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Aims: 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 (https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_final.pdf)., Methods: 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., Conclusions: 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., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Aim: Data are scant on the incidence and prognosis of heart failure (HF) with normal ejection fraction (HFNEF, EF >49%) in an acute myocardial infarction (AMI) setting. The aim of this study was to examine incidence and predictors of HFNEF during an index acute myocardial infarction (AMI) and its subsequent associations with patient outcomes., Methods and Results: This study analysed 91 360 patients with LVEF data from the SWEDEHEART registry on consecutive AMI patients between 1998 and 2010. Echocardiography or LV angiography was used to assess LVEF. In-hospital HF diagnoses required presence of crackles, and use of i.v. diuretics or inotropic drugs during admission. Among HF patients, the proportion of HFNEF patients increased (from 18% to 31%) during the period. Incidence of HFNEF in the AMI population remained fairly unchanged (from 7.7% to 8.1%). In contrast, the proportion of HF patients with reduced EF (HFREF, EF ≤49%) declined (from 47% to 26%), as did the proportion of REF patients without HF (from 20% to 16%). AMI patients with NEF without HF increased (from 25% to 50%). HFREF and HFNEF patients showed considerably higher long-term mortality compared with patients with no HF, irrespective of EF [the HFREF and HFNEF hazard ratio, compared with NEF, was 4.5 (4.4-4-6) and 3.3 (3.1-3.4), respectively, and 1.6 (1.5-1.65) for REF]. The adjusted HFNEF hazard ratio, compared with NEF, was 1.9 (1.8-2.0). Age, female gender, diabetes mellitus, hypertension, AF, and chronic kidney disease were strong predictors of HFNEF (P < 0.001)., Conclusion: The proportion of AMI patients with HFNEF is constant over time. HFNEF patients have a considerably worse long-term prognosis compared with patients without clinical HF, irrespective of EF., (© 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.)

Objectives: To identify electrocardiographic and echocardiographic predictors of mortality and hospitalizations for heart failure (HF) in the KaRen study., Background: KaRen is a prospective, observational study of the long-term outcomes of patients presenting with heart failure and a preserved ejection fraction (HFpEF)., Method: We identified 538 patients who presented with acute cardiac decompensation, a >100 pg/mL serum b-type natriuretic peptide (BNP) or >300 pg/mL N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and a left ventricular ejection fraction (LVEF) >45%. After 4-8 weeks of standard treatment, 413 patients (mean age = 76 ± 9 years, 55.9% women) returned for analyses of their clinical status, laboratory screen, and detailed electrocardiographic and Doppler echocardiographic recordings. They were followed for a mean of 28 months thereafter. The primary study endpoint was time to death from all causes or first hospitalization for heart failure., Results: Mean LVEF was 62.4 ± 6.9% and median NT-proBNP 1410 pmol/L. PR interval >200 ms was present in 11.2% of patients and 14.9% had a >120 ms QRS duration, with left bundle branch block in only 6.3%. Over a mean follow-up of 28 months, 177 patients (42.9%) reached a primary study endpoint, including 61 deaths and 116 hospitalizations for heart failure. After adjustment for age, gender, New York Heart Association class, atrial fibrillation history, creatinine, sodium, BNP, ejection fraction, and right ventricular fractional shortening, only E/e' remained as a predictor, with a hazard ratio = 1.49 and P = 0.0012., Conclusion: The incidence of hospitalizations for HF and deaths in KaRen was high and E/e' predicted adverse clinical outcomes. These observations should help in the risk stratification and therapy of HFpEF., (© 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.)

Aims: The prevalence of cardiovascular and non-cardiovascular co-morbidities and their relative importance for outcomes in heart failure with preserved ejection fraction (HFPEF) remain poorly characterized. This study aimed to investigate this., Methods and Results: The Karolinska-Rennes (KaRen) Study was a multinational prospective observational study designed to characterize HFPEF. Inclusion required acute HF, defined by the Framingham criteria, LVEF ≥ 45%, and NT-pro-BNP ≥ 300 ng/L or BNP ≥ 100 ng/L. Detailed clinical data were collected at baseline and patients were followed prospectively for 18 months. Predictors of the primary (HF hospitalization or all-cause mortality) and secondary (all-cause mortality) outcomes were assessed with multivariable Cox regression. A total of 539 patients [56% women; median (interquartile range) age 79 (72-84) years; NT-pro-BNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Known history of HF was present in 40%. Co-morbidities included hypertension (78%), atrial fibrillation/flutter (65%), anaemia (51%), renal dysfunction (46%), CAD (33%), diabetes (30%), lung disease (25%), and cancer (16%). The primary outcome occurred in 268 patients [50%; 106 deaths (20%) and 162 HF hospitalizations (30%)]. Important independent predictors of the primary and/or secondary outcomes were age, history of non-cardiovascular syncope, valve disease, anaemia, lower sodium, and higher potassium, but no cardiovascular co-morbidities. Renin-angiotensin system antagonist and mineralocorticoid receptor antagonist use predicted improved prognosis., Conclusion: HFPEF was associated with higher age, female gender, hypertension, atrial fibrillation/flutter, and numerous non-cardiovascular co-morbidities. Prognosis was determined by non-cardiovascular co-morbidities, but use of conventional heart failure medications may still be associated with improved outcomes., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)