Assessment of Cardiac, Vascular, and Pulmonary Pathobiology In Vivo During Acute COVID‐19

Background: Acute COVID‐19–related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID‐19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results: Consecutive patients presenting with acute COVID‐19 were prospectively recruited during hospital admission in this cross‐sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2‐deoxy‐2‐[fluorine‐18]fluoro‐D‐glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance–defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0–55.3] versus 3.5 ng/L [IQR: 2.5–5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4–8.3] versus 3.5 ng/L [IQR: 2.8–7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%–31%) and 11% (IQR: 7%–18%), respectively. Neither were associated with the presence of myocarditis. Conclusion: Myocarditis was present in a third patients with acute COVID‐19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process

Measurement of myocardial blood flow by cardiovascular magnetic resonance perfusion: comparison of distributed parameter and Fermi models with single and dual bolus

Background Mathematical modeling of cardiovascular magnetic resonance perfusion data allows absolute quantification of myocardial blood flow. Saturation of left ventricle signal during standard contrast administration can compromise the input function used when applying these models. This saturation effect is evident during application of standard Fermi models in single bolus perfusion data. Dual bolus injection protocols have been suggested to eliminate saturation but are much less practical in the clinical setting. The distributed parameter model can also be used for absolute quantification but has not been applied in patients with coronary artery disease. We assessed whether distributed parameter modeling might be less dependent on arterial input function saturation than Fermi modeling in healthy volunteers. We validated the accuracy of each model in detecting reduced myocardial blood flow in stenotic vessels versus gold-standard invasive methods. Methods Eight healthy subjects were scanned using a dual bolus cardiac perfusion protocol at 3T. We performed both single and dual bolus analysis of these data using the distributed parameter and Fermi models. For the dual bolus analysis, a scaled pre-bolus arterial input function was used. In single bolus analysis, the arterial input function was extracted from the main bolus. We also performed analysis using both models of single bolus data obtained from five patients with coronary artery disease and findings were compared against independent invasive coronary angiography and fractional flow reserve. Statistical significance was defined as two-sided P value <0.05. Results Fermi models overestimated myocardial blood flow in healthy volunteers due to arterial input function saturation in single bolus analysis compared to dual bolus analysis (P < 0.05). No difference was observed in these volunteers when applying distributed parameter-myocardial blood flow between single and dual bolus analysis. In patients, distributed parameter modeling was able to detect reduced myocardial blood flow at stress (<2.5 mL/min/mL of tissue) in all 12 stenotic vessels compared to only 9 for Fermi modeling. Conclusions Comparison of single bolus versus dual bolus values suggests that distributed parameter modeling is less dependent on arterial input function saturation than Fermi modeling. Distributed parameter modeling showed excellent accuracy in detecting reduced myocardial blood flow in all stenotic vessels

Cardiovascular risk factors and markers of myocardial injury and inflammation in people living with HIV in Nairobi, Kenya: a pilot cross-sectional study

Objectives: To determine the prevalence of cardiovascular disease (CVD) risk factors and explore associations with high-sensitivity cardiac troponin I (hscTnI) and high-sensitivity C-reactive protein (hsCRP) in people living with HIV (PLHIV) in Kenya. Design: Pilot cross-sectional study. Setting: Data were collected from community HIV clinics across two sites in Nairobi, Kenya, from July 2019 to May 2020. Participants: Convenience sample of 200 PLHIV (≥30 years with no prior history of CVD). Outcome measures: Prevalence of cardiovascular risk factors and its association with hsTnI and hsCRP levels. Results: Across 200 PLHIV (median age 46 years, IQR 38–53; 61% women), the prevalence of hypercholesterolaemia (total cholesterol \u3e6.1 mmol/L) and hypertension were 19% (n=30/199) and 30% (n=60/200), respectively. Smoking and diabetes prevalence was 3% (n=5/200) and 4% (n=7/200). HscTnI was below the limit of quantification (\u3c2.5 ng/L) in 65% (n=109/169). High (\u3e3 mg/L), intermediate (1–3 mg/L) and low (\u3c1 mg/L) hsCRP levels were found in 38% (n=75/198), 33% (n=65/198) and 29% (n=58/198), respectively. Framingham laboratory-based risk scores classified 83% of PLHIV at low risk with 12% and 5% at intermediate and high risk, respectively. Older age (adjusted OR (aOR) per year increase 1.05, 95% CI 1.01 to 1.08) and systolic blood pressure (140–159 mm Hg (aOR 2.96; 95% CI 1.09 to 7.90) and \u3e160 mm Hg (aOR 4.68, 95% CI 1.55 to 14) compared with \u3c140 mm Hg) were associated with hscTnI levels. No associations were observed between hsCRP and CVD risk factors. Conclusion: The majority of PLHIV—using traditional risk estimation systems—have a low estimated CVD risk likely reflecting a younger aged population predominantly consisting of women. Hypertension and hypercholesterolaemia were common while smoking and diabetes rates remained low. While hscTnI values were associated with increasing age and raised blood pressure, no associations between hsCRP levels and traditional cardiovascular risk factors were observed

Ferumoxytol-enhanced magnetic resonance imaging in acute myocarditis

Objectives Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect tissue-resident macrophage activity and identify cellular inflammation within tissues. We hypothesised that USPIO-enhanced MRI would provide a non-invasive imaging technique that would improve the diagnosis and management of patients with acute myocarditis. Methods Ten volunteers and 14 patients with suspected acute myocarditis underwent T2, T2* and late gadolinium enhancement (LGE) 3T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Myocardial oedema and USPIO enhancement were determined within areas of LGE as well as throughout the myocardium. Results Myocarditis was confirmed in nine of the 14 suspected cases of myocarditis. There was greater myocardial oedema in regions of LGE in patients with myocarditis when compared with healthy volunteer myocardium (T2 value, 57.1±5.3 vs 46.7±1.6 ms, p0.05). Imaging after 3 months in patients with myocarditis revealed a reduction in volume of LGE, a reduction in oedema measures within regions displaying LGE and improvement in ejection fraction (mean −19.7 mL, 95% CI (−0.5 to −40.0)), −5.8 ms (−0.9 to −10.7) and +6% (0.5% to 11.5%), respectively, p<0.05 for all). Conclusion In patients with acute myocarditis, USPIO-enhanced MRI does not provide additional clinically relevant information to LGE and T2 mapping MRI. This suggests that tissue-resident macrophages do not provide a substantial contribution to the myocardial inflammation in this condition. Clinical trial registration NCT02319278; Results

Cardiovascular risk factors and markers of myocardial injury and inflammation in people living with HIV in Nairobi, Kenya: a pilot cross-sectional study.

OBJECTIVES: To determine the prevalence of cardiovascular disease (CVD) risk factors and explore associations with high-sensitivity cardiac troponin I (hscTnI) and high-sensitivity C-reactive protein (hsCRP) in people living with HIV (PLHIV) in Kenya. DESIGN: Pilot cross-sectional study. SETTING: Data were collected from community HIV clinics across two sites in Nairobi, Kenya, from July 2019 to May 2020. PARTICIPANTS: Convenience sample of 200 PLHIV (≥30 years with no prior history of CVD). OUTCOME MEASURES: Prevalence of cardiovascular risk factors and its association with hsTnI and hsCRP levels. RESULTS: Across 200 PLHIV (median age 46 years, IQR 38-53; 61% women), the prevalence of hypercholesterolaemia (total cholesterol >6.1 mmol/L) and hypertension were 19% (n=30/199) and 30% (n=60/200), respectively. Smoking and diabetes prevalence was 3% (n=5/200) and 4% (n=7/200). HscTnI was below the limit of quantification (3 mg/L), intermediate (1-3 mg/L) and low (160 mm Hg (aOR 4.68, 95% CI 1.55 to 14) compared with <140 mm Hg) were associated with hscTnI levels. No associations were observed between hsCRP and CVD risk factors. CONCLUSION: The majority of PLHIV-using traditional risk estimation systems-have a low estimated CVD risk likely reflecting a younger aged population predominantly consisting of women. Hypertension and hypercholesterolaemia were common while smoking and diabetes rates remained low. While hscTnI values were associated with increasing age and raised blood pressure, no associations between hsCRP levels and traditional cardiovascular risk factors were observed

Assessment of Cardiac, Vascular, and Pulmonary Pathobiology In Vivo During Acute COVID-19.

Background Acute COVID-19-related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID-19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results Consecutive patients presenting with acute COVID-19 were prospectively recruited during hospital admission in this cross-sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance-defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0-55.3] versus 3.5 ng/L [IQR: 2.5-5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4-8.3] versus 3.5 ng/L [IQR: 2.8-7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%-31%) and 11% (IQR: 7%-18%), respectively. Neither were associated with the presence of myocarditis. Conclusions Myocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN12154994