Sirtuin 3 (SIRT3) is a mitochondrial NAD(+)-dependent deacetylase that regulates energy metabolic enzymes by reversible protein lysine acetylation in various extracardiac tissues. The role of SIRT3 in myocardial energetics and in the development of mitochondrial dysfunction in cardiac pathologies, such as the failing heart, remains to be elucidated. To investigate the role of SIRT3 in the regulation of myocardial energetics and function SIRT3(-/-) mice developed progressive age-related deterioration of cardiac function, as evidenced by a decrease in ejection fraction and an increase in enddiastolic volume at 24 but not 8 weeks of age using echocardiography. Four weeks following transverse aortic constriction, ejection fraction was further decreased in SIRT3(-/-) mice compared to WT mice, accompanied by a greater degree of cardiac hypertrophy and fibrosis. In isolated working hearts, a decrease in cardiac function in SIRT3(-/-) mice was accompanied by a decrease in palmitate oxidation, glucose oxidation, and oxygen consumption, whereas rates of glycolysis were increased. Respiratory capacity and ATP synthesis were decreased in cardiac mitochondria of SIRT3(-/-) mice. HPLC measurements revealed a decrease of the myocardial ATP/AMP ratio and of myocardial energy charge. Using LC-MS/MS, we identified increased acetylation of 84 mitochondrial proteins, including 6 enzymes of fatty acid import and oxidation, 50 subunits of the electron transport chain, and 3 enzymes of the tricarboxylic acid cycle. Lack of SIRT3 impairs mitochondrial and contractile function in the heart, likely due to increased acetylation of various energy metabolic proteins and subsequent myocardial energy depletion.

RVSD is an independent predictor of all-cause mortality in HFPEF. Patients with HFPEF and RVSD had significantly higher one-year all-cause and cardiovascular mortality than those with normal RV function.

OBJECTIVE: The aim of this study was to evaluate characteristics of patients with heart failure (HF) with preserved ejection fraction (HFPEF) and to assess prognostic predictors in 2-year follow-up. METHODS: We included prospectively 109 patients admitted to the internal department for HF, grouped into HFPEF (EF>40 %, n = 63) and HF with reduced EF (HFREF) (EF ≤ 40 %, n = 46). Preserved right ventricular systolic function (PRV) was defi ned as the peak systolic tricuspid annular velocity (S') > 10.8 cm/s. RESULTS: HFPEF and HFREF patients had non-signifi cantly different 2-year all-cause and CV mortality (28.6 % vs 37.0 %, 17.5 % vs 21.7 %). Patients with HFPEF and PRV vs dysfunctional RV had a better survival (76.6 % vs 56.3 %, p=0.045). In HFPEF, the patients who survived had a trend to better S' (13.6 ± 3.1 cm/s vs 11.9 ± 3.4 cm/s, p=0.055), shorter QTc (427 ± 42ms vs 454 ± 42ms, p = 0.058), and all-cause mortality was lowered only by anticoagulants (12.0 % vs 39.5 %, p = 0.02). QTc interval and PRV emerged as predictors of all-cause mortality (HR 1.7 per 40 ms change, 95 % CI 1.1-2.6, p = 0.02, HR 0.38, 95 % CI 0.15-0.93, p = 0.03). CONCLUSIONS: In HFPEF, we observed a trend to lower all-cause and CV mortality compared to HFREF and anticoagulants were the only therapy that signifi cantly lowered mortality. PRV and QTc interval emerged as independent predictors of survival (Tab. 6, Fig. 2 Limitations:The results of our study are limited by the relatively small groups of patients with both HFPEF and HFREF and by the mid-term follow-up period. The assessment of the RV systolic function was limited to just one parameter -the peak systolic velocity of the lateral tricuspid annulus in tissue Doppler imaging.

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Aim:To assess the influence of atrial fibrillation on mortality in heart failure with preserved ejection fraction (HFPEF) in a prospective study compared to heart failure with reduced ejection fraction (HFREF). We have hypothesized that atrial fibrillation decreases survival in HFPEF. Patients and Methods:The study included a total of 109 patients admitted to Medical wards for heart failure within one year's period (2010)(2011). The follow-up was 24 months. Patients were divided into two groups based on left ventricular ejection fraction (LVEF); HFPEF with LVEF more than 40% (n=64) and HFREF with LVEF less than 40% (n=45). For each patient we evaluated the presence of atrial fibrillation (AF) on ECG in the history and on admission. Data were analyzed using JMP9 statistical program. Unless otherwise specified, the data are presented as means. Results:The prevalence of history of AF was significantly higher in HFPEF vs. HFREF (67% vs. 44%, p<0.05). We observed a trend of higher prevalence of AF on admission in HFPEF vs. HFREF (50% vs. 29%, p=0.058) and significantly higher prevalence of non-sinus rhythm on admission in HFPEF vs. HFREF (56% vs. 34%, p<0.05). There was no significant difference in hospital mortality, cardiovascular mortality and all-cause mortality among patients with and without the history of AF neither in HFPEF nor in HFREF. The same results were found when comparing patients with and without the presence of AF on admission. AF was not an independent predictor of mortality. Conclusion: We observed significantly higher prevalence of history of AF and significantly higher prevalence of nonsinus rhythm on admission in HFPEF vs. HFREF. We found a trend of higher prevalence of AF on admission in HFPEF vs. HFREF. We did not find AF to be a predictor of two-year mortality neither in patients with HFPEF nor in patients with HFREF.