The present Euro-Filling study demonstrates that the new 2016 recommendations for assessing LVFP non-invasively are fairly reliable and clinically useful, as well as superior to the 2009 recommendations in estimating invasive LVEDP.

The NORRE study provides the reference values for the most useful Doppler parameters in the evaluation of heart physiology. These data highlight the need of using age-specific reference values especially for the diagnosis of LV systolic and diastolic dysfunction and for the estimation of LV filling pressures.

Aims The present study sought to evaluate the correlation between indices of non-invasive myocardial work (MW) and left ventricle (LV) size, traditional and advanced parameters of LV systolic and diastolic function by 2D echocardiography (2DE). Methods and results A total of 226 (85 men, mean age: 45 ± 13 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. Global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE) were estimated from LV pressure-strain loops using custom software. Peak LV pressure was estimated non-invasively from brachial artery cuff pressure. LV size, parameters of systolic and diastolic function and ventricular-arterial coupling were measured by echocardiography. As advanced indices of myocardial performance, global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained. On multivariable analysis, GWI was significantly correlated with GLS (standardized beta-coefficient = −0.23, P < 0.001), ejection fraction (EF) (standardized beta-coefficient = 0.15, P = 0.02), systolic blood pressure (SBP) (standardized beta-coefficient = 0.56, P < 0.001) and GRS (standardized beta-coefficient = 0.19, P = 0.004), while GCW was correlated with GLS (standardized beta-coefficient = −0.55, P < 0.001), SBP (standardized beta-coefficient = 0.71, P < 0.001), GRS (standardized beta-coefficient = 0.11, P = 0.02), and GCS (standardized beta-coefficient = −0.10, P = 0.01). GWE was directly correlated with EF and inversely correlated with Tei index (standardized beta-coefficient = 0.18, P = 0.009 and standardized beta-coefficient = −0.20, P = 0.004, respectively), the opposite occurred for GWW (standardized beta-coefficient =−−0.14, P = 0.03 and standardized beta-coefficient = 0.17, P = 0.01, respectively). Conclusion The non-invasive MW indices show a good correlation with traditional 2DE parameters of myocardial systolic function and myocardial strain.

The NORRE study provides applicable 3D echocardiographic reference ranges for LV function assessment. Our data highlight the importance of age- and gender-specific reference values for both LV volumes and strain.

In patients with heart failure, exercise echocardiography can help in risk stratification and decision making. The prognostic significance of exercise pulmonary hypertension (PH) in patients with secondary mitral regurgitation (MR) remains unknown. The aim of the present study was to assess the prognostic value of exercise PH in patients with secondary MR and narrow QRS intervals. From 2005 to 2012, 159 consecutive patients with secondary MR, narrow QRS intervals, left ventricular dysfunction (mean ejection fraction 36 -7%), and measurable systolic pulmonary arterial pressure (SPAP) during exercise echocardiography were included. Resting and exercise PH were defined as SPAP >50 and >60 mm Hg, respectively. Exercise PH was more frequent than resting PH (40% vs 13%, p <0.0001). On multivariate logistic regression, the independent determinants of exercise PH were resting SPAP (p <0.0001), exercise MR severity (p <0.0001), and e 0 -wave velocity (p [ 0.004). The incidence of cardiac events during follow-up was significantly higher in patients with exercise PH compared with those without exercise PH (4 years: 40 -7% vs 20 -5%, p <0.0001). Patients with exercise PH exhibited higher rates of cardiac events and death than those with resting PH. In a multivariate Cox proportional hazards model, exercise PH was independently associated with the occurrence of cardiac events (p <0.0001). In conclusion, in patients with secondary MR, exercise PH is determined mainly by resting SPAP, left ventricular diastolic burden, and exercise MR severity. Exercise PH is a powerful predictor of poor outcomes, with a 5.3-fold increased risk for cardiac-related death during follow-up. These results highlight the added value of exercise echocardiography in secondary MR. Ó 2015 Elsevier Inc. All rights reserved. (Am J Cardiol 2015;-:-e-)In asymptomatic valvular heart disease, exercise pulmonary hypertension (PH) was recently identified by our group as a powerful marker of advanced risk for cardiac events. 1,2 In secondary mitral regurgitation (MR), exercise systolic pulmonary arterial pressure (SPAP) is determined mainly by dynamic MR 3 and is involved in the pathogenesis of acute pulmonary edema. 4 The most recent guidelines recommend mitral valve surgery in asymptomatic patients with preserved left ventricular (LV) ejection fractions and severe primary MR, in the presence of exercise PH (a European Society of Cardiology class IIb indication 5 ). There is no overt indication for surgery in patients with secondary MR and exercise PH, but the European Society of Cardiology guidelines state that exercise PH might be an additional motivation to perform surgery in patients with moderate MR who undergo coronary artery bypass graft surgery (level of evidence C). Nevertheless, the prognostic significance of exercise PH in patients with secondary MR remains unknown. The aim of the present study was to assess the prognostic value of exercise PH in patients with secondary MR. We hypothesized that exercise PH is an independent predictor of the occurrenc...

The effects of angiotensin converting enzyme (ACE) inhibitors result from the inhibition of the ACE (kininase II) to ultimately influence both the renin-angiotensin system and the degradation of the bradykinin (BK) metabolism. ACE inhibitors block the degradation of BK and substance P by ACE. In addition, an active metabolite of BK (Des-Arg9-BK) is catalysed by kininase I and its degradation is controlled in part by the conversion enzyme. These molecules have been associated with increased plasma extravasation associated with ACE inhibitors. ACE inhibitors are the leading cause of drug-induced Angioedema (AE). Symptoms of AE mainly occur after the first month of treatment by ACE. However, very late onset cases, sometimes after several years of stable therapy, are also described in the literature. It has been observed that patients previously stable under ACE inhibitor will most likely develop AE soon after the addition of another medication, including the combination of aspirin or non-steroid anti-inflammatory drugs with ACE inhibitor which has proved to be the most common cause, accounting for close to 50% of all AE cases related to ACE inhibitors. This side effect of ACE inhibitors, sometimes very late and rare, deserves to be recalled ARTICLE HISTORY

B-type natriuretic peptide (BNP) is often used as a complementary finding in the diagnostic work-up of patients with aortic stenosis (AS). Whether soluble ST2, a new biomarker of cardiac stretch, is associated with symptomatic status and outcome in asymptomatic AS is unknown. sST2 and BNP levels were measured in 86 patients (74±13 years; 59 asymptomatic, 69%) with AS (<1.5 cm2) and preserved left ventricular ejection fraction who were followed-up for 26±16 months. Both BNP and sST2 were associated with NYHA class but sST2 (>23 ng/mL, AUC = 0.68, p<0.01) was more accurate to identify asymptomatic patients or those who developed symptoms during follow-up. sST2 was independently related to left atrial index (p<0.0001) and aortic valve area (p = 0.004; model R2 = 0.32). A modest correlation was found with BNP (r = 0.4, p<0.01). During follow-up, 29 asymptomatic patients (34%) developed heart failure symptoms. With multivariable analysis, peak aortic jet velocity (HR = 2.7, p = 0.007) and sST2 level (HR = 1.04, p = 0.03) were independent predictors of cardiovascular events. In AS, sST2 levels could provide complementary information regarding symptomatic status, new onset heart failure symptoms and outcome. It might become a promising biomarker in these patients.

Aims The present study sought to assess the impact of aortic stenosis (AS) on myocardial function as assessed by layer-specific longitudinal strain (LS) and its relationship with symptoms and outcome. Methods and results We compared 211 patients (56% males, mean age 73 ± 12 years) with severe AS and left ventricular ejection fraction (LVEF) ≥50% (114 symptomatic, 97 asymptomatic) with 50 controls matched for age and sex. LS was assessed from endocardium, mid-myocardium, and epicardium by 2D speckle-tracking echocardiography. Despite similar LVEF, multilayer strain values were significantly lower in symptomatic patients, compared to asymptomatic and controls [global LS: 17.9 ± 3.4 vs. 19.1 ± 3.1 vs. 20.7 ± 2.1%; endocardial LS: 20.1 ± 4.9 vs. 21.7 ± 4.2 vs. 23.4 ± 2.5%; epicardial LS: 15.8 ± 3.1 vs. 16.8 ± 2.8 vs. 18.3 ± 1.8%; P < 0.001 for all]. On multivariable logistic regression analysis, endocardial LS was independently associated to symptoms (P = 0.012), together with indexed left atrial volume (P = 0.006) and LV concentric remodelling (P = 0.044). During a mean follow-up of 22 months, 33 patients died of a cardiovascular event. On multivariable Cox-regression analysis, age (P = 0.029), brain natriuretic peptide values (P = 0.003), LV mass index (P = 0.0065), LV end-systolic volume (P = 0.012), and endocardial LS (P = 0.0057) emerged as independently associated with cardiovascular death. The best endocardial LS values associated with outcome was 20.6% (sensitivity 70%, specificity 52%, area under the curve = 0.626, P = 0.022). Endocardial LS (19.1 ± 3.3 vs. 20.7 ± 3.3, P = 0.02) but not epicardial LS (15.2 ± 2.8 vs. 15.9 ± 2.5, P = 0.104) also predicted the outcome in patients who were initially asymptomatic. Conclusion In patients with severe AS, LS impairment involves all myocardial layers and is more prominent in the advanced phases of the disease, when the symptoms occur. In this setting, the endocardial LS is independently associated with symptoms and patient outcome.