Computed tomography and nuclear medicine for the assessment of coronary inflammation: clinical applications and perspectives.

There is increasing evidence that in patients with atherosclerotic cardiovascular disease (ASCVD) under optimal medical therapy, a persisting dysregulation of the lipid and glucose metabolism, associated with adipose tissue dysfunction and inflammation, predicts a substantial residual risk of disease progression and cardiovascular events. Despite the inflammatory nature of ASCVD, circulating biomarkers such as high-sensitivity C-reactive protein and interleukins may lack specificity for vascular inflammation. As known, dysfunctional epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) produce pro-inflammatory mediators and promote cellular tissue infiltration triggering further pro-inflammatory mechanisms. The consequent tissue modifications determine the attenuation of PCAT as assessed and measured by coronary computed tomography angiography (CCTA). Recently, relevant studies have demonstrated a correlation between EAT and PCAT and obstructive coronary artery disease, inflammatory plaque status and coronary flow reserve (CFR). In parallel, CFR is well recognized as a marker of coronary vasomotor function that incorporates the haemodynamic effects of epicardial, diffuse and small-vessel disease on myocardial tissue perfusion. An inverse relationship between EAT volume and coronary vascular function and the association of PCAT attenuation and impaired CFR have already been reported. Moreover, many studies demonstrated that 18F-FDG PET is able to detect PCAT inflammation in patients with coronary atherosclerosis. Importantly, the perivascular FAI (fat attenuation index) showed incremental value for the prediction of adverse clinical events beyond traditional risk factors and CCTA indices by providing a quantitative measure of coronary inflammation. As an indicator of increased cardiac mortality, it could guide early targeted primary prevention in a wide spectrum of patients. In this review, we summarize the current evidence regarding the clinical applications and perspectives of EAT and PCAT assessment performed by CCTA and the prognostic information derived by nuclear medicine.

Generation of four human induced pluripotent stem cell lines from COVID-19 hospitalized patients with increased levels of cardiac Troponin in the acute infection phase developing or not myocarditis.

Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2 virus, leading to mild to severe respiratory symptoms. Cardiovascular involvement is frequent and mainly manifests with myocarditis, arrhythmias, cardiac arrests, heart failure and coagulation abnormality. We generated human induced pluripotent stem cells (hiPSCs) from four COVID-19 patients, all characterized by increased levels of high-sensitivity Troponin I (hsTnI) during the infection acute phase, who developed (n = 2) or not (n = 2) severe myocarditis, as COVID-19 complication. The established hiPSCs were characterized for pluripotency and genomic stability, and constitute a useful resource for studying the mechanisms underlying the variability in COVID-19 severe cardiac manifestations.

A case of myopericarditis recurrence after third dose of BNT162b2 vaccine against SARS-CoV-2 in a young subject: link or causality?

The rate of post-vaccine myocarditis is being studied from the beginning of the massive vaccination campaign against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a direct cause-effect relationship has been described, in most cases, the vaccine pathophysiological role is doubtful. Moreover, it is not quite as clear as having had a previous myocarditis could be a risk factor for a post-vaccine disease relapse. A 27-year-old man presented to the emergency department for palpitations and pericardial chest pain radiated to the upper left limb, on the 4th day after the third dose of BNT162b2 vaccine. He experienced a previous myocarditis 3 years before, with full recovery and no other comorbidities. Electrocardiogram showed normal atrioventricular conduction, incomplete right bundle branch block, and diffuse ST-segment elevation. A cardiac echo showed lateral wall hypokinesis with preserved ejection fraction. Troponin-T was elevated (160 ng/L), chest X-ray was normal, and the SARS-CoV-2 molecular buffer was negative. High-dose anti-inflammatory therapy with ibuprofen and colchicine was started; in the 3rd day high-sensitivity Troponin I reached a peak of 23000 ng/L. No heart failure or arrhythmias were observed. A cardiac magnetic resonance was performed showing normal biventricular systolic function and abnormal tissue characterization suggestive for acute non-ischaemic myocardial injury (increased native T1 and T2 values, increased signal intensity at T2-weighted images and late gadolinium enhancement, all findings with matched subepicardial distribution) at the level of mid to apical septal, anterior, and anterolateral walls. A left ventricular electroanatomic voltage mapping was negative (both unipolar and bipolar), while the endomyocardial biopsy showed a picture consistent with active myocarditis. The patient was discharged in good clinical condition, on bisoprolol 1.25 mg, ramipril 2.5 mg, ibuprofen 600 mg three times a day, colchicine 0.5 mg twice a day. We presented the case of a young man with history of previous myocarditis, admitted with a non-complicated acute myopericarditis relapse occurred 4 days after SARS-CoV-2 vaccination (3rd dose). Despite the observed very low incidence of cardiac complications following BNT162b2 administration, and the lack of a clear proof of a direct cause-effect relationship, we think that in our patient this link can be more than likely. In the probable need for additional SARS-CoV-2 vaccine doses in the next future, studies addressing the risk-benefit balance of this subset of patient are warranted. We described a multidisciplinary management of a case of myocarditis recurrence after the third dose of SARS-CoV-2 BNT162b2 vaccine.

Case Report: Acute Heart Failure Induced by the Combination of Takayasu's, Takotsubo and Coronary Vasospasm in an Elementary School Teacher-A Reaction to Return-to-Work Stress After COVID-19?

Introduction: Takayasu's arteritis (TA) is a systemic inflammatory disease that affects aorta and its major branches. There are several cardiac manifestations of TA and an association with Takotsubo syndrome (TTS) - but not coronary vasospasm - has been previously reported. The role of emotional stress in this context is unknown. Case presentation: A 58-year-old Caucasian female elementary school teacher, with a history of generalized anxiety disorder (GAD), severe asymptomatic aortic regurgitation (AR), and TA in remission under corticosteroids, was admitted in the emergency department with worsening chest pain and dyspnea, initiated after a period of intense emotional stress (increased workload during COVID-19 pandemic). Physical examination revealed signs of heart failure (HF) with hemodynamic stability and an early diastolic heart murmur. The electrocardiogram showed sinus tachycardia, T wave inversion in left precordial and lateral leads, and a corrected QT of 487 ms. Laboratorial evaluation presented high values of high-sensitivity troponin I (3494 ng/L) and B-type natriuretic peptide (4759 pg/mL). The transthoracic echocardiogram revealed severe dilation of left ventricle (LV) with moderate systolic dysfunction, due to apical and midventricular akinesia, and severe AR. The coronary angiography showed normal coronary arteries. An acetylcholine provocative test induced spasm of both the left anterior descending and circumflex arteries, accompanied by chest pain and ST depression, completely reverted after intracoronary nitrates administration. The patient was switched to diltiazem and a drug multitherapy for HF was started. A cardiac magnetic resonance revealed severe dilation of the LV, mild apical hypokinesia, improvement of ejection fraction to 53%, signs of myocardial edema and increased extracellular volume in apical and mid-ventricular anterior and anterolateral walls, and absence of myocardial late gadolinium enhancement, compatible with TTS. At discharge, the patient was clinically stable, without signs of HF, and a progressive reduction of troponin and BNP levels was observed. A final diagnosis of TTS and coronary vasospasm in a patient with GAD and TA was done. Discussion: We present the first case of acute HF showing coexistence of TA, TTS and coronary vasospasm. TA is a rare inflammatory disease that can be associated with TTS and coronary vasospasm. Besides that, coronary vasospasm may also be involved in TTS pathophysiology, suggesting a complex interplay between these diseases. Mood disorders and anxiety influence the response to stress, through a gain of the hypothalamic-pituitary-adrenal axis and an increased cardiovascular system sensitivity to catecholamines. Therefore, although the mechanisms behind these three pathologies are not yet fully studied, this case supports the role of inflammatory and psychiatric diseases in TTS and coronary vasospasm.

Cardiac Care of Non-COVID-19 Patients During the SARS-CoV-2 Pandemic: The Pivotal Role of CCTA.

Aim: The aim of this study is to evaluate the potential use of coronary CT angiography (CCTA) as the sole available non-invasive diagnostic technique for suspected coronary artery disease (CAD) during the coronavirus disease 2019 (COVID-19) pandemic causing limited access to the hospital facilities. Methods and Results: A consecutive cohort of patients with suspected stable CAD and clinical indication to non-invasive test was enrolled in a hub hospital in Milan, Italy, from March 9 to April 30, 2020. Outcome measures were obtained as follows: cardiac death, ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina. All the changes in medical therapy following the result of CCTA were annotated. A total of 58 patients with a mean age of 64 ± 11 years (36 men and 22 women) were enrolled. CCTA showed no CAD in 14 patients (24.1%), non-obstructive CAD in 30 (51.7%) patients, and obstructive CAD in 14 (24.1%) patients. Invasive coronary angiography (ICA) was considered deferrable in 48 (82.8%) patients. No clinical events were recorded after a mean follow-up of 376.4 ± 32.1 days. Changes in the medical therapy were significantly more prevalent in patients with vs. those without CAD at CCTA. Conclusion: The results of the study confirm the capability of CCTA to safely defer ICA in the majority of symptomatic patients and to correctly identify those with critical coronary stenoses necessitating coronary revascularization. This characteristic could be really helpful especially when the hospital resources are limited.

Quantitative Evaluation of COVID-19 Pneumonia Lung Extension by Specific Software and Correlation with Patient Clinical Outcome.

Lung infection named as COVID-19 is an infectious disease caused by the most recently discovered coronavirus 2 (SARS-CoV-2). CT (computed tomography) has been shown to have good sensitivity in comparison with RT-PCR, particularly in early stages. However, CT findings appear to not always be related to a certain clinical severity. The aim of this study is to evaluate a correlation between the percentage of lung parenchyma volume involved with COVID-19 infection (compared to the total lung volume) at baseline diagnosis and correlated to the patient's clinical course (need for ventilator assistance and or death). All patients with suspected COVID-19 lung disease referred to our imaging department for Chest CT from 24 February to 6 April 2020were included in the study. Specific CT features were assessed including the amount of high attenuation areas (HAA) related to lung infection. HAA, defined as the percentage of lung parenchyma above a predefined threshold of -650 (HAA%, HAA/total lung volume), was automatically calculated using a dedicated segmentation software. Lung volumes and CT findings were correlated with patient's clinical course. Logistic regressions were performed to assess the predictive value of clinical, inflammatory and CT parameters for the defined outcome. In the overall population we found an average infected lung volume of 31.4 ± 26.3% while in the subgroup of patients who needed ventilator assistance and who died as well as the patients who died without receiving ventilator assistance the volume of infected lung was significantly higher 41.4 ± 28.5 and 72.7 ± 36.2 (p < 0.001). In logistic regression analysis best predictors for ventilation and death were the presence of air bronchogram (p = 0.006), crazy paving (p = 0.007), peripheral distribution (p < 0.001), age (p = 0.002), fever at admission (p = 0.007), dyspnea (p = 0.002) and cardiovascular comorbidities (p < 0.001). In multivariable analysis, quantitative CT parameters and features added incremental predictive value beyond a model with only clinical parameters (area under the curve, 0.78 vs. 0.74, p = 0.02). Our study demonstrates that quantitative evaluation of lung volume involved by COVID-19 pneumonia helps to predict patient's clinical course.

Role of multimodality imaging in evaluation of cardiovascular involvement in COVID-19.

The management of patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be difficult due to the need for dedicated in-hospital pathways, protective measures for healthcare professionals and isolated beds of intensive care, particularly in areas overwhelmed by wide viral spread. Although pneumonia is the most common clinical manifestation in coronavirus disease 2019 (COVID-19), a variety of cardiovascular complications have been reported. An integrated diagnostic algorithm in SARS-CoV-2-infected patients with suspected cardiac involvement (laboratory findings of myocardial injury and electrocardiographic changes) may help to avoid unnecessary examinations and minimize the risk of operator infection. Due to its mobility and bedside feasibility, echocardiography is the first-line imaging technique in this clinical setting. It quickly provides information on ventricular functions, pulmonary hypertension, valve disease and pericardial effusion. In case of ST-segment elevation (STE), urgent coronary angiography should be performed. Cardiac ultrasound helps distinguish between ischemic and non-ischemic myocardial disease and may detect pericardial disease. Transmural ischemic electrocardiographic changes, with or without early elevated troponin levels or echocardiographic wall motion abnormalities, will determine the need for early invasive coronary angiography. Computed tomography (CT) through its multiple applications (chest CT; CT pulmonary angiography and coronary CT angiography; late iodine enhancement CT) and cardiac magnetic resonance might be helpful in reinforcing or redirecting diagnostic hypothesis emerged by other clinical, electrocardiographic and echocardiographic findings. The current pandemic makes it challenging to perform serial invasive and non-invasive diagnostic testing in COVID-19 patients and high serum troponin level. Nevertheless, thoughtful and systematic use of an appropriate multimodality imaging strategy is clinically relevant to detect cardiac injury and distinguish myocardial infarction from, myocarditis, takotsubo syndrome and pulmonary embolism.

Role of computed tomography in COVID-19.

Coronavirus disease 2019 (COVID-19) has become a rapid worldwide pandemic. While COVID-19 primarily manifests as an interstitial pneumonia and severe acute respiratory distress syndrome, severe involvement of other organs has been documented. In this article, we will review the role of non-contrast chest computed tomography in the diagnosis, follow-up and prognosis of patients affected by COVID-19 pneumonia with a detailed description of the imaging findings that may be encountered. Given that patients with COVID-19 may also suffer from coagulopathy, we will discuss the role of CT pulmonary angiography in the detection of acute pulmonary embolism. Finally, we will describe more advanced applications of CT in the differential diagnosis of myocardial injury with an emphasis on ruling out acute coronary syndrome and myocarditis.