Progress and Challenges of Understanding Cardiorenal Syndrome Type 3.

The pathologies of the kidney and heart have instigated a large number of researchers around the world to try to better understand what the exact connectors responsible for the emergence and establishment of these diseases are. The classification of these pathologies into different types of cardiorenal syndromes (CRSs) over the last 15 years has greatly contributed to understanding pathophysiological and diagnostic aspects, as well as treatment strategies. However, with the advent of new technologies classified as "Omics", a new range of knowledge and new possibilities have opened up in order to effectively understand the intermediaries between the kidney-heart axis. The universe of micro-RNAs (miRNAs), epigenetic factors, and components present in extracellular vesicles (EVs) have been protagonists in studying different types of CRSs. Thus, the new challenge that is imposed is to select and link the large amount of information generated from the use of large-scale analysis techniques. The present review seeks to present some of the future perspectives related to understanding CRSs, with an emphasis on CRS type 3.

Accumulating Impact of Smoking and Co-morbidities on Severity and Mortality of COVID-19 Infection: A Systematic Review and Meta-analysis.

Background: High prevalence, severity, and formidable morbidity have marked the recent emergence of the novel coronavirus disease (COVID-19) pandemic. The significant association with the pre-existing co-morbid conditions has increased the disease burden of this global health emergency, pushing the patients, healthcare workers and facilities to the verge of complete disruption. Methods: Meta-analysis of pooled data was undertaken to assess the cumulative risk assessment of multiple co-morbid conditions associated with severe COVID-19. PubMed, Scopus, and Google Scholar were searched from January 1st to June 27th 2020 to generate a well-ordered, analytical, and critical review. The exercise began with keying in requisite keywords, followed by inclusion and exclusion criteria, data extraction, and quality evaluation. The final statistical meta-analysis of the risk factors of critical/severe and non-critical COVID-19 infection was carried out on Microsoft Excel (Ver. 2013), MedCalc (Ver.19.3), and RevMan software (Ver.5.3). Results: We investigated 19 eligible studies, comprising 12037 COVID-19 disease patients, representing the People's Republic of China (PRC), USA, and Europe. 18.2% (n = 2200) of total patients had critical/severe COVID-19 disease. The pooled analysis showed a significant association of COVID-19 disease severity risk with cardiovascular disease (RR: 3.11, p < 0.001), followed by diabetes (RR: 2.06, p < 0.001), hypertension (RR: 1.54, p < 0.001), and smoking (RR: 1.52, p < 006). Conclusion: The review involved a sample size of 12037 COVID-19 patients across a wide geographical distribution. The reviewed reports have focussed on the association of individual risk assessment of co-morbid conditions with the heightened risk of COVID-19 disease. The present meta-analysis of cumulative risk assessment of co-morbidity from cardiovascular disease, diabetes, hypertension, and smoking signals a novel interpretation of inherent risk factors exacerbating COVID-19 disease severity. Consequently, there exists a definite window of opportunity for increasing survival of COVID-19 patients (with high risk and co-morbid conditions) by timely identification and implementation of appropriately suitable treatment modalities.

The cardiovascular complications in COVID-19: Focus on acute cardiac injury.

At the end of 2019 a novel coronavirus was identified in Wuhan, China. The disease caused by the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) was designated COVID-19 (corona virus disease 2019) by the World Health Organization in early 2020. Up to 80% of patients with COVID-19 experience mild symptoms with severe or critical disease occurring in the remaining 20%. Severe disease is manifested by the development of pneumonia, hypoxia and radiographic lung involvement while critical disease indicates multiorgan involvement with significant respiratory or cardiac compromise. The current estimated case fatality rate from COVID-19 is approximately 1%. Epidemiological studies have shown that advanced age, male gender, previous chronic lung disease, cardiovascular and kidney disease, obesity and diabetes are risk factors for the severity of disease course. In the current focused review, we present an overview of the acute cardiovascular complications of COVID-19, their detection and impact upon prognosis.

Gracillin inhibits apoptosis and inflammation induced by lipopolysaccharide (LPS) to alleviate cardiac injury in mice via improving miR-29a.

Sepsis induces critical myocardial dysfunction, resulting in an increased mortality. Gracillin (GRA) is a natural steroidal saponin, showing strong capacities of anti-inflammation, but its pharmacological effects on lipopolysaccharide (LPS)-induced acute cardiac injury still remain unclear. In this study, we attempted to explore if GRA was effective to attenuate cardiac injury in LPS-challenged mice and the underlying mechanisms. First, we found that GRA treatments markedly up-regulated the expression of miR-29a in cardiomyocytes. LPS-induced cytotoxicity in cardiomyocytes was significantly alleviated by GRA treatment, as evidenced by the improved cell viability and reduced lactate dehydrogenase (LDH) release. In addition, LPS-triggered apoptotic cell death was clearly ameliorated in cardiomyocytes co-treated with GRA. Notably, LPS-exposed cells showed significantly reduced expression of miR-29a, while being rescued by GRA treatment. In vivo, LPS apparently impaired cardiac function in mice, which was, however, alleviated by GRA administration. In addition, GRA markedly attenuated apoptosis in hearts of LPS-challenged mice by decreasing the expression of cleaved Caspase-3. LPS-triggered inflammatory response in cardiac tissues was also suppressed by GRA through blocking nuclear factor κB (NF-κB) signaling pathway. We also found that miR-29a expression was highly reduced in hearts of LPS-treated mice but was rescued by GRA pretreatment. Besides, miR-29a mimic alleviated LPS-induced apoptosis and inflammation in cardiomyocytes; however, LPS-caused effects were further accelerated by miR-29a. Of note, the protective effects of GRA on LPS-injured cardiac tissues were significantly abrogated by miR-29a suppression. In conclusion, our findings demonstrated that GRA exerted an effective role against LPS-induced acute cardiac injury through impeding apoptosis and inflammation regulated by miR-29a.

Critical complications of COVID-19: A descriptive meta-analysis study.

The coronavirus disease 2019 (COVID-19) is a novel coronavirus infection that has rapidly spread worldwide, causing a pandemic. The main objective of this meta-analysis was to evaluate the prevalence of the most common symptoms and complications of COVID-19. All relevant studies on the clinical complications of COVID-19 have been identified by searching two web databases (i.e., PubMed and Scopus). Afterward, the relevant data were extracted from the selected studies, and then analyzed by the STATA (Version 14) random-effects model. The 30 studies selected for our meta-analysis covered 6,389 infected patients. The prevalence rates of the most common symptoms were as follows: fever: 84.30% (95% CI: 77.13-90.37; I2 = 97.74%), cough: 63.01% (95% CI: 57.63-68.23; I2 = 93.73%), dyspnea: 37.16% (95% CI: 27.31-47.57%; I2 = 98.32%), fatigue: 34.22% (95% CI: 26.29-42.62; I2 = 97.29%), and diarrhea: 11.47% (95% CI: 6.96-16.87; I2 = 95.58%). Moreover, the most prevalent complications were found to be acute respiratory distress syndrome (ARDS) with 33.15% (95% CI: 23.35-43.73; I2 = 98.56%), arrhythmia with 16.64% (95% CI: 9.34-25.5; I2 = 92.29%), acute cardiac injury with 15.68% (95% CI: 11.1-20.97; I2 = 92.45%), heart failure with 11.50% (95% CI: 3.45-22.83; I2 = 89.48%), and acute kidney injury (AKI) with 9.87% (95% CI: 6.18-14.25; I2 = 95.64%). In this study, we assessed the prevalence of the main clinical complications of COVID-19, and found that following respiratory complications, cardiac and renal complications are the most common clinical complications of COVID-19.

Covid-19 and cardiac involvement in childhood: state of the art.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has rapidly spread worldwide becoming the first pandemic of the 21st century. COVID-19 results in mild symptoms in most infected children but can cause acute cardiac injury and death. In comparison to younger children, teenagers and infants are at higher risk for morbidity and mortality, with particular risk factors including pre-existing conditions like cardiovascular disease. Since this is an emerging infectious disease, there are limited data about the effects of this infection on patients especially in the pediatric population. We summarize here with the data on cardiovascular involvement in children and adolescents.

Remote myocardial injury: the protective role of fluoxetine.

Aortic cross-clamping-induced ischemia-reperfusion (IR) is an important factor in the development of postoperative acute cardiac injury following abdominal aortic surgery. We investigated the possible anti-oxidant/anti-inflammatory effects of fluoxetine (FLX), which is used widely as a preoperative anxiolytic on cardiac injury induced by IR of the infrarenal abdominal aorta. FLX was administered to IR-performed (60 min of ischemia and 120 min of reperfusion) rats for 3 days, once daily at 20 mg/kg i.p. dosage. Results were compared to control and non-FLX-treated IR-performed rats. Serum creatine kinase (CK) and CK-MB levels, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels in the IR group were significantly higher whereas superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels were lower than for the control. IR also increased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 and decreased interleukin-10 levels. FLX decreased CK, CK-MB, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels while increasing superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels. FLX also decreased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels and increased interleukin-10 levels compared to IR. FLX attenuated the morphological changes associated with cardiac injury. Our study clearly demonstrates that FLX confers protection against aortic IR-induced cardiac injury, tissue leucocyte infiltration, and cellular integrity via its anti-oxidant/anti-inflammatory effects.

Importance of evaluation of heart-type fatty acid binding protein (H-FABP) in COVID-19 Patients.

INTRODUCTION: Recent studies have documented the cardiovascular consequences of acute coronavirus disease 2019 (COVID-19), although one of the early cardiac markers that can be used for diagnosis, the heart-type fatty acid-binding protein (H-FABP), has not been covered. Through the evaluation of H-FABP levels, we aim to contribute to the early diagnosis and treatment of cardiac problems in COVID-19 infection patients. METHODOLOGY: Seventy-five patients who were admitted to the emergency department of Mehmet Akif Ersoy Hospital with a complaint of chest pain in the last 6 hours and whose corona PCR tests were positive, were included in our study as the case group and 60 healthy volunteers as the control group. The routine cardiac markers such as creatine kinase MB (CK-MB) cardiac troponin T (cTnT), and H-FABP levels were analyzed by routine laboratory methods. RESULTS: The mean age and gender distributions of the groups did not differ statistically (p > 0.05). CK-MB, cTnT, and H-FABP measurements were statistically different between the groups (p = 0.001; p < 0.01). CONCLUSIONS: The relationship between AMI and COVID-19 with routine cardiac markers is already supported by recent studies. We also evaluated H-FABP levels in our study, as it affects the prognosis of the disease independent of the chronic disease history. At the same time, we showed that H-FABP levels increase earlier than routine cardiac markers, so it will be useful for COVID-19 patients with cardiac complaints.

The Potential Mechanisms Behind Adverse Effect of Coronavirus Disease-19 on Heart and Liver Damage: A Review.

Background: Coronaviruses (CoVs) belong to the RNA viruses family. The viruses in this family are known to cause mild respiratory disease in humans. The origin of the novel SARS-COV2 virus that caused the coronavirus-19 disease (COVID-19) is the Wuhan city in China from where it disseminated to cause a global pandemic. Although lungs are the predominant target organ for Coronavirus Disease-19 (COVID-19), since its outbreak, the disease is known to affect heart, blood vessels, kidney, intestine, liver and brain. This review aimed to summarize the catastrophic impacts of Coronavirus disease-19 on heart and liver along with its mechanisms of pathogenesis. Methods: The information used in this review was obtained from relevant articles published on PubMed, Google Scholar, Google, WHO website, CDC and other sources. Key searching statements and phrases related to COVID-19 were used to retrieve information. Original research articles, review papers, research letters and case reports were used as a source of information. Results: Besides causing severe lung injury, COVID-19 has also been reported to affect and cause dysfunction of many other organs. COVID-19 infection can affect people by downregulating membrane-bound active angiotensin-converting enzyme (ACE). People who have deficient ACE2 expression are more vulnerable to COVID-19 infection. The patients' pre-existing co-morbidities are major risk factors that predispose individuals to severe COVID-19. Conclusion: The disease severity and its broad spectrum phenotype is a result of combined direct and indirect pathogenic factors. Therefore, protocols that harmonize many therapeutic preferences should be the best alternatives to de-escalate the disease and obviate deaths caused as a result of multiple organ damage and dysfunction induced by the disease.

Development of a novel machine learning model based on laboratory and imaging indices to predict acute cardiac injury in cancer patients with COVID-19 infection: a retrospective observational study.

PURPOSE: Due to the increased risk of acute cardiac injury (ACI) and poor prognosis in cancer patients with COVID-19 infection, our aim was to develop a novel and interpretable model for predicting ACI occurrence in cancer patients with COVID-19 infection. METHODS: This retrospective observational study screened 740 cancer patients with COVID-19 infection from December 2022 to April 2023. The least absolute shrinkage and selection operator (LASSO) regression was used for the preliminary screening of the indices. To enhance the model accuracy, we introduced an alpha index to further screen and rank the indices based on their significance. Random forest (RF) was used to construct the prediction model. The Shapley Additive Explanation (SHAP) and Local Interpretable Model-Agnostic Explanation (LIME) methods were utilized to explain the model. RESULTS: According to the inclusion criteria, 201 cancer patients with COVID-19, including 36 variables indices, were included in the analysis. The top eight indices (albumin, lactate dehydrogenase, cystatin C, neutrophil count, creatine kinase isoenzyme, red blood cell distribution width, D-dimer and chest computed tomography) for predicting the occurrence of ACI in cancer patients with COVID-19 infection were included in the RF model. The model achieved an area under curve (AUC) of 0.940, an accuracy of 0.866, a sensitivity of 0.750 and a specificity of 0.900. The calibration curve and decision curve analysis showed good calibration and clinical practicability. SHAP results demonstrated that albumin was the most important index for predicting the occurrence of ACI. LIME results showed that the model could predict the probability of ACI in each cancer patient infected with COVID-19 individually. CONCLUSION: We developed a novel machine-learning model that demonstrates high explainability and accuracy in predicting the occurrence of ACI in cancer patients with COVID-19 infection, using laboratory and imaging indices.

Characteristics of COVID-19 patients with multiorgan injury across the pandemic in a large academic health system in the Bronx, New York.

Purpose: To investigate the evolution of COVID-19 patient characteristics and multiorgan injury across the pandemic. Methods: This retrospective cohort study consisted of 40,387 individuals tested positive for SARS-CoV-2 in the Montefiore Health System in Bronx, NY, between March 2020 and February 2022, of which 11,306 were hospitalized. Creatinine, troponin, and alanine aminotransferase were used to define acute kidney injury (AKI), acute cardiac injury (ACI) and acute liver injury, respectively. Demographics, comorbidities, emergency department visits, hospitalization, intensive care utilization, and mortality were analyzed across the pandemic. Results: COVID-19 positive cases, emergency department visits, hospitalization and mortality rate showed four distinct waves with a large first wave in April 2020, two small (Alpha and Delta) waves, and a large Omicron wave in December 2021. Omicron was more infectious but less lethal (p = 0.05). Among hospitalized COVID-19 patients, age decreased (p = 0.014), female percentage increased (p = 0.023), Hispanic (p = 0.028) and non-Hispanic Black (p = 0.05) percentages decreased, and patients with pre-existing diabetes (p = 0.002) and hypertension (p = 0.04) decreased across the pandemic. More than half (53.1%) of hospitalized patients had major organ injury. Patients with AKI, ACI and its combinations were older, more likely males, had more comorbidities, and consisted more of non-Hispanic Black and Hispanic patients (p = 0.005). Patients with AKI and its combinations had 4-9 times higher adjusted risk of mortality than those without. Conclusions: There were shifts in demographics toward younger age and proportionally more females with COVID-19 across the pandemic. While the overall trend showed improved clinical outcomes, a substantial number of COVID-19 patients developed multi-organ injuries over time. These findings could bring awareness to at-risk patients for long-term organ injuries and help to better inform public policy and outreach initiatives.

The Eye of the Storm: Investigating the Long-Term Cardiovascular Effects of COVID-19 and Variants.

COVID-19 had stormed through the world in early March of 2019, and on 5 May 2023, SARS-CoV-2 was officially declared to no longer be a global health emergency. The rise of new COVID-19 variants XBB.1.5 and XBB.1.16, a product of recombinant variants and sub-strains, has fueled a need for continued surveillance of the pandemic as they have been deemed increasingly infectious. Regardless of the severity of the variant, this has caused an increase in hospitalizations, a strain in resources, and a rise of concern for public health. In addition, there is a growing population of patients experiencing cardiovascular complications as a result of post-acute sequelae of COVID-19. This review aims to focus on what was known about SARS-CoV-2 and its past variants (Alpha, Delta, Omicron) and how the knowledge has grown today with new emerging variants, with an emphasis on cardiovascular complexities. We focus on the possible mechanisms that cause the observations of chronic cardiac conditions seen even after patients have recovered from the infection. Further understanding of these mechanisms will help to close the gap in knowledge on post-acute sequelae of COVID-19 and the differences between the effects of variants.

The Immunology of Takotsubo Syndrome.

Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused by the effects of a sudden catecholamine surge on the heart. Although the majority of patients exhibit prompt recovery of their cardiac dysfunction, TTS remains associated with increased mortality rates acutely and at long-term, and there is currently no cure for TTS. Inflammation has been shown to play a key role in determining outcomes in TTS patients, as well as in the early pathogenesis of the disorder. There are also cases of TTS patients that have been successfully treated with anti-inflammatory therapies, supporting the importance of the inflammatory response in TTS. In this article, we provide a comprehensive review of the available clinical and pre-clinical literature on the immune response in TTS, in an effort to not only better understand the pathophysiology of TTS but also to generate insights on the treatment of patients with this disorder.

Association Between COVID-19 Infection and Cardiac Biomarkers in Hospitalized Patients at a Tertiary Care Center.

Background The effects of coronavirus disease 2019 (COVID-19) on the cardiovascular system are well established. However, knowledge gaps in the clinical implications of cardiac involvement in COVID-19 patients are yet to be addressed. This study aimed to investigate acute cardiac injury (ACI) risk factors and outcomes associated with COVID-19 infection with cardiac involvement. Methodology In this retrospective study, we included hospitalized patients between March 2020 and May 2022 with confirmed COVID-19 infection and evidence of cardiac involvement. Results In total, 501 patients were included, of whom 396 (79%) had evidence of ACI. The median troponin level was 25.8 (interquartile range (IQR) = 10.8-71). Patients with evidence of ACI were significantly more likely to have diabetes mellitus (75% vs. 60%), cardiovascular disease (48% vs. 37%), chronic lung disease (22.2% vs. 12.4%), and chronic kidney disease (32.3% vs. 16.2%). Additionally, patients with ACI were significantly more likely to have cardiomegaly (60.6% vs. 44.8%) and bilateral lobe infiltrates (77.8% vs. 60%) on X-ray. Patients with ACI were significantly more likely to suffer from complications such as cardiogenic shock (5.3% vs. 0%), pneumonia (80.1% vs. 65.7%), sepsis (24.2% vs. 9.5%), and acute respiratory distress syndrome (33.1% vs. 8.6%). Patients with ACI were also significantly more likely to be admitted to the intensive care unit (ICU) (57% vs. 26.7%) and significantly more likely to die (38.1% vs. 11.4%). The results of the multivariate regression analysis indicated that mortality was significantly higher in patients with elevated troponin levels (adjusted odds ratio = 4.73; 95% confidence interval = 2.49-8.98). Conclusions In COVID-19-infected patients, old age, diabetes mellitus, cardiovascular disease, chronic lung disease, and chronic kidney disease were associated with an increased risk of ACI. The presence of ACI in the context of COVID-19 infection was noted to increase the risk for severe complications, such as cardiogenic shock, ICU admission, sepsis, and death.

Urolithin A protects severe acute pancreatitis-associated acute cardiac injury by regulating mitochondrial fatty acid oxidative metabolism in cardiomyocytes.

Severe acute pancreatitis (SAP) often develops into acute cardiac injury (ACI), contributing to the high mortality of SAP. Urolithin A (UA; 3,8-dihydroxy-6H-dibenzopyran-6-one), a natural polyphenolic compound, has been extensively studied and shown to possess significant anti-inflammatory effects. Nevertheless, the specific effects of UA in SAP-associated acute cardiac injury (SACI) have not been definitively elucidated. Here, we investigated the therapeutic role and mechanisms of UA in SACI using transcriptomics and untargeted metabolomics analyses in a mouse model of SACI and in vitro studies. SACI resulted in severely damaged pancreatic and cardiac tissues with myocardial mitochondrial dysfunction and mitochondrial metabolism disorders. UA significantly reduced the levels of lipase, amylase and inflammatory factors, attenuated pathological damage to pancreatic and cardiac tissues, and reduced myocardial cell apoptosis and oxidative stress in SACI. Moreover, UA increased mitochondrial membrane potential and adenosine triphosphate production and restored mitochondrial metabolism, but the efficacy of UA was weakened by the inhibition of CPT1. Therefore, UA can attenuate cardiac mitochondrial dysfunction and reduce myocardial apoptosis by restoring the balance of mitochondrial fatty acid oxidation metabolism. CPT1 may be a potential target. This study has substantial implications for advancing our understanding of the pathogenesis and drug development of SACI.

Relationship between lung injury extent and phenotype manifested in non-contrast CT and cardiac injury during acute stage of COVID-19.

PURPOSE: This study evaluated the diagnostic values of the extent of lung injury manifested in non-contrast enhanced CT (NCCT) images, the inflammatory and immunological biomarkers C-reactive protein (CRP) and lymphocyte for detecting acute cardiac injury (ACI) in patients with COVID-19. The correlations between the NCCT-derived parameters and arterial blood oxygen level were also investigated. METHODS: NCCT lung images and blood tests were obtained in 143 patients with COVID-19 in approximately two weeks after symptom onset, and arterial blood gas measurement was also acquired in 113 (79%) patients. The diagnostic values of normal, moderately and severely abnormal lung parenchyma volume relative to the whole lungs (RVNP, RVMAP, RVSAP, respectively) measured from NCCT images for detecting the heart injury confirmed with high-sensitivity troponin I assay was determined. RESULTS: RVNP, RVMAP and RVSAP exhibited similar accuracy for detecting ACI in COVID-19 patients. RVNP was significantly lower while both RVMAP and RVSAP were significantly higher in the patients with ACI. All of the NCCT-derived parameters exhibited poor linear and non-linear correlations with PaO2 and SaO2. The patients with ACI had a significantly higher CRP level but a lower lymphocyte level compared to the patients without ACI. Combining one of these two biomarkers with any of the three NCCT-derived parameter further improved the accuracy for predicting ACI in patients with COVID-19. CONCLUSION: The NCCT-delineated normal and abnormal lung parenchmyma tissues were statistically significant predictors of ACI in patients with COVID-19, but both exhibited poor correlations with the arterial blood oxygen level. The incremental diagnostic values of lymphocyte and CRP suggested viral infection and inflammation were closely related to the heart injury during the acute stage of COVID-19.

Cardiac complications in patients with COVID-19: a systematic review.

Cardiac complications in patients with COVID-19 have been described in the literature with an important impact on outcome. The primary objective of our systematic review was to describe the kind of cardiac complications observed in COVID-19 patients and to identify potential predictors of cardiovascular events. The secondary aim was to analyze the effect of cardiac complications on outcome.We performed this systematic review according to PRISMA guidelines using several databases for studies evaluating the type of cardiac complications and risk factors in COVID-19 patients. We also calculated the risk ratio (RR) and 95% CI. A random-effects model was applied to analyze the data. The heterogeneity of the retrieved trials was evaluated through the I2 statistic. Our systematic review included 49 studies. Acute cardiac injury was evaluated in 20 articles. Heart failure and cardiogenic shock were reported in 10 articles. Myocardial infarction was evaluated in seven of the papers retrieved. Takotsubo, myocarditis, and pericardial effusion were reported in six, twelve, and five articles, respectively. Arrhythmic complications were evaluated in thirteen studies. Right ventricular dysfunction was evaluated in six articles. We included 7 studies investigating 2115 patients in the meta-analysis. The RR was 0.20 (95% CI: 0.17 to 0.24; P < 0.00001, I2 = 0.75). Acute cardiac injury represented the prevalent cardiac complications observed in COVID-19 patients (from 20 to 45% of the patients). Patients with acute cardiac injury seemed to be significantly older, with comorbidities, more likely to develop complications, and with higher mortality rates. Acute cardiac injury was found to be an independent risk factor for severe forms of SARS-CoV-2 infection and an independent predictor of mortality. Due to the scarce evidence, it was not possible to draw any conclusion regarding Takotsubo, myocarditis, pleural effusion, and right ventricular dysfunction in COVID-19 patients. Noteworthy, possible arrhythmic alterations (incidence rate of arrhythmia from 3 to 60%) in COVID-19 patients have to be taken into account for the possible complications and the consequent hemodynamic instabilities. Hypertension seemed to represent the most common comorbidities in COVID-19 patients (from 30 to 59.8%). The prevalence of cardiovascular disease (CVD) was high in this group of patients (up to 57%), with coronary artery disease in around 10% of the cases. In the majority of the studies retrieved, patients with CVD had a higher prevalence of severe form, ICU admission, and higher mortality rates.

Increasing modified CHA2DS2-VASc risk score is associated with acute cardiac injury in hospitalised COVID-19 patients.

BACKGROUND: Prediction of hospital mortality in patients with COVID-19 by the CHA2DS2VASc (M-CHA2DS2VASc) has been recently shown. Because COVID-19 patients with acute cardiac injury have higher mortality compared to those without, we assumed that this risk score may also predict acute cardiac injury in these patients. METHODS: In this retrospective, single centre cohort study, we included 352 hospitalised patients with laboratory-confirmed COVID-19 and divided into three groups according to M-CHA2DS2VASc risk score which was created by changing gender criteria of the CHA2DS2VASc from female to male (Group 1, score 0-1 (n = 142); group 2, score 2-3 (n = 138) and group 3, score ≥4 (n = 72)). RESULTS: As the M-CHA2DS2VASc risk score increased, acute cardiac injury was also significantly increased (Group 1, 11.3%; group 2, 48.6%; group 3, 76%; p < 0.001). The higher M-CHA2DS2VASc tertile had higher prevalence of arrhythmias compared to lower tertile. The multivariate logistic regression analysis showed that M-CHA2DS2VASc risk score, admission to intensive care unit and invasive mechanical ventilation were independent predictors of acute cardiac injury (p = 0.001, odds ratio 1.675 per scale for M-CHA2DS2VASc). In receiver operating characteristic analysis, M-CHA2DS2VASc risk score was able to predict acute cardiac injury (Area under the curve value for acute cardiac injury was 0.80; p < 0.001). CONCLUSION: Admission M-CHA2DS2VASc risk score was associated with acute cardiac injury in hospitalised patients with COVID-19.

Identification of Crucial Genes and Key Functions in Type 2 Diabetic Hearts by Bioinformatic Analysis.

Type 2 diabetes (T2D) patients with SARS-CoV-2 infection hospitalized develop an acute cardiovascular syndrome. It is urgent to elucidate underlying mechanisms associated with the acute cardiac injury in T2D hearts. We performed bioinformatic analysis on the expression profiles of public datasets to identify the pathogenic and prognostic genes in T2D hearts. Cardiac RNA-sequencing datasets from db/db or BKS mice (GSE161931) were updated to NCBI-Gene Expression Omnibus (NCBI-GEO), and used for the transcriptomics analyses with public datasets from NCBI-GEO of autopsy heart specimens with COVID-19 (5/6 with T2D, GSE150316), or dead healthy persons (GSE133054). Differentially expressed genes (DEGs) and overlapping homologous DEGs among the three datasets were identified using DESeq2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were conducted for event enrichment through clusterProfile. The protein-protein interaction (PPI) network of DEGs was established and visualized by Cytoscape. The transcriptions and functions of crucial genes were further validated in db/db hearts. In total, 542 up-regulated and 485 down-regulated DEGs in mice, and 811 up-regulated and 1399 down-regulated DEGs in human were identified, respectively. There were 74 overlapping homologous DEGs among all datasets. Mitochondria inner membrane and serine-type endopeptidase activity were further identified as the top-10 GO events for overlapping DEGs. Cardiac CAPNS1 (calpain small subunit 1) was the unique crucial gene shared by both enriched events. Its transcriptional level significantly increased in T2D mice, but surprisingly decreased in T2D patients with SARS-CoV-2 infection. PPI network was constructed with 30 interactions in overlapping DEGs, including CAPNS1. The substrates Junctophilin2 (Jp2), Tnni3, and Mybpc3 in cardiac calpain/CAPNS1 pathway showed less transcriptional change, although Capns1 increased in transcription in db/db mice. Instead, cytoplasmic JP2 significantly reduced and its hydrolyzed product JP2NT exhibited nuclear translocation in myocardium. This study suggests CAPNS1 is a crucial gene in T2D hearts. Its transcriptional upregulation leads to calpain/CAPNS1-associated JP2 hydrolysis and JP2NT nuclear translocation. Therefore, attenuated cardiac CAPNS1 transcription in T2D patients with SARS-CoV-2 infection highlights a novel target in adverse prognostics and comprehensive therapy. CAPNS1 can also be explored for the molecular signaling involving the onset, progression and prognostic in T2D patients with SARS-CoV-2 infection.

Impact of congestive heart failure and role of cardiac biomarkers in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been reported to cause worse outcomes in patients with underlying cardiovascular disease, especially in patients with acute cardiac injury, which is determined by elevated levels of high-sensitivity troponin. There is a paucity of data on the impact of congestive heart failure (CHF) on outcomes in COVID-19 patients. METHODS: We conducted a literature search of PubMed/Medline, EMBASE, and Google Scholar databases from 11/1/2019 till 06/07/2020, and identified all relevant studies reporting cardiovascular comorbidities, cardiac biomarkers, disease severity, and survival. Pooled data from the selected studies was used for metanalysis to identify the impact of risk factors and cardiac biomarker elevation on disease severity and/or mortality. RESULTS: We collected pooled data on 5967 COVID-19 patients from 20 individual studies. We found that both non-survivors and those with severe disease had an increased risk of acute cardiac injury and cardiac arrhythmias, our pooled relative risk (RR) was - 8.52 (95% CI 3.63-19.98) (p < 0.001); and 3.61 (95% CI 2.03-6.43) (p = 0.001), respectively. Mean difference in the levels of Troponin-I, CK-MB, and NT-proBNP was higher in deceased and severely infected patients. The RR of in-hospital mortality was 2.35 (95% CI 1.18-4.70) (p = 0.022) and 1.52 (95% CI 1.12-2.05) (p = 0.008) among patients who had pre-existing CHF and hypertension, respectively. CONCLUSION: Cardiac involvement in COVID-19 infection appears to significantly adversely impact patient prognosis and survival. Pre-existence of CHF, and high cardiac biomarkers like NT-pro BNP and CK-MB levels in COVID-19 patients correlates with worse outcomes.