Systemic microvascular endothelial dysfunction and disease severity in COVID-19 patients: Evaluation by laser Doppler perfusion monitoring and cytokine/chemokine analysis.

BACKGROUND: Microvascular dysfunction, serum cytokines and chemokines may play important roles in pathophysiology of coronavirus disease 2019 (COVID-19), especially in severe cases. METHODS: Patients with COVID-19 underwent non-invasive evaluation of systemic endothelium-dependent microvascular reactivity - using laser Doppler perfusion monitoring in the skin of the forearm - coupled to local thermal hyperemia. Maximal microvascular vasodilatation (44 °C thermal plateau phase) was used as endpoint. A multiplex biometric immunoassay was used to assess a panel of 48 serum cytokines and chemokines. Severe COVID-19 (S-COVID) was defined according to WHO criteria, while all other cases of COVID-19 were considered mild to moderate (M-COVID). A group of healthy individuals who tested negative for SARS-CoV-2 served as a control group and was also evaluated with LDPM. RESULTS: Thirty-two patients with COVID-19 (25% S-COVID) and 14 controls were included. Basal microvascular flow was similar between M-COVID and controls (P = 0.69) but was higher in S-COVID than in controls (P = 0.005) and M-COVID patients (P = 0.01). The peak microvascular vasodilator response was markedly decreased in both patient groups (M-COVID, P = 0.001; S-COVID, P < 0.0001) compared to the healthy group. The percent increases in microvascular flow were markedly reduced in both patient groups (M-COVID, P < 0.0001; S-COVID, P < 0.0001) compared to controls. Patients with S-COVID had markedly higher concentrations of dissimilar proinflammatory cytokines and chemokines, compared to patients with M-COVID. CONCLUSIONS: In patients with COVID-19, especially with S-COVID, endothelium-dependent microvascular vasodilator responses are reduced, while serum cytokines and chemokines involved in the regulation of vascular function and inflammation are increased.

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19).

Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12-15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P = 0.85). The peak microvascular flow during LTH did also significantly increase (P = 0.02), and was not different form values obtained in healthy volunteers (P = 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

COVID-19 in patients with cardiac disease: Impact and variables associated with mortality in a cardiology center in Brazil.

BACKGROUND: Cardiovascular disease is associated with severe COVID-19. Our aim was to describe clinical and laboratory features (including electrocardiographic and echocardiographic ones) and outcomes of patients with cardiac disease hospitalized with COVID-19. METHODS: This is an observational retrospective study of consecutive adult patients admitted, between March and September of 2020, with confirmed SARSCoV-2 infection. Data were collected as per the ISARIC case report form and complemented with variables related to heart disease. RESULTS: One hundred twenty-one patients were included. Mean age was 60 SD 15.2 years and 80/121(66.1%) were male. Two-thirds of the patients (80/121, 66.1%) had COVID-19 at the time of hospital admission and COVID-19 was the reason for hospitalization in 42 (34.7%). Other reasons for hospital admission were acute coronary syndrome (26%) and decompensated heart failure (14.8%). Chronic cardiac diseases were found in 106/121 (87.6%), mostly coronary artery disease (62%) or valve disease (33.9%). A transthoracic echocardiogram was performed in 93/121(76.8%) and enlarged cardiac chambers were found in 71% (66/93); admission ECG was done in 93 cases (93/121, 76.8%), and 89.2% (83/93) were abnormal. Hospital-acquisition of COVID-19 occurred in 20 (16.5%) of patients and their mortality was 50%. On bivariate analysis for mortality, BNP levels and troponin levels were NOT associated with mortality. On multivariate analysis, only C reactive protein levels and creatinine levels were significant. CONCLUSIONS: COVID-19 impacted the profile of hospital admissions in cardiac patients. BNP and troponin levels were not associated with mortality and may not be good prognostic discriminators in cardiac patients.

Systemic microvascular dysfunction in COVID-19.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while having lung injury as its most prominent feature, has been increasingly shown to affect endothelial cell function and the microvasculature. In this report, a woman with COVID-19, cardiac valve disease and spherocytosis was assessed with laser Doppler perfusion monitoring. Systemic microvascular reactivity was impaired during a worsening phase of COVID-19, but improved after clinical recovery; microcirculatory dysfunction paralleled systemic inflammation and pulmonary involvement. The assessment of systemic microcirculatory function may therefore provide insights on COVID-19 pathophysiology.

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19)

Abstract Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12-15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P= 0.85). The peak microvascular flow during LTH did also significantly increase (P= 0.02), and was not different form values obtained in healthy volunteers (P= 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

Factors Associated With Coronary Artery Disease Progression Assessed By Serial Coronary Computed Tomography Angiography.

Background: Coronary computed tomography angiography (CCTA) allows for noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable. Objective: To identify factors associated with CAD progression in patients undergoing sequential CCTA testing. Methods: We retrospectively analyzed 384 consecutive patients who had at least two CCTA studies between December 2005 and March 2013. Due to limitations in the quantification of CAD progression, we excluded patients who had undergone surgical revascularization previously or percutaneous coronary intervention (PCI) between studies. CAD progression was defined as any increase in the adapted segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stent (in-stent restenosis was excluded from the analysis). Stepwise logistic regression was used to assess variables associated with CAD progression. Results: From a final population of 234 patients, a total of 117 (50%) had CAD progression. In a model accounting for major CAD risk factors and other baseline characteristics, only age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07), interstudy interval (OR 1.03, 95%CI 1.01-1.04), and past PCI (OR 3.66, 95%CI 1.77-7.55) showed an independent relationship with CAD progression. Conclusions: A history of PCI with stent placement was independently associated with a 3.7-fold increase in the odds of CAD progression, excluding in-stent restenosis. Age and interstudy interval were also independent predictors of progression.

Objetivo: Angiografia coronariana por tomografia computadorizada (ACTC) permite fenotipagem não invasiva da doença arterial coronariana (DAC). Fatores relacionados à progressão da DAC têm valor epidemiológico. Métodos: Nós analisamos retrospectivamente 384 pacientes consecutivos que apresentavam pelo menos duas avaliações por ACTC entre dezembro de 2005 e março de 2013. Devido às limitações na quantificação da progressão da DAC, os pacientes que haviam sido submetidos previamente à revascularização cirúrgica ou intervenção coronariana percutânea (ICP) entre as avaliações foram excluídos. A progressão da DAC foi definida como qualquer aumento no escore adaptado de estenose segmentar (calculado com utilização do número de segmentos afetados e gravidade da estenose) em todos os segmentos coronarianos sem stent (restenose intra-stent foi excluída da análise). Regressão logística stepwise foi utilizada para avaliar as variáveis associadas com a progressão da DAC. Resultados: De uma população final de 234 pacientes, um total de 117 (50%) pacientes apresentaram progressão da DAC. Em um modelo considerando os principais fatores de risco para DAC e outras características basais, apenas a idade (odds ratio [OR] 1,04, intervalo de confiança de 95% [IC95%] 1,01-1,07), intervalo entre avaliações (OR 1,03, IC95% 1,01-1,04) e ICP prévia (OR 3,66, IC95% 1,77-7,55) mostraram uma relação independente com a progressão da DAC. Conclusões: Uma história de ICP com implante de stent esteve independentemente associada a um aumento de 3,7 vezes na chance de progressão da DAC, excluindo a restenose intra-stent. Idade e intervalo entre avaliações também foram preditores independentes de progressão.

Real-time cardiac magnetic resonance cine imaging with sparse sampling and iterative reconstruction for left-ventricular measures: Comparison with gold-standard segmented steady-state free precession.

BACKGROUND: Segmented cine imaging with a steady-state free-precession sequence (Cine-SSFP) is currently the gold standard technique for measuring ventricular volumes and mass, but due to multi breath-hold (BH) requirements, it is prone to misalignment of consecutive slices, time consuming and dependent on respiratory capacity. Real-time cine avoids those limitations, but poor spatial and temporal resolution of conventional sequences has prevented its routine application. We sought to examine the accuracy and feasibility of a newly developed real-time sequence with aggressive under-sampling of k-space using sparse sampling and iterative reconstruction (Cine-RT). METHODS: Stacks of short-axis cines were acquired covering both ventricles in a 1.5T system using gold standard Cine-SSFP and Cine-RT. Acquisition parameters for Cine-SSFP were: acquisition matrix of 224×196, temporal resolution of 39ms, retrospective gating, with an average of 8 heartbeats per slice and 1-2 slices/BH. For Cine-RT: acquisition matrix of 224×196, sparse sampling net acceleration factor of 11.3, temporal resolution of 41ms, prospective gating, real-time acquisition of 1 heart-beat/slice and all slices in one BH. LV contours were drawn at end diastole and systole to derive LV volumes and mass. RESULTS: Forty-one consecutive patients (15 male; 41±17years) in sinus rhythm were successfully included. All images from Cine-SSFP and Cine-RT were considered to have excellent quality. Cine-RT-derived LV volumes and mass were slightly underestimated but strongly correlated with gold standard Cine-SSFP. Inter- and intra-observer analysis presented similar results between both sequences. CONCLUSIONS: Cine-RT featuring sparse sampling and iterative reconstruction can achieve spatial and temporal resolution equivalent to Cine-SSFP, providing excellent image quality, with similar precision measurements and highly correlated and only slightly underestimated volume and mass values.

Changes in Medical Management after Coronary CT Angiography.

INTRODUCTION: Coronary computed tomography angiography (CCTA) allows for non-invasive coronary artery disease (CAD) phenotyping. There are still some uncertainties regarding the impact this knowledge has on the clinical care of patients. OBJECTIVE: To determine whether CAD phenotyping by CCTA influences clinical decision making by the prescription of cardiovascular drugs and their impact on non-LDL cholesterol (NLDLC) levels. METHODS: We analysed consecutive patients from 2008 to 2011 submitted to CCTA without previous diagnosis of CAD that had two serial measures of NLDLC, one up to 3 months before CCTA and the second from 3 to 6 months after. RESULTS: A total of 97 patients were included, of which 69% were men, mean age 64 ± 12 years. CCTA revealed that 18 (18%) patients had no CAD, 38 (39%) had non-obstructive (< 50%) lesions and 41 (42%) had at least one obstructive ≥ 50% lesion. NLDLC was similar at baseline between the grups (138 ± 52 mg/dL vs. 135 ± 42 mg/dL vs. 131 ± 44 mg/dL, respectively, p = 0.32). We found significative reduction in NLDLC among patients with obstrctive lesions (-18%, p = 0.001). We also found a positive relationship between clinical treatment intensification with aspirin and cholesterol reducing drugs and the severity of CAD. CONCLUSION: Our data suggest that CCTA results were used for cardiovascular clinical treatment titration, with especial intensification seen in patients with obstructive ≥50% CAD.

Factors Associated With Coronary Artery Disease Progression Assessed By Serial Coronary Computed Tomography Angiography / Fatores Associados com Progressão da Doença Arterial Coronariana Avaliada por Angiografia Coronariana por Tomografia Computadorizada Seriada

Abstract Background: Coronary computed tomography angiography (CCTA) allows for noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable. Objective: To identify factors associated with CAD progression in patients undergoing sequential CCTA testing. Methods: We retrospectively analyzed 384 consecutive patients who had at least two CCTA studies between December 2005 and March 2013. Due to limitations in the quantification of CAD progression, we excluded patients who had undergone surgical revascularization previously or percutaneous coronary intervention (PCI) between studies. CAD progression was defined as any increase in the adapted segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stent (in-stent restenosis was excluded from the analysis). Stepwise logistic regression was used to assess variables associated with CAD progression. Results: From a final population of 234 patients, a total of 117 (50%) had CAD progression. In a model accounting for major CAD risk factors and other baseline characteristics, only age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07), interstudy interval (OR 1.03, 95%CI 1.01-1.04), and past PCI (OR 3.66, 95%CI 1.77-7.55) showed an independent relationship with CAD progression. Conclusions: A history of PCI with stent placement was independently associated with a 3.7-fold increase in the odds of CAD progression, excluding in-stent restenosis. Age and interstudy interval were also independent predictors of progression.

Resumo Fundamento: Angiografia coronariana por tomografia computadorizada (ACTC) permite fenotipagem não invasiva da doença arterial coronariana (DAC). Fatores relacionados à progressão da DAC têm valor epidemiológico. Objetivo: Identificar os fatores associados com a progressão da DAC em pacientes submetidos à avaliação sequencial por ACTC. Métodos: Nós analisamos retrospectivamente 384 pacientes consecutivos que apresentavam pelo menos duas avaliações por ACTC entre dezembro de 2005 e março de 2013. Devido às limitações na quantificação da progressão da DAC, os pacientes que haviam sido submetidos previamente à revascularização cirúrgica ou intervenção coronariana percutânea (ICP) entre as avaliações foram excluídos. A progressão da DAC foi definida como qualquer aumento no escore adaptado de estenose segmentar (calculado com utilização do número de segmentos afetados e gravidade da estenose) em todos os segmentos coronarianos sem stent (restenose intra-stent foi excluída da análise). Regressão logística stepwise foi utilizada para avaliar as variáveis associadas com a progressão da DAC. Resultados: De uma população final de 234 pacientes, um total de 117 (50%) pacientes apresentaram progressão da DAC. Em um modelo considerando os principais fatores de risco para DAC e outras características basais, apenas a idade (odds ratio [OR] 1,04, intervalo de confiança de 95% [IC95%] 1,01-1,07), intervalo entre avaliações (OR 1,03, IC95% 1,01-1,04) e ICP prévia (OR 3,66, IC95% 1,77-7,55) mostraram uma relação independente com a progressão da DAC. Conclusões: Uma história de ICP com implante de stent esteve independentemente associada a um aumento de 3,7 vezes na chance de progressão da DAC, excluindo a restenose intra-stent. Idade e intervalo entre avaliações também foram preditores independentes de progressão.

Changes in Medical Management after Coronary CT Angiography / Mudanças no Manejo Clínico após Angiotomografia Coronariana

AbstractIntroduction:Coronary computed tomography angiography (CCTA) allows for non-invasive coronary artery disease (CAD) phenotyping. There are still some uncertainties regarding the impact this knowledge has on the clinical care of patients.Objective:To determine whether CAD phenotyping by CCTA influences clinical decision making by the prescription of cardiovascular drugs and their impact on non-LDL cholesterol (NLDLC) levels.Methods:We analysed consecutive patients from 2008 to 2011 submitted to CCTA without previous diagnosis of CAD that had two serial measures of NLDLC, one up to 3 months before CCTA and the second from 3 to 6 months after.Results:A total of 97 patients were included, of which 69% were men, mean age 64 ± 12 years. CCTA revealed that 18 (18%) patients had no CAD, 38 (39%) had non-obstructive (< 50%) lesions and 41 (42%) had at least one obstructive ≥ 50% lesion. NLDLC was similar at baseline between the grups (138 ± 52 mg/dL vs. 135 ± 42 mg/dL vs. 131 ± 44 mg/dL, respectively, p = 0.32). We found significative reduction in NLDLC among patients with obstrctive lesions (-18%, p = 0.001). We also found a positive relationship between clinical treatment intensification with aspirin and cholesterol reducing drugs and the severity of CAD.Conclusion:Our data suggest that CCTA results were used for cardiovascular clinical treatment titration, with especial intensification seen in patients with obstructive ≥50% CAD.

ResumoFundamento:A Angiotomografia Coronariana (AngioTC Cor) permite a fenotipagem de Doença Arterial Coronariana (DAC) de forma não invasiva. Ainda há incertezas sobre o impacto que esse conhecimento promove no tratamento clínico do paciente.Objetivo:Avaliar se a fenotipagem da DAC por AngioTC Cor influencia na tomada de decisão sobre o início da terapêutica cardiovascular e seu impacto nos níveis séricos de colesterol não HDL (CNHDL).Métodos:Foram analisados pacientes consecutivos sem diagnóstico prévio de DAC que realizaram AngioTC Cor entre os anos 2008 e 2011 e que possuíam duas dosagens seriadas de colesterol até três meses antes da AngioTC Cor, e de três a seis meses após.Resultados:Um total de 97 pacientes foram incluídos, sendo 69% homens, idade média de 64 ± 12 anos. A AngioTC Cor revelou que 18 (18%) pacientes não tinham lesões detectáveis, 38 (39%) tinham lesões não obstrutivas < 50%, e 41 (42%) tinham ao menos uma lesão obstrutiva ≥ 50%. As medidas de CNHDL basal foram similares entre os grupos, (138 ± 52 mg/dL vs. 135 ± 42 mg/dL vs. 131 ± 44 mg/dL, respectivamente, p = 0,32). Observou-se redução significativa do CNHDL apenas no grupo com lesões obstrutivas ≥ 50% (-18%, p = 0,001). Observa-se ainda relação entre a intensificação do tratamento clínico com AAS e drogas redutoras de colesterol proporcional à gravidade da DAC pela AngioTC Cor.Conclusão:Esses dados sugerem que o resultado da AngioTC Cor foi utilizado para a titulação terapêutica de pacientes com DAC, sendo o tratamento intensificado especialmente em DAC obstrutiva ≥ 50%.