Three-Dimensional Combined Atrioventricular Coupling Index-A Novel Prognostic Marker in Dilated Cardiomyopathy.

Atrioventricular coupling has recently emerged as an outcome predictor. Our aim was to assess, through three-dimensional (3D) echocardiography, the role of the left atrioventricular coupling index (LACI), right atrioventricular coupling index (RACI) and a novel combined atrioventricular coupling index (CACI) in a cohort of patients with dilated cardiomyopathy (DCM). One hundred twenty-one consecutive patients with DCM underwent comprehensive 3D echocardiographic acquisitions. LACI was defined as the ratio between left atrial and left ventricular 3D end-diastolic volumes. RACI was defined as the ratio between right atrial and right ventricular 3D end-diastolic volumes. CACI was defined as the sum of LACI and RACI. Patients were prospectively followed for death, heart transplant, nonfatal cardiac arrest and hospitalization for heart failure. Fifty-five patients reached the endpoint. All three coupling indices were significantly more impaired in patients with events, with CACI showing the highest area under the curve (AUC = 0.66, p = 0.003). All three indices were independent outcome predictors when tested in multivariable Cox regression (HR = 2.62, p = 0.01 for LACI; HR = 2.58, p = 0.004 for RACI; HR = 2.37, p = 0.01 for CACI), but only CACI showed an incremental prognostic power over traditional risk factors such as age, left ventricular strain, right ventricular strain and mitral regurgitation severity (likelihood ratio χ2 test = 28.2, p = 0.03). CACI assessed through 3D echocardiography, reflecting both left and right atrioventricular coupling, is an independent predictor of adverse events in DCM, yielding an incremental prognostic power over traditional risk factors.

Left Ventricular-Arterial Coupling as an Independent Predictor of Adverse Events in Young Patients with ST Elevation Myocardial Infarction-A 3D Echocardiographic Study.

Left ventricular-arterial coupling (VAC) is a key determinant of global cardiovascular performance, calculated as the ratio between arterial elastance (EA) and left ventricular end-systolic elastance (EES). Over the years, acute myocardial infarction (STEMI) has remained an important cause of morbidity and mortality worldwide. Although, until recently, it was considered a disease occurring mostly in older patients, its prevalence in the young population is continuously rising. In this study, we aimed to investigate the role of 3D VAC and its derived indices in predicting adverse outcomes in young patients with STEMI. We prospectively enrolled 84 young patients (18-51 years) with STEMI who underwent primary PCI and 28 healthy age and sex-matched controls. A 3D echocardiography was used for non-invasive measurements of end-systolic elastance (EES), arterial elastance (EA), and VAC (EA/EES). The occurrence of major adverse cardiac events (MACE) was assessed one year after the index STEMI. Out of 84 patients, 15.4% had adverse events at 12 months follow-up. Patients were divided into two groups according to the presence or absence of MACE. There were no significant differences in arterial elastance between the two groups. EA was higher in the MACE group but without statistical significance (2.65 vs. 2.33; p = 0.09). EES was significantly lower in the MACE group (1.25 ± 0.34 vs. 1.91 ± 0.56. p < 0.0001) and VAC was higher (2.2 ± 0.62 vs. 1.24 ± 0.29, p < 0.0001). ROC analysis showed that VAC has a better predictive value for MACE (AUC 0.927) compared with EA or EEA but also compared with a classical determinant of LV function (LVEF and LVGLS). A VAC value over 1.71 predicts unfavourable outcome with 83.3% sensitivity and 97.1% specificity. In both univariate and multivariate COX regression analysis, VAC remained an independent predictor for MACE and demonstrated incremental prognostic value over LVEF and LVGLS in the proposed statistical models. In conclusion, 3D VAC is an independent predictor of adverse events in young patients with STEMI at a 12 month follow-ups and could be used for a more accurate risk stratification in the acute phase.

Increasing clinical impact and microbiological difficulties in diagnosing coagulase-negative staphylococci in infective endocarditis - a review starting from a series of cases.

Coagulase-negative staphylococci (CoNS) are an emergent aetiology of infective endocarditis (IE) on native valves in previously healthy individuals, its presence is associated with prosthetic valves or with other cardiac implants. The identification of CoNS in cultures was customarily seen as contamination, but more recent epidemiological studies have revealed an increasing number of causative and virulent new CoNS species. Starting from two clinical cases of community-acquired CoNS IE on native valves, the review debates the difficulties in identifying CoNS as the causal pathogens, comprising differentiation of contamination from infection in IE, alongside the challenges raised by antibiotic resistance. Even if the risk of CoNS IE is more increased in subjects with prosthetic materials or other foreign devices and immunodeficiencies, native valve infections with these staphylococci are increasing and should be considered important pathogens in IE. Despite the lack of sensitive and specific tools to correctly differentiate contamination from infection in CoNS endocarditis, a comprehensive evaluation with clinical and paraclinical data accurately succeeds in establishing the diagnosis. The genetic profile of CoNS predisposes to antibiotic multi-resistance, making the treatment of IE challenging; the rapid identification of antibiotic susceptibility is essential to prescribe the appropriate therapy and improve outcomes.

miR-146a-5p, miR-223-3p and miR-142-3p as Potential Predictors of Major Adverse Cardiac Events in Young Patients with Acute ST Elevation Myocardial Infarction-Added Value over Left Ventricular Myocardial Work Indices.

Acute ST elevation myocardial infarction (STEMI) remains a leading cause of morbidity and mortality worldwide despite continuous advances in diagnostic, prognostic and therapeutic methods. Myocardial work (MW) indices and miRNAs have both emerged as potential prognostic markers in acute coronary syndromes in recent years. In this study we aim to assess the prognostic role of myocardial work indices and of a group of miRNAs in young patients with STEMI. We enrolled 50 young patients (<55 years) with STEMI who underwent primary PCI and 10 healthy age-matched controls. We performed standard 2D and 3D echocardiography; we also calculated left ventricular global longitudinal strain (GLS) and the derived myocardial work indices. Using RT-PCR we determined the plasmatic levels of six miRNAs: miR-223-3p, miR-142-3p, miR-146a-5p, miR-125a-5p, miR-486-5p and miR-155-5p. We assessed the occurrence of major adverse cardiac events (MACE) at up to one year after STEMI. Out of 50 patients, 18% experienced MACE at the one-year follow-up. In a Cox univariate logistic regression analysis, myocardial work indices were all significantly associated with MACE. The ROC analysis showed that GWI, GCW and GWE as a group have a better predictive value for MACE than each separately (AUC 0.951, p = 0.000). Patients with higher miRNAs values at baseline (miR-223-3p, miR-142-3p and miR-146a-5p) appear to have a higher probability of developing adverse events at 12 months of follow-up. ROC curves outlined for each variable confirmed their good predictive value (AUC = 0.832, p = 0.002 for miR-223-3p; AUC = 0.732, p = 0.031 for miR-142-3p and AUC = 0.848, p = 0.001 for miR-146a-5p); the group of three miRNAs also proved to have a better predictive value for MACE together than separately (AUC = 0.862). Moreover, adding each of the miRNAs (miR-233, miR-142-3p and miR-146a-5p) or all together over the myocardial work indices in the regression models improved their prognostic value. In conclusion, both myocardial work indices (GWI, GCW and GWE) and three miRNAs (miR-223-3p, miR-142-3p and miR-146a-5p) have the potential to be used as prognostic markers for adverse events after acute myocardial infarction. The combination of miRNAs and MW indices (measured at baseline) rather than each separately has very good predictive value for MACE in young STEMI patients (C-statistic 0.977).

IL-6, IL-1RA and Resistin as Predictors of Left Ventricular Remodelling and Major Adverse Cardiac Events in Patients with Acute ST Elevation Myocardial Infarction.

Despite continuous advances in diagnostic and therapeutic methods, acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. Considering the role of inflammation in AMI etiopathogenesis, we aimed to explore the role of a group of three inflammatory cytokines (IL-1RA, IL-6 and resistin) as an independent prognostic factor for LVR assessed by 3D echocardiography and MACE in patients with STEMI. We enrolled 41 patients with STEMI who underwent primary PCI. We assessed the occurrence of LVR (defined as an increase of over 20% in end-diastolic left ventricular volume at 6 months compared with baseline values) and MACE. Using the enzyme-linked immunosorbent assays (ELISA) method, we measured plasmatic levels of IL-6, IL-1RA and resistin (within 48 h after AMI and at 6 months). Out of 41 STEMI patients, 20.5% presented signs of LVR at follow up, and in 24.4%, MACE occurred. In univariate logistic regression analysis, baseline levels of IL-6 (OR = 1.042, p = 0.004), IL-1RA (OR = 1.004, p = 0.05) and resistin (OR = 1.7, p = 0.007) were all significantly associated with LVR. ROC analysis showed that the three cytokines as a group (AUC 0.946, p = 0.000) have a better predictive value for LVR than any individual cytokine. The group of cytokines also proved to have a better predictive value for MACE together than separately (AUC = 0.875, p = 0.000 for ROC regression model). IL-6, IL-1RA and resistin plasma levels at baseline have a good predictive value both as independent variables and also as a group for the development of adverse LVR and MACE at 6 months follow up after STEMI.

MicroRNAs in Acute ST Elevation Myocardial Infarction-A New Tool for Diagnosis and Prognosis: Therapeutic Implications.

Despite diagnostic and therapeutic advances, coronary artery disease and especially its extreme manifestation, ST elevation myocardial infarction (STEMI), remain the leading causes of morbidity and mortality worldwide. Early and prompt diagnosis is of great importance regarding the prognosis of STEMI patients. In recent years, microRNAs (miRNAs) have emerged as promising tools involved in many pathophysiological processes in various fields, including cardiovascular diseases. In acute coronary syndromes (ACS), circulating levels of miRNAs are significantly elevated, as an indicator of cardiac damage, making them a promising marker for early diagnosis of myocardial infarction. They also have prognostic value and great potential as therapeutic targets considering their key function in gene regulation. This review aims to summarize current information about miRNAs and their role as diagnostic, prognostic and therapeutic targets in STEMI patients.

Exploring the Continuum of Hypertrophic Cardiomyopathy-From DNA to Clinical Expression.

The concepts underlying hypertrophic cardiomyopathy (HCM) pathogenesis have evolved greatly over the last 60 years since the pioneering work of the British pathologist Donald Teare, presenting the autopsy findings of "asymmetric hypertrophy of the heart in young adults". Advances in human genome analysis and cardiac imaging techniques have enriched our understanding of the complex architecture of the malady and shaped the way we perceive the illness continuum. Presently, HCM is acknowledged as "a disease of the sarcomere", where the relationship between genotype and phenotype is not straightforward but subject to various genetic and nongenetic influences. The focus of this review is to discuss key aspects related to molecular mechanisms and imaging aspects that have prompted genotype-phenotype correlations, which will hopefully empower patient-tailored health interventions.

The Winding Road of Cardiac Regeneration-Stem Cell Omics in the Spotlight.

Despite significant progress in treating ischemic cardiac disease and succeeding heart failure, there is still an unmet need to develop effective therapeutic strategies given the persistent high-mortality rate. Advances in stem cell biology hold great promise for regenerative medicine, particularly for cardiac regeneration. Various cell types have been used both in preclinical and clinical studies to repair the injured heart, either directly or indirectly. Transplanted cells may act in an autocrine and/or paracrine manner to improve the myocyte survival and migration of remote and/or resident stem cells to the site of injury. Still, the molecular mechanisms regulating cardiac protection and repair are poorly understood. Stem cell fate is directed by multifaceted interactions between genetic, epigenetic, transcriptional, and post-transcriptional mechanisms. Decoding stem cells' "panomic" data would provide a comprehensive picture of the underlying mechanisms, resulting in patient-tailored therapy. This review offers a critical analysis of omics data in relation to stem cell survival and differentiation. Additionally, the emerging role of stem cell-derived exosomes as "cell-free" therapy is debated. Last but not least, we discuss the challenges to retrieve and analyze the huge amount of publicly available omics data.