Effect of empagliflozin on left ventricular contractility and peak oxygen uptake in subjects with type 2 diabetes without heart disease: results of the EMPA-HEART trial.

BACKGROUND: The mechanism through which sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent the incidence of heart failure and/or affect cardiac structure and function remains unclear. METHODS: The EMPA-HEART trial is aimed at verifying whether empagliflozin improves myocardial contractility (left ventricle global longitudinal strain, LV-GLS) and/or cardiopulmonary fitness (peak oxygen uptake, VO2peak) in subjects with type 2 diabetes (T2D) without heart disease. Patients with T2D, normal LV systolic function (2D-Echo EF > 50%), and no heart disease were randomized to either empagliflozin 10 mg or sitagliptin 100 mg for 6 months and underwent repeated cardiopulmonary exercise tests with echocardiography and determination of plasma biomarkers. RESULTS: Forty-four patients completed the study, 22 per arm. Despite comparable glycaemic control, modest reductions in body weight (- 1.6; [- 2.7/- 0.5] kg, p = 0.03) and plasma uric acid (- 1.5; [- 2.3/- 0.6], p = 0.002), as well as an increase in haemoglobin (+ 0.7; [+ 0.2/+ 1.1] g/dL, p = 0.0003) were evident with empagliflozin. No difference was detectable in either LV-GLS at 1 month (empagliflozin vs sitagliptin: + 0.44; [- 0.10/+ 0.98]%, p = 0.11) and 6 months of therapy (+ 0.53; [- 0.56/+ 1.62]%), or in VO2peak (+ 0.43; [- 1.4/+ 2.3] mL/min/kg, p = 0.65). With empagliflozin, the subgroup with baseline LV-GLS below the median experienced a greater increase (time*drug p < 0.05) in LV-GLS at 1 month (+ 1.22; [+ 0.31/+ 2.13]%) and 6 months (+ 2.05; [+ 1.14/+ 2.96]%), while sitagliptin induced a modest improvement in LV-GLS only at 6 months (+ 0.92; [+ 0.21/+ 0.62]%). CONCLUSIONS: Empagliflozin has neutral impact on both LV-GLS and exercise tolerance in subjects with T2D and normal left ventricular function. However, in patients with subclinical dysfunction (LV-GLS < 16.5%) it produces a rapid and sustained amelioration of LV contractility. Trial registration EUDRACT Code 2016-002225-10.

Interactive role of diastolic dysfunction and ventricular remodeling in asymptomatic subjects at increased risk of heart failure.

Diastolic dysfunction (DD) and left ventricular remodeling (LVR) characterize patients at risk for heart failure (HF). To assess the prognostic impact of different diastolic function algorithms and a complex LVR classification (CRC) in asymptomatic subjects with preserved ejection fraction (EF) at risk for HF. We analyzed 1923 asymptomatic patients (male 43%; age 57, 33-76 years) with at least one cardiovascular risk factor and preserved (> 50%) EF. We used three algorithms for LV diastolic function assessment (Paulus et al. in Eur Heart J 28(20):2539-2550, 2007; Nagueh et al. in J Am Soc Echocardiogr 22(2):107-133, 2009, Eur Heart J Cardiovasc Imaging 17(12):1321-1360, 2016), and two algorithms for LVR (classic and CRC). We considered a composite end-point: cardiac death and hospitalization for HF. The highest presence of DD was diagnosed by Nagueh 2009 (211, 11%), while the prevalence according to Nagueh 2016 (63 patients, 3.2%) turned out to be the lowest (p < 0.001 vs the other algorithms). According to CRC, 780 (48.6%) patients had normal or physiologic hypertrophy, 298 (15.5%) concentric remodeling, 85 (4.4%) eccentric remodeling, 294 (15.3%) concentric hypertrophy, 39 (2%) mixed hypertrophy, 80 (4.1%) dilated hypertrophy, 73 (3.7%) eccentric hypertrophy and 294 (15.3%) were unclassifiable. After 39-month follow-up (261 events, 13.6%), Cox-regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification) identified CRC (p = 0.01) and Nagueh 2016 (p < 0.001) as independent predictors of end-point. The coexistence of an adverse LVR by CRC and DD by Nagueh 2016 was associated with the worst prognosis. A concurrent structural (CRC) and functional (Nagueh Op. Cit) analysis improves prognostic stratification in asymptomatic subjects at risk for HF with preserved EF.

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.

Prognostic Value of a Tissue Doppler Index of Systodiastolic Function in Patients with Asymptomatic Heart Failure.

INTRODUCTION: Doppler echocardiography with early diastolic transmitral velocity (E)/early mitral annular diastolic velocity (E') ratio has been proposed as the best predictor for evaluating left ventricle (LV) filling pressure. A dimensionless index E/(E' × S') ratio (S' = systolic mitral annulus velocity) resulted in readily, reproducible, and reliable predictor of LV filling pressure. We assessed the prognostic impact of E/E' × S') in patients with asymptomatic heart failure (HF). MATERIALS AND METHODS: We calculated E/(E' × S') in 337 patients (179 male, 53%; age 54.7 ± 13.7 years) using the average of septal and lateral mitral annular velocities. We considered a composite endpoint as follows: all-cause death, acute myocardial infarction, stroke, and HF exacerbation. RESULTS: Baseline ejection fraction resulted 60.2 ± 11.8%; E/E' × S') was 1.45 ± 0.8, with S' 7.4 ± 2.4 cm/s and E/E' 9.5 ± 5.4. After a 22-month median follow-up, there were 42 events: 5 deaths (12%), 3 acute myocardial infarctions (7%), 1 stroke (2%), and 33 HF hospitalizations (79%). In patients reaching the composite endpoint, E/(E' × S') resulted 2.07 ± 1.1 versus 1.3 ± 0.7 in event-free population (P < 0.001). In a Cox-regression analysis, adjusted for confounding clinical factors and conventional echo parameters, E/(E' × S') (P < 0.001), age (P < 0.001), and male gender (P = 0.03) resulted independent predictors of the composite endpoint. CONCLUSIONS: E/(E' × S') was an independent predictor for the future cardiac events in asymptomatic HF.

Three-dimensional full automated software in the evaluation of the left ventricle function: from theory to clinical practice.

Left ventricular systolic function evaluation is an essential part of all transthoracic echocardiographic (TTE) studies. 3D echocardiography (3DE) is superior to 2D and is recommended as the method of choice. However, since it is time consuming and requires training, it is rarely performed. Different automatic analysis software tries to overcome these limitations but they need to be accurate and reproducible before they can be used clinically. The aim of this study was to test the accuracy and reproducibility of new 3D automatic quantitative software in everyday clinical practice. 69 patients referred to our Echo Lab for a clinically indicated echocardiographic examination were included. All patients underwent a full TTE with 3D image acquisition. Left ventricular volumes and ejection fraction (LVEF) were obtained using Heart Model software, and compared with conventional 3D volumetric data. Automated analysis was performed using three different sliders setting, with or without regional editing if necessary. 20 patients underwent a cardiac magnetic resonance (CMR) study the same day of the echo and automated measurements were also compared with a CMR reference. Intra- and inter-technique comparisons including linear regression with Pearson correlation coefficients and Bland-Altman analyses were calculated. Mean age of the patients was 59 years, with 49.3% male. The automated 3DE model demonstrated excellent correlation with the conventional 3DE measurements of LVEF, using three different sliders settings (r = 0.906; r = 0.898 and r = 0.940). Correlations with CMR values were very good as well (r = 0.888; r = 0.869; r = 0.913). Similarly, no significant differences were noted between the values of EDV and ESV, measured with the automated model or CMR, with excellent correlation (EDV: r = 0.892, r = 0.842, 0.910; ESV: r = 0.925, r = 0.860, r = 0.907). Finally, volumes calculated with the automated software were significantly greater than those obtained manually, but they showed a very good correlation (EDV: r = 0.875, r = 0.856, r = 0.891; ESV: r = 0.929, r = 0.879, r = 949). 3D automatic software for LV quantification is feasible and shows excellent correlations with both CMR and 3D echocardiography, considered the gold standard. No clinically relevant differences were noted when applying different border settings. This technique holds promise to facilitate the integration of 3D TTE into clinical practice.

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.

[Amiodarone-induced thyrotoxicosis]. / Tireotossicosi indotta da amiodarone.

Amiodarone-induced thyroid dysfunction occurs in about 15-20% of patients under amiodarone therapy. Amiodarone-induced hypothyroidism (AIH) can develop in patients with an apparently normal thyroid gland or in those with an underlying chronic autoimmune thyroiditis. On a clinical ground, AIH is not challenging and can be easily treated with L-thyroxine therapy. Amiodarone-induced thyrotoxicosis (AIT) can occur in patients with (AIT 1) or without (AIT 2) an underlying thyroid disease. AIT 1 is a true iodine-induced hyperthyroidism occurring in patients with an underlying thyroid autonomy while AIT 2 is a drug-induced destructive thyroiditis. According to the different pathogenetic mechanism, AIT 2 is treated with glucocorticoids while AIT 1 usually responds to thionamides. Thyroidectomy should be considered when AIT represents an imminent risk for cardiac conditions, when patients require a prompt resolution of thyrotoxicosis or when they do not respond to the medical therapy. An effective collaboration between cardiologists and endocrinologists is crucial in each part of the management of AIT patients, including the evaluation of cardiological conditions with regard to thyroid hormone excess and whether, or not, it is necessary to continue amiodarone therapy.

Left ventricular stiffness predicts outcome in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

OBJECTIVES: Assessment of the prognostic role of left ventricular stiffness (LVS) in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS: We performed a complete two-dimensional transthoracic echocardiographic study before and after TAVI in patients with severe AS at high surgical risk. In order to assess LVS, we measured LV end-diastolic pressure (EDP) invasively during TAVI and LV end-diastolic volume (EDV) by means of echocardiography. We defined LVS as the EDV indexed by body surface area at an EDP of 20 mm Hg (EDVI20 ). Our aim was to assess the impact of LVS on one-year all-cause mortality after TAVI. RESULTS: One hundred sixty-six patients undergoing TAVI (64% female; mean age 82.7 ± 5.1 years) were enrolled. Seven patients died within the first 30 days after TAVI and 21 within 1 year. Overall follow-up duration was 580 ± 478 days. At multivariate analysis, independent predictors of 1-year all-cause mortality were moderate-to-severe paravalvular leak (PVL; HR 4.7, 95% confidence interval [CI] 1.9-11, P=.0003), female gender (HR 3.5, 95% CI 1.0-12, P=.045), and EDVI20 (HR 0.94, 95% CI 0.90-0.98, P=.015). In particular, patients with higher LVS (EDVI20 ≤48 mL/m2 ) had a 1-year mortality of 26.9% vs 7.4% in patients with lower LVS (EDVI20 >48 mL/m2 ; HR 4.2, 95% CI 1.6-10.6, P=.0007). Patients with higher LVS who developed moderate-to-severe PVL had the worst outcome (incremental chi-square test, P=.014). CONCLUSION: In patients with AS, an increased LVS has a negative prognostic impact. Development of significant PVL in patients with higher LVS had an incremental adverse effect.

Classification and Prognostic Evaluation of Left Ventricular Remodeling in Patients With Asymptomatic Heart Failure.

Patients with asymptomatic heart failure (HF; stage A and B) are characterized by maladaptive left ventricular (LV) remodeling. Classic 4-group classification of remodeling considers only LV mass index and relative wall thickness as variables. Complex remodeling classification (CRC) includes also LV end-diastolic volume index. Main aim was to assess the prognostic impact of CRC in stage A and B HF. A total of 1,750 asymptomatic subjects underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors. LV dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated, together with LV remodeling. We considered a composite end point: all-cause death, myocardial infarction, coronary revascularizations, cerebrovascular events, and acute pulmonary edema. CRC was suitable for 1,729 patients (men 53.6%; age 58.3 ± 13 years). Two hundred thirty-eight patients presented systolic dysfunction (ejection fraction <50%) and 483 diastolic dysfunction. According to the CRC, 891 patients were normals or presented with physiologic hypertrophy, 273 concentric remodeling, 47 eccentric remodeling, 350 concentric hypertrophy, 29 mixed hypertrophy, 86 dilated hypertrophy, and 53 eccentric hypertrophy. Age and gender distribution was noticed (p <0.001). After a median follow-up of 21 months, Kaplan-Meier analysis showed different survival distribution (p <0.001) of the CRC patterns. In multivariate Cox regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification, systolic, and diastolic dysfunction), CRC was independent predictor of primary end point (p = 0.044, hazard ratio 1.101, 95% CI 1.003 to 1.21), confirmed in a logistic regression (p <0.03). In conclusion, CRC could help physicians in prognostic stratification of patients in stage A and B HF.

Disease activity and lifestyle influence comorbidities and cardiovascular events in patients with acromegaly.

OBJECTIVE: The primary objective of this study is to identify the predictors of comorbidities and major adverse cardiovascular events (MACE) that can develop after diagnosis of acromegaly. The role of therapy for acromegaly in the event of such complications was also evaluated. DESIGN AND METHODS: Retrospective cohort study was conducted on 200 consecutive acromegalic patients in a tertiary referral center. The following outcomes were evaluated: diabetes, hypertension and MACE. Each patient was included in the analysis of a specific outcome, unless they were affected when acromegaly was diagnosed, and further classified as follows: (i) in remission after adenomectomy (Hx), (ii) controlled by somatostatin analogues (SSA) (SSAc) or (iii) not controlled by SSA (SSAnc). Data were evaluated using Cox regression analysis. RESULTS: After diagnosis of acromegaly, diabetes occurred in 40.8% of patients. The SSAnc group had a three-fold higher risk of diabetes (HR: 3.32, P = 0.006), whereas the SSAc group had a 1.4-fold higher risk of diabetes (HR: 1.43, P = 0.38) compared with the Hx group. Hypertension occurred in 35.5% of patients, after diagnosis. The determinants of hypertension were age (HR: 1.06, P = 0.01) and BMI (HR: 1.05, P = 0.01). MACE occurred in 11.8% of patients, after diagnosis. Age (HR: 1.09, P = 0.005) and smoking habit (HR: 5.95, P = 0.01) were predictors of MACE. Conversely, therapy for acromegaly did not influence hypertension or MACE. CONCLUSION: After diagnosis of acromegaly, control of the disease (irrespective of the type of treatment) and lifestyle are predictors of comorbidities and major adverse cardiovascular events.

Micro-RNA-21 (biomarker) and global longitudinal strain (functional marker) in detection of myocardial fibrotic burden in severe aortic valve stenosis: a pilot study.

AIMS: Myocardial fibrosis (MF) is a deleterious consequence of aortic valve stenosis (AVS). Global longitudinal strain (GLS) is a novel left ventricular (LV) functional parameter potentially useful to non-invasively estimate MF. MicroRNAs (miRNAs) are non-coding small ribonucleic acids (RNA) modulating genes function, mainly through RNA degradation. miRNA-21 is a biomarker associated with MF in pressure overload. The aim of the present study was to find an integrated algorithm for detection of MF using a combined approach with both bio- and functional markers. METHODS: Thirty-six patients (75.2 ± 8 y.o.; 63 % Female) with severe AVS and preserved LV ejection fraction (EF), candidate to surgical aortic valve replacement (sAVR) were enrolled. Clinical, bio-humoral evaluation (including plasmatic miRNA-21 collected using specific tubes, PAXgene, for stabilization of peripheral RNA) and a complete echocardiographic study, including GLS and septal strain, were performed before sAVR. Twenty-eight of those patients underwent sAVR and, in 23 of them, an inter-ventricular septum biopsy was performed. Tissues were fixed in formalin and embedded in paraffin. Sections were stained with Hematoxylin and Eosin for histological evaluation and with histochemical Masson trichrome for collagen fibers. The different components were calculated and expressed as micrometers(2). To evaluate tissue miRNA components, sections 2-µm thick were cut using a microtome blade for each slide. Regression analysis was performed to test association between dependent variable and various predictors included in the model. RESULTS: Despite a preserved EF (66 ± 11 %), patients presented altered myocardial deformation parameters (GLS -14,02 ± 3.8 %; septal longitudinal strain, SSL -9.63 ± 2.9 %; septal longitudinal strain rate, SL-Sr -0.58 ± 0.17 1/s; Septal Longitudinal early-diastolic strain rate, SL-SrE 0.62 ± 0.32 1/s). The extent of MF showed an inverse association with both GLS and septal longitudinal deformation indices (GLS: R(2) = 0.30; p = 0.02; SSL: R(2) = 0.36; p = 0.01; SL-Sr: R(2) = 0.39; p < 0.001; SL-SrE: R(2) = 0.35; p = 0.001). miRNA-21 was mainly expressed in fibrous tissue (p < 0.0001). A significant association between MF and plasmatic miRNA-21, alone and weighted for measures of structural (LVMi R(2) = 0.50; p = 0.0005) and functional (SSL R(2) = 0.35; p = 0.006) remodeling, was found. CONCLUSIONS: In AVS, MF is associated with alterations of regional and global strain. Plasmatic miRNA-21 is directly related to MF and associated with LV structural and functional impairment.

Prevalence and Prognostic Impact of Metabolic Syndrome in Asymptomatic (Stage A and B Heart Failure) Patients.

BACKGROUND: Metabolic syndrome (MS) has an increased risk of cardiovascular events. Its relationship with asymptomatic left ventricular dysfunction (LVD) and prognosis has not been completely clarified. OBJECTIVES: To determine, in asymptomatic patients (Stage A, B heart failure, HF), whether MS is associated with left ventricular systolic dysfunction (LVSD) and left ventricular diastolic dysfunction and its predictive role for cardiovascular events. MATERIALS AND METHODS: We included 1920 nonconsecutive patients without symptoms of HF, with at least one cardiovascular risk factor, undergoing echocardiographic evaluation as preventive screening. We subdivided the study population according to the presence (Group 1) or absence (Group 2) of MS. The primary endpoint was a composite of cardiac death, myocardial infarction, coronary artery revascularization, stroke, and acute pulmonary edema. Secondary endpoints were hospitalization for HF and HF progression. RESULTS: Overall prevalence of MS was 13.4% (n = 262, Group 1). In Group 2 (n = 1658), the prevalence of LVSD was 12.2%, while the prevalence of LVSD was 21.8% in Group 1 (relative risk [RR] 2.01; 95% confidence interval 1.4-2.8; P < 0.001). Adjusting for age and gender, MS resulted an independent predictor of LVSD (P < 0.001). After a median follow-up of 22 months, Group 1 patients had a significantly higher incidence of primary events (P < 0.001), including cardiac death (P = 0.04), and secondary events (P < 0.001). Both primary and secondary endpoints were more frequent in patients with LVSD (P < 0.001). In multivariate survival analysis, MS (but not its specific components) and LVSD were independently associated both with primary and secondary events (P ≤ 0.003). Incremental chi-square analysis showed the presence of combined LVD added to MS, and age raised significantly the predictive value of the model for the primary endpoint (Incremental chi-square = 8.6). CONCLUSIONS: In stage A and B HF subjects, the coexistence of MS with functional or structural cardiac abnormalities, detected by echocardiography, showed a significant incremental value in predicting clinical cardiovascular events.

Non-invasive one-point carotid wave intensity in a large group of healthy subjects: A ventricular-arterial coupling parameter.

The analysis of wave intensity (WI) evaluates the working condition of the heart interacting with the arterial system. WI in normal subjects has two peaks, the first (W 1) reflects left ventricle (LV) contractile performance, the second (W 2) is related to the ability of the LV to actively stop aortic blood flow. The aim of the study was to investigate the reference values of W 1 and W 2 in a group of apparently healthy subjects through a radiofrequency-based system. 680 subjects (388 men mean age 43.0 ± 17.4 years, range 16-92; 292 women mean age 44.8 ± 17.7 years, range 16-86) were enrolled and underwent physical examination, blood pressure (BP) and heart rate (HR) measurements and comprehensive transthoracic echocardiogram was performed. Measurement of local WI was obtained at the level of the left common carotid artery before the bifurcation, using a high definition echo-tracking system. W 1 was (12.37 ± 6.89) × 10(3) and (9.76 ± 4.8) × 10(3) mmHg m/s(3), p < 0.0001; W 2 was (3.21 ± 1.81) × 10(3) and (2.98 ± 1.69) × 10(3) mmHg m/s(3), p = ns in men and women, respectively. The cohort was divided into 5 age groups (ages 16-29; 30-39; 40-49; 50-59; >60) and stratified by gender. After adjustment for height, systolic BP and HR, W 1 decreased with age (p < 0.0001 in men and p = 0.026 in women for trend) while no relation was found for W 2. Multivariable regression analysis using age, gender, height, systolic BP, HR, ejection fraction and stroke volume indexed by body surface are predicted W 1 and age, systolic BP, HR and E/A as a measure of diastolic function, predicted W 2. Inter and intra-observer variability and feasibility of WI analysis were satisfactory. We reported the values and their clinical correlations of the two peaks (W 1 and W 2) of WI, a non-invasive hemodynamic index for assessing ventricular-arterial coupling in a large group of apparently healthy subjects.