Characterization of hemodynamic and metabolic abnormalities in the heart failure spectrum: the role of combined cardiopulmonary and exercise echocardiography stress test.

Heart failure (HF) is a complex clinical syndrome characterized by different etiologies and a broad spectrum of cardiac structural and functional abnormalities. Current guidelines suggest a classification based on left ventricular ejection fraction (LVEF), distinguishing HF with reduced (HFrEF) from preserved (HFpEF) LVEF. HF should also be thought of as a continuous range of conditions, from asymptomatic stages to clinically manifest syndrome. The transition from one stage to the next is associated with a worse prognosis. While the rate of HF-related hospitalization is similar in HFrEF and HFpEF once clinical manifestations occur, accurate knowledge of the steps and risk factors leading to HF progression is still lacking, especially in HFpEF. Precise hemodynamic and metabolic characterization of patients with or at risk of HF may help identify different disease trajectories and risk factors, with the potential to identify specific treatment targets that might offset the slippery slope towards overt clinical manifestations. Exercise can unravel early metabolic and hemodynamic alterations that might be silent at rest, potentially leading to improved risk stratification and more effective treatment strategies. Cardiopulmonary exercise testing (CPET) offers valuable aid to investigate functional alterations in subjects with or at risk of HF, while echocardiography can assess cardiac structure and function objectively, both at rest and during exercise (exercise stress echocardiography [ESE]). The purpose of this narrative review was to summarize the potential advantages of using an integrated CPET-ESE evaluation in the characterization of both subjects at risk of developing HF and patients with stable HF.

Saliva as a non-invasive tool for monitoring oxidative stress in swimmers athletes performing a VO2max cycle ergometer test.

Biomarkers of oxidative stress are generally measured in blood and its derivatives. However, the invasiveness of blood collection makes the monitoring of such chemicals during exercise not feasible. Saliva analysis is an interesting approach in sport medicine because the collection procedure is easy-to-use and does not require specially-trained personnel. These features guarantee the collection of multiple samples from the same subject in a short span of time, thus allowing the monitoring of the subject before, during and after physical tests, training or competitions. The aim of this work was to evaluate the possibility of following the changes in the concentration of some oxidative stress markers in saliva samples taken over time by athletes under exercise. To this purpose, ketones (i.e. acetone, 2-butanone and 2-pentanone), aldehydes (i.e. propanal, butanal, and hexanal), α,ß-unsaturated aldehydes (i.e. acrolein and methacrolein) and di-carbonyls (i.e. glyoxal and methylglyoxal) were derivatized with 2,4-dinitrophenylhydrazine, and determined by ultra-high performance liquid chromatography coupled to diode array detector. Prostaglandin E2, F2/E2-isoprostanes, F2-dihomo-isoprostanes, F4-neuroprostanes, and F2-dihomo-isofuranes were also determined by a reliable analytical procedure that combines micro-extraction by packed sorbent and ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry. Overall the validation process showed that the methods have limits of detection in the range of units of ppb for carbonyls and tens to hundreds of ppt for isoprostanes and prostanoids, very good quantitative recoveries (90-110%) and intra- and inter-day precision lower than 15%. The proof of applicability of the proposed analytical approach was investigated by monitoring the selected markers of oxidative stress in ten swimmers performing a VO2max cycle ergo meter test. The results highlighted a clear increase of salivary by-products of oxidative stress during exercise, whereas a sharp decrease, approaching baseline values, of these compounds was observed in the recovery phase. This study opens up a new approach in the evaluation of oxidative stress and its relation to aerobic activity.

α-Synuclein Aggregated with Tau and ß-Amyloid in Human Platelets from Healthy Subjects: Correlation with Physical Exercise.

The loss of protein homeostasis that has been associated with aging leads to altered levels and conformational instability of proteins, which tend to form toxic aggregates. In particular, brain aging presents characteristic patterns of misfolded oligomers, primarily constituted of ß-amyloid (Aß), tau, and α-synuclein (α-syn), which can accumulate in neuronal membranes or extracellular compartments. Such aging-related proteins can also reach peripheral compartments, thus suggesting the possibility to monitor their accumulation in more accessible fluids. In this respect, we have demonstrated that α-syn forms detectable hetero-aggregates with Aß or tau in red blood cells (RBCs) of healthy subjects. In particular, α-syn levels and its heteromeric interactions are modulated by plasma antioxidant capability (AOC), which increases in turn with physical activity. In order to understand if a specific distribution of misfolded proteins can occur in other blood cells, a cohort of human subjects was enrolled to establish a correlation among AOC, the level of physical exercise and the concentrations of aging-related proteins in platelets. The healthy subjects were divided depending on their level of physical exercise (i.e., athletes and sedentary subjects) and their age (young and older subjects). Herein, aging-related proteins (i.e., α-syn, tau and Aß) were confirmed to be present in human platelets. Among such proteins, platelet tau concentration was demonstrated to decrease in athletes, while α-syn and Aß did not correlate with physical exercise. For the first time, α-syn was shown to directly interact with Aß and tau in platelets, forming detectable hetero-complexes. Interestingly, α-syn interaction with tau was inversely related to plasma AOC and to the level of physical activity. These results suggested that α-syn heterocomplexes, particularly with tau, could represent novel indicators to monitor aging-related proteins in platelets.