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

Heart Failure, Diastolic Clinical Trial

— PREFERS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03671122
• Other study ID #: AZ, Molndal, Sweden grant 1377
• Status: Completed
• Start date: January 1, 2015
• Est. completion date: February 28, 2021

Study information

• Verified date: March 2022
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 683
• Est. completion date: February 28, 2021
• Est. primary completion date: January 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Diastolic
• Heart Failure,Congestive

Intervention

Diagnostic Test:
• Cardiac imaging in the PREFERS and CABG PREFERS cohorts
performed at baseline and after 1 year

Other:
• Biomarker analysis in the PREFERS and CABG PREFERS chorts
blood samples will be taken for biomarker analysis at baseline and after 1 year

Procedure:
• Cardiac biopsies in the CABG PREFERS cohort
myocardial biopsies from the right trium the left and right ventricles will be taken during elective CABG

Locations

Country	Name	City	State
Sweden	Karolinska Institutet	Stockholm

Sponsors (3)

Lead Sponsor	Collaborator
Karolinska Institutet	Region Stockholm, The Swedish Research Council

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

Asp M, Salmén F, Ståhl PL, Vickovic S, Felldin U, Löfling M, Fernandez Navarro J, Maaskola J, Eriksson MJ, Persson B, Corbascio M, Persson H, Linde C, Lundeberg J. Spatial detection of fetal marker genes expressed at low level in adult human heart tissue. — View Citation

Hage C, Löfgren L, Michopoulos F, Nilsson R, Davidsson P, Kumar C, Ekström M, Eriksson MJ, Lyngå P, Persson B, Wallén H, Gan LM, Persson H, Linde C. Metabolomic Profile in HFpEF vs HFrEF Patients. J Card Fail. 2020 Dec;26(12):1050-1059. doi: 10.1016/j.car — View Citation

Linde C, Eriksson MJ, Hage C, Wallén H, Persson B, Corbascio M, Lundeberg J, Maret E, Ugander M, Persson H; Stockholm County/Karolinska Institutet 4D heart failure investigators. Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in fibrotic biomarkers	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.	2 years
Primary	Reverse remodeling	diastolic function	2 years
Secondary	cardiac magnetic resonance tomography imaging	ECV by cMRI will be correlated to type of HF whether HFpEF or HFrEF and to echocardiographic findings	2 years