Cardiac Imaging in SARS-CoV-2 (COVID-19)

Study Overview
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Brief Summary
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One-in-four patients with COVID-19 pneumonia develop life-threatening heart problems. Through cardiovascular imaging and biomarkers analyses this study aims to evaluate whether COVID-19 infection results in heart injury. The investigators will also investigate which patients are at risk of heart injury as a result of COVID-19 and why only some patients suffer heart problems as a consequence of the infection. The study will also assess multisystem involvement including the lungs and kidneys.

Detailed Description
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Our study is supported through the Chief Scientist Office Rapid Research in Covid-19 (RARC-19) programme. Our study will clarify the pathogenesis of cardiopulmonary injury, notably endotypes of myocardial injury including myocarditis, in patients with COVID-19. The study involves a prospective, observational, multicentre, longitudinal cohort design.The investigators aim to minimise selection bias by adopting consecutive screening of all-comers hospitalised with COVID-19 and the eligibility criteria are broad. For example, severe renal dysfunction is not an exclusion criterion. The sample size is 180 patients enrolled at baseline with 160 attending for the primary outcome evaluation (cardiac imaging) at 28 days post-discharge. The investigators will use advanced cardiovascular imaging to identify the number (proportion) of patients with myocardial inflammation (myocarditis) that is sub-clinical (i.e. not diagnosed) or clinically overt. Cardiovascular MRI and CT coronary angiography will provide a comprehensive examination one month after discharge is intended to detect persisting cardiovascular complications and diagnose clinical endotypes. The investigators aim to clarify the pathological significance of serial changes in circulating troponin, NTproBNP and renal function. By correlating the MRI findings with troponin I and other measures of cardiovascular injury, such as NTproBNP, our results will inform care pathways that use these blood tests to guide the management of patients with COVID-19. Correlation of imaging findings with baseline clinical information, biomarkers, patient reported outcome measures and well-being in the longer term will help to clarify the clinical significance of cardiovascular complications in COVID-19. Since the design is observational, an interim analysis may be undertaken with the timing informed by the enrolment rate. Longer term follow-up will include a 5-year visit, contingent on funding and ethics approval, and electronic health record linkage of vital status and episodes of NHS care.

Official Title
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Cardiovascular and Pulmonary Imaging in SARS-CoV-2: A Study of the Heart, Lungs and Wellbeing After COVID-19.

Conditions
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COVID

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of hospital attendance or hospitalisation for COVID-19, confirmed by a clinical diagnosis, laboratory test e.g. PCR and/or a radiological test e.g. CT chest or chest X-ray Age 18 years or more Capacity to provide written informed consent Able to comply with study procedures Exclusion Criteria: Contra-indication to CMR e.g. severe claustrophobia, metallic foreign body Lack of informed consent Women who are pregnant, breast-feeding or of child-bearing potential without a negative pregnancy test

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19<br>Patients with confirmed COVID-19 meeting the eligibility criteria specified in the protocol. | |
| Control<br>COVID-19 negative. Age/sex matched to the COVID-19 cohort. Age range 40-80 years. At least one cardiovascular risk factor by ASSIGN criteria. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary cardiac outcome is the proportion of patients with a diagnosis of myocardial inflammation (myocarditis). | Myocardial inflammation (or myocarditis) will be revealed by cardiovascular magnetic resonance imaging (MRI) according to contemporary guidelines including the modified Lake Louise Criteria. The endotypes of myocardial injury are 1) myocardial inflammation due to 1.1) viral myocarditis, 1.2) ischaemia, or 1.3) stress (Takotsubo) cardiomyopathy, 2) myocardial infarction, 3) indeterminate, or 4) none. The final diagnosis will be a consensus-based determination by an expert panel. This information will provide insights into the incidence, nature, time-course and clinical significance of cardiovascular involvement in patients with COVID-19. The clinical significance of our findings will be assessed through associations with patient reported outcome measures (PROMS) and health outcomes in the longer term. | 28 days after discharge from hospital | 
| The primary cardio-pulmonary outcome is the proportion of patients with thrombosis | Thrombosis of the right heart, pulmonary arteries and left heart will be determined contrast-enhanced CT chest, angiography and MRI. | 28 days after discharge from hospital | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial injury | Assess mechanisms using circulating biomarkers of cardiac injury, high sensitivity troponin I (ng/L) and its change over time from baseline. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Myocardial stress | Assess the significance of myocardial injury by measuring circulating concentrations of NTproBNP (pg/mL) and its change over time from baseline. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Systemic inflammation | Assess systemic inflammation by measurement of the peak circulating concentration of C-reactive protein (mg/dL) and its change over time. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Vascular injury | Assess vascular injury/inflammation by measurement of the peak circulating concentration of IL-6 (pg/mL) and its change over time. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Endothelial activation and haemostasis | Assess endothelial injury by immunoassay measurement of the peak circulating concentration of VWF:ag (IU/dL) and its change over time. Other measures of haemostasis will also be measured. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Fibrin lysis | Assess fibrin lysis by measurement of the peak circulating concentration of fibrin D-dimer (IU/dL) and its change over time. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Coagulation | Assess coagulation by measurement of Activated Partial Thromboplastin Time (APTT) in seconds. Other measures of coagulation will also be measured. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Platelet count | Assess platelet count (n/microlitre), minimum value (thrombocytopaenia) and change over time. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Renal function | Assess renal function using urine albumin:creatinine ratio and its change over time. Other measures of renal function/injury will also be assessed. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Quantify myocardial perfusion as a measure of coronary microvascular function | Stress perfusion MRI will provide quantitative assessments of myocardial perfusion (ml/min/g) and classify perfusion abnormalities according to other MRI findings e.g. scar, inflammation and coronary artery disease as revealed by CT coronary angiography. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Association of the primary outcome according to a prior history of cardiovascular disease or no history of prior cardiovascular disease. | Imaging for coronary disease, PTE and lung pathology will be correlated with NHS clinical data on prior history of cardiovascular disease. | 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months) | 
| Patient reported outcome measures (PROMS) - health status | Health status, well being and function will be prospectively assessed using prespecified PROMS : EuroQOL EQ-5D-5L score. Other measures of health status will also be assessed. | 1 year | 
| PROMS - functional capacity | Patient reported functional activity using the Duke Activity Status Index (DASI), measured by the score generated from the questionnaire (https://www.mdcalc.com/duke-activity-status-index-dasi) | 1 year |