Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types.

Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis.

Determinants of Ventricular Arrhythmias in Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) may be associated with ventricular arrhythmias (VA) even in the absence of significant valvular regurgitation. Curling, mitral annulus disjunction (MAD) and myocardial fibrosis (late gadolinium enhancement [LGE]) may account for arrhythmogenesis. OBJECTIVES: This study investigated the determinants of VA in patients with MVP without significant regurgitation. METHODS: This study included 108 patients with MVP (66 female; median age: 48 years) without valve regurgitation. All patients underwent 12-lead electrocardiography, 12-lead 24-hour electrocardiographic Holter monitoring, exercise stress test, and cardiac magnetic resonance. Patients were divided into 2 groups (arrhythmic and no-arrhythmic MVP), according to the presence of VA with a right bundle branch block pattern. RESULTS: The 62 patients (57%) with arrhythmic MVP showed: 1) higher MAD (median length: 6.0 vs 3.2 mm; P = 0.017); 2) higher prevalence of curling (79% vs 52%; P = 0.012); and 3) higher prevalence of left ventricular LGE (79% vs 52%; P = 0.012). Mediation analysis showed that curling had both a direct (P = 0.03) and indirect effect mediated by LGE (P = 0.04) on VA, whereas the association between MAD and VA was completely mediated by LGE. Patients with severe VA showed more pronounced morphofunctional alterations, in terms of MAD (7.0 vs 4.6 mm; P = 0.004) and presence and severity of curling (respectively, 91% vs 64%; P = 0.010; and 4 vs 3 mm; P = 0.004), compared to those without severe VA. CONCLUSIONS: In patients with MVP the occurrence of VA with right bundle branch block morphology is the expression of more severe morphologic, mechanical, and tissue alterations. Curling has both a direct and an indirect effect on VA.

Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes-an analysis of CENTER-TBI data.

PURPOSE: We analysed the impact of early systemic insults (hypoxemia and hypotension, SIs) on brain injury biomarker profiles, acute care requirements during intensive care unit (ICU) stay, and 6-month outcomes in patients with traumatic brain injury (TBI). METHODS: From patients recruited to the Collaborative European neurotrauma effectiveness research in TBI (CENTER-TBI) study, we documented the prevalence and risk factors for SIs and analysed their effect on the levels of brain injury biomarkers [S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and protein Tau], critical care needs, and 6-month outcomes [Glasgow Outcome Scale Extended (GOSE)]. RESULTS: Among 1695 TBI patients, 24.5% had SIs: 16.1% had hypoxemia, 15.2% had hypotension, and 6.8% had both. Biomarkers differed by SI category, with higher S100B, Tau, UCH-L1, NSE and NfL values in patients with hypotension or both SIs. The ratio of neural to glial injury (quantified as UCH-L1/GFAP and Tau/GFAP ratios) was higher in patients with hypotension than in those with no SIs or hypoxia alone. At 6 months, 380 patients died (22%), and 759 (45%) had GOSE ≤ 4. Patients who experienced at least one SI had higher mortality than those who did not (31.8% vs. 19%, p < 0.001). CONCLUSION: Though less frequent than previously described, SIs in TBI patients are associated with higher release of neuronal than glial injury biomarkers and with increased requirements for ICU therapies aimed at reducing intracranial hypertension. Hypotension or combined SIs are significantly associated with adverse 6-month outcomes. Current criteria for hypotension may lead to higher biomarker levels and more negative outcomes than those for hypoxemia suggesting a need to revisit pressure targets in the prehospital settings.

Causes of sudden cardiac arrest and death and the diagnostic yield of sport preparticipation screening in children.

OBJECTIVE: Evidence on the increased risk of sports-related sudden cardiac arrest and death (SCA/D) and the potential benefit of cardiovascular preparticipation screening (PPS) in children is limited. We assessed the burden and circumstances of SCA/D and the diagnostic yield of cardiovascular PPS in children aged 8-15 years. METHODS: Data on the incidence and causes of SCA/D from 2011 to 2020 were obtained from the Veneto region (Italy) sudden death registry, hospital records and local press. During the same period, we assessed the results of annual PPS in 25 251 young competitive athletes aged 8-15 years who underwent 58 185 evaluations (mean 2.3/athlete) in Padua, Italy. RESULTS: Over 10 years, 26 SCA/D occurred in children aged 8-15 years in the Veneto region: 6 in athletes (incidence 0.7/100 000/year, all ≥12 years) versus 20 in non-athletes (0.7/100 000/year, 17/20 ≥12 years). In total, 4/6 athletes versus 1/20 non-athletes survived. The cause of SCA/D remained unexplained in four athletes and in nine non-athletes. No athlete suffered SCA/D from structural diseases potentially identifiable by PPS. The incidence of SCA/D in athletes and non-athletes was 0.2/100 000/year in the 8-11 years group versus 1.3/100 000/year in the 12-15 years group. PPS identified 26 new diagnoses of cardiovascular diseases (CVDs) at risk of SCA/D, more often in children ≥12 years old (0.06%/evaluation) than <12 years old (0.02%/evaluation, p=0.02). Among athletes with a negative PPS, two suffered unexplained SCA/D during follow-up, one during exercise. CONCLUSIONS: In children aged 8-15 years, the incidence of SCA/D and the yield of PPS for identifying at-risk CVD were both substantially higher in those ≥12 years, suggesting that systematic PPS may be more useful beyond this age.

Feasibility of high-frequency percussions in people with severe acquired brain injury and tracheostomy: an observational study.

People with severe acquired brain injury (pwSABI) frequently experience pulmonary complications. Among these, atelectasis can occur as a result of pneumonia, thus increasing the chance of developing acute respiratory failure. Respiratory physiotherapy contribution to the management of atelectasis in pwSABI is yet poorly understood. We conducted a retrospective analysis on 15 non-cooperative pwSABI with tracheostomy and spontaneously breathing, hospitalized and treated with high-frequency percussion physiotherapy between September 2018 and February 2021 at the Neurological Rehabilitation Unit of the IRCCS "S.Maria Nascente - Fondazione Don Gnocchi", Milan. Our primary aim was to investigate the feasibility of such a physiotherapy intervention method. Then, we assessed changes in respiratory measures (arterial blood gas analysis and peripheral night-time oxygen saturation) and high-resolution computed tomography lung images, evaluated before and after the physiotherapy treatment. The radiological measures were a modified radiological atelectasis score (mRAS) assigned by two radiologists, and an opacity score automatically provided by the software CT Pneumonia Analysis® that identifies the regions of abnormal lung patterns. Treatment diaries showed that all treatments were completed, and no adverse events during treatment were registered. Among the 15 pwSABI analyzed, 8 were treated with IPV® and 7 with MetaNeb®. After a median of 14 (I-III quartile=12.5-14.5) days of treatment, we observed a statistical improvement in various arterial blood gas measures and peripheral night-time oxygen saturation measures. We also found radiological improvement or stability in more than 80% of pwSABI. In conclusion, our physiotherapy approach was feasible, and we observed respiratory parameters and radiological improvements. Using technology to assess abnormal tomographic patterns could be of interest to disentangle the short-term effects of respiratory physiotherapy on non-collaborating people.

Left ventricular fibrosis in arrhythmic mitral valve prolapse: quantification and comparison of semi-automated techniques assessed by cardiac magnetic resonance.

PURPOSE: Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in patients with mitral valve prolapse (MVP). Cardiac magnetic resonance identifies LV fibrosis by using late gadolinium enhancement (LGE) technique. LGE assessment and quantification in patients with MVP lacks of standardization protocols. METHODS: 66 MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding techniques using full width at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with the visual assessment, considered as the gold standard. RESULTS: LGE was identified in 41 MVP patients (62%) and quantified. The mean quantity of LGE visually assessed was 2.40 ± 1.07% or 1.40 ± 0.82 g. With FWHM, LGE resulted 3.56 ± 1.23% or 1.99 ± 1.13 g. Using thresholding, the mean LGE quantity was 9.2 ± 3.1% or 4.82 ± 2.28 g for 2-SD, 5.72 ± 1.75% or 3.06 ± 1.47 g for 3-SD and 2.36 ± 0.99% or 1.29 ± 0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.40 ± 1.07 vs. 2.363 ± 0.9909, p = 0.543). When compared with the gold standard, the 5-SD threshold quantification, both in percentage and in grams, revealed the least intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935). CONCLUSION: The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility in MVP patient.

Recurrent intracranial anaplastic ependymoma with late-onset giant scalp metastasis.

Key Clinical Message: Ependymomas are primary brain tumors that predominantly affect individuals between 0 and 4 years of age. Although ependymomas have a propensity for recurrence and the potential to spread within the central nervous system through cerebrospinal fluid (resulting in drop metastases), reports of extra-neural metastatic localizations are exceedingly rare in the existing literature. This case report presents a unique and rare instance of recurrent intracranial anaplastic ependymoma with a late-onset giant scalp metastasis. Abstract: A 55-year-old male patient with a medical history of partial resection of an atypical supratentorial left temporal ependymoma presented with a recurrent anaplastic ependymoma, which had been managed with surgery and radiotherapy. After a 4-year follow-up, the patient developed a subcutaneous mass in the left parietal region of the scalp. A multidisciplinary team of neurosurgeons and plastic surgeons performed a surgical procedure, which included en bloc removal of the scalp lesion, resection of 1 cm of unaffected skin, and craniotomy to address an osteolytic area in the parietal skull bone. Skin autografts were used for reconstruction. Histological examination confirmed metastasis of anaplastic ependymoma in the scalp. After a delay in starting chemotherapy due to concerns related to the COVID-19 pandemic, the patient eventually initiated chemotherapy, leading to disease stability at a short-term follow-up. Scalp metastases from ependymoma are rarely reported in the literature. Management of such cases necessitates aggressive surgical resection, followed by adjuvant chemotherapy and radiotherapy. A multidisciplinary approach is recommended to ensure effective and targeted therapy, with a focus on preserving aesthetics, particularly in pediatric cases.

New Trends in Neurosurgery: Toward a Future of Integration and Equity Among Male and Female Neurosurgeons.

The gradual rise of women in medical schools and residencies, surpassing men in medical school applications, contrasts with the male dominance in surgical fields, including neurosurgery (only 18% women). Reasons include concerns about work-life balance, traditional childcare roles, and gender biases. In response, Women in Neurosurgery (WINs) was founded in 1989 to address gender disparities. However, WINs sessions at conferences evolved into segregated scientific sessions, deviating from their original purpose. This contradicts the ideal of a unified neurosurgical community. While some support segregated spaces, many advocate against gender-based divisions. Today WINs' existence is deemed outdated, with a call for integration, inclusivity, and equality in the modern era of neurosurgery.

Spinal Cord Stimulation Meets Them All: An Effective Treatment for Different Pain Conditions. Our Experience and Literature Review.

IntroductionSpinal Cord Stimulation (SCS) is an emerging minimally invasive technique which uses neuromodulation to manage different forms of intractable pain. SCS is a well-established option for the treatment of various pain conditions, and nowadays, indications are ever increasing.Materials and MethodsIn this study, we present our case series of 49 patients who underwent SCS at our Institution for the treatment of pain from different etiologies, and discuss our 10-year experience in SCS. For the purpose of this study, we also performed a systematic review of current indications and new perspectives in SCS.ResultsAmong our case series, patients were differentiated into two groups upon prior spinal surgery: patients who had undergone prior spinal surgery for back pain were defined as the "FBSS (failed back surgery syndrome) group," instead patient suffering from different types of pain but who had never undergone surgery were defined as the "naive group." As regards clinical response to SCS, 20 patients out of 36 (55.56%) were classified as responders in the FBSS group; in the "naïve" group, 10 patients out of 13 (76.92%) were classified as responders. Among the "not responders" group, several patients suffered from infections.Of the recent literature about SCS, 2124 records were screened and 37 studies were finally included in the qualitative synthesis for our systematic review.DiscussionIn case of FBSS, surgical revision is often associated with a high morbidity and corresponding low rates of success. Unfortunately, patients affected by chronic pain often become refractory to conservative treatments. Spinal Cord Stimulation (SCS) is nowadays considered as an effective therapy for several chronic and neuropathic pain conditions, such as failed back surgery syndrome. As regards the economic impact of SCS, implantation of an SCS system results in short-term costs increase, but the annual cumulative costs decrease during the following years after implantation, when compared to the costs of conventional management. Beyond the application for the treatment of FBSS, SCS has also been used for the treatment of other types of chronic non-oncological pain such as neuropathic pain and chronic back pain ineligible for surgical intervention. This evidence paved the way to establishing the potential role of SCS also for the treatment of oncological pain. However, the effectiveness and relative safety of SCS for cancer-related pain has not yet been adequately established.ConclusionsSpinal Cord Stimulation is a well-established treatment option in for FBSS. Beyond that, SCS has also been used for the treatment of "naive" patients, suffering from other types of chronic, both oncological and non-oncological, medical-refractory pain such as neuropathic pain and chronic back pain ineligible for surgical intervention.

Fluoroscopy-Assisted Freehand Versus 3D-Navigated Imaging-Assisted Pedicle Screw Insertion: A Multicenter Study.

INTRODUCTION: Pedicle screw placement is a widely accepted surgical procedure for spinal fixation. Despite increases in knowledge about and expertise in pedicle screw insertion techniques, overall reported screw misplacement rates are still high. Spinal neuronavigation and intraoperative computed tomography (CT) imaging improves the accuracy and safety of pedicle screw placement through the continuous monitoring of screw trajectory. The purpose of this study is to compare pedicle screw placement under an O-arm intraoperative imaging system assisted by the StealthStation navigation system with screw placement under conventional fluoroscopy (C-arm). METHODS: For 222 patients, 1288 implanted pedicle screws in total were evaluated between 2018 and 2020. All patients underwent pedicle screw placement in the thoracic and lumbosacral regions through a posterior approach. Moreover, 107 patients (48.2%), 48 men and 59 women, underwent freehand screw placement under conventional fluoroscopy (C-arm group), whereas 115 patients (51.8%), 53 men and 62 women, underwent pedicle screw insertion under O-arm guidance with the help of the StealthStation neuronavigation system (Medtronic Navigation, Louisville, CO, USA) (O-arm group). Data were recorded and retrospectively analyzed. The accuracy of pedicle screw placement was postoperatively examined by using CT imaging and analyzed according to the Gertzbein-Robbins classification. RESULTS: Of the 1288 pedicle screws, 665 (51.6%) were placed with C-arm image-guided assistance with a mean of 6.21 ± 2.1 screws per patient and 643 (48.4%) with O-arm image-guided assistance with a mean of 5.59 ± 1.6 screws. The average time for the screw placement procedure was 3:57 ± 1:07 h in the C-arm group and 4:21 ± 1:41 h in the O-arm group. A correct screw placement was detected in 92.78% of patients in the C-arm group and in 98.13% of patients in the O-arm group. Medial cortical breach was shown in 13 Grade B screws (1.95%), 19 Grade C (2.86%), 14 Grade D (2.11%), and two Grade E (0.3%) in the C-arm group, whereas this was shown in 11 Grade B screws (1.71%) and one Grade C (0.16%) in the O-arm group. Lateral breach occurred in eight screws in both groups. Anterior vertebral body breach was shown in eight screws in the C-arm group, whereas it was shown in four screws in the O-arm group. Reoperation for screw misplacement was mandatory in five patients in the C-arm group and two patients in the O-arm group. CONCLUSION: Pedicle screw placement under an O-arm intraoperative imaging system assisted by spinal navigation showed greater accuracy compared with placement under conventional fluoroscopic control, thus avoiding the onset of major postoperative complications. Notably, a reduction in medial and anterior breaches has been demonstrated.

Ventricular arrhythmias recorded on 12-lead ambulatory electrocardiogram monitoring in healthy volunteer athletes and controls: what is common and what is not.

AIMS: Premature ventricular beats (PVBs) in athletes are often benign, but sometimes they may be a sign of an underlying disease. We evaluated the prevalence, burden, and morphology of PVBs in healthy voluntary athletes and controls with the main purpose of defining if certain PVB patterns are 'common' and 'training related' and, as such, are more likely benign. METHODS AND RESULTS: We studied 433 healthy competitive athletes [median age 27 (18-43) years, 74% males] and 261 age- and sex-matched sedentary subjects who volunteered to undergo 12-lead 24 h ambulatory electrocardiogram (ECG) monitoring (24H ECG), with a training session in athletes. Ventricular arrhythmias (VAs) were evaluated in terms of their number, complexity [i.e. couplet, triplet, or non-sustained ventricular tachycardia (NSVT)], exercise inducibility, and morphology. Eighty-six percent of athletes and controls exhibited a total of ≤10 PVBs/24 h, and >90% did not show any couplets, triplets, or runs of NSVT > 3 beats. An higher number of PVBs correlated with increasing age (P < 0.01) but not with sex and level of training. The most frequent morphologies among the 36 athletes with >50 PVBs were the infundibular (44%) and fascicular (22%) ones. In a comparison between athletes and sedentary individuals, and male and female athletes, no statistically significant differences were found in PVBs morphologies. CONCLUSION: The prevalence and complexity of VAs at 24H ECG did not differ between athletes and sedentary controls and were not related to the type and amount of sport or sex. Age was the only variable associated with an increased PVB burden. Thus, no PVB pattern in the athlete can be considered 'common' or 'training related'.

Exoscopic Microsurgery: A Change of Paradigm in Brain Tumor Surgery? Comparison with Standard Operative Microscope.

BACKGROUND: The exoscope is a high-definition telescope recently introduced in neurosurgery. In the past few years, several reports have described the advantages and disadvantages of such technology. No studies have compared results of surgery with standard microscope and exoscope in patients with glioblastoma multiforme (GBM). METHODS: Our retrospective study encompassed 177 patients operated on for GBM (WHO 2021) between February 2017 and August 2022. A total of 144 patients were operated on with a microscope only and the others with a 3D4K exoscope only. All clinical and radiological data were collected. Progression-free survival (PFS) and overall survival (OS) have been estimated in the two groups and compared by the Cox model adjusting for potential confounders (e.g., sex, age, Karnofsky performance status, gross total resection, MGMT methylated promoter, and operator's experience). RESULTS: IDH was mutated in 9 (5.2%) patients and MGMT was methylated in 76 (44.4%). Overall, 122 patients received a gross total resection, 14 patients received a subtotal resection, and 41 patients received a partial resection. During follow-up, 139 (73.5%) patients experienced tumor recurrence and 18.7% of them received a second surgery. After truncation to 12 months, the median PFS for patients operated on with the microscope was 8.82 months, while for patients operated on with the exoscope it was >12 months. Instead, the OS was comparable in the two groups. The multivariable Cox model showed that the use of microscope compared to the exoscope was associated with lower progression-free survival (hazard ratio = 3.55, 95%CI = 1.66-7.56, p = 0.001). CONCLUSIONS: The exoscope has proven efficacy in terms of surgical resection, which was not different to that of the microscope. Furthermore, patients operated on with the exoscope had a longer PFS. A comparable OS was observed between microscope and exoscope, but further prospective studies with longer follow-up are needed.

Interpretation and management of premature ventricular beats in athletes: An expert opinion document of the Italian Society of Sports Cardiology (SICSPORT).

Premature ventricular beats (PVBs) are recorded in a sizeable proportion of athletes during pre-participation screening, especially if the evaluation includes both resting and exercise ECG. While in the majority of cases no underlying heart disease is present, in others PVBs may be the sign of a condition at risk of sudden cardiac death, including cardiomyopathies, congenital, coronary artery, heart valves and ion channels diseases. In this expert opinion document of the Italian Society of Sports Cardiology, we propose a multiparametric interpretation approach to PVBs in athletes and a stepwise diagnostic algorithm. The clinical work-up should include the assessment of the probable site of origin based on the ECG pattern of the ectopic QRS and of the arrhythmia behavior (including the number of different PVB morphologies, complexity, response to exercise and reproducibility), as well as first-line tests such as echocardiography. Based on this initial evaluation, most athletes can be reassured of the benign nature of PVBs and cleared for competition under periodical follow-up. However, when the clinical suspicion is high, further investigations with non-invasive (e.g. cardiac magnetic resonance, cardiac computed tomography, genetic testing) and, in very selected cases, invasive (e.g. endocardial voltage mapping and endomyocardial biopsy) tests should be carried out to rule out a high-risk condition. Importantly, such advanced tests should be performed in centers with a consolidated experience not only in the technique, but also in evaluation of athletes.

Electrocardiographic characteristics of right-bundle-branch-block premature ventricular complexes predicting absence of left ventricular scar in athletes with apparently structural normal heart.

AIMS: Left ventricular scar is an arrhythmic substrate that may be missed by echocardiography and diagnosed only by cardiac magnetic resonance (CMR), which is a time-consuming and expensive imaging modality. Premature ventricular complexes (PVCs) with a right-bundle-branch-block (RBBB) pattern are independent predictors of late gadolinium enhancement (LGE) but their positive predictive value is low. We studied which electrocardiographic features of PVCs with an RBBB pattern are associated with a higher probability of the absence of an underlying LGE. METHODS: The study included 121 athletes (36 ± 16 years; 48.8% men) with monomorphic PVCs with an RBBB configuration and normal standard clinical investigations who underwent CMR. LGE was identified in 35 patients (29%), predominantly in those with PVCs with a superior/intermediate axis (SA-IntA) compared to inferior axis (IA) (38% vs. 10%, P = 0.002). Among patients with SA-IntA morphology, the contemporary presence of qR pattern in lead aVR and V1 was exclusively found in patients without LGE at CMR (51.0% vs. 0%, P < 0.0001). Among patients with IA, the absence of LGE correlated to a narrow ectopic QRS (145 ± 16 vs. 184 ± 27 msec, P < 0.001). CONCLUSIONS: Among athletes with apparently idiopathic PVCs with a RBBB configuration, the presence of a concealed LGE at CMR was documented in 29% of cases, mostly in those with a SA-IntA. In our experience, the contemporary presence of qR pattern in lead aVR and V1 in PVCs with RBBB/SA-IntA morphology or, on the other hand, a relatively narrow QRS in PVCs with an IA, predicted absence of LGE.

Evolving spectrum of arrhythmogenic cardiomyopathy: Implications for Sports Cardiology.

Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease, structurally characterized by progressive fibro-fatty replacement of the normal myocardium and clinically by ventricular arrhythmias (VAs). Predominantly thanks to the use of cardiac magnetic resonance, we have learnt that the spectrum of the disease encompasses not only the classical right ventricular phenotype, but also biventricular and left dominant variants. Sport activity contributes to the phenotypic expression and progression of ACM and may trigger life-threatening VAs and sudden cardiac death (SCD). We conducted a review of the literature about ACM and its implications in Sport Cardiology and summarized the main findings in this topic. Early identification of affected athletes through preparticipation screening (PPS) is fundamental but, while classical right-ventricular or biventricular phenotypes are usually suspected because of electrocardiogram (ECG) and echocardiographic abnormalities, variants with predominant left ventricular involvement are often characterized by normal ECG and unremarkable echocardiography. Usually the only manifestations of such variants are exercise-induced VAs and for this reason exercise testing may empower the diagnostic yield of the PPS. Patients with ACM are not eligible to competitive sports activity, but low-to-moderate intensity physical activity under medical supervision is possible in most cases.

Scarring/arrhythmogenic cardiomyopathy.

The designation of 'arrhythmogenic cardiomyopathy' reflects the evolving concept of a heart muscle disease affecting not only the right ventricle (ARVC) but also the left ventricle (LV), with phenotypic variants characterized by a biventricular (BIV) or predominant LV involvement (ALVC). Herein, we use the term 'scarring/arrhythmogenic cardiomyopathy (S/ACM)' to emphasize that the disease phenotype is distinctively characterized by loss of ventricular myocardium due to myocyte death with subsequent fibrous or fibro-fatty scar tissue replacement. The myocardial scarring predisposes to potentially lethal ventricular arrhythmias and underlies the impairment of systolic ventricular function. S/ACM is an 'umbrella term' which includes a variety of conditions, either genetic or acquired (mostly post-inflammatory), sharing the typical 'scarring' phenotypic features of the disease. Differential diagnoses include 'non-scarring' heart diseases leading to either RV dilatation from left-to-right shunt or LV dilatation/dysfunction from a dilated cardiomyopathy. The development of 2020 upgraded criteria ('Padua criteria') for diagnosis of S/ACM reflected the evolving clinical experience with the expanding spectrum of S/ACM phenotypes and the advances in cardiac magnetic resonance (CMR) imaging. The Padua criteria aimed to improve the diagnosis of S/ACM by incorporation of CMR myocardial tissue characterization findings. Risk stratification of S/ACM patients is mostly based on arrhythmic burden and ventricular dysfunction severity, although other ECG or imaging parameters may have a role. Medical therapy is crucial for treatment of ventricular arrhythmias and heart failure. Implantable cardioverter defibrillator (ICD) is the only proven life-saving treatment, despite its significant morbidity because of device-related complications and inappropriate shocks. Selection of patients who can benefit the most from ICD therapy is one of the most challenging issues in clinical practice.