Immune Checkpoint Inhibitors-Associated Myocarditis: Diagnosis, Treatment and Current Status on Rechallenge.

Immune checkpoint molecules like cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1), play a critical role in regulating the immune response, and immune checkpoint inhibitors (ICIs) targeting these checkpoints have shown clinical efficacy in cancer treatment; however, their use is associated with immune-related adverse events (irAEs), including cardiac complications. The prevalence of cardiac irAEs, particularly myocarditis, is relatively low, but they can become a severe and potentially life-threatening condition, usually occurring shortly after initiating ICI treatment; moreover, diagnosing ICI-related myocarditis can be challenging. Diagnostic tools include serum cardiac biomarkers, electrocardiography (ECG), echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB). The treatment of ICI-induced myocarditis involves high-dose corticosteroids, which have been shown to reduce the risk of major adverse cardiac events (MACE). In refractory cases, second-line immunosuppressive drugs may be considered, although their effectiveness is based on limited data. The mortality rates of ICI-induced myocarditis, particularly in severe cases, are high (38-46%). Therapy rechallenge after myocarditis is associated with a risk of recurrence and severe complications. The decision to rechallenge should be made on a case-by-case basis, involving a multidisciplinary team of cardiologists and oncologists. Further research and guidance are needed to optimize the management of cancer patients who have experienced such complications, evaluating the risks and benefits of therapy rechallenge. The purpose of this review is to summarize the available evidence on cardiovascular complications from ICI therapy, with a particular focus on myocarditis and, specifically, the rechallenge of immunotherapy after a cardiac adverse event.

The Use of Multimodality Imaging for the Diagnosis of Myocardial Outpouchings and Invaginations: A Systematic Review.

Cardiac ventricular outpouchings and invaginations are rare structural abnormalities and usually incidental findings during cardiac imaging. A definitive diagnosis is possible through the use of multimodality imaging. A systematic review of the literature was carried out in November 2022 to identify studies regarding ventricular outpouchings and invaginations. The main aim of the review is to summarize knowledge regarding epidemiology, etiology, diagnosis and prognosis of patients with ventricular outpouchings (aneurisms or diverticula) and invaginations (crypts and recesses). Overall, 26 studies published between 2000 and 2020 were included in the review. Diverticula and congenital aneurysms incidence ranges between 0.6 and 4.1%. Myocardial recesses and crypts range between 9% in the general population and up to 25% in patients with hypertrophic cardiomyopathy. The combined use of echocardiography, cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) is useful to establish tissue contractility, fibrosis, extension and relationship with adjacent structures for differential diagnosis of both invaginations and outpouchings. In conclusion, both outpouchings and invaginations are rare entities: a definitive diagnosis may be aided by the use of combining multiple imaging techniques, and the treatment depends both on the lesion-specific risk of complications and on the potential association of some lesions with cardiomyopathy.

[Screening for atrial fibrillation in the general population: experience from a cardiovascular risk campaign in the Emilia-Romagna Region]. / Screening della fibrillazione atriale nella popolazione generale: esperienza della campagna educazionale sul rischio cardiovascolare della Regione Emilia-Romagna.

BACKGROUND: Atrial fibrillation (AF) is a major cause of cerebral ischemia, and its early detection may impact on health. Both invasive and non-invasive devices can be used for the diagnosis of AF. The aim of our study was to estimate the prevalence of AF using a single-lead ECG device (MyDiagnostickTM) on an adult, asymptomatic population during a screening campaign. METHODS: A total of 2547 subjects underwent AF screening. RESULTS: The device detected an arrhythmia in 42 subjects (1.65%), and AF was confirmed on 12-lead ECG in 14 (0.55%) of them. The prevalence of confirmed AF increased in subjects over 65 years of age (1.21%) or with a CHA2DS2-VASc score ≥2 in males or ≥3 in females (1.33%). Furthermore, heart failure (odds ratio [OR] 8.62, 95% confidence interval [CI] 1.87-39.6, p=0.006) and diabetes (OR 4.55, 95% CI 1.25-16.5, p=0.021) significantly increased the risk of AF. CONCLUSIONS: During a screening campaign, the diagnosis of AF increases when subjects with a high thromboembolic risk are selected.

[Acute aortic dissection: a challenging pitfall on the acute coronary syndrome pathway]. / Dissezione aortica acuta: un trabocchetto insidioso nel percorso della sindrome coronarica acuta.

Acute aortic dissection is a life-threatening condition that is challenging and difficult to recognize since symptoms may mimic other time-dependent conditions like acute coronary syndrome, acute pulmonary embolism or abdominal conditions. We here describe the case of a middle-aged male with thoraco-abdominal pain, positive ECG and troponin tests that demonstrated a large type A aortic dissection at echocardiography done as part of the acute coronary syndrome work-up. This case report reminds clinicians that acute aortic dissection, although rare, should be considered as a differential diagnosis in the work-up of acute coronary syndrome to avoid critical pitfalls, and echocardiography is crucial to rule out it.

SARS-CoV-2 infection and return to play in junior competitive athletes: is systematic cardiac screening needed?

BACKGROUND: SARS-CoV-2 infection might be associated with cardiac complications in low-risk populations, such as in competitive athletes. However, data obtained in adults cannot be directly transferred to preadolescents and adolescents who are less susceptible to adverse clinical outcomes and are often asymptomatic. OBJECTIVES: We conducted this prospective multicentre study to describe the incidence of cardiovascular complications following SARS-CoV-2 infection in a large cohort of junior athletes and to examine the effectiveness of a screening protocol for a safe return to play. METHODS: Junior competitive athletes suffering from asymptomatic or mildly symptomatic SARS-CoV-2 infection underwent cardiac screening, including physical examination, 12-lead resting ECG, echocardiogram and exercise ECG testing. Further investigations were performed in cases of abnormal findings. RESULTS: A total of 571 competitive junior athletes (14.3±2.5 years) were evaluated. About half of the population (50.3%) was mildly symptomatic during SARS-CoV-2 infection, and the average duration of symptoms was 4±1 days. Pericardial involvement was found in 3.2% of junior athletes: small pericardial effusion (2.6%), moderate pericardial effusion (0.2%) and pericarditis (0.4%). No relevant arrhythmias or myocardial inflammation was found in subjects with pericardial involvement. Athletes with pericarditis or moderate pericardial effusion were temporarily disqualified, and a gradual return to play was achieved after complete clinical resolution. CONCLUSIONS: The prevalence of cardiac involvement was low in junior athletes after asymptomatic or mild SARS-CoV-2 infection. A screening strategy primarily driven by cardiac symptoms should detect cardiac involvement from SARS-CoV-2 infection in most junior athletes. Systematic echocardiographic screening is not recommended in junior athletes.

Causes of sudden cardiac death in young athletes and non-athletes: systematic review and meta-analysis: Sudden cardiac death in the young.

INTRODUCTION: The etiology of sudden cardiac death (SCD) in young people continues to attract much attention. This meta-analysis aimed to identify the most frequent causes of SCD in individuals aged ≤35 years, the differences between athletes and non-athletes and geographic areas. METHODS: Studies published between 01/01/1990 and 01/31/2020 and evaluating post-mortem the aetiology of SCD in young individuals (≤35 years) were included. Individuals were divided into athletes and non-athletes. Studies that did not report separate data between athletes and non-athletes were excluded. RESULTS: Thirty-four studies met the inclusion criteria, and a total population of 5,060 victims of SCD were analyzed (2,890 athletes, 2,170 non-athletes). Comparing the causes of SCD between athletes and non-athletes, non-ischemic left ventricular scar (NILVS) (5.1% vs. 1.1%, p=0.01) was more frequent in the former, while coronary artery disease (CAD) (19.6% vs. 9.1%, p=0.009), arrhythmogenic cardiomyopathy (ACM) (11.5% vs. 4.7%, p=0.03) and channelopathies (8.4% vs. 1.9%, p=0.02) were more frequent in the latter. In studies published in the last decade, hypertrophic cardiomyopathy (HCM) (p=0.002), dilated cardiomyopathy (p=0.047), and anomalous origin of coronary arteries (AOCA) (p=0.009) were more frequently the causes of SCD in athletes while aortic dissection (0.022) was the cause in non-athletes. HCM (p=0.01) and AOCA (p=0.004) were more frequently the causes of SCD in the US while ACM (p=0.001), structurally normal heart (p=0.02), and channelopathies (p=0.02) were more frequent in Europe. CONCLUSIONS: Among the causes of SCD, NILVS was the more frequent cause in athletes, while CAD, ACM and channelopathies were more frequent causes in non-athletes. The causes of SCD differ between the US and Europe.

A prospective study on the consequences of SARS-CoV-2 infection on the heart of young adult competitive athletes: Implications for a safe return-to-play.

OBJECTIVES: The COVID-19 pandemic has shocked the sports world because of the suspension of competitions and the spread of SARS-CoV-2 among athletes. After SARS-CoV-2 infection, cardio-pulmonary complications can occur and, before the resumption of sports competitions, a screening has been recommended. However, few data are available and discrepancies exist in the screening modalities. We conducted this prospective study to investigate the incidence of cardiovascular consequences following SARS-CoV-2 infection in young adult competitive athletes and the appropriate screening strategies for a safe return-to-play. METHODS: Ninety competitive athletes (24 ± 10 years) after asymptomatic or mildly symptomatic SARS-CoV-2 infection were screened by physical examination, blood testing, spirometry, 12­lead resting ECG, 24-h ambulatory ECG monitoring, echocardiogram, and cardiopulmonary exercise testing (CPET). RESULTS: Sixty-four athletes (71.1%) were male, and most (76.7%) were mildly symptomatic. After SARS-CoV-2 infection, spirometry and resting ECG were normal in all athletes. Ambulatory ECG monitoring demonstrated <50/24 h supraventricular and ventricular premature beats in 53.3% and 52.2% of athletes, respectively, in the absence of malignant arrhythmias. CPET did not demonstrate cardiopulmonary limitations. Echocardiography showed pericardial effusion in 3 athletes (all females) with symptomatic SARS-CoV-2 infection (3.3%; 4.4% in the symptomatic group) with a definitive diagnosis of myopericarditis in 1 athlete (1.1%) and pericarditis in 2 athletes (2.2%). CONCLUSIONS: Cardiac consequences of SARS-CoV-2 infection were found in 3.3% of competitive athletes. An appropriate screening primarily based on the detection of uncommon arrhythmias and cardiac symptoms should be recommended in competitive athletes after SARS-CoV-2 infection to detect a cardiac involvement and guarantee a safe return-to-play.