Utility of cardiac bioenzymes in predicting cardiovascular outcomes in SARS-CoV-2.

The relationship between coronavirus disease-19 (COVID-19) and cardiovascular diseases has been an important issue. Therefore, cardiac biomarkers and cardiac imaging have an important place in the diagnostic phase. It is important to know the relationship of biomarkers in COVID-19 so that we can understand the diagnosis of the disease, the predicted course and results after diagnosis.

COVID-19-related cardiomyopathy: Can dual-energy computed tomography be a diagnostic tool?

BACKGROUND: No study on dual energy computed tomography (DECT) has been found in the literature to evaluate possibly fatal cardiac/myocardial problems in corona virus disease 2019 (COVID-19) patients. Myocardial perfusion deficits can be found in COVID-19 patients even without any significant coronary artery occlusion, and these deficits can be shown via DECT with a perfect interrater agreement. AIM: To assess lung perfusion alterations in COVID-19 patients. To our knowledge, no study using DECT has been performed to evaluate possibly fatal cardiac/ myocardial problems in COVID-19 patients. The purpose of this study is to evaluate the role of DECT in the detection of COVID-19-related cardiac diseases. METHODS: Two blinded independent examiners evaluated CT images using the 17-segment model according to the American Heart Association's classification of the segmentation of the left ventricular myocardium. Additionally, intraluminal diseases and abnormalities in the main coronary arteries and branches were investigated. Following segment-by-segment analysis, perfusion deficiencies identified on the iodine map pictures on DECT were identified. RESULTS: The study enrolled a total of 87 patients. Forty-two of these individuals were classified as COVID-19 positive, and 45 were classified as controls. Perfusion deficits were identified in 66.6% (n = 30) of the cases. All control patients had a normal iodine distribution map. Perfusion deficits were found on DECT iodine map images with subepicardial (n = 12, 40%), intramyocardial (n = 8, 26.6%), or transmural (n = 10, 33.3%) anatomical locations within the left ventricular wall. There was no subendocardial involvement in any of the patients. CONCLUSION: Myocardial perfusion deficits can be found in COVID-19 patients even without any significant coronary artery occlusion. These deficits can be shown via DECT with a perfect interrater agreement. Additionally, the presence of perfusion deficit is positively correlated with D-dimer levels.

Distribution of Aeration and Pulmonary Blood Volume in Healthy, ARDS and COVID-19 Lungs: A Dual-Energy Computed Tomography Retrospective Cohort Study.

RATIONALE AND OBJECTIVES: Few reports have studied lung aeration and perfusion in normal lungs, COVID-19, and ARDS from other causes (NC-ARDS) using dual-energy computed tomography pulmonary angiograms (DE-CTPA). To describe lung aeration and blood-volume distribution using DE-CTPAs of patients with NC-ARDS, COVID-19, and controls with a normal DE-CTPA ("healthy lungs"). We hypothesized that each of these conditions has unique ranges of aeration and pulmonary blood volumes. MATERIALS AND METHODS: This retrospective, single-center study of DE-CTPAs included patients with COVID-19, NC-ARDS (Berlin criteria), and controls. Patients with macroscopic pulmonary embolisms were excluded. The outcomes studied were the (1) lung blood-volume in areas with different aeration levels (normal, ground glass opacities [GGO], consolidated lung) and (2) aeration/blood-volume ratios. RESULTS: Included were 20 patients with COVID-19 (10 milds, 10 moderate-severe), six with NC-ARDS, and 12 healthy-controls. Lung aeration was lowest in patients with severe COVID-19 24% (IQR13%-31%) followed by those with NC-ARDS 40%(IQR21%-46%). Blood-volume in GGO was lowest in patients with COVID-19 [moderate-severe:-28.6 (IQR-33.1-23.2); mild: -30.1 (IQR-33.3-23.4)] and highest in normally aerated areas in NC-ARDS -37.4 (IQR-52.5-30.2-) and moderate-severe COVID-19 -33.5(IQR-44.2-28.5). The median aeration/blood-volume ratio was lowest in severe COVID-19 but some values overlapped with those observed among patients with NC-ARDS. CONCLUSION: Severe COVID-19 disease is associated with low total aerated lung volume and blood-volume in areas with GGO and overall aeration/blood volume ratios, and with high blood volume in normal lung areas. In this hypothesis-generating study, these findings were most pronounced in severe COVID disease. Larger studies are needed to confirm these preliminary findings.

Persistent respiratory failure after SARS-CoV-2 infection: The role of dual energy computed tomography. A case report.

Background: COVID-19 disease is often complicated by respiratory failure, developing through multiple pathophysiological mechanisms, with pulmonary embolism (PE) and microvascular thrombosis as key and frequent components. Newer imaging modalities such as dual-energy computed tomography (DECT) can represent a turning point in the diagnosis and follow-up of suspected PE during COVID-19. Case presentation: A 78-year-old female presented to our internal medicine 3 weeks after initial hospitalization for COVID-19 disease, for recrudescent respiratory failure needing oxygen therapy. A computed tomography (CT) lungs scan showed a typical SARSCoV-2 pneumonia. Over the following 15 days, respiratory function gradually improved. Unexpectedly, after 21 days from symptom onset, the patient started complaining of breath shortening with remarkable desaturation requiring high-flow oxygen ventilation. CT pulmonary angiography and transthoracic echocardiography were negative for signs of PE. Thereby, Dual-energy CT angiography of the lungs (DECT) was performed and detected diffuse peripheral microembolism. After 2 weeks, a second DECT was performed, showing a good response to the anticoagulation regimen, with reduced extent of microembolism and some of the remaining emboli partially recanalized. Discussion: DECT is an emerging diagnostic technique providing both functional and anatomical information. DECT has been reported to produce a much sharper delineation of perfusion defects than pulmonary scintigraphy, using a significantly lower equivalent dose of mSv. We highlight that DECT is particularly useful in SARS-Cov-2 infection, in order to determine the predominant underlying pathophysiology, particularly when respiratory failure prolongs despite improved lung parenchymal radiological findings.

Step-by-step surveillance in children with multisystem inflammatory syndrome associated with COVID-19 infection: proposal of a cardiologic follow-up

Introduction: Multisystem Inflammatory Syndrome Associated with COVID-19 Infection (MIS-C) shows many matches with children with Kawasaki disease (KD) and most children with MIS-C have incomplete or complete KD-like phenotype. In these patients cardiologic involvement mimics KD, showing, however, a higher incidence of severe acute manifestations. Objectives: In children with MIS-C and clinical findings related to heart disease, ECG and echocardiography are the first-line imaging. Until now, there are no international guidelines on the management of these patients. We suggest to take inspiration from the recommendations for KD for the significant phenotypic overlap between MIS-C and KD. Methods: We propose a step-by-step cardiologic imaging follow-up: - in all the patients, we recommend ECG and echocardiography at the diagnosis, at the worsening of the clinical and/or blood chemist parameters (CRP, ESR, ferritin;proBNP, troponin, D-Dimer), at any change of treatment supported by clinical worsening, at 8, 30, 45, 60, 90, 180 days since the diagnosis. The time-table may be changed in consideration of the outcome of the patient. -In patients with coronary artery dilatation (CAL), documented by echocardiography, it is advisable to follow-up them, since the diagnosis, with ECG, echocardiography, D-dimer, pro-BNP, troponin. -If CAL are oversized with z-score >- 2,5, according to age and body surface or increase during the follow-up: -it is recommended to perform Coronary Computed Tomography (CT) (CCA) or Cardiac Magnetic Resonance Angiography (CMRA). In fact, echocardiography cannot visualize the whole coronary artery vessels. Results: Both allow visualization of coronary artery aneurysms, vessels thickening, myocardial perfusion defects, permitting risk stratification and handing treatment decisions. CMRA is the first choice, because it is a radiation-free imaging method. It can evaluate the entire coronary artery system and provides details on myocardial function ischemia (detecting areas of inducible myocardial ischemia with pharmacological stress), infarction, inflammation, fibrosis. However, the new generation Multidetector Single -Source CT scanners and Dual Source Ct scanner allow a fast heart CT study with low radiation dose and reduce the need for sedation. CMR is less suitable because it is a lengthy examination and very often requires general anesthesia. If echocardiography demonstrates myocardial dysfunction or valve regurgitation at admission or during hospitalization, we suggest performing CMR. There is no consensus on the right timing. Conclusion: We suggest performing CMR during the acute or subacute phase: it is a step of the relieve in the cardiologic diagnosis to assess ventricular function and myocardial active injuries (oedema, hyperemia, ischemia, necrosis) and to repeat the imaging at the discharge in patients with the first pathological CMR, to evaluate fibrosis by myocardial delayed enhancement. CMR at the discharge is suggested also in cases with the first CMR normal, who showed a worsening of the echocardiographic parameters, the relieve of newinsurance valvulitis, persistent arrhythmia. At 3-6 months since the patient showed the remission, the CMR must be repeated to avoid any fibrotic lesions.

Diagnosis of Pulmonary Embolism in Unenhanced Dual Energy CT Using an Electron Density Image.

Dual-energy computed tomography (CT) is a promising tool, providing both anatomical information and material properties. Using spectral information such as iodine mapping and virtual monoenergetic reconstruction, dual-energy CT showed added value over pulmonary CT angiography in the diagnosis of pulmonary embolism. However, the role of non-contrast-enhanced dual energy CT in pulmonary embolism has never been reported. Here, we report a case of acute pulmonary embolism detected on an electron density image from an unenhanced dual-energy CT using a dual-layer detector system.

Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study.

BACKGROUND: Critically ill COVID-19 patients have pathophysiological lung features characterized by perfusion abnormalities. However, to date no study has evaluated whether the changes in the distribution of pulmonary gas and blood volume are associated with the severity of gas-exchange impairment and the type of respiratory support (non-invasive versus invasive) in patients with severe COVID-19 pneumonia. METHODS: This was a single-center, retrospective cohort study conducted in a tertiary care hospital in Northern Italy during the first pandemic wave. Pulmonary gas and blood distribution was assessed using a technique for quantitative analysis of dual-energy computed tomography. Lung aeration loss (reflected by percentage of normally aerated lung tissue) and the extent of gas:blood volume mismatch (percentage of non-aerated, perfused lung tissue-shunt; aerated, non-perfused dead space; and non-aerated/non-perfused regions) were evaluated in critically ill COVID-19 patients with different clinical severity as reflected by the need for non-invasive or invasive respiratory support. RESULTS: Thirty-five patients admitted to the intensive care unit between February 29th and May 30th, 2020 were included. Patients requiring invasive versus non-invasive mechanical ventilation had both a lower percentage of normally aerated lung tissue (median [interquartile range] 33% [24-49%] vs. 63% [44-68%], p < 0.001); and a larger extent of gas:blood volume mismatch (43% [30-49%] vs. 25% [14-28%], p = 0.001), due to higher shunt (23% [15-32%] vs. 5% [2-16%], p = 0.001) and non-aerated/non perfused regions (5% [3-10%] vs. 1% [0-2%], p = 0.001). The PaO2/FiO2 ratio correlated positively with normally aerated tissue (ρ = 0.730, p < 0.001) and negatively with the extent of gas-blood volume mismatch (ρ = - 0.633, p < 0.001). CONCLUSIONS: In critically ill patients with severe COVID-19 pneumonia, the need for invasive mechanical ventilation and oxygenation impairment were associated with loss of aeration and the extent of gas:blood volume mismatch.

Case Studies in Physiology: Temporal variations of the lung parenchyma and vasculature in asymptomatic COVID-19 pneumonia: a multispectral CT assessment.

This study reports systematic longitudinal pathophysiology of lung parenchymal and vascular effects of asymptomatic COVID-19 pneumonia in a young, healthy never-smoking male. Inspiratory and expiratory noncontrast along with contrast dual-energy computed tomography (DECT) scans of the chest were performed at baseline on the day of acute COVID-19 diagnosis (day 0), and across a 90-day period. Despite normal vital signs and pulmonary function tests on the day of diagnosis, the CT scans and corresponding quantification metrics detected abnormalities in parenchymal expansion based on image registration, ground-glass (GGO) texture (inflammation) as well as DECT-derived pulmonary blood volume (PBV). Follow-up scans on day 30 showed improvement in the lung parenchymal mechanics as well as reduced GGO and improved PBV distribution. Improvements in lung PBV continued until day 90. However, the heterogeneity of parenchymal mechanics and texture-derived GGO increased on days 60 and 90. We highlight that even asymptomatic COVID-19 infection with unremarkable vital signs and pulmonary function tests can have measurable effects on lung parenchymal mechanics and vascular pathophysiology, which may follow apparently different clinical courses. For this asymptomatic subject, post COVID-19 regional mechanics demonstrated persistent increased heterogeneity concomitant with return of elevated GGOs, despite early improvements in vascular derangement.NEW & NOTEWORTHY We characterized the temporal changes of lung parenchyma and microvascular pathophysiology from COVID-19 infection in an asymptomatic young, healthy nonsmoking male using dual-energy CT. Lung parenchymal mechanics and microvascular disease followed different clinical courses. Heterogeneous perfused blood volume became more uniform on follow-up visits up to 90 days. However, post COVID-19 mechanical heterogeneity of the lung parenchyma increased after apparent improvements in vascular abnormalities, even with normal spirometric indices.

DUAL-energy computed tomography findings in a case of COVID-19.

BACKGROUND: COVID-19 pneumonia has lesions with a decreased blood flow. Dual-energy computed tomography is suitable to elucidate the pathogenesis of COVID-19 pneumonia because it highlights the blood flow changes in organs. We report the dual-energy computed tomography findings of a successfully treated case of COVID-19 pneumonia. CASE PRESENTATION: An obese 49-year-old man with COVID-19 pneumonia was transferred from another hospital on day 11 after onset of illness. Although he was hypoxemic (PaO2/FiO2 = 100), tracheal intubation was not performed after anticipating difficulty in weaning from mechanical ventilation. Prone position therapy and nasal high flow therapy were administered, and the patient was discharged after his condition improved. Dual-energy computed tomography was performed three times during hospitalization, and it revealed improvement in the blood flow defect, unlike plain computed tomography that did not show much improvement. CONCLUSION: Dual-energy computed tomography can assess perfusion in COVID-19 pneumonia in real time and may be able to predict its severity.

Dual-energy CT angiography reveals high prevalence of perfusion defects unrelated to pulmonary embolism in COVID-19 lesions.

BACKGROUND: Lung perfusion defects (PDs) have been described in COVID-19 using dual-energy computed tomography pulmonary angiography (DE-CTPA). We assessed the prevalence and characteristics of PDs in COVID-19 patients with suspected pulmonary embolism (PE) and negative CTPA. METHODS: This retrospective study included COVID-19 and non-COVID-19 pneumonia groups of patients with DE-CTPA negative for PE. Two radiologists rated the presence of PD within the lung opacities and analyzed the type of lung opacities and PD pattern (i.e. homogeneous or heterogeneous). The clinical, biological, radiological characteristics including time from first symptoms and admission to DE-CTPA, oxygen requirements, CRP, D-dimer levels, duration of hospital admission and death were compared within the COVID-19 group between patients with (PD +) or without PD (PD-). RESULTS: 67 COVID-19 and 79 non-COVID-19 patients were included. PDs were more frequent in the COVID-19 than in the non-COVID-19 group (59.7% and 26.6% respectively, p < 0.001). Patterns of PDs were different, with COVID-19 patients exhibiting heterogenous PDs (38/40, 95%) whereas non-COVID-19 patients showed mostly homogeneous perfusion defects (7/21 heterogeneous PDs, 33%), p < 0.001. In COVID-19 patients, most consolidations (9/10, 90%) exhibited PDs while less than a third of consolidations (19/67, 28%) had PDs in non-COVID-19 patients. D-dimer, oxygen levels and outcome were similar between COVID-19 PD + and PD- patients; however, time between admission and DE-CTPA was longer in PD + patients (median [IQR], 1 [0-7] and 0 [0-2]; p = 0.045). CONCLUSION: Unlike in bacterial pneumonia, heterogeneous PDs within lung opacities are a frequent feature of COVID-19 pneumonia in PE-suspected patients.

Rescue therapy with thrombolysis in patients with severe COVID-19-associated acute respiratory distress syndrome.

Acute respiratory distress syndrome in patients with Coronavirus disease 19 is associated with an unusually high incidence of pulmonary embolism and microthrombotic disease, with evidence for reduced fibrinolysis. We describe seven patients requiring invasive ventilation for COVID-19-associated acute respiratory distress syndrome with pulmonary thromboembolic disease, pulmonary hypertension ± severe right ventricular dysfunction on echocardiography, who were treated with alteplase as fibrinolytic therapy. All patients were non-smokers, six (86%) were male and median age was 56.7 (50-64) years. They had failed approaches including therapeutic anticoagulation, prone ventilation (n = 4), inhaled nitric oxide (n = 5) and nebulised epoprostenol (n = 2). The median duration of mechanical ventilation prior to thrombolysis was seven (5-11) days. Systemic alteplase was administered to six patients (50 mg or 90 mg bolus over 120 min) at 16 (10-22) days after symptom onset. All received therapeutic heparin pre- and post-thrombolysis, without intracranial haemorrhage or other major bleeding. Alteplase improved PaO2/FiO2 ratio (from 97.0 (86.3-118.6) to 135.6 (100.7-171.4), p = 0.03) and ventilatory ratio (from 2.76 (2.09-3.49) to 2.36 (1.82-3.05), p = 0.011) at 24 h. Echocardiographic parameters at two (1-3) days (n = 6) showed right ventricular systolic pressure (RVSP) was 63 (50.3-75) then 57 (49-66) mmHg post-thrombolysis (p = 0.26), tricuspid annular planar systolic excursion (TAPSE) was unchanged (from 18.3 (11.9-24.5) to 20.5 (15.4-24.2) mm, p = 0.56) and right ventricular fractional area change (from 15.4 (11.1-35.6) to 31.2 (16.4-33.1)%, p = 0.09). At seven (1-13) days after thrombolysis, using dual energy computed tomography imaging (n = 3), average relative peripheral lung enhancement increased from 12.6 to 21.6% (p = 0.06). In conclusion, thrombolysis improved PaO2/FiO2 ratio and ventilatory ratio at 24 h as rescue therapy in patients with right ventricular dysfunction due to COVID-19-associated ARDS despite maximum therapy, as part of a multimodal approach, and warrants further study.