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Aims  Increased shedding of extracellular vesicles (EVs)—small, lipid bilayer-delimited particles with a role in paracrine signalling—has been associated with human pathologies, e.g. atherosclerosis, but whether this is true for cardiac diseases is unknown. Methods and results  Here, we used the surface antigen CD172a as a specific marker of cardiomyocyte (CM)-derived EVs; the CM origin of CD172a+ EVs was supported by their content of cardiac-specific proteins and heart-enriched microRNAs. We found that patients with aortic stenosis, ischaemic heart disease, or cardiomyopathy had higher circulating CD172a+ cardiac EV counts than did healthy subjects. Cellular stress was a major determinant of EV release from CMs, with hypoxia increasing shedding in in vitro and in vivo experiments. At the functional level, EVs isolated from the supernatant of CMs derived from human-induced pluripotent stem cells and cultured in a hypoxic atmosphere elicited a positive inotropic response in unstressed CMs, an effect we found to be dependent on an increase in the number of EVs expressing ceramide on their surface. Of potential clinical relevance, aortic stenosis patients with the highest counts of circulating cardiac CD172a+ EVs had a more favourable prognosis for transcatheter aortic valve replacement than those with lower counts. Conclusion  We identified circulating CD172a+ EVs as cardiac derived, showing their release and function and providing evidence for their prognostic potential in aortic stenosis patients. [ABSTRACT FROM AUTHOR]

Aims  Cardiac magnetic resonance (CMR) is recommended in the diagnosis of cardiomyopathies, but it is time-consuming, expensive, and limited in availability in some European regions. The aim of this study was to determine the use of CMR in cardiomyopathy patients enrolled into the European Society of Cardiology (ESC) cardiomyopathy registry [part of the EURObservational Research Programme (EORP)]. Methods and results  Three thousand, two hundred, and eight consecutive adult patients (34.6% female; median age: 53.0 ± 15 years) with cardiomyopathy were studied: 1260 with dilated (DCM), 1739 with hypertrophic (HCM), 66 with restrictive (RCM), and 143 with arrhythmogenic right ventricular cardiomyopathy (ARVC). CMR scans were performed at baseline in only 29.4% of patients. CMR utilization was variable according to cardiomyopathy subtypes: from 51.1% in ARVC to 36.4% in RCM, 33.8% in HCM, and 20.6% in DCM (P  < 0.001). CMR use in tertiary referral centres located in different European countries varied from 1% to 63.2%. Patients undergoing CMR were younger, less symptomatic, less frequently had implantable cardioverter-defibrillator (ICD)/pacemaker implanted, had fewer cardiovascular risk factors and comorbidities (P  < 0.001). In 28.6% of patients, CMR was used along with transthoracic echocardiography (TTE); 67.6% patients underwent TTE alone, and 0.9% only CMR. Conclusion  Less than one-third of patients enrolled in the registry underwent CMR and the use varied greatly between cardiomyopathy subtypes, clinical profiles of patients, and European tertiary referral centres. This gap with current guidelines needs to be considered carefully by scientific societies to promote wider availability and use of CMR in patients with cardiomyopathies. [ABSTRACT FROM AUTHOR]

BACKGROUND Hypertensive urgencies (HypUrg) are defined as severe elevation in blood pressure (BP) without acute target organ damage. In the office setting, treated asymptomatic patients, with severe BP elevation meeting criteria for urgency are often seen. We evaluate incident Cardiovascular (CV) events (n = 311) during follow-up (FU) in patients with HypUrg at first outpatient visit. METHODS HypUrg was defined by systolic BP ≥180 mm Hg and/or diastolic BP ≥110 mm Hg. Patients were >18 years old, with available ultrasound data, without prevalent CV disease, and no more than stage III Chronic Kidney Disease. BP control was defined as the average BP during FU <140/90 mm Hg. RESULTS Four hundred and sixty-nine of 6,929 patients presented with HypUrg at first visit. Patients with HypUrg were more likely to be women, obese and diabetic and with higher prevalence of left ventricle (LV) hypertrophy and carotid plaque (all P <  0.05). During FU patients with HypUrg had 5-fold higher risk of uncontrolled BP (95% confidence interval (CI) 4.1–6.8, P < 0.0001). In Cox regression presenting with HypUrg was not associated with increased CV risk after adjusting for significant covariates, including age, sex, BP control, LV hypertrophy, and carotid plaque (hazard ratio (HR) 1.42, 95% CI (0.96–2.11), P = 0.08). CONCLUSIONS Patients with HypUrg have worst CV risk profile, reduced probability of BP control during FU and greater prevalence of target organ damage, but the excess CV event risk appears to be mediated through BP control, non-BP cardio-vascular disease risk factors, and demographic attributes. CLINICALTRIALS.GOV IDENTIFIER NCT02211365. [ABSTRACT FROM AUTHOR]

Aims Little is known about regional longitudinal strain (LS) distribution in early stages of Anderson-Fabry disease (AFD) cardiomyopathy. We investigated regional left ventricular (LV) patterns of LS strain and base-to-apex behaviour of LS in treatment-naïve AFD patients. Methods and results Twenty-three consecutive AFD patients at diagnosis and 23 healthy controls without cardiovascular risk factors and matched for age and sex to the patients, underwent a comprehensive evaluation of target organs. An echo-Doppler exam, including determination of regional and global LS strain (GLS) was obtained. The average LS of 6 basal (BLS), 6 middle (MLS), and 5 apical (ALS) segments and relative regional strain ratio [ALS/(BLS + MLS)] were also calculated. Ejection fraction and diastolic indices did not differ between the two groups. LV mass index was greater in AFD (P  <   0.01). GLS (P  =   0.006), BLS (P  <   0.0001), and MLS (P  =   0.003), but not ALS, were lower in AFD patients and relative regional strain ratio was higher in AFD (P  <   0.01) than in controls. These analyses were confirmed separately in the two genders and even after excluding patients with wall hypertrophy. By subdividing AFD patients according to lysoGB3 levels, 9 patients with lysoGB3 ≥ 1.8 ng/L had lower ALS compared to 11 patients with lysoGB3 < 1.8 ng/L (P <  0.01). Conclusion In naïve AFD patients, we observed an early reduction of LV LS, involving mainly LV basal myocardial segments. Nevertheless, the association found between the higher lysoGB3 levels and the lower apical cap LS demonstrates that apical segments LS, despite still normal, is not spared at diagnosis. [ABSTRACT FROM AUTHOR]

BACKGROUND Aortic root (AR) dimension (ARD) at the Valsalva sinuses has been associated with incident cardiovascular (CV) events in population-based studies, but this effect could be due to the association with increased left ventricular (LV) mass. There is also uncertainty on how to define clear-cut AR dilatation. Thus, we analyzed the Campania Salute Network (CSN) registry to (i) establish criteria for evaluation of ARD, (ii) propose cut-points for AR dilatation, and (iii) determine whether AR dilatation has prognostic value independent of LV hypertrophy (LVH). METHODS We analyzed hypertensive patients with available follow-up, in sinus rhythm and free of prevalent valvular and CV disease (n = 8,573). AR exceeding the 75th percentile of the AR z -score (Ao-Z) obtained by comparison with the value predicted by age, sex, and height (i.e. Ao-Z > 0.80) was considered dilated. RESULTS Patients with baseline-dilated ARD by Ao-Z were more likely to be younger, men, and obese and had higher baseline blood pressure (BP; all <0.02) but similar kidney function as those without ARD dilatation. In multivariable Cox regression model, dilated ARD predicted 36% increased rate of CV events, independently of older age, male sex, systolic BP, LVH, and class of antihypertensive medications used during follow-up (95% confidence interval: 1.07–1.71, P = 0.011). CONCLUSIONS In the context of a population of treated hypertensive patients, ARD defined by z -score of predicted values is an independent predictor of CV events regardless of LVH and other common confounders. CLINICAL TRIALS REGISTRATION Trial Number NCT02211365. [ABSTRACT FROM AUTHOR]

Lowering systolic blood pressure (SBP) below the conventional threshold (140 mm Hg) reduces left ventricular (LV) hypertrophy and incident cardiovascular (CV) events. We assessed whether different thresholds of SBP as the average value during follow-up (FU) have different impact on changes in target organ damage (TOD). METHODS From the Campania Salute Network registry, we selected 4,148 hypertensive patients with average SBP-FU <140 mm Hg, and without history of prevalent CV or chronic kidney disease (i.e., 2.7), carotid intimal-medial thickness (IMT, mm), and glomerular filtration rate by CKD-EPI equation (GFR, ml/min/1.73 m2) as markers of TOD. Time trend of TOD for tight and usual subgroups were compared, adjusting for significant confounders. RESULTS During a median of 74 months (interquartile range: 35-108 months), 1,824 patients (44%) were classified as tight control. They were younger, with less prevalent obesity, diabetes, lower initial LVMi, and IMT, and were taking less Ca++-channel blockers during FU than the usual control subgroup (all P < 0.05). In both subgroups, there were no changes over time in LVMi and GFR, whereas the IMT increased during the FU (P < 0.004), with no significant effect of degree of SBP control. CONCLUSIONS In a registry of treated hypertensive patients from a tertiary care center, progression of TODs is not related to average SBP during FU. [ABSTRACT FROM AUTHOR]

Background. Hypertension is a leading cause of chronic kidney disease (CKD) and a decrease in glomerular filtration rate (GFR) is associated with a higher prevalence of hypertension and an increased proportion of suboptimal blood pressure (BP) control. Methods. To investigate characteristics associated with GFR decline, we selected 4539 hypertensive patients from the Campania Salute Network (mean age 53611 years) with at least 3 years of follow-up (FU) and no more than Stage III CKD. GFR was calculated at baseline and at the last available visit using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. GFR decline was defined as a≤30% decrease frominitial GFR for patients in Stage III CKD or by a composite ≥30% decrease from baseline and a final value of<60 for those< with Stage III or higher CKD. Results. At amean FU of 7.5 years, 432 patients (10%) presented with GFR decline. Those patients were older, more likely to be diabetic, with lower GFR and ejection fraction, higher systolic and lower diastolic BP and higher left ventricular (LV) mass and relative wall thickness at baseline; during FU, patients with GFR decline exhibited higher systolic BP, took more drugs and developed more atrial fibrillation (all P<0.02). The probability of GFR decline was independently associated with older age, prevalent diabetes, baseline lower GFR, higher systolic BP during FU, FU duration, increased LVmass and incident AF with no impact from antihypertensive and antiplateletmedications. Conclusions. During antihypertensive therapy, kidney function declines in patients with initially lower GFR, increased LV mass and suboptimal BP control during FU. [ABSTRACT FROM AUTHOR]

Aims: Preliminary data on Sapien 3 valve (S3-THV) use for transcatheter aortic valve implantation have shown an increased permanent pacemaker implantation (PPMI) rate with respect to Sapien XT valve. Aim of this study was to investigate the role of S3-THV position in the left ventricular outflow tract (LVOT) on electrocardiographic changes suggestive of atrioventricular (ΔPR) and/or intraventricular (ΔQRS) conduction abnormalities and 30 days PPMI rate.Methods and results: Eighty-six consecutive patients treated with S3-THV were included in the study. All patients underwent clinical and electrocardiogram evaluation. Left ventricular outflow tract prosthesis depth was assessed by fluoroscopy and expressed quantitatively (mm) and as aorto-ventricular ratio (AVR). Eight patients (9.3%) needed PPMI at 30 days. A low AVR (≤60/40) predicted PPMI (OR = 6.09, 95% CI 1.19-31.01, P = 0.030) and resulted into higher PPMI rate, compared with higher AVR (30.0 vs. 6.6%, P = 0.017). For each millimetre increase in the LVOT prosthesis depth PPMI risk increased by 1.41 times (95% CI 1.06-1.87, P = 0.017). In patients with low AVR, ΔPR was higher than in those with higher AVR (33.4 ± 56.7 vs. 12.1 ± 19.4 ms, P = 0.021) and ΔPR was associated to LVOT prosthesis depth (β = 0.286, P = 0.009). Furthermore, ΔPR was associated with risk of PPMI (OR = 1.03, 95% CI 1.01-1.06, P = 0.024).Conclusions: A low AVR is associated to higher ΔPR and PPMI rates. The correlation between LVOT prosthesis depth with ΔPR and higher PPMI rate suggests the need of a careful S3-THV implantation. [ABSTRACT FROM AUTHOR]

Aims The determinants of discrepancies among two-dimensional echocardiographic (2D-E) methods for left atrial volume (LAV) assessment are poorly investigated. Methods and results Maximal LAV was measured in 613 individuals (282 healthy subjects,180 athletes, and 151 hypertensives; age 45 + 20 years, 62% male) using the ellipsoid model (LAVEllips), the area-length method (LAVAL), and the Simpson's rule (LAVSimps). On the basis of a mathematical model, two left atrial (LA) geometry indexes were tested as predictors of discrepancies between methods: the ratio between LA medial-lateral diameter (MLD) and LA anteroposterior diameter (APD); and the ratio between LA area in the four-chamber view and that of an ellipse with the same diameters [deviation from ellipse (DE)-coefficient]. Discrepancies among methods were consistently present in the overall population and across all study groups. MLD/APD and the DE-coefficient together predicted 76 and 68% of differences between biplane LAVAL and LAVEllips, and between biplane LAVSimps and LAVEllips, respectively. The DE-coefficient was the only determinant of LAVAL/LAVSimps difference (β = 0.167, P < 0.0001). Body mass index was the strongest predictor of discrepancies between single-plane and biplane approaches of LAVAL (β = 0.427, P < 0.0001) and LAVSimps (β = 0.424, P < 0.0001). In additional analyses, biplane LAVAL showed the best agreement with LAV obtained by three-dimensional echocardiography and the best reproducibility and repeatability. Conclusion LA geometry is the main determinant of inconsistencies between 2D-E methods for measuring maximal LAV. Body mass index is the strongest determinant of differences between single-plane and biplane approaches. Different 2D-E methods cannot be used interchangeably for diagnosis and follow-up. The biplane area-length method should be preferred, particularly in overweight-obese subjects. [ABSTRACT FROM AUTHOR]

BACKGROUND Left atrial (LA) dilatation is associated with unfavorable outcome in hypertension. However, there are few data on clinical, demographic, and echocardiographic findings correlated with LA dilatation development. METHODS From the Campania-Salute Network registry, we identified 5,375 hypertensive patients (52 ± 11 years, 38% women) in normal sinus rhythm, with normal LA diameter (parasternal short-axis <24.0 in women and <25.4 mm/m in men), with normal left ventricular (LV) ejection fraction, and with at least 12 months of echocardiographic follow-up. We included in the clinic evaluation type of antihypertensive drugs. RESULTS Follow-up duration was of 70 ± 48 months. During follow-up, 647 patients (12%) showed LA dilatation. Patients with incident LA dilatation were older, most likely to be women, more obese, more diabetics, with lower Modification of Diet in Renal Disease, higher total cholesterol, lower uric acid, higher pulse pressure, lower heart rate, higher LV mass, concentric geometry and lower E/A ratio at mitral level, longer E deceleration time, and higher intima-media carotid thickness. They take more drugs, and follow-up was longer (overall P < 0.05). In the Cox analysis, age, female gender, obesity, higher LV mass, LA diameter at baseline, and longer E deceleration time were determinants of LA dilatation. Furthermore, the use of diuretics protected against LA dilatation. CONCLUSIONS Our data identify a risk profile for LA dilatation, characterized by older age, female sex, obesity, higher LV mass, and worse diastolic function. In this subgroup of patients, the use of diuretics seems to protect against LA dilatation. [ABSTRACT FROM AUTHOR]

Aims Asynchronous myocardial contraction adversely influences left ventricular (LV) function and is therefore associated with a poor prognosis in heart failure. Exercise-induced change in ventricular dyssynchrony may be an important determinant of dynamic changes in cardiac output and mitral regurgitation. Methods and results A prospective, longitudinal study was designed with pre-defined dyssynchrony index and outcome variables to test the hypothesis that dynamic dyssynchrony is associated with worse long-term event-free survival in patients with dilated cardiomyopathy (DCM) and ‘narrow’ QRS complex. One-hundred eighty patients (62 ± 8 years; 110 males) with NYHA class II–III, idiopathic DCM, ejection fraction ≤35%, and QRS duration <120 ms were selected. All the patients underwent standard Doppler echo, colour tissue velocity imaging (DTI), and supine bicycle exercise stress echocardiography. Cardiac synchronicity was defined, at rest and at peak exercise, as DTI velocity opposing-wall delay (significant if ≥65 ms). Outcome was defined as freedom from death, heart transplantation, or LV-assist device implantation, over a median follow-up of 48 months, and a Cox proportional hazards model was used for survival analysis. At baseline examination, DCM patients showed a reduced LV ejection fraction (31 + 4%). A significant electromechanical delay in 58 patients (32%). At the peak of physical exercise, a significant electromechanical delay was detected in 103 patients (57%). There were 41 events during the follow-up (23%): 28 cardiac deaths, 8 heart transplantations, and 5 LV-assist device implantations over 4 years. When adjusted for confounding baseline variables, LV end-diastolic volume, restrictive mitral flow pattern, severity of mitral regurgitation, and the presence of exercise-induced intraventricular dyssynchrony were the only independent determinants of an adverse outcome. Conclusion In patients with idiopathic DCM and narrow QRS, the increase in echocardiographic dyssynchrony during exercise was the strongest predictor of less favourable event-free survival. [ABSTRACT FROM PUBLISHER]

Background. Left ventricular (LV) diastolic dysfunction is linked to myocardial collagen content in many cardiac diseases. There are no data regarding such relationship in patients with end-stage renal disease (ESRD) undergoing haemodialysis. [ABSTRACT FROM PUBLISHER]