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AIMS: The prevalence of iron deficiency (ID) in newly diagnosed heart failure (HF) and the progression of ID in patients after initiation of HF therapy are unknown. We aimed to describe the natural trajectory of ID in patients with new onset HF during the first year after HF diagnosis, assessing associations between ID, clinical factors, and quality of life (QoL). METHODS AND RESULTS: A prospective cohort of patients with new onset HF in hospitals or outpatient clinics at five major hospitals in Stockholm, Sweden, during 2015-2018 were analysed with clinical assessment, electrocardiogram, blood samples including iron levels, Minnesota living with heart failure questionnaire (MLHFQ), and echocardiogram at baseline and after 12 months. Of 547 patients with new-onset HF, 482 (88%) had complete iron data at baseline. Mean age was 70 years (interquartile range 61-77) and 311 (65%) were men; 55% of patients had ejection fraction (EF) ≤ 40%, 19% had EF 41-49%, and 26% had HF with preserved EF (HFpEF). At baseline, 163 patients (34%) had ID defined as ferritin <100 µg/L or ferritin 100-299 µg/L and transferrin saturation <20%. After 12 months of follow-up, 119 (32%) had ID of the 368 patients who had complete iron data both at baseline and after 12 months and did not receive intravenous (i.v.) iron during follow-up. During the first year after HF diagnosis, 19% had persistent ID, 13% developed ID, 11% resolved ID, and 57% never had ID, consequently 24% changed their classification. Anaemia at baseline was the strongest independent predictor of ID 1 year after diagnosis [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.88-8.13, P < 0.001], followed by HF hospitalization (OR 2.21, 95% CI 1.24-3.95, P < 0.01), female sex (OR 2.04, 95% CI 1.25-3.32, P < 0.01), HFpEF (OR 1.96, 95% CI 1.13-3.39, P < 0.05), and diabetes mellitus (OR 1.92, 95% CI 1.06-3.48, P < 0.05). ID was associated with low QoL at baseline (MLHFQ score mean difference 7.4 points, 95% CI 3.1-11.7, P < 0.001), but not at follow-up. CONCLUSIONS: About one third of patients with new onset HF had ID both at the time of HF diagnosis and after 1 year, though a quarter of the patients changed their ID status. Patients with anaemia, HF hospitalization, female gender, HFpEF, or diabetes mellitus at baseline were more likely to have ID after 1 year implying that these should be carefully screened for ID to find those in need of i.v. iron treatment.
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Aims: Extracellular vesicles (EVs) were investigated as potential biomarkers associated with heart failure (HF) pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by HF phenotype. Materials and methods: Patients with preoperative proxy-diagnoses of HF types i.e., preserved (HFpEF; n = 19) or reduced ejection fraction (HFrEF; n = 20) were studied and compared to patients with normal left ventricular function (n = 42). EVs in plasma samples collected from the coronary sinus, an arterial line, and from the right atrium were analyzed by flow cytometry. We studied EVs of presumed cardiomyocyte origin [EVs exposing Connexin-43 + Caveolin-3 (Con43 + Cav3) and Connexin-43 + Troponin T (Con43 + TnT)], of endothelial origin [EVs exposing VE-Cadherin (VE-Cad)] and EVs exposing inflammatory markers [myeloperoxidase (MPO) or pentraxin3 (PTX3)]. Results: Median concentrations of EVs exposing Con43 + TnT and Con43 + Cav3 were approximately five to six times higher in coronary sinus compared to radial artery indicative of cardiac release. Patients with HFrEF had high trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas HFpEF had elevated gradients of Con43 + Cav3 EVs but lower gradients of Con43 + TnT. Coronary sinus concentrations of both Con43 + TnT and Con43 + Cav3 correlated significantly with echocardiographic and laboratory measures of HF. MPO-EV concentrations were around two times higher in the right atrium compared to the coronary sinus, and slightly higher in HFpEF than in HFrEF. EV concentrations of endothelial origin (VE-Cad) were similar in all three patient groups. Conclusion: Con43 + TnT and Con43 + Cav3 EVs are released over the heart indicating cardiomyocyte origin. In HFrEF the EV release profile is indicative of myocardial injury and myocardial stress with elevated trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury.
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AIM: We present the baseline characteristics of the PREFERS Stockholm epidemiological study on the natural history and course of new onset heart failure (HF) aiming to improve phenotyping focusing on HF with preserved left ventricular ejection fraction (HFpEF) pathophysiology. METHODS AND RESULTS: New onset HF patients diagnosed in hospital or at outpatient HF clinics were included at five Stockholm hospitals 2015-2018 and characterized by N-terminal pro brain natriuretic peptide (NT-proBNP), biomarkers, echocardiography, and cardiac magnetic resonance imaging (subset). HFpEF [left ventricular ejection fraction (LVEF) ≥ 50%] was compared with HF with mildly reduced LVEF (HFmrEF; LVEF 41-49%) and with HF with reduced LVEF (HFrEF; LVEF ≤ 40%). We included 547 patients whereof HFpEF (n = 137; 25%), HFmrEF (n = 61; 11%), and HFrEF (n = 349; 64%). HFpEF patients were older (76; 70-81 years; median; interquartile range) than HFrEF (67; 58-74; P < 0.001), more often women (49% vs. 30%; P < 0.001), and had significantly higher comorbidity burden. They more often had atrial fibrillation, hypertension, and renal dysfunction. NT-proBNP was lower in HFpEF (896; 462-1645 ng/L) than in HFrEF (1160; 563-2370; P = 0.005). In HFpEF, left ventricular (LV) diameters and volumes were smaller (P < 0.001) and septal and posterior wall thickness and relative wall thickness higher (P < 0.001). E/é ≥ 14 was present in 26% of HFpEF vs. 32% of HFrEF (P = 0.017) and left atrial volume index > 34 mL/m2 in 57% vs. 61% (P = 0.040). HFmrEF patients were intermediary between HFpEF and HFrEF for LV mass, LV volumes, and RV volumes but had the highest proportion of left ventricular hypertrophy and the lowest proportion of elevated E/é. CONCLUSIONS: Phenotype data in new onset HF patients recruited in a broad clinical setting showed that 25% had HFpEF, were older, more often women, and had greater comorbidity burden. PREFERS is well suited to further explore biomarker and imaging components of HFpEF pathophysiology and may contribute to the emerging knowledge of HF epidemiology. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03671122.