Unique association of rare cardiovascular disease in an athlete with ventricular arrhythmias

Ventricular arrhythmias are a leading cause of non-elegibility to competitive sport. The failure to detect a significant organic substrate in the initial stage of screening does not preclude the identification of structural pathologies in the follow-up by using advanced imaging techniques. Here we report the case of a senior athlete judged not elegible because an arrhythmia with the morphology consistent with the origin of the left ventricle, in which subsequent execution of a cardiac MR and a thoracic CT scan has allowed the identification of an unique association between an area of myocardial damage, probable site of origine of the arrhythma, and a rare aortic malformation

The Life Span Determinant p66Shc Localizes to Mitochondria Where It Associates with Mitochondrial Heat Shock Protein 70 and Regulates Trans-membrane Potential

P66Shc regulates life span in mammals and is a critical component of the apoptotic response to oxidative stress. It functions as a downstream target of the tumor suppressor p53 and is indispensable for the ability of oxidative stress-activated p53 to induce apoptosis. The molecular mechanisms underlying the apoptogenic effect of p66Shc are unknown. Here we report the following three findings. (i) The apoptosome can be properly activated in vitro in the absence of p66Shc only if purified cytochrome c is supplied. (ii) Cytochrome c release after oxidative signals is impaired in the absence of p66Shc. (iii) p66Shc induces the collapse of the mitochondrial trans-membrane potential after oxidative stress. Furthermore, we showed that a fraction of cytosolic p66Shc localizes within mitochondria where it forms a complex with mitochondrial Hsp70. Treatment of cells with ultraviolet radiation induced the dissociation of this complex and the release of monomeric p66Shc. We propose that p66Shc regulates the mitochondrial pathway of apoptosis by inducing mitochondrial damage after dissociation from an inhibitory protein complex. Genetic and biochemical evidence suggests that mitochondria regulate life span through their effects on the energetic metabolism (mitochondrial theory of aging). Our data suggest that mitochondrial regulation of apoptosis might also contribute to life span determination

Biomarkers of Response to Low-Dose Aspirin in Familial Adenomatous Polyposis Patients

Background: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial. Methods: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas. Results: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B2 generation ex vivo (serum TXB2). However, enhanced residual urinary 11-dehydro-TXB2 and urinary PGEM, primary metabolites of TXA2 and prostaglandin (PG)E2, respectively, were detected in association with incomplete acetylation of COX-1 in normal colorectal biopsies and adenomas. Proteomics of adenomas showed that Aspirin significantly modulated only eight proteins. The upregulation of vimentin and downregulation of HBB (hemoglobin subunit beta) distinguished two groups with high vs. low residual 11-dehydro-TXB2 levels, possibly identifying the nonresponders and responders to Aspirin. Conclusions: Although low-dose Aspirin appropriately inhibited the platelet, persistently high systemic TXA2 and PGE2 biosynthesis were found, plausibly for a marginal inhibitory effect on prostanoid biosynthesis in the colorectum. Novel chemotherapeutic strategies in FAP can involve blocking the effects of TXA2 and PGE2 signaling with receptor antagonists

The Athlete after COVID-19 infection: what the scientific evidence? What to do?

The coronavirus-19 disease (COVID-19) related pandemic have deeply impacted human health, economy, psychology and sociality. Possible serious cardiac involvement in the infection has been described, raising doubts about complete healing after the disease in many clinical settings. Moreover, there is the suspicion that the vaccines, especially those based on mRNA technology, can induce myopericarditis. Myocarditis or pericarditis related scars can represent the substrate for lifethreatening arrhythmias, triggered by physical activity. A crucial point is how to evaluate an athlete after a Covid-19 infection ensuring a safe return to play without increasing the number of unnecessary disqualifications from sports competitions. The lack of conclusive scientific data significantly increases the difficulty to propose recommendations and guidelines on this topic. At the same time, the psychological and physical negative consequences of unnecessary sports restriction must be taken into account. The present document aims to provide an updated brief review of the current knowledge about the COVID-19 cardiac involvement and how to recognize it and to offer a roadmap for the management of the athletes after a Covid-19 infections, including subsequent impact on exercise recommendations. Our document exclusively refers to cardiovascular implications of the disease, but pulmonary consequences are also considered

Electroanatomic mapping in athletes: Why and when. An expert opinion paper from the Italian society of sports cardiology

: Three-dimensional electroanatomical mapping (EAM) has the potential to identify the pathological substrate underlying ventricular arrhythmias (VAs) in different clinical settings by detecting myocardial areas with abnormally low voltages, which reflect the presence of different cardiomyopathic substrates. In athletes, the added value of EAM may be to enhance the efficacy of third-level diagnostic tests and cardiac magnetic resonance (CMR) in detecting concealed arrhythmogenic cardiomyopathies. Additional benefits of EAM in the athlete include the potential impact on disease risk stratification and the consequent implications for eligibility to competitive sports. This opinion paper of the Italian Society of Sports Cardiology aims to guide general sports medicine physicians and cardiologists on the clinical decision when to eventually perform an EAM study in the athlete, highlighting strengths and weaknesses for each cardiovascular disease at risk of sudden cardiac death during sport. The importance of early (preclinical) diagnosis to prevent the negative effects of exercise on phenotypic expression, disease progression, and worsening of the arrhythmogenic substrate is also addressed

Molecular genetic testing in athletes: Why and when a position statement from the Italian society of sports cardiology

: Molecular genetic testing is an increasingly available test to support the clinical diagnosis of inherited cardiovascular diseases through identification of pathogenic gene variants and to make a preclinical genetic diagnosis among proband's family members (so-called "cascade family screening"). In athletes, the added value of molecular genetic testing is to assist in discriminating between physiological adaptive changes of the athlete's heart and inherited cardiovascular diseases, in the presence of overlapping phenotypic features such as ECG changes, imaging abnormalities or arrhythmias ("grey zone"). Additional benefits of molecular genetic testing in the athlete include the potential impact on the disease risk stratification and the implications for eligibility to competitive sports. This position statement of the Italian Society of Sports Cardiology aims to guide general sports medical physicians and sports cardiologists on clinical decision as why and when to perform a molecular genetic testing in the athlete, highlighting strengths and weaknesses for each inherited cardiovascular disease at-risk of sudden cardiac death during sport. The importance of early (preclinical) diagnosis to prevent the negative effects of exercise on phenotypic expression, disease progression and worsening of the arrhythmogenic substrate is also addressed