Effectiveness and safety of mycophenolate mofetil and rituximab combination therapy for immune idiopathic myopathies.

INTRODUCTION: Idiopathic inflammatory myopathies (IIM) represent a rare and heterogenous group diseases, and their treatment is not fully defined yet. According to previous small case series, the combination of mycophenolate mofetil (MMF) and rituximab (RTX) may be effective in controlling difficult-to-treat patients. Our aim was to further explore the efficacy and safety of this combined approach in patients with IIM. METHODS: Patients with IIM treated with the RTX/MMF combination in our Center were retrospectively identified. After the start of combination therapy, the efficacy was evaluated at 12 months (T12) according the 2016 ACR/EULAR response criteria for IIM. Cardiac imaging and pulmonary function tests were used to monitor disease activity in patients with myocarditis and interstitial lung disease, respectively. Adverse events were recorded over the follow-up period. RESULTS: Among the 20 patients (median age 61 years; 70% female) included in the study, anti-synthetase syndrome was the most prevalent IIM subgroup (60%). At treatment start, muscle, heart, and lung were the most commonly actively affected organs. After 12 months, a moderate or major response was observed in all patients, and creatine kinase was significantly decreased (p-value = 0.012). Cardiac imaging and enzymes monitoring showed a reduction of heart inflammation, while pulmonary function tests improved in patients with lung involvement. No severe side effects were observed. CONCLUSION: Our data show that combination of RTX and MMF is effective and safe in patients with severe and refractory IIM. Therefore, this combined treatment might represent a feasible approach for difficult-to-treat IIM cases.

Cardiac Wolframinopathies: A Case Report of Myocarditis and a Literature Review of Cardiac Involvement in Wolfram Syndrome 1.

Purpose: Myocarditis is frequently a sporadic disease, but may also occur in the context of genetic disorders which may increase susceptibility to cardiac inflammation. Cardiac involvement in Wolfram syndrome type 1 (WS1) has been scarcely characterized. To our knowledge, no cases of virus-negative myocarditis have been reported in the WS1 pediatric population. Methods: We report the description of a pediatric case of acute myocarditis in the context of WS1, followed by a literature review of cardiovascular involvement associated with wolframin variants, and discuss potential pathophysiological mechanisms and therapeutic options. Results: A young patient with WS1, treated with insulin and liraglutide, was admitted for acute chest pain. Cardiac magnetic resonance and endomyocardial biopsy were performed to confirm the clinical suspicion of myocarditis. While congenital heart diseases and arrhythmias have been described previously in patients with WS1, this is the first description of virus-negative myocarditis. Conclusions: Myocarditis may represent a possible manifestation of cardiovascular involvement in WS1. Cardiovascular screening may be considered in patients with WS1.

Value of a short non-contrast CMR protocol in MINOCA.

OBJECTIVES: To evaluate the diagnostic performance of a short non-contrast CMR (ShtCMR) protocol relative to a matched standard comprehensive CMR (StdCMR) protocol in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA). METHODS: This multicenter retrospective study included patients with a working diagnosis of MINOCA who underwent a StdCMR between January 2019 and December 2020. An expert and a non-expert reader performed a blinded reading with the ShtCMR (long-axis cine images, T2w-STIR, T1- and T2-mapping). A consensus reading of the StdCMR (reference standard) was performed at least 3 months after the ShtCMR reading session. Readers were asked to report the following: (1) diagnosis; (2) level of confidence in their diagnosis with the ShtCMR; (3) number of myocardial segments involved, and (4) functional parameters. RESULTS: A total of 179 patients were enrolled. The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). ShtCMR allowed reaching the same diagnosis as StdCMR in 85% of patients when interpreted by expert readers (rising from 66% for poor confidence to 99% for good, p = 0.0001) and in 73% (p = 0.01) by non-expert ones (60% for poor vs 89% for good confidence, p = 0.0001). Overall, the ShtCMR overestimated the ejection fraction, underestimated cardiac volumes (p < 0.01), and underestimated the number of segments involved by pathology (p = 0.0008) when compared with the StdCMR. CONCLUSION: The ShtCMR was found to be a debatable alternative to the StdCMR in patients with MINOCA. Nevertheless, when an experienced reader reaches a good or very good diagnostic confidence using the ShtCMR, the reader may choose to stop the examination, reducing the length of the CMR without affecting the patient's diagnosis. CLINICAL RELEVANCE STATEMENT: A short non-contrast CMR protocol may be a viable alternative to standard protocols in selected CMR studies of patients with MINOCA, allowing for faster diagnosis while reducing time and resources and increasing the number of patients who can be scanned. KEY POINTS: • The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). • In 57% of patients with MINOCA, the experienced reader considers that contrast medium is probably not necessary for diagnosis without affecting the patient's diagnosis (99% of agreement rate between ShtCMR and StdCMR).

Clinical profiling and outcomes of viral myocarditis manifesting with ventricular arrhythmias.

Aims: Clinical features and risk stratification of patients with viral myocarditis (VM) complicated by ventricular arrhythmias (VA) are incompletely understood. We aim to describe arrhythmia patterns and outcomes in patients with VM and early-onset VA. Methods and results: We present a single-centre study, enrolling patients with VM proven by endomyocardial biopsy, and evidence of VA within 24 h of hospitalization. The incidence of major adverse events (MAE), including all-cause death, severe heart failure, advanced atrioventricular blocks, or major VA, was evaluated during a 24-month follow-up (FU) and compared with a matched group of virus-negative myocarditis. Of patients with VM (n = 74, mean age 47 ± 16 years, 66% males, and left ventricular ejection fraction 51 ± 13%), 20 (27%) presented with major VA [ventricular tachycardia/ventricular fibrillation (VT/VF)], and 32 (44%) had polymorphic VA. Patients with polymorphic VA more commonly had evidence of ongoing systemic infection (24/32 vs. 10/42, P = 0.004) and experienced greater occurrence of MAE at discharge (15/32 vs. 2/42, P < 0.001). However, the incidence of MAE during FU was higher in patients with monomorphic VA compared to those with polymorphic VA (17/42 vs. 2/28, P = 0.002). Patients with monomorphic VA displayed frequently signs of chronic cardiomyopathy and had outcomes comparable with virus-negative myocarditis (log rank P = 0.929). Presentation with VT/VF was independently associated with MAE [at discharge: hazard ratio (HR) 4.7, 95% confidence interval (CI) 1.6-14.0, P = 0.005; during FU: HR 6.3, 95% CI 2.3-17.6, P < 0.001]. Conclusion: In patients with VM, polymorphic VA point to ongoing systemic infection and early adverse outcomes, whereas monomorphic VA suggest chronic cardiomyopathy and greater incidence of MAE during FU. Presentation with VT/VF is independently associated with MAE.

Myocarditis in anti-synthetase syndrome: clinical features and diagnostic modalities.

OBJECTIVES: Myocarditis is an overlooked manifestation of anti-synthetase syndrome (ASS). Our study describes the clinical and instrumental features of ASS-myocarditis and evaluates the diagnostic performance of cardiac magnetic resonance (CMR) with mapping techniques. METHODS: Data from ASS-patients were retrospectively analyzed. CMR data of patients diagnosed with myocarditis, including late gadolinium enhancement (LGE), T2-ratio, T1-mapping, extra-cellular volume (ECV) and T2-mapping, were reviewed. Myocarditis was defined by the presence of symptoms of heart involvement with increased high-sensitive troponin T (hs-TnT) and/or NT-proBNP and at least an instrumental abnormality. Clinical features of ASS patients with and without myocarditis were compared. A p value<0.05 was considered. RESULTS: Among a cohort of 43 ASS-patients (median age 58[48.0-66.0] years; females 74.4%; anti-Jo1 53.5%), 13(30%) were diagnosed with myocarditis. In 54% of patients, myocarditis was diagnosed at clinical onset. All ASS-myocarditis patients had at least one CMR abnormality: increased ECV in all cases, presence of LGE, increased T1 and T2-mapping in 91%. The 2009-Lake Louis criteria (LLC) were satisfied by 6 patients, the 2018-LLC by 10. With the updated LLC, the sensitivity for myocarditis improved from 54.6% to 91.0%. ASS-patients with myocarditis were more frequently males(53% vs 13%;p=0.009) with fever(69% vs 17%;p=0.001), and had higher hs-TnT (88.0[23.55-311.5] vs 9.80[5.0-23.0]ng/L; p < 0.001), NT-proBNP(525.5[243.5-1575.25] vs 59.0[32.0-165.5;p=0.013]pg/ml;p=0.013) and C-reactive protein(CRP)(7.0[1.7-15.75] vs 1.85[0.5-2.86]mg/L;p=0.011) compared to those without myocarditis. CONCLUSION: In ASS, myocarditis is frequent, even at clinical onset. ASS-patients with myocarditis frequently presented with fever and increased CRP, suggesting the existence of an inflammatory phenotype. The use of novel CMR mapping techniques may increase the diagnostic sensitivity for myocarditis in ASS.

Multimodal Detection and Targeting of Biopsy-Proven Myocardial Inflammation in Genetic Cardiomyopathies: A Pilot Report.

The authors present a clinical report focused on the overlap between myocarditis and genetic cardiomyopathies of the dilated and arrhythmogenic spectrum. Our cohort was composed of 25 patients undergoing extensive baseline characterization and prospective reassessment by a dedicated multidisciplinary disease unit during a median follow-up of 69 months. We showed that the use of multimodal imaging allowed both discrimination of specific genotypes and identification of myocardial inflammation proven using endomyocardial biopsy. In addition, we showed that the use of immunomodulatory therapy was beneficial for most patients.

Chest CT opportunistic biomarkers for phenotyping high-risk COVID-19 patients: a retrospective multicentre study.

OBJECTIVE: To assess the value of opportunistic biomarkers derived from chest CT performed at hospital admission of COVID-19 patients for the phenotypization of high-risk patients. METHODS: In this multicentre retrospective study, 1845 consecutive COVID-19 patients with chest CT performed within 72 h from hospital admission were analysed. Clinical and outcome data were collected by each center 30 and 80 days after hospital admission. Patients with unknown outcomes were excluded. Chest CT was analysed in a single core lab and behind pneumonia CT scores were extracted opportunistic data about atherosclerotic profile (calcium score according to Agatston method), liver steatosis (≤ 40 HU), myosteatosis (paraspinal muscle F < 31.3 HU, M < 37.5 HU), and osteoporosis (D12 bone attenuation < 134 HU). Differences according to treatment and outcome were assessed with ANOVA. Prediction models were obtained using multivariate binary logistic regression and their AUCs were compared with the DeLong test. RESULTS: The final cohort included 1669 patients (age 67.5 [58.5-77.4] yo) mainly men 1105/1669, 66.2%) and with reduced oxygen saturation (92% [88-95%]). Pneumonia severity, high Agatston score, myosteatosis, liver steatosis, and osteoporosis derived from CT were more prevalent in patients with more aggressive treatment, access to ICU, and in-hospital death (always p < 0.05). A multivariable model including clinical and CT variables improved the capability to predict non-critical pneumonia compared to a model including only clinical variables (AUC 0.801 vs 0.789; p = 0.0198) to predict patient death (AUC 0.815 vs 0.800; p = 0.001). CONCLUSION: Opportunistic biomarkers derived from chest CT can improve the characterization of COVID-19 high-risk patients. CLINICAL RELEVANCE STATEMENT: In COVID-19 patients, opportunistic biomarkers of cardiometabolic risk extracted from chest CT improve patient risk stratification. KEY POINTS: • In COVID-19 patients, several information about patient comorbidities can be quantitatively extracted from chest CT, resulting associated with the severity of oxygen treatment, access to ICU, and death. • A prediction model based on multiparametric opportunistic biomarkers derived from chest CT resulted superior to a model including only clinical variables in a large cohort of 1669 patients suffering from SARS- CoV2 infection. • Opportunistic biomarkers of cardiometabolic comorbidities derived from chest CT may improve COVID-19 patients' risk stratification also in absence of detailed clinical data and laboratory tests identifying subclinical and previously unknown conditions.

Extracellular volume fraction (ECV) derived from pre-operative computed tomography predicts prognosis in patients undergoing transcatheter aortic valve implantation (TAVI).

AIMS: Transcatheter aortic valve implantation (TAVI) is the treatment of choice for high-risk patients with severe aortic stenosis (AS). A portion of TAVI recipients has no long-term clinical benefit, and myocardial fibrosis may contribute to unfavourable outcomes. We aimed to assess the prognostic value of an interstitial fibrosis marker, extracellular volume fraction (ECV), measured at planning computed tomography (CT) before TAVI. METHODS AND RESULTS: From October 2020 to July 2021, 159 consecutive patients undergoing TAVI planning CT were prospectively enroled. ECV was calculated as the ratio of myocardium and blood pool differential attenuations before and 5 min after contrast administration, pondered for haematocrit. A composite endpoint including heart failure hospitalization (HFH) and death was collected by telehealth or in-person follow-up visits in the 113 patients constituting the final study population. Cox proportional hazards model was used to assess association between ECV and the composite endpoint.Median follow-up was 13 (11-15) months. The composite endpoint occurred in 23/113 (20%) patients. These patients had lower aortic valve mean pressure gradient [39 (29-48) vs. 46 (40-54) mmHg, P = 0.002] and left ventricular and right ventricular ejection fraction [51 (37-69) vs. 66 (54-74)%, P = 0.014; 45 (31-53) vs. 49 (44-55)%, P = 0.010] and higher ECV [31.5 (26.9-34.3) vs. 27.8 (25.3-30.2)%, P = 0.006]. At multivariable Cox analysis, ECV higher than 31.3% was associated to increased risk of death or HFH at follow-up (hazard ratio = 5.92, 95% confidence interval 2.37-14.75, P < 0.001). CONCLUSION: In this prospective observational cohort study, ECV measured at TAVI planning CT predicts the composite endpoint (HFH or death) in high-risk severe AS patients.

Cardiovascular involvement in Erdheim-Chester diseases is associated with myocardial fibrosis and atrial dysfunction.

PURPOSE: Erdheim-Chester disease (ECD) is a rare multisystem histiocytosis, whose cardiovascular involvement has not been systematically characterized so far. We aimed to systematically (qualitatively and quantitatively) describe the features of cardiovascular involvement in a large cohort of ECD patients and to evaluate its impact on myocardial fibrosis extension and cardiac function. MATERIAL AND METHODS: Among 54 patients with biopsy-proven ECD, 29 patients (59 ± 12 years, 79% males) underwent 1.5-T CMR using a standardized protocol for qualitative and quantitative assessment of disease localization, evaluation of atrial and ventricular function, and assessment of non-dense and dense myocardial fibrosis. RESULTS: The right atrioventricular (AV) groove was the most commonly affected cardiac site (76%) followed by the right atrial walls (63%), thoracic aorta (59%), and superior vena cava (38%). Right AV groove involvement, encasing the right ventricular artery, was associated with non-dense myocardial fibrosis in the infero-septal (20/26 patients) and the inferior (14/26 patients) mid-basal left ventricular (LV) wall. In two patients with right AV groove localization, LGE revealed myocardial infarction in the same myocardial segments. Three out of five patients with left AV groove involvement had non-dense LGE on the lateral LV mid-basal wall. Bulky right atrial pseudomass was associated with atrial dysfunction and superior and inferior vena cava stenosis. CONCLUSIONS: In ECD patients, AV groove localization is associated with LV wall fibrosis in the downstream coronary territories, suggesting hemodynamic alterations due to coronary encasement. Conversely, atrial pseudomass ECD localizations impact on atrial contractility causing atrial dysfunction and are associated with atrio-caval junction stenosis.

Cardiac magnetic resonance findings in acute and post-acute COVID-19 patients with suspected myocarditis.

INTRODUCTION: Cardiac injury is commonly reported in COVID-19 patients, resulting associated to pre-existing cardiovascular disease, disease severity, and unfavorable outcome. Aim is to report cardiac magnetic resonance (CMR) findings in patients with myocarditis-like syndrome during the acute phase of SARS-CoV-2 infection (AMCovS) and post-acute phase (cPACS). METHODS: Between September 2020 and January 2022, 39 consecutive patients (24 males, 58%) were referred to our department to perform a CMR for the suspicion of myocarditis related to AMCovS (n = 17) and cPACS (n = 22) at multimodality evaluation (clinical, laboratory, ECG, and echocardiography). CMR was performed for the assessment of volume, function, edema and fibrosis with standard sequences and mapping techniques. CMR diagnosis and the extension and amount of CMR alterations were recorded. RESULTS: Patients with suspected myocarditis in acute and post-COVID settings were mainly men (10 (59%) and 12 (54.5%), respectively) with older age in AMCovS (58 [48-64]) compared to cPACS (38 [26-53]). Myocarditis was confirmed by CMR in most of cases: 53% of AMCovS and 50% of cPACS with negligible LGE burden (3 [IQR, 1-5] % and 2 [IQR, 1-4] %, respectively). Myocardial infarction was identified in 4/17 (24%) patients with AMCovS. Cardiomyopathies were identified in 12% (3/17) and 27% (6/22) of patients with AMCovS and cPACS, including DCM, HCM and mitral valve prolapse. CONCLUSIONS: In patients with acute and post-acute COVID-19 related suspected myocarditis, CMR improves diagnostic accuracy characterizing ischemic and non-ischemic injury and unraveling subclinical cardiomyopathies.

Cardiac magnetic resonance abnormalities in patients with acute myocarditis proven by septal endomyocardial biopsy.

BACKGROUND: Previous studies suggest low diagnostic sensitivity of cardiac magnetic resonance (CMR) imaging based on Lake Louise criteria (LLC) to identify patients with complicated presentations of acute myocarditis (AM). We evaluated classic and updated LLC in patients with AM proven by right ventricular septal endomyocardial biopsy (RVS-EMB). METHODS: From an initial population of 499 patients with clinically suspected AM from a multicenter retrospective cohort, we included 74 patients with histologically proven myocarditis on RVS-EMB and available CMR within 30 days since admission. The prevalence of total and septal CMR abnormalities [namely, T2-weighted images (T2W), late gadolinium enhancement (LGE), T2 and T1 mapping, and extracellular volume (ECV)] were assessed in patients with complicated vs. uncomplicated AM. RESULTS: Among 74 patients [mean age 38 ± 15 years, 65% males, left ventricular ejection fraction (LVEF) 40 ± 18%] with RVS-EMB-proven AM, 53 (72%) had a complicated presentation. The classic LLC were positive in 56/74 patients (76%), whereas the updated ones were positive in 41/41 of cases (100%). Septal involvement, documented in 48/74 patients (65%) by conventional T2W/LGE and in 39/41 cases (95%) by mapping techniques (p < 0.001), was more common in patients with complicated AM. In the 41 patients undergoing both evaluations, CMR sensitivity for myocarditis was 85% for the classic LLC vs. 100% for the updated LLC (p = 0.006). CONCLUSION: In patients with myocarditis on RVS-EMB, CMR using updated LLC has high sensitivity in the detection of AM when performed within 30 days. Septal abnormalities are more common in patients with complicated AM.

Clinical Applications of FDG-PET Scan in Arrhythmic Myocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan has no recognized role in diagnosis, prognosis, and disease monitoring in patients with arrhythmic myocarditis. OBJECTIVES: The purpose of this study was to investigate the value of FDG-PET scan in arrhythmic myocarditis. METHODS: The authors enrolled 75 consecutive patients (age 47 ± 14 years, 65% men) undergoing FDG-PET scan for arrhythmic myocarditis. Myocarditis was diagnosed by endomyocardial biopsy (EMB) and, whenever applicable, cardiac magnetic resonance (CMR). RESULTS: Indications for FDG-PET scan included either contraindication to CMR (n = 50) or mismatch between CMR and EMB (n = 25). Overall, 50 patients (67%) had positive FDG-PET. Sensitivity was 75% referring to EMB, and 73% to CMR. Specificity was 67% referring to EMB, and 59% to CMR. FDG-PET accuracy was lower in the presence of borderline myocarditis, and either late (>30 days) or on-immunosuppression FDG-PET scanning. Anteroseptal distribution pattern, found in 12 of 50 (24%) patients including 7 of 7 cardiac sarcoidosis cases, was associated with greater occurrence of ventricular arrhythmias and atrioventricular blocks in 4.2 ± 1.7 years of follow-up (10 of 12 vs 7 of 38, and 7 of 12 vs 0 of 38, respectively; both P < 0.001). In 39 patients (52%), FDG-PET was repeated by 13 ± 2 months, allowing immunosuppression withdrawal after FDG uptake normalization either by first (76%) or second reassessment (24%). CONCLUSIONS: FDG-PET scan may be a clinically useful diagnostic technique in arrhythmic myocarditis, in particular when CMR is unsuitable because of irregular heartbeat or implantable cardioverter-defibrillator-related artifacts. Anteroseptal FDG distribution is associated with a worse arrhythmic outcome and should raise the suspicion of cardiac sarcoidosis. During follow-up, repeated FDG-PET allows myocarditis monitoring to guide immunosuppression withdrawal.

Exercise Stress Test Late after Arrhythmic versus Nonarrhythmic Presentation of Myocarditis.

Background. Exercise stress test (EST) has been scarcely investigated in patients with arrhythmic myocarditis. Objectives. To report the results of EST late after myocarditis with arrhythmic vs. nonarrhythmic presentation. Methods. We enrolled consecutive adult patients with EST performed at least six months after acute myocarditis was diagnosed using gold-standard techniques. Patients with ventricular arrhythmia (VA) at presentation were compared with the nonarrhythmic group. Adverse events occurring during follow-up after EST included cardiac death, disease-related rehospitalization, malignant VA, and proven active myocarditis. Results. The study cohort was composed of 128 patients (age 41 ± 9 y, 70% males) undergoing EST after myocarditis. Of them, 64 (50%) had arrhythmic presentation. EST was performed after 15 ± 4 months from initial diagnosis, and was conducted on betablockers in 75 cases (59%). During EST, VA were more common in the arrhythmic group (43 vs. 4, p < 0.001), whereas signs and symptoms of ischemia were more prevalent in the nonarrhythmic one (6 vs. 1, p = 0.115). By 58-month mean follow-up, 52 patients (41%) experienced adverse events, with a greater prevalence among arrhythmic patients (39 vs. 13, p < 0.001). As documented both in the arrhythmic and nonarrhythmic subgroups, patients had greater prevalence of adverse events following a positive EST (40/54 vs. 12/74 with negative EST, p < 0.001). Electrocardiographic features of VA during EST correlated with the subsequent inflammatory restaging of myocarditis. Nonarrhythmic patients with uneventful EST both on- and off-treatment were free from subsequent adverse events. Conclusions. Late after the arrhythmic presentation of myocarditis, EST was frequently associated with recurrent VA. In both arrhythmic and nonarrhythmic myocarditis, EST abnormalities correlated with subsequent adverse outcomes.

AI-SCoRE (artificial intelligence-SARS CoV2 risk evaluation): a fast, objective and fully automated platform to predict the outcome in COVID-19 patients.

PURPOSE: To develop and validate an effective and user-friendly AI platform based on a few unbiased clinical variables integrated with advanced CT automatic analysis for COVID-19 patients' risk stratification. MATERIAL AND METHODS: In total, 1575 consecutive COVID-19 adults admitted to 16 hospitals during wave 1 (February 16-April 29, 2020), submitted to chest CT within 72 h from admission, were retrospectively enrolled. In total, 107 variables were initially collected; 64 extracted from CT. The outcome was survival. A rigorous AI model selection framework was adopted for models selection and automatic CT data extraction. Model performances were compared in terms of AUC. A web-mobile interface was developed using Microsoft PowerApps environment. The platform was externally validated on 213 COVID-19 adults prospectively enrolled during wave 2 (October 14-December 31, 2020). RESULTS: The final cohort included 1125 patients (292 non-survivors, 26%) and 24 variables. Logistic showed the best performance on the complete set of variables (AUC = 0.839 ± 0.009) as in models including a limited set of 13 and 5 variables (AUC = 0.840 ± 0.0093 and AUC = 0.834 ± 0.007). For non-inferior performance, the 5 variables model (age, sex, saturation, well-aerated lung parenchyma and cardiothoracic vascular calcium) was selected as the final model and the extraction of CT-derived parameters was fully automatized. The fully automatic model showed AUC = 0.842 (95% CI: 0.816-0.867) on wave 1 and was used to build a 0-100 scale risk score (AI-SCoRE). The predictive performance was confirmed on wave 2 (AUC 0.808; 95% CI: 0.7402-0.8766). CONCLUSIONS: AI-SCoRE is an effective and reliable platform for automatic risk stratification of COVID-19 patients based on a few unbiased clinical data and CT automatic analysis.

Advanced cardiac imaging in the spectrum of COVID-19 related cardiovascular involvement.

Cardiovascular involvement is a common complication of COVID-19 infection and is associated to increased risk of unfavorable outcome. Advanced imaging modalities (coronary CT angiography and Cardiac Magnetic Resonance) play a crucial role in the diagnosis, follow-up and risk stratification of patients affected by COVID-19 pneumonia with suspected cardiovascular involvement. In the present manuscript we firstly review current knowledge on the mechanisms by which SARS-CoV-2 can trigger endothelial and myocardial damage. Secondly, the implications of the cardiovascular damage on patient's prognosis are presented. Finally, we provide an overview of the main findings at advanced cardiac imaging characterizing COVID-19 in the acute setting, in the post-acute syndrome, and after vaccination, emphasizing the potentiality of CT and CMR, the indication and their clinical implications.

Myosteatosis Significantly Predicts Persistent Dyspnea and Mobility Problems in COVID-19 Survivors.

Background: Persistent symptoms including dyspnea and functional impairment are common in COVID-19 survivors. Poor muscle quality (myosteatosis) associates with poor short-term outcomes in COVID-19 patients. The aim of this observational study was to assess the relationship between myosteatosis diagnosed during acute COVID-19 and patient-reported outcomes at 6 months after discharge. Methods: Myosteatosis was diagnosed based on CT-derived skeletal muscle radiation attenuation (SM-RA) measured during hospitalization in 97 COVID-19 survivors who had available anthropometric and clinical data upon admission and at the 6-month follow-up after discharge. Dyspnea in daily activities was assessed using the modified Medical Research Council (mMRC) scale for dyspnea. Health-related quality of life was measured using the European quality of life questionnaire three-level version (EQ-5D-3L). Results: Characteristics of patients with (lowest sex- and age-specific tertile of SM-RA) or without myosteatosis during acute COVID-19 were similar. At 6 months, patients with myosteatosis had greater rates of obesity (48.4 vs. 27.7%, p = 0.046), abdominal obesity (80.0 vs. 47.6%, p = 0.003), dyspnea (32.3 vs. 12.5%, p = 0.021) and mobility problems (32.3 vs. 12.5%, p = 0.004). Myosteatosis diagnosed during acute COVID-19 was the only significant predictor of persistent dyspnea (OR 3.19 [95% C.I. 1.04; 9.87], p = 0.043) and mobility problems (OR 3.70 [95% C.I. 1.25; 10.95], p = 0.018) at 6 months at logistic regression adjusted for sex, age, and BMI. Conclusion: Myosteatosis diagnosed during acute COVID-19 significantly predicts persistent dyspnea and mobility problems at 6 months after hospital discharge independent of age, sex, and body mass. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04318366].

Appropriateness criteria for the use of cardiac computed tomography, SIC-SIRM part 2: acute chest pain evaluation; stent and coronary artery bypass graft patency evaluation; planning of coronary revascularization and transcatheter valve procedures; cardiomyopathies, electrophysiological applications, cardiac masses, cardio-oncology and pericardial diseases evaluation.

In the past 20 years, cardiac computed tomography (CCT) has become a pivotal technique for the noninvasive diagnostic workup of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Randomized clinical trials documented the value of CCT in increasing the cost-effectiveness of the management of patients with acute chest pain presenting in the emergency department, also during the pandemic. Beyond the evaluation of stents and surgical graft patency, the anatomical and functional coronary imaging have the potential to guide treatment decision-making and planning for complex left main and three-vessel coronary disease. Furthermore, there has been an increasing demand to use CCT for preinterventional planning in minimally invasive procedures, such as transcatheter valve implantation and mitral valve repair. Yet, the use of CCT as a roadmap for tailored electrophysiological procedures has gained increasing importance to assure maximum success. In the meantime, innovations and advanced postprocessing tools have generated new potential applications of CCT from the simple coronary anatomy to the complete assessment of structural, functional and pathophysiological biomarkers of cardiac disease. In this complex and revolutionary scenario, it is urgently needed to provide an updated guide for the appropriate use of CCT in different clinical settings. This manuscript, endorsed by the Italian Society of Cardiology (SIC) and the Italian Society of Medical and Interventional Radiology (SIRM), represents the second of two consensus documents collecting the expert opinion of cardiologists and radiologists about current appropriate use of CCT.

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.

Cardiac magnetic resonance in systemic sclerosis myocarditis: the value of T2 mapping to detect myocardial inflammation.

OBJECTIVES: Myocarditis in SSc is associated with a poor prognosis. Cardiac magnetic resonance (CMR) is the non-invasive diagnostic modality of choice for SSc myocarditis. Our study investigates the performance of the mapping techniques included in the revised Lake Louise criteria (LLC) for the identification of SSc myocarditis. METHODS: CMR data (right and left ventricular function and morphology, early and late gadolinium enhancement [LGE], T2 ratio, and T1 mapping, extracellular volume [ECV] and T2 mapping) of SSc patients diagnosed with myocarditis were reviewed. Myocarditis was defined by the presence of symptoms of SSc heart involvement with increased high-sensitive troponin T (hs-TnT) and/or NT-proBNP and at least an abnormality at 24 h ECG Holter and/or echocardiography and/or CMR. A P-value < 0.05 was considered as statistically significant. RESULTS: Nineteen patients (median age 54 [46-70] years; females 78.9%; diffuse SSc 52.6%; anti-Scl70+ 52.6%) were identified: 11 (57.9%) had echocardiographic, and 8 (42.8%) 24 h ECG Holter abnormalities. All patients had at least one CMR abnormality: LGE in 18 (94.7%), increased ECV in 10 (52.6%) and T2 mapping >50 ms in 15 (78.9%). Median T1 and T2 mapping were 1085 [1069-1110] ms and 53.1 [52-54] ms, respectively. T1 mapping directly correlated with NT-proBNP (r = 0.620; P = 0.005), ESR (r = 0.601; P = 0.008), CRP (r = 0.685; P = 0.001) and skin score (r = 0.507; P = 0.027); ECV correlated with NT-proBNP serum levels (r = 0.702; P = 0.001). No correlations emerged between T2 mapping and other parameters. Ten patients satisfied the 2009 LLC, 17 the 2018 LLC. With the new criteria including T2 mapping, the sensitivity improved from 52.6% to 89.5%. CONCLUSION: The CMR mapping techniques improve the sensitivity to detect myocardial inflammation in patients with SSc heart involvement. The evaluation of T2 mapping increases diagnostic accuracy for the recognition of myocardial inflammation in SSc.