AIMS: Patients with heart failure (HF) display metabolic alterations, including heightened ketogenesis, resulting in increased beta-hydroxybutyrate (β-OHB) formation. We aimed to investigate the determinants and prognostic impact of circulating β-OHB levels in patients with advanced HF and reduced ejection fraction (HFrEF). METHODS AND RESULTS: A total of 867 patients with advanced HFrEF (age 57 ± 11 years, 83% male, 45% diabetic, 60% New York Heart Association class III), underwent clinical and echocardiographic examination, circulating metabolite assessment, and right heart catheterization (n = 383). The median β-OHB level was 64 (interquartile range [IQR] 33-161) μmol/L (normal 0-74 μmol/L). β-OHB levels correlated with increased markers of lipolysis (free fatty acids [FFA]), higher natriuretic peptides, worse pulmonary haemodynamics, and lower humoral regulators of ketogenesis (insulin/glucagon ratio). During a median follow-up of 1126 (IQR 410-1781) days, there were 512 composite events, including 324 deaths, 81 left ventricular assist device implantations and 107 urgent cardiac transplantations. In univariable Cox regression, increased β-OHB levels (T3 vs. T1: hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13-1.72, p = 0.002) and elevated FFA levels (T3 vs. T1: HR 1.39, 95% CI 1.09-1.79, p = 0.008) were both predictors of a worse prognosis. In multivariable Cox analysis evaluating the simultaneous associations of FFA and β-OHB levels with outcomes, only FFA levels remained significantly associated with adverse outcomes. CONCLUSIONS: In patients with advanced HFrEF, increased plasma β-OHB correlate with FFA levels, worse right ventricular function, greater neurohormonal activation and other markers of HF severity. The association between plasma β-OHB and adverse outcomes is eliminated after accounting for FFA levels, suggesting that increased β-OHB is a consequence reflecting heightened lipolytic state, rather than a cause of worsening HF.
- MeSH
- biologické markery * krev MeSH
- echokardiografie MeSH
- kyselina 3-hydroxymáselná * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- prognóza MeSH
- senioři MeSH
- srdeční katetrizace MeSH
- srdeční selhání * krev patofyziologie MeSH
- tepový objem * fyziologie MeSH
- transplantace srdce MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
There is no biomarker reflecting right ventricular dysfunction in HFrEF patients used in clinical practice. We have aimed to look for a circulating marker of RV dysfunction employing a quantitative proteomic strategy. The Olink Proteomics Multiplex panels (Cardiovascular Disease II, III, Cardiometabolic, and Inflammation Target Panels) identified FGF-23 to be the most differentially abundant (more than 2.5-fold) in blood plasma of HF patients with severe RV dysfunction (n = 30) compared to those with preserved RV function (n = 31). A subsequent ELISA-based confirmatory analysis of circulating FGF-23 in a large cohort of patients (n = 344, 72.7% NYHA III/IV, LVEF 22.5%, 54.1% with moderate/severe RV dysfunction), followed by multivariable regression analysis, revealed that the plasma FGF-23 level was most significantly associated with RV dysfunction grade (p = 0.0004) and congestion in the systemic circulation (p = 0.03), but not with LV-ejection fraction (p = 0.69) or estimated glomerular filtration rate (eGFR, p = 0.08). FGF-23 was associated with the degree of RV dysfunction in both sub-cohorts (i.e. in patients with and without congestion, p < 0.0001). The association between FGF-23 and RV-dysfunction remained significant after the adjustment for BNP (p = 0.01). In contrast, when adjusted for BNP, FGF-23 was no longer associated with LV dysfunction (p = 0.59). The Cox proportional hazard model revealed that circulating FGF-23 was significantly associated with adverse outcomes even after adjusting for BNP, LVEF, RV dysfunction grade and eGFR. Circulating FGF-23 is thus a biomarker of right ventricular dysfunction in HFrEF patients regardless of congestion status.
BACKGROUND: Right ventricular (RV) function is currently being evaluated solely according to the properties of RV myocardium. We have tested a concept that in patients with heart failure with reduced ejection fraction (HFrEF), RV assessment should integrate the information about both RV function as well as size. METHODS: A total of 836 stable patients with HFrEF (LVEF 23.6 ± 5.8%, 82.8% males, 68% NYHA III/IV) underwent echocardiographic evaluation and were prospectively followed for a median of 3.07 (IQRs 1.11; 4.89) years for the occurrence of death, urgent heart transplantation or implantation of mechanical circulatory support. RESULTS: RV size (measured as RV-basal diameter, RVD1) was significantly associated with an adverse outcome independent of RV dysfunction grade (p = 0.0002). The prognostic power of RVD1 was further improved by indexing to body surface area (RVD1i, p < 0.05 compared to non-indexed value). A novel parameter named RV global dysfunction score (RVGDs) was calculated as a product of RVD1i and the degree of RV dysfunction (1-4 for preserved RV function, mild, moderate and severe dysfunction, respectively). RVGDs showed a superior prognostic role compared to RV dysfunction grade alone (ΔAUC >0.03, p < 0.0001). In every subgroup of RVGDs (<20, 20-40, 40-60, >60), patients with milder degree of RV dysfunction but more dilated RV had similar outcome as those with more severe degree of RV dysfunction but smaller RV size (all p > 0.50), independent of tricuspid regurgitation severity and degree of pulmonary hypertension. CONCLUSION: RV dilatation is a manifestation of RV dysfunction. The evaluation of RV performance should integrate the information about both RV size and function.
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
The role of metformin (MET) in the treatment of patients with advanced HFrEF and type 2 diabetes mellitus (DM) is not firmly established. We studied the impact of MET on metabolic profile, quality of life (QoL) and survival in these patients. A total of 847 stable patients with advanced HFrEF (57.4 ± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6 ± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Despite worse insulin sensitivity and more severe DM (higher BMI, HbA1c, worse insulin resistance), MET-treated patients exhibited more stable HF marked by lower BNP level (400 vs. 642 ng/l), better LV and RV function, lower mitral and tricuspid regurgitation severity, were using smaller doses of diuretics (all p < 0.05). Further, they had higher eGFR (69.23 vs. 63.34 ml/min/1.73 m2) and better QoL (MLHFQ: 36 vs. 48 points, p = 0.002). Compared to diabetics treated with other glucose-lowering agents, MET-treated patients had better event-free survival even after adjustment for BNP, BMI and eGFR (p = 0.035). Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p = 0.01). MET treatment in patients with advanced HFrEF and DM is associated with improved outcome by mechanisms beyond the improvement of blood glucose control.
- MeSH
- diabetes mellitus 2. typu * chemicky indukované komplikace farmakoterapie MeSH
- inzulinová rezistence * MeSH
- kvalita života MeSH
- lidé MeSH
- metformin * terapeutické užití MeSH
- srdeční selhání * MeSH
- tepový objem MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
1. vydání 150 stran : ilustrace, tabulky ; 26 cm
Publikace se zaměřuje na tyflografiku; reliéfní, taktilní, grafiku, která pomáhá zrakově postiženým lidem. Určeno odborné veřejnosti.
Monografie
1. vydání 177 stran : barevné ilustrace, tabulky ; 21 cm
Publikace se zabývá problematikou prostorové orientace a samostatného pohybu osob s těžkým zrakovým postižením, kdy se na tuto problematiku dívá komplexně. V první části publikace jsou zpracovány teoretické poznatky z oblasti klasifikace osob s těžkým zrakovým postižením, metodiky nácviku prostorové orientace u osob nevidomých a osob se zbytky zraku, na tyto pak navazují informace z oblasti rozvoje prostorové orientace a samostatného pohybu v jednotlivých věkových obdobích a pomůcky a prostředky, které je možno k samostatnému pohybu a prostorové orientaci využít. Takříkajíc teoretická část publikace je doplněna o výkladový slovníček pojmů z dané oblasti. Poslední část publikace představuje empirický vhled do zkoumané oblasti a zabývá se zpracováním dotazníkového šetření určeného pro samotné osoby s těžkým zrakovým postižením. Nakladatelská anotace
- Konspekt
- Senzorické a motorické funkce. Emoce. Vůle
- NLK Obory
- zdravotně postižení
- NLK Publikační typ
- kolektivní monografie
1. elektronické vydání 1 online zdroj (328 stran)
Více než tisícovka hesel slovníku zachycuje soudobý stav speciální pedagogiky a seznámí vás s nejdůležitějšími pojmy oboru. Najdete zde odborně definované, ale zároveň srozumitelně vysvětlené klíčové termíny a jejich anglické ekvivalenty.
- Klíčová slova
- Speciální pedagogika, Slovníky,
- MeSH
- lingvistika MeSH
- speciální vzdělávání MeSH
- NLK Obory
- pedagogika
- lingvistika, lékařská terminologie
Pedagogika
Vydání 1. 326 stran ; 22 cm
- MeSH
- lingvistika MeSH
- speciální vzdělávání MeSH
- Publikační typ
- terminologické slovníky MeSH
Monografie
1. vydání 128 stran : ilustrace (převážně barevné) ; 25 cm
- Konspekt
- Ortopedie. Chirurgie. Oftalmologie
- NLK Obory
- oftalmologie
- pedagogika
- NLK Publikační typ
- kolektivní monografie
