A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries. This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition. Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients. Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly. This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2. The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction. And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition. The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2.

Low-density lipoprotein cholesterol (LDL-C) is considered one of the leading risk factors for cardiovascular disorders, primarily owing to its causal relationship with atherosclerotic cardiovascular disease (ASCVD).^1,2 High LDL-C levels are estimated to cause up to 4.3 million deaths annually, accounting for 7.7% of deaths worldwide.³ Thus, LDL-C has been robustly proven to be a treatment target in randomized clinical trials. Lipid-lowering treatments, especially statins, have been widely applied as basic clinical strategies for primary and secondary prevention of ASCVD.⁴

Sudden death could be the first symptom of patients with arrhythmogenic cardiomyopathy (AC), a disease for which clinical indicators predicting adverse progression remain lacking. Recent findings suggest that metabolic dysregulation is present in AC. We performed this study to identify metabolic indicators that predicted major adverse cardiac events (MACEs) in patients with AC and their relatives. Comparing explanted hearts from patients with AC and healthy donors, we identified deregulated metabolic pathways using quantitative proteomics. Right ventricles (RVs) from patients with AC displayed elevated ketone metabolic enzymes, OXCT1 and HMGCS2, suggesting higher ketone metabolism in AC RVs. Analysis of matched coronary artery and sinus plasma suggested potential ketone body synthesis at early-stage AC, which was validated using patient-derived induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) in vitro. Targeted metabolomics analysis in RVs from end-stage AC revealed a “burned-out” state, with predominant medium-chain fatty acid rather than ketone body utilization. In an independent validation cohort, 65 probands with mostly non–heart failure manifestations of AC had higher plasma β-hydroxybutyrate (β-OHB) than 62 healthy volunteers (P < 0.001). Probands with AC with MACE had higher β-OHB than those without MACE (P < 0.001). Among 94 relatives of probands, higher plasma β-OHB distinguished 25 relatives having suspected AC from nonaffected relatives. This study demonstrates that elevated plasma β-OHB predicts MACE in probands and disease progression in patients with AC and their clinically asymptomatic relatives.

Aims: Arrhythmogenic cardiomyopathy (AC) shows large heterogeneity in its clinical, genetic, and pathological presentation. This study aims to provide a comprehensive atlas of end-stage AC and illustrate the relationships among clinical characteristics, genotype, and pathological profiles of patients with this disease. Methods and results: We collected 60 explanted AC hearts and performed standard pathology examinations. The clinical characteristics of patients, their genotype and cardiac magnetic resonance imaging findings were assessed along with pathological characteristics. Masson staining of six representative sections of each heart were performed. Digital pathology combined with image segmentation was developed to calculate distribution of myocardium, fibrosis, and adipose tissue. An unsupervised clustering based on fibrofatty distribution containing four subtypes was constructed. Patients in Cluster 1 mainly carried desmosomal mutations (except for desmoplakin) and were subjected to transplantation at early age; this group was consistent with classical ‘desmosomal cardiomyopathy’. Cluster 2 mostly had non-desmosomal mutations and showed regional fibrofatty replacement in right ventricle. Patients in Cluster 3 showed parallel progression, and included patients with desmoplakin mutations. Cluster 4 is typical left-dominant AC, although the genetic background of these patients is not yet clear. Multivariate regression analysis revealed precordial QRS voltage as an independent indicator of the residual myocardium of right ventricle, which was validated in predicting death and transplant events in the validation cohort (n = 92). Conclusion: This study provides a novel classification of AC with distinct genetic backgrounds indicating different potential pathogenesis. Cluster 1 is distinct in genotype and clinicopathology and can be defined as ‘desmosomal cardiomyopathy’. Precordial QRS amplitude is an independent indicator reflecting the right ventricular remodelling, which may be able to predict transplant/death events for AC patients.

MicroRNAs (miRNAs) are non-coding RNAs that function as regulators of gene expression and thereby contribute to the complex disease phenotypes. Hypertrophic cardiomyopathy (HCM) and Dilated cardiomyopathy (DCM) can cause sudden cardiac death and eventually develop into heart failure. However, they have different clinical and pathophysiological phenotype and the expressional spectrum of miRNAs in left ventricles of HCM and DCM has never been compared before. This study selected 30 human left ventricular heart samples belonged to three diagnostic groups (Control, HCM, DCM). Each group has ten samples. Based on previous findings, the expression of 13 different microRNAs involving heart failure and hypertrophy (miR-1-3p, miR-10b, miR-21, miR-23a, miR-27a, miR-29a, miR-133a-3p, miR-142-3p, miR-155, miR-199a-3p, miR-199a-5p, miR-214, miR-497) was measured. 17 HCM patients were included as second group to validate the associations. We found miR-155, miR-10b and miR-23a were highly expressed in both HCM and DCM compared with control. MiR-214 was downregulated and miR-21 was upregulated in DCM but not in HCM. We also identified miR-1-3p and miR-27a expressed significantly different between HCM and DCM and both miRNAs downregulated in HCM. And only miR-1-3p correlated with left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) that reflected the cardiac function in HCM. A second HCM group also confirmed this correlation. We then predicted Chloride voltage-gated channel 3 (Clcn3) as a direct target gene of miR-1-3p using bioinformatics tools and confirmed it by Luciferase reporter assay. Our data demonstrated that different cardiomyopathies had unique miRNA expression pattern. And the expression levels of miR-1-3p and miR-27a had disease-specificity and sensitivity in HCM, whereas only miR-1-3p was significantly associated with left ventricular function in HCM identifying it as a potential target to improve the cardiac function in end-stage HCM. We also provide Clcn3 as a direct target of miR-1-3p which sheds light on the mechanism of HCM.