Characterisation of Ferritin-Lymphocyte Ratio in COVID-19.

Introduction: The ferritin-lymphocyte ratio (FLR) is a novel inflammatory biomarker for the assessment of acute COVID-19 patients. However, the prognostic value of FLR for predicting adverse clinical outcomes in COVID-19 remains unclear, which hinders its clinical translation. Methods: We characterised the prognostic value of FLR in COVID-19 patients, as compared to established inflammatory markers. Results: In 217 study patients (69 years [IQR: 55-82]; 60% males), FLR was weakly correlated with CRP (R = 0.108, p = 0.115) and white cell count (R = -0.144; p = 0.034). On ROC analysis, an FLR cut-off of 286 achieved a sensitivity of 86% and a specificity of 30% for predicting inpatient mortality (AUC 0.60, 95% CI: 0.53-0.67). The negative predictive values of FLR for ruling out mortality, non-invasive ventilation requirement and critical illness (intubation and/or ICU admission) were 86%, 85% and 93%, respectively. FLR performed similarly to CRP (AUC 0.60 vs. 0.64; p = 0.375) for predicting mortality, but worse than CRP for predicting non-fatal outcomes (all p < 0.05). On Kaplan-Meier analysis, COVID-19 patients with FLR values > 286 had worse inpatient survival than patients with FLR ≤ 286, p = 0.041. Conclusions: FLR has prognostic value in COVID-19 patients, and appears unrelated to other inflammatory markers such as CRP and WCC. FLR exhibits high sensitivity and negative predictive values for adverse clinical outcomes in COVID-19, and may be a good "rule-out" test. Further work is needed to improve the sensitivity of FLR and validate its role in prospective studies for guiding clinical management.

Low CRB-65 Scores Effectively Rule out Adverse Clinical Outcomes in COVID-19 Irrespective of Chest Radiographic Abnormalities.

Background: CRB-65 (Confusion; Respiratory rate ≥ 30/min; Blood pressure ≤ 90/60 mmHg; age ≥ 65 years) is a risk score for prognosticating patients with COVID-19 pneumonia. However, a significant proportion of COVID-19 patients have normal chest X-rays (CXRs). The influence of CXR abnormalities on the prognostic value of CRB-65 is unknown, limiting its wider applicability. Methods: We assessed the influence of CXR abnormalities on the prognostic value of CRB-65 in COVID-19. Results: In 589 study patients (71 years (IQR: 57-83); 57% males), 186 (32%) had normal CXRs. On ROC analysis, CRB-65 performed similarly in patients with normal vs. abnormal CXRs for predicting inpatient mortality (AUC 0.67 ± 0.05 vs. 0.69 ± 0.03). In patients with normal CXRs, a CRB-65 of 0 ruled out mortality, NIV requirement and critical illness (intubation and/or ICU admission) with negative predictive values (NPVs) of 94%, 98% and 99%, respectively. In patients with abnormal CXRs, a CRB-65 of 0 ruled out the same endpoints with NPVs of 91%, 83% and 86%, respectively. Patients with low CRB-65 scores had better inpatient survival than patients with high CRB-65 scores, irrespective of CXR abnormalities (all p < 0.05). Conclusions: CRB-65, CXR and CRP are independent predictors of mortality in COVID-19. Adding CXR findings (dichotomised to either normal or abnormal) to CRB-65 does not improve its prognostic accuracy. A low CRB-65 score of 0 may be a good rule-out test for adverse clinical outcomes in COVID-19 patients with normal or abnormal CXRs, which deserves prospective validation.

Comparison of Lymphocyte-CRP Ratio to Conventional Inflammatory Markers for Predicting Clinical Outcomes in COVID-19.

Background: In COVID-19 patients, lymphocyte-CRP ratio (LCR) is a promising biomarker for predicting adverse clinical outcomes. How well LCR performs compared to conventional inflammatory markers for prognosticating COVID-19 patients remains unclear, which hinders the clinical translation of this novel biomarker. Methods: In a cohort of COVID-19 inpatients, we characterised the clinical applicability of LCR by comparing its prognostic value against conventional inflammatory markers for predicting inpatient mortality and a composite of mortality, invasive/non-invasive ventilation and intensive care unit admissions. Results: Of the 413 COVID-19 patients, 100 (24%) patients suffered inpatient mortality. On Receiver Operating Characteristics analysis, LCR performed similarly to CRP for predicting mortality (AUC 0.74 vs. 0.71, p = 0.049) and the composite endpoint (AUC 0.76 vs. 0.76, p = 0.812). LCR outperformed lymphocyte counts (AUC 0.74 vs. 0.66, p = 0.002), platelet counts (AUC 0.74 vs. 0.61, p = 0.003) and white cell counts (AUC 0.74 vs. 0.54, p < 0.001) for predicting mortality. On Kaplan-Meier analysis, patients with a low LCR (below a 58 cut-off) had worse inpatient survival than patients with other LCR values (p < 0.001). Conclusion: LCR appears comparable to CRP, but outperformed other inflammatory markers, for prognosticating COVID-19 patients. Further studies are required to improve the diagnostic value of LCR to facilitate clinical translation.

Normal high-sensitivity cardiac troponin for ruling-out inpatient mortality in acute COVID-19.

INTRODUCTION: Assessment of inpatient mortality risk in COVID-19 patients is important for guiding clinical decision-making. High sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiac injury associated with a worse prognosis in COVID-19. We explored how hs-cTnT could potentially be used in clinical practice for ruling in and ruling out mortality in COVID-19. METHOD: We tested the diagnostic value of hs-cTnT in laboratory-confirmed COVID-19 patients (≥18 years old) admitted to the Royal Berkshire Hospital (UK) between 1st March and 10th May 2020. A normal hs-cTnT was defined as a value within the 99th percentile of healthy individuals (≤14 ng/L), and an elevated hs-cTnT was defined as >14 ng/L. Adverse clinical outcome was defined as inpatient mortality related to COVID-19. RESULTS: A total of 191 COVID-19 patients (62% male; age 66±16 years) had hs-cTnT measured on admission. Of these patients, 124 (65%) had elevated hs-cTnT and 67 (35%) had normal hs-cTnT. On a group level, patients with elevated hs-cTnT had worse inpatient survival (p = 0.0014; Kaplan-Meier analysis) and higher risk of inpatient mortality (HR 5.84 [95% CI 1.29-26.4]; p = 0.02; Cox multivariate regression) compared to patients with normal hs-cTnT. On a per-patient level, a normal hs-cTnT had a negative predictive value of 94% (95% CI: 85-98%) for ruling out mortality, whilst an elevated hs-cTnT had a low positive predictive value of 38% (95% CI: 39-47%) for ruling in mortality. CONCLUSIONS: In this study cohort of COVID-19 patients, the potential clinical utility of hs-cTnT appears to rest in ruling out inpatient mortality. This finding, if prospectively validated in a larger study, may allow hs-cTnT to become an important biomarker to facilitate admission-avoidance and early safe discharge.

Radiologist opinions regarding reporting incidental coronary and cardiac calcification on thoracic CT.

Objectives: Coronary and cardiac calcification are frequent incidental findings on non-gated thoracic computed tomography (CT). However, radiologist opinions and practices regarding the reporting of incidental calcification are poorly understood. Methods: UK radiologists were invited to complete this online survey, organised by the British Society of Cardiovascular Imaging (BSCI). Questions included anonymous information on subspecialty, level of training and reporting practices for incidental coronary artery, aortic valve, mitral and thoracic aorta calcification. Results: The survey was completed by 200 respondents: 10% trainees and 90% consultants. Calcification was not reported by 11% for the coronary arteries, 22% for the aortic valve, 35% for the mitral valve and 37% for the thoracic aorta. Those who did not subspecialise in cardiac imaging were less likely to report coronary artery calcification (p = 0.005), aortic valve calcification (p = 0.001) or mitral valve calcification (p = 0.008), but there was no difference in the reporting of thoracic aorta calcification. Those who did not subspecialise in cardiac imaging were also less likely to provide management recommendations for coronary artery calcification (p < 0.001) or recommend echocardiography for aortic valve calcification (p < 0.001), but there was no difference for mitral valve or thoracic aorta recommendations. Conclusion: Incidental coronary artery, valvular and aorta calcification are frequently not reported on thoracic CT and there are differences in reporting practices based on subspeciality. Advances in knowledge: On routine thoracic CT, 11% of radiologists do not report coronary artery calcification. Radiologist reporting practices vary depending on subspeciality but not level of training.

Reporting incidental coronary, aortic valve and cardiac calcification on non-gated thoracic computed tomography, a consensus statement from the BSCI/BSCCT and BSTI.

Incidental coronary and cardiac calcification are frequent findings on non-gated thoracic CT. We recommend that the heart is reviewed on all CT scans where it is visualised. Coronary artery calcification is a marker of coronary artery disease and it is associated with an adverse prognosis on dedicated cardiac imaging and on non-gated thoracic CT performed for non-cardiac indications, both with and without contrast. We recommend that coronary artery calcification is reported on all non-gated thoracic CT using a simple patient-based score (none, mild, moderate, severe). Furthermore, we recommend that reports include recommendations for subsequent management, namely the assessment of modifiable cardiovascular risk factors and, if the patient has chest pain, assessment as per standard guidelines. In most cases, this will not necessitate additional investigations. Incidental aortic valve calcification may also be identified on non-gated thoracic CT and should be reported, along with ancillary findings such as aortic root dilation. Calcification may occur in other parts of the heart including mitral valve/annulus, pericardium and myocardium, but in many cases these are an incidental finding without clinical significance.

Proportion of acute ischaemic strokes attributable to a cardiac aetiology in an unselected young patient population: A single centre experience.

The incidence of acute ischaemic stroke in young patients is increasing and identifying the underlying cause is critically important with regards to their optimal management. The true proportion of cardiac causes of stroke in young patients is poorly defined. We aimed to determine the proportion of strokes attributable to cardiac causes in an unselected, consecutive cohort of young patients. We used the database of a large stroke service to identify patients aged ≤55 years presenting with stroke between 01 January 2015 and 31 December 2017. We reviewed their clinical notes and investigations and then categorised patients by the cause of their stroke.We screened 202 cases, and excluded 35, resulting in a study population of 167 patients; 24.0% (40/167) had a cardiac cause of stroke including 9.6% (16/167) had patent foramen ovale, 9.0% (15/167) had intracardiac source of embolus and 5.4% (9/167) had atrial fibrillation; 50.8% (85/167) had other more likely causes; and 25.1% (42/167) had no clear underlying cause.A high proportion (24%) of strokes in young patients are secondary to a cardiac cause. Thorough investigation in these patients is warranted and requires close interdisciplinary links between cardiologists and stroke physicians to ensure optimal management.

Myopericarditis and myositis in a patient with COVID-19: a case report.

BACKGROUND: Concurrent myopericarditis and myositis can present in patients with pre-existing systemic inflammatory diseases. Here we present a case of myopericarditis and myositis associated with COVID-19, in the absence of respiratory symptoms. CASE SUMMARY: We present a middle-aged female with a history of hypertension and previous myopericarditis. The patient was admitted with symptoms of central chest pain, and ECG and echocardiographic features of myopericarditis. Her symptoms did not improve, and CT thorax suggested possible SARS-CoV-2 infection for which she tested positive, despite no respiratory symptoms. Whilst on the ward, she developed bilateral leg weakness and a raised creatine kinase (CK), and magnetic resonance imaging (MRI) of her thighs confirmed myositis. A cardiac MRI confirmed myopericarditis. She was treated with colchicine 500 µg twice daily, ibuprofen 400 mg three times day, and prednisolone 30 mg per day, and her symptoms and weakness improved. DISCUSSION: We describe the first reported case of concurrent myopericarditis, and myositis associated with COVID-19. Conventional therapy with colchicine, non-steroidal anti-inflammatory drugs, and glucocorticoids improved her symptoms, and reduced biochemical markers of myocardial and skeletal muscle inflammation.

Ascending aortic dissection in a pregnant patient with neonatally repaired coarctation of aorta and bicuspid aortic valve.

Aortic dissection is characterised by a tear in the intimal and medial layers of the endovascular aortic wall which propagates distally. Here, we discuss the case of a 35-year-old woman who was 37 weeks pregnant and presented with dizziness and blurred vision. She had a history of a neonatal end-to-end repair of a coarctation of aorta, a known bicuspid aortic valve and a dilated ascending aorta under surveillance. A transthoracic echocardiogram revealed an ascending aortic dissection. An emergency CT aortogram was performed which confirmed the diagnosis. The patient underwent emergency caesarean section and aortic surgery, with a good outcome for mother and baby. The case highlights the atypical nature of presentation and the absence of haemodynamic instability. Atypical and unexplained symptoms on a background of congenital heart disease should trigger a referral to cardiology with thorough investigation, often with echocardiography, to exclude rare and life-threatening complications.

A unique case of "double-orifice aortic valve"-comprehensive assessment by 2-, 3-dimensional, and color Doppler echocardiography.

Transesophageal echocardiography (TEE) is a powerful imaging tool for the comprehensive assessment of valvular structure and function. TEE may be of added benefit when anatomy is difficult to delineate accurately by transthoracic echocardiography. In this article, we present 2-, 3-dimensional, and color Doppler TEE images from a male patient with aortic stenosis. A highly unusual and complex pattern of valvular calcification created a functionally "double-orifice" valve. Such an abnormality may have implications for the accuracy of continuous-wave Doppler echocardiography, which assumes a single orifice valve in native aortic valves.

Recommendations for accurate CT diagnosis of suspected acute aortic syndrome (AAS)--on behalf of the British Society of Cardiovascular Imaging (BSCI)/British Society of Cardiovascular CT (BSCCT).

Accurate and timely assessment of suspected acute aortic syndrome is crucial in this life-threatening condition. Imaging with CT plays a central role in the diagnosis to allow expedited management. Diagnosis can be made using locally available expertise with optimized scanning parameters, making full use of recent advances in CT technology. Each imaging centre must optimize their protocols to allow accurate diagnosis, to optimize radiation dose and in particular to reduce the risk of false-positive diagnosis that may simulate disease. This document outlines the principles for the acquisition of motion-free imaging of the aorta in this context.

Inducible myocardial ischaemia diagnosed using computed tomography dipyridamole stress myocardial perfusion technique.

Improved multi-detector computed tomography (MDCT) temporal and spatial resolution allows for the assessment of coronary artery disease, left ventricular systolic function and resting myocardial perfusion defects with high sensitivity and specificity. Here we present a case using a novel combination technique of cardiac computed tomography scanning with dipyridamole stress for the detection of functionally significant coronary disease, and demonstrate that dipyridamole-induced myocardial ischaemia is both detectable and quantifiable by cardiac MDCT.

Implications for single phase prospective CT coronary angiography for the diagnosis of significant coronary stenoses in clinical practice.

BACKGROUND: CT coronary angiography (CTA) with 64 slice multi-detector CT (64-MDCT) has assumed an increasing role in clinical practice; however the high radiation dose associated with retrospective ECG-gated CTA has led to suggestions that a low dose prospectively gated strategy may be more appropriate. This study aims to assess the feasibility of this proposed strategy amongst standard referral for CTA in our centre. METHODS: We retrospectively analyzed 200 consecutive clinical CTA studies assessing the number of cardiac phases required to allow full diagnostic visualisation of the coronary tree. We assessed whether the pre-test likelihood of coronary disease, heart rate, heart rate variability and range, current beta-blockers use, coronary calcium score, breathing artefact or study quality affected the number of phases required. RESULTS: 125/200 patients (62.5%) required only a single phase for full diagnostic visualisation of the coronary tree [most commonly 65% of the R-R interval-109/125 (87.2%)]. A successful diagnostic single cardiac phase was most likely in patients with a low heart rate (Heart rate < 70 bpm OR = 2.64; p = 0.003 and heart rate < 60 bpm OR = 4.81; p < 0.001 respectively) and low likelihood of coronary disease [OR = 1.97 95% CI (1.09, 3.58) p = 0.025]. CONCLUSION: High image quality is possible using single phase analysis in those patients with low likelihood of coronary disease, low heart rates and full cooperation with inspiratory breath hold. In patients with HR of <60, prospective ECG-gated acquisitions reduce radiation dose but may be non-diagnostic in as many as one third. Careful patient selection is therefore essential.

Attenuation of adenosine-induced myocardial perfusion heterogeneity by atenolol and other cardioselective beta-adrenoceptor blockers: a crossover myocardial perfusion imaging study.

UNLABELLED: Little is known about the effect of chronic beta-blockade on adenosine actions. We sought to investigate the effect of oral beta-blockers on the presence, extent, and severity of myocardial perfusion abnormality induced by adenosine in patients with coronary artery disease. METHODS: In this crossover study, 45 male patients with coronary artery disease on beta-blocker therapy with atenolol, bisoprolol, or metoprolol underwent adenosine myocardial perfusion imaging both on and off beta-blockade in a random order on separate days. Myocardial perfusion was assessed both qualitatively and quantitatively. Hemodynamic response, image analysis, and sensitivity for the detection of coronary stenosis (>or=50% luminal diameter reduction on x-ray coronary angiography) were compared between the on and off beta-blocker studies. RESULTS: Rate pressure product both at baseline and at peak adenosine infusion decreased by 23% +/- 15% and 21% +/- 18%, respectively, after beta-blockade (P < 0.001 for all). The median (interquartile range) summed difference score, a measure of defect reversibility, and quantitative defect size were both significantly lower after beta-blockade (median, 7.0 [interquartile range, 2.0-9.5] vs. median, 5.0 [interquartile range, 0-8.0], P = 0.002; and quantitative defect size, 18% [interquartile range, 9%-34%] vs. quantitative defect size, 6% [interquartile range, 0%-19%], P < 0.001, respectively). The overall sensitivity for the detection of coronary stenosis decreased from 0.76 (95% confidence interval, 0.65-0.88) to 0.58 (95% confidence interval, 0.45-0.71) after beta-blockade (P = 0.03). CONCLUSION: beta-blockade causes a small but significant reduction in the extent and severity of perfusion abnormality by adenosine. This may reduce the diagnostic sensitivity of adenosine myocardial perfusion imaging for the detection of flow-limiting coronary stenosis.

Defining the appropriate CTA stenosis threshold for gatekeeping to invasive angiography: 50% or 70%?

There is currently much debate around the limited positive predictive value (PPV) of CT coronary angiography (CTA). There remain no published studies comparing different thresholds to define significant visual stenoses on CTA compared to the gold standard quantitative coronary angiography (QCA). The spatial resolution for ICA is (0.1 mm)(3) compared with (0.5 mm)(3) in clinical CTA and direct comparison introduces a systematic overestimation of stenosis severity by CTCA. Assessing both ≥ 50% and ≥ 70% visual stenoses on CTA with QCA we found that the negative predictive value (NPV) of CTA is equally high for both. The PPV of CTA improves using ≥ 70% but with a loss of sensitivity. Using ≥ 70% stenosis on CTA for referral for ICA would reduce the number of ICA that does not lead to percutaneous intervention (PCI) but a functional test for intermediate lesions (visual stenoses of 50%-69%) on CTA is recommended to overcome the reduction in sensitivity.

Clinical management and short-term cost - 64-slice MDCT vs. myocardial perfusion scintigraphy.

There are currently no published studies of the impact of CT coronary angiography (CTA) on patient management or cost when compared with other established imaging techniques. We assessed the short term investigation and treatment costs of CTA compared with myocardial perfusion scintigraphy (MPS) using real clinical scenarios. Clinical information with either their CTA or MPS results were presented to 20 cardiologists in a random order. They decided further investigations and treatment required based on these data. Short term cost was calculated for each imaging strategy. Whilst the total number of further investigations requested did not differ between groups patients undergoing CTA were more likely to be referred for invasive coronary angiography, receive aspirin, statins, ACE inhibitors, ß-blockers or clopidogrel. Overall cost and investigation costs were similar between CTA and MPS; however treatment costs were higher with CTA. There are significant differences in further clinical management when using CTA compared with MPS, in particular with greater use of secondary preventative medication.