 
outcomes and patient service experience, as well as being cost-effective for the trust. 
 
6. 
PRELIMINARY STUDIES  
This is the first study undertaken in response to the recent study by Reddy et al. (2018). 
7. 
AIMS AND OBJECTIVES 
7.1 
Primary Objective 
 
The primary objective of the investigator’s project is to test if the H2FPEF score proposed by 
Reddy et al (2018) accurately predicts HFpEF on the population at QAH, Portsmouth.  
 
7.2 
Secondary Objectives 
 
The investigator’s secondary objectives are to: 
 
• Investigate if H2FPEF overestimates HFpEF diagnosis on the patient population when 
compared against known BNP levels. 
• To evaluate if H2FPEF can be validated on the patient population and be utilised to improve 
patient pathway for HFpEF. 
• Follow patients up over one year to monitor outcomes 
 
8. 
STUDY DESIGN 
8.1 
Summary of Study Design 
 
Data will be collected retrospectively from consecutive patients who meet the inclusion 
criteria to calculate a H2FPEF score: weight, number of hypertensive medications 
prescribed, presence of AF or not, presence of pulmonary hypertension or not, age and filling 
pressure. A total H2FPEF score will then be calculated for each patient as per Reddy et al. 
(2018) protocol: BMI > 30 kg/m2 (2 points), ≥2 anti-hypertensive medications (1 point), 
paroxysmal or permanent AF (3 points), pulmonary artery systolic pressure >35mmHg (1 
point), age >60 years (1 point), E/e’ filling pressure > 9 (1 point).   
 
8.2 
Primary and Secondary Outcome Measures 
Primary outcome measure  
 
Accuracy of H2FPEF at predicting HFpEF on the patient population will be assessed 
as specificity and sensitivity as calculated by logistic regression 
 
Secondary outcome measure 

 
 
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 
Investigate if H2FPEF overestimates HFpEF diagnosis on the patient population 
when compared against known BNP levels. 
 
To evaluate if H2FPEF can be validated on the patient population and be utilised to 
improve patient pathway for HFpEF. 
 
To assess patient outcomes after one year, including any changes in medication or 
treatment as well as number of hospital admissions and reported symptoms. 
 
9. 
STUDY PARTICIPANTS 
9.1 
Study Setting 
Participants will have attended a heart failure clinic with a cardiology consultant at QAH 
between 01/01/2016-31/12/2016. 
9.2 
Overall Description of Study Participants 
All participants will be patients who have attended heart failure clinics at QAH between 
01/01/2016 – 31/12/2016. Eligibility will be met by the inclusion and exclusion criteria. 
9.3 
Eligibility Criteria 
Inclusion Criteria 
The participant must meet ALL of the following criteria to be considered eligible for the study: 
 
Age 18-85yrs inclusive  
 
Currently or previously attended a heart failure clinic with a cardiology consultant at 
QAH 
 
Had an echocardiogram, ECG, BNP blood biomarker test in addition to a routine clinical 
evaluation (including age, weight and number of hypertensive medications) during 
January 1st 2016 – December 31st 2016.  
 
Exclusion Criteria 
The participant may not enter the study if ANY of the following apply: 
 
 
Known structural heart disease 
 
Significant heart valve disease (greater than mild stenosis, greater than moderate 
regurgitation) 
 
Pulmonary arterial hypertension 
 
Constrictive pericarditis 
 
Pre-existing cardiomyopathy 
 
Heart transplantation 
 
10. 
SAMPLING 
All eligible participants between 01/01/2016 – 31/12/2016 will be included in the study. This 
is to allow sufficient time to be able to follow patient outcomes up. Outcomes such as any 
changes to medication and treatment as well as any hospital admissions and reported 
symptoms will be assessed. Including patients from 2016 will allow us to assess these 
outcomes one year after their clinic appointment. 
 

 
 
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11. 
STUDY PROCEDURES 
 
All data collection will be performed retrospectively. All data will be obtained from the heart 
failure clinic database. One year follow-up to assess patient outcomes will also be performed 
retrospectively where data is available. 
 
11.1    Recruitment 
Data will be collected retrospectively from eligible participants with data already held on the 
heart failure clinic database. A member of the patient’s direct clinical care team will identify 
the participants who meet the eligibility criteria for data extraction. 
All data obtained will be anonymised with no patient identifiable data being recorded as part 
of the initial part of the study. A separate pseudonymised document including patient hospital 
number only will recorded to allow clinical outcome data to be obtained for the follow-up 
study. 
11.2   Screening and Enrolment 
The heart failure clinic database will be screened during the study dates for eligible 
participants. Any eligible participants will then be included in the study, with only the relevant 
clinical data being recorded. Patients will be anonymised, with a separate document detailing 
pseudonymisation. No personally identifiable data will be included in the analysis or results. 
 
11.3 Randomisation 
N/A 
 
11.4 Study Assessments 
All data will be collected retrospectively from the heart failure clinic database at QAH. Data 
will be collected on: weight, number of hypertensive medications prescribed, presence of AF 
or not, presence of pulmonary hypertension or not, age and filling pressure. These are the 
factors that make up Reddy et al. (2018) H2FPEF score. In addition the patient’s ejection 
fraction and BNP will also be recorded as a measure to determine HFpEF diagnosis. All data 
will be anonymised and recorded on a Microsoft Excel spreadsheet, with a separate 
document documenting the pseudonymised data. All data will have been routinely collected 
as part of the heart failure patient pathway: 
 
Echocardiography - A non-invasive ultrasound test which takes approximately 30 
minutes and has no radiation risk. Echocardiogram results will be used to ascertain 
pulmonary pressure and diastolic filling pressure. This will have been performed 
routinely as part of the heart failure patient pathway at QAH. All scans will have been 
performed on GE Healthcare Vivid echocardiography machines by a trained 
sonographer from the Cardiac Investigations Unit at QAH. A standard operating 
procedure exists for performing echocardiogram. In accordance with local practice 
personal protective equipment is worn for this test. ECG electrodes and ultrasound 
gel can be a potential risk to the patient with regards to dermatological 
reaction/sensitivity, however both are hypoallergenic substances. 
 
12-lead electrocardiogram (ECG) - A non-invasive test of the electrical conduction of 
the heart assessing heart rate and rhythm. ECG results will be used to determine if 
the patient is in AF or not. All ECG will have been recorded with the use of the 
hospitals standard machine (MAC 1200, GE Healthcare). All tests will have been 

 
 
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performed by trained staff within the Cardiac Investigations Unit at QAH. Standard 
operating procedures are followed to perform ECG. ECG will have been performed 
routinely as part of the heart failure patient pathway at QAH. 
 
Weight - Using a standard trust scale (Marsden Weighing Company, UK) 
 
Age and Number of hypertensive medications taken - Assessed from patient records 
   
12. 
DATA HANDLING AND RECORD KEEPING 
12.1 
Data Collection Forms 
All data will be collected and stored electronically using the following format. 
 
 
 
12.2     Data Management 
Data management will be conducted by the investigators using clinical, access databases and 
excel documents. All study data obtained will be documented electronically on a Microsoft 
Excel document on a personal Trust drive at the investigator site and will be accessible only 
by the research team. Data will be monitored at the investigator site. The participants will be 
identified by a study specific participants number and/or code in any database.  The name 
and any other identifying detail will not be included in any study data electronic file.  
 
13. 
DATA ANALYSIS 
13.1      Description of Analysis Populations  
All eligible participants will be analysed the same as per protocol.  
Participant 
ID 
BMI    
(>30Kg/m2) 
Yes/No 
≥2 
anti-
hypertensive 
medications 
Yes/No 
AF 
Yes/
No 
PASP  
>35mmHg 
Yes/No 
Age 
(>60 
years) 
Yes/No 
E/e’ 
(>9) 
Yes/No 
H2FPEF 
Score 
Patient 
Outcomes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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13.2      Analysis of Outcome Measures  
To determine if the H2FPEF score was accurate in predicting HFpEF the calculated H2FPEF 
score will be compared against BNP blood test results using the cut-off points stated by the 
European Society of Cardiology (Ponikowski et al., 2016). To test our hypothesis an analysis 
of variance test (ANOVA) will be performed to provide one simultaneous evaluation of the 
data to determine if there is a significant difference between H2FPEF score and diagnosis of 
HFpEF. A logistic regression analysis will then be carried out to give an odds ratio and 
provide a predictive analysis of the data. All statistical analysis will be performed using SPSS 
software. 
13.3     Procedure for Dealing with Missing, Unused and Spurious Data  
Only data relating to the H2FPEF score will be collected; as per inclusion/ exclusion criteria 
no patient will be included in the study unless they had all of the necessary tests at their clinic 
visit. If no data is available for one year follow-up then the patient will be excluded from this 
assessment, but will still be included in the initial assessment of the H2FPEF diagnostic 
criterion. 
13.4     Procedures for Reporting any Deviation(s) from the Original Statistical 
Analysis Plan 
If any queries regarding statistical analysis are raised by any of the study team then a 
consultation with a qualified statistician will be undertook to find a suitable solution that all 
members are satisfied with. 
13.5      Interim analysis and criteria for early study termination  
N/A 
 
14. 
ETHICS 
The main ethical issue associated with the investigator’s study design is due to the 
retrospective nature of the data collection meaning that consent is unable to be obtained. 
However, all data is already stored on the heart failure clinic database at QAH from when 
they will have attended, with all tests being performed routinely as part of their clinical patient 
pathway. In addition no personally identifiable data will be used during analysis or results of 
the study. Patients will be anonymised during the initial data collection, with a separate 
document detailing pseudonymisation using patient hospital number only. 
 
14.1 
Participant Confidentiality 
The study staff will ensure that the participants’ anonymity is maintained. Only the relevant 
clinical data will be collected, and will only be accessed by members of the research team that 
are involved in the clinical care and would have access anyway. All documents will be stored 
securely on secured personal hospital drives with password protection and only accessible by 
study staff and authorised personnel. The study will comply with the Data Protection Act 
which requires data to be anonymised as soon as it is practical to do so.   
14.2     Other Ethical Considerations 
N/A 
14.3     Declaration of Helsinki 
Where appropriate the study protocol will be carried out in accordance with the Declaration of 
Helsinki: No unnecessary suffering will be caused to participants and the benefits of the study 

 
 
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outweigh any risks. 
14.4     ICH Guidelines for Good Clinical Practice 
All staff involved in the study will be GCP trained as per NIHR and will be monitored by the 
sponsor to ensure adherence to GCP.  
 
15. 
PATIENT PUBLIC INVOLVEMENT (PPI) 
 
15.1    Study design 
This proposal originated from clinicians, with the proposal being presented to the PPI team at 
QAH for review. Review from PPI team was positive with agreement of the research 
background and requirement, as well as retrospective study design. Lay people will not be 
participating in data collection or analysis, but will be included as part of the ethical review 
panel and forming of lay summaries. 
15.2    Study implementation 
Public and patient involvement will be considered before data collection begins. Patient 
Research Ambassadors have been presented with and discussed to give their input and 
advice. 
15.3    Dissemination 
Initial study write-up will be submitted to Manchester Metropolitan University to satisfy the 
major project module of the primary investigators MSc programme. Results of the study will 
be presented at local and national conferences, as well as being submitted for journal 
publication. Patient Research Ambassadors will be invited for advice on areas for public 
dissemination of results. 
 
16. 
FINANCING AND INSURANCE 
 
This study is funded through The Scientist Training Programme (STP) as part of Mr Paul 
Evans’s Clinical Scientist training. Portsmouth Hospitals NHS Trust will be the sponsor of this 
study. 
 

 
 
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17. 
TIMETABLE AND ORGANISATIONAL CHART 
 
18. 
RESOURCES, EQUIPMENT AND PHYSICAL FACILITIES 
All of the study protocol will be carried out on a Portsmouth Hospitals NHS Trust computer at 
QAH 
19. 
DISSEMINATION AND OUTCOME 
Initial study write-up will be submitted to Manchester Metropolitan University to satisfy the 
major project module of the primary investigators MSc programme. Applications will be made 
to present study results at local level at Portsmouth Hospitals NHS Trust Healthcare Scientist 
conferences, as well as national conferences such as BSE. Final write-up of the study will 
also be submitted for journal publication. 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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20. 
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