Increased Prevalence of Myocardial Injury in Patients with SARS-CoV-2 Viremia

BackgroundPatients with coronavirus disease 2019 (COVID-19) have a high prevalence of detectable troponin and myocardial injury. In addition, a subset of patients with COVID-19 has detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral loads. The objective of this study was to understand the relationship among SARS-CoV-2 viremia, detectable troponin, and myocardial injury in hospitalized patients with COVID-19.MethodsSARS-CoV-2 plasma viral load was measured in plasma samples drawn from patients hospitalized for COVID-19 at 2 academic medical centers. Baseline characteristics and clinically obtained high-sensitivity cardiac troponin T (hs-cTnT) values were abstracted from the medical record. The main outcome was detectable hs-cTnT (≥6 ng/mL) and myocardial injury (hs-cTnT ≥14 ng/mL; >99th percentile for assay).ResultsA total of 70 hospitalized patients with COVID-19 were included in this study, with 39% females and median age 58 ± 17 years; 21 patients (30%) were found to have detectable SARS-CoV-2 viral load and were classified in the viremia group. Patients with viremia were significantly older than those without viremia. All of the patients with viremia (100%) had detectable troponin during hospitalization compared with 59% of patients without viremia (P = 0.0003). Myocardial injury was seen in 76% of patients with viremia and 38% of those patients without viremia (P = 0.004).ConclusionsHospitalized patients with COVID-19 with SARS-CoV-2 viremia have a significantly higher prevalence of detectable troponin and myocardial injury during their hospitalization compared with patients who did not. This first report of the relationship among SARS-CoV-2 viremia, detectable troponin, and myocardial injury in patients with COVID-19 points to additional mechanistic pathways that require deeper study to understand the complex interplay among these unique findings, cardiovascular outcomes, and mortality in COVID-19.     

Wide QRS Complex and Lateral ST-T Segment Abnormality Are Associated With Worse Clinical Outcomes in COVID-19 Patients

BackgroundThe information on electrocardiographic features of patients with coronavirus disease 2019 (COVID-19) is limited. Our aim was to determine if baseline electrocardiographic features of hospitalized COVID-19 patients are associated with markers of myocardial injury and clinical outcomes.MethodsIn this retrospective, single center cohort study, we included 223 hospitalized patients with laboratory-confirmed COVID-19. Clinical, electrocardiographic and laboratory data were collected and analyzed. Primary composite endpoint of mortality, need for invasive mechanical ventilation, or admission to the intensive care unit was assessed.ResultsForty patients (17.9%) reached the primary composite endpoint. Patients with the primary composite endpoint were more likely to have wide QRS complex (>120 ms) and lateral ST-T segment abnormality. The multivariable Cox regression showed increasing odds of the primary composite endpoint associated with acute respiratory distress syndrome (odds ratio 7.76, 95% CI 2.67–22.59; p < 0.001), acute cardiac injury (odds ratio 3.14, 95% CI 1.26–7.99; p = 0.016), high flow oxygen therapy (odds ratio 2.43, 95% CI 1.05–5.62; p = 0.037) and QRS duration longer than >120 ms (odds ratio 3.62, 95% CI 1.39–9.380; p = 0.008) Patients with a wide QRS complex (>120 ms) had significantly higher median level of troponin T and pro-BNP than those without it. Patients with abnormality of lateral ST-T segment had significantly higher median level of troponin T and pro-BNP than patients without.ConclusionsThe presence of QRS duration longer than 120 ms and lateral ST-T segment abnormality were associated with worse clinical outcomes and higher levels of myocardial injury biomarkers.     

Using human umbilical cord mesenchymal stem cells combined with allogenic platelet-rich fibrin membrane for the treatment of dual limb ischemia in an elderly patient: A case report

Rationale:To describe the clinical effects of human umbilical cord mesenchymal stem cells (UCMSCs) combined with allogenic platelet-rich fibrin (PRF) for the treatment of lower limb ischemia in an elderly patient.Patient concerns:The patient was a 93-year-old Chinese woman with bilateral foot gangrene and ulcers lasting for 6 months. She had a prior history of Behcet''s disease.Diagnoses:The admitting diagnosis for this episode was atherosclerosis bilateral limb ischemia.Interventions:First, treatment consisting of immunosuppressants, anticoagulation, antiplatelets, and anti-microbials were instituted. A UCMSC suspension was administered intravenously and injected into the lower limbs twice. An allogenic PRF membrane was externally applied 15 times over the lower limbs.Outcomes:The patient''s pain improved and the 6 ulcers healed.Lessons:The combination of UCMSCs with a PRF membrane for the treatment of lower limb ischemia in an elderly patient is effective and safe. More and larger trials are needed before incorporating this therapy into mainstream treatment.     

Free-floating and spinning thrombus of the basilar artery: A case report

Rationale:Free-floating thrombi in the intracranial artery are rare. We report a case of a free-floating and spinning thrombus caused by turbulent flow distal to the basilar artery stenosis. We compare thrombus changes in a series of images according to time and describe the approach to treatment and thrombosis resolution.</abstract>Patient concerns:A 55-year-old man presented to the emergency department on March 21, 2020, with left-sided weakness, bilateral limb ataxia, and a one-day history of dysarthria. Brain magnetic resonance imaging showed multifocal infarctions in the pons and cerebellum with severe basilar stenosis.Diagnoses:Digital subtraction angiography showed severe focal stenosis. A relatively large oval-shaped mobile thrombus was observed spinning due to turbulent flow at the distal portion of the stenosis.Interventions:We administered a combination antithrombotic regimen of warfarin and clopidogrel for 50 days.Outcomes:No thrombus was observed on the third follow-up digital subtraction angiography.Lessons:No previous study has directly observed a mobile thrombus in the intracranial artery using digital subtraction angiography. We used a combination antithrombotic strategy, which was effective after long-term, rather than short-term, use.     

Clinical Characteristics and Short-Term Outcomes of Patients Presenting with Acute Myocardial Infarction having Multi-vessel disease - A Single Middle- eastern Tertiary-Care Center Experience

ObjectivePatients with multi-vessel coronary artery disease (MVD) compared to single-vessel coronary artery disease (CAD) have more comorbidities and poor in-hospital outcomes. We aim to analyze MVD-AMI patients regarding clinical data and short-term outcomes.MethodsThis is a retrospective analysis of the prospectively collected data registry, a single-center study reviewing the clinical details and hospital outcome measures of AMI patients referred to our center for early revascularization from 2016 to 2019.ResultOut of 3041 patients presented with AMI, 491 (16%) had MVD on coronary angiogram. MVD-AMI patients were older, had a higher prevalence of DM, HTN, and prior history of ischemic heart disease compared to the non- MVD -AMI group (p < 0.001 for all). However, they presented more with non-anterior myocardial infarction, showed higher rates of post-myocardial infarction LV dysfunction, and mortality (p < 0.001). Older MVD-AMI patients showed higher rates of in-hospital morbidities and mortality compared to younger ones (p < 0.001). MVD- AMI women and Middle Eastern patients were older and showed a higher prevalence of cardiovascular risk factors compared to MVD-AMI men and South Asian patient population respectively. There were no significant differences recorded among the different subgroups of MVD-AMI patients regarding the hospital outcome measures.ConclusionOur study highlighted the clinical characters and poor outcomes of a high-risk group of MVD-AMI with different demographic backgrounds. Although age was a strong predictor for in-hospital poor outcomes, neither gender nor ethnicity affected the outcomes in them.     

Phenotype-dependent alteration of pathways and networks reveals a pure synergistic mechanism for compounds treating mouse cerebral ischemia

Aim:

Our previous studies have showed that ursodeoxycholic acid (UA) and jasminoidin (JA) effectively reduce cerebral infarct volume in mice. In this study we explored the pure synergistic mechanism of these compounds in treatment of mouse cerebral ischemia, which was defined as synergistic actions specific for phenotype variations after excluding interference from ineffective compounds.

Methods:

Mice with focal cerebral ischemia were treated with UA, JA or a combination JA and UA (JU). Concha margaritifera (CM) was taken as ineffective compound. Cerebral infarct volume of the mice was determined, and the hippocampi were taken for microarray analysis. Particular signaling pathways and biological functions were enriched based on differentially expressed genes, and corresponding networks were constructed through Ingenuity Pathway Analysis.

Results:

In phenotype analysis, UA, JA, and JU significantly reduced the ischemic infarct volume with JU being superior to UA or JA alone, while CM was ineffective. As a result, 4 pathways enriched in CM were excluded. Core pathways in the phenotype-positive groups (UA or JA) were involved in neuronal homeostasis and neuropathology. JU-contributing pathways included all UA-contributing and the majority (71.7%) of JA-contributing pathways, and 10 new core pathways whose effects included inflammatory immunity, apoptosis and nervous system development. The functions of JU group included all functions of JA group, the majority (93.1%) of UA-contributing functions, and 3 new core functions, which focused on physiological system development and function.

Conclusion:

The pure synergism between UA and JA underlies 10 new core pathways and 3 new core functions, which are involved in inflammation, immune responses, apoptosis and nervous system development.     

The edaravone and 3-n-butylphthalide ring-opening derivative 10b effectively attenuates cerebral ischemia injury in rats

Aim:

Compound 10b is a hybrid molecule of edaravone and a ring-opening derivative of 3-n-butylphthalide (NBP). The aim of this study was to examine the effects of compound 10b on brain damage in rats after focal cerebral ischemia.

Methods:

SD rats were subjected to 2-h-middle cerebral artery occlusion (MCAO). At the onset of reperfusion, the rats were orally treated with NBP (60 mg/kg), edaravone (3 mg/kg), NBP (60 mg/kg)+edaravone (3 mg/kg), or compound 10b (70, 140 mg/kg). The infarct volume, motor behavior deficits, brain water content, histopathological alterations, and activity of GSH, SOD, and MDA were analyzed 24 h after reperfusion. The levels of relevant proteins in the ipsilateral striatum were examined using immunoblotting.

Results:

Administration of compound 10b (70 or 140 mg/kg) significantly reduced the infarct volume and neurological deficits in MCAO rats. The neuroprotective effects of compound 10b were more pronounced compared to NBP, edaravone or NBP+edaravone. Furthermore, compound 10b significantly upregulated the protein levels of the cytoprotective molecules Bcl-2, HO-1, Nrf2, Trx, P-NF-κB p65, and IκB-α, while decreasing the expression of Bax, caspase 3, caspase 9, Txnip, NF-κB p65, and P-IκB-α.

Conclusion:

Oral administration of compound 10b effectively attenuates rat cerebral ischemia injury.     

Assessment of lesion-associated myocardial ischemia based on fusion coronary CT imaging – the FUSE-HEART study: A protocol for non-randomized clinical trial

Introduction:Multimodality assessment of coronary artery lesions has demonstrated superior effectiveness compared to the conventional approach, for assessing both anatomical and functional significance of a coronary stenosis. Multiple imaging modalities can be integrated into a fusion imaging tool to better assess myocardial ischemia.Material and methods:The FUSE-HEART trial is a single center, prospective, cohort study that will assess the impact of a coronary artery stenosis on myocardial function and viability, based on advanced fusion imaging technics derived from Cardiac Computed Tomography Angiography (CCTA). Moreover, the study will investigate the correlation between morphology and composition of the coronary plaques and myocardial ischemia in the territory irrigated by the same coronary artery. At the same time, imaging parameters will be correlated with inflammatory status of the subjects. The trial will include 100 subjects with coronary lesions found on CCTA examination. The study population will be divided into 2 groups: first group will consist of subjects with anatomically significant coronary lesions on native coronary arteries and the second one will include subjects surviving an acute myocardial infarction. The vulnerability score of the subjects will be calculated based on presence of CCTA vulnerability markers of the coronary plaques: napkin ring sign, positive remodeling, spotty calcifications, necrotic core, and low-density plaques. 3D fusion images of the coronary tree will be generated, integrating the images reflecting wall motion with the ones of coronary circulation. The fusion models will establish the correspondence between plaque composition and wall motion in the subtended myocardium of the coronary artery. The study primary outcome will be represented by the rate of major adverse cardiac events related to myocardial ischemia at 1-year post assessment, in correlation with the degree of coronary artery stenosis and myocardial ischemia or viability.The secondary outcomes are represented by the rate of re-hospitalization, rate of survival and rate of major adverse cardiovascular events (including cardiovascular death or stroke), in correlation with the morphology and composition of atheromatous plaques located in a coronary artery, and myocardial ischemia in the territory irrigated by the same coronary artery.Conclusion:In conclusion, FUSE-HEART will be a study based on modern imaging tools that will investigate the impact of a coronary artery stenosis on myocardial function and viability, using advanced fusion imaging technics derived from CCTA, sighting to validate plaque composition and morphology, together with inflammatory biomarkers, as predictors to myocardial viability.     

Valor Prognóstico de Níveis Elevados de Troponina I Isolados em Pacientes sem Síndrome Coronariana Aguda Admitidos no Serviço de Emergência

Background:Although non-ischemic troponin elevation is frequently seen in patients admitted to the emergency department (ED), consensus regarding its management is lacking.Objectives:This study aimed to characterize patients admitted to the ED with non-ischemic troponin elevation and to identify potential mortality predictors in this population.Methods:This retrospective observational study included ED patients with a positive troponin test result between June and July of 2015. Patients with a clinical diagnosis of acute coronary syndrome (ACS) were excluded. Data on patient demographics and clinical and laboratory variables were extracted from medical records. Follow-up data were obtained for 16 months or until death occurred. The statistical significance level was 5%.Results:Troponin elevation without ACS was found in 153 ED patients. The median (IQR) patient age was 78 (19) years, 80 (52.3%) were female and 59(38.6%) died during follow-up. The median (IQR) follow-up period was 477(316) days. Survivors were significantly younger 76 (24) vs. 84 (13) years; p=0.004) and featured a higher proportion of isolated troponin elevation (without creatine kinase or myoglobin elevation) in two consecutive evaluations: 48 (53.9%) vs. 8 (17.4%), p<0.001. Survivors also presented a lower rate of antiplatelet treatment and same-day hospitalization. In the multivariate logistic regression with adjustment for significant variables in the univariate analysis, isolated troponin elevation in two consecutive evaluations showed a hazard ratio= 0.43 (95%CI 0.17–0.96, p=0.039); hospitalization, previous antiplatelet treatment and age remained independently associated with mortality.Conclusions:Isolated troponin elevation in two consecutive measurements was a strong predictor of survival in ED patients with troponin elevation but without ACS.     

Evaluation of myocardial performance index in patients with COVID-19: An echocardiographic follow-up study

Introduction and ObjectivesMyocardial performance may be impaired in cytokine-mediated immune reactions. The myocardial performance index (MPI) is a practical parameter that reflects systolic and diastolic cardiac function. We aimed to assess the MPI in patients with COVID-19.MethodsThe study population consisted of 40 healthy controls and 40 patients diagnosed with COVID-19 who had mild pneumonia and did not need intensive care treatment. All participants underwent echocardiographic examination. First, the MPI and laboratory parameters were compared between healthy controls and patients in the acute period of infection. Second, the MPI and laboratory parameters were compared between the acute infection period and after clinical recovery.ResultsCompared with healthy controls, patients with COVID-19 had a significantly higher MPI (0.56±0.09 vs. 0.41±0.06, p<0.001), longer isovolumic relaxation time (IRT) (112.3±13.4 vs. 90.6±11.2 ms, p<0.001), longer deceleration time (DT) (182.1±30.6 vs. 160.8±42.7 ms, p=0.003), shorter ejection time (ET) (279.6±20.3 vs. 299.6±34.7 ms, p<0.001) and higher E/A ratio (1.53±0.7 vs. 1.21±0.3, p<0.001). Statistically significantly higher MPI (0.56±0.09 vs. 0.44±0.07, p<0.001), longer IRT (112.3±13.4 vs. 91.8±12.1 ms, p<0.001), longer DT (182.1±30.6 vs. 161.5±43.5 ms, p=0.003), shorter ET 279.6±20.3 vs. 298.8±36.8 ms, p<0.001) and higher E/A ratio (1.53±0.7 vs. 1.22±0.4, p<0.001) were observed during the acute infection period than after clinical recovery. Left ventricular ejection fraction was similar in the controls, during the acute infection period and after clinical recovery.ConclusionsSubclinical diastolic impairment without systolic involvement may be observed in patients with COVID-19. This impairment may be reversible on clinical recovery.