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Aims In breast cancer (BC) patients treated with anthracyclines-based therapies, we aim at assessing whether adjuvant drugs impact cardiac function differently and whether their cardiotoxicity has a regional pattern. Methods and results In a multicentre study, 146 BC patients (56 ± 11 years) were prospectively enrolled and divided into three groups according to the received treatments: AC/EC-Group (doxorubicin or epirubicin + cyclophosphamide), AC/EC/Tax-Group (AC/EC + taxanes), FEC/Tax-Group (fluorouracil + EC + taxanes). Fifty-six patients of the total cohort also received trastuzumab. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were calculated before starting chemotherapy (T0), at 3 months (T3), at 6 (T6), and 12 months (T12). A ≥10% drop of EF, while remaining within the normal range, was reached at T6 in 25.3% of patients from the whole cohort with an early decrease only in FEC/Tax-Group (P = 0.04). A ≥15% GLS reduction was observed in many more (61.6%) patients. GLS decreased early both in the whole population (P Conclusions The decrease of GLS is more precocious and pronounced in BC patients who received FEC + taxanes. Cardiac function further worsens after 6 months of adjuvant trastuzumab. All LV segments are damaged, with the anterior septum and the apex showing the greatest impairments.

Background: The assessment of coronary flow velocity reserve (CFVR) in left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on stress-induced regional wall motion abnormalities (RWMA). Objectives: The purpose of this study was to assess the feasibility and functional correlates of CFVR. Methods: This prospective, observational, multicenter study initially screened 3,410 patients (2,061 [60%] male; age 63 ± 11 years; ejection fraction 61 ± 9%) with known or suspected coronary artery disease and/or heart failure. All patients underwent SE (exercise, n = 1,288; vasodilator, n = 1,860; dobutamine, n = 262) based on new or worsening RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. A subset of 1,867 patients was followed up. Results: The success rate for CFVR on LAD was 3,002 of 3,410 (feasibility = 88%). Reduced (≤2.0) CFVR was found in 896 of 3,002 (30%) patients. At multivariable logistic regression analysis, inducible RWMA (odds ratio [OR]: 6.5; 95% confidence interval [CI]: 4.9 to 8.5; p < 0.01), abnormal left ventricular contractile reserve (OR: 3.4; 95% CI: 2.7 to 4.2; p < 0.01), and B-lines (OR: 1.5; 95% CI: 1.1 to 1.9; p = 0.01) were associated with reduced CFVR. During a median follow-up time of 16 months, 218 events occurred. RWMA (hazard ratio: 3.8; 95% CI: 2.3 to 6.3; p < 0.001) and reduced CFVR (hazard ratio: 1.5; 95% CI: 1.1 to 2.2; p = 0.009) were independently associated with adverse outcome. Conclusions: CFVR is feasible with all SE protocols. Reduced CFVR is often accompanied by RWMA, abnormal LVCR, and pulmonary congestion during stress, and shows independent value over RWMA in predicting an adverse outcome.

Background: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. Methods: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years, ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) &lt, 1.85 identified chronotropic incompetence. Results: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve &lt, 1.85, 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610, 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579, 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. Conclusions: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.

OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. CONCLUSION In this large dataset of patients with recent onset non-valvular atrial fibrillation, a small proportion were treated with cardioversion. Direct current cardioversion was performed twice as often as pharmacological cardioversion, and there appeared to be no major difference in outcome events for these two cardioversion modalities. For the overall cardioversion group, after adjustments for confounders, a significantly lower risk of mortality was found in patients who received early cardioversion compared with those who did not receive early cardioversion. STUDY REGISTRATION ClinicalTrials.gov NCT01090362.

Background The new methodological standard in stress echo (SE) is the comprehensive approach with ABCDE protocol: step A for regional wall motion abnormalities (RWMA); step B for B-lines by lung ultrasound; step C for left ventricular contractile reserve (LVCR); step D for Doppler-based coronary flow velocity reserve (CFVR) in left anterior descending coronary artery; and step E for imaging-independent EKG-based heart rate reserve (HRR). Purpose To assess the feasibility of ABCDE-SE in a prospective, large scale, multicenter, international, effectiveness study. Methods From September 2016 to December 2019, we enrolled 4,585 all-comers patients (age 63±11 years, 2,566 males, 56%; ejection fraction 61±9%) with known or suspected chronic coronary artery disease referred to clinically-driven SE with exercise (n=1,774, 38.7%), dipyridamole (n=2,403, 52.4%), dobutamine (n=375, 8.2%) or adenosine (n=33, 0.7%). Recruitment involved 13-certified laboratories of 7 countries. All patients underwent ABCDE-SE. The same transducer was used for cardiac and lung scan. Criteria for abnormal response were: stress-induced changes in RWMA in 2 contiguous segments for step A; stress-rest increase in B-lines ≥2 for step B (4-site simplified scan, each site scored from 0= A-lines or black lung to 10= white lung for coalescing B-lines); LVCR ≤2.0 for exercise and dobutamine (≤1.1 for vasodilators) for step C; CFVR in LAD ≤2.0 for step D; HRR (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators) for step E. Results Success rate was 98%, 100%, 99%, 86% and 100% for A, B, C, D and E steps, respectively. The positivity rate was 19% for A, 27% for B, 35% for C, 27% for D and 37% for E. All 5 parameters were normal in 1,496 patients (32.6%), all 5 were abnormal in 183 patients (4.0%). Most patients had abnormal response of 1 (n=1,356, 29.6%), 2 (n=788, 17.2%), 3 (n=477, 9.7%) or 4 (n=315, 6.9%) criteria (see Figure). Conclusions ABCDE-SE is extremely feasible, user-friendly, with minimal increase in imaging and off-line analysis time. It allows a comprehensive and personalized functional stratification assessing different vulnerabilities: epicardial coronary artery stenosis (step A), pulmonary congestion (step B), global myocardial dysfunction (step C), coronary microcirculatory dysfunction (step D), and cardiac autonomic nervous system imbalance (step E). The SE response is not only black and white with step A but can be effectively titrated from benign green code (all steps negative) to more functionally malignant red code (at least 3 steps positive). Figure 1 Funding Acknowledgement Type of funding source: None

Background Bicuspid aortic valve (BAV) is the most common congenital heart disease, affecting 0.5%–2% of the general population. It is associated with valvular dysfunction (aortic stenosis and/or regurgitation, endocarditis) but also with a wide spectrum of aortopathy with unpredictable clinical presentations. The role of the raphe is still controversial. Methods The REgistro della Valvola Aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging is a retrospective/prospective, multicenter, observational registry, with definitive diagnosis of BAV. Anamnestic, demographic, clinical, and instrumental data are collected into dedicated software at first evaluation and during follow-up. Aortopathy was defined as: annulus ≥14 mm/m2; root ≥20 mm/m2; sino-tubular junction (STJ) ≥16 mm/m2; ascending aorta (AA) ≥17 mm/m2; it was classified in: type A, dilation of the ascending aorta; type B, dilation of the aortic root and the ascending aorta; and type C, isolated dilation of the aortic root. Patients were divided in two groups; those with raphe and those without. Results At December 2019, 800 patients with BAV (Male, 73.3%; M:F ratio 2.9; Mean Age at diagnosis 44±23 years) have been included in the registry. Prevalence of hypertension was 29%, diabetes mellitus 3%, smoking-habit 8%. We reported a majority (42.7%, 342) of patients with type 1, followed by type 2 (10.2%, 82) and type 3 (3.7%, 30). No gender differences were observed according to BAV phenotypes, while male gender was associated to higher prevalence of aortic valve regurgitation (p=0.0003). Moreover, in patients with raphe, aortic stenosis (49.8% vs 38.4%; p=0.014) and aortopathy (57.4% vs 46.1%; p=0.034) were significantly prevalent (see Table 1). Of note no difference about aortic regurgitation (62.8% vs 48.7%; p=0.064) between two groups were detected. At univariable logistic regression analysis the presence of raphe was significantly associated with aortopathy [OR: 1.57; 95% CI: 1.02–1.42; p=0.037] especially with Type B Aortopathy [OR: 0.55: 95% CI: 0.33–0.93: p=0.02]. Conclusion Preliminary data from Italian Multicenter REBECCA registry highlight that, in patients with BAV, the raphe is not an innocent bystander but a risk factor for aortic stenosis and type B aortopathy. Funding Acknowledgement Type of funding source: None

Background Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). Methods We enrolled 4,735 patients (age 63.6 ± 11.3 yrs, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (n=1,992 patients) and adenosine (n=18); ≤2.0 for exercise (n=2,087) or dobutamine (n=638). Results Force-based LVCR was obtained in all 4,735 pts. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57 % of patients with abnormal LVCR nevertheless showed increase in stroke volume. Conclusions Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Objectives The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE). Background B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE. Methods The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up. Results According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction. Conclusions Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020 - The International Stress Echo Study [SE2020]; NCT03049995)

Background: According to the actual guidelines regarding severe aortic valve stenosis (AS), symptoms are the most important trigger for aortic valve replacement (AVR). However, the objective analysis of cardiological clinic can be confused, considering the aging population this disease affects and the comorbidities. Objectives: Looking for an objective marker of disease, useful for scheduling the correct AVR, we researched the relation between some biochemical markers of left ventricular (LV) dysfunction and its global longitudinal strain. Materials and Methods: We analyzed 74 consecutive patients (82 ± 4 years) with severe AS. We identified 61 patients with symptoms (angina, dyspnea, and syncope) and 13 asymptomatic patients. The clinical and echocardiographic parameters were compared between these two groups. LV ejection fraction (LVEF), LV global longitudinal strain (LVGLS), NT-pro-B-type brain natriuretic peptide (BNP), troponin T (TNT), creatine kinase-MB (CPK-MB), and myoglobin were determined at the time of evaluation. Results: Compared with the asymptomatic group, patients in the symptomatic group had a lower LVGLS (P = 0.002) and an increased pro-BNP (P = 0.0002). LVGLS showed a good correlation with pro-BNP as a marker of myocardial damage, with a linear increase of pro-BNP in patients with a linear decrease of LVGLS (r = 0.43). Despite the normal value of LVEF > 50% in asymptomatic patients, some of them (46%) have an early dysfunction of LVGLS. No other statistically significant difference emerged from the biochemical analysis, in TNT (P = 0.29), CPK-MB (P = 0.36), and myoglobin (P = 0.38). Conclusions: Pro-BNP and LVGLS can be considered an objective marker of clinical severity of AS disease, useful for management and scheduling of AVR, especially in asymptomatic patients.

Background: Low-gradient aortic stenosis (LG-AS) is characterized by the combination of an aortic valve area compatible with severe stenosis and a low transvalvular mean gradient with low-flow state (i.e., indexed stroke volume

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.

An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = −0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293–5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111–4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion.

Anderson-Fabry disease (AFD) is a rare X-linked metabolic disorder due to deficiency in lysosomal enzyme activity of a-galactosidase A, resulting in pathological accumulation of glycosphingolipids in several tissues and a progressive multi-organ dysfunction. The Global Longitudinal Strain (GLS) of the left ventricle (LV) by Speckle-tracking echocardiography (STE) has been show to detect subclinical cardiac involvement in many cardiomyopathies. The Mechanical Dispersion (MD), derived from STE is considered able to reflect a heterogeneous myocardial contraction, evaluated in many cardiopathies. A reduction in GLS was associated with myocardial fibrosis in the subclinical stages of AFD cardiomyopathy, but there is no MD data in AFD. The aim of the study was to evaluate the distribution of GLS and MD of LV in patients with AFD. 47 consecutive AFD adult patients treated (37F, 12 M, age 45 + 17 years) were examined by a complete echocardiographic examination from a Vivid E95 ultrasound scanner (Horten, Norway). The STE post-processing was performed by Echopac 2.02, in apical long-axis, 4-chambers, and 2-chambers views to determine GLS and MD. Data were expressed as mean± standard deviation. The comparison between the AFD group and 20 normal subjects (N) was performed with unpaired T-test. Compared to N, the AFD group showed higher values of LVMi, LAVi, E/E’, and MD, but a lower value of GLS (Table). GLS was significantly lower in the basal (sept p In patients with AFD, MD added to GLS seems to be a promising tool for the early diagnosis of segmental dysfunction . Table1: Results AFD N p< m SD m SD LVMi g/sqm 77.1 29.8 62.3 14.1 0.008 LVEF % 65.7 5 63.6 3.5 0.04 LAVi ml/sqm 25.5 11 18.2 4.5 0.000 E/E" 8.3 3 5.4 1.1 0.000 TV vmax m/s 2.2 0.4 2.1 0.3 - LV GLS % -17 4 -20 2 0.003 LV MD ms 52 38 29 8 0.000

Valvular heart diseases (VHD) may be observed in patients with cancer for several reasons, including preexisting valve lesions, radiotherapy, infective endocarditis, and secondary to LV dysfunction. The incidence of VHD is especially in younger survivors treated with thoracic radiotherapy for certain malignancies, such as Hodgkin’s lymphoma and breast cancer. The mechanism of radiation-induced damage to heart valves is not clear and includes diffuse fibro-calcific thickening of the valve. VHD is commonly diagnosed after a long latent period, in the context of clinical symptoms, or suspected on the basis of a new murmur. The evaluation includes identification of anatomical valve abnormalities and valve dysfunction and assessment of the functional consequences of valve dysfunction on the ventricles. Echocardiography is the optimal imaging technique for diagnostic and therapeutic management. Cardiovascular magnetic resonance (CMR) and computed tomography (CT) may be used to assess the severity of VHD, but cardiac CT is mainly useful for detecting extensive calcifications of the ascending aorta. Patients exposed to mediastinal radiotherapy and minimal valve dysfunction require follow-up every 2 to 3 years, with moderate valve disease yearly, and when severe should be assessed for valve surgery.

Notwithstanding the steady progress in survival rates of children and adolescents suffering from cancer, the benefits associated with chemotherapy do not come without risks involving multiple organs and systems, including the cardiovascular apparatus. Anthracyclines-often administered in combination with radiation therapy and/or surgery-are the most used chemotherapeutic compounds in order to treat tumours and blood malignancies even in paediatric age. Being an important side-effect of anthracyclines, carduitoxicity may limit their efficacy during the treatment and induce long-term sequelae, observed even many years after therapy completion. The purpose of this review was to perform an overview about all the possible strategies to prevent and/or limit the anthracyclines adverse side-effects for the cardiovascular system in childhood cancer survivors.

Background Twenty-four-hour blood pressure (BP) variability is an important predictor of organ damage and cardiovascular events. Although epidemiological data are widely based on evaluation of office (clinic) BP, 24-hour ambulatory BP monitoring (ABPM) accurately assess the severity of hypertension to predict cardiovascular events in hypertensive patients, because it more accurately reflects BP load on heart and blood vessels. Conventional transthoracic echocardiography (TTE), such as M-mode and two-dimensional (2D), and more advanced techniques, such as tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE), are used to identify pathological changes of the hypertensive heart disease. In addition, the study of systemic arterial compliance (SAC) predicts the impact of the arterial stiffness on the LV remodeling. Methods Fifty-eight patients (34 males and 24 females, aged 53±12 years) with hypertension for at least one year were studied using Ambulatory Blood Pressure Monitoring (ABPM), with evaluation of 24-hour, day time, night time and sleep and awake average systolic and diastolic BP, and subsequently with TTE, to evaluate the influence of the 24-hour average BP, integrated with echocardiographic parameters, on cardiovascular adaptations in hypertensive patients. ECHO parameters examined were: left ventricle (LV) mass indexed to body surface area (LVMi), LV ejection fraction (EF), left atrial volume indexed to body surface area (LAVi), mitral inflow velocities (E, A and E/A), mitral annulus velocities (S' and E') and E/E' ratio by TDI, LV global longitudinal strain (GLS) using 2D STE. SAC was derived by the ratio SVi/PP, using echocardiographic stroke volume index to body surface area (SVi) and pulse pressure (PP). Results LVMi showed a correlation with the 24-hour average BP (SBP r=0.32; DBP r=0.26), SBPd (r=0.32), DBPd (r=0.28) and SBPn (r=0.29). GLS was correlated with the 24-hour average BP (SBP r=0.30; DBP r=0.32), SBPd (r=0.32), DBPd (r=0.32) and with LVMi (r=0.42), LAVi with 24 hour SBP (r=0.28), while SAC with LVMi (r=0.29) and LAVi (r=0.33). Conclusions ABPM and TTE evaluation can be particularly useful in hypertensive patients, even with normal office BP, to highlight the influence of 24-hour blood pressure profile on LVM, and to a lesser extent, on LAV. SAC, instead, seems to be correlated both to LVM and LAV, independently of BP levels.

The B-Profile of normal lung sliding with B-lines by lung ultrasound (LUS) identifies pulmonary congestion at rest and during exercise stress echocardiography (SE) in coronary artery disease (CAD) [(1)][1] or heart failure (HF) patients with either reduced [(2)][2] or preserved [(3)][3] resting

The diagnosis of aortic stenosis (AS) is reached through clinical and instrumental assessment of patients [1]. The symptomatic forms are characterized by angina, dyspnea, and syncope, but the diagnostic suspicion can be supported by the presence of typical physical signs, such as harsh diamond-shaped systolic murmur, often matched by a more intense fremitus along the right upper sternal margin and irradiated to the neck, parvus et tardus pulse, fourth sound, and attenuation or disappearance of the aortic component of the second sound. A complete picture of heart failure can be found where a systolic murmur is often faint or lacking. In asymptomatic forms, physical findings can be the only evidence of aortic valve (AV) disease. With regard to instrumental examinations, standard electrocardiogram (ECG) can highlight signs of left ventricular hypertrophy. However, even in the more severe forms of AS, ECG may not show any alteration.

Background: A lot of studies have shown a positive effect of transcatheter aortic valve implantation (TAVI) on left ventricular ejection fraction (LVEF). Objectives: We aimed to investigate the effect of TAVI on left ventricular function and correlate this phenomenon with hypertrophy degree in an early follow-up. Materials and Methods: Between August 2015 and July 2016, 250 consecutive patients with symptomatic severe aortic stenosis (AS) underwent TAVI in our institution. Given the aim of this analysis, only patients with an LVEF

Background: Bicuspid aortic valve (BAV) is the most common congenital heart disease, affecting 0.5%–2% of the general population. It is associated not only with notable valvular risk (aortic stenosis and/or regurgitation, endocarditis) but also with aortopathy with a wide spectrum of unpredictable clinical presentations, including aneurysmal dilation of the aortic root and/or ascending thoracic aorta, isthmic coarctation, aortic dissection, or wall rupture. Methods: The REgistro della Valvola Aortica Bicuspide della Societa Italiana di ECocardiografia e CArdiovascular Imaging is a retrospective (from January 1, 2010)/prospective, multicenter, observational registry, expected to enroll 3000 patients with definitive diagnosis of BAV made by transthoracic and/or transesophageal echocardiography, computed tomography, cardiovascular magnetic resonance, or at surgery. Inclusion criteria were definitive diagnosis of BAV. Patients will be enrolled regardless of the presence and severity of aortic valve dysfunction or aortic vessel disease and the coexistence of other congenital cardiovascular malformations. Exclusion criteria were uncertain BAV diagnosis, impossibility of obtaining informed consent, inability to carry out the follow-up. Anamnestic, demographic, clinical, and instrumental data collected both at first evaluation and during follow-up will be integrated into dedicated software. The aim is to derive a data set of unselected BAV patients with the main purpose of assessing the current clinical presentation, management, and outcomes of BAV. Conclusions: A multicenter registry covering a large population of BAV patients could have a profound impact on the understanding of the natural history of this disease and could influence its management.

Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood. This is due to the targeted approach that allowed identifying one or a few genes associated with IRI and cardioprotection. Genes critical for signaling pathways in cardioprotection include protectomiRs (e.g., microRNA 125b*), ZAC1 transcription factor, pro-inflammatory genes such as cycloxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), antioxidant enzymes such as hemoxygenase (HO)-1, extracellular and manganese superoxidase dismutases (ec-SOD and Mg-SOD), heat shock proteins (HSPs), growth factors such as insulin like growth factor (IGF)-1 and hepatocyte growth factor (HGF), antiapoptotic proteins such as Bcl-2 and Bcl-xL, pro-apoptotic proteins such as FasL, Bcl-2, Bax, caspase-3 and p53, and proangiogenic genes such as TGFbeta, sphingosine kinase 1 (SPK1), and PI3K-Akt. By identifying the gene expression profiles of IRI and ischemic conditioning, one may reveal potential gene targets responsible for cardioprotection. In this manuscript, we review the current state of the art of gene therapy in cardioprotection and propose that gene expression analysis facilitates the identification of individual genes associated with cardioprotection. We discuss signaling pathways associated with cardioprotection that can be targeted by gene therapy to achieve cardioprotection.

Subclinical myocardial dysfunction has been identified in obese subjects without cardiovascular risks factors and has been defined as “obesity cardiomyopathy”. We evaluated left ventricular (LV) function and geometry in obese patients by using a 3 dimensional echocardiography (3DE). We also aimed to look at the influence of ventricular geometry upon functional parameters of the LV by using 3D speckle tracking imaging (3D-STI). 30 consecutive and asymptomatic obese cases (OB group) with no comorbidities were prospectively enrolled. The control group included 30 healthy volunteers (HS group), matched for age and sex. All subjects underwent 3DE and 3D-STI. Ventricular geometry was evaluated with the LV sphericity index (LV SpI) and the LV diastolic volume to mass ratio (LV EDV/Mass ratio). LV Mass was significantly increased in OB group and the LV EDV/Mass ratio had a significantly lower mean value in this group (p

The US National Cancer Institute estimates that cardiotoxicity (CTX) from target therapy refers mostly to four groups of drugs: epidermal growth factor receptor 2 inhibitors, angiogenic inhibitors, directed Abelson murine leukemia viral oncogene homolog inhibitors, and proteasome inhibitors. The main cardiotoxic side-effects related to antiepidermal growth factor receptor 2 therapy are left ventricular systolic dysfunction and heart failure. Angiogenesis inhibitors are associated with hypertension, left ventricular dysfunction/heart failure, myocardial ischemia, QT prolongation, and thrombosis. Moreover, other agents may be related to CTX induced by treatment. In this study, we review the guidelines for a practical approach for the management of CTX in patients under anticancer target therapy.

Anthracyclines are the mainstay of treatment of a variety of haematological malignancies and solid tumours. Unfortunately, the clinical use of these drugs is limited by cumulative, dose-related cardiotoxicity which may ultimately lead to a severe and irreversible form of cardiomyopathy. Thus, there is an increasing need for close cooperation among cardiologists, oncologists and haemato-oncologists. As anthracyclines save lives, the logical goal of this cooperation, besides preventing or mitigating cardiotoxicity, is to promote an acceptable balance between the potential cardiac side effects and the vital benefit of anticancer treatment. This manuscript, which is specifically addressed to the cardiologist who has not accumulated much experience in the field of cancer therapy, focuses on several topics, that is old and new mechanisms of cardiac toxicity, late cardiac toxicity, the importance of overall risk assessment, the key role of a cardiology consult before starting cancer therapy, and the pros and cons of primary and secondary prevention programmes.

Because of the recent advances in chemotherapeutic protocols, cancer survival has improved significantly, although cardiovascular disease has become a major cause of morbidity and mortality among cancer survivors: in addition to the well-known cardiotoxicity (CTX) from anthracyclines, biologic drugs that target molecules that are active in cancer biology also interfere with cardiovascular homeostasis.Pharmacological and non-pharmacological strategies to protect the cardiovascular structure and function are the best approaches to reducing the prevalence of cardiomyopathy linked to anticancer drugs. Extensive efforts have been devoted to identifying and testing strategies to achieve this end, but little consensus has been reached on a common and shared operability.Timing, dose and mode of chemotherapy administration play a crucial role in the development of acute or late myocardial dysfunction. Primary prevention initiatives cover a wide area that ranges from conventional heart failure drugs, such as β-blockers and renin-angiotensin-aldosterone system antagonists to nutritional supplementation and physical training. Additional studies on the pathophysiology and cellular mechanisms of anticancer-drug-related CTX will enable the introduction of novel therapies.We present various typologies of prevention strategies, describing the approaches that have already been used and those that could be effective on the basis of a better understanding of pharmacokinetic and pharmacodynamic CTX mechanisms.

The evaluation by cardiovascular imaging of chemotherapy patients became a central topic in the last several years. The use of drugs for the treatment of cancers increased, and new molecules and protocols were developed to improve outcomes in these patients. Although, these novel approaches also produced a progressive increase in side effects, particularly myocardial dysfunction. Imaging of the heart was highly accurate in the early diagnosis of cancer therapeutics related-cardiac dysfunction. Echocardiography is the first-line method to assess ventricular function alterations, and it is required to satisfy the need for an early, easy and accurate diagnosis to stratify the risk of heart failure and manage treatments. A careful monitoring of cardiac function during the course of therapy should prevent the onset of severe heart impairment. This review provides an overview of the most important findings of the role of echocardiography in the management of chemotherapy-treated patients to create a clear and complete description of the efficacy of conventional measurements, the importance of comprehensive heart evaluations, the additional role of new echocardiographic techniques, the utility of integrated studies using other imaging tools and the positions of the most important international societies on this topic.

Chemotherapy-induced cardiotoxicity (CTX) is a determining factor for the quality of life and mortality of patients administered potentially cardiotoxic drugs and in long-term cancer survivors. Therefore, prevention and early detection of CTX are highly desirable, as is the exploration of alternative therapeutic strategies and/or the proposal of potentially cardioprotective treatments. In recent years, cardiovascular imaging has acquired a pivotal role in this setting. Although echocardiography remains the diagnostic method most used to monitor cancer patients, the need for more reliable, reproducible and accurate detection of early chemotherapy-induced CTX has encouraged the introduction of second-line advanced imaging modalities, such as cardiac magnetic resonance (CMR) and nuclear techniques, into the clinical setting. This review of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to afford an overview of the most important findings from the literature about the role of CMR and nuclear techniques in the management of chemotherapy-treated patients, describe conventional and new parameters for detecting CTX from both diagnostic and prognostic perspectives and provide integrated insight into the role of CMR and nuclear techniques compared with other imaging tools and versus the positions of the most important international societies.

Background: Stress echocardiography represents one of the best possible imaging choice for the diagnosis and stratification of patients with coronary artery disease (CAD). However, this imaging technique presents some limitations such as the quality of the image, high inter-observer variability, and the operator-dependent expertise. New technologies have been recently developed to provide an objective, operator-independent, and quantitative analysis of regional myocardial function. Objectives: The aim of this study was to investigate regional myocardial dyssynchrony using tissue synchronization imaging (TSI) during exercise stress echocardiography (ESE). Patients and Methods: The ESE and TSI analysis of left ventricular (LV) segments was performed for 30 patients with CAD previously treated with revascularization therapy (CADr group) and the results were compared to those in 30 healthy subjects (norm group). The echo protocol comprised echocardiographic examinations at baseline, at the peak of exercise, and at 5 minutes after recovery as well as biplane and triplane acquisitions, pulsed wave of mitral flow, continuous wave of tricuspid regurgitation, tissue Doppler at the mitral annulus, TSI with an automatically detected positive time-to-peak velocity (Tp), and the measurement of the maximum activation time delay between myocardial segments and its standard deviation at baseline and peak stress for each patient. Results: The CADr group showed a lower increase in E (P = 0.005), A (P = 0.006), S' (P < 0.001), and E' (P = 0.006) velocities at both baseline and peak stress and a significantly increased ventricular dyssynchrony at baseline and at peak stress (P < 0.01) compared to the norm group. The baseline-peak variations in the CADr group did not show significant dierences. The relationships between the maximum activation delay and the other echocardiographic parameters showed a significant negative correlation with LV ejection fraction (r = 0.217; P = 0.031) and S' velocity (r = -0.393; P < 0.001) and a positive correlation with the E/E' ratio (r = 0.376; P < 0.001). The comparison between the dierent ischemic territories revascularized in terms of the delay in ventricular activation showed the greatest delay in the revascularized territory in 63% of the patients with ischemia. Conclusions: The TSI analysis in patients with CAD may be considered an interesting parameter in addition to the conventional echocardiographic parameters during ESE.

Aims To assess the incremental value of real-time three-dimensional echocardiography (RT-3DTE) over contrast transthoracic echocardiography (TTE), compared with contrast transesophageal echocardiography (TEE) in the identification of patent foramen ovale (PFO). Methods and results Eighty-one consecutive patients with history of migraine headache (MH) or unexplained cerebrovascular events (CE) were examined using RT-3DTE, contrast TTE, and contrast TEE in sequence. Feasibility of RT-3DE in patients with MH and CE was 98 and 91%, respectively. Mean time for 3D colour data set acquisition was 9 ± 5 min. PFO was diagnosed using contrast TEE in 36 patients (overall prevalence = 44%). Diagnostic accuracy of RT-3DE was significantly higher than that of contrast TTE: sensitivity 83 vs. 44%, P < 0.001; specificity 100 vs. 100%, P 7 = NS; positive predictive value 100 vs. 100%, P = NS; negative predictive value 88 vs. 69%, P < 0.01; accuracy 93 vs. 75%, P < 0.003. Five of the six patients in whom RT-3DTE did not identify PFOs showed a defect diameter smaller than 2 mm. Conclusion RT-3DTE is a feasible, accurate, and reproducible technique to detect PFO without the need of saline contrast injection. Its accuracy is superior to contrast 2D TTE and close to that of contrast TEE.

Spontaneous coronary artery dissection is a rare pathology that has no exact incidence, etiology, pathogenesis and evolution in literature. We report two cases of two women with coronary artery dissection, uncommon clinical presentation of acute coronary syndrome and without identifiable risk factors. A review of the literature and the management of this condition are presented.

Introduction Current guidelines recommend three-dimensional echocardiography (3DE) as the reference technique to assess left ventricular (LV) volumes and ejection fraction (EF). We performed a meta-analysis to identify normative reference values by real time 3DE in healthy subjects. Methods We searched MEDLINE and the Cochrane Library databases using the key search terms three-dimensional echocardiography, volumes, and healthy. Data were pooled using random-effects meta-analysis, and source of variation was investigated using meta-regression. After selection, 13 articles were included (2806 subjects). Four studies were conducted in children and young adolescents; one study provided data in an independent pediatric subgroup. Results In adults, pooled mean value for LV EDV was 98.4 mL (95%CI, 87–110 mL), while LV ESV mean value was 37.0 mL (95%CI, 32–42 mL). LV EF mean value was 62.9% (95%CI 61.7–64.2%). Male subjects showed a significant increase in both LV EDV index (mean difference 5.3 mL/m2; P

We report the case of a 45-year-old Caucasian male with negative cardiovascular history, heavy-smoker, who was referred to our Cardiology Unit for recurrent inexplicable tachycardia. Chaotic atrial tachycardia with intermittent fibrillation was observed at ECG, whereas a smoothed mass (approximately sized 8 × 8 cm) was unexpectedly found at echocardiography likely infiltrating the right atrial wall. Multi-detector computed tomography confirmed the mediastinal mass and the digital post-processing clearly identified its anatomic characteristics and invasivity. This study demonstrates that recurrent and refractory atrial arrhythmias can be early signs of cardiac infiltrating mediastinal masses. The combined approach by echocardiography and computed tomography was confirmed to provide precise anatomical and functional characteristics of the arrhythmogenic disease in this patient.

We describe a case of a 69-year-old female referred for the evaluation of exertional dyspnea, with a small membranous ventricular septal defect (VSD) and right ventricle (RV) outflow tract obstruction. Using transthoracic echo was diagnosed VSD with left to right shunting and transesophageal echo (TEE) was used to a better anatomical characterization. TEE showed a perimembranous subaortic VSD that developed a high-velocity flow in RV. Pulmonary valve appears normal and right ventricular infundibular hypertrophy or double-chambered RV was excluded from the study. Furthermore, TEE showed a malaligned VSD and the presence of perimembranous mobile tissue protruding in RV. We hypothesized that this tissue can be attributed to broken septum aneurysm and protruding during systole, it causes a dynamic RV output tract obstruction.

Aims: Fabry disease (FD) is a rare X-linked genetic disorder caused by the deficiency or absent activity of lysosomal ?-galactosidase A. Cardiovascular remodelling is a hallmark of FD. The present study aimed to comprehensively evaluate the cardiac, vascular and microvascular status in a population of patients with genetic mutations for FD without left ventricular hypertrophy (LVH). Methods and results: This study includes subjects carrying genetic mutations for FD (Fabry disease mutation-carrier, FDMC) without LVH (n = 19). A group of control subjects (n = 19) matched for age, sex, body mass index and cardiovascular risk factors were also included. All subjects underwent echocardiography, carotid ultrasound scan, endothelial flow-mediated dilatation (FMD) and nailfold capillaroscopy (NFC) assessment. When compared to the subjects in the control group, FDMC patients showed significantly lower mean values of systolic myocardial velocity (7.33 ± 1.28 vs. 10.08 ± 1.63 cm/s, p < 0.0001), longitudinal systolic strain (-18.07 ± 1.72 vs. -21.15 ± 2.22 %, p < 0.0001), significantly higher E/E' mean values (7.15 ± 1.54 vs. 5.98 ± 1.27, p = 0.016) and intima-media thickness mean values (0.80 ± 0.20 vs. 0.61 ± 0.19 mm, p = 0.005), significantly lower FMD (8.3 ± 4.6 vs. 12.2 ± 5.0 %, p = 0.02), more atypical capillaries and irregular NFC architecture in FDMC than control subjects (52.6 vs. 0 %, p < 0.0001; 78.9 vs. 36.8 %, p = 0.02 respectively). Conclusions: FD progressively involves cardiac, macrovascular and microvascular systems in an early stage. These features are present even in asymptomatic mutation carriers without LVH. © 2013 SSIEM and Springer Science+Business Media Dordrecht.

Atrial septal aneurysm when associated to other cardiac abnormalities, such as patent foramen ovale, Chiari network or Eustachian Membrane, is a well-known recognised risk factor for cerebral embolism. Aim of study is to assess if isolated atrial septal aneurysm could be considered statistically related to cryptogenic stroke, considering the strong clinical impact that this association could have on these patients outcome. 579 patients were investigated for a suspected patent foramen ovale using transthoracic echocardiography, in order to evaluate the presence of atrial septal aneurysm and to identify other potential cardiac embolic sources. The patients with atrial septal aneurysm underwent transcranic echodoppler and transoesophageal echocardiography examination with contrast solution during Valsalva manoeuvre.209/579 (36%) patients where we made diagnosis of atrial septal aneurysm. In this cohort of patients transcranic echodoppler showed a patent foramen ovale in 114/209 (54%), whereas transoesophageal echocardiography in 111/209 (53%); 6/114 (5%) pa-tients with a positive transcranic echodoppler had a normal transoesophageal echocardiography examination and 3/95 (3%) with normal transcranic echodoppler had a positive transoesophageal echocardiography. Transcranic echodoppler vs. transoesophageal echocardiography sensibility was 97% and specificity 94%. Only 13/98 (13%) of patients with isolated atrial septal aneurysm and 23/111 (26%) with patent foramen ovale had history of cryptogenic stroke. According to our data, isolated atrial septal aneurysm could not be considered an independent risk factor for cryptogenic stroke.

Recent studies have reported early atherosclerosis in patients with inflammatory bowel disease (IBD). In these patients, the chronic low-grade inflammation may predispose to vascular remodelling and arterial stiffening. We aimed at studying arterial stiffness in IBD patients.Thirty-two IBD patients without cardiovascular risk factors and 32 matched controls were enrolled (age 19-49 years). SphygmoCor device (AtCor Medical, Sydney, Australia) was used to measure carotid-femoral and carotid-radial (muscular artery) pulse wave velocity (PWV), augmentation index and central blood pressure.Carotid-femoral PWV was higher in IBD patients than in controls (6.6 ± 1.4 vs. 6.0 ± 0.8 m/s, respectively, P 0.05), as well as carotid-radial PWV (8.5 ± 1.2 vs. 7.2 ± 1.0 m/s, P 0.001). Central pulse pressure was higher in IBD than in controls (32 ± 6 vs. 28 ± 7 mmHg, P 0.05). Aging was an important determinant of carotid-femoral PWV in both groups and carotid-radial PWV only in IBD patients. In fully adjusted model performed in both groups of patients considered as a whole, age was positively associated with carotid-femoral PWV [R(2) = 0.10; +0.05 m/s per 1 year of aging, 95% confidence interval (CI) 0.01-0.08 m/s, P 0.05], as well as IBD (R(2) = 0.10; +0.72 m/s if IBD present, 95% CI 0.19-1.26 m/s, P 0.05). In IBD patients, carotid-radial PWV was positively associated with the disease duration (R(2) = 0.20; +0.11 m/s per 1 year of aging, 95% CI 0.03-0.19 m/s, P 0.05).Arterial stiffness is increased in patients with IBD independently of conventional cardiovascular risk factors.

Iron-mediated cardiomyopathy is the leading cause of death in patients with thalassemia major (TM). The identification of subclinical cardiac involvement in the early phases of the disease is important to optimize therapeutic strategies. The aim of this study was to identify early markers of cardiac dysfunction through new parameters of cardiac rotational dynamics and to look for a relationship with parameters of iron overload.Twenty-seven asymptomatic patients with TM and 27 healthy control subjects were prospectively enrolled. All subjects underwent standard echocardiography and subsequent offline analysis to assess left ventricular (LV) rotation and longitudinal mechanics using speckle-tracking echocardiography. In all patients with TM, ferritin levels were measured, and a subgroup underwent cardiac magnetic resonance imaging.All subjects had normal parameters of cardiac function, although patients with TM showed significantly lower S' values (P = .030) and E' values (P = .025), with increased E/E' ratio (P = .003) and indexed left atrial volumes (P = .022). Compared with controls, patients with TM had significantly reduced systolic apical rotation (P = .006), LV twist (P = .002), and LV torsion (P = .001). Systolic and diastolic rotational peak velocities at the apical level were also significantly decreased in the TM group (P = .003 and P = .011, respectively) with reductions of twisting and untwisting rates (P = .003 and P = .001, respectively). Patients with TM also showed a significant reduction of longitudinal displacement from the two-chamber apical view (P = .042) but preserved longitudinal strain and strain rate. Patients with T2* values20 msec had preserved rotational function, while those with T2* values20 msec showed significantly lower mean values of LV peak basal systolic rotation (-3.1 ± 1.4° vs -6.2 ± 2.6°, P = .016), LV peak apical systolic rotation (3.4 ± 1.3° vs 6.4 ± 3.1°, P = .045), LV twist (4.8 ± 2.5° vs 10.9 ± 4.9°, P = .012), and LV torsion (0.6 ± 0.2°/cm vs 1.4 ± 1.6°/cm, P = .010). LV torsion was negatively related to ferritin levels (r = -0.47, P = .013) and directly to T2* values (r = 0.64, P = .007).LV rotational dynamics in asymptomatic patients with TM are negatively related to iron overload. Rotational function of the left ventricle is preserved in patients with normal T2* values. These new parameters are useful for an early diagnosis of cardiac involvement.

A B S T R AC T BACKGROUND Mineralocorticoid antagonists improve survival among patients with chronic, se- vere systolic heart failure and heart failure after myocardial infarction. We evalu- ated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms. METHODS In this randomized, double-blind trial, we randomly assigned 2737 patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35% to receive eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from car- diovascular causes or hospitalization for heart failure. RESULTS The trial was stopped prematurely, according to prespecified rules, after a median follow-up period of 21 months. The primary outcome occurred in 18.3% of patients in the eplerenone group as compared with 25.9% in the placebo group (hazard ra- tio, 0.63; 95% confidence interval (CI), 0.54 to 0.74; P

This multicenter study consisted of echocardiographic examination of subjects with stage A heart failure (HF) with cardiovascular risk factors and normal electrocardiogram and clinical examination results to (a) define whether stage A subjects with risk factors are really free of functional or structural cardiac abnormalities and (b) assess the impact of the presence of risk factors and incremental value of echocardiographic parameters in the prediction of progression of HF or in the development of cardiovascular events.A total of 1097 asymptomatic subjects underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors. Left ventricular (LV) dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated according to standard criteria. The subjects were divided according to different criteria: the presence of one or more risk factors, presence or absence of LV systolic dysfunction, and presence or absence of LV diastolic dysfunction. A follow-up period of 26 ± 11 months was performed, observing primary (cardiac death, myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, acute pulmonary edema, stroke, and transient ischemic attack) and secondary (cardiologist-made diagnosis of HF and HF hospitalization) end points.The multivariate analysis for independent predictors of primary end points showed that age (P = .001), gender (P = .02), dyslipidemia (P = .01), obesity (P = .001), and systolic dysfunction (P = .048) represented the significant predictors. The multivariate logistic regression analysis for independent predictors of secondary end points showed that gender (P = .02), LV systolic dysfunction (P = .01), and LV diastolic dysfunction (P.01) represented the significant predictors. The multivariate analysis for independent predictors of combined end points showed that only age (P.003), gender (male: P.001), obesity (P.04), and systolic dysfunction (P.001) represented the significant predictors. Echocardiography showed a high incremental value in the detection of systolic LV dysfunction and the prediction of cardiovascular events during follow-up in subjects with at least two risk factors.This study demonstrated that preclinical functional or structural myocardial abnormalities could be detected by echocardiography in asymptomatic subjects with two or more cardiovascular risk factors and without electrocardiogram abnormalities (stage A of HF classification). The presence or absence of LV systolic dysfunction or LV diastolic dysfunction, as demonstrated by echocardiography, has an incremental value to cardiovascular risk factors in predicting both the evolution toward more severe HF stage C and the occurrence of cardiovascular events.

The aims of this study were to evaluate through Color Doppler Myocardial Imaging (CDMI) echocardiography if atrial or ventricular myocardial alterations could be detectable in patients with thalassemia major (THAL) and if these alterations could be considered as predictive elements for supra-ventricular arrhythmic events. Twenty-three patients with THAL underwent clinical and electrocardiographic evaluation; patients were grouped in THAL1 (9 with supra-ventricular arrhythmias) and THAL2 (14 without arrhythmias); 12 healthy subjects were considered as control group (C). We examined through conventional 2D Color Doppler echocardiography some morphological and functional parameters regarding left ventricular (LV) systolic and diastolic function, and through CDMI the velocities at mitral annulus level, the regional LV and left atrial (LA) strain and strain rate. All THAL patients had LV dimension (pless than 0.05), LA area (p less than 0.01) and E/Em ratio (pless than 0.001) to be significantly higher than controls. The mitral annulus longitudinal velocities were significantly lower in THAL1 than in THAL2 (pless than 0.001); the E/Em ratio was higher in THAL1 than THAL2 (pless than 0.001). The THAL1 showed a lower systolic strain rate of atrial wall than THAL2 and C (pless than 0.05). The multiple regression highlighted a significantly inverse correlation among E/Em and atrial strain (pless than 0.02). CDMI showed both THAL subgroups had subtle systolic and diastolic left ventricular myocardial alterations, which could represent the onset of developing “iron cardiomyopathy” and are related to supra-ventricular arrhythmia. Monitoring these parameters in the THAL patients could contribute to decisions about follow-up and therapy.

Background: Atrial septal defect (ASD) represents a common congenital heart malformation, cause of right ventricle (RV) volume overload, pulmonary hypertension, atrial arrhythmias, and paradoxical emboli. Percutaneous closure represents the treatment of choice for ASD. However, it is still difficult to associate symptoms to the success of ASD treatment. Objective: To investigate any possible correlation between transthoracic echocardiography (TTE) findings and patients’ symptoms after ASD treatment. Materials and Methods: Thirty patients (mean age 49 ± 17 years; 10 younger ≤40 years and 20 > 40 years) underwent percutaneous closure of ASD type ostium secundum. Every patient underwent clinical examination, electrocardiogram (ECG) and TTE before procedure and at 1, 6, and 12 months after procedure and a multichoice questionnaire to collect patients’ symptoms and complain severity. Statistical analysis: Continuous variables were summarized by means and standard deviation. Estimates of occurrence of events were expressed as percentages. Comparison between mean follow-ups was achieved using paired t-test sample. Results: At end of follow-up, TTE showed a decrease of RV dimensions (34.4 vs 37.5 mm preclosure; P = 0.01), pulmonary artery systolic pressure (PAPs 28.4 vs 39.5 mmHg; P = 0.00003), atrial dimensions (51 vs 56 mm; P = 0.085), and of right myocardial performance index (MPI; 0.39 vs 0.42; P = 0.05). PAPs was significantly reduced in group more than 40-years-old (P = 0.00004), while the reduction was not significant in the less or equal than 40 years of age (P = 0.08) group because the baseline value was significantly lower. Many patients after procedure complained headache, insomnia, palpitations, fatigue, and dyspnea; but no cardiac morphological abnormalities related to symptoms were found. Conclusions: Our data showed a great improvement in symptoms and positive cardiac remodeling after closure of ASD, more effective in elderly patients compared to younger patients. The symptoms are not correlated with the principal disease or procedure.