MicroRNAs distribution in different phenotypes of Aortic Stenosis.

Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern. Circulating micro RNAs may reflect specific pathophysiological processes and could be useful biomarkers to identify disease. We assessed 80 patients (81, 76.7-84 years; 46, 57.5%females) with severe AVS. We performed bio-humoral evaluation (including circulating miRNA-1, 21, 29, 133) and 2D-echocardiography. Patients were classified according to ACC/AHA groups (D1-D3) and flow-gradient classification, considering normal/low flow, (NF/LF) and normal/high gradient, (NG/HG). Patients with reduced ejection fractionwere characterized by higher levels of miRNA1 (p = 0.003) and miRNA 133 (p = 0.03). LF condition was associated with higher levels of miRNA1 (p = 0.02) and miRNA21 (p = 0.02). Levels of miRNA21 were increased in patients with reduced Global longitudinal strain (p = 0.03). LF-HG and LF-LG showed higher levels of miRNA1 expression (p = 0.005). At one-year follow-up miRNA21 and miRNA29 levels resulted significant independent predictors of reverse remodeling and systolic function increase, respectively. Different phenotypes of AVS may express differential levels and types of miRNAs, which may retain a pathophysiological role in pro-hypertrophic and pro-fibrotic processes.

Three-Dimensional Echographic Evaluation of Carotid Artery Disease.

The introduction of three-dimensional echography (3D echo) in vascular field is not recent, but it still remains a seldom-used technique because of the costs of ultrasound probe and the need of dedicated laboratories. Therefore, despite significant prognostic implications, the high diagnostic accuracy in plaque definition, and the relative ease of use, 3D echo in vascular field is a niche technique. The purpose of this review is mainly clinical and intends to demonstrate the potential strength of a 3D approach, including technical aspects, in order to present to clinicians and imagers the appealing aspects of a noninvasive and radiation-free methodology with relevant diagnostic and prognostic correlates in the assessment of carotid atherosclerosis. A comprehensive literature search (since 1990s to date) using the PubMed, MEDLINE, and Cochrane libraries databases has been conducted. Articles written in English have been assessed, including reviews, clinical trials, meta-analyses, and interventional/observational studies. Manual cross-referencing was also performed, and relevant references from selected articles were reviewed. The search was limited to studies conducted in humans. Search terms, retrieved also with PubMed Advanced search and AND/OR Boolean operators (mainly in title and abstract), included three-dimensional, echo, stroke/transient ischemic attack, predictors, carotid, imaging, and biomarkers.

Critical Limb Ischemia: A Practical Up-To-Date Review.

Critical limb ischemia (CLI) is the most advanced form of peripheral artery disease. It is associated with significant morbidity and mortality and high management costs. It carries a high risk of amputation and local infection. Moreover, cardiovascular complications remain a major concern. Although it is a well-known entity and new technological and therapeutic advances have been made, this condition remains poorly addressed, with significantly heterogeneous management, especially in nonexperienced centers. This review, from a third-level dedicated inpatient and outpatient cardioangiology structure, aims to provide an updated summary on the topic of CLI of its complexity, encompassing epidemiological, social, economical and, in particular, diagnostic/imaging issues, together with potential therapeutic strategies (medical, endovascular, and surgical), including the evaluation of cardiovascular risk factors, the diagnosis, and treatment together with prognostic stratification.

Impact of empagliflozin on subclinical left ventricular dysfunctions and on the mechanisms involved in myocardial disease progression in type 2 diabetes: rationale and design of the EMPA-HEART trial.

BACKGROUND: Asymptomatic left ventricular (LV) dysfunction is highly prevalent in type 2 diabetes patients. Unlike the other hypoglycemic drugs, SGLT2 inhibitors have shown potential benefits for reducing cardiovascular death and risk factors, aside from lowering plasma glucose levels. With this study we aim at determining whether the treatment with empagliflozin is associated with an improvement in LV functions in diabetic patients with asymptomatic LV dysfunction against Sitagliptin, which is presumably neutral on myocardial function. To determine changes in LV systolic and diastolic functions we will use speckle-tracking echocardiography, a novel sensitive, non-invasive, bedside method allowing the calculation of LV global longitudinal strain (GLS), an index of myocardial deformability, as well as 3D echocardiography, which allows a better evaluation of LV volumes and mass. METHODS: The EMPA-HEART trial will be a phase III, open label, active-controlled, parallel groups, single centre, exploratory study conducted in Pisa, Italy. A cohort of 75 diabetic patients with normal LV systolic (2D-Echo EF > 50%) and renal (eGFR sec MDRD > 60 ml/min/1.73 mq) functions and no evidence of valvular and/or ischemic heart disease will be randomized to either Empagliflozin 10 mg/die or Sitagliptin 100 mg/die. The primary outcome is to detect a change in GLS from baseline to 1 and 6 months after treatment initiation. The secondary outcomes include changes from baseline to 6 months in 3-D Echocardiography EF, left atrial volume and E/E', VO2max as measured at cardiopulmonary test, cardiac autonomic function tests (R-R interval during Valsalva manoeuvre, deep-breathing, lying-to-standing), and the determination of a set of plasma biomarkers aimed at studying volume, inflammation, oxidative stress, matrix remodelling, myocyte strain and injury. DISCUSSION: SGLT2 inhibitors might affect myocardial functions through mechanisms acting both directly and indirectly on the myocardium. The set of instrumental and biohumoral tests of our study might actually detect the presence and entity of empagliflozin beneficial effects on the myocardium and shed light on the mechanisms involved. Further, this study might eventually provide information to design a clinical strategy, based on echocardiography and/or biomarkers, to select the patients who might benefit more from this intervention. Trial registration EUDRACT Code 2016-0022250-10.

The integrated value of sST2 and global longitudinal strain in the early stratification of patients with severe aortic valve stenosis: a translational imaging approach.

Aortic valve stenosis (AVS) is associated with significant myocardial fibrosis (MF). Global longitudinal strain (GLS) is a sensible indicator of systolic dysfunction. ST2 is a member of the interleukin (IL)-1 receptor family and a modulator of hypertrophic and fibrotic responses. We aimed at assessing: (a) the association between adverse LV remodeling, LV functional parameters (including GLS) and sST2 level. (b) The association between MF (detected by endo-myocardial biopsy) and sST2 in patients with AVS undergoing surgical valve replacement. Twenty-two patients with severe AVS and preserved EF underwent aortic valve replacement. They performed laboratory analysis, including serum ST2 (sST2), echocardiography and inter-ventricular septum biopsy to assess MF (%). We included ten controls for comparison. Compared to controls, patients showed higher sST2 levels (p < 0.0001). sST2 showed correlation with Age (r = 0.58; p = 0.0004), E/e' average (r = 0.58; p = 0.0007), GLS (r = 0.61; p = 0.0002), LAVi (r = 0.51; p = 0.003), LVMi (r = 0.43; p = 0.01), sPAP (r = 0.36; p = 0.04) and SVi (r = -0.47; p < 0.005). No correlation was found between MF and sST2. At ROC analysis, a sST2 ≥ 284 ng/mL had the best accuracy to discriminate controls from patients with impaired GLS, i.e. GLS ≤ 17% (AUC 0.80; p = 0.003; sensitivity 95%; specificity 83%) and increased E/e' average (AUC 0.87; p = 0.0001; sensitivity 96%; specificity 74%). At multivariate regression analysis GLS resulted the only independent predictor of sST2 levels (R2 = 0.35; p =  0.0004). Patients with severe AVS present elevated sST2 levels. LV GLS resulted the only independent predictor of sST2 levels.

Incremental prognostic value of a complex left ventricular remodeling classification in asymptomatic for heart failure hypertensive patients.

We evaluated the prognostic impact of a complex remodeling classification (CRC) in asymptomatic patients with arterial hypertension (AH). We retrospectively included 749 hypertensive patients (female 325, 43.4% age 62 ± 11.3 years) in Stages A and B of heart failure. CRC was evaluated including indexed left ventricular mass, end-diastolic volume, and relative wall thickness. After 45-month follow-up, we considered a composite endpoint: total mortality, myocardial infarction, myocardial revascularization, cerebrovascular events, and acute pulmonary edema. Blood pressure was controlled in 265 patients (35.4%), 317 (42.3%) were in Grade 1 of AH, 123 (16.4%) in Grade 2, and 44 (5.9%) in Grade 3. Considering CRC, 292 patients (38%) presented normal/physiological hypertrophy, 102 (13.6%) concentric remodeling, 29 (3.9%) eccentric remodeling, 157 (21%) concentric hypertrophy, 11 (1.5%) mixed hypertrophy, 52 (6.9%) dilated hypertrophy, and 36 (4.8%) eccentric hypertrophy. We observed a total of 73 events (9.7%). Kaplan-Meier method demonstrated a significant different survival in CRC-derived classes (P < .001). Cox regression demonstrated CRC as independent predictor (P = .01), after adjusting for age, gender, diabetes mellitus, grade of hypertension, antihypertensive therapy, stable ischemic heart disease, obesity, systolic and diastolic dysfunction, and classic remodeling classification. In asymptomatic patients with AH, CRC is an independent predictor of poor outcome.

Review in Translational Cardiology: MicroRNAs and Myocardial Fibrosis in Aortic Valve Stenosis, a Deep Insight on Left Ventricular Remodeling.

MicroRNAs (miRNAs) are a huge class of noncoding RNAs that regulate protein-encoding genes (degradation/inhibition of translation). miRNAs are nowadays recognized as regulators of biological processes underneath cardiovascular disorders including hypertrophy, ischemia, arrhythmias, and valvular disease. In particular, circulating miRNAs are promising biomarkers of pathology. This review gives an overview of studies in aortic valve stenosis (AS), exclusively considering myocardial remodeling processes. We searched through literature (till September 2016), all studies and reviews involving miRNAs and AS (myocardial compartment). Although at the beginning of a new era, clear evidences exist on the potential diagnostic and prognostic implementation of miRNAs in the clinical setting. In particular, for AS, miRNAs are modulators of myocardial remodeling and hypertrophy. In our experience, here presented in summary, the principal findings of our research were a confirm of the pathophysiological role in AS of miRNA-21, in particular, the interdependence between textural miRNA-21 and fibrogenic stimulus induced by an abnormal left ventricular pressure overload. Moreover, circulating miRNA-21 (biomarker) levels are able to reflect the presence of significant myocardial fibrosis (MF). Thus, the combined evaluation of miRNA-21, a marker of MF, and hypertrophy, together with advanced echocardiographic imaging (two-dimensional speckle tracking), could fulfill many existing gaps, renewing older guidelines paradigms, also allowing a better risk prognostic and diagnostic strategies.