Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Heart Failure With Preserved Ejection Fraction (HFpEF) Pathophysiology Study. (IDENTIFY-HF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03186833
Recruitment Status : Completed
First Posted : June 14, 2017
Last Update Posted : September 27, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospitals Coventry and Warwickshire NHS Trust

Brief Summary:

The study addresses the hypothesis that a gradual build-up in arterial resistance and microvascular endothelial dysfunction due to common comorbidities such as hypertension and diabetes mellitus, on top of age related vascular and cardiac changes (mainly fibrosis and hypertrophy), is responsible for HFpEF. The HFpEF syndrome is commonly seen in elderly subjects (often females) with hypertension and diabetes.

The investigators will investigate the vascular function, cardiovascular performance and myocardial fibrosis in different cohorts of subjects to try and prove this hypothesis. There will be 5 groups of subjects, all ≥ 70 years of age, as follows:

A) Normal healthy volunteers without major comorbidities including hypertension or diabetes B) Patients with hypertension only (without diabetes mellitus) C) Patients with hypertension AND diabetes mellitus D) Patients with HFpEF. E) A parallel group of patients with Heart Failure with reduced Ejection Fraction (HFrEF) group.

Arterial resistance measured by pulse wave velocity will be the primary measure and will be compared between groups A to D. A separate comparison will be made between groups D and E. Other secondary measures will focus on endothelial function (Laser Doppler measurements) and other cardiovascular performance measures (peak VO2 by CPEX, 6-minute walk distance). Bloods samples will be taken for NT-proBNP, high sensitivity Troponin T, Galectin 3 and also stored for testing later for vascular biomarkers.


Condition or disease Intervention/treatment
Heart Failure With Normal Ejection Fraction Other: no intervention

Detailed Description:

The study will be a pathophysiological, single-centre, observational study, in which all 4 groups, including the parallel-group will be investigated in terms of qualitative-, echocardiographic-, arterial resistance, exercise testing (CPEX and 6-MWT), endothelial dysfunction assessment by Laser Doppler and vascular biomarker measurements. We intend to investigate if there is increasing arterial resistance from group "A" to group "D" and a significant difference in arterial resistance between groups "D" and "E" by measuring the PWV.

Primary Outcome Our primary outcome will be a difference in arterial resistance between the groups and the parallel group, as measured by aortic PWV.

Secondary Outcomes

The secondary outcomes are to assess and compare endothelial function and cardiovascular performance in all groups as measured by the following:

  • Blood tests: NTproBNP, Galectin-3
  • Urinalysis: Albumin, Creatinine and Metabolite profiles ("metabolomics"), related to cardiovascular risk and insulin resistance
  • Transthoracic echocardiography (TTE) indices of LV diastolic function, tissue Doppler imaging and strain rate imaging
  • Exercise tolerance: 6-minute walk test and a Cardiopulmonary Exercise Test (CPEX)
  • Microvascular function: Laser Doppler

Layout table for study information
Study Type : Observational
Actual Enrollment : 85 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: The Heart Failure With Preserved Ejection Fraction (HFpEF) Pathophysiology Study. Does Ageing Coupled With Vascular Effects of Comorbidities Lead to HFpEF? An In-depth Understanding From a Tertiary Centre
Actual Study Start Date : June 6, 2017
Actual Primary Completion Date : December 31, 2018
Actual Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Group/Cohort Intervention/treatment
Group A
males or females aged > 70 years without major systemic comorbidities (resting blood pressure <140/90 mmHg, no history diabetes mellitus according to WHO criteria).
Other: no intervention
no intervention

Group B
males or females aged >70 years with hypertension, defined as a documented blood pressure of Systolic Blood Pressure (SP >140 mmHg or >90mmHg Diastolic Blood Pressure) without diabetes mellitus and HF defined as: a) relevant symptoms/signs/radiographic findings as indicated by Boston criteria b) need for diuretic therapy.
Other: no intervention
no intervention

Group C
male or female aged > 70 years with diabetes mellitus (defined according to the World Health Organization (WHO)) AND hypertension, without HF defined as: a) relevant symptoms/signs/radiographic findings as indicated by Boston criteria38 b) need for diuretic therapy.
Other: no intervention
no intervention

Group D
male or female aged >70 years with HFPEF, defined as signs and symptoms of HF with LVEF>50% and raised natriuretic peptides (BNP>35pg/ml or NT-proBNP>125pg/ml) along with one other criteria: i) structural heart disease (left atrial enlargement or left ventricular hypertrophy) on TTE, ii) evidence of LV diastolic dysfunction based on ESC Guidelines 2016, or iii) hospitalization with heart failure within 12 months prior to study entry.
Other: no intervention
no intervention

Group E
male or female aged >70 years with HFREF, defined as HF with LVEF <40% on TTE)
Other: no intervention
no intervention




Primary Outcome Measures :
  1. Arterial stiffness [ Time Frame: 30 minutes ]
    As measured by the Pulse Wave Velocity


Secondary Outcome Measures :
  1. Endothelial function [ Time Frame: 15 minutes ]
    Laser Doppler Flowmetry

  2. Blood test [ Time Frame: 5 minutes ]
    NT-proBNP

  3. Blood test, marker of fibrosis [ Time Frame: 15 minutes ]
    Galectin-3

  4. Transthoracic echocardiography [ Time Frame: 45 minutes ]
    Left ventricular systolic and diastolic function, Left atrial size, Valvular assessments, Tissue Doppler imaging, strain rate imaging

  5. Exercise Tolerance [ Time Frame: 30 minutes ]
    Cardio-pulmonary exercise

  6. Urinalysis [ Time Frame: 10 minutes ]
    Albumin, Creatinine and Metabolite profiles ("metabolomics"), related to cardiovascular risk and insulin resistance


Biospecimen Retention:   Samples Without DNA
Serum analysis for galectin-3


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Group A: males or females aged > 70 years without major systemic

Group B: males or females aged >70 years with hypertension

Group C: male or female aged > 70 years with diabetes mellitus AND hypertension, without HF

Group D: male or female aged >70 years with HFpEF

Group E: male or female aged >70 years with HFREF, defined as HF with LVEF <40% on TTE)

Criteria

Inclusion Criteria:

  • Group A: males or females aged > 70 years without major systemic comorbidities (resting blood pressure <140/90 mmHg, no history diabetes mellitus according to WHO criteria).
  • Group B: males or females aged >70 years with hypertension, defined as a documented blood pressure of Systolic Blood Pressure (SP >140 mmHg or >90mmHg Diastolic Blood Pressure) without diabetes mellitus and HF defined as: a) relevant symptoms/signs/radiographic findings as indicated by Boston criteria b) need for diuretic therapy.
  • Group C: male or female aged > 70 years with diabetes mellitus (defined according to the World Health Organization (WHO)) AND hypertension, without HF defined as: a) relevant symptoms/signs/radiographic findings as indicated by Boston criteria38 b) need for diuretic therapy.
  • Group D: male or female aged >70 years with HFPEF, defined as signs and symptoms of HF with LVEF>50% and raised natriuretic peptides (BNP>35pg/ml or NT-proBNP>125pg/ml) along with one other criteria: i) structural heart disease (left atrial enlargement or left ventricular hypertrophy) on TTE, ii) evidence of LV diastolic dysfunction based on ESC Guidelines 2016, or iii) hospitalization with heart failure within 12 months prior to study entry.
  • Group E (parallel group): male or female aged >70 years with HFREF, defined as HF with LVEF <40% on TTE)

Exclusion Criteria:

  • Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within 3 months, or urgent percutaneous coronary intervention (PCI) within 30 days of entry.
  • Patients who have had an MI, coronary artery bypass graft (CABG) or other event within the 6 months prior to entry unless an echo measurement performed after the event confirms a LVEF ≥50%.
  • Current acute decompensated HF requiring intravenous therapy
  • Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, haemoglobin (Hb) <10 g/dl, or body mass index (BMI) > 40 kg/m2.
  • Severe left-sided valvular heart disease
  • Hypotension (systolic BP <100 mm Hg).
  • Severe Liver failure
  • Primary pulmonary hypertension
  • Bedbound/immobile patients
  • Chronic renal failure with creatinine of >250 μmol/l
  • Significant Peripheral Vascular Disease (PVD), defined as having signs of absent peripheral pulses or reported claudication pain or documented history of PVD

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03186833


Locations
Layout table for location information
United Kingdom
University Hospital Coventry and Warwickshire
Coventry, United Kingdom, CV2 2DX
Sponsors and Collaborators
University Hospitals Coventry and Warwickshire NHS Trust
Investigators
Layout table for investigator information
Study Director: Prithwish Banerjee, MD, FRCP University Hospital Coventry and Warwickshire, Coventry University
Study Chair: Francesco Cappuccio, MD, MSc, DSc University of Warwick
Study Chair: Martin Weickert, MD, FRCP University Hospital Coventry and Warwickshire
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University Hospitals Coventry and Warwickshire NHS Trust
ClinicalTrials.gov Identifier: NCT03186833    
Other Study ID Numbers: PB186316
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Failure
Heart Diseases
Cardiovascular Diseases