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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: Lung ultrasound detects pulmonary congestion as B-lines at rest, and more frequently, during exercise stress echocardiography (ESE). Methods: We performed ESE plus lung ultrasound (4-site simplified scan) in 4392 subjects referred for semi-supine bike ESE in 24 certified centers in 9 countries. B-line score ranged from 0 (normal) to 40 (severely abnormal). Five different populations were evaluated: control subjects (n=103); chronic coronary syndromes (n=3701); heart failure with reduced ejection fraction (n=395); heart failure with preserved ejection fraction (n=70); ischemic mitral regurgitation ≥ moderate at rest (n=123). In a subset of 2478 patients, follow-up information was available. Results: During ESE, B-lines increased in all study groups except controls. Age, hypertension, abnormal ejection fraction, peak wall motion score index, and abnormal heart rate reserve were associated with B-lines in multivariable regression analysis. Stress B lines (hazard ratio, 2.179 [95% CI, 1.015–4.680]; P =0.046) and ejection fraction P =0.012) were independent predictors of all-cause death (n=29 after a median follow-up of 29 months). Conclusions: B-lines identify the pulmonary congestion phenotype at rest, and more frequently, during ESE in ischemic and heart failure patients. Stress B-lines may help to refine risk stratification in these patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 03049995.

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.

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 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)

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.

Anthracyclines are the cornerstone for many oncologic treatments, but their cardiotoxicity has been recognized for several decades. Female subjects, especially before puberty and adolescence, or after menopause, seem to be more at increased risk, with the prognostic impact of this sex issue being less consistent compared to other cardiovascular risk factors. Several studies imply that sex differences could depend on the lack of the protective effect of sex hormones against the anthracycline-initiated damage in cardiac cells, or on differential mitochondria-related oxidative gene expression. This is also reflected by the results obtained with different diagnostic methods, such as cardiovascular biomarkers and imaging techniques (echocardiography, magnetic resonance, and nuclear medicine) in the diagnosis and monitoring of cardiotoxicity, confirming that sex differences exist. The same is true about protective strategies from anthracycline cardiotoxicity. Indeed, first studied to withstand oxidative damage in response to ischemia/reperfusion (I/R) injury, cardioprotection has different outcomes in men and women. A number of studies assessed the differences in I/R response between male and female hearts, with oxidative stress and apoptosis being shared mechanisms between the I/R and anthracyclines heart damage. Sex hormones can modulate these mechanisms, thus confirming their importance in the pathophysiology in cardioprotection not only from the ischemia/reperfusion damage, but also from anthracyclines, fueling further cardio-oncologic research on the topic.

Background: Haemophilia is a disease of genetic origin, which causes a defect in blood coagulation. Under normal conditions, in the case of leakage from the blood vessels, the blood forms a clot that reduces or blocks the bleeding. This process involves the activation of several plasma proteins in a cascade-like species. Two of these proteins, produced in the liver, factor VIII and factor IX, are deficient or present a functional defect in people with haemophilia. Because of this deficit, the haemophiliacs easily suffer external and internal bleeding. Surgical treatment of these patients is to be observed, and often their treatment is delayed due to unclear guidelines and risks in treating these patients. The aim is to provide clear guidelines in the case of surgical treatment of these patients. Methods: In this study, we have considered all the guidelines that refer to the gold-maxillofacial surgery, focusing on the literature of the last 10 years. Results: Surely, this collection of guidelines will favor the choice of the clinician towards safer and predictable protocols. This study does not want to create a guideline but evaluates the literature of the last 10 years, and highlights the latest for the treatment of these patients., with the aim of informing the pathology and at the same time making the surgical maneuvers safer. Conclusions: Despite the research of literature has produced few results, it was nevertheless possible to draw up a guideline thanks to additional information extrapolated from textbooks and other scientific articles. According to the guidelines, it is possible to proceed to the treatment of these patients, if with appropriate therapy in a safe and risk-free manner. Background: Haemophilia is a disease of genetic origin, which causes a defect in blood coagulation. Under normal conditions, in the case of leakage from the blood vessels, the blood forms a clot that reduces or blocks the bleeding. This process involves the activation of several plasma proteins in a cascade-like species. Two of these proteins, produced in the liver, factor VIII and factor IX, are deficient or present a functional defect in people with haemophilia. Because of this deficit, the haemophiliacs easily suffer external and internal bleeding. Surgical treatment of these patients is to be observed, and often their treatment is delayed due to unclear guidelines and risks in treating these patients. The aim is to provide clear guidelines in the case of surgical treatment of these patients. Methods: In this study, we have considered all the guidelines that refer to the gold-maxillofacial surgery, focusing on the literature of the last 10 years. Results: Surely, this collection of guidelines will favor the choice of the clinician towards safer and predictable protocols. This study does not want to create a guideline but evaluates the literature of the last 10 years, and highlights the latest for the treatment of these patients., with the aim of informing the pathology and at the same time making the surgical maneuvers safer. Conclusions: Despite the research of literature has produced few results, it was nevertheless possible to draw up a guideline thanks to additional information extrapolated from textbooks and other scientific articles. According to the guidelines, it is possible to proceed to the treatment of these patients, if with appropriate therapy in a safe and risk-free manner.

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.

Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme &alpha, galactosidase A (&alpha, Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the &alpha, Gal A. To date, more than 900 mutations in this gene have been described. In our laboratories, the study of genetic and enzymatic alterations related to FD was performed in about 17,000 subjects with a symptomatology referable to this disorder. The accumulation of globotriaosylsphingosine (LysoGb3) was determined in blood of positives. Exonic mutations in the GLA gene were detected in 471 patients (207 Probands and 264 relatives): 71.6% of mutations were associated with the classic phenotype, 19.8% were associated with the late-onset phenotype, and 8.6% of genetic variants were of unknown significance (GVUS). The accumulation of LysoGb3 was found in all male patients with a mutation responsible for classic or late-onset FD. LysoGb3 levels were consistent with the type of mutations and the symptomatology of patients. &alpha, Gal A activity in these patients is absent or dramatically reduced. In recent years, confusion about the pathogenicity of some mutations led to an association between non-causative mutations and FD. Our study shows that the identification of FD patients is possible by associating clinical history, GLA gene analysis, &alpha, Gal A assay, and blood accumulation of LysoGB3. In our experience, LysoGB3 can be considered a reliable marker, which is very useful to confirm the diagnosis of Fabry disease.

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

Background: The trial "Stress Echo (SE) 2020" evaluates novel applications of SE beyond coronary artery disease. The aim of the study was control quality and harmonize reading criteria.Methods: One reader from 78 centers of the SE 2020 network asked for credentials to read a set of 20 SE videoclips selected by the core lab. All aspiring centers met the pre-requisite of high-volume and the years of experience in SE ranged from 5 to 31 years (mean value 18 years). The diagnostic gold standard was a reading by the core lab. The a priori determined pass threshold was 18/20 (>= 90%).Results: Of the initial 78 who started, 57 completed the first attempt: individual readers' score on first attempt ranged from 07/20 to 20/20 (accuracy from 35% to 100%, mean 78.7 +/- 13%) and 44 readers passed it. There was a very poor correlation between years of experience and the reader's score on first attempt (r = -0.161, p = 0.231). Of the 13 readers who failed the first attempt, 12 took it again after the web-based session and their accuracy improved (74% vs. 96%, p < 0.001). The kappa inter-observer agreement before and after web-based training was 0.59 on first attempt and rose to 0.91 on the last attempt.Conclusions: In SE reading, the volume of activity or years of experience is not synonymous with diagnostic quality. Qualitative analysis and operator-dependence can become a limiting weakness in clinical practice, in the absence of strict pathways of learning, credentialing and audit. (C) 2017 Elsevier B.V. All rights reserved.

Significance: Antineoplastic therapies have significantly improved the prognosis of oncology patients. However, these treatments can bring to a higher incidence of side-effects, including the worrying cardiovascular toxicity (CTX). Recent Advances: Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is, therefore, crucial for effective cardioprotection, without compromising the efficacy of anti-cancer treatments. Critical Issues: CTX can occur within a few days or many years after treatment. Type I CTX is associated with irreversible cardiac cell injury, and it is typically caused by anthracyclines and traditional chemotherapeutics. Type II CTX is generally caused by novel biologics and more targeted drugs, and it is associated with reversible myocardial dysfunction. Therefore, patients undergoing anti-cancer treatments should be closely monitored, and patients at risk of CTX should be identified before beginning treatment to reduce CTX-related morbidity. Future Directions: Genetic profiling of clinical risk factors and an integrated approach using molecular, imaging, and clinical data may allow the recognition of patients who are at a high risk of developing chemotherapy-related CTX, and it may suggest methodologies to limit damage in a wider range of patients. The involvement of redox mechanisms in cancer biology and anticancer treatments is a very active field of research. Further investigations will be necessary to uncover the hallmarks of cancer from a redox perspective and to develop more efficacious antineoplastic therapies that also spare the cardiovascular system.

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

Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal models of chemotherapy-induced cardiomyopathy. This Position Paper of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to: (1) define the distinctive etiopatogenetic features of cardiac toxicity induced by cancer therapy in humans, which include new aspects of mitochondrial function and oxidative stress, neuregulin-1 modulation through the ErbB receptor family, angiogenesis inhibition, and cardiac stem cell depletion and/or dysfunction; (2) review the new, more promising therapeutic strategies for cardioprotection, aimed to increase the survival of patients with severe antineoplastic-induced cardiotoxicity; (3) recommend the distinctive pathological features of cardiotoxicity induced by cancer therapy in humans that should be present in animal models used to identify or to test new cardioprotective therapies.

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.

Fabry disease is a metabolic and lysosomal storage disorder caused by the functional defect of the α-galactosidase A enzyme; this defect is due to mutations in the GLA gene, that is composed of seven exons and is located on the long arm of the X-chromosome (Xq21–22). The enzymatic deficit is responsible for the accumulation of glycosphingolipids in lysosomes of different cellular types, mainly in those ones of vascular endothelium. It consequently causes a cellular and microvascular dysfunction. In this paper, we described five novel mutations in the GLA gene, related to absent enzymatic activity and typical manifestations of Fabry disease. We identified three mutations (c.846_847delTC, p.E341X and p.C382X) that lead to the introduction of a stop codon in positions 297, 341 and 382. Moreover we found a missense mutation (p.R227P) in the exon 5 of the GLA gene and a single point mutation (c.639 + 5 G > T) occurring five base pairs beyond the end of the exon 4. These mutations have never been found in our group of healthy control subjects > 2300. The studied patients presented some clinical manifestations, such as cornea verticillata, hypo-anhidrosis, left ventricular hypertrophy, cerebrovascular disorders and renal failure, that, considering the null enzymatic activity, suggest that the new mutations reported here are related to the classic form of Fabry disease. The identification of novel mutations in patients with symptomatology referable to FD increases the molecular knowledge of the GLA gene and it gives clinicians an important support for the proper diagnosis of the disease.

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.

Fabry disease (FD) is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolaseα-galactosidase A (α-GAL). The impairment ofα-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male patients is not related to differences inα-GAL enzymatic activity: though both have no enzymatic activity, the youngest shows severe symptoms, while the eldest is asymptomatic. It is noticeable that for two female patients with the M51I mutation the initial clinical diagnosis was different from FD. One of them was diagnosed with Familial Mediterranean Fever, the other with Multiple Sclerosis. Overall, this study confirms that the extreme variability of the clinical manifestations of FD is not entirely attributable to different mutations in the GLA gene and emphasizes the need to consider other factors or mechanisms involved in the pathogenesis of Fabry Disease.

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

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.

Background.Left ventricular (LV) longitudinal deformation can be assessed with new echocardiographic techniques like triplane echocardiography (3PE) and four-dimensional echocardiography (4DE). We aimed to assess the feasibility, reproducibility, and agreement between these different speckle-tracking techniques for the assessment of longitudinal deformation.Methods. 101 consecutive subjects underwent echocardiographic examination. 2D cine loops from the apical views, a triplane view, and an LV 4D full volume were acquired in all subjects. LV longitudinal strain was obtained for each imaging modality.Results. 2DE analysis of LV strain was feasible in 90/101 subjects, 3PE strain in 89/101, and 4DE strain in 90/101. The mean value of 2DE and 3PE longitudinal strains was significantly higher with respect to 4DE. The relationship between 2DE and 3PE derived strains (r=0.782) was significantly higher (z=3.72,P<0.001) than that between 2DE and 4DE (r=0.429) and that between 3PE and 4DE (r=0.510;z=3.09,P=0.001). The mean bias between 2DE and 4DE strains was-6.61±7.31%while-6.42±6.81%between 3PE and 4DE strains; the bias between 2DE and 3PE strain was of0.21±4.16%. Intraobserver and interobserver variabilities were acceptable among the techniques.Conclusions. Echocardiographic techniques for the assessment of longitudinal deformation are not interchangeable, and further studies are needed to assess specific reference values.

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.

Inflammatory abdominal aortic aneurysm (IAAA) is defined as an unusually thickened aneurysmatic wall, encircled by a wide dense perianeurysmal and/or retroperitoneal fibrosis with adjacent tissues adhesion, and is now considered as an extreme shape of the common phlogistic process involved in atherosclerotic plaque formation. Latest studies demonstrated that inflammation plays an important role in coronary disease and in other atherosclerosis manifestations. We introduce the clinical case of a patient with IAAA who developed an acute myocardial infarction 6 months after the surgical procedure on the aorta. Through a literature review about IAAA we stress the clinical usefulness of the inflammatory markers as independent predictors in management of patients with coronary disease and we present the hypothesis, related to the introduced case, of an advanced coronary disease, aggravated or clinically revealed after the cytokine storm related to important localized inflammatory engagements or great vascular surgery treatments.

The preoperative cardiac evaluation of a patient who undergoes noncardiac surgery is a very important problem, particularly for diagnostic tools used. Aim of this study is to test the usefulness of 4 most used clinical indexes for the evaluation of cardiovascular risk in the management of patients who undergo noncardiac surgery.The study is based on a retrospective analysis of a group of 45 patients, who underwent extracardiac surgery in biennium 2002-2004. The cardiovascular risk scores of Goldman, Detsky, Lee and Eagle were used; a comparison among the different scores was done.Six out of our 45 patients had perioperative cardiovascular complications, and 4 of them died. The Eagle and Lee scores were more predictive than Goldman and Detsky ones. About the 13 echocardiographic tests recorded, no one of them modified the patient preoperative risk.In the preoperative assessment of risk, the Eagle score was more useful than the others ones and improved the negative predictive value of the Goldman and Detsky scores. The preventive application of the clinical indexes allows optimizing the preoperative stratification of the risk, limiting the request of useless examinations and offering to the patient a well appropriated preoperative management, reducing the incidence of complications.

Strain rate (SR) is considered as an accurate index of myocardial contractility, capable of differentiating regional myocardial contractions from hypokinetic ones. It is not dependent on adjacent myocardial motion or heart translation. Clinical studies proved this method to be useful in case of heart disease but detailed analyses, homogeneous normal reference parameters, and studies about atrial myocardium are still scanty. The aim of this study was to evaluate longitudinal SR of the left myocardial ventricle and atrium in normal subjects.Nineteen normal subjects were examined with tissue Doppler imaging; SR values were obtained off-line on images stored by internal software using the curved M-mode of the left ventricle and atrium. Mean SR values were obtained at the distal, mid, and basal left ventricular segments of the septum and lateral wall, and at the basal and distal left atrial segments of the septum and lateral wall.Ventricular SR values showed a negative systolic peak, two positive peaks at rapid filling and one at late filling. In the distal segments systolic SR values were lower and that of rapid filling were higher. Systolic events showed a progression from the base to the apex; the diastolic ones had an opposite trend. SR values of the closest atrial segments to the annulus showed the same progression as the ventricular ones; in the distal segments systolic SR was positive and diastolic SR was negative. The atrioventricular sequence of the cardiac cycle is identified.The method to obtain SR is semiautomatic and objective; image acquisition at a frame rate100/s identifies accurately the components of the SR curves. The analysis of the progression of events can allow to study ventricular and atrial synchronization of contraction, relaxation, and compliance.

The double-chamber right ventricle is a congenital cardiac malformation usually associated with other cardiac defects, seldom isolated and in adult subject. It is characterized by the presence of an anomalous bundle that divides the right ventricle into two chambers. The clinical and electrocardiographic signs of isolated double-chamber right ventricle are few and not specific. An echocardiographic diagnosis of isolated double-chamber right ventricle is reported. In a 18-year-old asymptomatic male with systolic murmur 2/6 at third space over the left sternal border, right ventricular hypertrophy and intraventricular conduction delay at ECG, two-dimensional echo showed an anomalous transversal muscle bundle that divided the right ventricle into two chambers, superior and inferior. Color Doppler showed a diastolic tricuspidal-like flow through a paraseptal discontinuity of the bundle and a systolic jet that reached the right atrium, with a pressure gradient of 30.9 mmHg. The absence of symptoms and other cardiopathy, without significant right outflow tract obstruction, was considered as an index of a good prognosis; therefore cardiac catheterization was not advised.

Aim of the study was to examine the role of echocardiography to classify patients with heart failure. Fifty-seven subjects (32 dilated cardiomyopathy (DCM), 9 aortic regurgitation (AR), 16 hypertensives (HT)--4 in Class (CI) NYHA I, 24 II, 15 III, 14 IV--were studied by M-2D echo. Eighty-seven normals (N) were the control group; 11 were controlled after clinical improvement (3.4 +/- 3.8 months); 11 after worsening (12 +/- 17). We have evaluated: left ventricular diastolic dimension (LVIDd), wall thickness/radius ratio (H/R), diastolic (D) and systolic volume (S Vol), ejection fraction (EF), systolic arterial pressure/end-systolic volume ratio (P/V), and stress. LVIDd and stress were increased in all groups; H/R reduced, except in HT and in Cl I; EF and P/V reduced except in Cl I. Between I and II LVIDd was different; between II and III all parameters were different, between III and IV only EF and P/V. According to regression S-D Vol, EF-P/V and EF-stress we identify the reduction of EF and the related mechanisms, ie reduced contractility or increased afterload. Thus, according to P/V and stress, we classify the patients in 4 pathopysiologic classes: 1 and 2 with P/V within 2 SD N: 1 with stress within 2SD N, EF and H/R normal; 2 with stress greater than +2SD, H/R normal and EF reduced; 3 and 4 with P/C less than -2 SD N: 3 with normal, 4 with stress greater than +2 SD. In the 1 and 2, 1 out 14 is in III Cl NYHA, none in IV; in 3,6 out 8 are in II, in 4, 9 out 35 are in Cl less than III. In the follow-up, in 8 of the improved patients, EF and P/V were increased and stress reduced; in 3, EF was reduced. In 8 of the worsened, EF and P/V were reduced, LVIDd and stress increased; in 3 EF and LVIDd were increased, P/V reduced. This study demonstrates discordance between Cl NYHA and echo, and how classification of NYHA does not give information about the several components of heart failure. However LVID and EF are not sufficient. By a correlation of echo-parameters of contractility, afterload and pump performance, we may suggest a classification of heart failure in pathophysiologic classes.

The aim of the study was to compare antihypertensive efficacy and safety of ketanserin with those of enalapril in the treatment of hypertension. The study design was controlled, cross-over, with randomized sequences. The efficacy was evaluated from data of 19 (9 males, 10 females) mean age 59.5 +/- 10.1 years, weight kg 68 +/- 12.1 with hypertension lasting over 5 years. Posology was ketanserin 20-40 mg bid, and enalapril 10-20 mg bid; both for three weeks. The efficacy was good with both treatments and the effects similar. In fact, at the end of the treatment with ketanserin, supine SBP was decreased 10 +/- 20 and DBP 5 +/- 10 mmHg, standing SBP was reduced 15 +/- 19 and DBP 7 +/- 15 mmHg. With enalapril supine SBP decreased 25 +/- 16 and DBP 10 +/- 13 mmHg, standing SBP was reduced 16 +/- 19 and DBP 8 +/- 18 mmHg. Changes of heart rate by either treatment were of no clinical importance. The safety of treatment with ketanserin was excellent, while 14.3% of the patients treated with enalapril had undesirable effects.

Percutaneous balloon mitral valvuloplasty (PBMV) in patients with positive valve morphology has been recognized as an effective alternative to surgical treatment of mitral stenosis. In selected cases, PBMV has been used also in the treatment of bioprosthetic (Bp) valve dysfunction. We report one case of PBMV of a Bp: in this patient the advantage of such procedure has been the possibility to defer of some years the unavoidable substitution of the Bp, thus making also possible a new and complete surgical treatment for coronary artery disease.

Aim of the study was to evaluate the left ventricular (LV) diastolic flow propagation. Ten healthy subjects (28 +/- 6 years) were examined. Two-dimensional echocardiography and color-Doppler at mitral valve were performed. A cine-loop was transferred on-line to a color image processor. Selected digitized images were stored on microdisk. LV end-diastolic, end-systolic and early filling (EF) volumes were measured. Doppler measurements across the mitral valve were obtained: peak E, peak A, E/A, the integral (VTI) of E and A, acceleration and filling time. Extension of color and time base to apex, time of EF and atrial filling (AF) were obtained by M-color, along the base-apex axis. On frames of EF and AF of 2D-color, diastolic maps were processed: surface area and pixel velocity, mean (mv) and peak (pv), were obtained of the entire color area and of 4 selected areas, 2 mm wide: 1 along the annulus-apex axis (LAx), and 3 transverse, planes, at the annulus, at papillary (1/3) and at the apex (2/3 of LAx). Three-dimensional plot and velocity distribution were obtained. Values of pixel of the entire color area were stored on microdisk and processed using a Macintosh PC. For each transverse section, 1 pixel wide, mv and pv were obtained, and data were referred to normalized axis and the mean was calculated.end-diastolic volume index (EDVI): 66 +/- 7, end-systolic volume index (ESVI): 26 +/- 5 ml.(ABSTRACT TRUNCATED AT 250 WORDS)