Clinical trial NCT03671122: PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm Heart Failure Study
Official title: PREFERS PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm Heart Failure Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure, Diastolic
Heart Failure，Congestive
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: The Swedish Research Council
name: Region Stockholm
First posted: 2018-09-14
Enrollment: 683
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in fibrotic biomarkers
timeFrame: 2 years
measure: Reverse remodeling
timeFrame: 2 years
Secondary outcomes:
measure: cardiac magnetic resonance tomography imaging
timeFrame: 2 years
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska Institutet
Study officials:
affiliation: Institution of Internal medicine, Karolinska University Hospital and Karolinska Institutet
name: Cecilia M Linde, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.