Iron deficiency in new onset heart failure: association with clinical factors and quality of life.

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.

Extracellular vesicles in heart failure - A study in patients with heart failure with preserved ejection fraction or heart failure with reduced ejection fraction characteristics undergoing elective coronary artery bypass grafting.

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.

Baseline characteristics of 547 new onset heart failure patients in the PREFERS heart failure study.

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.

Reorganization of heart failure management and improved outcome - the 4D HF Project.

OBJECTIVES: Heart failure (HF) management is suboptimal in Sweden despite available evidence-based guidelines. To improve HF treatment, a comprehensive HF management program (4D project) was implemented in the Stockholm County (>2.1 million inhabitants). Design. A standardized care program centralized at five hospital-based HF clinics was implemented in 2014-2017. We registered from 2012 to 2017: (1) numbers of referrals and visits to HF clinics, (2) numbers of hospital admitted patients per million inhabitants, (3) dispensed HF medications after admission, and (4) covariate-adjusted 1-year all-cause mortality or HF readmission. Results. Yearly visits to the five HF outpatient clinics increased 3.4 times from 3,372 to 11,527. Dispensed HF drug prescriptions increased, in particular, for readmitted patients, compared to 2012 (p<.0001). Total number of hospital admitted HF patients as well as new-onset or readmitted HF patients decreased by 16, 13, and 20%, respectively (p < .0001). The combined 1-year mortality or HF readmission over the period was 48% (n = 17,124/35,880) and improved per year (HR 0.98 [0.97-0.99], p < .001) from 2012. Conclusion. A comprehensive standardized care HF management program including expanded HF clinics was associated with improved evidence-based medication, reduced HF hospitalization, and improvement of the combined outcome of 1-year mortality or HF readmission in Stockholm.

Do Patients With Acute Heart Failure and Preserved Ejection Fraction Have Heart Failure at Follow-Up: Implications of the Framingham Criteria.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) may be misdiagnosed. We assessed prevalence and consistency of Framingham criteria signs and symptoms in acute vs subsequent stable HFpEF. METHODS: Three hundred ninety-nine patients with acute HFpEF according to Framingham criteria were re-assessed in stable condition. Four definitions of HFpEF at follow-up: (1) Framingham criteria alone, (2) Framingham criteria and natriuretic peptides (NPs), (3) Framingham criteria, NPs, and European Society of Cardiology HF guidelines echocardiographic criteria, (4) Framingham criteria, NPs, and the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON) trial echocardiographic criteria. RESULTS: At follow-up, HFpEF was still present in 27%, 22%, 21%, and 22%, respectively. Most prevalent in acute HFpEF were dyspnea at exertion (90%), pulmonary rales (71%), persisting at follow-up in 70% and 13%, respectively. Characteristics at acute HF with greater or lesser odds of stable HFpEF; (1) jugular venous distention (odds ratio [OR] 1.80, 95% confidence interval [CI] 1.13-2.87; P = .013) and pleural effusion (OR 0.45, 95% CI 0.24-0.85; P = .014) and (4), older age (1.04, 95% CI 1.01-1.08; P = .014) and tachycardia (>100 bpm) 0.52, 95% CI 0.27-1.00; P = .048). CONCLUSIONS: In patients with acute HFpEF, one-quarter met the HF definition according to Framingham criteria at ambulatory follow-up. The proportion of patients with postdischarge HFpEF was largely unaffected by additional echocardiographic or NP criteria Older age and jugular venous distention at acute presentation predicted persistent HFpEF at follow-up, whereas pleural effusion and tachycardia may yield false HFpEF diagnoses. This finding has implications for HFpEF trial design.

Prognostic impact of Framingham heart failure criteria in heart failure with preserved ejection fraction.

AIMS: This study aims to assess prognostic impact of Framingham criteria for heart failure (FC-HF) in patients with stable heart failure (HF) with preserved ejection fraction (HFpEF). METHODS AND RESULTS: In the prospective Karolinska-Rennes (KaRen) study, we assessed stable HFpEF patients after an acute HF episode. We evaluated associations between the four descriptive models of HFpEF and the composite endpoint of all-cause mortality and HF hospitalization. The descriptive models were FC-HF alone, FC-HF + natriuretic peptides (NPs) according to the PARAGON trial, FC-HF + NPs + echocardiographic HFpEF criteria according to European Society of Cardiology HF guidelines, and FC-HF + NPs + echocardiographic criteria according to the PARAGON trial. Out of the 539 patients enrolled in KaRen, 438 returned for the stable state revisit after 4-8 weeks, 13 (2.4%) patients died before the planned follow-up, and 88 patients (16%) declined or were unable to return. Three hundred ninety-nine patients have FC registered at follow-up, and among these, the four descriptive models were met in 107 (27%), 82 (22%), 61 (21%), and 69 (22%) patients, and not met in 292 (73%). The 107 patients that had FC-HF at stable state (descriptive model 1) could also be part of the other models because all patients in models 1-4 had to fulfil the FC-HF. The patients in model 0 did not fulfil the criteria for FC-HF but could have single FC. Of single FC, only pleural effusion predicted the endpoint [hazard ratio (HR) 3.38, 95% confidence interval (CI) 1.47-7.76, P = 0.004]. Patients without FC-HF had better prognosis than patients meeting FC-HF. The unadjusted associations between the four HFpEF descriptive models and the endpoint were HR 1.54, 95% CI 1.14-2.09, P = 0.005; HR 1.71, 95% CI 1.24-2.36, P = 0.002; HR 1.95, 95% CI 1.36-2.81, P = 0.001; and HR 2.05, 95% CI 1.45-2.91, P < 0.001, for descriptive models 1-4, respectively. No descriptive model independently predicted the endpoint. CONCLUSIONS: In ambulatory HFpEF patients, a quarter met FC-HF, while most met NP and echocardiography criteria for HF. Residual FC-HF tended to be associated with increased risk for mortality and HF hospitalization, further strengthened by NPs and echocardiographic criteria, highlighting its role in clinical risk assessment.