Circulating microRNAs (miRs) are promising biomarkers for heart failure (HF). Previous studies have provided inconsistent miR "signatures." The phenotypic and pathophysiologic heterogeneity of HF may ...have contributed to this inconsistency. In this study we assessed whether advanced HF (AHF) patients present a distinct miR signature compared with healthy subjects (HS) and mild to moderate HF (MHF) patients.
The study consisted of 2 phases: a screening phase and a validation phase. In the screening phase, 752 miRs were profiled in HS and MHF and AHF patients (N = 15), using the real-time quantitative polymerase chain reaction (RT-qPCR) technique and global mean normalization. In the validation phase, the miRs found to be significantly dysregulated in AHF patients compared with both HS and MHF patients were validated in 15 HS, 25 patients with MHF and 29 with AHF, using RT-qPCR, and normalizing to exogenous (cel-miR-39) and endogenous controls.
In the screening phase, 5 miRs were found to be significantly dysregulated: -26a-5p; -145-3p; -150-5p; -485-3p; and -487b-3p. In the validation phase, miR-150-5p was confirmed to be significantly downregulated in AHF patients when compared with both HS and MHF patients, irrespective of the normalization method used. miR-26a-5p was confirmed to be significantly dysregulated only when normalized to cell-miR-39. Dysregulation of the other miRs could not be confirmed. miR-150-5p was significantly associated with maladaptive remodeling, disease severity and outcome.
Our data suggest miR-150-5p as a novel circulating biomarker for AHF. The association of miR-150-5p with maladaptive remodeling, disease severity and outcome supports the pathophysiologic relevance of downregulated miR-150-5p expression to AHF.
Frameworks for human activity recognition (HAR) can be applied in the clinical environment for monitoring patients' motor and functional abilities either remotely or within a rehabilitation program. ...Deep Learning (DL) models can be exploited to perform HAR by means of raw data, thus avoiding time-demanding feature engineering operations. Most works targeting HAR with DL-based architectures have tested the workflow performance on data related to a separate execution of the tasks. Hence, a paucity in the literature has been found with regard to frameworks aimed at recognizing continuously executed motor actions. In this article, the authors present the design, development, and testing of a DL-based workflow targeting continuous human activity recognition (CHAR). The model was trained on the data recorded from ten healthy subjects and tested on eight different subjects. Despite the limited sample size, the authors claim the capability of the proposed framework to accurately classify motor actions within a feasible time, thus making it potentially useful in a clinical scenario.
•Congestion is a marker of adverse prognosis in patients with heart failure (HF).•BNP, ePVS, BIVA, and BUN/Cr ratio are independent prognostic biomarkers in HF.•Combining BNP, eVPS, BIVA, and BUN/Cr ...explain the 40% risk of death in HF.
Congestion is a marker of adverse prognosis in patients with heart failure (HF). In addition to brain natriuretic peptide (BNP), estimated plasma volume status (ePVS), bioimpedance vector analysis (BIVA), and blood urea nitrogen/creatinine ratio (BUN/Cr) are emerging as new markers for congestion. The aim of this study was to evaluate the prognostic value of BNP, ePVS, BIVA, and BUN/Cr in HF.
We analyzed the data from 436 patients with acute or chronic heart failure (AHF, n=184, and CHF, n=252, respectively). BNP, ePVS, hydration index (HI%), and BUN/Cr were collected from all patients at admission. The endpoint was all-cause mortality.
Ninety-two patients died after a median follow-up of 463 days (IQR: 287–669). The cumulative mortality of all of the patients was 21% (31% and 13% in AHF and CHF, respectively, p<0.0001). The optimal cut-offs for death occurrence were BNP: >441pg/mL, ePVS: >5.3dL/gr, HI: >73.8%, BUN/Cr: >25. Multivariate Cox regression analysis maintained an independent predictive value for mortality (HR 2. 1, HR 2.2, HR 2.1, and HR 1.7; C-index 0.756). AHF status was no longer associated with death. Together, these variables explained 40% of the risk of death (R2 adjusted=0.40). Patients with all four parameters below or above their optimal cut-off had mortality rates of 4% and 59%, respectively.
BNP, ePVS, BIVA, and BUN/Cr at admission provide independent and complementary prognostic information in patients with HF and, when combined, explain the 40% risk of death in these patients independent from the acute or chronic HF condition.
Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF). ID is estimated to be present in up to 50% of outpatients and is a strong independent predictor of ...HF outcomes. ID has been shown to reduce quality of life, exercise capacity and survival, in both the presence and absence of anemia. The most recent 2016 guidelines recommend starting replacement treatment at ferritin cutoff value <100 mcg/l or between 100 and 299 mcg/l when the transferrin saturation is <20%. Beyond its effect on hemoglobin, iron plays an important role in oxygen transport and in the metabolism of cardiac and skeletal muscles. Mitochondria are the most important sites of iron utilization and energy production. These factors clearly have roles in the diminished exercise capacity in HF. Oral iron administration is usually the first route used for iron repletion in patients. However, the data from the IRONOUT HF study do not support the use of oral iron supplementation in patients with HF and a reduced ejection fraction, because this treatment does not affect peak VO
2
(the primary endpoint of the study) or increase serum ferritin levels. The FAIR-HF and CONFIRM-HF studies have shown improvements in symptoms, quality of life and functional capacity in patients with stable, symptomatic, iron-deficient HF after the administration of intravenous iron (i.e., FCM). Moreover, they have shown a decreased risk of first hospitalization for worsening of HF, as later confirmed in a subsequent meta-analysis. In addition, the EFFECT-HF study has shown an improvement in peak oxygen consumption at CPET (a parameter generally considered the gold standard of exercise capacity and a predictor of outcome in HF) in patients randomized to receive ferric carboxymaltose. Finally, the AFFIRM AHF trial evaluating the effects of FCM administration on the outcomes of patients hospitalized for acute HF has found significantly fewer hospital readmissions due to HF among patients treated with FCM rather than placebo.
Acute heart failure is a leading cause of hospitalization and death,and it is an increasing burden on health care systems. The correct risk stratification of patients could improve clinical outcome ...and resources allocation,avoiding the overtreatment of low-risk subjects or the early,inappropriate discharge of high-risk patients. Many clinical scores have been derived and validated for in-hospital and post-discharge survival; predictive models include demographic,clinical,hemodynamic and laboratory variables. Data sets are derived from public registries,clinical trials,and retrospective data. Most models show a good capacity to discriminate patients who reach major clinical end-points,with C-indices generally higher than 0.70,but their applicability in realworld populations has been seldom evaluated. No study has evaluated if the use of risk score-based stratification might improve patient outcome. Some variables(age,blood pressure,sodium concentration,renal function) recur in most scores and should always be considered when evaluating the risk of an individual patient hospitalized for acute heart failure. Future studies will evaluate the emerging role of plasma biomarkers.
Natriuretic peptides (NP) are recognized as the most powerful predictors of adverse outcomes in heart failure (HF). We hypothesized that a measure of functional limitation, as assessed by 6-min ...walking test (6MWT), would improve the accuracy of a prognostic model incorporating a NP. This was a multicenter observational retrospective study. We studied the prognostic value of severe functional impairment (SFI), defined as the inability to perform a 6MWT or a distance walked during a 6MWT < 300 m, in 1696 patients with HF admitted to cardiac rehabilitation. The primary outcome was 1-year all-cause mortality. After adjusting for the baseline multivariable risk model-including age, sex, systolic blood pressure, anemia, renal dysfunction, sodium level, and NT-proBNP-or for the MAGGIC score, SFI had an odds ratio of 2.58 (95% CI 1.72-3.88; p < 0.001) and 3.12 (95% CI 2.16-4.52; p < 0.001), respectively. Adding SFI to the baseline risk model or the MAGGIC score yielded a significant improvement in discrimination and risk classification. Our data suggest that a simple, 6MWT-derived measure of SFI is a strong predictor of death and provide incremental prognostic information over well-established risk markers in HF, including NP, and the MAGGIC score.
The whole-body bioelectrical phase-angle (PhA) is emerging as a new tool in stratifying prognosis in patients with both acute (AHF) and chronic heart failure (CHF).
To evaluate the determinants of ...PhA in HF patients.
We analyzed data from 900 patients with AHF or CHF (mean age: 76±10 years, 54% AHF). Clinical, serum biochemical, echocardiographic and bioelectrical measurements were collected from all of patients. PhA was quantified in degrees. Congestion was assessed by a multiparametric approach, including the presence of peripheral edema, brain natriuretic peptides (BNP) plasma levels, blood urea nitrogen to creatinine ratio (BUN/Cr), and relative plasma volume status (PVS) calculated by Kaplan-Hakim's formula. Geriatric Nutritional Risk Index (GNRI) was adopted as indicator for nutritional status.
At univariate analysis, PhA was significantly lower in females, in patients with peripheral edema, and AHF. PhA significantly correlates age, BNP, PVS, BUN/Cr, and GNRI. At multivariate analysis, congestion biomarkers emerged as the major determinant of PhA as they explained the 34% of data variability, while age, GNRI, and gender only explained 6%, 0.5%, and 0.5%, respectively (adjusted R2 = 0.41). In particular, PVS (regression of coefficient B=−0.17) explained the 20% of PhA variability, while peripheral congestion (B=−0.27) and BNP (B=−0.15) contributed to 10% and 2%, respectively.
The main determinant of bioelectrical PhA in patients with HF is congestion and PVS in particular, while nutritional status has marginal impact.
There is still room for further studies analyzing the long-term health impact of specific dietary patterns observable in regions belonging to the Mediterranean area. The aim of the study is to ...evaluate how much a diet practiced in southern Italy is associated to a risk of mortality. The study population included 2472 participants first investigated in 1985, inquiring about their frequencies of intake of 29 foods using a self-administered questionnaire covering the previous year. The population was followed up for mortality until 31 December 2017. Cox-based risk modeling referred to single foods, food groups, the results of principal component analysis (PCA), and a priori indexes. Single food analysis revealed eggs, fatty meat, and fatty/baked ham to be inversely associated with mortality. Furthermore, one of the 5 PCA derived dietary patterns, the "Farmhouse" pattern, showed a higher hazard ratio (HR), mostly driven by dairy products. In subsequent analyses, the increased risk of mortality for fresh cheese and decreased risk for fatty ham and eggs were confirmed. The a priori diet indexes (Italian Meddiet, Meddietscore, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay diet (MIND) indexes) showed borderline inverse relationships. In a Mediterranean population with an overall healthy diet, foods such as eggs and fatty meat, reflecting dietary energy and wealth, played a role in prolonging the life of individuals. Our study confirms that some dairy products might have a detrimental role in mortality in the Mediterranean setting.