Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy.

BACKGROUND: Myocardial metabolic impairment is a major feature in chronic heart failure. As the major coenzyme in fuel oxidation and oxidative phosphorylation and a substrate for enzymes signaling energy stress and oxidative stress response, nicotinamide adenine dinucleotide (NAD+) is emerging as a metabolic target in a number of diseases including heart failure. Little is known on the mechanisms regulating homeostasis of NAD+ in the failing heart. METHODS: To explore possible alterations of NAD+ homeostasis in the failing heart, we quantified the expression of NAD+ biosynthetic enzymes in the human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by Serum Response Factor transcription factor depletion in the heart (SRFHKO) or of cardiac hypertrophy triggered by transverse aorta constriction. We studied the impact of NAD+ precursor supplementation on cardiac function in both mouse models. RESULTS: We observed a 30% loss in levels of NAD+ in the murine failing heart of both DCM and transverse aorta constriction mice that was accompanied by a decrease in expression of the nicotinamide phosphoribosyltransferase enzyme that recycles the nicotinamide precursor, whereas the nicotinamide riboside kinase 2 (NMRK2) that phosphorylates the nicotinamide riboside precursor is increased, to a higher level in the DCM (40-fold) than in transverse aorta constriction (4-fold). This shift was also observed in human failing heart biopsies in comparison with nonfailing controls. We show that the Nmrk2 gene is an AMP-activated protein kinase and peroxisome proliferator-activated receptor α responsive gene that is activated by energy stress and NAD+ depletion in isolated rat cardiomyocytes. Nicotinamide riboside efficiently rescues NAD+ synthesis in response to FK866-mediated inhibition of nicotinamide phosphoribosyltransferase and stimulates glycolysis in cardiomyocytes. Accordingly, we show that nicotinamide riboside supplementation in food attenuates the development of heart failure in mice, more robustly in DCM, and partially after transverse aorta constriction, by stabilizing myocardial NAD+ levels in the failing heart. Nicotinamide riboside treatment also robustly increases the myocardial levels of 3 metabolites, nicotinic acid adenine dinucleotide, methylnicotinamide, and N1-methyl-4-pyridone-5-carboxamide, that can be used as validation biomarkers for the treatment. CONCLUSIONS: The data show that nicotinamide riboside, the most energy-efficient among NAD precursors, could be useful for treatment of heart failure, notably in the context of DCM, a disease with few therapeutic options.

Factors associated with adherence to asthma treatment with inhaled corticosteroids: A cross-sectional exploratory study.

BACKGROUND: Understanding factors at the patient, provider or organizational level associated with inhaled corticosteroids (ICSs) adherence is important when planning adherence-enhancing interventions. OBJECTIVE: To explore factors associated with adherence to ICS among patients with asthma aged 12-45 years. METHODS: A cross-sectional study was conducted among patients with asthma reporting ICS prescription during the baseline interview of an intervention study. Three methods were used to measure ICS adherence: a 4-item self-report questionnaire, a single question (SQ) measuring past 7-day exposure to ICS and a medication possession ratio (MPR, i.e., the sum of ICS days of supply/365). We assessed 46 potential factors of ICS adherence derived from the Predisposing, Reinforcing and Enabling Constructs in Educational Diagnosis and Evaluation (PRECEDE) model. Their association with ICS adherence was measured using multivariate logistic regressions. RESULTS: Among the 319 participants included, 16.0% were deemed adherent according to the 4-item questionnaire. This proportion was 43.0% and 9.1% for the SQ and the MPR method, respectively. Ten factors were associated with good ICS adherence. Among these factors, four were associated with adherence through one of the measuring methods: a low family income level, a high number of asthma drugs used, a good knowledge of asthma pathophysiology and the perception that following the ICS prescription was easy. Two factors emerged through more than one measure: perceiving asthma severity as moderate to very severe and perceiving a high risk of death if ICSs are not taken as prescribed. CONCLUSION: ICS adherence was poor in those individuals with asthma. Future adherence-enhancing interventions could target the identified modifiable risk factors. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02093013.

Number of patients needed to prescribe statins in primary cardiovascular prevention: mirage and reality.

Background: Number of patients needed to treat (NNT) with a statin in primary prevention of coronary heart disease (CHD) is often misinterpreted because this single statistic averages results from heterogeneous studies. Objective: To provide estimates of the number of individuals needed to be prescribed a statin to prevent one CHD event accounting for their level of CHD risk and for persistence to treatment. Methods: A post hoc analysis was conducted based on a Cochrane review on statins for the primary prevention of cardiovascular diseases. Five-year NNTs were calculated separately from randomized clinical trials (RCTs), including 'lower' and 'higher' risk populations (CHD mean event rates of 3.7 and 14.4 per 1000 person-years, respectively). NNTs were adjusted for 5-year persistence to treatment using a value of 65%. Results: Persistence-adjusted 5-year NNTs to prevent one CHD for the lower and higher CHD risk categories were 146 [95% confidence interval (CI): 117-211] and 53 (95% CI: 39-88) respectively, values 25% and 15% higher than their unadjusted counterpart (117, 95% CI: 94-167 and 46, 95% CI: 34-78). Conclusions: Five-year NNTs for statins to prevent a first CHD is almost three times higher in those at lower versus higher risk populations. Reporting combined results from RCTs including subjects at different cardiovascular risks should be avoided. Individualizing the risk of CHD should orient family physicians and their patients in their choice of preventive approaches and generate more realistic expectations about compliance and outcomes.

Comprehensive Characterization of the Interaction between Pulsed Electric Fields and Live Cells by Confocal Raman Microspectroscopy.

This study reports a comprehensive analysis of the effect of 100 µs electric pulses on the biochemical composition of live cells using a label-free approach, confocal Raman microspectroscopy. We investigated different regions of interest around the nucleus of the cells and the dose-effect relationship related to different electric pulse parameters. We also extended the study to another cell type. Membrane resealing was monitored by pulsing the cells in reversible or irreversible electropermeabilization condition at different temperatures. Our results confirmed a previous publication showing that proteins and lipids were highly impacted by the delivery of electric pulses. These chemical changes were similar in different locations around the cell nucleus. By sweeping the field magnitude, the number of electric pulses, or their repetition rate, the Raman signatures of live cells appeared to be related to the electropermeabilization state, verified by Yo-Pro-1 uptake. We also demonstrated that the chemical changes in the Raman signatures were cell-dependent even if common features were noticed between the two cell types used.

Exploring the Applicability of Nano-Poration for Remote Control in Smart Drug Delivery Systems.

Smart drug delivery systems represent an interesting tool to significantly improve the efficiency and the precision in the treatment of a broad category of diseases. In this context, a drug delivery mediated by nanosecond pulsed electric fields seems a promising technique, allowing for a controlled release and uptake of drugs by the synergy between the electropulsation and nanocarriers with encapsulated drugs. The main concern about the use of electroporation for drug delivery applications is the difference in dimension between the liposome (nanometer range) and the cell (micrometer range). The choice of liposome dimension is not trivial. Liposomes larger than 500 nm of diameter could be recognized as pathogen agents by the immune system, while liposomes of smaller size would require external electric field of high amplitudes for the membrane electroporation that could compromise the cell viability. The aim of this work is to theoretically study the possibility of a simultaneous cell and liposomes electroporation. The numerical simulations reported the possibility to electroporate the cell and a significant percentage of liposomes with comparable values of external electric field, when a 12 nsPEF is used.

Cell Membrane Electropulsation: Chemical Analysis of Cell Membrane Modifications and Associated Transport Mechanisms.

The transport of substances across the cell membrane is complex because the main physiological role of the membrane is the control of the substances that would enter or exit the cells. Life would not be possible without this control. Cell electropulsation corresponds to the delivery of electric pulses to the cells and comprises cell electroporation and cell electropermeabilization. Cell electropulsation allows for the transport of non-permeant molecules across the membrane, bypassing the physiological limitations. In this chapter we discuss the changes occurring in the cell membrane during electroporation or electropermeabilization as they allow to understand which molecules can be transported as well as when and how their transport can occur. Electrophoretic or diffusive transports across the cell membrane can be distinguished. This understanding has a clear impact on the choice of the electrical parameters to be applied to the cells as well as on other aspects of the experimental protocols that have to be set to load the cells with non-permeant molecules.

Optimization of the Electroformation of Giant Unilamellar Vesicles (GUVs) with Unsaturated Phospholipids.

Giant unilamellar vesicles (GUV) are widely used cell membrane models. GUVs have a cell-like diameter and contain the same phospholipids that constitute cell membranes. The most frequently used protocol to obtain these vesicles is termed electroformation, since key steps of this protocol consist in the application of an electric field to a phospholipid deposit. The potential oxidation of unsaturated phospholipids due to the application of an electric field has not yet been considered even though the presence of oxidized lipids in the membrane of GUVs could impact their permeability and their mechanical properties. Thanks to mass spectrometry analyses, we demonstrated that the electroformation technique can cause the oxidation of polyunsaturated phospholipids constituting the vesicles. Then, using flow cytometry, we showed that the amplitude and the duration of the electric field impact the number and the size of the vesicles. According to our results, the oxidation level of the phospholipids increases with their level of unsaturation as well as with the amplitude and the duration of the electric field. However, when the level of lipid oxidation exceeds 25 %, the diameter of the vesicles is decreased and when the level of lipid oxidation reaches 40 %, the vesicles burst or reorganize and their rate of production is reduced. In conclusion, the classical electroformation method should always be optimized, as a function of the phospholipid used, especially for producing giant liposomes of polyunsaturated phospholipids to be used as a cell membrane model.

Effectiveness of an asthma integrated care program on asthma control and adherence to inhaled corticosteroids.

OBJECTIVE: To measure the effectiveness of an integrated care program for individuals with asthma aged 12-45 years, on asthma control and adherence to inhaled corticosteroids (ICS). METHODS: Researchers used a theoretical model to develop the program and assessed effectiveness at 12 months, using a pragmatic controlled clinical trial design. Forty-two community pharmacists in Quebec, Canada recruited participants with either uncontrolled or mild-to-severe asthma. One group was exposed to the program; another received usual care. Asthma control was measured with the Asthma Control Questionnaire; ICS adherence was assessed with the Morisky medication adherence scale and the medication possession ratio. Program effectiveness was assessed with an intention-to-treat approach using multivariate generalized estimating equation models. RESULTS: Among 108 exposed and 241 non-exposed, 52.2% had controlled asthma at baseline. At 12-months, asthma control had improved in both groups but the interaction between study groups and time was not significant (p = 0.09). The proportion of participants with good ICS adherence was low at baseline. Exposed participants showed improvement in adherence and the interaction between study groups and time was significant (p = 0.02). CONCLUSION: An integrated intervention, with healthcare professionals collaborating to optimize asthma control, can improve ICS adherence.

High-yield nontoxic gene transfer through conjugation of the CM18-Tat11 chimeric peptide with nanosecond electric pulses.

We report a novel nontoxic, high-yield, gene delivery system based on the synergistic use of nanosecond electric pulses (NPs) and nanomolar doses of the recently introduced CM18-Tat11 chimeric peptide (sequence of KWKLFKKIGAVLKVLTTGYGRKKRRQRRR, residues 1-7 of cecropin-A, 2-12 of melittin, and 47-57 of HIV-1 Tat protein). This combined use makes it possible to drastically reduce the required CM18-Tat11 concentration and confines stable nanopore formation to vesicle membranes followed by DNA release, while no detectable perturbation of the plasma membrane is observed. Two different experimental assays are exploited to quantitatively evaluate the details of NPs and CM18-Tat11 cooperation: (i) cytofluorimetric analysis of the integrity of synthetic 1,2-dioleoyl-sn-glycero-3-phosphocholine giant unilamellar vesicles exposed to CM18-Tat11 and NPs and (ii) the in vitro transfection efficiency of a green fluorescent protein-encoding plasmid conjugated to CM18-Tat11 in the presence of NPs. Data support a model in which NPs induce membrane perturbation in the form of transient pores on all cellular membranes, while the peptide stabilizes membrane defects selectively within endosomes. Interestingly, atomistic molecular dynamics simulations show that the latter activity can be specifically attributed to the CM18 module, while Tat11 remains essential for cargo binding and vector subcellular localization. We argue that this result represents a paradigmatic example that can open the way to other targeted delivery protocols.

Life cycle assessment of alternative pulp mill sludge treatment methods in Finland.

Proper management of wastewater treatment plant side streams in pulp and paper mills is a matter of great interest. This study evaluates the environmental impact of different strategies in the management of biosludge from pulp and paper mills in Finland through a Life Cycle Assessment methodology. The base industrial standard practice, biosludge incineration for energy recovery and ash landfill disposal (Scenario 1), was compared to the alternative process of hydrothermal carbonization. The hydrochar generated from hydrothermal carbonization was evaluated for energy recovery through incineration (Scenario 2), or for use in composting for nutrient recovery (Scenario 3). The results showed that the hydrothermal process improved the overall environmental performance of the sludge management, particularly in terms of energy consumption and greenhouse gas emissions. The use of hydrochar as a soil amendment in composting also resulted in a significant reduction on the environmental impact compared to the other two scenarios. Overall, this study highlights the potential of hydrothermal carbonization and hydrochar utilization as sustainable options for managing biosludge from pulp mills.

Transport of siRNA through lipid membranes driven by nanosecond electric pulses: an experimental and computational study.

The use of small interfering RNA (siRNA) is a blossoming technique for gene regulation. However, its therapeutic potential is today severely hampered by the lack of an efficient means of safely delivering these nucleic acids to the intracellular medium. We report here that a single 10 ns high-voltage electric pulse can permeabilize lipid vesicles and allow the delivery of siRNA to the cytoplasm. Combining experiments and molecular dynamics simulations has allowed us to provide the detailed molecular mechanisms of such transport and to give practical guidance for the design of protocols aimed at using nanosecond-pulse siRNA electro-delivery in medical and biotechnological applications.

Microsecond and nanosecond electric pulses in cancer treatments.

New local treatments based on electromagnetic fields have been developed as non-surgical and minimally invasive treatments of tumors. In particular, short electric pulses can induce important non-thermal changes in cell physiology, especially the permeabilization of the cell membrane. The aim of this review is to summarize the present data on the electroporation-based techniques: electrochemotherapy (ECT), nanosecond pulsed electric fields (nsPEFs), and irreversible electroporation (IRE). ECT is a safe, easy, and efficient technique for the treatment of solid tumors that uses cell-permeabilizing electrical pulses to enhance the activity of a non-permeant (bleomycin) or low permeant (cisplatin) anticancer drug with a very high intrinsic cytotoxicity. The most interesting feature of ECT is its unique ability to selectively kill tumor cells without harming normal surrounding tissue. ECT is already used widely in the clinics in Europe. nsPEFs could represent a drug free, purely electrical cancer therapy. They allow the inhibition of tumor growth, and interestingly, nsPEF can target intracellular organelles. However, many questions remain on the mechanism of action of these pulses. Finally, IRE is a new ablation procedure using pulses that provoke the permanent permeabilization of the cells resulting in their death. This technique does not result in any thermal effect, which is its main advantage in current physical ablation technologies. For both the nsPEF and the IRE, the preservation of the normal tissue, which is characteristic of ECT, has not yet been shown and their safety and efficacy still have to be investigated thoroughly in vivo and in the clinics.

Protonation of lipids impacts the supramolecular and biological properties of their self-assembly.

We assessed in this work how a chemical structure difference could influence a supramolecular organization and then its biological properties. In our case study, we considered two amphiphilic lipidic gene vectors. The chemical difference was situated on their hydrophilic part which was either a pure neutral thiourea head or a mixture of three thiourea function derivatives, thiourea, iminothiol, and charged iminothiol. This small difference was obtained thanks to the last chemical deprotection conditions of the polar head hydroxyl groups. Light, neutron, and X-ray scattering techniques have been used to investigate the spatial structure of the liposomes and lipoplexes formed by the lipids. The chemical structure difference impacts the supramolecular assemblies of the lipids and with DNA as shown by fluorescence correlation spectroscopy (FCS), X-ray, and neutron scattering. Hence the structures formed were found to be highly different in terms of liposomes to DNA ratio and size and polydispersity of the aggregates. Finally, the transfection and internalization results proved that the differences in the structure of the lipid aggregates fully affect the biological properties of the lipopolythiourea compounds. The lipid containing three functions is a better gene transfection agent than the lipid which only contains one thiourea moiety. As a conclusion, we showed that the conditions of the last chemical step can influence the lipidic supramolecular structure which in turn strongly impacts their biological properties.

Solvatochromic dissociation of non-covalent fluorescent organic nanoparticles upon cell internalization.

Amorphous red-emitting materials involving solvatochromic small molecules have been processed by the reprecipitation method as non-doped nanospheres characterized by a remarkably low polydispersity. Their mean diameter could simply be tuned by the concentration of the organic solution giving rise to time-stable dispersion of 85-200 nm-sized nanoparticles. Time-resolved measurements performed on solid nanoparticles showed significant size-dependence effects of the emission lifetime and maxima evidencing populations with distinct molecular conformations. Nanoparticle internalization has proved successful in NIH-3T3 murine fibroblasts with normal toxicity effects after 48 h. Fluorescence confocal microscopy under one- and two-photon excitations revealed dual emission enabling localization of the organic material within the plasma membrane and the cytoplasm. Model experiments resorting to suspended artificial lipid bilayers allowed us to conclude on the dissolution of nanoparticles by the phospholipid membrane during the internalization process. They let us to assume that uptake of hydrophobic nanoparticles by living cells implies an endocytosis mechanism operating through the formation of plasmic vesicles.

Risk of perinatal mortality associated with inhaled corticosteroid use for the treatment of asthma during pregnancy.

BACKGROUND: Four studies investigating the association between inhaled corticosteroid (ICS) use during pregnancy and perinatal mortality reported no significantly increased risk. These studies must be interpreted with caution because they have insufficient statistical power and a lack of adjustment for potential confounders. OBJECTIVES: We sought to evaluate whether asthmatic women exposed to ICSs during pregnancy are more at risk of perinatal mortality than asthmatic women not exposed. We also sought to estimate the risk of perinatal mortality as a function of the daily ICS dose taken during pregnancy. METHODS: From the linkage of 3 administrative databases from Quebec, a cohort including 13,004 single pregnancies from asthmatic women was constructed. We used a 2-stage sampling cohort design to obtain information on cigarette smoking from the medical charts of 487 mothers. The final estimates of the odds ratios (ORs) of perinatal mortality were estimated with a logistic regression model. RESULTS: The cohort was formed of 4,140 women who used greater than 0 to 250 µg/d ICS, 1,140 women who used greater than 250 µg/d ICS, and 7,724 nonusers of ICSs during pregnancy. Women exposed to ICSs (any dose) had a nonsignificant increased risk of perinatal mortality (OR, 1.07; 95% CI, 0.70-1.61). The use of greater than 250 µg/d ICS was associated with a nonsignificant 52% increased risk of perinatal mortality (OR, 1.52; 95% CI, 0.62-3.76). CONCLUSION: The risk of perinatal mortality was not found to be significantly associated with ICS use during pregnancy. The result associated with higher doses of ICSs is limited due to a lack of statistical power and a possibility of residual confounding by asthma severity and control.

Comparative gene transfer between cationic and thiourea lipoplexes.

BACKGROUND: We have previously developed lipopolythiourea lipids as neutral DNA condensing agents for systemic gene delivery. Optimization of the lipopolythiourea structure led to efficient transfecting agents. To further evaluate these lipids, we investigated the internalization process of the thiourea lipoplexes and their intracellular mechanism of transfection versus that of cationic lipoplexes. METHODS: The MTT test was used for cytotoxicity assessment. Transfection efficiency was determined by luciferase read-out. Permeation to propidium iodide and enhanced green fluorescent protein was evaluated by flow cytometry. Kinetics of internalization and DNA release were monitored by confocal microscopy with labelled DNA. Endocytosis inhibitors were used to study the mechanisms of lipoplex internalization. RESULTS: Although thiourea/DNA complexes exhibit an almost similar level of transfection compared to that of cationic complexes, the thiourea lipoplexes were shown to be six-fold less internalized. Complexes were able to permeabilize the cytoplasmic membrane to 30 kDa molecules. Finally, DNA was shown to be released in less than 10 min in the cellular cytoplasm versus 30 min for cationic lipoplexes. CONCLUSIONS: Despite a weaker internalization compared to cationic lipids, the thiourea lipoplexes were able to transfect cells at a similar level as a result of its greater ability to destabilize the cytoplasmic membrane and release DNA.

The impact of obesity on walking and cycling performance and response to pulmonary rehabilitation in COPD.

BACKGROUND: We examined the influence of overweight and obesity on pulmonary function, exercise tolerance, quality of life and response to pulmonary rehabilitation in COPD. METHODS: 261 patients with COPD were divided into three groups: normal body mass index (BMI), overweight and obese. Baseline and post rehabilitation pulmonary function, 6-min walking test (6MWT), endurance time during a constant workrate exercise test (CET) and St. George's Respiratory Questionnaire (SGRQ) scores were compared between all three classes of BMI. RESULTS: At baseline, obese and overweight patients had less severe airflow obstruction compared to normal BMI patients. There was no baseline difference in CET performance or SGRQ scores across BMI classes and 6MWT was reduced in the presence of obesity (p < 0.01). Compared to baseline, post-rehabilitation 6MWT, CET performance and SGRQ scores improved significantly in each group (p < 0.01), but 6MWT was still significantly lower in the presence of obesity. CONCLUSIONS: Walking, but not cycling performance was worse in obese patients. This difference was maintained post rehabilitation despite significant improvements. Weight excess may counterbalance the effect of a better preserved respiratory function in the performance of daily activities such as walking. However, obesity and overweight did not influence the magnitude of improvement after pulmonary rehabilitation.

Cost-effectiveness of alternative strategies for vaccination of adolescents against serogroup B IMD with the MenB-FHbp vaccine in Canada.

OBJECTIVE: Serogroup B meningococci (MnB) are now the largest cause of invasive meningococcal disease (IMD) in Canada. We assessed the clinical and economic impact of 3 adolescent MenB-FHbp immunization strategies. METHODS: A population-based dynamic transmission model was developed to simulate the transmission of MnB among the entire Canadian population over a 30-year time horizon. Age group-based IMD incidence, bacterial carriage and transmission, disease outcomes, costs, and impact on quality of life were obtained from Canadian surveillance data and published literature. The vaccine was assumed to provide 85% protection against IMD and 26.6% against carriage acquisition. The model estimated the impact of routine vaccination with MenB-FHbp in 3 strategies: (1) age 14, along with existing school-based programs, with 75% uptake; (2) age 17 with 75% uptake, assuming school vaccination; and (3) age 17 with 30% uptake, assuming vaccination outside of school. Costs were calculated from the Canadian societal perspective. RESULTS: With no vaccination, an estimated 3974 MnB cases would be expected over 30 years. Vaccination with strategies 1-3 were estimated to avert 688, 1033, and 575 cases, respectively. These outcomes were associated with incremental costs per quality-adjusted life-year of $976,000, $685,000, and $490,000. CONCLUSIONS: Our model indicated that if the vaccine reduces risk of carriage acquisition, vaccination of older adolescents, even at lower uptake, could have a significant public health impact. Due to low disease incidence, MnB vaccination is unlikely to meet widely accepted cost-effectiveness thresholds, but evaluations of new programs should consider the overall benefits of the vaccination.

Blood NAD levels are reduced in very old patients hospitalized for heart failure.

BACKGROUND: Age-associated decline in nicotinamide adenine dinucleotide (NAD) tissue levels has emerged as potential driving mechanism in the establishment of energy metabolism perturbations in the context of chronic diseases, notably heart failure. OBJECTIVE: The aim of this study was to measure the blood NAD levels in a healthy blood donor population and in a population of elderly patients hospitalized for decompensated heart failure. METHOD: Whole blood sample was collected from 151 healthy voluntary blood donors, aged 19 to 68 years, and from 19 patients aged 75 to 101 years and hospitalized for decompensated heart failure in a geriatric ward. Metabolites were extracted by the hot buffered ethanol procedure and NAD was quantified in triplicate for each sample. RESULTS: The mean concentration of NAD in blood of healthy donors was 23.4 (SD 4.05) µmol/L. There was no significant correlation between NAD levels and donors' age nor sex in the healthy population when studied as a whole. However, the linear regression curves of NAD concentration plotted against age differed between males and females (p = 0.0283) with a trend in males to decline with age that was not observed in females. The mean concentration of NAD in whole blood samples of the geriatric population was 20.7 (SD 3.6) µmol/L (p = 0.007 versus the healthy blood donor population). There were no differences between males and females (p = 0.7) nor between patients with ejection fraction inferior or superior to 50% (p = 0.86) in the geriatric population. CONCLUSION: This study highlighted a diminution of NAD blood levels for elderly patients hospitalized for decompensated heart failure in comparison to a healthy population, suggesting that new therapeutics to restore NAD stock and energy metabolism would be a major progress in the management of this type of geriatric patients.