The role of coronary CT angiography in athletes.

The sudden death of a young or high-level athlete or adolescent during recreational sports is one of the events with the greatest impact on public opinion in modern society. Sudden cardiac death (SCD) is the principal medical cause of death in athletes and can be the first and last clinical presentation of underlying disease. To prevent such episodes, pre-participation screening has been introduced in many countries to guarantee cardiovascular safety during sports and has become a common target among medical sports/governing organizations. Different cardiac conditions may cause SCD, with incidence depending on definition, evaluation methods, and studied populations, and a prevalence and etiology changing according to the age of athletes, with CAD most frequent in master athletes, while coronary anomalies and non-ischemic causes prevalent in young. To detect silent underlying causes early would be of considerable clinical value. This review summarizes the pre-participation screening in athletes, the specialist agonistic suitability visit performed in Italy, the anatomical characteristics of malignant coronary anomalies, and finally, the role of coronary CT angiography in such arena. In particular, the anatomical conditions suggesting potential disqualification from sport, the post-treatment follow-up to reintegrate young athletes, the diagnostic workflow to rule-out CAD in master athletes, and their clinical management are analyzed.

The role of echocardiography in sports cardiology: An expert opinion statement of the Italian Society of Sports Cardiology (SIC sport).

Transthoracic echocardiography (TTE) is routinely required during pre-participation screening in the presence of symptoms, family history of sudden cardiac death or cardiomyopathies <40-year-old, murmurs, abnormal ECG findings or in the follow-up of athletes with a history of cardiovascular disease (CVD). TTE is a cost-effective first-line imaging modality to evaluate the cardiac remodeling due to long-term, intense training, previously known as the athlete's heart, and to rule out the presence of conditions at risk of sudden cardiac death, including cardiomyopathies, coronary artery anomalies, congenital, aortic and heart valve diseases. Moreover, TTE is useful for distinguishing physiological cardiac adaptations during intense exercise from pathological behavior due to an underlying CVD. In this expert opinion statement endorsed by the Italian Society of Sports Cardiology, we discussed common clinical scenarios where a TTE is required and conditions falling in the grey zone between the athlete's heart and underlying cardiomyopathies or other CVD. In addition, we propose a minimum dataset that should be included in the report for the most common indications of TTE in sports cardiology clinical practice.

Cardiopulmonary Exercise Testing after Surgical Repair of Tetralogy of Fallot-Does Modality Matter?

BACKGROUND: Despite a successful repair of tetralogy of Fallot (rToF) in childhood, residual lesions are common and can contribute to impaired exercise capacity. Although both cycle ergometer and treadmill protocols are often used interchangeably these approaches have not been directly compared. In this study we examined cardiopulmonary exercise test (CPET) measurements in rToF. METHODS: Inclusion criteria were clinically stable rToF patients able to perform a cardiac magnetic resonance imaging (CMR) and two CPET studies, one on the treadmill (incremental Bruce protocol) and one on the cycle ergometer (ramped protocol), within 12 months. Demographic, surgical and clinical data; functional class; QRS duration; CMR measures; CPET data and international physical activity questionnaire (IPAQ) scores of patients were collected. RESULTS: Fifty-seven patients were enrolled (53% male, 20.5 ± 7.8 years at CPET). CMR measurements included a right ventricle (RV) end-diastolic volume index of 119 ± 22 mL/m2, a RV ejection fraction (EF) of 55 ± 6% and a left ventricular (LV) EF of 56 ± 5%. Peak oxygen consumption (VO2)/Kg (25.5 ± 5.5 vs. 31.7 ± 6.9; p < 0.0001), VO2 at anaerobic threshold (AT) (15.3 ± 3.9 vs. 22.0 ± 4.5; p < 0.0001), peak O2 pulse (10.6 ± 3.0 vs. 12.1± 3.4; p = 0.0061) and oxygen uptake efficiency slope (OUES) (1932.2 ± 623.6 vs. 2292.0 ± 639.4; p < 0.001) were significantly lower on the cycle ergometer compared with the treadmill, differently from ventilatory efficiency (VE/VCO2) max which was significantly higher on the cycle ergometer (32.2 ± 4.5 vs. 30.4 ± 5.4; p < 0.001). Only the VE/VCO2 slope at the respiratory compensation point (RCP) was similar between the two methodologies (p = 0.150). CONCLUSIONS: The majority of CPET measurements differed according to the modality of testing, with the exception being the VE/VCO2 slope at RCP. Our data suggest that CPET parameters should be interpreted according to test type; however, these findings should be validated in larger populations and in a variety of institutions.

Evaluation of Metabolic and Cardiovascular Risk Measured by Laboratory Biomarkers and Cardiopulmonary Exercise Test in Children and Adolescents Recovered from Brain Tumors: The CARMEP Study.

In recent decades, the improvement of treatments and the adoption of therapeutic protocols of international cooperation has led to an improvement in the survival of children affected by brain tumors. However, in parallel with the increase in survival, long-term side effects related to treatments have been observed over time, including the activation of chronic inflammatory processes and metabolic alterations, which can facilitate the onset of metabolic syndrome and increased cardiovascular risk. The aim of this study was to find possible statistically significant differences in the serum concentrations of early biomarkers of metabolic syndrome and in the results of cardiopulmonary exercise testing between survivors of childhood brain tumors and healthy controls. This is a prospective and observational study conducted on a group of 14 male patients who survived childhood brain tumors compared with the same number of healthy controls. The concentrations of early metabolic syndrome biomarkers [adiponectin, leptin, TNF-α, IL-1, IL-6, IL-10, endothelin-1, apolipoprotein B, and lipoprotein (a)] were measured and a cardiopulmonary exercise test (CPET) was performed. Results: Childhood brain tumor survivors performed worse on average than controls on the CPET. Furthermore, they showed higher endothelin-1 values than controls (p = 0.025). The CPET results showed an inverse correlation with leptin. The differences found highlight the greater cardiovascular risk of brain tumor survivors, and radiotherapy could be implicated in the genesis of this greater cardiovascular risk.

Spina bifida and cardiorespiratory profile: the impact of leisure sport activities on physical fitness.

PURPOSE: The aim of the present study is to evaluate a population of young patients affected by Spina Bifida (SB) to describe their cardiorespiratory function and bone mineral density profile, analyzing any differences between people performing and those who do not perform sports activity. The study also aimed to rule out possible congenital heart disease associated with spina bifida, considering the common origin of certain cardiac structures with those found to be altered in SB patients. METHODS: Thirty-four young patients, aged between 12 and 22 years, diagnosed with spinal dysraphism (SD), have been clinically described and, in order to evaluate their physical fitness, functional capacity and bone mass, almost all of them underwent a complete cardiorespiratory assessment, including electrocardiogram (ECG), echocardiogram, Cardiopulmonary Exercise Test (CPET), body composition analysis using bioimpedance analysis (BIA) and Dual Energy X-ray Absorptiometry (DEXA), as well as the estimation of bone mineral density (BMD) with Computerized Bone Mineralometry (CBM). RESULTS: Collected data demonstrated that only 35% of the subjects practiced physical activity during the week. BMI and percentage FM values were pathological in at least 50% of the population. On cardiological investigations (ECG and echocardiogram), no significant alterations were found. In all patients who performed CPET (79.4%), pathological values of the main functional capacity parameters were revealed, especially peak oxygen consumption (VO2 peak), even when corrected for BCM or FFM estimated at BIA and DEXA, respectively. In the CBM analysis, out of 27 patients in whom the femoral T-score was evaluated, a condition of osteopenia was revealed in 40.7% of the patients (11/27) and osteoporosis in 18.5% (5/27); out of 27 patients in whom the lumbar T-score was evaluated, 37% of the patients showed osteopenia (10/27) and 29.6% osteoporosis (8/27). When the comparison between exercising and non-exercising patients was performed, the only statistically significant difference that emerged was the median lumbar T-score value, which appeared lower in the group not performing physical activity (p = 0,009). CONCLUSIONS: The extensive cardiorespiratory evaluation, including CPET, of our cohort of spina bifida patients showed altered values of the main parameters related to cardiorespiratory fitness and is the only study in the literature that analysed bone mineralization values in physically active and sedentary spina bifida patients and demonstrated a statistically significant difference. Furthermore, it is the only study to date that investigated the possible association of congenital heart diseases with SD, without demonstrating the existence of pathological conditions.

Congenital coronary artery anomalies in sports medicine. Why to know them.

The anomalous origin of a coronary artery (AOCA) is a challenging topic, due to its rarity, the complexity of the pathophysiological aspects, the clinical presentation (often silent), the difficulty of diagnosis, and the potential risk of causing acute cardiovascular events up to sudden cardiac death, particularly when triggered by heavy physical exercise or sport practice. Increasing interest in sport medical literature is being given to this topic. This paper reviews current knowledge of AOCAs in the specific context of the athletic setting addressing epidemiological and pathophysiological aspects, diagnostic work-up, sports participation, individual risk assessment, therapeutic options, and return to play decision after surgery.

Pomegranate Fruit Cracking during Maturation: From Waste to Valuable Fruits.

The pomegranate is an emerging functional food which is nowadays becoming more and more commercially attractive. Each part of this fruit (peels, arils and seeds) has a specific phytocomplex, rich in anti-oxidant and anti-radical compounds. Among these, punicalagin and ellagic acid continue to be widely studied for their numerous beneficial effects on human health (anti-inflammatory effects, anti-diabetes activity, cardio-protection, cancer prevention). Despite their exceptionally valuable composition and high adaptability to different climatic conditions, pomegranate fruits are highly susceptible to splitting during different stages of ripening, so much so that an estimated 65% of the production may be lost. A "zero-kilometer" approach should therefore be adopted to utilize such a valuable product otherwise destined to be downgraded or even incinerated, with a very high environmental impact. The aim of this work is to highlight and compare the compositional differences between whole and split pomegranates belonging to the cultivar Dente di Cavallo, grown in Apulia (Italy), to assess a valuable role for this split fruit usually considered as waste. The arils and peels are subjected to extraction procedures and the extracts analyzed by CIEL*a*b*, HPLC-DAD and HS-SPME/GC-MS. Moreover, an assessment of the inhibitory activity against α-glucosidase, acetylcholinesterase and tyrosinase enzymes has also been applied. The data show a better chemical profile in split fruits (namely 60% more anthocyanin content than intact fruit) with very interesting results in terms of α-glucosidase inhibition. The juices obtained by squeezing are also compared to commercial juices ("Salus Melagrana" and "La Marianna") processed from the same cultivar and subjected to the same protocol analysis.

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.

Italian return to play protocol after COVID-19 in young competitive and professional athletes: diagnostic yield and cost-benefit analysis.

BACKGROUND: Return to play (RTP) protocols have been proposed to early detect cardiovascular involvement due to COVID-19 and reduce the risk of sports-related sudden cardiac death. However, uncertainties remain about the true prevalence of COVID-19 myopericarditis, the arrhythmic risk and the cost of this protocol. METHODS: We collected data from 217 competitive and professional athletes of both genders who underwent RTP protocol (clinical history, resting and exercise ECG, and echocardiography). Holter monitoring and/or cardiac magnetic resonance (CMR) were performed in case of abnormalities. In 107 athletes, the RTP data were compared with those of preparticipation evaluation (PPE) performed prior to COVID-19 infection. RESULTS: Out of 217 consecutive athletes evaluated with the RTP protocol, 7 underwent CMR: among these we found alterations compatible with myopericarditis in 3 (1.4%), with a cost per person of € 223.93 and a cost per diagnosis of € 16,197.53. Of the 107 athletes previously evaluated with PPE, 4 underwent RMC: we made a final diagnosis of myocarditis in 1 athlete (0.9%), whereas another athlete (0.9%) showed moderate pericardial effusion. The clinical presentation of both these athletes was characterized by the presence of ventricular arrhythmias newly detected during RTP. Compared to PPE, during RTP higher values were observed for shortness of breath, weight, heart rate and corrected QT interval, whereas lower values for sinus bradycardia and the E/A ratio of mitral flow. CONCLUSIONS: The prevalence of myopericarditis was similar to that reported in previous cross-sectional and case-control studies. The availability of data recorded before COVID-19 was important in the evaluation of athletes with arrhythmias. The RTP protocol has proven to be less cost effective than normal PPE.

Myocardial bridge evaluation towards personalized medicine: study design and preliminary results of the RIALTO registry.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to calcium-channel blockers (CCBs) at discharge (Angio + ACH + CCBs group) and those who underwent functional assessment with fractional flow reserve (FFR) with indication to beta-blockers (BBs) at discharge (Angio + FFR + BBs group). After 2 years of FUP, the rate of MACE was significantly reduced in both Angio + ACH + CCBs group (6 vs. 25%, P = 0.029) and Angio + FFR + BBs group (3 vs. 25%, P = 0.005) compared with Angio group. The preliminary results of our study showed that MB may be a cause of angina and adverse cardiac events in patients referred to CA for suspected coronary artery disease (CAD). Full-physiology assessment unmasking MB-related ischaemia mechanisms, allowed to guide the treatment, personalizing the clinical management, improving the quality of life, and cardiovascular outcomes in patients with MB.

Comprehensive functional and anatomic assessment of myocardial bridging: Unlocking the Gordian Knot.

Myocardial bridging (MB) is the most frequent congenital coronary anomaly in which a segment of an epicardial coronary artery takes a tunneled course under a bridge of the myocardium. This segment is compressed during systole, resulting in the so-called "milking effect" at coronary angiography. As coronary blood flow occurs primarily during diastole, the clinical relevance of MB is heterogeneous, being usually considered an asymptomatic bystander. However, many studies have suggested its association with myocardial ischemia, anginal symptoms, and adverse cardiac events. The advent of contemporary non-invasive and invasive imaging modalities and the standardization of intracoronary functional assessment tools have remarkably improved our understanding of MB-related ischemia, suggesting the role of atherosclerotic lesions proximal to MB, vasomotor disorders and microvascular dysfunction as possible pathophysiological substrates. The aim of this review is to provide a contemporary overview of the pathophysiology and of the non-invasive and invasive assessment of MB, in the attempt to implement a case-by-case therapeutic approach according to the specific endotype of MB-related ischemia.

Incidental Echocardiographic Finding of a Membranous Ventricular Septal Aneurysm in an 18-Year-Old Asymptomatic Athlete.

Membranous ventricular septal aneurysm (VSA) is an uncommon cardiac abnormality, potentially leading to several cardiac complications such as aortic valve prolapse, arrhythmias, and aneurysm rupture. A young competitive soccer player presented for a post-COVID sports cardiology assessment, denying any previous cardiological evaluations. On transthoracic echocardiography, a membranous VSA was incidentally found with no other cardiac abnormality nor hemodynamic impairment associated. A well-oriented anamnesis guided by echocardiographic findings revealed that a ventricular septal defect was diagnosed at birth with spontaneous closure at 4 years old. From that moment, no further follow-up was performed. Before granting cardiological approval to competitive sport, transesophageal echocardiography and Holter electrocardiogram were performed to confirm the absence of interventricular shunt and any other cardiac abnormality or arrhythmias associated with VSA. This case highlights the value of an accurate and comprehensive clinical and echocardiographic evaluation when performing a cardiological sports assessment, even in a young asymptomatic athlete.

Bicuspid Aortic Valve and Premature Ventricular Beats in Athletes.

BACKGROUND: The aim of this study was to identify a possible link between bicuspid aortic valve (BAV) and premature ventricular beats (PVBs), particularly from left and right ventricular outflow tracts, and to investigate possible associations between these arrhythmias and echocardiographic abnormalities. METHODS: A comparison of sportspeople with and without BAV was performed to identify PVBs' occurrence in these two series. Then, subdividing the BAV group on the presence of cardiovascular complications due to BAV, we compared arrhythmic features between these two subgroups and echocardiographic findings between athletes with and without left and right outflow tract PVBs. RESULTS: PVBs in 343 athletes with BAV were compared with 309 athletes without BAV, showing an increased frequency (29% vs. 11.8%, p < 0.001; OR 3.1; CI 2.1-4.7) and origin from the left (18.4% vs. 3.2%, p < 0.001, OR 6.7; CI 3.4-13.4) and right (15.2% vs. 3.6%, p < 0.001, OR 4.8; CI 2.5-9.5) outflow tracts compared to other ventricular areas (fascicular PVBs p = 0.81, other morphologies p = 0.58). No difference in PVBs' occurrence was found between near normal valve BAV and pathological BAV, nor was a difference in echocardiographic characteristics found between patients with and without outflow tract arrhythmias. CONCLUSIONS: A possible causal link between BAV and PVBs was highlighted, but no association between PVBs and complicated BAV was emphasized.

Application of a Decision Tree Model to Predict the Outcome of Non-Intensive Inpatients Hospitalized for COVID-19.

Many studies have identified predictors of outcomes for inpatients with coronavirus disease 2019 (COVID-19), especially in intensive care units. However, most retrospective studies applied regression methods to evaluate the risk of death or worsening health. Recently, new studies have based their conclusions on retrospective studies by applying machine learning methods. This study applied a machine learning method based on decision tree methods to define predictors of outcomes in an internal medicine unit with a prospective study design. The main result was that the first variable to evaluate prediction was the international normalized ratio, a measure related to prothrombin time, followed by immunoglobulin M response. The model allowed the threshold determination for each continuous blood or haematological parameter and drew a path toward the outcome. The model's performance (accuracy, 75.93%; sensitivity, 99.61%; and specificity, 23.43%) was validated with a k-fold repeated cross-validation. The results suggest that a machine learning approach could help clinicians to obtain information that could be useful as an alert for disease progression in patients with COVID-19. Further research should explore the acceptability of these results to physicians in current practice and analyze the impact of machine learning-guided decisions on patient outcomes.

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.

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.

Myocarditis in Athletes Recovering from COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: To assess the event rates of myocarditis detected by Cardiac Magnetic Resonance (CMR) in athletes who recovered from COVID-19. METHODS: A systematic literature search was performed to identify studies reporting abnormal CMR findings in athletes who recovered from COVID-19. Secondary analyses were performed considering increased serum high sensitivity troponin (hs-Tn) levels and electrocardiographic (ECG) and echocardiographic (ECHO) abnormalities. RESULTS: In total, 7988 athletes from 15 studies were included in the analysis. The pooled event rate of myocarditis was 1% (CI 1-2%), reaching 4% in the sub-group analysis. In addition, heterogeneity was observed (I2 43.8%). The pooled event rates of elevated serum hs-Tn levels, abnormal ECG and ECHO findings were 2% (CI 1-5%), 3% (CI 1-10%) and 2% (CI 1-6%), respectively. ECG, ECHO and serum hs-Tn level abnormalities did not show any correlation with myocarditis. CONCLUSIONS: The prevalence of COVID-19-related myocarditis in the athletic population ranges from 1 to 4%. Even if the event rate is quite low, current screening protocols are helpful tools for a safe return to play to properly address CMR studies. TRIAL REGISTRATION: the study protocol was registered in the PROSPERO database (registration number: CRD42022300819).

Reduced COVID-19 mortality linked with early antibodies against SARS-CoV-2, irrespective of age.

BACKGROUND: COVID-19 pandemic has generated a million deaths worldwide. The efficiency of the immune system can modulate individual vulnerability with variable outcomes. However, the relationships between disease severity and the titer of antibodies produced against SARS-CoV-2 in non-vaccinated, recently infected subjects need to be fully elucidated. METHODS: A total of 99 patients admitted to a COVID-unit underwent clinical assessment and measurement of serum levels of anti-spike protein (S1) IgM, and anti-nucleocapsid protein IgG. Patients were stratified according to the clinical outcome (i.e., discharged at home or in-hospital death). RESULTS: Following hospitalization, 18 died during the hospital stay. They were older, had lymphopenia, a higher co-morbidity rate, and longer hospital stay than 81 patients who were discharged after healing. Patients in this latter group had, at hospital admittance, 7.9-fold higher serum concentration of IgM, and 2.4-fold higher IgG levels. Multivariate Cox regression models indicated age and anti-nucleocapsid protein IgG concentration at admission as independently associated with the risk of in-hospital death. CONCLUSIONS: An efficient immunological response during the early phase of COVID-19 protects from mortality, irrespective of age. Advanced age is a critical risk factor for poor outcome in infected subjects. Further studies must explore potential therapeutic strategies able to restore a valid functional humoral immunity in elderly patients with poor antibody response during the early stage of COVID-19 infection.

Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level.

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO2 30 mL/kg/min (range 25-33); median percent predicted peak VO2 68% (range 61-78)). Peak VO2, correlated with biventricular stroke volumes (RVSV: ß = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: ß = 15.69 (95% CI 10.16 to 21.21), p < 0.0001) and LVEDVi (ß = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: ß = 6.88 (95%CI, 1.93 to 11.84), p = 0.008; LVSV: ß = 17.86 (95% CI 10.31 to 25.42), p < 0.0001) and peak O2 pulse (RVSV: ß = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: ß = 0.08 (95% CI 0.05 to 0.11), p < 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO2/kg (ß = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO2 irrespective of RV size. OUES and peak O2 pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO2, the incremental value of this parameter should be the focus of future studies.