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| Name | Class |
|---|---|
| The Swedish Research Council | OTHER_GOV |
| Region Stockholm | OTHER_GOV |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PREFERS main study | 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 | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cardiac imaging in the PREFERS and CABG PREFERS cohorts | Diagnostic Test | performed at baseline and after 1 year |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Reverse remodeling | diastolic function | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:CABG PREFERS
Inclusion criteria:
Inclusion criteria PREFERS:
Exclusion Criteria CABG PREFERS and PREFERS:
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CABG PREFERS: Patients undergoing elective coronary artery by pass surgery at the karolinska University hospital PREFERS: New onset heart failure patients at 5 hospitals in Stockholm ; Danderyds Hospital, Capio St Görans Hospital , Karolinska Solna Karolinska Huddinge, South Hospital
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| Name | Affiliation | Role |
|---|---|---|
| Cecilia M Linde, MD PhD | Institution of Internal medicine, Karolinska University Hospital and Karolinska Institutet | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karolinska Institutet | Stockholm | 17176 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27384611 | Result | Linde C, Eriksson MJ, Hage C, Wallen 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 Epidemiological Regional Study) Stockholm heart failure study: an epidemiological regional study in Stockholm county of 2.1 million inhabitants. Eur J Heart Fail. 2016 Oct;18(10):1287-1297. doi: 10.1002/ejhf.599. Epub 2016 Jul 7. | |
| 29021611 |
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In 500 of the included 1000 patients (CABG-PREFERS) needle biopsies are taken from the cardiac lateral wall of both the right and left ventricle before initiation of cardiac arrest and stored in -70 ∘C for histological and genetic analysis. Moreover biopsies are taken from the right atrial appendage (ample material), the right and left ventricular myocardium, as wellas from the internal mammary artery.
| Biomarker analysis in the PREFERS and CABG PREFERS chorts | Other | blood samples will be taken for biomarker analysis at baseline and after 1 year |
|
|
| Cardiac biopsies in the CABG PREFERS cohort | Procedure | myocardial biopsies from the right trium the left and right ventricles will be taken during elective CABG |
|
| Result |
| Asp M, Salmen F, Stahl PL, Vickovic S, Felldin U, Lofling 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. Sci Rep. 2017 Oct 11;7(1):12941. doi: 10.1038/s41598-017-13462-5. |
| 32750486 | Result | Hage C, Lofgren L, Michopoulos F, Nilsson R, Davidsson P, Kumar C, Ekstrom M, Eriksson MJ, Lynga P, Persson B, Wallen 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.cardfail.2020.07.010. Epub 2020 Aug 1. |
| 41967095 | Derived | Persson H, Winderud A, Hage C, Cabrera CC, Lofstrom U, Lynga P, Arslan T, Knudsen Malmqvist K, Eriksson MJ, Persson B, Wallen H, Ekstrom M, Linde C. Worse long-term outcomes in new-onset HFpEF vs HFrEF and HFmrEF: findings from the Stockholm PREFERS study. ESC Heart Fail. 2026 May 5;13(3):xvag105. doi: 10.1093/eschf/xvag105. |
| 40177505 | Derived | Lofstrom U, Linde C, Eriksson MJ, Maret E, Corbascio M, Ekstrom M, Lynga P, Wallen H, Persson B, Persson H, Hage C. Baseline characteristics and 1-year outcome by left ventricular function in the CABG PREFERS. Eur Heart J Open. 2025 Mar 5;5(2):oeaf014. doi: 10.1093/ehjopen/oeaf014. eCollection 2025 Mar. |
| 36931398 | Derived | Cabrera C, Frisk C, Lofstrom U, Lynga P, Linde C, Hage C, Persson H, Eriksson MJ, Wallen H, Persson B, Ekstrom M. Relationship between iron deficiency and expression of genes involved in iron metabolism in human myocardium and skeletal muscle. Int J Cardiol. 2023 May 15;379:82-88. doi: 10.1016/j.ijcard.2023.03.032. Epub 2023 Mar 15. |
| 35403374 | Derived | Linde C, Ekstrom M, Eriksson MJ, Maret E, Wallen H, Lynga P, Weden U, Cabrera C, Lofstrom U, Stenudd J, Lund LH, Persson B, Persson H, Hage C; Stockholm County/Karolinska Institutet 4D heart failure investigators. Baseline characteristics of 547 new onset heart failure patients in the PREFERS heart failure study. ESC Heart Fail. 2022 Aug;9(4):2125-2138. doi: 10.1002/ehf2.13922. Epub 2022 Apr 10. |
| ID | Term |
|---|---|
| D054144 | Heart Failure, Diastolic |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D015150 | Echocardiography, Doppler |
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D004452 | Echocardiography |
| D057791 | Cardiac Imaging Techniques |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D014463 | Ultrasonography |
| D018608 | Ultrasonography, Doppler |
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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