PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm Heart Failure Study

Completed

• Conditions: Heart Failure，Congestive; Heart Failure, Diastolic
• Interventions: Diagnostic Test: Cardiac imaging in the PREFERS and CABG PREFERS cohorts; Other: Biomarker analysis in the PREFERS and CABG PREFERS chorts; Procedure: Cardiac biopsies in the CABG PREFERS cohort

• Registration Number: NCT03671122
• Lead Sponsor: Karolinska Institutet

Brief Summary

Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF starting with a cardiac biopsy study in elective CABG patiens.

Detailed Description

Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank.We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis.In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF.

Study Timeline

• Study Start: 2015-01-01
• Study First Submitted: 2018-09-09
• Study First Submitted QC: 2018-09-13
• Study First Posted: 2018-09-14
• Primary Completion: 2021-01-31
• Study Completion: 2021-02-28
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-29
• Last Update Posted: 2022-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 683

Inclusion Criteria

CABG PREFERS

Inclusion criteria:

1. Patients undergoing elective coronary bypass surgery
2. History of heart failure not required
3. Age >18 years
4. Willingness to participate (written informed consent)
5. Possibility to obtain technically satisfactory echocardiography

Inclusion criteria PREFERS:

1. New-onset heart failure according to ESC guidelines including NT-proBNP >125 ng/L at heart failure clinic or >300 ng/L at emergency department visit or hospital admission
2. Age >18 years
3. Willingness to participate (written informed consent)
4. Possibility to obtain technically satisfactory echocardiography

Exclusion Criteria CABG PREFERS and PREFERS:

1. Cognitive impairment
2. Inability to understand Swedish language
3. Anaemia (haemoglobin level <90 g/L)
4. Heart failure primarily due to valvular disease, primary right ventricular failure, pulmonary artery hypertension, hypertrophic obstructive cardiomyopathy Infiltrative cardiomyopathy (e.g. amyloidosis, sarcoidosis, or haemochromatosis)
5. Severe co-morbidity, severe COPD, severe renal dysfunction (eGFR <30 mL/min/1.73m2). Any other co-morbid disease that will disable the ability to assess or treat heart failure.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PREFERS main study	Biomarker analysis in the PREFERS and CABG PREFERS chorts	500 patients with new onset heart failure will be characterized into those with HFpEFand HFrEF at baseline and undergo Cardiac imaging by Doppler echocardiography and cMRI, blood tests for biomarker analysis
CABG PREFERS	Cardiac biopsies in the CABG PREFERS cohort	500 Patients undergoing elective by pass surgery with or without diastolic or systolic dysfunction as Proxy for HFpEF and HFrEF will undergo Cardiac imaging by Doppler echocardiography and cMRI, blood tests for biomarker analysis and cardiac biopsies
CABG PREFERS	Cardiac imaging in the PREFERS and CABG PREFERS cohorts	500 Patients undergoing elective by pass surgery with or without diastolic or systolic dysfunction as Proxy for HFpEF and HFrEF will undergo Cardiac imaging by Doppler echocardiography and cMRI, blood tests for biomarker analysis and cardiac biopsies
CABG PREFERS	Biomarker analysis in the PREFERS and CABG PREFERS chorts	500 Patients undergoing elective by pass surgery with or without diastolic or systolic dysfunction as Proxy for HFpEF and HFrEF will undergo Cardiac imaging by Doppler echocardiography and cMRI, blood tests for biomarker analysis and cardiac biopsies
PREFERS main study	Cardiac imaging in the PREFERS and CABG PREFERS cohorts	500 patients with new onset heart failure will be characterized into those with HFpEFand HFrEF at baseline and undergo Cardiac imaging by Doppler echocardiography and cMRI, blood tests for biomarker analysis

Primary Outcome Measures

Name	Time	Method
Reverse remodeling	2 years	diastolic function
Change in fibrotic biomarkers	2 years	For the biopsies (CABG PREFERS), the sample size is based upon the number of patients undergoing elective CABG surgery. Investigators expect to discover mRNAs from genes of potential interest in this material with relevance to differences between preserved ejection fraction, reduced ejection fraction and normal groups by bioinformatics tools. These genes will be further investigated in the blood samples of the PREFERS study and potentially in future heart biopsies. for the PREFERS new onset heart failure study. Investigators calculated a 20% difference between HFrEF and HFpEF groups with regard to both PICP and CITP (higher PICP levels and lower CITP in HFpEF vs. HFrEF) as clinically meaningful. To detect a 20% difference between the HFpEF and the HFrEF groups with 80% power and with an estimated drop-out rate of 50 patients in each group, 250 patients in each group are needed to obtain samples from 200 per group.

Secondary Outcome Measures

Name	Time	Method
cardiac magnetic resonance tomography imaging	2 years	ECV by cMRI will be correlated to type of HF whether HFpEF or HFrEF and to echocardiographic findings

Trial Locations

Locations (1)

Karolinska Institutet; 🇸🇪 Stockholm, Sweden