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

NCT03186833 | Completed

• 1 other identifier: PB186316
• Study Type: observational
• Target: 85
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure With Normal Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Arterial stiffness

  As measured by the Pulse Wave Velocity

  30 minutes

Secondary Outcomes (6)

• Endothelial function

  15 minutes

• Blood test

  5 minutes

• Blood test, marker of fibrosis

  15 minutes

• Transthoracic echocardiography

  45 minutes

• Exercise Tolerance

  30 minutes

Study Arms (5)

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

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

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

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

Group E

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

Other: no intervention

Interventions

no intervention OTHER

no intervention

Group A; Group B; Group C; Group D; Group E

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)
• 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)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospitals Coventry and Warwickshire NHS Trust: lead

Study Sites (1)

University Hospital Coventry and Warwickshire

Coventry, CV2 2DX, United Kingdom

Location

Related Publications (1)

• Ali D, Callan N, Ennis S, Powell R, McGuire S, McGregor G, Weickert MO, Miller MA, Cappuccio FP, Banerjee P. Heart failure with preserved ejection fraction (HFpEF) pathophysiology study (IDENTIFY-HF): does increased arterial stiffness associate with HFpEF, in addition to ageing and vascular effects of comorbidities? Rationale and design. BMJ Open. 2019 Nov 19;9(11):e027984. doi: 10.1136/bmjopen-2018-027984.

  PMID: 31748285 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum analysis for galectin-3

Study Officials

• Prithwish Banerjee, MD, FRCP

  University Hospital Coventry and Warwickshire, Coventry University

  STUDY DIRECTOR

• Francesco Cappuccio, MD, MSc, DSc

  University of Warwick

  STUDY CHAIR

• Martin Weickert, MD, FRCP

  University Hospital Coventry and Warwickshire

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2017
• First Posted: June 14, 2017
• Study Start: June 6, 2017
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: September 27, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)