Heart Failure With Preserved Ejection Fraction: Evaluation and Recognition by CMR (PREFER-CMR)

PReserved Ejection Fraction Evaluation and Recognition by Cardiac Magnetic Resonance

Heart failure with preserved ejection fraction (HFpEF) is a common and growing condition with a poor prognosis but the pathophysiology and management are still being investigated. The PREFER-CMR project aims to evaluate and validate the application of novel 4D cardiac magnetic resonance flow dynamic methods to measure left ventricular pressures and validate these measurements with direct pressure measurement by coronary angiography. This is a prospective observational study of patients with HFpEF undergoing clinical evaluation with coronary angiography who will also undergo contemporaneous cardiac MRI. The primary outcome will be the level of agreement between the two methods using angiography as the reference method.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Diseases; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Diagnostic test: Multi Parametric Cardiac Magnetic Resonance

Detailed Description

Heart failure with preserved ejection fraction (HFpEF) is prevalent, increasing in incidence and has a poor prognosis. Accurate left ventricular (LV) haemodynamic assessment is needed to diagnose and manage patients with HFpEF. The reference method for assessment is an invasive study using catheters to measure intra-ventricular pressure but this is rarely done due to its invasive nature, high procedural costs and lack of expertise, despite the fact that haemodynamic guided therapy is associated with reduced re-hospitalisation and mortality. Non-invasive methods of LV haemodynamic assessment are inaccurate. The Investigators have developed an accurate four-dimensional flow cardiac magnetic resonance (4D flow CMR) protocol which is non-invasive and addresses the issues with existing practices to evaluate HFpEF. This observational-analytical study aims to assess the utility of a non-invasive 4D flow CMR protocol for haemodynamic assessment of HFpEF, to generate clinical data to support future clinical trials, clinical translation and patient benefit. This research study will involve generating a precise haemodynamic model using invasive and non-invasive data of prospectively recruited patients. This model will be also optimised in clinical patients with arrhythmias. Also, observational data will be collected to test the model's prognostic value.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Pankaj Garg, MD; Phone Number: +441603591721; Email: p.garg@uea.ac.uk
• Study Contact Backup: Name: Marcus D Flather, MBBS; Email: m.flather@uea.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• Suspected heart failure patients
• Suspected coronary artery disease patients

Description

Inclusion Criteria:

1. Adults: age≥18 years.
2. Typical HF symptoms (NYHA stage>I) within the last six months.
3. Raised NTproBNP (>400 pg/ml)
4. EF>50 % with the absence of structural heart disease on TTE (except left ventricular hypertrophy or left atrial enlargement).

Exclusion Criteria:

1. Patients unable/unwilling to provide informed consent.
2. Bodyweight>120 kg or inability to lie flat/still.
3. Contraindication for invasive workup (allergy to contrast, severe renal insufficiency with estimated glomerular filtration rate (eGRF)<30 ml/min).
4. Contraindications for a contrast-enhanced CMR study (allergy to contrast, incompatible devices or implants, severe claustrophobia).
5. Previous medical history of EF <50%
6. Pregnancy

The extended observational arm of the study will have wider eligibility criteria

- Patients undergoing cardiac MRI for clinical indications irrespective of EF

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HFpEF group; Suspected HFpEF group: 80 patients will be recruited with history of dyspnoea, LV ejection fraction ≥ 50%, raised NTproBNP	Diagnostic test: Multi Parametric Cardiac Magnetic Resonance; Research based Cardiac MRI evaluation to determine cardiovascular haemodynamics
Control group; 20 patients with suspected CAD but with no dyspnoea and normal echocardiogram.	Diagnostic test: Multi Parametric Cardiac Magnetic Resonance; Research based Cardiac MRI evaluation to determine cardiovascular haemodynamics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular pressure measured by invasive angiography (reference method) and modelled by cardiovascular magnetic resonance imaging	Agreement of invasively measured left ventricular pressure in millimeters of mercury (mmHg) by invasive angiography to non-invasively modelled left ventricular pressure by cardiac magnetic resonance imaging. The agreement will be tested by Bland-Altman plots..	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic relevance of left ventricular pressures measured by cardiac MRI	Is cardiovascular magnetic resonance modelled left ventricular pressure in millimeters of mercury (mmHg) associated with MACE events including re-hospitalization, stroke, myocardial infarction and death. Association between pressure measurements and MACE will be tested by Cox proportional hazards regression and Kaplan-Meier survival analysis.	Ten years

Collaborators and Investigators

• Sponsor: University of East Anglia
• Collaborators: Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
• Investigators: Principal Investigator: Pankaj Garg, MD, University of East Anglia

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): January 1, 2026
• Study Completion (Anticipated): January 1, 2032

Study Registration Dates

• First Submitted: September 28, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 10, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; Heart failure; hemodynamics
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Failure; Heart Diseases
• Other Study ID Numbers: IRAS 301141

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The dataset of this study are available at the discretion of the Principal Investigator on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No