Defects in fatty acid (FA) utilization have been well described in group 1 pulmonary hypertension (PH) and in heart failure (HF), yet poorly studied in group 2 PH. This study was to assess whether the metabolomic profile of patients with pulmonary hypertension (PH) due HF, classified as group 2 PH, differs from those without PH. We conducted a proof-of-principle cross-sectional analysis of 60 patients with chronic HF with reduced ejection fraction and 72 healthy controls in which the circulating level of 71 energy-related metabolites was measured using various methods. Echocardiography was used to classify HF patients as noPH-HF (n = 27; mean pulmonary artery pressure [mPAP] 21 mmHg) and PH-HF (n = 33; mPAP 35 mmHg). The profile of circulating metabolites among groups was compared using principal component analysis (PCA), analysis of covariance (ANCOVA), and Pearson’s correlation tests. Patients with noPH-HF and PH-HF were aged 64 ± 11 and 68 ± 10 years, respectively, with baseline left ventricular ejection fractions of 27 ± 7% and 26 ± 7%. Principal component analysis segregated groups, more markedly for PH-HF, with long-chain acylcarnitines, acetylcarnitine, and monounsaturated FA carrying the highest loading scores. After adjustment for age, sex, kidney function, insulin resistance, and N-terminal pro-brain natriuretic peptide (NT-proBNP), 5/15 and 8/15 lipid-related metabolite levels were significantly different from controls in noPH-HF and PH-HF subjects, respectively. All metabolites for which circulating levels interacted between group and NT-proBNP significantly correlated with NT-proBNP in HF-PH, but none with HF-noPH. FA-related metabolites were differently affected in HF with or without PH, and may convey adverse outcomes given their distinct correlation with NT-proBNP in the setting of PH.

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Purpose: NT-pro B-type natriuretic peptide (NT-proBNP) has predominantly ventricular origin, produced and released in response to increases in ventricular wall stress. It has been related both to systolic and diastolic left ventricular (LV) dysfunction. The purpose of this study was to investigate the correlations of NT-proBNP levels with echocardiographic measurements in patients with systolic heart failure. Methods: We prospectively investigated patients with symptoms/signs of CHF class II-IV and LV biplane ejection fraction (EF)<45%. After clinical evaluation an echocardiogram was done including M mode, 2D (ventricular dimensions and LV ejection fraction (EF)), conventional Doppler (LV inflow E wave, pulmonary artery systolic pressure (PASP), LV dP/dT). Early and late peak systolic myocardial velocity (Sm1 and Sm2), velocity time integral of Sm(SmVTI), early(Em) and late (Am) peak diastolic myocardial velocities were assessed by pulsed tissue Doppler of septal and lateral mitral annulus and tricuspid annulus. Blood was collected for NT-proBNP measurement. Results: Twenty patients were included 85% male, 71±9,5 years. Mean LV EF was 30±8%, dP/dT 557±164mmHg/s, NT-proBNP 7052±6314pg/mL. There was a trend toward higher NT-proBNP levels in those patients with lower inferior vena cava (IVC) colapse index (p=0,09) and a nonsignificant higher expiratory IVC diameter (p=0,15). Right ventricular end-diastolic dimension by 2D planimetry of four-chamber apical view showed a significant direct correlation to NT-pro-BNP levels (r 2 =0,24; p=0,03) as did PSAP (r 2 =0,37; p=0,009). No significant correlation was found with tissue Doppler measurements of tricuspid annulus. There was a trend to lower mitral E-wave deceleration time (r2=0,15; p=0,09) in patients with higher NT-pro BNP. No correlation was found to dP/dT and there was a nonsignificant trend to lower LV EF (p=0,07) in those with higher natriuretic peptides. Sm VTI of septal mitral annulus inversely correlated to 20; p=0,049). No other tissue Doppler measurements showed a signicant relation. PSAP was the only independent predictor of NT-proBNP in multiple regression analysis (p=0,029). Conclusion: NT-proBNP level relates to right ventricular dimention and PSAP in systolic heart failure patients. This relation sugests that right ventricular secretion of NT-proBNP may be an important contributor to serum levels of this natriuretic peptide in patients with systolic heart failure. Septal mitral annulus Sm VTI may be a more accurate estimate of global systolic function since it may be under influence of both the right and left ventricle.Background: Heart failure is characterized by neurohormonal activation that can be assessed with measurements of plasma brain natriuretic peptide (BNP). The purpose of this study was to assess changes in BNP levels after intravenous administration of levosimendan and their association with the extent of myocardial scar. Methods: We studied 14 patients (12 men, mean age 67.9±8.5 years) with a history of old myocardial infarction, left ven...

Introduction Heart failure (HF) is still a major cause of mortality worldwide. HF pathogenesis involves disturbances in cardiac energy metabolism. Studies have shown that preventive treatment with a diet supplemented with vitamins B3 or B9/B12 in experimental models of HF, exhibits beneficial effects on cardiac and mitochondrial functions and improves survival. Therefore, the overall objective of our pilot study is to evaluate the curative benefit of a synthetic diet enriched with vitamins B3 (nicotinamide riboside), B9 and B12 (BVit) in a mouse model of HF based on the hypothesis that this enriched diet is beneficial for cardiac function via an improvement of cardiac metabolism. Method Pressure overload was induced by transverse aortic constriction (TAC) in 8‐week‐old male and female C57Bl6/N mice. Four weeks post‐TAC and according to their cardiac function evaluated by echocardiography, mice were randomised to a BVit‐enriched diet or not and compared to SHAM animals. The criteria of selection for randomisation were as follows: 10% decrease in ejection fraction (EF), 30% increase in left ventricular (LV) mass and an average pressure gradient of 60mmHg. Mice survival was evaluated and cardiac function was assessed by echocardiography every 4 weeks. Blood samples were taken at 8 weeks of treatment in fasted mice (5 hours) for non‐targeted lipidomics mass spectrometry‐based analysis. Results Our pilot study show that survival is not improved in males while mortality is reduced in females from 12 weeks of treatment. In males, the reduced EF in the TAC group is not improved by BVit treatment and myocardial hypertrophy, as illustrated by the left ventricular mass (+20% in TAC), is exacerbated with BVit treatment. In contrast, in females, both EF and cardiac hypertrophy were improved (+20% and ‐13% respectively) after 12 weeks of BVit treatment. To better understand the sexual dimorphism in the response of BVit, non‐targeted lipidomics was used on plasma from mice following 8 weeks of treatment. In TAC‐females, compared to their SHAM controls, a decrease in triglycerides (TG) and an increase in choline phospholipids were observed while the lipid profile was normalized with BVit treatment. In TAC‐males vs SHAM, however, TGs were significantly increased and the treatment with BVit exacerbated the lipidomic profile both in terms of TGs and additional lipid species (identification in progress). Conclusion Our pilot study suggests a sexual dimorphism in the response to BVit treatment in experimental HF. Indeed, the benefit of BVit treatment is only shown in females with a delay in the mortality rate associated with improved cardiac function and normalisation of lipid disturbances. To explore and understand the mechanisms underlying this sexual dimorphism, the lipid profile hypothesis appears as a relevant avenue to explore in the future.