Short term outcome of myocarditis and pericarditis following COVID-19 vaccines: a cardiac magnetic resonance imaging study.

To evaluate clinical and cardiac magnetic resonance (CMR) short-term follow-up (FU) in patients with vaccine-associated myocarditis, pericarditis or myo-pericarditis (VAMP) following COVID-19 vaccination. We retrospectively analyzed 44 patients (2 women, mean age: 31.7 ± 15.1 years) with clinical and CMR manifestations of VAMP, recruited from 13 large tertiary national centers. Inclusion criteria were troponin raise, interval between the last vaccination dose and onset of symptoms < 25 days and symptoms-to-CMR < 20 days. 29/44 patients underwent a short-term FU-CMR with a median time of 3.3 months. Ventricular volumes and CMR findings of cardiac injury were collected in all exams. Mean interval between the last vaccination dose and the onset of symptoms was 6.2 ± 5.6 days. 30/44 patients received a vaccination with Comirnaty, 12/44 with Spikevax, 1/44 with Vaxzevria and 1/44 with Janssen (18 after the first dose of vaccine, 20 after the second and 6 after the "booster" dose). Chest pain was the most frequent symptom (41/44), followed by fever (29/44), myalgia (17/44), dyspnea (13/44) and palpitations (11/44). At baseline, left ventricular ejection fraction (LV-EF) was reduced in 7 patients; wall motion abnormalities have been detected in 10. Myocardial edema was found in 35 (79.5%) and LGE in 40 (90.9%) patients. Clinical FU revealed symptoms persistence in 8/44 patients. At FU-CMR, LV-EF was reduced only in 2 patients, myocardial edema was present in 8/29 patients and LGE in 26/29. VAMPs appear to have a mild clinical presentation, with self-limiting course and resolution of CMR signs of active inflammation at short-term follow-up in most of the cases.

Cardiac magnetic resonance imaging of myocarditis and pericarditis following COVID-19 vaccination: a multicenter collection of 27 cases.

OBJECTIVES: To assess clinical and cardiac magnetic resonance (CMR) imaging features of patients with peri-myocarditis following Coronavirus Disease 2019 (COVID-19) vaccination. METHODS: We retrospectively collected a case series of 27 patients who underwent CMR in the clinical suspect of heart inflammation following COVID-19 vaccination, from 16 large tertiary centers. Our patient's cohort was relatively young (36.6 ± 16.8 years), predominately included males (n = 25/27) with few comorbidities and covered a catchment area of approximately 8 million vaccinated patients. RESULTS: CMR revealed typical mid-subepicardial non-ischemic late gadolinium enhancement (LGE) in 23 cases and matched positively with CMR T2 criteria of myocarditis. In 7 cases, typical hallmarks of acute pericarditis were present. Short-term follow-up (median = 20 days) from presentation was uneventful for 25/27 patients and unavailable in two cases. CONCLUSIONS: While establishing a causal relationship between peri-myocardial inflammation and vaccine administration can be challenging, our clinical experience suggests that CMR should be performed for diagnosis confirmation and to drive clinical decision-making and follow-up. KEY POINTS: • Acute onset of dyspnea, palpitations, or acute and persisting chest pain after COVID-19 vaccination should raise the suspicion of possible myocarditis or pericarditis, and patients should seek immediate medical attention and treatment to help recovery and avoid complications. • In case of elevated troponin levels and/or relevant ECG changes, cardiac magnetic resonance should be considered as the best non-invasive diagnostic option to confirm the diagnosis of myocarditis or pericarditis and to drive clinical decision-making and follow-up.

Challenges and opportunities to delivering cardiac imaging training: a national survey by the Italian college of cardiac radiology.

BACKGROUND: Delivering consistent levels of training in cardiac imaging to radiologist is of pivotal importance because of the increasing clinical indications to coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR). Our study sought to capture the heterogeneity of cardiac imaging training programs and to explore residents' vision on cardiac imaging both in the present and in the future. METHODS: Two web-based surveys were created. The first was administered to all chief residents from the 42 University Hospitals within Italy, aiming to explore the local educational offer in cardiac imaging. The second was administered via social media to all Italian residents, including questions about their overall vision regarding cardiac imaging. RESULTS: 42/42 University Hospitals responded to the first survey and 235 residents to the second. There was at least a 64-slice CT scanner and a 1.5 T MR scanner per center. In the majority of sites, the weekly routine consisted of more than 10 CCTA and more than 5 CMR. Approximately, half of the centers used advanced CCTA and CMR techniques. The majority of the interviewed resident (94%) perceived cardiac imaging training to be moderately to very important, while requirement for external educational resources was advocated in 25% of the cases. CONCLUSION: Our survey highlighted a significant awareness of radiology residents regarding the importance of cardiac imaging in their training curriculum. All centers met the technical requirements for cardiac imaging, limiting its use to basic applications in around half of cases. Implementation of an educational network might be the key for supporting the growth of this subspecialty field.

Appropriate use criteria for cardiovascular MRI: SIC - SIRM position paper Part 2 (myocarditis, pericardial disease, cardiomyopathies and valvular heart disease).

Cardiovascular magnetic resonance (CMR) has emerged as an accurate diagnostic technique for the evaluation of patients with cardiac disease in the majority of clinical settings, thanks to an established additional diagnostic and prognostic value. This document has been developed by a joined group of experts of the Italian Society of Cardiology (SIC) and Italian Society of Radiology (SIRM) to provide a summary about the current state of technology and clinical applications of CMR, to improve the clinical diagnostic pathways and to promote its inclusion in clinical practice. The writing committee consisted of members and experts of both societies in order to develop a more integrated approach in the field of cardiac imaging. This section 2 will cover myocarditis, pericardial disease, cardiomyopathies and valvular heart disease.

Appropriate use criteria for cardiovascular magnetic resonance imaging (CMR): SIC-SIRM position paper part 1 (ischemic and congenital heart diseases, cardio-oncology, cardiac masses and heart transplant).

Cardiac magnetic resonance (CMR) has emerged as new mainstream technique for the evaluation of patients with cardiac diseases, providing unique information to support clinical decision-making. This document has been developed by a joined group of experts of the Italian Society of Cardiology and Italian society of Radiology and aims to produce an updated consensus statement about the current state of technology and clinical applications of CMR. The writing committee consisted of members and experts of both societies who worked jointly to develop a more integrated approach in the field of cardiac radiology. Part 1 of the document will cover ischemic heart disease, congenital heart disease, cardio-oncology, cardiac masses and heart transplant.

CMR in the diagnosis of ischemic heart disease.

Cardiovascular magnetic resonance has always been more often used in the last 10 years in evaluation of heart disease. Role in diagnosis of ischemia and in evaluation of myocardial infarction is well established by many scientific papers and included in current guidelines. High accuracy in evaluation of stress-induced ischemia, tissue characterization and functional parameters are the pillars the make the method widely used. In this paper are described role and techniques in diagnosis of ischemia, myocardial infarction and its sequelae.

Interatrial conduction times in paroxysmal atrial fibrillation patients with normal atrial volume and their correlation with areas of local prolonged bipolar electrograms.

BACKGROUND: Recent evidence has shown that the presence of abnormal substrate can be demonstrated also among patients with "lone" AF. OBJECTIVES: Interatrial conduction slowing is likely to characterize patients with paroxysmal atrial fibrillation (AF) and it could be correlated to the left atrium area of prolonged local bipolar endocardial electrograms. METHODS: P-wave duration (PWD), amplified PWD and endocavitary interatrial conduction time (IACT), were analyzed in 60 patients; 30 undergoing de novo ablation for paroxysmal AF with normal atrial volumes and without any other cardiac disease and 30 of similar age undergoing electrophysiological study for atrioventricular nodal reentrant tachycardia or atrioventricular re- entrant tachycardia. In patients with AF, voltage maps and local bipolar electrograms (LBE) duration map were evaluated. RESULTS: Although PWD was <120 ms in 28 patients with AF and in 29 controls, patients with AF exhibited longer PWD, amplified-PWD and IACT. Although low-voltage areas (<0.5 mV) were not found in the study population, 28 of them demonstrated areas with LBE longer than 60 ms. These LBE were found mainly in the roof of the left atrium and their extension was correlated to IACT (R = 0.51, p = 0.004). IACT >135.5 ms identified the subjects who experienced AF with 90% sensitivity and 97% specificity. CONCLUSION: A subclinical interatrial conduction disturbance is demonstrable in subjects with paroxysmal AF and normal left atrial volume. IACT has a good correlation to the areas of abnormal LBE in the left atrium. IACT >135 ms identified subjects who have experienced AF.

Italian Registry of Cardiac Computed Tomography.

PURPOSE: Cardiac CT (CCT) is an imaging modality that is becoming a standard in clinical cardiology. We evaluated indications, safety, and impact on patient management of routine CCT in a multicenter national registry. MATERIALS AND METHODS: During a period of 6 months, 47 centers in Italy enrolled 3,455 patients. RESULTS: CCT was performed mainly with 64-slice CT scanners (73.02 %). Contrast agents were administrated in 3,185 patients (92.5 %). Mean DLP changes with type of scanner and was lower in >64 row detector scanner. The most frequent indication for CCT was suspected CAD (44.8 %), followed by calcium scoring (9.6 %), post-angioplasty/stenting (8.3 %), post-CABGs (7.5 %), study of cardiac anatomy (4.22 %) and assessment in patients with known CAD (4.1 %) and acute chest pain (1.99 %). Most of the CCTs were performed in outpatient settings (2,549; 74 %) and a minority in inpatient settings (719, 20.8 %). Adverse clinical events (mild-moderate) occurred in 26 examinations (0.75 %). None of them was severe. In 45.3 % of the cases CCT findings impacted patient management. CONCLUSION: CCT is performed with different workloads in participating centers. It is a safe procedure and its results have a strong impact on patient management.

Correlation between epicardial fat and cigarette smoking: CT imaging in patients with metabolic syndrome.

BACKGROUND: The aim of our study was to assess the relationship between cigarette smoking and epicardial fat in a cohort of patients with metabolic syndrome (MetS) at risk for coronary artery disease. METHODS: We studied, in primary prevention, 54 subjects diagnosed with MetS. According to their smoking habits, the subjects were divided into two groups: smokers and non-smokers. Besides anthropometric characterization and screening laboratory tests, the subjects had a multidetector computerized tomography scan, which allowed epicardial fat quantification and calcium score (CS) evaluation. RESULTS: Compared with non-smokers, smokers showed older age (61.6 ± 1.8 vs 56.8 ± 1.2 yrs; p < 0.05). Also, the smokers displayed increased epicardial fat volume (138 [123; 150] vs 101[79; 130] ml; p < 0.01) as well as higher CS (94 [3; 301.5] vs 0 [0;10.2]; p < 0.001), in comparison with non-smokers. Notably, CS was positively correlated with smoking habit (rs 0.469; p < 0.01), epicardial fat (rs 0.377; p < 0.01), age (rs 0.502; p < 0.001) and uric acid (rs 0.498; p < 0.01). Accordingly, the associations between both CS or epicardial fat and cigarette smoking were still maintained after adjustment for age (r 0.317; p < 0.05; r 0.427; p < 0.01). Finally, multiple regression analysis showed that smoke was the variable that best predicted CS (R(2) 0.131; ß 0.362; p < 0.05) and epicardial fat (R(2) 0.177; ß 0.453; p = 0.01). CONCLUSIONS: Our findings suggest that, in subjects with MetS, cigarette smoking is an independent predictor of increased epicardial fat volume and higher CS.

Italian registry of cardiac magnetic resonance.

OBJECTIVES: Forty sites were involved in this multicenter and multivendor registry, which sought to evaluate indications, spectrum of protocols, impact on clinical decision making and safety profile of cardiac magnetic resonance (CMR). MATERIALS AND METHODS: Data were prospectively collected on a 6-month period and included 3376 patients (47.2 ± 19 years; range 1-92 years). Recruited centers were asked to complete a preliminary general report followed by a single form/patient. Referral physicians were not required to exhibit any specific certificate of competency in CMR imaging. RESULTS: Exams were performed with 1.5T scanners in 96% of cases followed by 3T (3%) and 1T (1%) magnets and contrast was administered in 84% of cases. The majority of cases were performed for the workup of inflammatory heart disease/cardiomyopathies representing overall 55.7% of exams followed by the assessment of myocardial viability and acute infarction (respectively 6.9% and 5.9% of patients). In 49% of cases the final diagnosis provided was considered relevant and with impact on patient's clinical/therapeutic management. Safety evaluation revealed 30 (0.88%) clinical events, most of which due to patient's preexisting conditions. Radiological reporting was recorded in 73% of exams. CONCLUSIONS: CMR is performed in a large number of centers in Italy with relevant impact on clinical decision making and high safety profile.

Enhanced brain performance in mice following postnatal stress.

The double postnatal stress model (brief maternal separation plus sham injection daily applied from birth to weaning) induces metabolic alterations similar to type 2 diabetes in young-adult male mice. We verify whether 1) the stress also induces brain metabolic-functional alterations connected to diabetes and 2) different alterations are modulated selectively by two stress-damaged endogenous systems (opioid- and/or ACTH-corticosteroid-linked). Here, diabetes-like metabolic plus neurophysiologic-neurometabolic parameters are studied in adult mice following postnatal stress and drug treatment. Surprisingly, together with 'classic' diabetes-like alterations, the stress model induces in young-adult mice significantly enhanced brain neurometabolic-neurophysiologic performances, consisting of decreased latency to flash-visual evoked potentials (- ~8%); increased level (+ ~40%) and reduced latency (- ~30%) of NAD(P)H autofluorescence postsynaptic signals following electric stimuli; enhanced passive avoidance learning (+ ~135% latency); and enhanced brain-derived neurotrophic factor level (+ ~70%). Postnatal treatment with the opioid receptor antagonist naloxone prevents some alterations, moreover the treatment with antisense (AS; AS vs proopiomelanocortin mRNA) draws all parameters to control levels, thus showing that some alterations are bound to endogenous opioid-system hyper-functioning, while others depend on ACTH-corticosterone system hyper-functioning. Our stress model induces diabetes-like metabolic alterations coupled to enhanced brain neurometabolic-neurophysiologic performances. Taken all together, these findings are compatible with an 'enduring acute-stress' reaction, which puts mice in favorable survival situations vs controls. However, prolonged hormonal-metabolic imbalances are expected to also produce diabetes-like complications at later ages in stressed mice.

Novel targeted therapies for eosinophilic disorders.

Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders.

Clinical expert panel on monitoring potential lung toxicity of inhaled oligonucleotides: consensus points and recommendations.

Oligonucleotides (ONs) are an emerging class of drugs being developed for the treatment of a wide variety of diseases including the treatment of respiratory diseases by the inhalation route. As a class, their toxicity on human lungs has not been fully characterized, and predictive toxicity biomarkers have not been identified. To that end, identification of sensitive methods and biomarkers that can detect toxicity in humans before any long term and/or irreversible side effects occur would be helpful. In light of the public's greater interests, the Inhalation Subcommittee of the Oligonucleotide Safety Working Group (OSWG) held expert panel discussions focusing on the potential toxicity of inhaled ONs and assessing the strengths and weaknesses of different monitoring techniques for use during the clinical evaluation of inhaled ON candidates. This white paper summarizes the key discussions and captures the panelists' perspectives and recommendations which, we propose, could be used as a framework to guide both industry and regulatory scientists in future clinical research to characterize and monitor the short and long term lung response to inhaled ONs.

Oligonucleotides: a multi-targeted approach for the treatment of respiratory diseases.

Reversing inflammatory lung disease remains the foremost challenge in treating respiratory diseases such as asthma and chronic obstructive pulmonary disease. Reducing (or modifying) the underlying inflammatory process with mono-target drugs has proven challenging. The era of designing 'one target for one disease' has evolved such that a growing body of evidence suggests a single drug that is capable of specifically targeting multiple targets and pathways would be better at arresting progression of these respiratory diseases and be an important advancement in current therapy. Oligonucleotide-based drugs represent an emerging class of drug candidates. Their properties, a broader range of targets over conventional small-molecule drugs and recent clinical proof-of-concept support their development as novel multi-targeting agents for the treatment of respiratory diseases.

Awakening responses and diurnal fluctuations of salivary cortisol, DHEA-S and α-amylase in healthy male subjects.

OBJECTIVES: Because the cortisol awakening response (CAR) has received increasing attention as a useful index of adrenocortical activity, the primary objective of this study was to investigate the presence of an awakening response for various salivary biomarkers of adrenocortical activity, including dehydroepiandrosterone-sulphate (DHEA-S), which acts as a cortisol antagonist, and α-amylase, which is a predictor of circulating catecholamine activity. Salivary biological indicators are considered to be valuable markers of hypothalamus-pituitary-adrenal (HPA) axis diurnal activity. METHODS: In an attempt to overcome problems associated with non-adherence to the requested sampling protocol, only young, healthy males with a physiological CAR value (defined as a 50% increase in salivary cortisol within 30 min after waking) were included in the study (67 out of 102 who initially enrolled met this criterion). RESULTS: Our results suggested that, as is already known for cortisol, DHEA-S and α-amylase have significant awakening responses. In addition, daily profile of salivary cortisol, α-amylase and DHEA-S fluctuations were analysed. Significant correlations were found between salivary cortisol, DHEA-S and α-amylase levels. The results showed that cortisol and DHEA-S concentrations were inversely correlated with α-amylase levels. CONCLUSION: This correlation confirmed the distinctiveness of the two regulatory systems: salivary cortisol and DHEA-S concentrations reflect the activity of the HPA axis, whereas α-amylase activity is more closely related to sympathetic activity. In addition, the present study emphasizes the potential value of saliva collection (which is both easy and stress-free) in monitoring changes of adrenal function, confirming that multiple sampling (especially within 1 h after awakening) is necessary to reliably characterise biomarker activity when investigating neuroendocrine changes under various conditions.

Isolated left ventricular noncompaction in a case of sotos syndrome: a casual or causal link?

A 16-year-old boy affected by Sotos syndrome was referred to our clinic for cardiac evaluation in order to play noncompetitive sport. Physical examination was negative for major cardiac abnormalities and rest electrocardiogram detected only minor repolarization anomalies. Transthoracic echocardiography showed left ventricular wall thickening and apical trabeculations with deep intertrabecular recesses, fulfilling criteria for isolated left ventricular noncompaction (ILVNC). Some sporadic forms of ILVNC are reported to be caused by a mutation on CSX gene, mapping on chromosome 5q35. To our knowledge, this is the first report of a patient affected simultaneously by Sotos syndrome and ILVNC.

Potential therapeutic effects of vitamin e and C on placental oxidative stress induced by nicotine: an in vitro evidence.

There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. The adverse effect of prenatal smoking exposure on human fetal development and growth has been a major public health issue. Active or passive smoking during pregnancy can result in a wide variety of adverse outcomes, including intrauterine growth retardation (IUGR), prematurity, stillbirth, and the sudden infant death syndrome. Smoking in pregnancy has also been associated with an increased risk of attention deficit and learning problems in childhood. Some studies argued that as a principal component of tobacco smoke, nicotine alone is responsible for the majority of negative reproductive outcomes. Nicotine and its major metabolite cotinine can cross the placental barrier. The level of nicotine in fetal tissues was found to be equal to or greater than the plasma nicotine level in the mothers. The oxidative stress induce by nicotine has been increasingly postulated as a major contributor to endothelial dysfunction. A large body of research has investigated the potential role of antioxidant nutrients in the prevention of endothelial dysfunction in women. Therefore, the present study was undertaken to assess the potential benefit of antioxidant supplementation on markers of placental oxidative stress in an in vitro model of endothelial dysfunction induced by nicotine, since it was previously found that nicotine is able to trigger the placental secretion of stress molecules. In this regard, we evaluated the effects of vitamin C, vitamin E and N-acetylcysteine (NAC), alone or in combination, in placental villi culture after exposure to nicotine. The effect of antioxidant nutrients on trophoblast cells proliferation and vitality was also evaluated. The results obtained suggest that in a patho-physiological condition, such as endothelial dysfunction induced by nicotine, the deleterious effect of reactive oxygen species may be counteracted by an antioxidant therapy, and there is the need to investigate the optimum dosing and timing of antioxidants administration, since an inappropriate antioxidant treatment in pregnant women may have deleterious consequences, reducing placental cells proliferation until to cell death.

Spatial and temporal expression of CCR3 and the common beta chain of the IL-3, IL-5 and GM-CSF receptor in the nasal epithelium and lymphoid tissues in a rat model of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) and asthma are closely related conditions that often co-exist, and are characterized by a Th2 inflammatory response where eosinophils occupy a predominant role. Strategies aimed at blocking signaling through the CC chemokine receptor 3 (CCR3) and/or the common beta chain of the IL-3, IL-5 and GM-CSF receptor (ßc) efficiently reduced eosinophilic inflammation in both animal models and in asthmatic patients. This study was therefore aimed at characterizing the spatio-temporal expression pattern of ßc and CCR3 using a rat model of AR. METHODS: Sensitized rats were challenged with ovalbumin and sacrificed at 2h, 8h, 16h or 24h post-challenge. Nasal tissues were microdissected and used for mRNA quantification by QPCR, while histological evaluation determined the presence of eosinophils and mucosubstances. RESULTS: Allergen-induced recruitment of eosinophils in the distal septum and turbinates was maximal at 8h post-challenge, and was correlated with 2-4-fold increase in CCR3 and ßc mRNA. Recruitment of eosinophils was also accompanied by upregulated IL-5, IL-4Rα, TNF-α and IFN-γ mRNA at early time-points. In contrast, IL-13 and MUC5AC mRNA, as well as production of mucosubstances were maximal at 24h. CONCLUSIONS: ßc and CCR3 could play important roles in the modulation of the allergic response, and their inhibition may represent a promising therapeutic approach for AR.