Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.

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COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives.

The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.

Biomarkers associated with COVID-19 disease progression.

Background and purpose The objective of our systematic review is to identify prognostic factors that may be used in decision-making related to the care of patients infected with COVID-19. Data sources We conducted highly sensitive searches in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase. The searches covered the period from the inception date of each database until April 28, 2020. No study design, publication status or language restriction were applied. Study selection and data extraction We included studies that assessed patients with confirmed or suspected SARS-CoV-2 infectious disease and examined one or more prognostic factors for mortality or disease severity. Reviewers working in pairs independently screened studies for eligibility, extracted data and assessed the risk of bias. We performed meta-analyses and used GRADE to assess the certainty of the evidence for each prognostic factor and outcome. Results We included 207 studies and found high or moderate certainty that the following 49 variables provide valuable prognostic information on mortality and/or severe disease in patients with COVID-19 infectious disease: Demographic factors (age, male sex, smoking), patient history factors (comorbidities, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, cardiovascular disease, cardiac arrhythmia, arterial hypertension, diabetes, dementia, cancer and dyslipidemia), physical examination factors (respiratory failure, low blood pressure, hypoxemia, tachycardia, dyspnea, anorexia, tachypnea, haemoptysis, abdominal pain, fatigue, fever and myalgia or arthralgia), laboratory factors (high blood procalcitonin, myocardial injury markers, high blood White Blood Cell count (WBC), high blood lactate, low blood platelet count, plasma creatinine increase, high blood D-dimer, high blood lactate dehydrogenase (LDH), high blood C-reactive protein (CRP), decrease in lymphocyte count, high blood aspartate aminotransferase (AST), decrease in blood albumin, high blood interleukin-6 (IL-6), high blood neutrophil count, high blood B-type natriuretic peptide (BNP), high blood urea nitrogen (BUN), high blood creatine kinase (CK), high blood bilirubin and high erythrocyte sedimentation rate (ESR)), radiological factors (consolidative infiltrate and pleural effusion) and high SOFA score (sequential organ failure assessment score). Conclusion Identified prognostic factors can help clinicians and policy makers in tailoring management strategies for patients with COVID-19 infectious disease while researchers can utilise our findings to develop multivariable prognostic models that could eventually facilitate decision-making and improve patient important outcomes. Systematic review registration Prospero registration number: CRD42020178802. Protocol available at: https://www.medrxiv.org/content/10.1101/2020.04.08.20056598v1.

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Prognostic Factors for Severity and Mortality in Patients Infected with COVID-19: A Systematic Review

Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study.

Rationale: Initial reports of case fatality rates (CFRs) among adults with coronavirus disease (COVID-19) receiving invasive mechanical ventilation (IMV) are highly variable.Objectives: To examine the CFR of patients with COVID-19 receiving IMV.Methods: Two authors independently searched PubMed, Embase, medRxiv, bioRxiv, the COVID-19 living systematic review, and national registry databases. The primary outcome was the "reported CFR" for patients with confirmed COVID-19 requiring IMV. "Definitive hospital CFR" for patients with outcomes at hospital discharge was also investigated. Finally, CFR was analyzed by patient age, geographic region, and study quality on the basis of the Newcastle-Ottawa Scale.Measurements and Results: Sixty-nine studies were included, describing 57,420 adult patients with COVID-19 who received IMV. Overall reported CFR was estimated as 45% (95% confidence interval [CI], 39-52%). Fifty-four of 69 studies stated whether hospital outcomes were available but provided a definitive hospital outcome on only 13,120 (22.8%) of the total IMV patient population. Among studies in which age-stratified CFR was available, pooled CFR estimates ranged from 47.9% (95% CI, 46.4-49.4%) in younger patients (age ≤40 yr) to 84.4% (95% CI, 83.3-85.4%) in older patients (age >80 yr). CFR was also higher in early COVID-19 epicenters. Overall heterogeneity is high (I2 >90%), with nonsignificant Egger's regression test suggesting no publication bias.Conclusions: Almost half of patients with COVID-19 receiving IMV died based on the reported CFR, but variable CFR reporting methods resulted in a wide range of CFRs between studies. The reported CFR was higher in older patients and in early pandemic epicenters, which may be influenced by limited ICU resources. Reporting of definitive outcomes on all patients would facilitate comparisons between studies.Systematic review registered with PROSPERO (CRD42020186997).

Case Fatality Rates for Patients with COVID-19 Requiring Invasive Mechanical Ventilation. A Meta-analysis.

Three-dimensional printing of left atrial appendage from echo images helps planning left atrial appendage occlusion

A 56-year-old male patient with a long history of hypertension and diabetes was admitted to our hospital because of lumbar spinal stenosis. In the preoperative routine echocardiogram, the basal inferior wall of the left ventricle was observed to have reduced wall thickness and bulged outwards (Fig. 1a). The size of the bulging wall was 40× 30 mm. It showed synchronization with normal myocardial contraction at echocardiogram and the left ventricular ejection fraction (LVEF) was normal. As the patient did not have a relevant history of coronary artery lesions, it was highly suggestive of a congenital left ventricular diverticulum. Coronary angiography showed severe stenosis of the proximal left anterior descending coronary artery and total occlusion of the distal left circumflex coronary artery and the right circumflex coronary artery (Fig. 1b) (see video, Supplemental digital content 1, http://links.lww.com/MCA/A18). Left ventricular angiography showed that the inferior wall protruded outward 39× 28 mm (Fig. 1c) (see video, Supplemental digital content 2, http://links.lww.com/MCA/A19). On the basis of the evidence of severe coronary artery disease, it was considered an aneurysm after myocardial infarction. Because the wide neck of the left ventricular wall protruded outward and as there was no history of heart rupture, a diagnosis of a true aneurysm, instead of pseudoaneurysm, was made. The patient underwent left ventricular aneurysm resection, left ventricular plasty, and coronary artery bypass grafting. During the surgery, the bulging wall showed a clear boundary with normal myocardium and the regional wall was thin with a hard property, smooth intima, and a few myocardial tissues (Fig. 2a), unlike a true aneurysm, which has a soft texture and an ambiguous boundary with adjacent myocardium. Therefore, it was considered a left ventricular diverticulum during the operation. The H&E staining showed considerable fibrous tissue and thrombus, only a few myocardial cells, and vasa vasorum in the bulging wall tissues (Fig. 2b).

A bulging left ventricular wall in three-vessel coronary artery disease: true aneurysm, pseudoaneurysm, or diverticulum?

Continous renal replacement theraphy (CRRT) is a strategy of clinical treatment in critically ill patients. Due to the complex of CRRT and variety of patients′ condition, establishment of a feasible and standardized protocol to ensure CRRT practice is needed urgently. The protocolized care includes four steps. First, assessing the indication of CRRT; Second, CRRT prescription; Third, monitoring management and parameters adjustment, and Fourth, evaluating the optimal weaning timing of CRRT. In order to carry out the protocolized care of CRRT in clinical practice, we should follow the these four steps strictly based on patients′ condition. This standardized CRRT protocol will further make continuously quality improvement of homogeneous management.


Key words: 
Continuous renal replacement theraphy; Protocolized care CRRT prescrption; Indication; Contraindication; Timing; Modality; Dose; Parameter of treatment; Anticoagulation; Fluid management; Monitoring

Protocolized care for continuous renal replacement theraphy

GW29-e1165 The predictive value of intra-left atrial mechanical delay for 1-year recurrence of atrial fibrillation after catheter ablation: a clinical follow-up study using dual Doppler echocardiography

Objective
To evaluate the effect of ultrasound guided via chest puncture injection and ultrasound targeted microbubble destruction(UTMD)-mediated the angiogenin 1 (Ang1) gene therapy in myocardial infarction (MI) canines.


Methods
Thirty-nine dogs were divided into three groups (each group 13 dogs): ①MI group (MI dogs without treatment); ②intravenous injection group (MI dogs with intravenous injection and UTMD treatment); ③myocardial injection group (MI dogs with myocardial injection and UTMD treatment). Four weeks later, the safety and incidence of complications were compared. The dimensions and systolic function of left ventricular were measured by echocardiography. The percentage of collagen fiber was assessed by Masson.CD31 was applied for quantifying capillary density. The Ang1 protein was detected by Western blotting.


Results
①The survival and complications showed no significant difference among the 3 groups(all P>0.05). ②Compared with MI group, the left ventricular end-systolic dimension (LVESD)reduced and the left ventricular ejection fraction (LVEF) increased in intravenous injection group; the left ventricular end-diastolic dimension(LVEDD)and LVESD were both reduced in myocardial injection group, the LVEF was increased significantly(all P<0.05). ③The immunohistochemistry showed lower collagen fiber percentage and higher blood vessel density in myocardial injection group than those in the other groups(P<0.05). ④The relative quantity of Ang1 was significantly higher in myocardial injection group than those of the other groups. The differences were statistically significant (P<0.05).


Conclusions
The combination of ultrasound guided via chest puncture injection and UTMD is a safe and effective method for gene transfection. It mediates Ang1 gene transfection that can promote angiogenesis after MI and improve left ventricular systolic function.


Key words: 
Sonication; Myocardial injection; Gene transfection; Myocardial infarction

The effect of ultrasound guided via chest puncture injection and ultrasound targeted microbubble destruction-mediated the Ang1 gene therapy in myocardial infarction canines

Bo Hu

Papers

Three-dimensional printing of left atrial appendage from echo images helps planning left atrial appendage occlusion

A bulging left ventricular wall in three-vessel coronary artery disease: true aneurysm, pseudoaneurysm, or diverticulum?

Protocolized care for continuous renal replacement theraphy

GW29-e1165 The predictive value of intra-left atrial mechanical delay for 1-year recurrence of atrial fibrillation after catheter ablation: a clinical follow-up study using dual Doppler echocardiography

The effect of ultrasound guided via chest puncture injection and ultrasound targeted microbubble destruction-mediated the Ang1 gene therapy in myocardial infarction canines