Coronary calcifications as a new prognostic marker in COVID-19 patients: role of CT.

OBJECTIVE: COVID-19 pneumonia, caused by the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic by the WHO on 11th March 2020. While Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) represents the diagnostic gold standard of infection, computed tomography (CT) has been shown to have an important role in supporting the diagnosis, quantifying the severity, and assessing the efficacy of treatment and its response. Coronary artery calcification (CAC) is a CT finding that estimates atherosclerosis and can be quantified using the coronary artery calcium score (CACS). The purpose of this study is to demonstrate the correlation between coronary artery calcification and mortality rate in COVID-19 patients. PATIENTS AND METHODS: Three hundred seventeen (317) hospitalized patients with SARS-CoV-2 infection were ruled in this retrospective study. All patients underwent a non-ECG-gated chest CT to evaluate lung parenchymal involvement. In the same cohort, we observed the two main coronary arteries (common trunk, circumflex, anterior interventricular and right coronary heart) using a visual score, so patients were divided into four groups based on Ordinal CAC Score (OCS) levels. RESULTS: The multivariate analysis proved that the OCS value was statistically correlated with the mortality rate (p < 0.001). In fact, in the group of patients with an OCS value of 0, the mortality rate was 10.1% (10/99 patients), in the group with OCS between 1 and 4 was 18.9% (21/111), in the OCS group of patients ranged from 5 to 8 was 30.4% (24/79) and in the OCS group between 9 and 12 was 46.4% (13/28). CONCLUSIONS: We suggest that calcific atheromasia of the coronary arteries in patients with COVID-19 can be considered a prognostic marker of clinical outcome.

Coronary artery calcifications and 6-month mortality in patients with COVID-19 without known atheromatous disease.

BACKGROUND: Coronary artery calcium (CAC) is an independent risk factor for major adverse cardiovascular events; however, its impact on coronavirus disease 2019 (COVID-19) mortality remains unclear, especially in patients without known atheromatous disease. AIMS: To evaluate the association between CAC visual score and 6-month mortality in patients without history of atheromatous disease hospitalized with COVID-19 pneumonia. METHODS: A single-centre observational cohort study was conducted, involving 293 consecutive patients with COVID-19 in Paris, France, between 13 March and 30 April 2020, with a 6-month follow-up. Patients with a history of ischaemic stroke or coronary or peripheral artery disease were excluded. The primary outcome was all-cause mortality at 6 months according to CAC score, which was assessed by analysing images obtained after the first routine non-electrocardiogram-gated computed tomography scan performed to detect COVID-19 pneumonia. RESULTS: A total of 251 patients (mean age 64.8±16.7 years) were included in the analysis. Fifty-one patients (20.3%) died within 6 months. The mortality rate increased with the magnitude of calcifications, and was 10/101 (9.9%), 15/66 (22.7%), 10/34 (29.4%) and 16/50 (32.0%) for the no CAC, mild CAC, moderate CAC and heavy CAC groups, respectively (p=0.004). Compared with the no calcification group, adjusted risk of death increased progressively with CAC: hazard ratio (HR) 2.37 (95% confidence interval [CI] 1.06-5.27), HR 3.1 (95% CI 1.29-7.45) and HR 4.02 (95% CI 1.82-8.88) in the mild, moderate and heavy CAC groups, respectively. CONCLUSIONS: Non-electrocardiogram-gated computed tomography during the initial pulmonary assessment of patients with COVID-19 without atherosclerotic cardiovascular disease showed a high prevalence of mild, moderate and heavy CAC. CAC score was related to 6-month mortality, independent of conventional cardiovascular risk factors. These results highlight the importance of CAC scoring for patients hospitalized with COVID-19, and calls for attention to patients with high CAC.

Lung Opacity and Coronary Artery Calcium Score: A Combined Tool for Risk Stratification and Outcome Prediction in COVID-19 Patients.

PURPOSE: To assess and correlate pulmonary involvement and outcome of SARS-CoV-2 pneumonia with the degree of coronary plaque burden based on the CAC-DRS classification (Coronary Artery Calcium Data and Reporting System). METHODS: This retrospective study included 142 patients with confirmed SARS-CoV-2 pneumonia (58 ± 16 years; 57 women) who underwent non-contrast CT between January 2020 and August 2021 and were followed up for 129 ± 72 days. One experienced blinded radiologist analyzed CT series for the presence and extent of calcified plaque burden according to the visual and quantitative HU-based CAC-DRS Score. Pulmonary involvement was automatically evaluated with a dedicated software prototype by another two experienced radiologists and expressed as Opacity Score. RESULTS: CAC-DRS Scores derived from visual and quantitative image evaluation correlated well with the Opacity Score (r=0.81, 95% CI 0.76-0.86, and r=0.83, 95% CI 0.77-0.89, respectively; p<0.0001) with higher correlation in severe than in mild stage SARS-CoV-2 pneumonia (p<0.0001). Combined, CAC-DRS and Opacity Scores revealed great potential to discriminate fatal outcomes from a mild course of disease (AUC 0.938, 95% CI 0.89-0.97), and the need for intensive care treatment (AUC 0.801, 95% CI 0.77-0.83). Visual and quantitative CAC-DRS Scores provided independent prognostic information on all-cause mortality (p=0.0016 and p<0.0001, respectively), both in univariate and multivariate analysis. CONCLUSIONS: Coronary plaque burden is strongly correlated to pulmonary involvement, adverse outcome, and death due to respiratory failure in patients with SARS-CoV-2 pneumonia, offering great potential to identify individuals at high risk.

Association of coronary calcification with prognosis of Covid-19 patients without known heart disease.

Risk factors that determine the severity of Covid-19 have not been fully elucidated. The aim of this study was to evaluate the role of coronary artery calcification (CAC) as a risk factor for death or mechanical ventilation (MV) of patients without known heart disease infected with Covid-19. We analyzed 283 consecutive in-patients with acute respiratory symptoms with chest computed tomography (chest-CT), without previous heart disease, and criteria for Covid-19 (RT-PCR positive and/or typical clinical and chest-CT findings). CAC was classified by the number of coronary segments affected as absent (0), mild (1-3), and severe calcification (more than 3). The association between CAC, CAC severity, and death or MV due to severe respiratory failure was assessed by logistic regression. The mean age was 58.7±15.7 years and 54.1% were men. Patients with CAC were older, more likely to have hypertension, and less likely to be obese. CAC was present in 75 patients (26.5%), of which 42 had a mild calcification and 33 had severe calcification, and was associated with death (OR=2.35, 95%CI: 1.01-5.48) or MV (OR=2.72, 95%CI: 1.20-6.20) adjusted for multiple confounders, with significant and increased odds ratio for the severe form of CAC (death: OR=3.70, 95%CI: 1.20-11.42; MV: OR=3.30, 95%CI: 1.09-9.95). We concluded that CAC was an independent risk factor for death or MV in Covid-19 patients without previous heart disease, particularly for those with severe calcification. CAC can be easily visualized on common chest-CT, widely used in evaluation of moderate to severe Covid-19.

Coronary calcium score as a predictor of outcomes in the hypertensive Covid-19 population: results from the Italian (S) Core-Covid-19 Registry.

Hypertension is associated with more severe disease and adverse outcomes in COVID-19 patients. Recent investigations have indicated that hypertension might be an independent predictor of outcomes in COVID-19 patients regardless of other cardiovascular and noncardiovascular comorbidities. We explored the significance of coronary calcifications in 694 hypertensive patients in the Score-COVID registry, an Italian multicenter study conducted during the first pandemic wave in the Western world (March-April 2020). A total of 1565 patients admitted with RNA-PCR-positive nasopharyngeal swabs and chest computed tomography (CT) at hospital admission were included in the study. Clinical outcomes and cardiovascular calcifications were analyzed independently by a research core lab. Hypertensive patients had a different risk profile than nonhypertensive patients, with more cardiovascular comorbidities. The deceased hypertensive patients had a greater coronary calcification burden at the level of the anterior descending coronary artery. Hypertension status and the severity cutoffs of coronary calcifications were used to stratify the clinical outcomes. For every 100-mm3 increase in coronary calcium volume, hospital mortality in hypertensive patients increased by 8%, regardless of sex, age, diabetes, creatinine, and lung interstitial involvement. The coronary calcium score contributes to stratifying the risk of complications in COVID-19 patients. Cardiovascular calcifications appear to be a promising imaging marker for providing pathophysiological insight into cardiovascular risk factors and COVID-19 outcomes.

In-hospital prognostic role of coronary atherosclerotic burden in COVID-19 patients.

AIMS: Currently, there are few available data regarding a possible role for subclinical atherosclerosis as a risk factor for mortality in Coronavirus Disease 19 (COVID-19) patients. We used coronary artery calcium (CAC) score derived from chest computed tomography (CT) scan to assess the in-hospital prognostic role of CAC in patients affected by COVID-19 pneumonia. METHODS: Electronic medical records of patients with confirmed diagnosis of COVID-19 were retrospectively reviewed. Patients with known coronary artery disease (CAD) were excluded. A CAC score was calculated for each patient and was used to categorize them into one of four groups: 0, 1-299, 300-999 and at least 1000. The primary endpoint was in-hospital mortality for any cause. RESULTS: The final population consisted of 282 patients. Fifty-seven patients (20%) died over a follow-up time of 40 days. The presence of CAC was detected in 144 patients (51%). Higher CAC score values were observed in nonsurvivors [median: 87, interquartile range (IQR): 0.0-836] compared with survivors (median: 0, IQR: 0.0-136). The mortality rate in patients with a CAC score of at least 1000 was significantly higher than in patients without coronary calcifications (50 vs. 11%) and CAC score 1-299 (50 vs. 23%), P < 0.05. After adjusting for clinical variables, the presence of any CAC categories was not an independent predictor of mortality; however, a trend for increased risk of mortality was observed in patients with CAC of at least 1000. CONCLUSION: The correlation between CAC score and COVID-19 is fascinating and under-explored. However, in multivariable analysis, the CAC score did not show an additional value over more robust clinical variables in predicting in-hospital mortality. Only patients with the highest atherosclerotic burden (CAC ≥1000) could represent a high-risk population, similarly to patients with known CAD.

Coronary artery calcium score may be a novel predictor of COVID-19 prognosis: a retrospective study.

BACKGROUND: Although several studies have reported an association between atherosclerosis-related diseases and COVID-19, the relationship between COVID-19 severity and atherosclerosis progression remains unclear. The aim of this study is to determine the coronary artery calcium score (CACS) prognostic value in patients with COVID-19 using indices such as deterioration in oxygenation and CT images of the chest. METHODS: This was a single-centre retrospective study of 53 consecutive patients with COVID-19 in Narita who were admitted to our hospital between March 2020 and August 2020. CACS was calculated based on non-gated CT scans of the chest performed on admission day. The patients were divided into the following two groups based on CACS: group 1 (CACS ≥180, n=11) and group 2 (CACS <180, n=42). Following univariate analysis of the main variables, multivariate analysis of variables that may be associated with COVID-19 progression was performed. RESULTS: Multivariable logistic regression analysis of age, sex, smoking history, diabetes, hypertension, dyslipidaemia, number of days from symptom onset to hospitalisation and CACS of ≥180 was performed. It revealed that unlike CACS of <180, CACS of ≥180 is associated with exacerbation of oxygenation or CT images of the chest during hospitalisation (OR: 12.879, 95% CI: 1.399 to 380.401). Furthermore, this model of eight variables showed good calibration (Hosmer-Lemeshow p=0.119). CONCLUSION: CACS may be a prognosis marker of COVID-19 severity. Although coronary artery calcification is not typically assessed in pneumonia cases, it may provide a valuable clinical indicator for predicting severe COVID-19 outcomes.

The hidden interplay between sex and COVID-19 mortality: the role of cardiovascular calcification.

Recent clinical and demographical studies on COVID-19 patients have demonstrated that men experience worse outcomes than women. However, in most cases, the data were not stratified according to gender, limiting the understanding of the real impact of gender on outcomes. This study aimed to evaluate the disaggregated in-hospital outcomes and explore the possible interactions between gender and cardiovascular calcifications. Data was derived from the sCORE-COVID-19 registry, an Italian multicentre registry that enrolled COVID-19 patients who had undergone a chest computer tomography scan on admission. A total of 1683 hospitalized patients (mean age 67±14 years) were included. Men had a higher prevalence of cardiovascular comorbidities, a higher pneumonia extension, more coronary calcifications (63% vs.50.9%, p<0.001), and a higher coronary calcium score (391±847 vs. 171±479 mm3, p<0.001). Men experienced a significantly higher mortality rate (24.4% vs. 17%, p=0.001), but the death event tended to occur earlier in women (15±7 vs. 8±7 days, p= 0.07). Non-survivors had a higher coronary, thoracic aorta, and aortic valve calcium score. Female sex, a known independent predictor of a favorable outcome in SARS-CoV2 infection, was not protective in women with a coronary calcification volume greater than 100 mm3. There were significant differences in cardiovascular comorbidities and vascular calcifications between men and women with SARS-CoV2 pneumonia. The differences in outcomes can be at least partially explained by the different cardiovascular profiles. However, women with poor outcomes had the same coronary calcific burden as men. The presumed favorable female sex bias in COVID-19 must therefore be reviewed in the context of comorbidities, especially cardiovascular ones.

Association between coronary artery calcifications and 6-month mortality in hospitalized patients with COVID-19.

PURPOSE: The purpose of this study was to evaluate the association between coronary artery calcium (CAC) visual score and 6-month mortality in patients with coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: A single-center prospective observational cohort was conducted in 169 COVID-19 consecutive hospitalized patients between March 13 and April 1, 2020, and follow-up for 6-months. A four-level visual CAC scoring was assessed by analyzing images obtained after the first routine non-ECG-gated CT performed to detect COVID-19 pneumonia. RESULTS: Among 169 confirmed COVID-19 patients (118 men, 51 women; mean age, 65.6 ± 18.8 [SD] years; age range: 30-95 years) 63 (37%) presented with either moderate (n = 26, 15.3%) or heavy (n = 37, 21.8%) CAC detected by CT and 20 (11.8%) had history of cardiovascular disease requiring specific preventive treatment. At six months, mortality rate (45/169; 26.6%) increased with magnitude of CAC and was 7/64 (10.9%), 11/42 (26.2%), 10/26 (38.5%), 17/37 (45.9%) for no-CAC, mild-CAC, moderate-CAC and heavy-CAC groups, respectively (P = 0.001). Compared to the no CAC group, risk of death increased after adjustment with magnitude of CAC (HR: 2.23, 95% CI: 0.73-6.87, P = 0.16; HR: 2.78, 95% CI: 0.85-9.07, P0.09; HR: 5.38, 95% CI: 1.57-18.40, P = 0.007; in mild CAC, moderate and heavy CAC groups, respectively). In patients without previous coronary artery disease (154/169; 91%), mortality increased from 10.9% to 45.8% (P = 0.001) according to the magnitude of CAC categories. After adjustment, presence of moderate or heavy CAC was associated with higher mortality (HR: 2.26, 95% CI: 1.09-4.69, P = 0.03). CONCLUSION: By using non-ECG-gated CT during the initial pulmonary assessment of COVID-19, heavy CAC is independently associated with 6-month mortality in patients hospitalized for severe COVID-19 pneumonia.

Coronary artery calcification and epicardial adipose tissue as independent predictors of mortality in COVID-19.

Recent epidemiological studies have demonstrated that common cardiovascular risk factors are strongly associated with adverse outcomes in COVID-19. Coronary artery calcium (CAC) and epicardial fat (EAT) have shown to outperform traditional risk factors in predicting cardiovascular events in the general population. We aim to determine if CAC and EAT determined by Computed Tomographic (CT) scanning can predict all-cause mortality in patients admitted with COVID-19 disease. We performed a retrospective, post-hoc analysis of all patients admitted to Montefiore Medical Center with a confirmed COVID-19 diagnosis from March 1st, 2020 to May 2nd, 2020 who had a non-contrast CT of the chest within 5 years prior to admission. We determined ordinal CAC scores and quantified the epicardial (EAT) and thoracic (TAT) fat volume and examined their relationship with inpatient mortality. A total of 493 patients were analyzed. There were 197 deaths (39.95%). Patients who died during the index admission had higher age (72, [64-80] vs 68, [57-76]; p < 0.001), CAC score (3, [0-6] vs 1, [0-4]; p < 0.001) and EAT (107, [70-152] vs 94, [64-129]; p = 0.023). On a competing risk analysis regression model, CAC ≥ 4 and EAT ≥ median (98 ml) were independent predictors of mortality with increased mortality of 63% (p = 0.003) and 43% (p = 0.032), respectively. As a composite, the group with a combination of CAC ≥ 4 and EAT ≥ 98 ml had the highest mortality. CAC and EAT measured from chest CT are strong independent predictors of inpatient mortality from COVID-19 in this high-risk cohort.

Coronary and total thoracic calcium scores predict mortality and provides pathophysiologic insights in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. OBJECTIVES: The aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients. METHODS: 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. RESULTS: Non-survivors compared to survivors had higher coronary artery [Agatston (467.76 â€‹± â€‹570.92 vs 206.80 â€‹± â€‹424.13 â€‹mm2, p â€‹< â€‹0.001); Volume (487.79 â€‹± â€‹565.34 vs 207.77 â€‹± â€‹406.81, p â€‹< â€‹0.001)], aortic valve [Volume (322.45 â€‹± â€‹390.90 vs 98.27 â€‹± â€‹250.74 mm2, p â€‹< â€‹0.001; Agatston 337.38 â€‹± â€‹414.97 vs 111.70 â€‹± â€‹282.15, p â€‹< â€‹0.001)] and thoracic aorta [Volume (3786.71 â€‹± â€‹4225.57 vs 1487.63 â€‹± â€‹2973.19 mm2, p â€‹< â€‹0.001); Agatston (4688.82 â€‹± â€‹5363.72 vs 1834.90 â€‹± â€‹3761.25, p â€‹< â€‹0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046-1.637, p â€‹= â€‹0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200-3.251, p â€‹= â€‹0.007) resulted to be independent predictors of in-hospital mortality. CONCLUSION: Coronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk.

Coronary artery calcification in COVID-19 patients: an imaging biomarker for adverse clinical outcomes.

BACKGROUND: Recent studies have demonstrated a complex interplay between comorbid cardiovascular disease, COVID-19 pathophysiology, and poor clinical outcomes. Coronary artery calcification (CAC) may therefore aid in risk stratification of COVID-19 patients. METHODS: Non-contrast chest CT studies on 180 COVID-19 patients ≥ age 21 admitted from March 1, 2020 to April 27, 2020 were retrospectively reviewed by two radiologists to determine CAC scores. Following feature selection, multivariable logistic regression was utilized to evaluate the relationship between CAC scores and patient outcomes. RESULTS: The presence of any identified CAC was associated with intubation (AOR: 3.6, CI: 1.4-9.6) and mortality (AOR: 3.2, CI: 1.4-7.9). Severe CAC was independently associated with intubation (AOR: 4.0, CI: 1.3-13) and mortality (AOR: 5.1, CI: 1.9-15). A greater CAC score (UOR: 1.2, CI: 1.02-1.3) and number of vessels with calcium (UOR: 1.3, CI: 1.02-1.6) was associated with mortality. Visualized coronary stent or coronary artery bypass graft surgery (CABG) had no statistically significant association with intubation (AOR: 1.9, CI: 0.4-7.7) or death (AOR: 3.4, CI: 1.0-12). CONCLUSION: COVID-19 patients with any CAC were more likely to require intubation and die than those without CAC. Increasing CAC and number of affected arteries was associated with mortality. Severe CAC was associated with higher intubation risk. Prior CABG or stenting had no association with elevated intubation or death.

Utility of visual coronary artery calcification on non-cardiac gated thoracic CT in predicting clinical severity and outcome in COVID-19.

BACKGROUND: Assessment of visual-coronary artery calcification on non-cardiac gated CT in COVID-19 patients could provide an objective approach to rapidly identify and triage clinically severe patients for early hospital admission to avert worse prognosis. PURPOSE: To ascertain the role of semi-quantitative scoring in visual-coronary artery calcification score (V-CACS) for predicting the clinical severity and outcome in patients with COVID-19. MATERIALS AND METHODS: With institutional review board approval this study included 67 COVID-19 confirmed patients who underwent non-cardiac gated CT chest in an inpatient setting. Two blinded radiologist (Radiologist-1 &2) assessed the V-CACS, CT Chest severity score (CT-SS). The clinical data including the requirement for oxygen support, assisted ventilation, ICU admission and outcome was assessed, and patients were clinically subdivided depending on clinical severity. Logistic regression analyses were performed to identify independent predictors. ROC curves analysis is performed for the assessment of performance and Pearson correlation were performed to looks for the associations. RESULTS: V-CACS cut off value of 3 (82.67% sensitivity and 54.55% specificity; AUC 0.75) and CT-SS with a cut off value of 21.5 (95.7% sensitivity and 63.6% specificity; AUC 0.87) are independent predictors for clinical severity and also the need for ICU admission or assisted ventilation. The pooling of both CT-SS and V-CACS (82.67% sensitivity and 86.4% specificity; AUC 0.92) are more reliable in terms of predicting the primary outcome of COVID-19 patients. On regression analysis, V-CACS and CT-SS are individual independent predictors of clinical severity in COVID-19 (Odds ratio, 1.72; 95% CI, 0.99-2.98; p = 0.05 and Odds ratio, 1.22; 95% CI, 1.08-1.39; p = 0.001 respectively). The area under the curve (AUC) for pooled V-CACS and CT-SS was 0.96 (95% CI 0.84-0.98) which correctly predicted 82.1% cases. CONCLUSION: Logistic regression model using pooled Visual-Coronary artery calcification score and CT Chest severity score in non-cardiac gated CT can predict clinical severity and outcome in patients with COVID-19.

Coronary calcium scoring assessed on native screening chest CT imaging as predictor for outcome in COVID-19: An analysis of a hospitalized German cohort.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, a number of risk factors for a poor outcome have been identified. Thereby, cardiovascular comorbidity has a major impact on mortality. We investigated whether coronary calcification as a marker for coronary artery disease (CAD) is appropriate for risk prediction in COVID-19. METHODS: Hospitalized patients with COVID-19 (n = 109) were analyzed regarding clinical outcome after native computed tomography (CT) imaging for COVID-19 screening. CAC (coronary calcium score) and clinical outcome (need for intensive care treatment or death) data were calculated following a standardized protocol. We defined three endpoints: critical COVID-19 and transfer to ICU, fatal COVID-19 and death, composite endpoint critical and fatal COVID-19, a composite of ICU treatment and death. We evaluated the association of clinical outcome with the CAC. Patients were dichotomized by the median of CAC. Hazard ratios and odds ratios were calculated for the events death or ICU or a composite of death and ICU. RESULTS: We observed significantly more events for patients with CAC above the group's median of 31 for critical outcome (HR: 1.97[1.09,3.57], p = 0.026), for fatal outcome (HR: 4.95[1.07,22.9], p = 0.041) and the composite endpoint (HR: 2.31[1.28,4.17], p = 0.0056. Also, odds ratio was significantly increased for critical outcome (OR: 3.01 [1.37, 6.61], p = 0.01) and for fatal outcome (OR: 5.3 [1.09, 25.8], p = 0.02). CONCLUSION: The results indicate a significant association between CAC and clinical outcome in COVID-19. Our data therefore suggest that CAC might be useful in risk prediction in patients with COVID-19.