Search

Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL (p ≤ 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification.

BackgroundCardiovascular complication in patients affected by novel Coronavirus respiratory disease (COVID-19) are increasingly recognized. However, although a cardiac tropism of SARS-CoV-2 for inflammatory cells in autopsy heart samples of COVID-19 patients has been reported, the presence of the virus in cardiomyocytes has not been documented yet.MethodsWe investigated for SARS-CoV-2 presence in heart tissue autopsies of 6 consecutive COVID-19 patients deceased for respiratory failure showing no signs of cardiac involvement and with no history of heart disease. Cardiac autopsy samples were analysed by digital PCR, Western blot, immunohistochemistry, immunofluorescence, RNAScope, and transmission electron microscopy assays.ResultsThe presence of SARS-CoV-2 into cardiomyocytes was invariably detected. A variable pattern of cardiomyocytes injury was observed, spanning from the absence of cell death and subcellular alterations hallmarks to the intracellular oedema and sarcomere ruptures. In addition, we found active viral transcription in cardiomyocytes, by detecting both sense and antisense SARS-CoV-2 spike RNA.ConclusionsIn this analysis of autopsy cases, the presence of SARS-CoV-2 into cardiomyocytes, determining variable patterns of intracellular involvement, has been documented. All these findings suggest the need of a cardiologic surveillance even in survived COVID-19 patients not displaying a cardiac phenotype, in order to monitor potential long-term cardiac sequelae.

Aims: Aortic valve sclerosis (AVSc), a non-uniform thickening of leaflets with an unrestricted opening, is characterized by inflammation, lipoprotein deposition, and matrix degradation. In the general population, AVSc predicts long-term cardiovascular mortality (+50%) even after adjustment for vascular risk factors and clinical atherosclerosis. We have hypothesized that AVSc is a risk-multiplier able to predict even short-term mortality. To address this issue, we retrospectively analyzed 90-day mortality of all patients who underwent isolated coronary artery bypass grafting (CABG) at Centro Cardiologico Monzino over a ten-year period (2006&ndash, 2016). Methods: We analyzed 2246 patients and 90-day all-cause mortality was 1.5% (31 deaths). We selected only patients deceased from cardiac causes (n = 29) and compared to alive patients (n = 2215). A cardiologist classified the aortic valve as no-AVSc (n = 1352) or AVSc (n = 892). Cox linear regression and integrated discrimination improvement (IDI) analyses were used to evaluate AVSc in predicting 90-day mortality. Results: AVSc 90-day survival (97.6%) was lower than in no-AVSc (99.4%, p &lt, 0.0001) with a hazard ratio (HR) of 4.0 (95%CI: 1.78, 9.05, 0.0001). The HR for AVSc, adjusted for propensity score, was 2.7 (95%CI: 1.17, 6.23, p = 0.02) and IDI statistics confirmed that AVSc significantly adds (p &lt, 0.001) to the identification of high-risk patients than EuroSCORE II alone. Conclusion: Our data supports the hypothesis that a risk stratification strategy based on AVSc, added to ESII, may allow better recognition of patients at high-risk of short-term mortality after isolated surgical myocardial revascularization. Results from this study warrant further confirmation.